CDC 2018 Information For International Travel
CDC 2018 Information For International Travel
CDC 2018 Information For International Travel
CDC
YELLOW BOOK 2018
Health Information for
International Travel
iii
CDC
YELLOW BOOK 2018
Health Information for
International Travel
Editor in Chief Gary W. Brunette, MD, MS
MANAGING EDITOR
Megan Crawley O’Sullivan, MPH
TECHNICAL EDITOR
1
Ronnie Henry
iv
1
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v
All CDC material in this publication is in the public domain and may be used and
reprinted without special permission; however, citation of the source is appreciated.
Suggested Citation
Centers for Disease Control and Prevention. CDC Yellow Book 2018: Health Information for
International Travel. New York: Oxford University Press; 2017.
Readers are invited to send comments and suggestions regarding this publication to Gary W.
Brunette, Editor in Chief, Centers for Disease Control and Prevention, Division of Global
Migration and Quarantine (E-03), Travelers’ Health Branch (proposed), 1600 Clifton Road NE,
Atlanta, GA 30333, USA.
Disclaimers
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References to non-CDC Internet sites are provided as a service to readers and do not
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publication.
Notice
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cont
vi
ents
╇vi
1 Introductionâ•…
1
viii CONTENTS
╇ix
CONTENTS ix
x
4 Select Destinationsâ•…
Rationale for Select Destinationsâ•… 425
425
x CONTENTS
╇xi
5 Post-╉Travel Evaluation╅
General Approach to the Returned Travelerâ•… 495
495
CONTENTS xi
xi
Appendicesâ•… 645
Appendix A: Promoting Quality in the Practice of Travel Medicineâ•… 645
Appendix B: Travel Vaccine Summary Tableâ•… 649
Indexâ•…653
Photography Creditsâ•… 667
xii CONTENTS
xi
Dengue
BOX 3-1. Guidelines for classifying dengue 166
FIGURE 3-1. Relative sensitivity of detection of dengue virus nucleic acid, antigen, and IgM 168
MAP 3-1. Dengue risk in the Americas and the Caribbean 163
MAP 3-2. Dengue risk in Africa and the Middle East 164
MAP 3-3. Dengue risk in Asia and Oceania 165
TABLE 8-4. Diseases for which VFR travelers are at increased risk, proposed reasons for risk variance, and
recommendations to reduce risks 586
Dermatologic Conditions
TABLE 5-5. Ten most common skin lesions in returned travelers, by cause 508
Diarrheal Illnesses
BOX 2-2. Travelers’ diarrhea definitions 53
TABLE 2-6. Travelers’ diarrhea treatment recommendations 53
TABLE 8-4. Diseases for which VFR travelers are at increased risk, proposed reasons for risk variance, and
recommendations to reduce risks 586
xvi
Escherichia coli
TABLE 3-1. Mechanism of pathogenesis and typical clinical syndrome of Escherichia coli pathotypes 176
Fever
TABLE 5-1. Illnesses associated with fever presenting in the first 2 weeks after travel 497
TABLE 5-2. Common causes of fever, by geographic area 500
Hepatitis A
TABLE 3-2. Vaccines to prevent hepatitis A 185
TABLE 8-4. Diseases for which VFR travelers are at increased risk, proposed reasons for risk variance, and
recommendations to reduce risks 586
Hepatitis B
MAP 3-4. Prevalence of hepatitis B virus infection 188
TABLE 3-3. Interpretation of serologic test results for hepatitis B virus infection 190
TABLE 3-4. Vaccines to prevent hepatitis B 192
TABLE 8-4. Diseases for which VFR travelers are at increased risk, proposed reasons for risk variance, and
recommendations to reduce risks 586
Hepatitis C
MAP 3-5. Prevalence of hepatitis C virus infection 194
TABLE 8-4. Diseases for which VFR travelers are at increased risk, proposed reasons for risk variance, and
recommendations to reduce risks 586
Hepatitis E
MAP 3-6. Hepatitis E endemic countries 200
TABLE 8-4. Diseases for which VFR travelers are at increased risk, proposed reasons for risk variance, and
recommendations to reduce risks 586
HIV
BOX 3-5. Summary of sexual health recommendations for travelers 318
TABLE 8-4. Diseases for which VFR travelers are at increased risk, proposed reasons for risk variance, and
recommendations to reduce risks 586
TABLE 8-1. Immunization of immunocompromised adults 559
Influenza
MAP 3-7. Distribution of highly pathogenic avian influenza A (H5N1) virus 208
TABLE 3-5. Recommended dosage and duration of antiviral medications for treatment and prophylaxis of
influenza A and B 212
Injury
FIGURE 2-2. Leading causes of injury death for US citizens in foreign countries, 2013 & 2014 95
TABLE 2-13. Recommended strategies to reduce injuries while abroad 96
Japanese Encephalitis
MAP 3-8. Distribution of Japanese encephalitis 216
TABLE 3-6. Vaccine to prevent Japanese encephalitis (JE) 217
Malaria
BOX 3-2. Clinical highlights for malaria 235
BOX 3-3. What is a reliable supply? 239
BOX 8-7. Practical advice on malaria prophylaxis for long-term travelers and expatriates 610
MAP 3-9. Malaria-endemic countries in the Western Hemisphere 234
MAP 3-10. Malaria-endemic countries in the Eastern Hemisphere 236
MAP 3-18. Malaria in Bolivia 380
MAP 3-19. Malaria in Botswana 381
MAP 3-21. Malaria in Brazil 383
MAP 3-24. Malaria in Colombia 388
MAP 3-26. Malaria in Ecuador 392
MAP 3-28. Malaria in Ethiopia 394
MAP 3-29. Malaria in India 398
MAP 3-31. Malaria in Kenya 401
MAP 3-32. Malaria in Mexico 404
MAP 3-33. Malaria in Nicaragua 406
MAP 3-35. Malaria in Panama 409
MAP 3-37. Malaria in Peru 412
MAP 3-38. Malaria in South Africa 416
MAP 3-40. Malaria in Venezuela 421
TABLE 3-8. Reliable supply regimens for the treatment of malaria 240
TABLE 3-9. Considerations when choosing a drug for malaria prophylaxis 241
TABLE 3-10. Drugs used in the prophylaxis of malaria 244
TABLE 3-11. Half-lives of malaria chemoprophylaxis drugs 248
TABLE 3-12. Changing medications as a result of side effects during chemoprophylaxis 250
TABLE 3-13. Food and Drug Administration recommendations for deferring blood donation in people returning
from malarious areas 251
TABLE 8-4. Diseases for which VFR travelers are at increased risk, proposed reasons for risk variance, and
recommendations to reduce risks 586
TABLE 8-6. Differences between CDC recommendations and US military’s use of malaria
chemoprophylaxis 619
Measles
TABLE 2-4. Recommended intervals between administration of antibody-containing products and
measles-containing vaccine or varicella-containing vaccine 35
Meningitis
MAP 3-11. Areas with frequent epidemics of meningococcal meningitis 262
TABLE 3-14. Meningococcal vaccines licensed in the United States 264
Rabies
BOX 3-4. World Health Organization, human rabies case definition 288
TABLE 3-15. Criteria for preexposure immunization for rabies 290
TABLE 3-16. Preexposure immunization for rabies 291
TABLE 3-17. Postexposure immunization for rabies 292
Schistosomiasis
MAP 3-12. Distribution of schistosomiasis 310
TABLE 8-4. Diseases for which VFR travelers are at increased risk, proposed reasons for risk variance, and
recommendations to reduce risks 586
Tickborne Encephalitis
TABLE 3-19. Tickborne encephalitis (TBE) vaccines licensed in Europe and Russia 329
Tuberculosis
MAP 3-13. Estimated tuberculosis incidence rates 336
TABLE 3-20. Estimated proportion of MDR TB cases in high-burden countries 338
TABLE 8-4. Diseases for which VFR travelers are at increased risk, proposed reasons for risk variance, and
recommendations to reduce risks 586
Typhoid
TABLE 3-21. Vaccines to prevent typhoid fever 344
TABLE 8-4. Diseases for which VFR travelers are at increased risk, proposed reasons for risk variance, and
recommendations to reduce risks 586
Varicella (Chickenpox)
TABLE 2-4. Recommended intervals between administration of antibody-containing products and
measles-containing vaccine or varicella-containing vaccine 35
Yellow Fever
FIGURE 3-2. Example International Certificate of Vaccination or Prophylaxis (ICVP) 362
FIGURE 3-3. Medical Contraindication to Vaccination section of the International Certificate of Vaccination
or Prophylaxis (ICVP) 363
MAP 3-14. Yellow fever vaccine recommendations in Africa 364
MAP 3-15. Yellow fever vaccine recommendations in the Americas 365
Zika
BOX 3-6. Zika in pregnancy 370
RESOURCES
General Resources
BOX 1-1. CDC contact information for clinicians 2
BOX 2-9. About dietary supplements and unproven therapies 116
FIGURE 1-1. CDC Travelers’ Health website homepage 4
MAP 1-1. Estimated number of US air travelers received 14
TABLE 1-1. Estimated number of US air passengers departing to the top 10 destination countries, 2015 14
Insect Avoidance
BOX 2-4. Maximizing protection from mosquitoes and ticks 82
BOX 2-5. Bed bugs and international travel 86
BOX 8-6. Practical advice on personal protective measures for clinicians counseling long-term travelers
and expatriates 609
FIGURE 2-1. Sample repellency awareness graphic for skin-applied insect repellents 84
Pretravel Consultation
BOX 8-1. Key patient education points for the immunocompromised traveler 570
BOX 8-2. Pretravel consultation checklist for pregnant travelers 577
TABLE 2-1. Information necessary for a risk assessment during pretravel consultations 17
TABLE 2-2. Vaccines to update or consider during pretravel consultations 19
TABLE 2-3. Major topics for discussion during pretravel consultations 21
Water Treatment
TABLE 2-10. Comparison of water disinfection techniques 73
TABLE 2-11. Microorganism size and susceptibility to filtration 74
TABLE 2-12. Summary of field water disinfection techniques 77
SPECIAL POPULATIONS
Immunocompromised
TABLE 8-1. Immunization of immunocompromised adults 559
TABLE 8-2. Immunosuppressive biologic agents that preclude use of live vaccines 566
Long-Term Travelers
BOX 8-5. Key findings from a review on studies relevant to long-term travelers and expatriates 608
BOX 8-6. Practical advice on personal protective measures for clinicians counseling long-term travelers
and expatriates 609
BOX 8-7. Practical advice on malaria prophylaxis for long-term travelers and expatriates 610
Medical Tourists
BOX 2-6. Guiding principles on medical tourism 112
BOX 2-7. Patient checklist for obtaining safe dental care during international travel 113
BOX 2-8. Helpful resources on medical tourism 114
Military
TABLE 8-5. Differences between military populations and civilian traveling populations 616
TABLE 8-6. Differences between CDC recommendations and US military’s use of malaria
chemoprophylaxis 619
Pregnant Travelers
BOX 8-2. Pretravel consultation checklist for pregnant travelers 577
BOX 8-3. Contraindications for travel during pregnancy 578
Returning Travelers
BOX 5-1. Important elements of a medical history in an ill returned traveler 496
TABLE 5-1. Illnesses associated with fever presenting in the first 2 weeks after travel 497
TABLE 5-2. Common causes of fever, by geographic area 500
TABLE 5-3. Common infections, by incubation period 501
TABLE 5-4. Common clinical findings and associated infections 502
TABLE 5-5. Ten most common skin lesions in returned travelers, by cause 508
Students
TABLE 8-7. Study-abroad resources 623
List of Maps
DISEASE MAPS
Dengue, the Americas and the Caribbean (Map 3-1) 163
Dengue, Africa and the Middle East (Map 3-2) 164
Dengue, Asia and Oceania (Map 3-3) 165
Hepatitis B (Map 3-4) 188
Hepatitis C (Map 3-5) 194
Hepatitis E (Map 3-6) 200
Influenza, Avian (H5N1) (Map 3-7) 208
Japanese encephalitis (Map 3-8) 216
Malaria, Eastern Hemisphere (Map 3-10) 236
Malaria, Western Hemisphere (Map 3-9) 234
Malaria, Bolivia (Map 3-18) 380
Malaria, Botswana (Map 3-19) 381
Malaria, Brazil (Map 3-21) 383
Malaria, Colombia (Map 3-24) 388
Malaria, Ecuador (Map 3-26) 392
xx LIST OF MAPS
xxi
Editorial Staff
Editor in Chief: Gary W. Brunette
Chief Medical Editor: Phyllis E. Kozarsky
Medical Editors: Clive M. Brown, Nicole J. Cohen, Douglas H. Esposito, Mark D. Gershman,
Stephen M. Ostroff, Edward T. Ryan, David R. Shlim, Richard W. Steketee,
Michelle Weinberg, and Mary Elizabeth Wilson
Managing Editor: Megan Crawley O’Sullivan
Technical Editor: Ronnie Henry
Design and Production Editor: Kelly Holton
Editorial Assistant: Kelly Winter
Cartographer: R. Ryan Lash
Assistant Cartographer: C. Virginia Lee
CDC Contributors
Abanyie, Francisca Brooks, John T. Esposito, Douglas H. Green, Michael D.
Abe, Karon Brown, Clive M. Fischer, Marc Griffin, Patricia M.
Alexander, James P. Brunette, Gary W. Fitzgerald, Collette Hall, Aron J.
Ansari, Armin Burdette, Erin Flannery, Brendan Hawley, William A.
Appiah, Grace Burke, Heather Fox, LeAnne M. Hendricks Walters, Kate
Arboleda, Nelson Cantey, Paul T. Francois Watkins, Henry, Ronnie
Arguin, Paul M. Cardemil, Cristina V. Louise K. Herwaldt, Barbara L.
Armstrong, Paige Chen, Tai-Ho Friedman, Cindy R. Hills, Susan L.
Averhoff, Francisco Chiller, Tom M. Fullerton, Katie Hlavsa, Michele C.
Baggett, Henry C. Choi, Mary Gaines, Joanna Holtzman, Deborah
Bair-Brake, Heather Chosewood, Casey Galland, G. Gale Hunter, Jennifer C.
Ballesteros, Michael F. Clemmons, Nakia S. Galloway, Renee L. Iwamoto, Martha
Barbre, Kira A. Cochi, Stephen L. Garrison, Laurel E. Jackson, Brendan
Beavers, Suzanne Cohen, Nicole J. Gastañaduy, Paul A. Jentes, Emily S.
Beckman, Michele G. Cope, Jennifer Gee, Jay E. Jones, Jeffrey L.
Benenson, Gabrielle A. Czarkowski, Alan G. Geissler, Aimee L. Judd, Michael C.
Berro, Andre Dhara, V. Ramana Gerber, Susan I. Kersh, Gilbert J.
Blaney, David D. Dubray, Christine Gershman, Mark D. Kharod, Grishma A.
Bowen, Anna Duong, Krista Kornylo Gibbins, John Kitt, Margaret
Bresee, Joseph Ederer, David J. Goodson, James L. Knust, Barbara
Brogdon, William G. Erskine, Stefanie K. Gould, L. Hannah Kozarsky, Phyllis E.
xxi
External Contributors
Adler, Tina Westat—National Center for Complementary and Integrative Health Clearinghouse,
Rockville, Maryland
Ansdell, Vernon E. University of Hawaii, Honolulu, HI
Atkinson, Gregory Teesside University, Middlesbrough, United Kingdom
Backer, Howard D. California Emergency Medical Services Authority, Sacramento, CA
Barbeau, Deborah Nicolls Tulane University, New Orleans, LA
Barnett, Elizabeth D. Boston University School of Medicine and Boston Medical Center, Boston, MA
Batterham, Alan M. Teesside University, Middlesbrough, United Kingdom
Benenson, Michael W. Armed Forces Research Institute of the Medical Sciences, Bangkok, Thailand (retired)
Boggild, Andrea K. University of Toronto, Toronto, Canada
Borwein, Sarah T. TravelSafe Medical Centre, Hong Kong, China
Carroll, I. Dale The Pregnant Traveler, Spring Lake, MI
Changizi, Roohollah United Family Hospital, subsidiary of United Family Healthcare, Beijing, China
Chen, Lin H. Mount Auburn Hospital—Travel Medicine Center, Cambridge, MA, and Harvard
Medical School, Boston, MA
* Deceased
Shurtleff, David National Center for Complementary and Integrative Health, National Institutes of
Health, Bethesda, MD
Staat, Mary Allen International Adoption Center, Cincinnati Children’s Hospital Medical Center,
Cincinnati, OH
Taggart, Linda R. University of Toronto, Toronto, Canada
Takiguchi, Rodd Department of Dermatology, Kaiser Permanente, Honolulu, Hawaii
Thompson, Andrew University of Liverpool, Liverpool, United Kingdom
Valk, Thomas H. VEI Inc., Marshall, VA
Van Tilburg, Christopher Providence Hood River Memorial Hospital, Hood River, OR
Wangu, Zoon Department of Pediatric Infectious Diseases, Boston Medical Center, Boston, MA
Wilson, Mary Elizabeth Harvard School of Public Health, Boston, MA
Wu, Henry M. Emory University, Department of Medicine, Atlanta, GA
Youngster, Ilan Children’s Hospital Boston and Harvard University, Boston, MA
All contributors have signed a statement indicating that they have no conflicts of interest with the subject
matter or materials discussed in the document(s) that they have written or reviewed for this book and that the
information that they have written or reviewed for this book is objective and free from bias.
Acknowledgments
The CDC Yellow Book 2018: Health Information • Elise Beltrami, Pamela Diaz and Scott
for International Travel editorial team grate- Santibanez for their extensive review of
fully acknowledges all the authors and review- the text.
ers for their commitment to this new edition.
We extend sincere thanks to the following peo-
• Courtney Ware, Aida Sawadogo, Laurie
Dieterich and Crystal Polite for their assis-
ple for their contributions to the production of
tance in preparing the text for publication.
this book:
Preface
To stay on the cutting edge of travel health infor- Centers for Disease Control and Prevention
mation, this latest edition of the CDC Yellow Anne Schuchat, MD, Acting Director
Book: Health Information for International Travel National Center for Emerging and Zoonotic
has been extensively revised. The book serves as Infectious Diseases
a guide to the practice of travel medicine, as well Rima Khabbaz, MD, Acting Director
as the authoritative source of US government rec- Division of Global Migration and
ommendations for immunizations and prophy- Quarantine
laxis for foreign travel. As international travel Martin S. Cetron, MD, Director
continues to become more common in the lives of Gary W. Brunette, MD, MS, Chief,
US residents, having at least a basic understand- Travelers’ Health Branch
ing of the medical problems that travelers face Phyllis E. Kozarsky, MD, Expert Consultant,
has become a necessary aspect of practicing med- Travelers’ Health Branch
icine. The goal of this book is to be a comprehen- Megan Crawley O’Sullivan, MPH,
sive resource for clinicians to find the answers to Health Communications Specialist,
their travel health–related questions. Travelers’ Health Branch
xvi
Alan J. Magill passed away on September 19, 2015, just days after work began on the CDC Yellow
Book 2018. He was a key figure in the evolution of this publication, serving as an author and medical
editor for three editions. Over the years, he provided invaluable insight and guidance as a singularly
experienced and knowledgeable contributor. The editorial board of the CDC Yellow Book respectfully
dedicate this edition to Alan.
Whatever Alan was involved in always seemed to go smoother, be more relevant, and even more fun.
At that point in time, Alan was the president-╉elect of the International Society of Travel Medicine. He
would subsequently serve as the president of the American Society of Tropical Medicine and Hygiene,
becoming the first person to be president of both societies. During a 26-╉year career in the US Army
Medical Corps, Alan focused mainly on malaria and leishmaniasis, but his research interests and
projects spanned an extraordinary range, including diagnostics, pharmaceuticals, and vaccine devel-
opment. He carried with him a nagging curiosity about the history of disease, and he often delved into
original sources of research that informed our present practice in new ways. Invariably kind, enthusias-
tic, supportive, tireless, and insightful, Alan improved any project with which he was involved, includ-
ing the Yellow Book.
Upon retiring from the military in 2012, Alan became the Malaria Program Director for the Gates
Foundation, charged with designing a strategy that could lead to the elimination of malaria in the
world. He had already played a large role in helping to shape an international strategy in this regard
when he died suddenly on September 19, 2015, near his home in Seattle, leaving behind his wife
and two daughters, and a devastated string of colleagues and admirers. Although tributes often end
with the words, “He will be missed,” in Alan’s case, we are left wondering what the world has missed
and what might have happened if he had been able to stay with us for many more years. He was
62 years old.
David R. Shlim, MD
Medical Editor of the Yellow Book
Recent Past-╉President of the ISTM
1
1
Introduction
INTRODUCTION TO TRAVEL
HEALTH & THE YELLOW BOOK
Phyllis E. Kozarsky
2 INTRODUCTION
3
BIBLIOGRAPHY
1. United Nations World Tourism Organization. Department of Commerce; 2016 [cited 2016 Mar. 21];
UNWTO World Tourism Barometer, Vol. 14 Available from: http://travel.trade.gov/tinews/archive/
(March). Madrid: United Nations World Tourism tinews2016/20160321.asp.
Organization; 2016 [cited 2016 Mar. 2]; Available from: 3. World Health Organization. International Health
http://www.e-unwto.org/toc/wtobarometereng/14/2. Regulations (2005). Geneva: World Health
2. US Department of Commerce, Office of Travel and Organization; 2008 [cited 2016 Apr. 11]; 2nd: Available
Tourism Industries. 2015 Monthly US Outbound Air from: http://www.who.int/ihr/publications/
Travel to International Regions. Washington, DC: US 9789241596664/en/.
4 INTRODUCTION
5
TRAVEL EPIDEMIOLOGY
Allison Taylor Walker, Regina C. LaRocque, Mark J. Sotir
1
Travelers are an epidemiologically important of travelers. Often, these studies were conducted
population because of their mobility, their
>20 years ago and might be of limited relevance
potential for exposure to diseases outside their to current travelers. Furthermore, these studies
home country, and the possibility that they may use a variety of methodologic designs, each with
carry nonendemic diseases between countries. its own set of strengths and weaknesses, making
International tourist arrivals were 1.2 billion in the findings difficult to compare or combine. They
2015 and are projected to increase to almost 2 bil- have also, for the most part, only examined a few
lion by 2030, so the public health impact of travel key diseases or conditions and have combined
will likely only increase. The destinations of trav- all travelers regardless of destination or purpose
elers are also changing. Increased travel to des- of travel. Many have been single-clinic or single-
tinations in Asia (arrivals up 5% from 2014 to destination studies that lead to conclusions that
2015) and the Middle East (arrivals up 3% from do not apply to groups of travelers with different
2014 to 2015) and anticipated increases in travel local, national, or cultural backgrounds.
to Africa will place more travelers at risk for a vari- A number of factors are relevant to epidemio-
ety of travel-related conditions, including malaria, logic data on travel-related diseases and adverse
dengue, measles, and other tropical or vaccine- health events. First, the characteristics of the dis-
preventable infections. ease itself must be considered, including mode of
The risk of travel-related illness varies depend- transmission, incubation period, signs and symp-
ing on destination and traveler characteristics. toms, duration of illness, and diagnostic testing.
Existing information regarding the actual risk for Second, the presence, frequency, seasonality, and
travelers (often expressed as number of events geographic distribution of the disease need to be
per 100,000 travelers) is limited for several rea- assessed; these might change over time because
sons. It is difficult to obtain an accurate numera- of outbreaks, emergence or reemergence in new
tor (number of cases of disease among travelers) areas or populations, successful public health
and denominator (number of travelers overall or interventions, or other factors. Third, travelers
travelers to a specific destination). Many travel- represent a unique subset of people, and their
ers who become infected will have returned to exposures, behaviors, and disease susceptibility
their home countries by the time they develop might differ dramatically from those of the local
symptoms so will not be included in the visited population at a tourist destination.
country’s surveillance data. Similarly, diseases Along with demographic characteristics, addi-
with short incubation periods or brief durations tional travel-specific factors that should be con-
may have resolved by the time a traveler returns sidered include trip length, destinations (both
home and thus may not be counted in surveil- current and previous), specific travel itineraries,
lance data of the traveler’s country of origin. If the use of preventive measures, and purpose of travel.
illness is mild, the traveler may never seek health Fourth, travelers themselves are a heterogeneous
care, or diagnostic tests may not be performed group, and different subgroups of travelers might
to accurately diagnose the cause. Travelers often have different risks because of activities, behav-
visit multiple locations, and it may be difficult to iors, and other factors during travel. For exam-
determine the location in which the exposure ple, travelers who are visiting friends and relatives
occurred. (VFR travelers) have consistently demonstrated
Frequently quoted studies on the incidence higher proportions of serious febrile illness, par-
of infection in travelers are based on extrapola- ticularly malaria, when compared with other
tions of limited data collected in limited samples types of travelers.
6 INTRODUCTION
7
During the past 2 decades, the most rele- malaria prophylaxis. Post-travel data from the
vant data on travel-related disease occurrence GeoSentinel network of 53 clinics around the
have come from surveillance of travelers them- world collected from 2007 through 2011 indicate
selves. Data on disease incidence in local popula- that Asia (33%) and sub-Saharan Africa (27%)
tions may identify the most important diseases to
monitor within a country, but relevance of such
were the most common regions where travel-
related illnesses were acquired. Malaria, dengue,
1
data to travelers—who have different risk behav- enteric fever, spotted-fever group rickettsioses,
iors, eating habits, accommodations, knowledge chikungunya, and nonspecific viral syndromes
of preventive measures, and activities—is usually were the most frequent contributors to the acute
limited. Surveillance data that are either focused systemic febrile illness category. Falciparum
on travelers or on illnesses that affect travelers are malaria was most commonly acquired in West
more useful in describing travel-related disease Africa, while enteric fever was most often con-
patterns and risks. tracted on the Indian subcontinent; leptospi-
Data collected by the Global TravEpiNet rosis, scrub typhus, and murine typhus were
(GTEN) network of pretravel visits in health clin- principally acquired in Southeast Asia. Common
ics across the United States provide a snapshot skin and soft tissue infections, mosquito bites
into the types of travelers seeking pretravel health (often infected), and allergic dermatitis were the
care and their travel practices. Health care pro- most common skin conditions affecting travel-
viders need to understand the epidemiologic fea- ers. Among the more exotic diagnoses, the most
tures of the traveling population to guide their important were hookworm- related cutaneous
pretravel recommendations and post-travel eval- larva migrans, leishmaniasis, myiasis, and tungi-
uations. In examining GTEN data collected from asis. The relative frequency of many diseases var-
2009 through 2011, 13,235 travelers ranged in age ied by travel destination and reason for travel,
from 1 month to 94 years (median 35 years). The and VFR travelers had a disproportionately high
median duration of travel that prompted the pre- prevalence of serious febrile illness (malaria) and
travel evaluation was 14 days, although 22% of low rates of seeking advice before travel (18%).
travelers were taking trips of >28 days, and 3% Only 40% of all ill GeoSentinel travelers reported
of the travelers were taking trips of >6 months. pretravel medical visits.
A total of 75% were traveling to malaria-endemic Investigations of travel-related outbreaks can
countries, and 38% were visiting yellow fever– also provide data on epidemiologic patterns of
endemic countries. Immunocompromising con- travel-
related illness. Outbreaks in travelers to
ditions, such as HIV infection and AIDS, organ the Caribbean are a reminder of travel-associated
transplantation, or receipt of immunocompro- risk of illness. Incidence of chikungunya was eval-
mising medications, were present in 3% of GTEN uated among 102 participants returning from the
travelers. Dominican Republic in 2014. Forty- two (41%)
Post-travel illness surveillance data are col- had evidence of recent chikungunya infection,
lected by the GeoSentinel Global Surveillance and of those, 37 (90%) reported rash or joint pain.
Network, a worldwide data collection and com- Outbreaks in travelers are sentinels to warn the
munication network composed of International international community of prevalent or unrec-
Society of Travel Medicine (ISTM) member ognized illnesses in destination countries. An
travel and tropical medicine clinics. Analyses of outbreak investigation of sarcocystosis in trav-
these data are used to describe the relationships elers returning from Tioman Island, Malaysia, in
between travel and travel-related illness in spe- 2011–2012 led to continued monitoring for addi-
cific subpopulations of travelers. A 2013 sum- tional cases and identified asymptomatic infection
mary of GeoSentinel data found that diarrheal, and late presentation. Diseases identified through
febrile/
systemic, and respiratory illnesses are medical tourism, a booming yet unregulated
the most common diagnoses reported. Another industry, can also highlight local transmission of
study found that >20% of travelers visiting malar- health care–associated infections. Mycobacterium
ious areas reported inconsistent or no use of abscessus infections in postsurgical wounds of
TRAVEL EPIDEMIOLOGY 7
8
medical tourists returning from the Dominican advice to their travelers. Clinical networks and
Republic and Venezuela have been reported. surveillance systems provide epidemiologic data
Familiarity with the epidemiology and preva- on new and prevalent global infectious disease
lence of these and other infections, coupled with threats. These data contribute to the evidence
1 demographic information on travelers and their
particular travel details, can help clinicians pro-
base in this growing field and allow for informed
preparation before travel, as well as clinical aware-
vide optimal health- related information and ness of travel epidemiology.
BIBLIOGRAPHY
1. Adachi K, Coleman MS, Khan N, Jentes ES, Arguin P, 6. Leder K, Torresi J, Libman MD, Cramer JP, Castelli F,
Rao SR, et al. Economics of malaria prevention in Schlagenhauf P, et al. GeoSentinel surveillance of illness
US travelers to West Africa. Clin Infect Dis. 2014 in returned travelers, 2007–2011. Ann Intern Med. 2013
Jan;58(1):11–21. Mar. 19;158(6):456–68.
2. CDC. Malaria surveillance—United States, 2011. MMWR 7. Millman AJ, Esposito DH, Biggs HM, Decenteceo M,
Surveill Summ. 2013 Nov 1;62(5):1–17. Klevos A, Hunsperger E, et al. Chikungunya and dengue
3. Esposito DH, Stich A, Epelboin L, Malvy D, Han PV, virus infections among United States community service
Bottieau E, et al. Acute muscular sarcocystosis: an inter- volunteers returning from the Dominican Republic.
national investigation among ill travelers returning from Am J Trop Med Hyg. 2014 Mar. 14;64(6):1336–41.
Tioman Island, Malaysia, 2011–2012. Clin Infect Dis. 2014 8. Sharp TM, Pillai P, Hunsperger E, Santiago GA,
Nov 15;59(10):1401–10. Anderson T, Vap T, et al. A cluster of dengue cases in
4. Harvey K, Esposito DH, Han P, Kozarsky P, Freedman DO, American missionaries returning from Haiti. Am J Trop
Plier DA, et al. Surveillance for travel-related Med Hyg. 2010 Jan.;86(1):6–22.
disease—GeoSentinel Surveillance System, United 9. Sotir M, Freedman D. Basic epidemiology of infec-
States, 1997–2011. MMWR Surveill Summ. 2013 Jul. tious diseases, including surveillance and reporting.
19;62:1–23. In: Zuckerman J, Leggat P, Brunette G, editors. Essential
5. LaRocque RC, Rao SR, Lee J, Ansdell V, Yates JA, Travel Medicine. Chichester (UK): John Wiley &
Schwartz BS, et al. Global TravEpiNet: a national Sons; 2015.
consortium of clinics providing care to inter- 10. United Nations World Tourism Organization. UNWTO
national travelers—analysis of demographic Tourism Highlights, 2016 ed. [Internet]. Madrid: World
characteristics, travel destinations, and pre- Tourism Organization; 2016 [cited 2016 Mar. 26].
travel healthcare of high-risk US international Available from: http://media.unwto.org/press-release/
travelers, 2009–2011. Clin Infect Dis. 2012 Feb. 2016-01-18/international-tourist-arrivals-4-reach-
15;54(4):455–62. record-12-billion-2015.
8 INTRODUCTION
9
…perspectives
WHY GUIDELINES DIFFER 1
David R. Shlim, Alan J. Magill*
* Deceased.
10 INTRODUCTION
11
1
scribe. The travel medicine the process for regulatory recommended after 2 years,
practitioner needs to review approvals varies greatly. but in most European coun-
the available literature to For example, registering a tries, a booster is recom-
keep up with changing anti- new vaccine or antimalarial mended after 3 years. In the
biotic resistance and the drug in the United States is a United States, a packet of
epidemiology of diarrhea in costly and rigorous process. 4 oral typhoid capsules
various destinations. If the market is insufficient is dispensed, whereas in
to justify the expense of Europe, 3 doses are con-
WHY DO registration, then a commer- sidered adequate. The reg-
GUIDELINES cial company may not seek ulatory agencies may have
DIFFER? registration in a particular reviewed the same data and
Guidelines in different coun- country. The standards for drawn different conclusions,
tries and organizations may licensure vary, and what may or they may have reviewed
differ in substantial ways. be sufficient for one regula- different data at separate
Some of the reasons why tory authority may not suffice times and reached different
guidelines differ include for another. For example, conclusions. Regulatory sub-
availability of products in dif- primaquine, an option for missions to various agencies
ferent countries, a different malaria chemoprophylaxis rarely are ready and occur at
cultural perception of risk, in the United States, is not the same time; therefore, the
lack of evidence (or differing registered or commercially data available for review by
interpretations of the same available in Switzerland. each agency may not be the
evidence), and sometimes Atovaquone-proguanil was same, for legitimate reasons.
just honest differences in available for malaria che-
opinion among experts. moprophylaxis in the United Perception of Risk
Occasionally, public opinion States before many other People from varying back-
may influence recommen- countries. On the other hand, grounds can view the
dations (for example, the a vaccine against tickborne same risk data and come
widespread adverse publicity encephalitis is approved for to different conclusions
about mefloquine that was use and widely available as to the cost and benefit
reported in the media). in many countries, but is of preventing that risk.
not approved by the FDA; For example, national-
Availability therefore, CDC and ACIP level recommendations
of Products guidelines do not include any to prevent malaria while
Travel health providers recommendations for the traveling to India vary
can only use the products use of this vaccine. widely. Germany does
that are available to them. Even when the same not recommend using
Availability is determined products are available, standard prophylaxis for
by the regulatory approval the recommendations for any travel to an Indian
status of the product and, their use may differ. The destination; standby emer-
to a lesser extent, the mar- injectable capsular polysac- gency treatment (SBET
keting and distribution plan charide typhoid vaccine and or self-treatment) is the
of the manufacturer. Among the oral typhoid vaccine are recommendation for iden-
the various vaccines and examples. In the United tified risk destinations.
(continued)
12 INTRODUCTION
3 1
1
7. World Health Organization.
from: https://www.gov.uk/ 5. German Society for Tropical International Health
government/uploads/system/ Medicine and International Regulations (2005).
uploads/attachment_data/ Health Association (DTG). Geneva: World Health
file/337761/Guidelines_for_ [Recommendations for Organization; 2008 [cited
malaria_prevention_in_ malaria prevention]. 2015 2016 June 14]; Available
travellers_UK_PC.pdf. [cited 2016 June 14]; Available from: http://www.who.int/ihr/
4. Committee to Advise on from: http://www.dtg.org/ 9789241596664/en/index.html.
Tropical Medicine and malaria.html. 8. World Health Organization.
Travel (CATMAT). Canadian 6. Hill DR, Ericsson CD, International Travel and
recommendations for the Pearson RD, Keystone JS, Health. Geneva: World Health
prevention and treatment of Freedman DO, Kozarsky PE, Organization; 2012 (with 2016
malaria. Ottawa: Public Health et al. The practice of travel updates) [cited 2016 June 14];
Agency of Canada; 2014 medicine: guidelines by the Available from: http://www.
[cited 2016 June 14]. Available Infectious Diseases Society of who.int/ith/en/.
from: http://publications.
Perspectives sections are written as editorial discussions aiming to add depth and clinical perspective to the official
recommendations contained in the book. The views and opinions expressed in this section are those of the authors and
do not necessarily represent the official position of CDC.
AIR TRAVEL TRENDS
Andre D. Berro
The increased complexity and extent of the global 2015. Map 1-1 shows the spatial distribution of
aviation network can accelerate the spread of these passengers by destination country. Five
communicable diseases of public health concern. destination countries (Mexico, Canada, United
Recently, air travel has been a factor in the spread of Kingdom, Japan, and China) account for 40% of
Ebola, Middle East respiratory syndrome (MERS), all outbound international air travel from the
and Zika. International airlines connect approxi- United States. Table 1-1 below shows the volume
mately 40,000 global cities and carry about 3 bil- and proportion of air travelers from the United
lion total passengers per year. Growth in air travel States into each of the top 10 destination coun-
over time reflects a volume growth on established tries in 2015.
routes and a nodal growth where more airports Seasonal trends in travel are discernible from
and cities globally are connected. Understanding year to year; overall outbound travel peaks in the
the overall trends of global air travel can inform the summer and has its nadir in February. Seasonal
response to issues of public health concern and trends also vary by destination. For example,
allow for targeted mitigating measures to limit the although outbound travel volume to Europe
spread of communicable diseases. peaks in June, the volume of passengers to the
About 100 million passengers flew from the Caribbean, Latin America, and sub- Saharan
United States to overseas destinations during Africa peaks during December.
14 INTRODUCTION
5 1
During 2014, approximately 83% of the US res- passengers per year by 2034. China and the United
idents who traveled overseas did so for vacation States are anticipated to lead the growth volume.
or to visit family and friends and 17% for business. The fastest-growing routes include those to
US residents traveling abroad made reservations Africa, Asia, and South America; travel to countries
on average 68 days before departure. This period
should allow travelers time to schedule a pretravel
such as the Central African Republic, Ethiopia,
Malawi, Rwanda, Sierra Leone, Tanzania, and
1
consultation to get recommended vaccinations Uganda, considered to be at high risk for travel-
and learn about health precautions. related diseases, is expected to double in volume
over the next decade. This growth could lead to
PROJECTIONS increased exposures to communicable diseases.
According to the International Air Transport Public health planners, responders, and cli-
Association (IATA), the combined global volume nicians will need to take these projections into
of inbound and outbound air travel is projected account when developing strategies to prevent
to more than double and reach 7 billion total the spread of communicable diseases of public
health concern through international travel.
BIBLIOGRAPHY
1. Chen LH, Wilson ME. The role of the traveler in emerg- 5. International Air Transport Association. FMg DM.
ing infections and magnitude of travel. Med Clin North Global passengers volume based on ticket settlement
Am. 2008 Nov;92(6):1409–32. data from ARC and IATA. 2015 [cited 2016 Apr. 05].
2. Hui DS, Perlman S, Zumla A. Spread of MERS to 6. Musa EO, Adedire E, Olayinka A, Adeoye O, Adewuyi P,
South Korea and China. Lancet Respir Me. 2015 Waziri N, et al. Epidemiological profile of the Ebola virus
Jun 4;3(7):509–10. disease outbreak in Nigeria July–September 2014. Pan
3. International Air Transport Association. Afr Med J. 2014;21(1):331.
100 Years of Commercial Flight | Small World, 7. Musso D. Zika Virus Transmission from French
Big Future. [cited 2016 Mar. 21]; Available from: Polynesia to Brazil (Letter). Emerg Infect Dis. 2015
http://flying100years.com/. Oct;21(10).
4. International Air Transport Association. IATA Air 8. US Department of Commerce International Trade
Passenger Forecast Shows Dip in Long-Term Demand. Administration. Profile of U.S. Resident Travelers
The International Air Transport Association (IATA), Visiting Overseas Destinations: 2014 Outbound. 2014
2015 [updated Nov. 2015; cited 2016 Apr. 5]; Available [cited 2016 Apr. 05]; Available from: http://travel.trade.
from: http://www.iata.org/pressroom/pr/Pages/ gov/outreachpages/download_data_table/2014_
2015-11-26-01.aspx. Outbound_Profile.pdf.
The Pretravel
Consultation
THE PRETRAVEL CONSULTATION
Lin H. Chen, Natasha S. Hochberg, Alan J. Magill
The pretravel consultation offers a dedicated time the health beliefs of the traveler. Counseling by
to prepare travelers for the health concerns that trained staff can effectively deliver many mes-
might arise during their trips. The objectives of sages, such as those regarding the need for appro-
the pretravel consultation are: priate immunizations, and malaria risk and
prevention. Familiarity with the traveler’s des-
1. To perform an individual risk assessment.
tination, its culture, infrastructure, and disease
2. To educate the traveler regarding anticipated patterns can assist the travel health advisor in
health risks and methods for prevention. providing more personalized advice.
Travel medicine specialists have in- depth
3. To provide immunizations for vaccine-
knowledge of immunizations, risks associated
preventable diseases and medications for
with specific destinations, and the implications
prophylaxis, self-treatment, or both.
of traveling with underlying conditions. Therefore,
a comprehensive consultation with a travel med-
THE TRAVEL HEALTH icine expert is indicated for any traveler with a
SPECIALIST complicated health history, special risks (such
The outcome of a pretravel consultation likely as traveling at high altitudes or working in refu-
depends on the fund of knowledge, expertise, and gee camps), or exotic or complicated itinerar-
communication skills of the provider, as well as ies. Those clinicians who wish to be travel health
providers are encouraged to take advantage of health risks at the destination and how to miti-
one of the many travel health educational oppor- gate them. The typical pretravel consultation does
tunities available, join the International Society of not include a physical examination; a separate
Travel Medicine, attend conferences, and obtain appointment with the same or a different pro-
their Certificate in Travel Health. vider may be necessary to assess a person’s fitness
to travel. Because the traveler does not need to be
COMPONENTS OF A PRETRAVEL physically present to receive pretravel education,
CONSULTATION
Effective pretravel consultations require atten-
pretravel consultations are ideally suited to be
done remotely. In addition, because travel medi-
2
tion to the health background of the traveler and cine clinics are not available in many communi-
incorporate the itinerary, trip duration, travel pur- ties, remote consultations can give more travelers
pose, and activities, all of which determine health access to the information they need.
risks (Table 2-1). The pretravel consultation is the Travel health advice should be personal-
major opportunity to educate the traveler about ized, highlighting the likely exposures and also
Trip Details
Itinerary • Countries and specific regions, including order of countries if >1 country
• Rural or urban
(continued)
reminding the traveler of ubiquitous risks, such may confront special risks. Recent hospitalization
as injury, foodborne and waterborne infec- for serious problems may lead the advisor to rec-
tions, vectorborne disease, respiratory tract ommend delaying travel. Air travel is contrain-
infections, and bloodborne and sexually trans- dicated for certain conditions, such as <3 weeks
mitted infections. Written information is essen- after an uncomplicated myocardial infarction and
tial to supplement the discussion and highlight <10 days after thoracic or abdominal surgery. The
key advice for travelers. Balancing the cautions travel health provider and traveler should con-
with an appreciation of the positive aspects of sult with the relevant health care providers most
the journey leads to a more meaningful pre- familiar with the underlying illnesses. Other trav-
travel consultation. Attention to the cost of elers with specific risks include travelers who are
recommended interventions may be critical. visiting friends and relatives, long-term travelers,
Some travelers may not be able to afford all of travelers with chronic illnesses, immunocompro-
the recommended immunizations and medica- mised travelers, pregnant travelers, and travelers
tions, a situation that requires prioritizing inter- with small children. More comprehensive dis-
ventions. (See Perspectives: Prioritizing for the cussion on advising travelers with specific needs
Resource-Limited Traveler later in this chapter.) is available in Chapter 8. Providers should deter-
mine whether recent outbreaks or other safety
Assess Individual Risk notices have been posted for the traveler’s desti-
Many elements merit consideration in assessing a nation; information is available on the CDC web-
traveler’s health risks (Table 2-1). Certain travelers site and in various other resources.
In addition to recognizing the traveler’s char- whether there is sufficient time before travel to
acteristics, health background, and destination- complete a vaccine series; the purpose of travel
specific risks, the exposures related to special and specific destination within a country will
activities also merit discussion. For example, inform the need for particular vaccinations. At
river rafting could expose a traveler to schistoso- the same time, the pretravel consultation pres-
miasis or leptospirosis, and spelunking in Central ents an opportunity to update routine vaccines
America could put the traveler at risk of histo- (Table 2-2). Particular attention should be paid
plasmosis. Flying from lowlands to high-altitude
areas and trekking or climbing in mountainous
to vaccines for which immunity may have waned
over time or a recent immunocompromising con-
2
regions introduces the risk of altitude illness. dition (such as after a hematopoietic stem cell
Therefore, the provider should inquire about transplant). Asking the question, “Do you have
plans for specific activities. any plans to travel again in the next 1–2 years?”
may help the traveler justify an immunization for
Manage Risk this particular trip, such as rabies preexposure or
Immunizations are a crucial component of pre- Japanese encephalitis. Travelers should receive
travel consultations, and the risk assessment a record of immunizations administered and
forms the basis of recommendations for travel instructions to follow up as needed to complete
vaccines. For example, providers should consider a vaccine series.
Routine Vaccines
Hepatitis B Recommended for travelers visiting countries where HBsAg prevalence is ≥2%.
Vaccination may be considered for all international travelers, regardless of destination,
depending upon the traveler’s behavioral risk and potential for exposure as determined by
the provider and traveler.
Human papillomavirus No report of travel-acquired infection; however, sexual activity during travel may lead
(HPV) to HPV and other sexually transmitted infections.
Influenza Year-round transmission may occur in tropical areas. Outbreaks have occurred on
cruise ships, and 2009 influenza A (H1N1) illustrated the rapidity of spread via travel.
Novel influenza viruses such as avian influenza H5N1 and H7N9 can be transmitted to
travelers visiting areas with circulation of these viruses.
Measles, mumps, Infections are common in countries and communities that do not immunize children
rubella routinely, including Europe. Outbreaks have occurred in the United States as a result of
infection in returning travelers.
Meningococcal Outbreaks occur regularly in sub-Saharan Africa in the “meningitis belt” during
the dry season, generally December through June, although transmission may
occur at other times for those with close contact with local populations. Outbreaks
have occurred with Hajj pilgrimage, and the Kingdom of Saudi Arabia requires the
quadrivalent vaccine for pilgrims.
(continued)
2 Polio Unimmunized or underimmunized travelers can become infected with either wild
poliovirus or vaccine-derived poliovirus. Because the international spread of wild
poliovirus in 2014 was declared a Public Health Emergency of International Concern
under the International Health Regulations, temporary recommendations for
polio vaccination are in place for countries with wild poliovirus circulation for their
residents, long-term visitors, and international travelers.
Rotavirus Common in developing countries, although not a common cause of travelers’ diarrhea
in adults. The vaccine is only recommended in young children.
Tetanus, diphtheria, Rare cases of diphtheria have been attributed to travel. Pertussis has occurred in
pertussis travelers, recently in adults whose immunity has waned.
Varicella Infections are common in countries that do not immunize children routinely, as in most
developing countries. Naturally occurring disease also occurs later in tropical countries.
Zoster Travel (a form of stress) may trigger varicella zoster reactivation, but causal
relationship is difficult to establish.
Travel Vaccines
Cholera Cases in travelers have occurred recently in association with travel to the Dominican
Republic and Haiti.
Hepatitis A Prevalence patterns of hepatitis A virus infection may vary among regions within a
country, and missing or obsolete data present a challenge. Serologic testing may
be considered in travelers from highly endemic countries since they may already be
immune. Some expert travel clinicians advise people traveling outside the United
States to consider hepatitis A vaccination regardless of their country of destination.
Japanese encephalitis Rare cases have occurred, estimated at <1 case/1 million travelers to endemic countries.
Tickborne encephalitis Cases have been identified in travelers with an estimated risk of 1/10,000 person-
(vaccine not available in months in travelers. Endemic areas are expanding in Europe.
the United States)
Typhoid UK surveillance found the highest risk to be travel to India (6 cases/100,000 visits),
Pakistan (9 cases/100,000 visits), and Bangladesh (21 cases/100,000 visits), although
risk is substantial in many destinations.
Yellow fever Risk occurs mainly in defined areas of sub-Saharan Africa and the Amazonian
regions of South America. Some countries require proof of vaccination for entry.
For travelers visiting multiple countries, order of travel may make a difference in the
requirements.
Another major focus of pretravel consultations to discuss with their primary care provider how to
for many destinations is the prevention of malaria. plan for treatment and bring necessary medication
Malaria continues to cause substantial morbidity in case of asthma exacerbation. Travelers should
and mortality in travelers. In 2011, the number of be counseled on how they can find reputable med-
US malaria cases reported to CDC was the highest ical facilities at their destination, such as using the
since 1971; therefore, pretravel consultation must ISTM website (www.istm.org) or the American
carefully assess travelers’ risk for malaria and rec- Society of Tropical Medicine and Hygiene website
ommend preventive measures. For travelers going
to malaria-endemic countries, it is imperative to
(www.astmh.org) to find suitable clinics. Any aller-
gies or serious medical conditions should be iden-
2
discuss malaria transmission, ways to reduce risk, tified on a bracelet or a card to expedite medical
and recommendations for chemoprophylaxis. care in emergency situations.
Travelers with underlying health conditions The pretravel consultation also provides another
require attention to their health issues as they setting to remind travelers of basic health practices
relate to the destination and activities. For exam- during travel, including frequent handwashing,
ple, a traveler with a history of cardiac disease wearing seatbelts, and using car seats for infants
should carry medical reports, including a recent and children. Topics to be explored are numerous
electrocardiogram. Asthma may flare in a trav- and could be organized into a checklist, placing pri-
eler visiting a polluted city or from physical exer- ority on the most serious and frequently encoun-
tion during a hike; travelers should be encouraged tered issues (Table 2-3). General issues such as
Other vectorborne • Define risk of disease in specific itinerary and insect precautions needed.
diseases
Respiratory • Discuss areas of particular concern (such as avian influenza in Asia or MERS in the
illnesses Arabian Peninsula).
• Consider influenza treatment for high-risk travelers.
Altitude illness • Determine if the itinerary puts the traveler at risk of altitude illness.
• Discuss preventive measures such as gradual ascent, adequate hydration, and
medications to prevent and treat.
(continued)
2 • Advise travelers to avoid wading or swimming in freshwater where there is risk for
schistosomiasis or leptospirosis.
• Remind travelers to apply sunscreen to skin exposed to the sun.
Personal safety • Discuss precautions travelers can take to minimize risks specific to the trip, such as
traffic accidents, alcohol excess, personal assault, robbery, or drowning.
• Provide information on travel health and medical evacuation insurance.
• Advise travelers to look for security bulletins related to their destination and consider
areas to avoid.
Sexual health • Caution the traveler to avoid activities that can lead to sexually transmitted infections,
and bloodborne unwanted pregnancy, or bloodborne infections.
pathogens • Remind travelers to use condoms if they do have sex.
• Inform travelers who will provide health care overseas what to do in case of needlestick
or bloodborne pathogen exposure.
preventing injury and sunburn also deserve men- 50% of the drugs on the shelves) makes it more
tion. Written information is essential to supple- important for travelers to bring quality manu-
ment oral advice and enable travelers to review factured drugs with them from a reliable sup-
the instructions from their clinic visits; educational plier in their own country (see Perspectives:
material is available on the CDC Travelers Health Pharmaceutical Quality & Falsified Drugs later in
webpage (http://www.cdc.gov/travel). Advice on this chapter).
self-treatable conditions may minimize the need Travel health providers need to recognize the
for travelers to seek medical care while abroad and conditions for which the traveler may be at risk
possibly lead to faster return to good health. and educate the traveler about the diagnosis and
treatment of those particular conditions. The keys
Self-Treatable Conditions to successful self-treatment strategies are provid-
Despite providers’ best efforts, some travelers will ing a simple disease or condition definition, pro-
become ill. Obtaining reliable and timely medical viding a treatment, and educating the traveler
care during travel can be problematic in many about the expected outcome of treatment. Using
destinations. As a result, prescribing certain med- travelers’ diarrhea as an example, a practitioner
ications in advance can empower the traveler to could provide the following advice:
self-diagnose and treat common health problems.
With some activities in remote settings, such as • “Travelers’ diarrhea” is the sudden onset of
trekking, the only alternative to self-treatment abnormally loose, frequent stools.
would be no treatment. Pretravel counseling may
actually result in a more accurate self-diagnosis
• Most cases will resolve within 2–5 days, and
symptoms can be managed with loperamide
and treatment than relying on local medical care
or bismuth subsalicylate.
in some areas. In addition, the increasing aware-
ness of substandard and counterfeit drugs in • For diarrhea severe enough to interrupt travel
pharmacies in the developing world (as many as plans, an antibiotic can be prescribed that
travelers can carry with them (see Travelers’ • Jet lag (see section in this chapter)
Diarrhea section in this chapter).
• Motion sickness (see section in this chapter)
• The traveler should feel better within
6–24 hours. • Respiratory infections (see section in this
chapter)
• If symptoms persist for 24–36 hours despite
self-treatment, it may be necessary to seek • Skin conditions: skin reactions due to allergic
medical attention. or irritant triggers usually respond to topical
steroids; discomfort from superficial fungal 2
To minimize the potential negative effects of a infections respond to antifungal creams. See
self-
treatment strategy, the recommendations Chapter 5, Skin and Soft Tissue Infections in
should follow a few key points: Returned Travelers.
• Drugs recommended must be safe, well toler- • Urinary tract infections: common among
ated, and effective for use as self-treatment. many women; carrying an antibiotic for
• A drug’s toxicity or potential for harm, if used empiric treatment may be valuable.
incorrectly or in an overdose situation, should • Vaginal yeast infections: self-treatment
be minimal. course of patient’s preferred antifungal med-
• Simple and clear directions are critical. ication can be prescribed for women who
Consider providing handouts describing are prone to infections, sexually active, or
how to use the drugs. Keeping the directions who may be receiving antibiotics for other
simple will increase the effectiveness of the reasons (including doxycycline for malaria
strategy. chemoprophylaxis).
The following are some of the most common situ- • Occupational exposure to HIV (see Chapter 8,
ations in which people would find self-treatment Health Care Workers)
useful. The extent of self-treatment recommen- • Malaria self-treatment (see Chapter 3,
dations offered to the traveler should reflect Malaria)
the remoteness and difficulty of travel and the
availability of reliable medical care at the partic- In sum, travelers should be encouraged to carry
ular destination. The recommended self-treat- a travel health kit with prescription and nonpre-
ment options for each disease are provided in scription medications. Providers should review
the designated section of the Yellow Book or medication lists for possible drug interactions.
discussed below. More detailed information for providers and trav-
elers is given in Chapter 2, Travel Health Kits;
• Travelers’ diarrhea (see section in this chapter) supplementary travel health kit information for
• Altitude illness (see section in this chapter) travelers with specific needs is given in Chapter 8.
BIBLIOGRAPHY
1. Freedman DO, Chen LH, Kozarsky P. Medical con- 4. International Society of Travel Medicine. Body of
siderations before travel. N Engl J Med. 2016 July knowledge for the practice of travel medicine—2012.
21;375:247–6 0. Atlanta: International Society of Travel Medicine; 2012
2. Hatz CFR, Chen LH. Pre-travel consultation. [cited 2016 Oct. 1]; Available from: http://www.istm.org/
In: Keystone JS, Freedman DO, Kozarsky PE, Connor bodyofknowledge.
BA, Nothdurft HD, editors. Travel Medicine. 3rd ed. 5. LaRocque RC, Rao SR, Lee J, Ansdell V, Yates JA,
Philadelphia: Saunders Elsevier; 2013. pp. 31–6. Schwartz BS, et al. Global TravEpiNet: a national con-
3. Hill DR, Ericsson CD, Pearson RD, Keystone JS, sortium of clinics providing care to international trav-
Freedman DO, Kozarsky PE, et al. The practice of elers—analysis of demographic characteristics, travel
travel medicine: guidelines by the Infectious Diseases destinations, and pretravel healthcare of high-risk US
Society of America. Clin Infect Dis. 2006 Dec international travelers, 2009–2011. Clin Infect Dis. 2012
15;43(12):1499–539. Feb 15;54(4):455–62.
6. Leder K, Chen LH, Wilson ME. Aggregate travel vs. 8. Schwartz BS, Larocque RC, Ryan ET. In the clinic: travel
single trip assessment: arguments for cumulative risk medicine. Ann Intern Med. 2012 Jun 5;156(11):ITC6:1–16.
analysis. Vaccine. 2012 Mar 28;30(15):2600–4. 9. Steffen R, Behrens RH, Hill RD, Greenaway C, Leder K.
7. Leder K, Torresi J, Libman MD, Cramer JP, Castelli F, Vaccine-preventable travel health risks: what is the
Schlagenhauf P, et al. GeoSentinel surveillance of illness evidence—what are the gaps? J Travel Med. 2015;22(1):1–12.
in returned travelers, 2007–2011. Ann Intern Med. 2013 10. Steffen R, Hill DR, DuPont HL. Traveler’s Diarrhea: a
Mar 19;158(6):456–68. clinical review. JAMA. 2015 Jan 6, 2015;313(1):71–80.
…perspectives
TRAVELERS’ PERCEPTION OF RISK
David R. Shlim
2
Travel medicine is based on deaths per 100,000 trekkers, just as the risks of staying
the concept of the reduc- but there is no objective way home are not zero. Even
tion of risk. In the context to determine whether this the act of trying to prevent a
of travel medicine, “risk” risk is high or low. When the risk—such as yellow fever—
refers to the possibility of manuscript that reported can lead to a fatal reaction
harm during the course of a this risk of dying while trek- to the vaccine in rare cases.
planned trip. Some risks may king was peer-reviewed, one Therefore, the goal in travel
be avoidable, and others may reviewer wrote, “You need to and in travel medicine should
not. Vaccine-preventable emphasize that these data be skillfully managing risk,
diseases may be mostly show how dangerous trek- rather than trying to eliminate
avoidable, depending on the king actually is.” The other risk. The pretravel consul-
risk of the disease and the reviewer wrote, “You should tation is an opportunity to
protective efficacy of the vac- make a point of stating that discuss risks and develop
cine. Non-disease risks, such these data show how safe plans that minimize these
as motor vehicle accidents trekking is.” risks. Each traveler will have
or drowning, account for a The subjective sense of individual concepts about the
much higher percentage of risk is based on one’s percep- risks and benefits of vaccines,
deaths among travelers than tion of risk (“15 per 100,000 prophylaxis, and behavior
infectious diseases. means it’s dangerous”) and modification.
For many years, travel one’s tolerance for risk (“it Travelers should also
medicine practitioners have may be 15 per 100,000, but consider the psychologi-
felt that if they knew the it’s worth it”). This subjective cal and emotional aspects
statistics for a given risk, sense of risk suffuses the of foreign travel. Culture
they could objectively advise field of travel medicine, but shock can occur on either
travelers about that risk. it is rarely discussed. Some end of a journey: on arrival
However, it has become travelers canceled travel when one encounters an
clear that the perception and plans to Asia because of their entirely strange new world,
tolerance of risk are sub- fear of H5N1 avian influenza, and on return when one’s
jective factors that must be even though the actual risk own world may temporarily
considered when addressing to travelers was virtually appear unfamiliar. Travelers
risks of travel. Travel health zero. Other travelers plan with underlying psychiat-
providers may know statistics to ascend Mount Everest, ric conditions should be
for a given risk, but whether even though the risk of dying cautious when heading out
the risk is considered high during an Everest climb is to a stressful new environ-
or low depends on the per- 1 in 40. ment, particularly if they are
ception of the traveler or the Regardless of the per- traveling alone.
travel medicine provider. For ception and tolerance of risk, Travel medicine providers
example, the risk of dying the hazards associated with should promote the under-
while trekking in Nepal is 15 travel cannot be eliminated, standing of the concept of
(continued)
commitment, the idea that country with no advanced Travel medicine practi-
certain parts of a journey cardiac services may have tioners should explore their
cannot easily be reversed. a difficult time getting to own perception and tolerance
A person trekking into a definitive medical care. If the of risk, so that they can help
2 remote area may need to traveler has already contem- travelers find their individual
accept that rescue, if avail- plated these concerns and comfort level when making
able at all, may be delayed accepted them, it will be eas- decisions about destinations,
for days. A person who has ier to deal with them if they activities, and prophylactic
a myocardial infarction in a come to pass. measures.
Perspectives sections are written as editorial discussions aiming to add depth and clinical perspective to the official
recommendations contained in the book. The views and opinions expressed in this section are those of the author and do
not necessarily represent the official position of CDC.
…perspectives
PRIORITIZING CARE FOR THE
RESOURCE-LIMITED TRAVELER
Zoon Wangu, Elizabeth D. Barnett
2
Travelers seen in pretravel health insurance and evacu- the traveler may be denied
clinic consultations often ation insurance before travel entry to the country without
have financial constraints. must also be considered proof of vaccination. Note
Prioritizing immunizations (see Travel Insurance, Travel that travelers who may be
and prophylactic medica- Health Insurance, & Medical staying in a yellow fever–
tions should be part of an Evacuation Insurance later endemic country only briefly
individualized assessment in this chapter). Clinicians (such as during an airport
based on the travel itinerary, need to understand trav- layover) may still need evi-
efficacy and safety of vac- elers’ financial constraints dence of vaccination to enter
cines and medications, and in order to provide realistic other countries on their
associated costs. Travelers recommendations. The itinerary. In a few specific
must often pay out of pocket variety of insurance plans, circumstances, travelers to
for pretravel care, as many number of travelers without countries that are exporting
health insurance plans do adequate insurance cover- polio may be asked to show
not cover travel immuni- age, and number of student proof of polio vaccination
zations or prophylaxis. As and budget travelers chal- before they are allowed
an example, the estimated lenges even the most savvy to leave those countries if
cost of a US pretravel con- travel medicine clinicians. they have spent >4 weeks in
sultation for a backpacker This section provides guid- the country (see Chapter 3,
planning a 4-week trip to ance for busy practitioners Poliomyelitis).
West Africa may be as high in prioritizing vaccine and
as $1,400 for the initial con- prophylaxis choices. Routine Vaccines
sultation and vaccinations, All travelers should be
excluding malaria chemo- VACCINES up-to-date with routine
prophylaxis. Travelers with Required Vaccines vaccines before interna-
limited budgets may be Only 2 vaccines are required tional travel, regardless of
at higher risk for travel- categorically for some destination. The benefits of
associated infections, as travelers: meningococcal vaccines extend beyond the
they often visit remote areas, vaccine for pilgrims travel- travel period, and in many
stay in lower-grade accom- ing to Mecca during the Hajj cases lifelong immunity is
modations, and are more and yellow fever vaccine for achieved. Routine vaccines
likely to eat local street food. travelers to certain countries are generally associated
Therefore, the cost of dis- in Africa and South America with lower costs, since they
ease (such as malaria) may, (see Chapter 3, Yellow Fever are mass-produced as part
in many cases, outweigh & Malaria Information, by of the scheduled national
costs of vaccination and Country). If either of these childhood and adult vacci-
prophylaxis. The financial vaccines is required for an nation programs, and many
benefits of obtaining travel itinerary, prioritize it since health insurance plans will
(continued)
reimburse the patient for duration is short) because advice about preventing
the cost of vaccine admin- of the relatively low efficacy, mosquito bites (see
Perspectives sections are written as editorial discussions aiming to add depth and clinical perspective to the official
recommendations contained in the book. The views and opinions expressed in this section are those of the authors and
do not necessarily represent the official position of CDC.
…perspectives
THE NEED FOR A COST ANALYSIS
TO JUSTIFY THE TRAVEL
2 MEDICINE CONSULT
Emily P. Hyle, Edward T. Ryan
are largely borne by the pub- not only to trace and limit A vaccination, typhoid vacci-
lic health sector and there- ongoing disease transmission nation, and travelers’ diarrhea
fore do not usually appear but also to mitigate the risk strategies. Unfortunately,
in the financial calculus of of establishing environmental many of these analyses were
the individual traveler or the or animal reservoirs in home performed decades ago.
2
insurance carrier. communities. Such a model A reasonable approach would
could then be used to exam- therefore be to develop mod-
MATHEMATICAL ine the effect of a pretravel eling approaches for major
MODELING FOR encounter on different popu- groups of travel-related
TRAVEL MEDICINE lations of travelers. Because illnesses, using available
Mathematical modeling only some travelers seek current data regarding the
allows for a comprehensive pretravel evaluation, a model pretravel encounter from
investigation of the value could examine the effect when the GlobalTravEpiNet (GTEN)
of the pretravel medical different percentages of the consortium (see Chapter 1,
encounter. By incorporating traveling population obtain Travel Epidemiology) and
best estimates of bene- pretravel evaluation. other large consortiums.
fits and costs for pretravel A modeling approach can The goals of such analyses
encounters, travel exposures, also be used to perform sen- could include defining core
and travel-related illness, a sitivity analyses, in which a metrics for pretravel encoun-
model can project possible range of values for a specific ters, improving the value of
outcomes and costs for dif- input parameter is exam- pretravel encounters, and
ferent travelers, exposures, ined in terms of the impact examining where improve-
risks of infection, and effec- on the outcome of interest. ments in pretravel medicine
tiveness of pretravel interven- Sensitivity analyses can evalu- would result in maximally
tions singly or in combination. ate thresholds, or the specific improved patient outcomes
A comprehensive model of value at which a parameter and cost-effectiveness. These
the pretravel encounter would results in a meaningful separate models could then
examine the range of possible change in clinical outcomes be incorporated into a single
illnesses posed by an itiner- or costs. Uncertain data esti- integrated analysis that would
ary, including those that pres- mates or assumptions are address a comprehensive
ent long after return (such as assessed by using a model in pretravel encounter. Such an
tuberculosis or HIV) or that a similar fashion, investigat- approach will not be easy, but
lead to chronic sequelae (such ing at what values such esti- it is necessary.
as neurologic damage from mates will result in clinically
cerebral malaria, Japanese meaningful changes. Results
encephalitis, or Zika infec- from a pretravel model could BIBLIOGRAPHY
tion). Such a model would highlight where further data
1. Adachi K, Coleman MS, Khan
incorporate the effect of any would be high-yield and worth N, Jentes ES, Arguin P, Rao SR,
pretravel intervention on investing research dollars. et al. Economics of malaria
mitigating the risk of infection A logical way forward is prevention in US travelers to
while traveling as well as to begin by focusing initial West Africa. Clin Infect Dis.
2014 Jan;58(1):11–21.
possible side effects of the analyses around a number of
2. Behrens RH, Roberts JA.
intervention. Models should core areas. Studies have been
Economic appraisal of prophy-
incorporate the costs of public published that investigate lactic measures against malaria,
health–related resources and a specific component of the hepatitis A, and typhoid in trav-
expenditures relating to the pretravel encounter, including ellers. BMJ Clinical Research Ed.
importation of pathogens, malaria prophylaxis, hepatitis 1994 Oct 8;309(6959):918–22.
(continued)
2
AE, Wallace GS. The economic Aug;10(8):681–3. Recommendations for report-
burden of sixteen measles out- 5. Reves RR, Johnson PC, ing cost-effectiveness analyses.
breaks on United States public Ericsson CD, DuPont HL. A JAMA. 1996;276(16): 1339–41.
health departments in 2011. cost-effectiveness comparison 7. Van Doorslaer E, Tormans
Vaccine. 2014;32(11):1311–7. of the use of antimicrobial G, Van Damme P. Cost-
4. Papadimitropoulos V, agents for treatment or effectiveness analysis of
Vergidis PI, Bliziotis I, Falagas prophylaxis of travelers’ vaccination against hepatitis
ME. Vaccination against diarrhea. Arch Intern Med. A in travellers. J Med Virol.
typhoid fever in travellers: a 1988;148(11):2421–7. 1994;44(4):463–9.
Perspectives sections are written as editorial discussions aiming to add depth and clinical perspective to the official
recommendations contained in the book. The views and opinions expressed in this section are those of the authors and
do not necessarily represent the official position of CDC.
GENERAL RECOMMENDATIONS
FOR VACCINATION &
IMMUNOPROPHYLAXIS
Andrew T. Kroger, Raymond A. Strikas
Recommendations for the use of vaccines and immunization issues and the use of specific vac-
other biologic products (such as immune globu- cines. Box 2-1 provides more information about
lin [IG] products) in the United States are devel- ACIP. This section is based primarily on the ACIP
oped by the Advisory Committee on Immunization General Recommendations on Immunization.
Practices (ACIP) and are harmonized with ACIP Evaluation of people before travel should
liaison organizations including the American include a review and provision of routine vac-
Academy of Pediatrics, the American Academy cines recommended based on age and other indi-
of Family Physicians, the American College of vidual characteristics. Additionally, some routine
Physicians, the American College of Obstetricians vaccines are recommended at earlier ages for
and Gynecologists, and others. Recommendations international travelers. For example, MMR (mea-
voted on by the ACIP are reviewed by the CDC sles-mumps-rubella) vaccine is recommended for
director and, if adopted, become official recom- infants aged 6–11 months who travel abroad to
mendations of the Department of Health and protect them from measles. Recommendations
Human Services/CDC upon publication in CDC’s for specific vaccines related to travel will depend
Morbidity and Mortality Weekly Report (MMWR). on itinerary, duration of travel, and host factors.
ACIP recommendations are based on scien- Vaccinations against diphtheria, tetanus, pertus-
tific evidence of benefits (disease immunity) and sis, measles, mumps, rubella, varicella, poliomyeli-
risks (vaccine adverse reactions) and, where tis, hepatitis A, hepatitis B, Haemophilus influenzae
few or no data are available, on expert opinion. type b (Hib), rotavirus, human papillomavirus
Recommendations include information on general (HPV), and pneumococcal and meningococcal
invasive disease are routinely administered in the most current schedules from the CDC Vaccines and
United States, usually in childhood or adolescence. Immunization website (www.cdc.gov/vaccines/
Influenza vaccine is routinely recommended for schedules). The text and many tables of this pub-
all people aged ≥6 months, each year. A dose of lication present recommendations for the use,
herpes zoster (shingles) vaccine is recommended number of doses, dose intervals, adverse reactions,
for adults aged ≥60 years. If a person does not have precautions, and contraindications for vaccines
a history of adequate protection against these dis- and toxoids that may be indicated for travelers.
eases, immunizations appropriate to age and pre- Recommendations for travelers are not always the
vious immunization status should be obtained, same as routine recommendations. For instance,
whether or not international travel is planned. most adults born after 1956 are recommended to
A visit to a clinician for travel-related immuniza- receive 1 dose of MMR vaccine; however, interna-
tions should be seen as an opportunity to bring an tional travelers of this age are recommended to
incompletely vaccinated person up-to-date on his receive 2 doses. For specific vaccines and toxoids,
or her routine vaccinations. additional details on background, adverse reac-
Both the child and adolescent vaccination tions, precautions, and contraindications, refer to
schedules, and an adult vaccination schedule, are the respective ACIP recommendations (www.cdc.
published annually. Clinicians should obtain the gov/vaccines/acip/index.html).
SPACING OF IMMUNOBIOLOGICS exceed its supply, and providers may have diffi-
culty obtaining vaccines. Information on vaccine
Simultaneous Administration shortages and recommendations can be found on
With some exceptions (such as PCV13 and the CDC Vaccines and Immunization website at
PPSV23, as well as PCV13 and MenACWY- D www.cdc.gov/vaccines/hcp/clinical-resources/
[Menactra]), all commonly used vaccines can shortages.html.
safely and effectively be given simultaneously (on In some cases, a scheduled dose of vaccine
2 the same day) at separate sites without impairing
antibody responses or increasing rates of adverse
may not be given on time. If this occurs, the dose
should be given at the next visit. However, trav-
reactions. This knowledge is particularly helpful elers may forget to return to complete a series or
for international travelers, for whom exposure to for a booster at the specified time. Available data
several infectious diseases might be imminent. indicate that intervals between doses longer than
Simultaneous administration of all indicated vac- those routinely recommended do not affect sero-
cines is encouraged for people who are the rec- conversion rate or titer when the schedule is com-
ommended age to receive these vaccines and for pleted. Consequently, it is not necessary to restart
whom no contraindications exist. If not admin- the series or add doses of any vaccine because of
istered on the same day, an inactivated vaccine an extended interval between doses. There are
may be given at any time before or after a differ- some exceptions to this rule. Some experts rec-
ent inactivated vaccine or a live-virus vaccine. ommend repeating the series of oral typhoid vac-
The immune response to an injected or intra- cine if the 4-dose series is extended to more than
nasal live-virus vaccine (such as MMR, varicella, 3 weeks. If an extended interval passes between
yellow fever, or live attenuated influenza vac- doses of the preexposure rabies vaccine series,
cines) might be impaired if administered within immune status should be assessed by serologic
28 days of another live- virus vaccine (within testing 7–14 days after the final dose in the series.
30 days for yellow fever vaccine). Whenever pos-
sible, injected live-virus vaccines administered Antibody-Containing Blood Products
on different days should be given ≥28 days apart Antibody- containing blood products from the
(≥30 days for yellow fever vaccine). If 2 injected United States, such as immune globulin (IG) prod-
or intranasal live-virus vaccines are not admin- ucts, do not interfere with the immune response
istered on the same day but <28 days apart to yellow fever vaccine and are not believed to
(<30 days for yellow fever vaccine), the second interfere with the response to live typhoid, live
vaccine should be repeated in ≥28 days (≥30 days attenuated influenza, rotavirus, or zoster vac-
for yellow fever vaccine). cines. When MMR and varicella vaccines are
Measles and other live- virus vaccines may given shortly before, simultaneously with, or after
interfere with the response to tuberculin skin test- an antibody-containing blood product, response
ing and the interferon-γ release assay. Tuberculin to the vaccine can be diminished. The dura-
testing, if otherwise indicated, can be done either tion of inhibition of MMR and varicella vaccines
on the day that live-virus vaccines are adminis- is related to the dose of IG in the product. MMR
tered or 4–6 weeks later. Tuberculin skin test- and varicella vaccines either should be adminis-
ing is not a prerequisite for administration of any tered ≥2 weeks before receipt of a blood product
vaccine. Oral typhoid vaccine, a live attenuated or should be delayed 3–11 months after receipt
bacterial vaccine, has not been associated with of the blood product, depending on the dose and
suppressing the response to tuberculosis testing. type of blood product (Table 2-4).
IG administration may become necessary for
Missed Doses and Boosters another indication after MMR or varicella vaccines
All vaccines require a primary dose or series have been given. In such a situation, the IG may
to ensure immunity, and some require periodic interfere with the immune response to the MMR
repeat, or booster, doses to maintain immu- or varicella vaccines. Vaccine virus replication and
nity. Occasionally, the demand for a vaccine may stimulation of immunity usually occur 2–3 weeks
(continued)
after vaccination. If the interval between adminis- serologic testing indicates antibodies have been
tration of one of these vaccines and the subsequent produced.
administration of an IG preparation is ≥14 days, the When IG is given with the first dose of hepatitis
vaccine need not be readministered. If the interval A vaccine, the proportion of recipients who develop
is <14 days, the vaccine should be readministered a protective level of antibody is not affected, but
after the interval shown in Table 2-4, unless sero- antibody concentrations are lower. Because the final
logic testing indicates that antibodies have been concentrations of antibody are many times higher
produced. Such testing should be performed after than those considered protective, this reduced
the interval shown in Table 2-4, to avoid detecting immunogenicity is not expected to be clinically rel-
antibodies from the IG preparation. evant. However, the effect of reduced antibody con-
If administration of IG becomes necessary, centrations on long-term protection is unknown.
MMR or varicella vaccines can be administered IG preparations interact minimally with other
simultaneously with IG, with the recognition inactivated vaccines and toxoids. Other inacti-
that vaccine-induced immunity can be com- vated vaccines may be given simultaneously, or
promised. The vaccine should be administered at any time interval before or after an antibody-
at a body site different from that chosen for the containing blood product is used. However, such
IG injection. Vaccination should be repeated vaccines should be administered at different sites
after the interval noted in Table 2- 4, unless from the IG.
(continued)
2
IPV-412 4–6 years 4 years NA
MPSV4–2 NA 7 years NA
PPSV-220 NA 7 years NA
(continued)
2
RV-222 4 months 10 weeks 4 weeks
1
Adapted from Table 1, CDC. General recommendations on immunization: recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 28;60(RR-2):1–61.
2
Combination vaccines are available. Use of licensed combination vaccines is generally preferred over separate injections
of their equivalent component vaccines (CDC. Combination vaccines for childhood immunization. MMWR Recomm
Rep. 1999 May 14;48[RR-5]:1–14.). When administering combination vaccines, the minimum age for administration is the
oldest age for any of the individual components (exception: the minimum age for the first dose of MenHibrix is 6 weeks); the
minimum interval between doses is equal to the largest interval of any of the individual components.
3
See www.cdc.gov/vaccines/schedules for recommended revaccination (booster) schedules.
4
Combination vaccines containing the HepB component are available (DTaP-HepB-IPV, HepA-HepB). DTaP-HepB-IPV
should not be administered to infants aged <6 weeks because of the other components ( DTaP, IPV). HepA-HepB is not
licensed in the United States for children aged <18 years.
5
Calendar months.
6
For Hib and PCV, children receiving the first dose of vaccine at ≥7 months of age require fewer doses to complete the
series (see the current childhood and adolescent immunization schedule at www.cdc.gov/vaccines).
7
If PRP-OMP (Pedvax-Hib, Merck Vaccine Division) was administered at 2 and 4 months of age, a dose at 6 months of age is
not indicated. The final dose has a minimum age of 12 months.
8
HepB-3 should be administered ≥8 weeks after Hep B-2 and ≥16 weeks after Hep B-1; it should not be administered
before age 24 weeks.
9
Herpes zoster (shingles) vaccine is recommended as a single dose for people aged ≥60 years.
10
Bivalent HPV vaccine is approved for girls/women aged 10–26 years. It is recommended to prevent cervical and other anogenital
cancers and precursors for girls/women aged 11–26 years. Quadrivalent HPV and 9vHPV vaccines are approved for boys/men and
girls/women aged 9–26 years. They are recommended to prevent cervical and other anogenital cancers, precursors, and genital
warts for girls/women aged 11–26 years. They are recommended for boys/men aged 11–21 years and high-risk boys or men
(men who have sex with men, HIV-positive men, or immunocompromised men) aged 22–26 years. They may be given to girls aged
9–10 years to prevent the same diseases, and to boys/men aged 9–10 years and 22–26 years to prevent genital warts.
11
The third dose of HPV should be administered ≥12 weeks after the second and ≥24 weeks after the first. Dose 3 need not
be repeated if administered ≥16 weeks after dose 1, as long as a minimum interval of 4 weeks is maintained between dose 1
and dose 2 and as long as a minimum interval of 12 weeks is maintained between dose 2 and dose 3.
12
For people receiving an all-IPV or all-OPV series, if the third dose is given after the fourth birthday, a fourth dose is not
needed. For IPV, the next-to-last and the last dose must be spaced by 6 months.
13
Two doses of influenza vaccine are recommended for children aged <9 years who are receiving the vaccine for the first
time, and for certain incompletely vaccinated children (see reference 2).
14
The minimum age for inactivated influenza vaccine varies by vaccine manufacturer. See package insert for vaccine-specific
minimum ages.
15
Ixiaro is approved by the Food and Drug Administration for people aged ≥2 months.
16
Combination MMR-varicella (MMRV) can be used for children aged 12 months through 12 years
17
If an infant 6–11 months of age is traveling internationally, a dose of MMR is recommended but does not count toward the
2-dose recommended series. The next dose should be administered at 12–15 months of age and a minimum of 4 weeks
from the international travel dose.
(continued)
lower antibody response than if given according shorter than the recommended minimum is dis-
to the recommended schedule. Intervals between couraged. Table 2-5 lists the minimum age and
doses longer than those routinely recommended minimum interval between doses for vaccines
do not decrease the immune response when the routinely recommended in the United States.
schedule is completed. Consequently, it is not Because some travelers visit their health
necessary to restart the series or add doses of any care providers at the last minute before depar-
vaccine because of an extended interval between ture, studies have been performed to deter-
doses, with the exceptions mentioned previously mine whether accelerated scheduling is
(oral typhoid vaccine and rabies vaccine). If a trav- adequate. This concern is primarily the case
eler needs yellow fever vaccination to meet a coun- for hepatitis B vaccine or the combined hep-
try requirement under the International Health atitis A and B vaccine. An accelerated sched-
Regulations, the yellow fever vaccine is not con- ule for combined hepatitis A and B vaccine
sidered valid until 10 days after administration. has been approved by the Food and Drug
Administration of a vaccine earlier than the Administration (FDA). It is unclear what level
recommended minimum age or at an interval of protection any given traveler will have if he
or she does not complete a full series of multi- an allergy should receive the vaccine. No recom-
dose vaccination. mended vaccine contains penicillin or penicillin
derivatives. Some vaccines (MMR vaccine, inac-
ALLERGY TO VACCINE tivated polio vaccine [IPV], hepatitis A vaccine,
COMPONENTS some hepatitis B vaccines, some influenza vac-
Vaccine components can cause allergic reac- cines, rabies vaccine, varicella vaccine, and small-
tions in some recipients. These reactions can be pox vaccine) contain trace amounts of neomycin
2 local or systemic and can include anaphylaxis or
anaphylactic-like responses. The vaccine compo-
or other antibiotics; the amount is less than would
normally be used for the skin test to determine
nents responsible can include the vaccine anti- hypersensitivity. However, people who have expe-
gen, animal proteins, antibiotics, preservatives rienced anaphylactic reactions to this antibiotic
(such as thimerosal), or stabilizers (such as gela- generally should not receive these vaccines. Most
tin). The most common animal protein allergen is often, neomycin allergy is a contact dermatitis—
egg protein in vaccines prepared by using embry- a manifestation of a delayed-type (cell-mediated)
onated chicken eggs (influenza and yellow fever immune response rather than anaphylaxis. A his-
vaccines). People with a history of egg allergy who tory of delayed-type reactions to neomycin is not
have experienced only hives after exposure to egg a contraindication to receiving these vaccines.
should receive influenza vaccine. Any licensed Thimerosal, an organic mercurial compound
influenza vaccine that is otherwise appropri- in use since the 1930s, has been added to cer-
ate for the recipient’s age and health status may tain immunobiologic products as a preservative.
be used. Thimerosal is present at preservative concentra-
People who report having had reactions to tions in multidose vials of some brands of vaccine.
egg involving symptoms other than hives, such Receiving thimerosal- containing vaccines has
as angioedema, respiratory distress, lighthead- been postulated to lead to induction of allergy.
edness, or recurrent emesis, or who required However, there is limited scientific evidence for
epinephrine or another emergency medical inter- this assertion. Allergy to thimerosal usually con-
vention, may similarly receive any licensed influ- sists of local delayed-type hypersensitivity reac-
enza vaccine that is otherwise appropriate for the tions. Thimerosal elicits positive delayed- type
recipient’s age and health status. If a person has hypersensitivity patch tests in 1%–18% of people
a severe egg sensitivity or has a positive skin test tested, but these tests have limited or no clinical
to yellow fever vaccine but the vaccination is rec- relevance. Most people do not experience reac-
ommended because of their travel destination- tions to thimerosal administered as a component
specific risk, desensitization can be performed of vaccines, even when patch or intradermal tests
under direct supervision of a physician experi- for thimerosal indicate hypersensitivity. A local-
enced in the management of anaphylaxis. In such ized or delayed-type hypersensitivity reaction to
circumstances, both yellow fever and influenza thimerosal is not a contraindication to receipt of a
vaccines should be administered in an inpatient vaccine that contains thimerosal.
or outpatient medical setting. Vaccine adminis- Since mid- 2001, vaccines routinely recom-
tration should be supervised by a health care pro- mended for infants have been manufactured
vider who is able to recognize and manage severe without thimerosal as a preservative. Additional
allergic reactions. A previous severe allergic reac- information about thimerosal and the thimerosal
tion to any vaccine, regardless of the component content of vaccines is available on the FDA web-
suspected of being responsible for the reaction, is site (www.fda.gov/cber/vaccine/thimerosal.htm).
a contraindication to future receipt of the vaccine.
Some vaccines contain a preservative or trace REPORTING ADVERSE EVENTS
amounts of antibiotics to which people might AFTER IMMUNIZATION
be allergic. Providers administering the vaccines Modern vaccines are extremely safe and effective.
should carefully review the prescribing informa- Benefits and risks are associated with the use of
tion before deciding if the rare person with such all immunobiologics—no vaccine is completely
effective or completely safe for all recipients. The method of administration of injectable vac-
Adverse events after immunization have been cines depends in part on the presence of an adju-
reported with all vaccines, ranging from frequent, vant in some vaccines. The term adjuvant refers
minor, local reactions to extremely rare, severe, to a vaccine component distinct from the anti-
systemic illness, such as that associated with yel- gen, which enhances the immune response to the
low fever vaccine. Adverse events following spe- antigen. Vaccines containing an adjuvant (DTaP,
cific vaccines and toxoids are discussed in detail DT, HPV, Td, Tdap, pneumococcal conjugate, Hib,
in each ACIP statement. In the United States,
clinicians are required by law to report selected
hepatitis A, hepatitis B) should be injected into a
muscle mass, because administration subcutane-
2
adverse events occurring after vaccination with ously or intradermally can cause local irritation,
any vaccine in the recommended childhood induration, skin discoloration, inflammation, and
series. In addition, CDC strongly recommends granuloma formation. Detailed discussion and
that all vaccine adverse events be reported to recommendations about vaccination of people
the Vaccine Adverse Event Reporting System with bleeding disorders or receiving anticoagu-
(VAERS), even if a causal relation to vaccination is lant therapy are available in the ACIP general rec-
not certain. VAERS reporting forms and informa- ommendations on immunization.
tion are available electronically at www.vaers.hhs. Routes of administration are recommended
gov, or they may be requested by telephone: 800- by the manufacturer for each immunobio-
822-7967 (toll-
free). Clinicians are encouraged logic. Deviation from the recommended route of
to report electronically at https://vaers.hhs.gov/ administration may reduce vaccine efficacy or
esub/step1. increase local adverse reactions. Detailed recom-
mendations on the route and site for all vaccines
INJECTION ROUTE AND have been published in ACIP recommendations; a
INJECTION SITE compiled list of these publications is available on
Injectable vaccines are administered by intra- the CDC website at www.cdc.gov/vaccines/hcp/
muscular, intradermal, and subcutaneous routes. acip-recs (also see Table B-1 in Appendix B).
BIBLIOGRAPHY
1. CDC. General recommendations on immuniza- PCV13 and PPSV23 vaccines: recommendations of
tion: recommendations of the Advisory Committee on the Advisory Committee on Immunization Practices
Immunization Practices (ACIP). MMWR Recomm Rep. (ACIP). MMWR Morb Mortal Wkly Rep. 2015 Sep
2011 Jan 28;60(2):1–6 4. 4;64(64):944–7.
2. CDC. Updated recommendations for use of tetanus 6. Kretsinger K, Broder KR, Cortese MM, Joyce MP, Ortega-
toxoid, reduced diphtheria toxoid, and acellular Sanchez I, Lee GM, et al. Preventing tetanus, diphtheria,
pertussis (Tdap) vaccine in adults aged 65 years and and pertussis among adults: use of tetanus toxoid,
older—Advisory Committee on Immunization Practices reduced diphtheria toxoid and acellular pertussis vac-
(ACIP), 2012. MMWR Morb Mortal Wkly Rep. 2012 Jun cine recommendations of the Advisory Committee on
29;61(25):468–70. Immunization Practices (ACIP) and recommendation
3. Cohn AC, MacNeil JR, Clark TA, Ortega-Sanchez IR, of ACIP, supported by the Healthcare Infection Control
Briere EZ, Meissner HC, et al. Prevention and control Practices Advisory Committee (HICPAC), for use of
of meningococcal disease: recommendations of the Tdap among health-care personnel. MMWR Recomm
Advisory Committee on Immunization Practices Rep. 2006 Dec 15;55(RR-17):1–37.
(ACIP). MMWR Recomm Rep. 2013 Mar 22;62(2):1–28. 7. McLean HQ, Fiebelkorn AP, Temte JL, Wallace GS,
4. Grohskopf LA, Sokolow LZ, Olsen SJ, Bresee JS, Broder CDC. Prevention of measles, rubella, congenital rubella
KR, Karron RA, et al. Prevention and control of sea- syndrome, and mumps, 2013: summary recommen-
sonal influenza with vaccines: recommendations of dations of the Advisory Committee on Immunization
the Advisory Committee on Immunization Practices— Practices (ACIP). MMWR Recomm Rep. 2013 Jun
United States, 2013–2014. MMWR Recomm Rep. 2015 14;62(RR-0 4):1–34.
Aug 7;64(30):818–25. 8. Nuorti JP, Whitney CG, CDC. Prevention of pneumo-
5. Kobayashi M, Bennett NM, Gierke R, Almendares coccal disease among infants and children—use of 13-
O, Moore MR, Whitney CG, et al. Intervals between valent pneumococcal conjugate vaccine and 23-valent
2
INTERACTIONS AMONG TRAVEL
VACCINES & DRUGS
Ilan Youngster, Elizabeth D. Barnett
Vaccines and medications are prescribed fre- to yellow fever and mumps components, com-
quently in pretravel consultations, and potential pared with responses following separate vaccina-
interactions between vaccines and medications, tion with MMR and yellow fever vaccines 30 days
including those already taken by the traveler, apart. (See “Simultaneous Administration” in
must be considered. The importance of this Yellow Fever section, Chapter 3.) A single study
topic is highlighted by a study identifying poten- suggested that in adults, concomitant adminis-
tial drug–drug interactions with travel- related tration of the 13-valent pneumococcal conjugate
medications in 45% of travelers using chronic vaccine with the trivalent inactivated influenza
medications. Although a comprehensive list of vaccine results in lower immunogenicity to the
interactions is beyond the scope of this section, PCV13 components. However, the clinical signifi-
some of the more serious interactions of com- cance of this observation is uncertain, as responses
monly used travel-related vaccines and medica- still met FDA criteria of noninferiority. In infants
tions are discussed here. given PCV13 and inactivated influenza vaccine
concomitantly, the risk of fever and febrile seizure
is slightly increased. However, this risk must be
INTERACTIONS BETWEEN weighed against the need for both vaccines before
VACCINES travel and the time available to separate them.
In general, concomitant administration of mul-
tiple vaccines, including live attenuated immu-
nizations, is safe and effective. Administering a
INTERACTIONS BETWEEN
live-virus vaccine within 4 weeks after adminis-
TRAVEL VACCINES AND DRUGS
tration of another live-virus vaccine can decrease Live Attenuated Oral Typhoid and
immunogenicity to the second administered vac- Cholera Vaccines
cine. This observation has given rise to the rec- Live attenuated vaccines should generally be
ommendation that live-virus vaccines should be avoided in immunocompromised travelers, includ-
administered the same day or ≥4 weeks apart. ing those who are taking immunomodulators,
If the 4-week span is not achievable, the second calcineurin inhibitors, cytotoxic agents, antimetab-
vaccine may be administered sooner to afford olites, and high-dose steroids (see Table 8-1).
some protection, but it should be readminis- Antimicrobial agents may be active against
tered ≥4 weeks later if the traveler is at continued the vaccine strain in the oral typhoid and cholera
risk. A study examining concurrent administra- vaccines and may prevent an adequate immune
tion of the yellow fever vaccine with the measles- response to the vaccine. Therefore, oral typhoid
mumps-rubella (MMR) vaccine in 12-month-old or cholera vaccine should not be given to peo-
children showed slightly reduced immunogenicity ple taking antibacterial agents. Vaccination with
oral typhoid vaccine should be delayed for >72 combination to treat people with uncomplicated
hours after the administration of any such agent. Plasmodium falciparum malaria), potentially
Parenteral typhoid vaccine may be a more appro- causing fatal prolongation of the QTc interval.
priate choice for these people. Live attenuated Lumefantrine should therefore be avoided or used
oral cholera vaccine should not be given to peo- with caution in patients taking mefloquine pro-
ple who have received oral or parenteral antibi- phylaxis. Although no conclusive data are availa
otics within 14 days prior to vaccination. There is ble with regard to coadministration of mefloquine
no parenteral cholera vaccine currently available,
and no killed oral cholera vaccines are licensed in
and other drugs that may affect cardiac conduc-
tion, mefloquine should be used with caution
2
the United States. or avoided in patients taking antiarrhythmic or
Chloroquine and atovaquone- proguanil at β-blocking agents, calcium- channel blockers,
doses used for malaria chemoprophylaxis may be antihistamines, H1-blocking agents, tricyclic anti-
given concurrently with the oral typhoid vaccine. depressants, selective serotonin reuptake inhibi-
Data from an older formulation of the CVD 103- tors (SSRIs), or phenothiazines. Mefloquine may
HgR oral cholera vaccine suggest that the immune also lower plasma levels of a number of anticon-
response to the vaccine may be diminished when vulsants, such as valproic acid, carbamazepine,
it is given concomitantly with chloroquine. Live phenobarbital, and phenytoin; concurrent use of
attenuated oral cholera vaccine should be given mefloquine with these agents should be avoided.
at least 10 days before beginning antimalarial pro- In general, mefloquine should be avoided in trav-
phylaxis with chloroquine, although a study in elers with a history of seizures, mood disorders
children using the oral cholera vaccine suggested or psychiatric disease. Mefloquine can also lead
no decrease in immunogenicity when given with to increased levels of calcineurin inhibitors and
atovaquone-proguanil. mTOR inhibitors (tacrolimus, cyclosporine A,
and sirolimus). Potent CYP3A4 inhibitors such
Rabies Vaccine as macrolides (azithromycin, clarithromycin,
Concomitant use of chloroquine may reduce the erythromycin), azole antifungals (ketoconazole,
antibody response to intradermal rabies vaccine voriconazole, posaconazole and itraconazole),
administered for preexposure vaccination. The SSRIs ( fluoxetine, sertraline, fluvoxamine), (anti
intramuscular route should be used for people retroviral protease inhibitors (ritonavir, lopinavir,
taking chloroquine concurrently. (Currently, intra- darunavir, atazanavir, saquinavir), and cobici-
dermal administration of rabies vaccine is not stat (available in a combination with elvitegravir)
approved in the United States.) may increase the levels of mefloquine, increasing
the risk for QT prolongation. CYP3A4 inducers
INTERACTIONS BETWEEN such as efavirenz, nevirapine, etravirine, rifampin,
ANTIMALARIALS AND SELECTED rifabutin, St John’s wort and glucocorticoids may
OTHER DRUGS reduce plasma concentrations of mefloquine, and
This section describes some of the more com- concurrent use should be avoided. Concurrent
monly encountered drug interactions. Any time use of mefloquine with the direct-acting protease
a new medication is prescribed, clinicians should inhibitors boceprevir and telaprevir used to treat
check for any interactions and inform the traveler hepatitis C should also be avoided. The newer
of the potential risk. direct-
acting protease inhibitors (grazoprevir,
paritaprevir, simeprevir) are believed to be asso-
Mefloquine ciated with fewer drug–drug interactions, but as
Mefloquine may interact with several catego- safety data are lacking, alternatives to mefloquine
ries of drugs, including other antimalarial drugs, could be considered pending additional data.
drugs that alter cardiac conduction, and anti-
convulsants. Mefloquine is associated with Chloroquine
increased toxicities of the antimalarial drug lume- Chloroquine may increase risk of prolonged QTc
fantrine (available in the United States in fixed interval when given with other QT-prolonging
agents (such as sotalol, amiodarone, and lume- reverse transcriptase inhibitors nevirapine, etra-
fantrine), and the combination should be avoided. virine, and efavirenz, resulting in decreased levels
The antiretroviral rilpivirine has also been shown of atovaquone-proguanil. Despite the potential
to prolong QTc, and coadministration should be for interactions, atovaquone-proguanil is well tol-
avoided. Chloroquine inhibits CYP2D6; when erated in most patients receiving these antivirals
given concomitantly with substrates of this and is the preferred antimalarial for short-term
enzyme (such as metoprolol, propranolol, fluoxe- travel. Cimetidine and fluvoxamine interfere with
2 tine, paroxetine, flecainide), increased monitoring
for side effects may be warranted. Chloroquine
the metabolism of proguanil and should therefore
be avoided.
absorption may be reduced by antacids or kaolin;
≥4 hours should elapse between doses of these Doxycycline
medications. Concomitant use of cimetidine and Phenytoin, carbamazepine, and barbiturates may
chloroquine should be avoided, as cimetidine can decrease the half-life of doxycycline. Patients on
inhibit the metabolism of chloroquine and may anticoagulants may need to reduce their antico-
increase drug levels. CYP3A4 inhibitors such as agulant dose while taking doxycycline because of
ritonavir, ketoconazole, and erythromycin may its ability to depress plasma prothrombin activity.
also increase chloroquine levels, and concomitant Absorption of tetracyclines may be impaired by bis-
use should be avoided. Chloroquine inhibits bioa- muth subsalicylate, preparations containing iron,
vailability of ampicillin, and 2 hours should elapse and antacids containing calcium, magnesium, or
between doses. Chloroquine is also reported to aluminum; these preparations should not be taken
decrease the bioavailability of ciprofloxacin and within 3 hours of taking doxycycline. Doxycycline
methotrexate. Chloroquine may increase digoxin may interfere with the bactericidal activity of pen-
levels; increased digoxin monitoring is warranted. icillin, so these drugs, in general, should not be
Use of chloroquine could possibly also lead to taken together. Doxycycline has no known interac-
increased levels of calcineurin inhibitors and tion with antiretroviral agents, but concurrent use
should be used with caution. may lead to increased levels of calcineurin inhibi-
tors and mTOR inhibitors (sirolimus).
Atovaquone-Proguanil
Tetracycline, rifampin, and rifabutin may reduce
plasma concentrations of atovaquone and should
INTERACTIONS WITH
not be used concurrently with atovaquone-
DRUGS FOR TREATMENT OF
proguanil. Metoclopramide may reduce bioavail-
TRAVELERS’ DIARRHEA
ability of atovaquone; unless no other antiemetics Azithromycin
are available, this antiemetic should not be used Close monitoring for side effects of azithromy-
to treat the vomiting that may accompany use cin is recommended when azithromycin is used
of atovaquone at treatment doses. Atovaquone- with nelfinavir. Increased anticoagulant effects
proguanil should not be used with other medica- have been noted when azithromycin is used with
tions that contain proguanil. Patients on warfarin warfarin; monitoring prothrombin time is rec-
may need to reduce their anticoagulant dose or ommended for people taking these drugs con-
monitor their prothrombin time more closely while comitantly. Additive QTc prolongation may occur
taking atovaquone-proguanil, although coadmin- when azithromycin is used with the antimalarial
istration of these drugs is not contraindicated. artemether, and concomitant therapy should be
The use of novel oral anticoagulants (dabiga- avoided. Drug interactions have been reported
tran, rivaroxaban and apixaban) is not expected with macrolides and antiretroviral protease inhib-
to cause significant interactions, and their use itors, as well as efavirenz and nevirapine, and
has been suggested as an alternative in patients can increase risk of QTc prolongation, though a
in need of anticoagulation. Atovaquone-proguanil short treatment course is not contraindicated for
may interact with the antiretroviral protease those without an underlying cardiac abnormal-
inhibitors ritonavir, darunavir, atazanavir, indina- ity. Concurrent use with macrolides may lead to
vir, and lopinavir, in addition to the nonnucleoside increased levels of calcineurin inhibitors.
BIBLIOGRAPHY
1. Frenck RW Jr, Gurtman A, Rubino J, Smith W, van on the immune response to yellow fever vaccine and a
Cleeff M, Jayawardene D, et al. Randomized, controlled combined vaccine against measles, mumps and rubella.
trial of a 13-valent pneumococcal conjugate vaccine Vaccine. 2011 Aug 26;29(37):6327–34.
administered concomitantly with an influenza vac- 5. Nielsen US, Jensen-Fangel S, Pedersen G, Lohse N,
cine in healthy adults. Clin Vaccine Immunol. 2012 Pedersen C, Kronborg G, et al. Travelling with HIV: a
Aug;19(8):1296–303. cross sectional analysis of Danish HIV-infected patients.
Self-Treatable Conditions
TRAVELERS’ DIARRHEA
Bradley A. Connor
Travelers’ diarrhea (TD) is the most predictable symptoms and collectively account for approxi-
travel-related illness. Attack rates range from 30% mately 10% of diagnoses in longer-term travelers.
to 70% of travelers, depending on the destination What is commonly known as “food poisoning”
and season of travel. Traditionally, it was thought involves the ingestion of preformed toxins in food.
that TD could be prevented by following simple In this syndrome, vomiting and diarrhea may both
recommendations such as “boil it, cook it, peel it, be present, but symptoms usually resolve sponta-
or forget it,” but studies have found that people neously within 12 hours.
who follow these rules may still become ill. Poor
hygiene practice in local restaurants is likely the INFECTIOUS AGENTS
largest contributor to the risk for TD. Bacteria are the most common cause of TD.
TD is a clinical syndrome that can result from Overall, the most common pathogen is enterotoxi-
a variety of intestinal pathogens. Bacterial patho- genic Escherichia coli, followed by Campylobacter
gens are the predominant risk, thought to account jejuni, Shigella spp., and Salmonella spp. Entero
for up to 80%–90% of TD. Intestinal viruses usually aggregative and other E. coli pathotypes are also
account for at least 5%–8% of illnesses, although commonly found in cases of TD. There is increas-
improved diagnostics may increase recognition ing discussion of Aeromonas spp., Plesiomonas
of norovirus infections in the future. Infections spp., and newly recognized pathogens (Acrobacter,
with protozoal pathogens are slower to manifest Larobacter, enterotoxigenic Bacteroides fragilis) as
potential causes of TD as well. Viral diarrhea can plumbing or latrines, the amount of stool con-
be caused by a number of pathogens, including tamination in the environment will be higher
norovirus, rotavirus, and astrovirus. and more accessible to flies. Inadequate electri-
Giardia is the main protozoal pathogen cal capacity may lead to frequent blackouts or
found in TD. Entamoeba histolytica is a relatively poorly functioning refrigeration, which can result
uncommon cause of TD, and Cryptosporidium is in unsafe food storage and an increased risk for
also relatively uncommon. The risk for Cyclospora disease. Lack of safe water may lead to contami-
is highly geographic and seasonal: the most
well-known risks are in Nepal, Peru, Haiti, and
nated foods and drinks prepared with such water;
inadequate water supply may lead to shortcuts in
2
Guatemala. Dientamoeba fragilis is a flagellate cleaning hands, surfaces, utensils, and foods such
occasionally associated with diarrhea in trav- as fruits and vegetables. In addition, handwashing
elers. Most of the individual pathogens are dis- may not be a social norm and could be an extra
cussed in their own sections in Chapter 3, and expense; thus there may be no handwashing sta-
persistent diarrhea in returned travelers is dis- tions in food preparation areas. In destinations
cussed in Chapter 5. in which effective food handling courses have
been provided, the risk for TD has been demon-
OCCURRENCE strated to decrease. However, even in developed
The most important determinant of the caus- countries, pathogens such as Shigella sonnei have
ative organism and risk for TD is travel destina- caused TD linked to handling and preparation of
tion. The world is generally divided into 3 grades food in restaurants.
of risk: low, intermediate, and high.
• Low-risk countries include the United States, CLINICAL PRESENTATION
Canada, Australia, New Zealand, Japan, and Bacterial and viral TD presents with the sud-
countries in Northern and Western Europe. den onset of bothersome symptoms that can
range from mild cramps and urgent loose stools
• Intermediate-risk countries include those to severe abdominal pain, fever, vomiting, and
in Eastern Europe, South Africa, and some bloody diarrhea, although with norovirus vom-
Caribbean islands. iting may be more prominent. Protozoal diar-
rhea, such as that caused by Giardia intestinalis or
• High-risk areas include most of Asia, the
Middle East, Africa, Mexico, and Central and E. histolytica, generally has a more gradual onset
South America. of low-grade symptoms, with 2–5 loose stools per
day. The incubation period between exposure and
RISK FOR TRAVELERS clinical presentation can be a clue to the etiology:
TD occurs equally in male and female travelers
• Bacterial toxins generally cause symptoms
and is more common in young adult travelers within a few hours.
than in older travelers. In short-term travelers,
bouts of TD do not appear to protect against • Bacterial and viral pathogens have an incuba-
future attacks, and >1 episode of TD may occur tion period of 6–72 hours.
during a single trip. A cohort of expatriates resid-
• Protozoal pathogens generally have an incu-
ing in Kathmandu, Nepal, experienced an aver- bation period of 1–2 weeks and rarely present
age of 3.2 episodes of TD per person in their in the first few days of travel. An exception
first year. In more temperate regions, there may can be Cyclospora cayetanensis, which can
be seasonal variations in diarrhea risk. In south present quickly in areas of high risk.
Asia, for example, much higher TD attack rates
are reported during the hot months preceding Untreated bacterial diarrhea usually lasts 3–7 days.
the monsoon. Viral diarrhea generally lasts 2–3 days. Protozoal
In environments in warmer climates where diarrhea can persist for weeks to months without
large numbers of people do not have access to treatment. An acute bout of gastroenteritis can lead
TRAVELERS’ DIARRHEA 49
05
to persistent gastrointestinal symptoms, even in causes blackening of the tongue and stool and may
the absence of continued infection (see Chapter 5, cause nausea, constipation, and rarely tinnitus.
Persistent Travelers’ Diarrhea). This presentation BSS should be avoided by travelers with aspirin
is commonly referred to as postinfectious irrita- allergy, renal insufficiency, and gout, and by those
ble bowel syndrome. Other postinfectious sequelae taking anticoagulants, probenecid, or methotrex-
may include reactive arthritis and Guillain-Barré ate. In travelers taking aspirin or salicylates for
syndrome. other reasons, the use of BSS may result in salicy-
2 PREVENTION
late toxicity. BSS is not generally recommended for
children aged <12 years; however, some clinicians
For travelers to high-risk areas, several approaches use it off-label with caution to avoid administer-
may be recommended that can reduce, but never ing BSS to children with viral infections, such as
completely eliminate, the risk for TD. These varicella or influenza, because of the risk for Reye
include instructions regarding food and beverage syndrome. BSS is not recommended for children
selection, using agents other than antimicrobial aged <3 years or pregnant women. Studies have
drugs for prophylaxis, using prophylactic anti- not established the safety of BSS use for periods >3
biotics, and carefully washing hands with soap weeks. Because of the number of tablets required
where available. Carrying small containers of and the inconvenient dosing, BSS is not commonly
alcohol-based hand sanitizers (containing ≥60% used as prophylaxis for TD.
alcohol) may make it easier for travelers to clean The use of probiotics, such as Lactobacillus
their hands before eating when handwashing is GG and Saccharomyces boulardii, has been stud-
not possible. No vaccines are available for most ied in the prevention of TD in small numbers
pathogens that cause TD, but travelers should of people. Results are inconclusive, partially
refer to the Cholera, Hepatitis A, and Typhoid & because standardized preparations of these bac-
Paratyphoid Fever sections in Chapter 3 regard- teria are not reliably available. Studies are ongo-
ing vaccines that can prevent other foodborne ing with prebiotics to prevent TD, but data are
or waterborne infections to which travelers are insufficient to recommend their use. There have
susceptible. been anecdotal reports of beneficial outcomes
after using bovine colostrum as a daily prophy-
Food and Beverage Selection laxis agent for TD. However, commercially sold
Care in selecting food and beverages can minimize preparations of bovine colostrum are marketed
the risk for acquiring TD. See the Food & Water as dietary supplements that are not Food and
Precautions section later in this chapter for CDC’s Drug Administration (FDA) approved for med-
detailed food and beverage recommendations. ical indications. Because no data from rigorous
Although food and water precautions continue clinical trials demonstrate efficacy, there is insuf-
to be recommended, travelers may not always be ficient information to recommend the use of
able to adhere to the advice. Furthermore, many of bovine colostrum to prevent TD.
the factors that ensure food safety, such as restau- Although not available in the United States, a
rant hygiene, are out of the traveler’s control. cholera vaccine (Dukoral) that provides partial
protection against enterotoxigenic E. coli is avail-
Nonantimicrobial Drugs able in some other countries. Several clinical tri-
for Prophylaxis als of new vaccines against TD pathogens are in
The primary agent studied for prevention of TD, progress.
other than antimicrobial drugs, is bismuth sub-
salicylate (BSS), which is the active ingredi- Prophylactic Antibiotics
ent in adult formulations of Pepto-Bismol and Although prophylactic antibiotics can prevent
Kaopectate. Studies from Mexico have shown that some TD, the emergence of antimicrobial resis-
this agent (taken daily as either 2 oz of liquid or 2 tance has made the decision of how and when
chewable tablets 4 times per day) reduces the inci- to use antibiotic prophylaxis for TD difficult.
dence of TD by approximately 50%. BSS commonly Controlled studies have shown that diarrhea
attack rates are reduced by 90% or more by the use and helps the traveler feel better more quickly.
of antibiotics. The prophylactic antibiotic of choice Travelers should remember to use only bever-
has changed over the past few decades as resis- ages that are sealed, treated with chlorine, boiled,
tance patterns have evolved. Fluoroquinolones or are otherwise known to be purified. For severe
have been the most effective antibiotics for the fluid loss, replacement is best accomplished with
prophylaxis and treatment of bacterial TD patho- oral rehydration solution (ORS) prepared from
gens, but increasing resistance to these agents packaged oral rehydration salts, such as those
among Campylobacter and Shigella species glob-
ally limits their potential use. Alternative consid-
provided by the World Health Organization. ORS
is widely available at stores and pharmacies in
2
erations include azithromycin and rifaximin, a most developing countries. ORS is prepared by
nonabsorbable broad-spectrum antibiotic. adding 1 packet to the indicated volume of boiled
At this time, prophylactic antibiotics should not or treated water—generally 1 liter. Travelers may
be recommended for most travelers. Prophylactic find most ORS formulations to be relatively unpal-
antibiotics afford no protection against nonbacte- atable due to their saltiness. In mild cases, rehy-
rial pathogens and can remove normally protec- dration can be maintained with any palatable
tive microflora from the bowel, increasing the risk liquid (including sports drinks), although overly
of infection with resistant bacterial pathogens. sweet drinks, such as sodas, can cause osmotic
Travelers may become colonized with extended- diarrhea if consumed in quantity.
spectrum β-lactamase (ESBL)–producing bac-
teria, and this risk is increased by exposure to Antimotility Agents
antibiotics while abroad. Additionally, the use Antimotility agents provide symptomatic relief
of antibiotics may be associated with allergic or and are useful therapy in TD. Synthetic opi-
adverse reactions, and prophylactic antibiotics ates, such as loperamide and diphenoxylate,
limit the therapeutic options if TD occurs; a trav- can reduce frequency of bowel movements and
eler relying on prophylactic antibiotics will need therefore enable travelers to ride on an airplane
to carry an alternative antibiotic to use if severe or bus. Loperamide appears to have antisecre-
diarrhea develops despite prophylaxis. The risks tory properties as well. The safety of loperamide
associated with the use of prophylactic antibi- when used along with an antibiotic has been well
otics should be weighed against the benefit of established, even in cases of invasive pathogens;
using prompt, early self-treatment with antibiot- however, acquisition of ESBL-producing patho-
ics when moderate to severe TD occurs, shorten- gens may be more common when loperamide
ing the duration of illness to 6–24 hours in most and antibiotics are coadministered. Antimotility
cases. Prophylactic antibiotics may be considered agents alone are not recommended for patients
for short-term travelers who are high-risk hosts with bloody diarrhea or those who have diarrhea
(such as those who are immunosuppressed) or and fever. Loperamide can be used in children,
who are taking critical trips (such as engaging in a and liquid formulations are available. In practice,
sporting event) without the opportunity for time however, these drugs are rarely given to small chil-
off in the event of sickness. dren (aged <6 years).
Antibiotics
TREATMENT Antibiotics are effective in reducing the duration
Oral Rehydration Therapy of diarrhea by about a day in cases caused by bac-
Fluids and electrolytes are lost during TD, and terial pathogens that are susceptible to the par-
replenishment is important, especially in young ticular antibiotic prescribed. However, there are
children or adults with chronic medical illness. In concerns about adverse consequences of using
adult travelers who are otherwise healthy, severe antibiotics to treat TD. Travelers who take anti-
dehydration resulting from TD is unusual unless biotics may acquire resistant organisms such as
vomiting is prolonged. Nonetheless, replacement ESBL-producing organisms, resulting in poten-
of fluid losses remains an adjunct to other therapy tial harm to travelers—particularly those who are
TRAVELERS’ DIARRHEA 51
5
2
immunosuppressed or women who may be prone trials and clinical experience. The best regimen for
to urinary tract infections—and the possibility of azithromycin treatment may also be a single dose
introducing these resistant bacteria into the com- of 1,000 mg, but side effects (mainly nausea) may
munity. In addition, there is concern about the limit the acceptability of this large dose. Giving
effects of antibiotic use on travelers’ microbiota azithromycin as 2 divided doses on the same day
and the potential for adverse consequences such may limit this adverse event.
as Clostridium difficile infection as a result. These Because of the competing concerns of effective
2 concerns have to be weighed against the conse-
quences of TD and the role of antibiotics in short-
treatment of TD episodes and a desire to avoid
the potential negative consequences of antibiotic
ening the acute illness and possibly preventing use, consensus guidelines have been developed
postinfectious sequelae (see Chapter 5, Persistent by the International Society of Travel Medicine to
Travelers’ Diarrhea). address this (Box 2-2 and Table 2-6). See the next
The effectiveness of a particular antimicrobial section in this chapter for more information on
drug depends on the etiologic agent and its antibi- the risks and benefits of antiobiotic use for TD.
otic sensitivity. As empiric therapy or to treat a spe-
cific bacterial pathogen, first-line antibiotics have Treatment of TD Caused
traditionally been the fluoroquinolones, such as by Protozoa
ciprofloxacin or levofloxacin. Increasing microbial The most common parasitic cause of TD is Giardia
resistance to the fluoroquinolones, especially among intestinalis, and treatment options include met-
Campylobacter isolates, may limit their usefulness in ronidazole, tinidazole, and nitazoxanide (see
many destinations, particularly South and Southeast Chapter 3, Giardiasis). Although cryptosporidio-
Asia, where both Campylobacter infection and fluo- sis is usually a self-limited illness in immunocom-
roquinolone resistance is prevalent. Increasing flu- petent people, nitazoxanide can be considered as
oroquinolone resistance has been reported from a treatment option. Cyclosporiasis is treated with
other destinations and in other bacterial pathogens, trimethoprim- sulfamethoxazole. Treatment of
including in Shigella and Salmonella. In addition, amebiasis is with metronidazole or tinidazole, fol-
the use of fluoroquinolones has been associated lowed by treatment with a luminal agent such as
with tendinopathies and the development of C. dif iodoquinol or paromomycin.
ficile infection. FDA warns that the potentially seri-
ous side effects of fluoroquinolones may outweigh Treatment for Children
their benefit in treating uncomplicated respiratory Children who accompany their parents on trips to
and urinary tract infections; however, because of the high-risk destinations can contract TD as well, with
short duration of therapy for TD, these side effects elevated risk if they are visiting friends and family.
are not believed to be a significant risk. Causative organisms include bacteria responsible
A potential alternative to fluoroquinolones for TD in adults as well as viruses including noro-
is azithromycin, although enteropathogens with virus and rotavirus. The main treatment for TD in
decreased azithromycin susceptibility have been children is ORS. Infants and younger children with
documented in several countries. Rifaximin has TD are at higher risk for dehydration, which is best
been approved to treat TD caused by noninvasive prevented by the early initiation of oral rehydra-
strains of E. coli. However, since it is often difficult tion. Empiric antibiotic therapy should be consid-
for travelers to distinguish between invasive and ered if there is bloody or severe watery diarrhea or
noninvasive diarrhea, and since they would have evidence of systemic infection. In older children
to carry a backup drug in the event of invasive and teenagers, treatment recommendations for
diarrhea, the overall usefulness of rifaximin as TD follow those for adults, with possible adjust-
empiric self-treatment remains to be determined. ments in the dose of medication. Among younger
Single-dose regimens are equivalent to mul- children, macrolides such as azithromycin are
tidose regimens and may be more convenient considered first-line antibiotic therapy, although
for the traveler. Single-dose therapy with a fluo- some experts now use short-course fluoroquino-
roquinolone is well established, both by clinical lone therapy (despite its not being FDA-approved
for this indication in children) for travelers aged diaper rash on their buttocks in response to the
<18 years. Rifaximin is approved for use in children liquid stool. Barrier creams, such as zinc oxide
aged ≥12 years. or petrolatum, could be applied at the onset
Breastfed infants should continue to nurse on of diarrhea to help prevent and treat rash.
demand, and bottle-fed infants can continue to Hydrocortisone cream is the best treatment for
drink formula. Older infants and children should an established rash. More information about diar-
be encouraged to eat and may consume a regular rhea and dehydration is discussed in Chapter 7,
diet. Children in diapers are at risk for developing Traveling Safely with Infants & Children.
BIBLIOGRAPHY
1. Black RE. Epidemiology of travelers’ diarrhea and rel- galacto-oligosaccharide mixture in reducing travellers’
ative importance of various pathogens. Rev Infect Dis. diarrhoea. Eur J Clin Nutr. 2010 Feb;64(2):146–52.
1990 Jan-Feb;12 Suppl 1:S73–9. 3. DuPont HL, Ericsson CD, Farthing MJ, Gorbach S,
2. Drakoularakou A, Tzortzis G, Rastall RA, Gibson Pickering LK, Rombo L, et al. Expert review of the evi-
GR. A double-blind, placebo-controlled, random- dence base for prevention of travelers’ diarrhea. J Travel
ized human study assessing the capacity of a novel Med. 2009 May-Jun;16(3):149–6 0.
TRAVELERS’ DIARRHEA 53
45
4. Farthing M, Salam MA, Lindberg G, Dite P, Khalif I, Salazar- 7. Raja MK, Ghosh AR. Laribacter hongkongensis: an
Lindo E, et al. Acute diarrhea in adults and children: a emerging pathogen of infectious diarrhea. Folia
global perspective. J Clin Gastroenterol. 2013 Jan;47(1):12–20. Microbiol (Praha) 2014 Jul;59(4):341–7.
5. Kantele A, Lääveri T, Mero S, Vilkman K, Pakkanen S, 8. Riddle MS, DuPont HL, Connor BA. ACG clinical guide-
Ollgren J, et al. Antimicrobials increase travelers’ risk line: diagnosis, treatment, and prevention of acute
of colonization by extended-spectrum betalactamase- diarrheal infections in adults. Am J Gastroenterol 2016
producing Enterobacteriaceae. Clin Infect Dis. 2015 Mar May;111(5):602–22.
15;60(6):837–46. 9. Shlim DR. Looking for evidence that personal hygiene
2 6. Kendall ME, Crim S, Fullerton K, Han PV, Cronquist AB,
Shiferaw B, et al. Travel-associated enteric infections
precautions prevent travelers’ diarrhea. Clin Infect Dis.
2005 Dec 1;41(Suppl 8):S531–5.
diagnosed after return to the United States, Foodborne 10. Steffen R, Hill DR, DuPont HL. Traveler’s diarrhea: a
Diseases Active Surveillance Network (FoodNet), clinical review. JAMA. 2015 Jan 6;313(1):71–80.
2004–2009. Clin Infect Dis. 2012 Jun;54 Suppl 5:S480–7.
…perspectives
ANTIBIOTICS IN TRAVELERS’
DIARRHEA—BALANCING
THE RISKS & BENEFITS 2
Mark S. Riddle, Bradley A. Connor
For the last 30 years, ran- the benefits appear to out- spread of resistance with the
domized controlled trials weigh the risks. More recently, health benefits of antibiotic
have consistently and clearly there has been concern that treatment of TD. Although the
demonstrated that antibiot- antibiotics used by travelers role of travelers in the trans-
ics slightly but significantly might result in significant location of infectious disease
shorten the duration of changes in the host microbi- and resistance cannot be
illness and alleviate the ome as well as the acquisition ignored, the ecology of ESBL-
disability associated with of multidrug-resistant bac- PE infections is complex and
travelers’ diarrhea (TD). teria. Multiple observational includes environmental, diet,
Treatment with an effective studies have found that peo- immigration, and local noso-
antibiotic shortens the aver- ple who travel (in particular comial transmission dynam-
age duration of a TD episode to regions of Asia), develop ics. ESBL-PE infections are
by about a day, and if the TD, and take antibiotics are an emerging health threat,
traveler combines an antibi- at incrementally increas- and addressing this complex
otic with an antimotility agent ing risk for colonization problem will require multiple
such as loperamide, the with extended-spectrum strategies.
duration is shortened even β-lactamase–producing How, then, to prepare a
further. Emerging data on the Enterobacteriaceae (ESBL- traveler with a prescription
potential long-term health PE). The effect of coloniza- for empiric self-treatment
consequences of TD, such tion on the average traveler before a trip? There needs
as irritable bowel syndrome, appears limited; carriage is to be a conversation with
dyspepsia, and chronic con- most often transient but does the traveler about the multi-
stipation, might suggest a persist in a small percentage level (individual, community,
benefit of early antibiotic of those who are colonized. global) risks of travel, travel-
therapy given the association However, international travel ers’ diarrhea, preventing TD
between more severe and by a household member is through hand hygiene and
longer disease and risk of associated with ESBL colo- careful selection of foods
postinfectious consequences. nization among US children, and beverages, and antibiotic
Although these clinical which suggests that there treatment. Reserving antibi-
results are impressive, anti- may be larger public health otics for moderate to severe
biotics, like any drug, are not consequences from acquiring TD should be emphasized
without consequences. Each ESBL-PE during travel. strongly, and using antimo-
of the antibiotics commonly The challenge that we face tility agents alone may be
used to treat TD have side as providers and travelers suggested for mild TD.
effects, but these are gener- is how to balance the risk of Elderly travelers or those
ally mild and self-limiting, and colonization and the global with recurrent urinary tract
(continued)
Perspectives sections are written as editorial discussions aiming to add depth and clinical perspective to the official
recommendations contained in the book. The views and opinions expressed in this section are those of the authors and
do not necessarily represent the official position of CDC.
ALTITUDE ILLNESS
Peter H. Hackett, David R. Shlim
The high- altitude environment exposes trav- the most hypoxemia; day trips to high altitude
elers to cold, low humidity, increased ultravio- with return to low altitude are much less stress-
let radiation, and decreased air pressure, all of ful on the body. Typical high-altitude destina-
which can cause problems. The biggest con- tions include Cusco (11,000 ft; 3,300 m), La Paz
cern, however, is hypoxia. At 10,000 ft (3,000 m), (12,000 ft; 3,640 m), Lhasa (12,100 ft; 3,650 m),
for example, the inspired PO2 is only 69% of Everest Base Camp (17,700 ft; 5,400 m), and
sea-level value. The magnitude of hypoxic stress Kilimanjaro (19,341 ft; 5,895 m).
depends on altitude, rate of ascent, and duration The human body adjusts very well to moder-
of exposure. Sleeping at high altitude produces ate hypoxia, but requires time to do so (Box 2-3).
The process of acute acclimatization to high Some common destinations such as the ones
altitude takes 3– 5 days; therefore, acclima- mentioned above require rapid ascent by airplane
tizing for a few days at 8,000–9,000 ft (2,500– to >3,400 meters and thus place travelers in the
2,750 m) before proceeding to a higher altitude high-risk category (see Table 2-7). Chemopro
is ideal. Acclimatization prevents altitude ill- phylaxis may be necessary for these travelers, in
ness, improves sleep, and increases comfort and addition to 2–4 days of acclimatization before
well-being, although exercise performance will going higher. In some cases, such as Cuzco and La
always be reduced compared with low altitude. Paz, the traveler can descend to altitudes much
Increase in ventilation is the most important lower than the airport to sleep.
factor in acute acclimatization; therefore, respi-
ratory depressants must be avoided. Increased CLINICAL PRESENTATION
red-cell production does not play a role in acute Altitude illness is divided into 3 syndromes: acute
acclimatization. mountain sickness (AMS), high-altitude cerebral
edema (HACE), and high- altitude pulmonary
RISK FOR TRAVELERS edema (HAPE).
Inadequate acclimatization may lead to altitude
illness in any traveler going to 8,000 ft (2,500 m) Acute Mountain Sickness
or higher, and sometimes even at lower altitude. AMS is the most common form of altitude illness,
Susceptibility and resistance to altitude illness affecting, for example, 25% of all visitors sleeping
are genetic traits, and no simple screening tests above 8,000 ft (2,500 m) in Colorado. Symptoms
are available to predict risk. Risk is not affected by are similar to those of an alcohol hangover: head-
training or physical fitness. Children are equally ache is the cardinal symptom, sometimes accom-
susceptible as adults; people aged >50 years have panied by fatigue, loss of appetite, nausea, and
slightly lower risk. How a traveler has responded occasionally vomiting. Headache onset is usually
to high altitude previously is the most reliable 2–12 hours after arrival at a higher altitude and
guide for future trips if the altitude and rate of often during or after the first night. Preverbal chil-
ascent are similar, but this is not infallible. Given dren may develop loss of appetite, irritability, and
certain baseline susceptibility, risk is largely influ- pallor. AMS generally resolves with 12–48 hours of
enced by the altitude, rate of ascent, and exertion acclimatization.
(see Table 2-7). Creating an itinerary that will
avoid any occurrence of altitude illness is difficult High-Altitude Cerebral Edema
because of variations in individual susceptibility, HACE is a severe progression of AMS and is rare; it
as well as in starting points and terrain. The goal is most often associated with HAPE. In addition to
for the traveler may not be to avoid all symptoms AMS symptoms, lethargy becomes profound, with
of altitude illness but to have no more than mild drowsiness, confusion, and ataxia on tandem gait
illness. test, similar to alcohol intoxication. A person with
ALTITUDE ILLNESS 57
85
Low • People with no prior history of altitude illness and ascending to Acetazolamide
less than 9,000 ft (2,750 m) prophylaxis generally
(1,000 m)
Moderate • People with prior history of AMS and ascending to 8,200–9,200 ft Acetazolamide
(2,500–2,800 m) or higher in 1 day prophylaxis would be
• No history of AMS and ascending to more than 9,200 ft (2,800 m) beneficial and should
in 1 day be considered.
• All people ascending more than 1,600 ft (500 m) per day (increase
in sleeping elevation) at altitudes above 9,900 ft (3,000 m), but with
an extra day for acclimatization every 3,300 ft (1,000 m)
High • History of AMS and ascending to more than 9,200 ft (2,800 m) in Acetazolamide
1 day prophylaxis strongly
• All people with a prior history of HAPE or HACE recommended.
• All people ascending to more than 11,400 ft (3,500 m) in 1 day
• All people ascending more than 1,600 ft (500 m) per day (increase
in sleeping elevation) above 9,800 ft (3,000 m), without extra days
for acclimatization
• Very rapid ascents (such as less than 7-day ascents of Mount
Kilimanjaro)
Abbreviations: AMS, acute mountain sickness; HACE, high-altitude cerebral edema; HAPE, high-altitude pulmonary edema.
HACE requires immediate descent; death can high-altitude medical issues before undertaking
ensue within 24 hours of developing ataxia, if the high-altitude travel (see Table 2-8). The risk for
person fails to descend. new ischemic heart disease in previously healthy
travelers does not appear to be increased at high
High-Altitude Pulmonary Edema altitudes. Patients with asthma, hypertension,
HAPE can occur by itself or in conjunction with atrial arrhythmia, and seizure disorders that are
AMS and HACE; incidence is 1 per 10,000 ski- well controlled at low altitude generally do well at
ers in Colorado and up to 1 per 100 climbers at high altitude. All patients with OSA should receive
more than 14,000 ft (4,270 m). Initial symptoms acetazolamide; those with mild to moderate OSA
are increased breathlessness with exertion, and may do well without their CPAP machines, while
eventually increased breathlessness at rest, asso- those with severe OSA should avoid altitude travel
ciated with weakness and cough. Oxygen or unless given supplemental oxygen in addition to
descent is life-saving. HAPE can be more rapidly their CPAP. People with diabetes can travel safely
fatal than HACE. to high altitudes, but they must be accustomed
to exercise and carefully monitor their blood glu-
Preexisting Medical Problems cose. Diabetic ketoacidosis may be triggered by
Travelers with medical conditions, such as heart altitude illness and may be more difficult to treat
failure, myocardial ischemia (angina), sickle cell in those on acetazolamide. Not all glucose meters
disease, any form of pulmonary insufficiency or read accurately at high altitudes.
preexisting hypoxemia, or obstructive sleep apnea Most people do not have visual problems at
(OSA) should consult a physician familiar with high altitudes. However, at very high altitudes
Children and adolescents Infants <6 weeks old Sickle cell anemia
2
Elderly people Compensated heart failure Severe–very severe chronic obstructive
Sedentary people Morbid obesity pulmonary disease
Mild obesity Cystic fibrosis (FEV1 30%–50% Pulmonary hypertension with
Well-controlled asthma predicted) pulmonary artery systolic pressure
Diabetes mellitus Poorly controlled arrhythmia >60 mm Hg
Coronary artery disease Poorly controlled asthma Unstable angina
following revascularization Poorly controlled hypertension Decompensated heart failure
Mild chronic obstructive Moderate chronic obstructive High-risk pregnancy
pulmonary disease pulmonary disease Cystic fibrosis (FEV1 <30% predicted)
Low-risk pregnancy Severe obstructive sleep apnea Recent myocardial infarction or stroke
Mild–moderate obstructive Stable angina (<90 days)
sleep apnea Nonrevascularized coronary Untreated cerebral vascular aneurysms
Controlled hypertension artery disease or arteriovenous malformations
Controlled seizure disorder Sickle cell trait Cerebral space-occupying lesions
Psychiatric disorders Poorly controlled seizure disorder
Neoplastic diseases Cirrhosis
Mild pulmonary hypertension
Radial keratotomy surgery
some people who have had radial keratotomy descend ≥300 m, and symptoms will rapidly abate.
may develop acute farsightedness and be unable Alternatively, supplemental oxygen at 2 L per min-
to care for themselves. LASIK and other newer ute will relieve headache quickly and resolve AMS
procedures may produce only minor visual distur- over hours, but it is rarely available. People with
bances at high altitudes. AMS can also safely remain at their current alti-
There are no studies or case reports of harm to tude and treat symptoms with nonopiate analge-
a fetus if the mother travels briefly to high altitudes sics and antiemetics, such as ondansetron. They
during pregnancy. However, it may be prudent to may also take acetazolamide, which speeds accli-
recommend that pregnant women do not stay at matization and effectively treats AMS, but is better
sleeping altitudes higher than 10,000 ft (3,048 m). for prophylaxis than treatment. Dexamethasone
In addition, the pregnancy should be verified as is more effective than acetazolamide at rapidly
low risk and the mother in good health. The dan- relieving the symptoms of moderate to severe
gers of having a pregnancy complication in remote, AMS. If symptoms are getting worse while the
mountainous terrain should also be discussed. traveler is resting at the same altitude, or in spite
of medication, he or she must descend.
HACE is an extension of AMS characterized
DIAGNOSIS AND TREATMENT by neurologic findings, particularly ataxia, con-
Acute Mountain Sickness/ fusion, or altered mental status. HACE may also
High-Altitude Cerebral Edema occur in the presence of HAPE. People developing
The differential diagnosis of AMS/ HACE HACE in populated areas with access to medical
includes dehydration, exhaustion, hypoglyce- care can be treated at altitude with supplemen-
mia, hypothermia, or hyponatremia. Focal neu- tal oxygen and dexamethasone. In remote areas,
rologic symptoms, or seizures, are rare in HACE descent should be initiated in any person sus-
and should lead to suspicion of an intracranial pected of having HACE. If descent is not feasible
lesion or seizure disorder. Patients with AMS can because of logistical issues, supplemental oxygen
ALTITUDE ILLNESS 59
06
or a portable hyperbaric chamber in addition to or high-altitude medical clinic, for example) may
dexamethasone can be lifesaving. not need to descend to lower elevation and can
be treated with oxygen at the current elevation. In
High-Altitude Pulmonary Edema the field setting, where resources are limited and
Although the progression of decreased exercise there is a lower margin for error, nifedipine can be
tolerance, increased breathlessness, and breath- used as an adjunct to descent, oxygen, or portable
lessness at rest is almost always recognizable as hyperbaric therapy. A phosphodiesterase inhibi-
2 HAPE, the differential diagnosis includes pneu-
monia, bronchospasm, myocardial infarction, or
tor may be used if nifedipine is not available, but
concurrent use of multiple pulmonary vasodila-
pulmonary embolism. Descent in this situation tors is not recommended.
is urgent and mandatory, and should be accom-
plished with as little exertion as is feasible for Medications
the patient. If descent is not immediately possi- In addition to the discussion below, recommen-
ble, supplemental oxygen or a portable hyper- dations for the usage and dosing of medications
baric chamber is critical. Patients with mild to prevent and treat altitude illness are outlined
HAPE who have access to oxygen (at a hospital in Table 2-9.
Acetazolamide AMS, HACE Oral 125 mg twice a day; 250 mg twice a day if >100 kg
prevention Pediatrics: 2.5 mg/kg every 12 h
Abbreviations: AMS, acute mountain sickness; HACE, high-altitude cerebral edema; HAPE, high-altitude pulmonary edema;
IM, intramuscular; IV, intravenous; SR, sustained release.
1
Acetazolamide can also be used at this dose as an adjunct to dexamethasone in HACE treatment, but dexamethasone
remains the primary treatment for that disorder.
2
Should not be used as monotherapy and should only be used in conjunction with oral medications.
ALTITUDE ILLNESS 61
62
BIBLIOGRAPHY
1. Bartsch P, Swenson ER. Acute high-altitude illnesses. Society consensus guidelines for the prevention and
N Engl J Med. 2013 Oct 24;369(17):1666–7. treatment of acute altitude illness. Wilderness Environ
2. Hackett P. High altitude and common medical con- Med. 2010 Jun;21(2):146–55.
ditions. In: Hornbein TF, Schoene RB, editors. High 7. Luks AM, Swenson ER. Medication and dosage con
Altitude: an Exploration of Human Adaptation. siderations in the prophylaxis and treatment of high-
New York: Marcel Dekker; 2001. p. 839–85. altitude illness. Chest. 2008 Mar;133(3):744–55.
JET LAG
Gregory Atkinson, Ronnie Henry, Alan M. Batterham, Andrew Thompson
RISK FOR TRAVELERS new time zone, some people may prefer to anchor
Jet lag results from a mismatch between a per- their sleep–wake schedule to time of day at home
son’s circadian (24-hour) rhythms and the time as much as is practical. Thereby, the total “bur-
of day in the new time zone. When establishing den” of jet lag resulting from the short round trip
risk, clinicians should first determine how many is minimized.
time zones the traveler will cross and what the
discrepancy will be between time of day at home CLINICAL PRESENTATION
and at the destination. During the first few days Jet-lagged travelers typically experience the fol-
after a flight to a new time zone, a person’s circa- lowing symptoms after a flight across >3 time
dian rhythms are still “anchored” to time of day at zones:
home. Rhythms then adjust gradually to the new
time zone. A useful web-based tool for world time • Poor sleep, including difficulty initiating
zone travel information can be found at: www. sleep at the usual time of night (after east-
timeanddate.com/worldclock/converter.html. If ward flights), early awakening (after westward
≤3 time zones are being crossed, the risk of signif- flights), and fractionated sleep (after flights in
icant jet lag is likely to be negligible. either direction)
Many people traveling over >3 time zones for
a vacation accept the risk of jet lag as a transient
• Poor performance in physical and mental
tasks during the new daytime
and mild inconvenience, while other people who
are traveling on business or to compete in athletic • Negative feelings such as fatigue, headache,
events desire clear advice on prophylactic mea- irritability, anxiety, inability to concentrate,
sures and treatments. If ≤2 days are spent in the and depression
JET LAG 63
46
on other symptoms of jet lag and the timing of cir- fatigue compared with the comparator group and
cadian rhythms are not as clear. improved aspects of health-related behavior such
as physical activity, snacking, and sleep quality but
Combination Treatments not other measures of sleep (latency, duration, use
Multiple therapies to decrease jet lag symp- of sleep-related medication).
toms may be combined into treatment packages. In conclusion, there is still no “cure” for jet lag.
Although marginal gains from multiple treatments Counseling should focus on the factors that are
2 may aggregate, evidence from robust randomized
controlled trials is lacking for most of these treat-
known, from laboratory simulations, to alter cir-
cadian timing. Nevertheless, more randomized
ment packages. One treatment package offer- controlled trials of treatments prescribed before,
ing tailored advice via a mobile application was during, or after transmeridian flights are needed
piloted recently to be used over several months before the clinician can provide robust, evidence-
of frequent flying. Participants reported reduced based advice.
BIBLIOGRAPHY
1. Atkinson G, Batterham AM, Dowdall N, Thompson A, 6. Thompson A, Batterham AM, Jones H, Gregson W, Scott
Van Drongelen A. From animal cage to aircraft cabin: an D, Atkinson G. The practicality and effectiveness of
overview of evidence translation in jet lag research. Eur supplementary bright light for reducing jet-lag in elite
J Appl Physiol. 2014 Dec;114(12):2459–68. female athletes. Int J Sports Med. 2013 Jul;34(7):582–9.
2. Herxheimer A. Jet lag. BMJ Clin Evid. 2014 Apr 29. 7. Van Drongelen A, Boot CR, Hlobil H, Twisk JW, Smid T,
3. Herxheimer A, Petrie KJ. Melatonin for the preven- Van der Beek AJ. Evaluation of an mHealth intervention
tion and treatment of jet lag. Cochrane Database of aiming to improve health-related behavior and sleep
Systematic Reviews 2002, Issue 2. Art. No.: CD001520. and reduce fatigue among airline pilots. Scand J Work
Environ Health. 2014 Nov;40(6):557–68.
4. Sack RL. Clinical practice. Jet lag. N Engl J Med. 2010 Feb
4;362(5):440–7. 8. Waterhouse J, Reilly T, Atkinson G. Jet-lag. Lancet. 1997
Nov 29;350(9091):1611–6.
5. Samuels CH. Jet lag and travel fatigue: a comprehensive
management plan for sport medicine physicians and 9. Waterhouse J, Reilly T, Atkinson G, Edwards B. Jet
high-performance support teams Clin J Sport Med. 2012 lag: trends and coping strategies. Lancet. 2007 Mar
May;22(3):268–73. 31;369(9567):1117–29.
MOTION SICKNESS
Stefanie K. Erskine
MOTION SICKNESS 65
6
BIBLIOGRAPHY
1. Golding JF, Gresty MA. Pathophysiology and treatment of 5. Shupak A, Gordon CR. Motion sickness: advances
motion sickness. Curr Opin Neurol. 2015 Feb;28(1):83–8. in pathogenesis, prediction, prevention, and treat-
2. Murdin L, Golding J, Bronstein A. Managing motion ment. Aviat Space Environ Med. 2006 Dec;77(12)
sickness. BMJ. 2011 Dec 2;343:d7430. :1213–23.
3. Priesol AJ. Motion sickness. Deschler DG, editor. 6. Zhang L, Wang J, Qi R, Pan L, Li M, Cai Y. Motion sick-
Waltham MA: UpToDate; 2012. ness: current knowledge and recent advance.
CNS Neurosci Ther. 2016 Jan;22(1):15–24.
4. Schmäl F. Neuronal mechanisms and the treat-
ment of motion sickness. Pharmacology. 2013
May;91(3-4):229–41.
RESPIRATORY INFECTIONS
Regina C. LaRocque, Edward T. Ryan
Respiratory infection is a leading cause of seeking are rare. Clinicians must inquire about history of
medical care in returning travelers. Respiratory travel when evaluating a patient for respiratory
infections occur in up to 20% of all travelers, infections.
which is almost as common as travelers’ diarrhea.
Upper respiratory infection is more common than INFECTIOUS AGENT
lower respiratory infection. In general, the types Viral pathogens are the most common cause
of respiratory infections that affect travelers are of respiratory infection in travelers; causative
similar to those in nontravelers, and exotic causes agents include rhinoviruses, respiratory syncytial
virus, influenza virus, parainfluenza virus, human including respiratory tract inflammation, exac-
metapneumovirus, measles, mumps, adenovirus, erbations of asthma and chronic obstructive pul-
and coronaviruses. Clinicians also need to con- monary disease (COPD), impaired lung function,
sider novel viral causes of respiratory infection in bronchitis, and pneumonia. Certain travelers have
travelers, including Middle East respiratory syn- a higher risk for respiratory tract infection, includ-
drome (MERS) coronavirus and highly pathogenic ing children, the elderly, and people with comorbid
avian influenza viruses. Respiratory infection pulmonary conditions such as asthma and COPD.
due to viral pathogens may predispose to bacte-
rial sinusitis, bronchitis, or pneumonia. Bacterial
The risk for tuberculosis among most travelers
is low (see Chapter 3, Tuberculosis).
2
pathogens are less common but can include
Streptococcus pneumoniae, Mycoplasma pneumo DIAGNOSIS
niae, Haemophilus influenzae, and Chlamydophila Identifying a specific etiologic agent, especially
pneumoniae. Coxiella burnetii and Legionella pneu in the absence of pneumonia or serious disease,
mophila can also cause outbreaks and sporadic is not always clinically necessary. If indicated, the
cases of respiratory illness. following methods of diagnosis can be used:
RESPIRATORY INFECTIONS 67
86
headache, and cough. At present, MERS should makes it problematic to decide whether to pre-
be considered in travelers who develop fever scribe travelers a neuraminidase inhibitor for self-
and pneumonia within 14 days after traveling treatment. This practice should probably be limited
from countries in or near the Arabian Peninsula. to travelers with a specific underlying condition
Certain other patients with illness following con- that may predispose them to severe influenza.
tact with a confirmed or suspected MERS case, or Specific situations that may require medical
with health care facilities with MERS transmis- intervention include the following:
2 sion, should also be evaluated.
Practitioners should be aware that regions
• Pharyngitis without rhinorrhea, cough, or
other symptoms that may indicate infection
associated with MERS may expand or change
with group A Streptococcus.
(www.cdc.gov/coronavirus/mers). H5N1 and
H7N9 should be considered in patients with new- • Sudden onset of cough, chest pain, and fever
onset severe acute respiratory illness requiring that may indicate pneumonia (or pulmonary
hospitalization when no alternative etiology has embolism), resulting in a situation where the
been identified and if the patient has recently traveler may be sick enough to seek medical
(within 10 days) been to a country with recently care right away.
confirmed human or animal cases of H5N1 (www.
cdc.gov/flu/avianflu/h5n1/case-definitions.htm)
• Travelers with underlying medical conditions,
such as asthma, pulmonary disease, or heart
or H7N9 (www.cdc.gov/flu/avianflu/h7n9/case-
disease, who may need to seek medical care
definitions.htm) or has had close contact with an
earlier than otherwise healthy travelers.
ill person who has traveled to these areas in the
last 10 days. It should also be noted that highly
pathogenic avian influenza A H5 virus has now PREVENTION
been reported in wild birds and domestic poultry Vaccines are available to prevent a number of
in the United States. Pulmonary embolism should respiratory diseases, including influenza, S. pneu
be considered in the differential diagnosis of trav- moniae infection, H. influenzae type B infection
elers who present with dyspnea, cough, or pleu- (in young children), pertussis, diphtheria, vari-
risy and fever, especially those who have recently cella, and measles. Unless contraindicated, trav-
been on long car or plane rides. elers should be vaccinated against influenza and
be up-to-date on other routine immunizations.
TREATMENT Preventing respiratory illness while traveling may
Affected travelers are usually managed similarly not be possible, but common-sense preventive
to nontravelers, although travelers with progres- measures include the following:
sive or severe illness should be evaluated for ill-
nesses specific to their travel destinations and
• Minimizing close contact with people who
are coughing and sneezing.
exposure history. Most respiratory infections are
due to viruses, are mild, and do not require spe- • Frequent handwashing, either with soap and
cific treatment or antibiotics. Self-treatment with water or alcohol-based hand sanitizers (con-
antibiotics during travel can be considered for taining ≥60% alcohol) when soap and water
higher-risk travelers who develop symptoms of are not available.
lower respiratory tract infections, such as those
who have chronic bronchitis and who have been
• Using a vasoconstricting nasal spray immedi-
ately before air travel, if the traveler has a pre-
instructed by their providers to take an antibiotic
existing eustachian tube dysfunction, may help
for exacerbations. A respiratory-spectrum fluo-
lessen the likelihood of otitis or barotrauma.
roquinolone such as levofloxacin or a macrolide
such as azithromycin may be prescribed to the Appropriate infection control measures should
traveler for this purpose before travel. be used while managing any patient with a respi-
The rate of influenza among travelers is not ratory infection (www.cdc.gov/flu/professionals/
known. The difficulty in self-diagnosing influenza infectioncontrol).
BIBLIOGRAPHY
1. Benkouiten S, Charrel R, Belhouchat K, Drali T, 6. Jennings L, Priest PC, Psutka RA, Duncan AR, Anderson
Nougairede A, Salez N, et al. Respiratory viruses and T, Mahagamasekera P, et al. Respiratory viruses in air-
bacteria among pilgrims during the 2013 Hajj. Emerg line travellers with influenza symptoms: Results of an
Infect Dis. 2014 Nov.;20(11):1821–7. airport screening study. J Clin Virol. 2015 Jun;67:8–13.
2. Camps M, Vilella A, Marcos MA, Letang E, Munoz J, 7. Leder K, Sundararajan V, Weld L, Pandey P, Brown G,
Salvado E, et al. Incidence of respiratory viruses among Torresi J. Respiratory tract infections in travelers: a
travelers with a febrile syndrome returning from tropical
and subtropical areas. J Med Virol. 2008 Apr;80(4):711–5.
review of the GeoSentinel surveillance network. Clin
Infect Dis. 2003 Feb 15;36(4):399–4 06. 2
3. Foxwell AR, Roberts L, Lokuge K, Kelly PM. 8. Leder K, Torresi J, Libman MD, Cramer JP, Castelli F,
Transmission of influenza on international flights, May Schlagenhauf P, et al. GeoSentinel surveillance of illness
2009. Emerg Infect Dis. 2011 Jul;17(7):1188–94. in returned travelers, 2007–2011. Ann Intern Med. 2013
4. Freedman DO, Weld LH, Kozarsky PE, Fisk T, Robins R, Mar 19;158(6):456–68.
von Sonnenburg F, et al. Spectrum of disease and rela- 9. Luna LK, Panning M, Grywna K, Pfefferle S, Drosten C.
tion to place of exposure among ill returned travelers. N Spectrum of viruses and atypical bacteria in interconti-
Engl J Med. 2006 Jan 12;354(2):119–30. nental air travelers with symptoms of acute respiratory
5. German M, Olsha R, Kristjanson E, Marchand-Austin infection. J Infect Dis. 2007 Mar 1;195(5):675–9.
A, Peci A, Winter AL, et al. Acute respiratory infections 10. Mangili A, Gendreau MA. Transmission of infectious
in travelers returning from MERS-CoV-affected areas. diseases during commercial air travel. Lancet. 2005 Mar
Emerg Infect Dis. 2015 Sep.;21(9):1654–6. 1218;365(9463):989–9 6.
Contaminated food and water often pose a risk pathogens. (Some fish harvested from tropical
for travelers. Many of the infectious diseases asso- waters can transmit toxins that survive cook-
ciated with contaminated food and water are ing; see Food Poisoning from Marine Toxins sec-
caused by pathogens transmitted via the fecal–oral tion in this chapter.) In areas where hygiene and
route. Swallowing, inhaling aerosols of, or coming sanitation are inadequate or unknown, travelers
in contact with contaminated water, including should avoid consuming salads, uncooked veg-
natural freshwater, marine water, or the water in etables, unpasteurized fruit juices, unpasteur-
inadequately treated swimming pools, water play- ized milk, or cheese made from unpasteurized
grounds (splash parks or splash pads), or hot tubs milk. Raw fruits that are eaten unpeeled (such as
and spas can transmit pathogens that can cause strawberries) should be avoided, and fruits that
diarrhea, vomiting, or infection of the ears, eyes, are eaten peeled (such as bananas and mangoes)
skin, or the respiratory or nervous system. should be peeled by the person who eats them.
Produce should be washed under safe running
FOOD water or soaked in water that has been purified,
Travelers should be advised to select food with and then rinsed with safe water just before eat-
care. Raw food is especially likely to be contami- ing (see Water Disinfection for Travelers section
nated. Raw or undercooked meat, fish, and shell- in this chapter). It is safest to eat only food that
fish can carry various intestinal and systemic is fully cooked and served hot. Always refrigerate
with tap water and iced drinks. Because ice might concentrations are not adequately maintained.
be made from contaminated water, travelers in Travelers at increased risk for legionellosis, such
areas with unsafe tap water should request that as the elderly and those with immunocompro-
beverages be served without ice. mising conditions, may choose to avoid entering
or walking near higher-risk areas such as hot tubs
Recreational Water and spas (see Chapter 3, Legionellosis). Travelers
Pathogens that cause gastrointestinal, respira- should avoid pools, water playgrounds, and hot
tory, skin, ear, eye, and neurologic illnesses can
be transmitted by contaminated recreational
tubs or spas where bather limits are not enforced
or where the water is cloudy. Additional guid-
2
water in inadequately treated pools, water play- ance can be found at www.cdc.gov/healthywater/
grounds (splash pads or spray parks), or hot swimming.
tubs and spas or in freshwater or marine water. To protect their health in oceans, lakes, and
Recreational water contaminated by human rivers, travelers should try not to swim or wade
feces from swimmers, sewage, animal waste, (1) near storm drains; (2) in water that may be
or wastewater runoff can appear clear but still contaminated with sewage, human or animal
contain disease-causing infectious or chemical feces, or wastewater runoff; (3) in lakes or riv-
agents. Ingesting even small amounts of such ers after heavy rainfall; 4) in freshwater streams,
water can cause illness. To protect other peo- canals, and lakes in schistosomiasis- endemic
ple, children and adults with diarrhea should areas of the Caribbean, South America, Africa,
not enter recreational water. Infectious patho- and Asia (see Chapter 3, Schistosomiasis); (5) in
gens, such as Cryptosporidium, can survive for water that might be contaminated with urine
days even in well-maintained pools, water play- from animals infected with Leptospira (see
grounds, and hot tubs and spas. Chapter 3, Leptospirosis); or (6) in warm seawater
Maintaining proper pH and free chlorine or when they have wounds. A traveler with an open
bromine concentration is necessary to prevent wound should stay out of the water if the wound
transmission of most infectious pathogens in is not covered with a water-occlusive bandage.
water in pools, water playgrounds, and hot tubs To help prevent a rare but fatal infection caused
and spas. If travelers would like to test recre- by Naegleria fowleri (www.cdc.gov/parasites/
ational water prior to use, CDC recommends pH naegleria), a parasite found in warm freshwater
7.2–7.8 and a free available chlorine concentration around the world, travelers should prevent water
of at least 3 ppm in hot tubs and spas and at least from entering the nose by holding the nose shut
1 ppm in pools and water playgrounds (or a free or wearing a nose clip when swimming, diving, or
available bromine concentration of at least 4 ppm participating in similar activities in warm fresh-
in hot tubs and spas and at least 3 ppm in pools water (including lakes, rivers, ponds, hot springs,
and water playgrounds). Test strips may be pur- or locations with water warmed by discharge
chased at most superstores, hardware stores, and from power plants and industrial complexes), and
pool supply stores. Pseudomonas, which can cause avoid digging in or stirring up sediment, especially
“hot tub rash” or “swimmer’s ear,” and Legionella in warm water. This infection has also been linked
(see Chapter 3, Legionellosis) can multiply in to use of contaminated tap water for sinus and
hot tubs and spas in which chlorine or bromine nasal irrigation.
BIBLIOGRAPHY
1. Cartwright RY, Colbourne JS. Cryptosporidiosis and 3. CDC. Naegleria fowleri—Primary amebic meningo-
hotel swimming pools—a multifaceted challenge. Water encephalitis (PAM). Atlanta, GA: CDC; 2012 [updated
SciTechnol: Water Supply. 2002 Jan 2(3):47–54. Sep. 24, 2015; cited 2016 Apr. 15]; Available from: www.
2. CDC. Drinking water: camping, hiking, travel. cdc.gov/parasites/naegleria/index.html.
Atlanta: CDC; 2012 [cited 2016 Apr. 15]; Available 4. CDC. Legionellosis resource site. Atlanta: CDC; 2013
from: www.cdc.gov/healthywater/drinking/travel/ [cited 2016 Apr. 15]; Available from: www.cdc.gov/
index.html legionella/index.html.
5. CDC. Notes from the field: primary amebic meningo- 8. Eberhart-Phillips J, Besser RE, Tormey MP, Koo D, Feikin
encephalitis associated with ritual nasal rinsing—St. D, Araneta MR, et al. An outbreak of cholera from food
Thomas, US Virgin Islands, 2012. MMWR Morb Mortal served on an international aircraft. Epidemiol Infect.
Wkly Rep. 2013 Nov 15;62(45):903. 1996 Feb;116(1):9–13.
6. CDC. Otitis externa: Swimmer’s ear. Atlanta: CDC; 9. Finelli L, Swerdlow D, Mertz K, Ragazzoni H, Spitalny
2016 [updated May 4, 2016; cited 2016 Apr. 15]; K. Outbreak of cholera associated with crab brought
Available from: www.cdc.gov/healthywater/swimming/ from an area with epidemic disease. J Infect Dis. 1992
swimmers/rwi/ear-infections.html. Dec;166(6):1433–5.
WATER DISINFECTION
FOR TRAVELERS
Howard D. Backer
Heat • Does not impart additional taste or color • Does not improve taste, smell, or appearance
• Single step that inactivates all enteric of source water
pathogens • Fuel sources may be scarce, expensive, or
• Efficacy is not compromised by contaminants
or particles in the water as for halogenation
and filtration
unavailable
• Does not prevent recontamination during
storage
2
Filtration • Simple to operate • Adds bulk and weight to baggage
• Requires no holding time for treatment • Many filters do not reliably remove viruses
• Large choice of commercial product designs • Channeling of water or high pressure can
• Adds no unpleasant taste and often improves force microorganisms through the filter
taste and appearance of water • More expensive than chemical treatment
• Can be combined with halogens to remove or • Eventually clogs from suspended particulate
kill all pathogenic waterborne microbes matter and may require some field
maintenance or repair
• Does not prevent recontamination during
storage
Halogens • Inexpensive and widely available in liquid or • Impart taste and odor to water
(chlorine, tablet form • Flexible dosing requires understanding of
iodine) • Taste can be removed by simple techniques principles
• Flexible dosing • Iodine is physiologically active, with potential
• Equally easy to treat large and small volumes adverse effects
• Will preserve microbiologic quality of stored • Not readily effective against Cryptosporidium
water oocysts
• Efficacy decreases with low water
temperature and decreasing water clarity
• Corrosive and stains clothing
Chlorine • Low doses have no taste or color • Volatile and sensitive to sunlight: do not
dioxide • Simple to use and available in liquid or expose tablets to air, and use generated
tablet form solutions rapidly
• More potent than equivalent doses of chlorine • No persistent residual concentration, so does
• Effective against all waterborne pathogens not prevent recontamination during storage
spores, which are rarely waterborne enteric boil should be adequately disinfected; however, if
pathogens, are killed in seconds at boiling tem- fuel supplies are adequate, travelers may wish to
perature. In addition, the time required to heat boil for 1 minute to allow for a margin of safety.
the water from 60°C to boiling works toward Although the boiling point decreases with alti-
heat disinfection. Any water that is brought to a tude, at common terrestrial travel elevations it
is still above temperatures required to inactivate Progressively finer levels of filtration known as
enteric pathogens. ultrafiltration, nanofiltration, and reverse osmo-
If no other means of water treatment is avail- sis can remove particles of 0.01, 0.001, and 0.0001
able, a potential alternative to boiling is to use tap µm, respectively. All of these filters can remove
water that is too hot to touch, which is probably viruses. Nanofiltration will remove organic mol-
at a temperature between 131°F (55°C) and 140°F ecules, while reverse osmosis will remove mon-
(60°C). This temperature may be adequate to kill ovalent salts, thus achieving desalination. One
2 pathogens if the water has been kept hot in the
tank for some time. Travelers with access to elec-
new portable filter design incorporates hollow
fiber technology, which is a cluster of tiny tubules
tricity can bring a small electric heating coil or a with variable pore sizes that can achieve nano-
lightweight beverage warmer to boil water. filtration and remove virus-size particles. These
are now available in various designs at reason-
Filtration and Clarification able prices, including hand-pump, gravity drip,
Portable hand-pump or gravity-drip filters with and drink through. All are effective, although
various designs and types of filter media are drink-through is least practical due to the nega-
commercially available to international travel- tive pressure required for flow. The high price and
ers. Filter pore size is the primary determinant of slow output of small hand-pump reverse-osmosis
a filter’s effectiveness, but microorganisms also units prohibit use by land-based travelers; how-
adhere to filter media by electrochemical reac- ever, they are survival aids for ocean voyagers, and
tions. Microfilters with “absolute” pore sizes of 0.1– larger powered devices are used for military and
0.4 µm are usually effective to remove cysts and refugee situations. Microfilters that commonly
bacteria but may not adequately remove viruses, use ceramic, synthetic fiber, compressed carbon,
which are a major concern in water with high lev- or large-pore hollow-fiber filter elements are suf-
els of fecal contamination (Table 2-11). Filters that ficient to remove bacteria and protozoan cysts in
claim Environmental Protection Agency (EPA) water with low levels of contamination (wilder-
designation of water “purifier” undergo company- ness water with little human and animal activ-
sponsored testing that has demonstrated removal ity), but hollow-fiber filters with ultrafiltration or
of 106 bacteria, 104 (9,999 of 10,000) viruses, and nanofiltration should be used for water with high
103 Cryptosporidium oocysts or Giardia cysts. levels of human and animal activity in the water-
(EPA does not independently test the validity of shed. A 2-step process of halogen (see below) and
these claims.) microfiltration can also assure virus removal.
Filters made from ceramic clay or simple sand world. Other chlorine- containing compounds
and gravel (slow sand or biosand) filters are suc- such as calcium hypochlorite and sodium
cessfully used for households in developing coun- dichloroisocyanurate, available in granular or
tries. Gravel and sand filters can be improvised tablet formulation, are also effective for water
in remote or austere situations when no other treatment. An advantage of halogens is flexible
means of disinfection is available. dosing that allows use by individual travelers,
Coagulation-flocculation (CF) removes sus- small or large groups, or communities.
pended particles that cause a cloudy appear-
ance and bad taste and do not settle by gravity;
Given adequate concentrations and length
of exposure (contact time), chlorine and iodine
2
this process removes many but not all micro- have similar activity and are effective against
organisms. CF is easily applied in the field. bacteria and viruses (www.cdc.gov/safewater/
Alum—an aluminum salt that is widely used effectiveness-on-pathogens.html). Giardia cysts
in food, cosmetic, and medical applications— are more resistant to halogens; however, field-
or one of several other natural substances is level concentrations are effective with longer
added to the water and stirred. The clumped contact times. For this reason, dosing and con-
particulates that form are allowed to settle, centrations of halogen products are targeted to
then poured through a coffee filter or fine cloth the cysts. Some common waterborne parasites,
to remove the sediment. Tablets or packets of such as Cryptosporidium, are poorly inactivated
powder that combine flocculent and hypochlo- by halogen disinfection at practical concentra-
rite disinfection are available (products include tions, even with extended contact times.
Chlor-floc and PUR Purifier of Water [Proctor Chemical disinfection may be supplemented
and Gamble—for humanitarian use, not sold with filtration to remove resistant oocysts from
commercially]). CF removes most microorgan- drinking water. Cloudy water contains sub-
isms but should not be used as the sole means stances that will neutralize disinfectant, so it will
of disinfection. It also improves the effective- require higher concentrations or contact times
ness of filtration by causing microorganisms, or, preferably, clarification through settling, CF, or
including viruses, to clump with larger parti- filtration before disinfectant is added.
cles, facilitating their removal. Both chlorine and iodine are available in liquid
Granular- activated carbon (GAC) purifies and tablet form. Because iodine has physiologic
water by adsorbing organic and inorganic chem- activity, WHO recommends limiting iodine water
icals and most heavy metals, thereby improving disinfection to a few weeks. Iodine use is not
odor, taste, and safety. GAC is a common compo- recommended for people with unstable thyroid
nent of household and field filters. It may trap but disease or known iodine allergy. In addition, preg-
does not kill organisms. In field water treatment, nant women should not use iodine to disinfect
GAC is best used after chemical disinfection to water over the long term because of the poten-
remove disinfection byproducts as well as the tial effect on the fetal thyroid. Pregnant travelers
taste of iodine and chlorine (see Halogens below). who have other options should use an alternative
means such as heat, chlorine, or filtration.
Some prefer the taste of iodine to chlorine, but
Chemical Disinfection
neither is appealing in doses often recommended
HALOGENS for field use. The taste of halogens in water can be
The most common chemical water disinfec- improved by:
tants are halogens, mainly chlorine and iodine,
although bromine has similar qualities. Sodium • Reducing concentration and increasing
hypochlorite, the active ingredient in com- contact time;
mon household bleach, is the primary disinfec-
tant promoted by CDC and the World Health
• Or, following contact time,
Organization Safe Water System at a 1.5% con- > Running water through a filter containing
centration for household use in the developing activated carbon or
> Adding a 25mg tablet of vitamin C, a tiny turbidity, because suspended particles can shield
pinch of powdered ascorbic acid, or a microorganisms from UV rays.
small amount of hydrogen peroxide.
Solar Irradiation and Heating
IODINE RESINS UV irradiation by sunlight in the UVA range can
Iodine resins transfer iodine to microorganisms substantially improve the microbiologic quality
that come into contact with the resin but leave lit- of water and may be used in austere emergency
2 tle iodine dissolved in the water. The resins have
been incorporated into various filter designs
situations. Recent work has confirmed the effi-
cacy and optimal procedures of the solar disin-
available for field use. Most contain a 1-µm cyst fection (SODIS) technique. Solar disinfection is
filter, which should effectively remove protozoan not effective on turbid water. If the headlines in
cysts. Few models are sold in the United States a newspaper cannot be read through the bottle
because of inconsistent test results. of water, then the water must be clarified before
solar irradiation is used. Under cloudy weather
SALT (SODIUM CHLORIDE) ELECTROLYSIS conditions, water must be placed in the sun for 2
Passing a current through a simple brine salt solu- consecutive days.
tion generates oxidants, including hypochlorite,
which can be used to disinfect microbes. This Silver and Other Products
technique has been engineered into a pocket- Silver ion has bactericidal effects in low doses,
sized, battery-powered product, which is com- and some attractive features include lack of
mercially available. color, taste, and odor, and the ability of a thin
coating on the container to maintain a steady,
CHLORINE DIOXIDE low concentration in water. Silver is widely used
Chlorine dioxide (ClO2) can kill most waterborne by European travelers as a primary drinking
pathogens, including Cryptosporidium oocysts, at water disinfectant. In the United States, silver
practical doses and contact times. Tablets and liq- is approved only for maintaining microbiologic
uid formulations are available to generate chlo- quality of stored water because its concentration
rine dioxide in the field for small-quantity water can be strongly affected by adsorption onto the
treatment. Although extensive data show the effi- surface of the container, and there has been lim-
cacy of chlorine dioxide in municipal and indus- ited testing on viruses and cysts. Silver is avail-
trial systems, fewer data are available to show able alone or in combination with chlorine in
the efficacy of small-quantity treatment compa- tablet formulation.
rable to other halogens—mainly concentrations Several other common products, includ-
achieved and contact time required. ing hydrogen peroxide, citrus juice, and potas-
sium permanganate have antibacterial effects
Ultraviolet (UV) Light in water and are marketed in commercial prod-
UV light kills bacteria, viruses, and Cryptos ucts for travelers. None have sufficient data to
poridium oocysts in water. The effect depends recommend them for primary water disinfection
on UV dose and exposure time. Portable battery- at low doses in the field.
operated units that deliver a metered, timed dose
of UV are an effective way to disinfect small quan- THE PREFERRED TECHNIQUE
tities of clear water in the field. Larger units with Tables 2-10 and 2-12 summarize advantages and
higher output are available where a power source disadvantages of field water disinfection tech-
is available. These units have limited effectiveness niques and their bacteriological efficacy. It is
in water with high levels of suspended solids and advisable to test a method before travel.
Heat + + + + +
Filtration + +/–1 + + +
Halogens + + +2 – +/–3
2
Chlorine dioxide + + + + +
1
Most filters make no claims for viruses. Hollow-fiber filters with ultrafiltration pore size and reverse osmosis are effective.
2
Require higher concentrations and contact time than for bacteria or viruses.
3
Eggs are not very susceptible to halogens, but risk of waterborne transmission is very low.
BIBLIOGRAPHY
1. Backer H. Field water disinfection. In: Auerbach PS, edi- 6. Sobsey MD, Stauber CE, Casanova LM, Brown JM,
tor. Wilderness Medicine. 6th ed. Philadelphia: Mosby Elliott MA. Point of use household drinking water
Elsevier; 2012. pp. 1324–59. filtration: a practical, effective solution for provid-
2. Backer H, Hollowell J. Use of iodine for water disinfec- ing sustained access to safe drinking water in the
tion: iodine toxicity and maximum recommended dose. developing world. Environ Sci Technol. 2008 Jun
Environ Health Perspect. 2000 Aug;108(8):679–84. 15;42(12):4261–7.
3. Bielefeldt AR. Appropriate and sustainable water 7. Swiss Federal Institute of Aquatic Science
disinfection methods for developing communities. and Technology. SODIS method. Dübendorf,
In: Buchaman K, editor. Water Disinfection. New York Switzerland: Swiss Federal Institute of Aquatic Science
City: Nova Science 2011. pp. 41–75. and Technology; 2012 [cited 2016 Sep. 21]; Available
from: www.sodis.ch/methode/index_EN.
4. CDC. Safe water systems for the developing world: a
handbook for implementing household-based water 8. World Health Organization. Boil water. Technical
treatment and safe storage projects. Atlanta: CDC, 2000 Brief. WHO; 2015 [cited 2016 Mar. 13]; Available
[cited 2016 Sep 19]. Available from: http://www.cdc.gov/ from: http://apps.who.int/iris/bitstream/10665/
safewater/pdf/sws-for-the-developing-world-manual.pdf. 155821/1/WHO_F WC_W SH_15.02_eng.pdf ?ua=1.
5. Clasen T, Roberts I, Rabie T, Schmidt W, Cairncross 9. World Health Organization. Guidelines for drinking-
S. Interventions to improve water quality for pre- water quality. WHO; 2011 [cited 2016 Mar. 13]; Available
venting diarrhoea. Cochrane Database Syst Rev. from: http://apps.who.int/iris/bitstream/10665/4 4584/
2006;(3):CD004794. 1/9789241548151_eng.pdf.
around coral reefs. Dinoflagellates are ingested but may be delayed for up to 30 hours. Sym
by herbivorous fish. The toxins produced by ptoms include:
G. toxicus are then modified and concentrated
as they pass up the marine food chain to car- • Gastrointestinal: diarrhea, nausea, vomiting,
and abdominal pain.
nivorous fish and finally to humans. Ciguatoxins
are concentrated in fish liver, intestines, roe, • Cardiovascular: bradycardia, heart block,
and heads. hypotension.
2 G. toxicus may proliferate on dead coral
reefs more effectively than other dinoflagel- • Neurologic: paresthesias, weakness, pain in
the teeth or a sensation that the teeth are
lates. The risk of ciguatera is likely to increase as
loose, burning or metallic taste in the mouth,
more coral reefs deteriorate because of climate
generalized itching, sweating, and blurred
change, ocean acidification, construction, and
vision. Cold allodynia (abnormal sensation
nutrient runoff.
when touching cold water or objects) has
been reported as characteristic, but there
Risk for Travelers can be acute sensitivity to both hot and cold.
Ciguatera poisoning is underrecognized and
Neurologic symptoms usually last a few days
underreported; up to 50,000 cases occur globally
to several weeks but may persist for months
every year. The incidence in travelers to highly
or even years.
endemic areas has been estimated as high as
3 per 100. Ciguatera is widespread in tropical • Neuropsychiatric: fatigue, general malaise,
and subtropical waters, usually between the lat- insomnia.
itudes of 35°N and 35°S; it is particularly com-
The overall death rate from ciguatera poison-
mon in the Pacific and Indian Oceans and the
ing is <0.1% but varies according to the toxin
Caribbean Sea. The incidence and geographic
dose and availability of medical care to deal
distribution of ciguatera poisoning are increas-
with complications. The diagnosis of ciguat-
ing. Newly recognized areas of risk include the
era poisoning is based on the characteristic
Canary Islands, the eastern Mediterranean,
signs and symptoms and a history of eating
and the western Gulf of Mexico. Medical prac-
species of fish that are known to carry ciguat-
titioners must be aware that cases of ciguatera
era toxin. Fish testing can be done by the Food
fish poisoning acquired by travelers in endemic
and Drug Administration (FDA) in their labora-
areas may present in nonendemic (temperate)
tory at Dauphin Island. There is no readily avail-
areas. In addition, cases of ciguatera fish poison-
able test for ciguatera toxins in human clinical
ing are seen with increasing frequency in nonen-
specimens.
demic areas as a result of the increasing global
trade in seafood products.
Fish that are most likely to cause ciguatera poi- Prevention
soning are large carnivorous reef fish, such as bar- Travelers can take the following precautions to
racuda, grouper, moray eel, amberjack, sea bass, prevent ciguatera fish poisoning:
or sturgeon. Omnivorous and herbivorous fish
such as parrot fish, surgeonfish, and red snapper
• Avoid or limit consumption of reef fish.
can also be a risk. • Never eat high-risk fish such as barracuda or
moray eel.
Clinical Presentation • Avoid the parts of the fish that concentrate
Ciguatera poisoning may cause gastrointestinal, ciguatera toxin: liver, intestines, roe, and head.
cardiovascular, neurologic, and neuropsychiat-
ric illness. The first symptoms usually develop Remember that ciguatera toxins do not affect the
within 3–6 hours after eating contaminated fish texture, taste, or smell of fish, and they are not
destroyed by gastric acid, cooking, smoking, freez- there may be respiratory compromise, malig-
ing, canning, salting, or pickling. nant arrhythmias, and hypotension requiring
hospitalization. There are no long-term sequelae.
Treatment Diagnosis is usually clinical. A clustering of cases
There is no specific antidote for ciguatoxin or mai- helps exclude the possibility of true fish allergy.
totoxin poisonings. Symptomatic treatment may
include gabapentin or pregabalin (neuropathic Prevention
symptoms), amitriptyline (chronic paresthesias,
depression, and pruritus), fluoxetine (chronic
Fish contaminated with histamine may have a
peppery, sharp, salty, taste or “bubbly” feel but will
2
fatigue), and nifedipine or acetaminophen (head- usually look, smell, and taste normal. The key to
aches). Intravenous mannitol has been reported prevention is to make sure that the fish is prop-
in uncontrolled studies to reduce the severity and erly iced or refrigerated at temperatures <38°F
duration of neurologic symptoms, particularly if (<3.3°C), or immediately frozen after it is caught.
given within 48 hours of the appearance of symp- Cooking, smoking, canning, or freezing will not
toms. It should only be given to hemodynamically destroy histamine in contaminated fish.
stable, well-hydrated patients.
After recovering from ciguatera poisoning, Treatment
patients may want to avoid any fish, nuts, alcohol, Scombroid poisoning usually responds well to
or caffeine for at least 6 months as they may cause antihistamines (H1- receptor blockers, although
a relapse in symptoms. H2-receptor blockers may also be of benefit).
BIBLIOGRAPHY
1. Ansdell V. Food-borne illness. In: Keystone JS, Freedman 6. Isbister GK, Kiernan MC. Neurotoxic marine poisoning.
DO, Kozarsky PE, Connor BA, Nothduft HD, editors. Lancet Neurol. 2005 Apr;4(4):219–28.
Travel Medicine. 3rd ed. Philadelphia: Saunders 7. Palafox NA, Buenoconsejo-Lum LE. Ciguatera fish poi-
Elsevier; 2013. pp. 425–32. soning: review of clinical manifestations. J Toxicol Toxin
2. Chan TY. Ciguatera fish poisoning in East Asia and Rev. 2001 May;20(2):141–6 0.
Southeast Asia. Marine Drugs. 2015 Jun 2;13(6):3466–78. 8. Schnorf H, Taurarii M, Cundy T. Ciguatera fish poison-
3. Chan TY. Characteristic features and contributory fac-
tors in fatal ciguatera fish poisoning—implications for
ing: a double-blind randomized trial of mannitol ther-
apy. Neurology. 2002 Mar 26;58(6):873–80. 2
prevention and public education. Am J Trop Med Hyg. 9. Sobel J, Painter J. Illnesses caused by marine toxins. Clin
2016 Apr;94(4):704–9. Infect Dis. 2005 Nov 1;41(9):1290–6.
4. Dickey RW, Plakas SM. Ciguatera: a public health per- 10. Stewart I, Lewis RJ, Eaglesham GK, Graham GC, Poole S,
spective. Toxicon. 2010 Aug 15;56(2):123–36. Craig SB. Emerging tropical diseases in Australia. Part 2.
5. Hungerford JM. Scombroid poisoning: a review. Toxicon. Ciguatera fish poisoning. Ann Trop Med Parasitol. 2010
2010 Aug 15;56(2):231–43. Oct;104(7):557–71.
PROTECTION AGAINST
MOSQUITOES, TICKS,
& OTHER ARTHROPODS
John-Paul Mutebi, William A. Hawley, William G. Brogdon
Wear appropriate clothing. Travelers can Insecticides and spatial repellents. More
minimize areas of exposed skin by wearing long- spatial repellent products are becoming com-
sleeved shirts, long pants, boots, and hats. Tucking mercially available. These products, containing
in shirts, tucking pants into socks, and wearing active ingredients such as metofluthrin and alle-
closed shoes instead of sandals may reduce risk. thrin, augment aerosol insecticide sprays, vapor-
Repellents or insecticides, such as permethrin, can izing mats, and mosquito coils that have been
be applied to clothing and gear for added protec- available for some time. Such products can help
2 tion. (Additional information on clothing is below.)
Check for ticks. Travelers should inspect them-
to clear rooms or areas of mosquitoes (spray aero-
sols) or repel mosquitoes from a circumscribed
selves and their clothing for ticks during outdoor area (coils, spatial repellents). Although many of
activity and at the end of the day. Prompt removal these products appear to have repellent or insec-
of attached ticks can prevent some infections. ticidal activity under particular conditions, they
Showering within 2 hours of being in a tick-infested have not yet been adequately evaluated in peer-
area reduces the risk of some tickborne diseases. reviewed studies for their efficacy in preventing
Bed nets. When accommodations are not ade- vectorborne disease. Travelers should supplement
quately screened or air conditioned, bed nets are the use of these products with repellent on skin or
essential in providing protection and reducing dis- clothing and using bed nets in areas where vector-
comfort caused by biting insects. If bed nets do not borne diseases are a risk or biting arthropods are
reach the floor, they should be tucked under mat- noted. Since some products available internation-
tresses. Bed nets are most effective when they are ally may contain pesticides that are not registered
treated with a pyrethroid insecticide. Pretreated, in the United States, it may be preferable for trav-
long-lasting bed nets can be purchased before elers to bring their own. Insecticides and repel-
traveling, or nets can be treated after purchase. lent products should always be used with caution,
Effective, treated nets may also be available in des- avoiding direct inhalation of spray or smoke.
tination countries. Nets treated with a pyrethroid Optimum protection can be provided by
insecticide will be effective for several months if applying the repellents described in the fol-
they are not washed. Long-lasting pretreated nets lowing sections to clothing and to exposed
may be effective for much longer. skin (Box 2-4).
BIBLIOGRAPHY
1. Barnard DR, Xue RD. Laboratory evaluation of spp.—a literature review. Travel Med Infect Dis. 2013
mosquito repellents against Aedes albopictus, Nov-Dec;11(6):374–411.
Culex nigripalpus, and Ochlerotatus triseria 5. Montemarano AD, Gupta RK, Burge JR, Klein K. Insect
tus (Diptera: Culicidae). J Med Entomol. 2004 repellents and the efficacy of sunscreens. Lancet. 1997
Jul;41(4):726–3 0. Jun 7;349(9066):1670–1.
2. Fradin MS, Day JF. Comparative efficacy of insect repel- 6. Murphy ME, Montemarano AD, Debboun M, Gupta
lents against mosquito bites. N Engl J Med. 2002 Jul R. The effect of sunscreen on the efficacy of insect
4;347(1):13–8. repellent: a clinical trial. J Am Acad Dermatol. 2000
3. Goodyer LI, Croft AM, Frances SP, Hill N, Moore SJ, Aug;43(2 Pt 1):219–22.
Onyango SP, et al. Expert review of the evidence base 7. Pages F, Dautel H, Duvallet G, Kahl O, de Gentile L,
for arthropod bite avoidance. J Travel Med. 2010 Boulanger N. Tick repellents for human use:
May-Jun;17(3):182–92. prevention of tick bites and tick-borne diseases.
4. Lupi E, Hatz C, Schlagenhauf P. The efficacy of repel- Vector Borne Zoonotic Dis. 2014 Feb;14(2):
lents against Aedes, Anopheles, Culex and Ixodes 85–93.
SUN EXPOSURE
Vernon E. Ansdell, Rodd Takiguchi
Increased exposure to ultraviolet (UV) radia- carcinoma, squamous cell carcinoma, and mela-
tion occurs near the equator, during summer
months, at high elevation, and between 10 am
noma. Repeated exposure to sunlight in the eyes
can also result in ocular pterygium formation, cat-
2
and 4 pm. Reflection from the snow, sand, and aracts, and macular degeneration.
water increases exposure, a particularly import-
ant consideration for snow skiing, beach activi- PREVENTION
ties, swimming, and sailing. In addition, several
Avoid Overexposure to the Sun
common medications may cause photosensitiv-
Sun exposure is the most preventable risk fac-
ity reactions:
tor for skin cancer, including melanoma. Staying
• Acetazolamide indoors or seeking shade between 10 am and
4 pm is very important in limiting exposure to UV
• Amiodarone rays, particularly UVB rays. The intensity of UV
• Antibiotics ( fluoroquinolones, sulfonamides, rays varies seasonally, peaking at the solstice, and
and tetracyclines) gets stronger at the equator and at high altitudes.
Be aware that sunburn and sun damage can occur
• Diuretics ( furosemide, hydrochlorothiazide) even on cloudy days. Sunburn can occur in a fair-
• Nonsteroidal anti-inflammatory drugs skinned person after as little as 10–15 minutes
(celecoxib, ibuprofen, ketoprofen, naproxen, of unprotected sun exposure. Tanning beds and
piroxicam) sun lamps are also carcinogenic and should be
avoided.
• Sulfonylureas (glipizide, glyburide)
Medical conditions such as connective tissue Protective Clothing
diseases, polymorphous light eruption, rosacea, Wide-brimmed hats, long sleeves, and long pants
and vitiligo can increase sun sensitivity. Alcohol protect against UV rays. Tightly woven cloth-
consumption can lead to behavioral changes ing and darker fabrics provide additional pro-
that increase the risk of sunburn. tection. High-UPF (ultraviolet protection factor
Both UVA rays (320–400 nm) and UVB rays >30) clothing is recommended for travelers at
(290–320 nm) are carcinogenic. UVA rays are increased risk of sunburn or with a history of skin
present throughout the day and can pass through cancer. This type of clothing contains colorless
window glass. UVA rays cause premature aging of compounds, fluorescent brighteners, or treated
the skin and are primarily responsible for drug- resins that absorb UV rays. Sunglasses that pro-
related phototoxicity and photoallergic reactions. vide 100% protection against both UVA and UVB
UVB rays are most intense from 10 am to 4 pm, are radiation are strongly recommended.
blocked by window glass, and are most responsi-
ble for sunburn. Sunscreens
Serious burns are painful, and the skin may Sun protection factor (SPF) defines the extra pro-
be red, tender, swollen, and blistered. These sun- tection against UVB rays that a person receives
burns may be accompanied by fever, headache, by using a sunscreen. Although higher-SPF sun-
itching, and malaise. Cumulative overexposure screens provide more protection than lower-SPF
to the sun leads to premature aging of the skin, sunscreens, SPF is not linear. An SPF 30 sun-
including wrinkling and age spots, as well as an screen does not offer twice the protection of SPF
increased risk for skin cancer, including basal cell 15. Sunscreens with at least an SPF of 15 and
SUN EXPOSURE 87
8
that offer protection from both UVA and UVB • Apply to all exposed areas, including the ears,
rays (labeled “broad-spectrum SPF”) are recom- scalp, back of the neck, tops of the feet, and
mended for best protection. backs of the hands.
Physical sunscreens contain titanium diox-
ide or zinc oxide, inorganic molecules that are • Use a lip balm or lipstick with broad-spectrum
confined to the stratum corneum and reflect SPF ≥15.
and scatter both visible and UV light. They are • Reapply every 2 hours and after sweat-
2 effective, broad-spectrum sunscreens that pro-
tect against both UVA and UVB radiation. With
ing, swimming, or towel-drying (even on
cloudy days).
the advent of nanotechnology, these products
no longer cause an opaque white film on the • The FDA requires that all sunscreens retain
skin and have become cosmetically accept- their original strength for at least 3 years.
able for widespread use. They are recom- Always check the expiration date and discard
mended for people who burn easily or who take all expired product.
medications that may cause photosensitivity • Sunscreens should be applied to the skin
reactions. before insect repellents. (Note: DEET-con-
Chemical sunscreens absorb rather than taining insect repellents may decrease the
reflect UV radiation. A combination of chem- SPF of sunscreens by one-third. Sunscreens
ical agents is recommended to provide broad- may increase absorption of DEET through
spectrum protection against UVA and UVB rays. the skin.)
The Food and Drug Administration (FDA) rec-
ommends using sunscreen with 15 SPF or higher • Avoid products that contain both sunscreens
regularly and as directed. and insect repellents, because sunscreen may
Travelers should consider the following need to be reapplied more often and in larger
key points regarding physical and chemical amounts than the repellent.
sunscreens:
TREATMENT
• Choose a broad-spectrum sunscreen with Travelers with sunburn should maintain hydra-
≥15 SPF to ensure adequate UVA and UVB tion and stay in a cool, shaded, or indoor
protection. environment. Topical and oral nonsteroidal
anti-inflammatory drugs decrease skin redness
• For UVA protection, look for the following if used before or soon after sun exposure and
active ingredients: zinc oxide, titanium diox-
may relieve symptoms such as headache, fever,
ide, avobenzone, ecamsule, oxybenzone,
and local pain. Pain is usually most intense 6–48
dioxybenzone, or sulisobenzone.
hours after sun exposure, and skin usually peels
• Select a waterproof or water-resistant prod- 4–7 days later. Topical steroids are of limited
uct. Waterproof sunscreens confer approxi- benefit, and systemic steroids appear to be inef-
mately 80 minutes of protection in the water, fective in alleviating pain. Cool compresses, col-
and water-resistant products offer 40 minutes loidal oatmeal baths, moisturizing creams, and
of protection. topical aloe vera gel may relieve symptoms. Oral
diphenhydramine may relieve itching. If blisters
• Apply to dry skin 15 minutes to one-half hour occur, they should be left intact to promote
before exposure to the sun.
faster healing. Open erosions should be coated
• At least 1 oz (2 tablespoons or enough to fill with petroleum jelly and covered with sterile
a shot glass) of sunscreen is needed to cover gauze to decrease the risk of infection. If infec-
the exposed areas of the body. Most people tion occurs, oral antibiotics may be necessary. In
only apply 25%–50% of the recommended severe cases of sunburn, dehydration and hypo-
amount of sunscreen, which decreases the volemia may occur, presenting with severely
achieved SPF. inflamed or reddened skin, disorientation,
dizziness or fainting, nausea, chills, high fever, rehydration and narcotic analgesics for pain
and headache. Hospitalization for intravenous relief may be required in these extreme cases.
BIBLIOGRAPHY
1. Gu X, Wang T, Collins DM, Kasichayanula S, Burczynski 4. Krakowski AC, Kaplan LA. Exposure to radiation from
FJ. In vitro evaluation of concurrent use of commercially the sun. In: Auerbach PS, editor. Wilderness Medicine.
available insect repellent and sunscreen preparations.
Br J Dermatol. 2005 Jun;152(6):1263–7.
6th ed. Philadelphia: Mosby Elsevier; 2012. pp. 294–313.
5. McLean DI, Gallagher R. Sunscreens. Use and misuse. 2
2. Han A, Maibach HI. Management of acute sunburn. Am Dermatol Clin. 1998 Apr;16(2):219–26.
J Clin Dermatol. 2004;5(1):39–47. 6. Wang SQ, Stanfield JW, Osterwalder U. In vitro assess-
3. Henry WL, Steven QW. The Skin Cancer ments of UVA protection by popular sunscreens avail-
Foundation’s Guide to Sunscreens New York: Skin able in the United States. J Am Acad Dermatol. 2008
Cancer Foundation; 2012 [cited 2016 Dec;59(6):934–42.
Sep. 22]; Available from: www.skincancer. 7. Wang SQ, Tooley IR. Photoprotection in the era
org/prevention/sun-protection/sunscreen/ of nanotechnology. Semin Cutan Med Surg. 2011
the-skin-cancer-foundations-guide-to-sunscreens. Dec;30(4):210–3.
PROBLEMS WITH HEAT & COLD
Howard D. Backer, David R. Shlim
International travelers encounter environments behaviors are more important. The major means
that may include extremes of climate to which the of heat dissipation are radiation while at rest
traveler is not accustomed. Exposure to heat and and evaporation of sweat during exercise, both
cold can result in serious injury or death. Travelers of which become minimal with air temperatures
should investigate climate extremes that they will above 95°F (35°C) and high humidity.
face during their journey and prepare with proper The major organs involved in temperature reg-
clothing, knowledge, and equipment. ulation are the skin, where sweating and heat
exchange take place, and the cardiovascular sys-
PROBLEMS ASSOCIATED WITH tem, which must increase blood flow to shunt heat
A HOT CLIMATE from the core to the surface, while meeting the
metabolic demands of exercise. Cardiovascular
Risk for Travelers status and conditioning are the major physiologic
Many of the most popular travel destinations are variables affecting the response to heat stress at
tropical or desert areas. Travelers who sit on the all ages. Many chronic illnesses limit tolerance to
beach or by the pool and do only short walking heat and predispose to heat illness, including car-
tours incur minimal risk of heat illness. Those who diovascular disease, extensive skin disorders or
do strenuous hiking, biking, or work in the heat scarring that limits sweating, diabetes, and renal
are at risk, especially travelers coming from cool disease.
or temperate climates who are not in good physi- In addition to environmental conditions and
cal condition and are not acclimatized to the heat. intensity of exercise, dehydration is the most
important predisposing factor in heat illness.
Clinical Presentations Dehydration also reduces exercise performance,
PHYSIOLOGY OF HEAT INJURIES decreases time to exhaustion, and increases inter-
Tolerance to heat depends largely on physiologic nal heat load. Temperature and heart rate increase
factors, unlike cold environments where adaptive in direct proportion to the level of dehydration.
PROBLEMS WITH HEAT & COLD 89
09
Sweat is a hypotonic fluid containing sodium boundary shared with heat stroke. Transient
and chloride. Sweat rates commonly reach 1 L mental changes, such as irritability, confusion, or
per hour and may even exceed this level, which irrational behavior may be present in heat exhaus-
results in substantial fluid and sodium loss. tion, but major neurologic signs such as seizures
or coma indicate heat stroke or hyponatremia.
MINOR HEAT DISORDERS Body temperature may be normal or mildly to
Heat cramps are painful muscle contractions fol- moderately elevated.
2 lowing exercise. They begin an hour or more after
stopping exercise and most often involve heav-
Most cases can be treated with supine rest in the
shade or other cool place and oral water or fluids
ily used muscles in the calves, thighs, and abdo- containing glucose and salt; subsequently, sponta-
men. Rest and passive stretching of the muscle, neous cooling occurs, and patients recover within
supplemented by commercial rehydration solu- hours. An oral solution for treating heat exhaus-
tions or water and salt, will rapidly relieve symp- tion can be made by adding one-fourth to one-half
toms. Water with a salty snack is sufficient. An teaspoon of table salt (or two 1-g salt tablets) to
oral salt solution can be made by adding one- 1 L of water plus 4–6 teaspoons of sugar. To fur-
fourth to one-half teaspoon of table salt (or two ther improve taste, add one-quarter cup of orange
1-g salt tablets) to 1 L of water. To improve taste, juice or 2 teaspoons of lemon juice. Commercial
add a few teaspoons of sugar and/or orange juice sports-electrolyte drinks are also effective. Plain
or lemon juice. water plus salty snacks may be more palatable
Heat syncope is sudden fainting that occurs in and equally effective. Subacute heat exhaustion
unacclimatized people while standing in the heat may develop over several days and is often mis-
or after 15–20 minutes of exercise. Consciousness diagnosed as “summer flu” because of findings of
rapidly returns to normal when the patient is weakness, fatigue, headache, dizziness, anorexia,
supine. Rest, relief from heat, and oral fluids are nausea, vomiting, and diarrhea. Treatment is as
sufficient treatment. described for acute heat exhaustion.
Heat edema is mild swelling of the hands and
feet (more frequent in women) during the first EXERCISE-ASSOCIATED HYPONATREMIA
few days of heat exposure. It resolves sponta- Hyponatremia (low sodium [salt] levels in the
neously and should not be treated with diuretics, blood) occurs in both endurance athletes and
which may delay heat acclimatization and cause recreational hikers, likely due to replacement of
dehydration. fluids with excessive amounts of water. The kid-
Prickly heat (miliaria or heat rash) manifests as neys fail to correct the excess water because of
small, red, raised itchy bumps on the skin caused the influence of inappropriate amounts of anti-
by obstruction of the sweat ducts. It resolves spon- diuretic hormone that act on the kidney to cause
taneously, aided by avoiding continued sweating retention of water and loss of sodium. Loss
and relief from heat. It is best prevented by wear- of sodium through sweat also contributes to
ing light, loose clothing and avoiding heavy, con- hyponatremia.
tinuous sweating. In the field setting, altered mental status
with normal body temperature and a history of
MAJOR HEAT DISORDERS large volumes of water intake suggest hypona-
HEAT EXHAUSTION tremia. The vague and nonspecific symptoms
Most people who experience acute collapse or are the same as those described for hyponatre-
other symptoms associated with exercise in the mia in other settings, including anorexia, nau-
heat are suffering from heat exhaustion— the sea, emesis, headache, muscle weakness, lethargy,
inability to continue exertion in the heat. The confusion, and seizures. Symptoms of heat
presumed cause of heat exhaustion is loss of exhaustion and early hyponatremia are similar.
fluid and electrolytes, but there are no objective Hyponatremia can be distinguished from other
markers to define the syndrome, which is a spec- heat illnesses by persistent alteration of men-
trum ranging from minor complaints to a vague tal status without elevated temperature, delay
in onset of major neurologic symptoms (confu- Early symptoms are similar to those of heat
sion, seizures, or coma), or deterioration up to exhaustion, with confusion or change in personal-
24 hours after cessation of exercise and removal ity, loss of coordination, dizziness, headache, and
from heat. In organized events, measurement of nausea that progress to more severe symptoms.
serum sodium should be used to diagnose hypo- A presumptive diagnosis of heat stroke is made in
natremia and guide treatment. Gaining weight or the field when people have elevation of body tem-
failure to lose weight increases risk of symptom- perature (hyperpyrexia) and marked alteration of
atic hyponatremia.
The recommendation to force fluid intake
mental status, including delirium, convulsions,
and coma. Body temperatures in excess of 106°F
2
during prolonged exercise and the attitude that (41°C) can occur in heat stroke; even without a
“you can’t drink too much” are major contributors thermometer, people will feel hot to the touch. If a
to exercise-associated hyponatremia. Prevention thermometer is available, a rectal temperature is
includes drinking only enough to relieve thirst. the safest and most reliable way to check the tem-
During prolonged exercise (>12 hours) or heat perature of someone who may have heat stroke;
exposure, supplemental sodium should be taken. an axillary temperature may give a reasonable
Most sports-electrolyte drinks do not contain suf- estimation.
ficient amounts of sodium to prevent hyponatre- In the field, immediately institute cooling mea-
mia; on the other hand, salt tablets often cause sures by these methods:
nausea and vomiting. For hikers, food is the most
efficient vehicle for salt replacement. Trail snacks
• Maintain the airway if victim is unconscious.
should include not just sweets, but salty foods • Move to the shade or a cool place out of the sun.
such as trail mix, crackers, and pretzels.
If hyponatremia is suspected along with neu-
• Use evaporative cooling: remove excess cloth-
ing to maximize skin exposure, spray tepid
rologic symptoms in the absence of hyperther-
water on the skin, and maintain air move-
mia or other diagnoses, restrict fluid. In conscious
ment over the body by fanning. Alternatively,
patients who can tolerate oral intake, salty snacks
place cool or cold wet towels over the body
may be given with sips of water or a solution of
and fan to promote evaporation.
concentrated broth (2–4 bouillon cubes in 1/2 cup
of water). Obtunded patients may require hyper- • Apply ice or cold packs to the neck, axillas,
tonic saline. groin, and as much of the body as possible.
Vigorously massage the skin to limit constric-
tion of blood vessels and prevent shivering,
HEAT STROKE
which will increase body temperature.
Heat stroke is an extreme medical emergency
requiring aggressive cooling measures and hos- • Immerse the person in cool or cold water,
pitalization for support. Heat stroke is the only such as a nearby pool or natural body of
form of heat illness in which the mechanisms for water or bath—an ice bath cools fastest.
thermal homeostasis have failed, and the body Always attend and hold the person while in
does not spontaneously restore the temperature the water.
to normal. As a result of uncontrolled fever and
circulatory collapse, organ damage can occur in
• Encourage rehydration for those able to take
oral fluids.
the brain, liver, kidneys, and heart. Damage is
related to duration as well as peak elevation of Heat stroke victims usually have significant dehy-
body temperature. The onset of heat stroke may dration, so intravenous or oral fluid replace-
be acute (exertional heat stroke), which can affect ment is indicated. Heat stroke is life threatening,
healthy people who are exercising in the heat, or and many complications may occur in the first
gradual (nonexertional heat stroke, also referred 24–48 hours, including liver or kidney damage
to as classic or epidemic), which occurs from pas- and abnormal bleeding. Most victims require hos-
sive heat exposure in those with chronic illness. pital intensive care management. If evacuation to
PROBLEMS WITH HEAT & COLD 91
92
a hospital will be delayed, monitor closely for sev- advantage over plain water. However, for those
eral hours for temperature swings. exercising many hours in heat, salt replacement is
recommended. Eating salty snacks or lightly salt-
Prevention of Heat Disorders ing mealtime food or fluids is the most efficient
HEAT ACCLIMATIZATION way to replace salt losses. Salt tablets, when swal-
Heat acclimatization is a process of physiologic lowed whole, may cause gastrointestinal irrita-
adaptation to a hot environment that occurs in tion and vomiting but may be better tolerated if
2 both residents and visitors. The result of acclimati-
zation is increased sweating with less salt content,
2 tablets are dissolved in 1 L of water. Urine vol-
ume and color are a reasonable means to monitor
and decreased energy expenditure with lower rise fluid needs.
in body temperature for a given workload. Only
partial adaptation occurs by passive exposure to PROBLEMS ASSOCIATED WITH
heat. Full acclimatization, especially cardiovas- A COLD CLIMATE
cular response, requires 1–2 hours of exercise in
Risk for Travelers
the heat each day. Most acclimatization changes
Travelers do not have to be in an arctic or high-
occur within 10 days, provided a suitable amount
altitude environment to encounter problems with
of daily exercise. After this time, only increased
the cold. Humidity, rain, and wind can produce
physical fitness will result in further exercise toler-
hypothermia even with temperatures around 50°F
ance. Decay of acclimatization occurs within days
(10°C). Even in a temperate climate, a traveler
to weeks if there is no heat exposure.
in a small boat that overturns in cold water can
PHYSICAL CONDITIONING AND rapidly become hypothermic. However, reports
ACCLIMATIZATION of severe hypothermia in international travel-
ers are rare. Many high-altitude destinations are
Higher levels of physical fitness improve exercise
not wilderness areas, and villages offer an escape
tolerance and capacity in heat, but not as much as
from extreme weather. In Nepal, trekkers almost
acclimatization. If possible, travelers should accli-
never experience hypothermia except in the rare
matize before leaving by exercising ≥1 hour daily
instance in which they get lost in a storm.
in the heat. If this is not possible before depart-
ing, limit exercise intensity and duration during
the first week of travel in a hot climate. It is a good Clinical Presentations
idea to conform to the local practice in most hot HYPOTHERMIA
regions and avoid strenuous activity during the Hypothermia can be defined as having a core
hottest part of the day. body temperature below 95°F (35°C). When peo-
ple are faced with an environment in which they
CLOTHING cannot keep warm, they first feel chilled, then
Clothing should be lightweight, loose, and light- begin to shiver, and eventually stop shivering
colored to allow maximum air circulation for as their metabolic reserves are exhausted. Body
evaporation yet give protection from the sun. temperature continues to decrease, depending
A wide-brimmed hat markedly reduces radiant on the ambient temperatures. As the core tem-
heat exposure. perature falls, neurologic functioning decreases
until almost all hypothermic people with a core
FLUID AND ELECTROLYTE REPLACEMENT temperature of 86°F (30°C) or lower are coma-
During exertion, fluid intake improves perfor- tose. The record low core body temperature in
mance and decreases the likelihood of illness. an adult who survived is 56°F (13°C). Travelers
Reliance on thirst alone is not sufficient to pre- headed to a cold climate should ask questions
vent mild dehydration, but forcing a person who and research clothing and equipment. Modern
is not thirsty to drink water creates the potential clothing, gloves, and particularly footwear have
danger of hyponatremia. During mild to moder- greatly decreased the chances of suffering cold
ate exertion, electrolyte replacement offers no injury in extreme climates. Cold injuries occur
more often after accidents, such as avalanches Once frostbite has occurred, little can be done
or unexpected nights outside, than during nor- to reverse the changes. Therefore, taking great
mal recreational activities. care to prevent frostbite is crucial. Frostbite is
Travelers engaging in recreational activities or usually graded like burns. First-degree frostbite
working around cold water face a different sort of involves reddening of the skin without deeper
risk. Immersion hypothermia can render a person damage. The prognosis for complete healing is vir-
unable to swim or keep floating in <15 minutes. In tually 100%. Second-degree frostbite involves blis-
these cases, a personal flotation device is critical,
as is knowledge about self-rescue and righting a
ter formation. Blisters filled with clear fluid have a
better prognosis than blood-tinged blisters. Third-
2
capsized boat. degree frostbite represents full-thickness injury to
The other medical conditions associated with the skin and possibly the underlying tissues. No
cold affect mainly the skin and the extremities. blister forms, the skin darkens over time and may
These can be divided into nonfreezing cold inju- turn black. If the tissue is completely devascular-
ries and freezing injuries ( frostbite). ized, amputation will be necessary.
Frostbitten skin is numb and appears whitish
NONFREEZING COLD INJURY or waxy. The generally accepted method for treat-
Nonfreezing cold injuries include trench foot ing a frozen digit or limb is through rapid rewarm-
(immersion foot), pernio (chilblains), and cold ing in water heated to 104°F–108°F (40°C–42°C).
urticaria. Trench foot is caused by prolonged The frozen area should be completely immersed
immersion of the feet in cold water (32°F–59°F; in the warm water. A thermometer is needed to
0°C–15°C). The damage is mainly to nerves and ensure the water is kept at the correct tempera-
blood vessels, and the result is pain that is aggra- ture. Rewarming can be associated with severe
vated by heat and a dependent position of the pain, so analgesics can be given if needed. Once
limb. Severe cases can take months to resolve. the area is rewarmed, it must be safeguarded
Unlike the treatment for frostbite, immersion foot against freezing again. It is better to keep digits
should not be rapidly rewarmed, which can make frozen a little longer and rapidly rewarm them,
the damage much worse. than to allow them to thaw out slowly or to thaw
Pernio are localized, inflammatory lesions that and refreeze. A cycle of freeze-thaw-refreeze is
occur mainly on the hands and with exposure devastating to tissue and can lead to amputation.
to only moderately cold weather. The bluish-red Once the area has rewarmed, it can be exam-
lesions are thought to be caused by prolonged, ined. If blisters are present, note whether they
cold-induced vasoconstriction. As with trench extend to the end of the digit. Proximal blisters
foot, rapid rewarming should be avoided, as it usually mean that the tissue distal to the blister
makes the pain worse. Nifedipine may be an effec- has suffered full-thickness damage. For treatment,
tive treatment. avoid further mechanical trauma to the area and
Cold urticaria involves the formation of local- prevent infection. In the field, wash the area thor-
ized or general wheals and itching. It is not the oughly with a disinfectant such as povidone-
absolute temperature that induces this form of iodine, put dressings between the toes or fingers
urticaria but the rate of change of temperature in to prevent maceration, use fluffs (expanded gauze
the skin. sponges) for padding, and cover with a roller gauze
bandage. These dressings can safely be left on for
FREEZING COLD INJURY up to 3 days at a time. By leaving the dressings on
Frostbite is the term that is used to describe tissue longer, the traveler can preserve what may be lim-
damage from direct freezing of the skin. Modern ited supplies of bandages. Prophylactic antibiotics
equipment and clothing have decreased the risk are not needed in most situations.
of frostbite resulting from adventure tourism, In the rare situation in which a foreign trav-
and frostbite occurs mainly during an accident, eler suffers frostbite and can be evacuated to an
severe unexpected weather, or as a result of poor advanced medical setting within 24– 72 hours,
planning. there may be a role for thrombolytics, such as
PROBLEMS WITH HEAT & COLD 93
49
prostacyclin and recombinant tissue plasmino- Once the patient has reached a definitive med-
gen activator. If you are managing frostbite in the ical setting, there should be no rush to do surgery.
first 72 hours, you should consult someone with The usual time from injury to surgery is 4–5 weeks.
expertise in frostbite as soon as possible. The risks Technetium (Tc)- 99 scintigraphy and magnetic
and benefits of using these drugs should be care- resonance imaging can be used to help define the
fully considered in each patient. Beyond 72 hours extent of the damage. Once the delineation between
after thawing, these interventions are probably not dead tissue and viable becomes clear, surgery that
2 beneficial. preserves the remaining digits can be planned.
BIBLIOGRAPHY
1. Armstrong LE, Casa DJ, Millard-Stafford M, Moran DS, 5. Freer L, Imray CHE. Frostbite. In: Auerbach PS, editor.
Pyne SW, Roberts WO. American College of Sports Wilderness Medicine. 6th ed. Philadelphia: Mosby
Medicine position stand. Exertional heat illness during Elsevier; 2012. pp. 181–201.
training and competition. Med Sci Sports Exerc. 2007 6. Hadad E, Rav-Acha M, Heled Y, Epstein Y, Moran DS.
Mar;39(3):556–72. Heat stroke: a review of cooling methods. Sports Med.
2. Bennett BL, Hew-Butler T, Hoffman MD, Roger sIR, 2004;34(8):501–11.
Rosner MH, Wilderness Medical Society. Wilderness 7. Lipman GS, Eifling KP, Ellis MA, Gaudio FG, Otten EM,
Medical Society practice guidelines for treatment Grissom CK, et al. Wilderness Medical Society practice
of exercise-associated hyponatremia: 2014 update. guidelines for the prevention and treatment of heat-
Wilderness Environ Med. 2014 Dec;25(4 Suppl):S30–42. related illness: 2014 update. Wilderness Environ Med.
3. Cauchy E, Cheguillaume B, Chetaille E. A controlled 2014 Dec;25(4 Suppl):S55–65.
trial of a prostacyclin and rt-PA in the treatment of 8. O’Brien KK, Leon LR, Kenefick RW. Clinical manage-
severe frostbite. N Engl J Med. 2011 Jan 13;364(2): ment of heat-related illnesses. In: Auerbach PS, editor.
189–9 0. Wilderness Medicine. 6th ed. Philadelphia: Mosby
4. Epstein Y, Moran DS. Extremes of temperature Elsevier; 2012. pp. 232–8.
and hydration. In: Keystone JS FD, Kozarsky PE, 9. Rogers IR, Hew-Butler T. Exercise-associated hypona-
Connor BA, Nothdurft HD, editor. Travel Medicine. tremia: overzealous fluid consumption. Wilderness
Philadelphia: Saunders Eslevier; 2013. pp. 381–9 0. Environ Med. 2009 Summer;20(2):139–43.
INJURY PREVENTION
David A. Sleet, David J. Ederer, Michael F. Ballesteros
According to the World Health Organization In 2013 and 2014, an estimated 1,670 US citi-
(WHO), injuries are among the leading causes of zens died from nonnatural causes, such as injuries
death and disability in the world, and they are the and violence, while in foreign countries (exclud-
leading cause of preventable death in travelers. ing deaths occurring in the wars in Iraq and
An estimated 18%–24% of deaths among travelers Afghanistan). Motor vehicle crashes—not crime
in foreign countries are caused by injuries, com- or terrorism—are the number 1 killer of healthy
pared with only 2% of deaths caused by infectious US citizens living, working, or traveling overseas.
diseases. Contributing to the injury toll while In 2013 and 2014, 456 Americans died in road traf-
traveling are unfamiliar and perhaps risky envi- fic crashes abroad (27% of nonnatural deaths).
ronments, differences in language and communi- Another 350 were victims of homicide (21%), 286
cations, less stringent product safety and vehicle committed suicide (17%), and 220 drowned (13%)
standards, unfamiliar rules and regulations, and a (Figure 2-2).
carefree holiday or vacation spirit leading to more If a traveler is seriously injured in a foreign
risk-taking behavior. country, emergency care may not be available
500
400
300
2
200
100
0
fic
ed
ng
e
n
e
r
n
e
id
id
io
de
th
af
at
ni
ic
ic
ct
lo
tr
ow
el
i
m
Su
ta
cc
-r
ad
Ho
Al
Dr
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is
ug
Ro
r
Ai
ro
Dr
r
Te
FIGURE 2-2 . Leading causes of injury death for US citizens in foreign countries, 2013 & 20141,2
1
Data from US Department of State. Death of US citizens abroad by non-natural causes. Washington, DC: US Department of
State; 2016 [cited 2016 Mar. 24]. Available from: http://travel.state.gov/content/travel/english/statistics/deaths.html.
2
Excludes deaths of US citizens fighting wars in Afghanistan or Iraq, and deaths that were not reported to the nearest US
Embassy or Consulate.
or acceptable by US standards. Trauma cen- deaths were related to motorcycle use in these
ters capable of providing optimal care for seri- countries. The reported rate of motorbike inju-
ous injuries are uncommon outside urban areas ries in Bermuda is much higher in tourists than
in many foreign destinations. Travelers should in the local population, and the rate is highest
be aware of the increased risk of certain injuries among those aged 50–59 years. Motor vehicle
while traveling or residing abroad, particularly rentals for tourists in Bermuda and some other
in developing countries, and be prepared to take small Caribbean islands are typically limited to
preventive steps. motorbikes, possibly contributing to the higher
rates of motorbike injuries. Loss of vehicular con-
ROAD TRAFFIC INJURIES trol, unfamiliar equipment, and inexperience with
Globally, an estimated 3,300 people, including 720 motorized 2-wheelers contribute to crashes and
children, are killed each day in road traffic crashes injuries, even at speeds <30 miles per hour.
involving cars, buses, motorcycles, bicycles, Road traffic crashes are common among for-
trucks, and pedestrians. Annually, 1.24 million eign travelers for a number of reasons: lack of
are killed and 20–50 million are injured in traf- familiarity with the roads, driving on the opposite
fic crashes—a number likely to double by 2030. side of the road, lack of seat belt use, the influence
Although only 53% of the world’s vehicles are in of alcohol, poorly made or maintained vehicles,
developing countries, more than 90% of road traf- travel fatigue, poor road surfaces without shoul-
fic casualties occur in these countries. ders, unprotected curves and cliffs, and poor vis-
According to US Department of State data, ibility due to lack of adequate lighting. In many
road traffic crashes are the leading cause of injury developing countries, unsafe roads and vehicles
deaths to US citizens while abroad (Figure 2-2). and an inadequate transportation infrastructure
Motorcycle use is a risk factor for road traffic contribute to the traffic injury problem. In many
crashes; in 2013 and 2014, approximately 20% of of these countries, motor vehicles often share the
road traffic deaths while abroad involved motor- road with vulnerable road users such as pedestri-
cycles. Road deaths per million trips are highest ans, bicyclists, and motorcycle users. The mix of
in Thailand and Vietnam, and most American traffic including cars, buses, taxis, rickshaws, large
INJURY PREVENTION 95
96
trucks, and even animals increases the risk for International Road Travel (www.asirt.org) and
crashes and injuries. Make Roads Safe (www.makeroadssafe.org)
Strategies to reduce the risk of traffic injury have useful safety information for international
are shown in Table 2- 13. The Association for travelers, including road safety checklists and
Lack of seat belts Always use safety belts and child safety seats. Rent vehicles with seat belts; when possible,
and child safety ride in taxis with seat belts and sit in the rear seat; bring child safety seats and booster
seats seats from home for children to ride properly restrained.
Driving hazards When possible, avoid driving at night in developing countries; always pay close attention to
the correct side of the road when driving in countries that drive on the left.
Country-specific Check the Association for Safe International Road Travel website for driving hazards or
driving hazards risks by country (www.asirt.org).
Motorcycles, Always wear helmets (bring a helmet from home, if needed). When possible, avoid driving
motorbikes, and or riding on motorcycles or motorbikes, including motorcycle and motorbike taxis. Traveling
bicycles overseas is a bad time to learn to drive a motorcycle or motorbike.
Alcohol-impaired Alcohol increases the risk for all causes of injury. Do not drive after consuming alcohol, and
driving avoid riding with someone who has been drinking. Penalties can be severe overseas.
Cellular Do not use a cellular telephone or text while driving. Many countries have enacted laws
telephones banning cellular telephone use while driving, and some countries have made using any kind
of telephone, including hands-free, illegal while driving.
Taxis or hired Ride only in marked taxis, and try to ride in those that have safety belts accessible. Hire
drivers drivers familiar with the area.
Bus travel Avoid riding in overcrowded, overweight, or top-heavy buses or minivans and avoid riding in
mountainous terrains, at night, and with a drinking or distracted bus driver.
Pedestrian Be alert when crossing streets, especially in countries where motorists drive on the left side
hazards of the road. Walk with a companion or someone from the host country.
Other Tips
Airplane travel Avoid using local, unscheduled aircraft. If possible, fly on larger planes (>30 seats), in good
weather, during the daylight hours, and with experienced pilots.Children <2 years should sit
in a child safety seat, not on a parent’s lap. Whenever possible, parents should travel with a
safety seat for use before, during, and after a plane ride.
Drowning Avoid swimming alone or in unfamiliar waters. Wear life jackets while boating or during
water recreation activities.
Burns In hotels, stay below the 6th floor to maximize the likelihood of being rescued in a fire. Bring
your own smoke alarm.
country-specific driving risks. The Department in developing countries where building codes do
of State has safety information useful to interna- not exist or are not enforced, there are no smoke
tional travelers, including road safety and security alarms, there is no access to emergency services,
alerts, international driving permits, and travel and the fire department’s focus is on putting
insurance (www.travel.state.gov). out fires rather than on fire prevention or victim
rescue.
WATER AND AQUATIC INJURIES In 2013 and 2014, an estimated 50 US citi-
In 2013 and 2014, drowning accounted for 13%
of all deaths of US citizens abroad. Although risk
zens abroad were killed in aircraft crashes.
Travel by local, lightweight aircraft in many
2
factors have not been clearly defined, these deaths countries can be risky. Travel on unscheduled
are most likely related to unfamiliarity with local flights, in small aircraft, at night, in inclement
water currents and conditions, inability to swim, weather, and with inexperienced pilots carries
and the absence of lifeguards on duty. Rip cur- the highest risk.
rents can be especially dangerous, as are sea ani- Before flying with children, parents and care-
mals such as urchins, jellyfish, coral, and sea lice. givers should check to make sure that their child
Alcohol also contributes to drowning and boating restraint system is approved for use on an air-
mishaps. craft. This approval should be printed on the sys-
Drowning is often the leading cause of injury tem’s information label or on the device itself. The
death to US citizens visiting countries where Federal Aviation Administration (FAA) recom-
water recreation is a major activity, such as Fiji, mends that a child weighing <20 pounds use a
the Bahamas, Jamaica, and Costa Rica. Young rear-facing child restraint system. A forward-fac-
men are particularly at risk of head and spinal ing child safety seat should be used for children
cord injuries from diving into shallow water, and weighing 20–40 pounds. FAA has also approved a
alcohol is a factor in some cases. harness-type device for children weighing 22–44
Boating can be a hazard, especially if boaters pounds.
are unfamiliar with the boat, do not know proper
boating etiquette or rules for watercraft naviga- TRAVEL TIPS
tion, or are new to the water environment in a Health care providers, vendors of travel services,
foreign country. In 2013 and 2014, maritime acci- and travelers themselves should consider the
dents resulted in 16 deaths to healthy Americans following:
abroad. Many boating fatalities result from inex- • Travelers may wish to purchase special travel
perience or failure to wear lifejackets. health and medical evacuation insurance if
Scuba diving is a frequent pursuit of travelers their destinations include countries where
in coastal destinations. The death rate among all there may not be access to good medical
divers worldwide is thought to be 15–20 deaths care (see the Travel Insurance, Travel Health
per 100,000 divers per year. Travelers should Insurance, & Medical Evacuation Insurance
either be experienced divers or dive with a reli- section later in this chapter).
able dive shop and instructors. See the Scuba
Diving section later in this chapter for a more • Adventure activities, such as mountain
detailed discussion about diving risks and pre- climbing, skydiving, whitewater rafting,
ventive measures. dune-buggying, kayaking, skiing, and snow-
boarding are popular with travelers. The
lack of rapid emergency trauma response,
OTHER UNINTENTIONAL inadequate trauma care in remote loca-
INJURIES tions, and sudden, unexpected weather
In 2013 and 2014, other unintentional injuries
changes that compromise safety and ham-
such as aviation incidents, drug- related inci-
per rescue efforts can delay care and reduce
dents, natural disasters, and deaths classified as
survivability.
“other unintentional injuries” (including fires and
falls) accounted for 19% of deaths to healthy US • Travelers should avoid using local, unsched-
citizens abroad. Fires can be a substantial risk uled, small aircraft and refrain if possible from
INJURY PREVENTION 97
89
flying in bad weather and at night. If avail- own smoke alarm. Two escape routes
able, choose larger aircraft (>30 seats), as they from buildings should always be identified.
are more likely to have undergone more strict Crawling low under smoke and covering
and regular safety inspections. Larger aircraft one’s mouth with a wet cloth are helpful in
also provide more protection in the event escaping a fire. Families should agree on a
of a crash. For country-specific airline crash meeting place outside the building in case a
events, see www.airsafe.com. fire erupts.
2 • When traveling by air with young chil- • Improperly vented heating devices may cause
dren, consider bringing a child safety seat poisoning from carbon monoxide. Carbon
approved for use on an aircraft, helmets if monoxide (CO) at the back of boats near the
considering riding bicycles or motorbikes, engine can be especially dangerous. Travelers
and life preservers if travelers will be in may want to carry a personal CO detector
the water. that can sound an alert in the presence of
this lethal gas.
• To prevent fire-related injuries, travelers
should select accommodations no • Travelers should consider learning basic
higher than the sixth floor ( fire ladders first aid and CPR before travel overseas
generally cannot reach higher than the with another person. Travelers should bring
sixth floor). Hotels should be checked for a travel health kit, which should be cus-
smoke alarms and preferably sprinkler tomized to the anticipated itinerary and
systems. Travelers may want to bring their activities.
BIBLIOGRAPHY
1. Balaban V, Sleet DA. Pediatric travel injuries: risk, 6. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K.
prevention, and management. In: Kamat DM, Fischer Global and regional mortality from 235 causes of death
PR, editors. American Academy of Pediatrics Textbook for 20 age groups in 1990 and 2010: a systematic analysis
of Global Child Health. 2nd ed. Elk Grove Village, for the Global Burden of Disease Study 2010. Lancet.
IL: American Academy of Pediatrics; 2015. 2012 Dec 15;380(9859):2095–128.
2. Ederer D, Parker E, Sleet DA. Motorcycle helmets as a 7. Sherry MK, Mossallam M, Mulligan M, Hyder AA,
vaccine: CDC and Asia Injury Prevention Foundation Bishai D. Rates of intentionally caused and road
Partner in Cambodia and Uganda. CDC’s Division of crash deaths of US citizens abroad. Inj Prev. 2015
Global Health Protection; 2014 [cited 2016 Sep. 29]; Apr;21(e1):e10–4.
Spring 2014, Issue 14. Available from: www.cdc.gov/ 8. US Department of Commerce. 2015 US travel and
globalhealth/healthprotection/fieldupdates/pdf/dghp- tourism statistics. Washington, DC: US Department
field-updates-2014-spring.pdf. of Commerce; 2016 [cited 2016 Sep. 29]; Available
3. Guse CE, Cortes LM, Hargarten SW, Hennes HM. from: http://travel.trade.gov/outreachpages/outbound.
Fatal injuries of US citizens abroad. J Travel Med. 2007 general_information.outbound_overview.asp.
Sep-Oct;14(5):279–87. 9. US Department of State. Tips for traveling abroad.
4. Lawson CJ, Dykewicz CA, Molinari NA, Lipman H, Washington, DC: US Department of State; 2012 [cited
Alvarado-Ramy F. Deaths in international travelers 2016 Sep. 22]; Available from: https://travel.state.gov/
arriving in the United States, July 1, 2005 to June 30, content/passports/en/go/checklist.html.
2008. J Travel Med. 2012 Mar-Apr;19(2):96–103. 10. World Health Organization. WHO global status
5. Li G, Pressley JC, Qiang Y, Grabowski JG, Baker SP, report on road safety 2015. Geneva: World Health
Rebok GW. Geographic region, weather, pilot age, and Organization; 2015 [cited 2016 Sep. 22] Available from
air carrier crashes: a case-control study. Aviat Space http://www.who.int/violence_injury_prevention/road_
Environ Med. 2009 Apr;80(4):386–9 0. safety_status/2015/en/.
Violence is a leading worldwide public health to receive updated information about safety and
problem and a growing concern of US citi-
zens traveling, working, or residing abroad.
security conditions and messages about emergent
threats while they are abroad. The governments of
2
International terrorism and crime are risks any- the United Kingdom, Canada, and Australia also
where in the world, but international travelers have excellent websites with safety and security
operating in an unfamiliar environment face par- information for travelers.
ticular hurdles. Travelers may not have access to
networks of friends or family to assist them. Local CRIME
government responses to problems may be differ- One of the most common threats to the safety of
ent from what US residents expect, or an effective US citizens abroad comes from criminal activity.
local government may not exist to respond at all. Travelers to foreign countries are viewed by many
Language barriers, unexpected costs, or different criminals as wealthy, naïve targets, who are inex-
cultural mores can also complicate what happens perienced, unfamiliar with the culture, and inept
in an emergency. The best way for US residents at seeking assistance if victimized. Traveling in
going overseas to manage their risk is to prepare high-poverty areas or regions of civil unrest, using
before they travel. Travelers should research con- alcohol or drugs, and traveling in unfamiliar envi-
ditions at their destination to learn what risks ronments at night increase the likelihood that a
they are likely to face and have a plan to mitigate traveler will be the victim of crime.
those risks while they are abroad. Travelers should take the time to research crime
trends and patterns at their destination through
RESEARCH AND PREPARATION the Overseas Security Advisory Council at www.
Travelers need information to make good deci- osac.gov. Strategies for avoiding becoming the vic-
sions about risks while traveling and to make tim of a crime overseas are, for the most part, the
plans to deal with those risks. The Department same common-sense habits that people should fol-
of State’s Bureau of Consular Affairs publishes low everywhere, but the following actions should
comprehensive information on safety and secu- be stressed with international travelers:
rity concerns for every independent nation,
along with basic advice for safe travel anywhere,
• Limit travel at night, travel with a companion,
and vary routine travel habits.
at http://travel.state.gov. More information can
also be found at individual embassy and consul- • Do not wear expensive clothing or
ate websites, all of which can be found at www. accessories.
usembassy.gov. The Department of State also
publishes travel alerts and travel warnings that
• Avoid accommodations on the ground floor
or immediately next to the stairs, and lock all
focus on emergent or chronic safety issues in
doors and windows.
countries around the world. They encourage all
US citizens to avoid travel to areas with major • Take only recommended and safe modes of
threats to safety and security. Travelers should local transportation.
take these warnings seriously as they cover areas
where security threats and instability severely
• If confronted in a robbery, give up all valu-
ables and do not resist attackers. Resistance
limit the help the US government can offer to its
can escalate to violence and result in injury
citizens in those areas.
or death.
Travelers should enroll with the Department of
State’s Smart Traveler Enrollment Program (STEP) Victims of a crime overseas should contact the
before leaving on their trip. This will allow them nearest US embassy, consulate, or consular agency.
The Department of State can help replace a stolen aware of surroundings and adopting protective
passport, contact family and friends, obtain appro- measures.
priate medical care, explain the local criminal jus-
tice process, and connect victims of crime with OTHER ISSUES
available resources. However, they do not have the Just as important as learning about safety and
legal authority to conduct a criminal investigation security conditions at a traveler’s destination
and prosecution. country is to learn about legal differences that
2 TERRORISM
may cause problems for US citizens. Many coun-
tries have weapons laws that are much stricter
International terrorism is also a threat to US cit- than those in the United States, such that a sin-
izens abroad. The Department of State main- gle loose bullet in a suitcase can lead to arrest and
tains a worldwide caution addressing this threat possible jail time. Some countries prohibit certain
on its consular affairs website. Terrorist groups religious activities or the possession of religious
continue to plan attacks against Western inter- literature. Prescription medications that are com-
ests in multiple regions, including Europe, Asia, monly used in the United States may be illegal
Africa, and the Middle East. These attacks may in another country. Some countries do not have
employ a wide variety of tactics, including sui- the same free speech protections as those in the
cide operations, assassinations, kidnappings, United States, and statements made in public or
hijackings, and bombings. Possible targets online can lead to arrest or detention. These and
include high- profile sporting events, public other legal differences can be researched online at
transportation systems, residential areas, busi- the Department of State website.
ness offices, hotels, clubs, restaurants, places Since travelers may become the victim of a
of worship, schools, shopping malls, and other crime, regardless of the precautions they take,
tourist destinations where US citizens gather in they should have plans for what they will do
large numbers. in an emergency. Travelers should make pho-
Although terrorism is a worldwide threat tocopies of their travel documents and leave
and can be a major cause of concern to travel- a copy with a friend or relative at home along
ers, it should be seen in context. In 2014, 24 pri- with a detailed itinerary and contact informa-
vate US citizens were killed in terrorist attacks tion if possible. They should also have the con-
overseas, 8 were injured, and 3 were kidnapped. tact information for the nearest US embassy or
Although threats of this type cannot be totally consulate where they are traveling. Many medi-
eliminated, travelers can lower the chance cal insurance programs, including Medicare and
they will be a victim through knowledge and Medicaid, will not pay for medical treatment
planning: overseas. Travelers should ensure they have ade-
quate medical coverage before going overseas. If
• Look out for unattended packages or bags in their current insurance does not cover their trip
public places and other crowded areas.
abroad, they should consider additional insur-
• Be cautious of unexpected packages. ance that can pay for their medical expenses
abroad or help return them to the United States
• When packing, choose clothing that does if that becomes necessary. For more infor-
not identify one as a tourist (such as T-shirts
mation, see Travel Insurance, Travel Health
emblazoned with the US flag or logos of the
Insurance, & Medical Evacuation Insurance in
traveler’s local sports team).
this chapter.
• Try to blend in with the locals.
These strategies incorporate the same defensive
USEFUL WEBSITES
Department of State Consular Affairs
alertness and good judgment that people should
use to keep safe from crime at home or abroad. • Know Before You Go: http://travel.state.gov/
Awareness is key— taking precautions to be content/passports/english/go.html
ANIMAL-ASSOCIATED HAZARDS
Heather Bair-Brake, Ryan M. Wallace, G. Gale Galland, Nina Marano
trying to ascertain the species of snake that bit seen or recognized at the time of injury. In such
the victim may be critical. cases, treatment is based on the injury. Symptoms
of venomous injuries can range from mild swell-
Insects and Other Arthropods ing and redness at the site to more severe symp-
Bites and stings from spiders and scorpions can toms, such as difficulty breathing or swallowing,
be painful and can result in illness and death, chest pain, or intense pain at the site of the sting,
particularly among infants and children. Other for which immediate medical treatment should
insects and arthropods, such as mosquitoes and
ticks, can transmit infections. See the Protection
be sought. Management will vary according to
the severity of symptoms and can include medi-
2
against Mosquitoes, Ticks, & Other Arthropods cations, such as diphenhydramine, steroids, pain
section earlier in this chapter. medication, and antibiotics.
as possible after leaving the cave. If travelers, par- choriomeningitis, Lassa fever, tickborne enceph-
ticularly adventure travelers, know they will enter- alitis, poxvirus, tularemia, and bartonellosis (see
ing high-density bat habitats or plan on having Chapter 3) should be included in the list of pos-
direct contact with bats or other rabies reservoir sible diagnoses.
species, preexposure rabies vaccination should be
considered. Birds
Both ill and asymptomatic birds have been asso-
2 Rodents
Rodents carry a variety of viral, bacterial, and par-
ciated with cases of highly pathogenic avian
influenza in humans. When traveling in an area
asitic agents that may pose a threat to human where outbreaks of avian influenza have been
health. Human exposure can occur directly by a reported, travelers should avoid contact with
bite or scratch or indirectly by exposure to sur- live poultry (such as chickens, ducks, geese,
faces or water contaminated with urine or feces. pigeons, turkeys, and quail) or any wild birds
Rodents can also be reservoirs for vectorborne and should avoid settings where avian influenza
infections carried by fleas, ticks, and mites. A (H5N1 or H7N9)– infected poultry may be
Wild rodents should never be handled. present, such as commercial or backyard poul-
Travelers should avoid places that have evidence try farms and live poultry markets. Other patho-
of rodent infestation and should avoid contact gens from birds may infect humans through
with rodent feces. Travelers should not eat or infected feces or by aerosol. These cause dis-
drink anything that is suspected to be contami- eases such as histoplasmosis (see Chapter 3,
nated by rodent feces or urine. Histoplasmosis), salmonellosis (see Chapter 3,
Travelers who were exposed to rodents or who Salmonellosis [Nontyphoidal]), psittacosis, and
have a history of flea or tick bites or mite infes- avian mycobacteriosis.
tation may develop febrile illness shortly after Travelers should not eat uncooked or under-
exposure and should be evaluated by a clinician. cooked poultry or poultry products, including
Depending on the history and symptoms, dis- dishes that contain uncooked eggs or poultry
eases such as plague, leptospirosis, hantavirus, blood. Travelers should wash their hands if they
rickettsial infections, Lyme disease, lymphocytic come in contact with bird feces.
BIBLIOGRAPHY
1. Callahan M. Bites, stings and envenoming injuries. age of global travel: a review of travel-and trade-associ-
In: Keystone JS, Freedman DO, Kozarsky PE, Connor ated rabies events—United States, 1986–2012. Zoonoses
BA, Nothdurft HD, editors. Travel Medicine. 3rd ed. Public Health. 2014 Aug;61(5):305–16.
Philadelphia: Saunders Elsevier; 2013. pp. 413–24. 7. Meerburg BG, Singleton GR, Kijlstra A. Rodent-borne
2. Cohen JI, Davenport DS, Stewart JA, Deitchman S, diseases and their risks for public health. Crit Rev
Hilliard JK, Chapman LE. Recommendations for pre- Microbiol. 2009;35(3):221–70.
vention of and therapy for exposure to B virus (cer- 8. Pan American Health Organization. Rabies. In: Acha
copithecine herpesvirus 1). Clin Infect Dis. 2002 Nov PN, Szyfres B, editors. Zoonoses and Communicable
15;35(10):1191–203. Diseases Common to Man and Animals. 3rd ed.
3. Diaz JH. The global epidemiology, syndromic classifica- Washington, DC: Pan American Health Organization;
tion, management, and prevention of spider bites. Am J 2003. pp. 246–76.
Trop Med Hyg. 2004 Aug;71(2):239–5 0. 9. Smith KE, Dunn JR, Castrodale L, Daly R, Wohrle R,
4. Gibbons RV. Cryptogenic rabies, bats, and the ques- Journal of the American Veterinary Medical Association.
tion of aerosol transmission. Ann Emerg Med. 2002 Compendium of measures to prevent disease associ-
May;39(5):528–36. ated with animals in public settings, 2013. J Am Vet Med
5. Gold BS, Dart RC, Barish RA. Bites of venomous snakes. Assoc. 2013 Nov 1;243(9):1270–88.
N Engl J Med. 2002 Aug 1;347(5):347–56. 10. World Health Organization. WHO Expert Consultation
6. Lankau EW, Cohen NJ, Jentes ES, Adams LE, Bell TR, on rabies. World Health Organ Tech Rep Ser.
Blanton JD, et al. Prevention and control of rabies in an 2005;931:1–88.
ENVIRONMENTAL HAZARDS
Armin Ansari, Suzanne Beavers
• Keep hands, skin, and eyes clean and free and monitor the situation, access requirements
from mold-contaminated dust. and travel advisories change. The Department of
State recommends against all unnecessary travel
• Review the CDC guidance, Mold Prevention to areas designated by the Japanese government.
Strategies and Possible Health Effects in the For up-to-date information or any travel adviso-
Aftermath of Hurricanes and Major Floods ries, see the Department of State’s information for
(www.cdc.gov/mmwr/preview/mmwrhtml/ Japan (http://travel.state.gov/content/passports/
2 rr5508a1.htm), which provides recommenda-
tions for dealing with mold in these settings.
english/country/japan.html).
In most countries, areas of known radioactive
contamination are fenced or marked with signs.
RADIATION Any traveler seeking long-term (more than a few
Natural background radiation levels can vary sub- months) residence near a known or suspected
stantially from region to region, but these varia- contaminated area should consult with staff of the
tions are not a health concern. Travelers should nearest US embassy and inquire about any adviso-
be aware of regions known to have been contam- ries regarding drinking water quality or purchase
inated with radioactive materials, such as the of meat, fruit, and vegetables from local farmers.
areas surrounding the Chernobyl nuclear power Radiation emergencies are rare events. In case of
plant in Ukraine and the Fukushima Daiichi such an emergency, however, travelers should fol-
nuclear power plant in Japan. low instructions provided by local authorities. If
The Chernobyl plant is located 100 km (62 such information is not forthcoming, US travelers
miles) northwest of Kiev. The 1986 accident con- should seek advice from the nearest US embassy
taminated regions in 3 republics— Ukraine, or consulate.
Belarus, and Russia—but the highest radioactive Natural disasters (such as floods) may also dis-
ground contamination is within 30 km (19 miles) place industrial or clinical radioactive sources. In
of Chernobyl. all circumstances, travelers should exercise cau-
The Fukushima Daiichi plant is located 240 km tion when they encounter unknown objects or
(150 miles) north of Tokyo. After the accident in equipment, especially if they bear the basic radi-
2011, the area within a 20-km (32-mile) radius of ation tri-foil symbol or other radiation signs (see
the plant was evacuated, and Japanese authorities www.remm.nlm.gov/radsign.htm for examples).
also advised evacuation from locations farther Travelers who encounter a questionable object
away to the northwest of the plant. As Japanese should not touch or move the object and should
authorities continue to clean the affected areas notify local authorities.
BIBLIOGRAPHY
1. Ansari A. Radiation threats and your safety: a guide to 5. Guarnieri M, Balmes JR. Outdoor air pollution and
preparation and response for professionals and commu- asthma. Lancet. 2014;383(9928):1581–92.
nity. Boca Raton (FL): Chapman & Hall/CRC; 2009. 6. Langrish JP, Mills NL, Chan JK, Leseman DL, Aitken RJ,
2. Brandt M, Brown C, Burkhart J, Burton N, Cox-Ganser J, Fokkens PH, et al. Beneficial cardiovascular effects of
Damon S, et al. Mold prevention strategies and possible reducing exposure to particulate air pollution with a
health effects in the aftermath of hurricanes and major simple facemask. Part Fibre Toxicol. 2009;6:8.
floods. MMWR Recomm Rep. 2006 Jun 9;55(RR-8):1–27. 7. Nuclear Emergency Response Headquarters,
3. Brook RD, Rajagopalan S, Pope CAr, Brook JR, Government of Japan. Report of Japanese Government
Bhatnagar A, Diez-Roux AV, et al. Particulate matter to IAEA Ministerial Conference on Nuclear Safety: the
air pollution and cardiovascular disease: An update accident at TEPCO’s Fukushima nuclear power stations.
to the scientific statement from the American Heart 2011 [cited 2016 Sep. 19]. Available from: http://japan.
Association. Circulation. 2010 Jun 1;121(21):2331–78. kantei.go.jp/kan/topics/201106/iaea_houkokusho_
4. Eisenbud M, Gesell TF. Environmental e.html
Radioactivity: from Natural, Industrial, and Military 8. Scientific Committee on the Effects of Atomic
Sources. 4th ed. San Diego Academic Press; 1997. Radiation. Annex J: exposure and effects of the
Chernobyl accident. In: Sources and Effects of Ionizing to tobacco smoke: a report of the Surgeon General.
Radiation. New York: United Nations; 2000. pp. 451–556. Atlanta, GA: U.S. Department of Health and Human
9. Shofer S, Chen TM, Gokhale J, Kuschner WG. Outdoor Services, Centers for Disease Control and Prevention,
air pollution: counseling and exposure risk reduction. Coordinating Center for Health Promotion, National
Am J Med Sci. 2007 Apr;333(4):257–6 0. Center for Chronic Disease Prevention and Health
Promotion, Office on Smoking and Health; 2006 [cited
10. US Department of Health and Human Services. 2016 Sep. 22]; Available from: www.ncbi.nlm.nih.gov/
The health consequences of involuntary exposure books/NBK44324/.
2
SCUBA DIVING
Daniel A. Nord, Gregory A. Raczniak
Published estimates report anywhere from one- a physical examination to assess their cardiovas-
half to 4 million people who participate in rec- cular fitness. This may include an electrocardio-
reational diving in the United States, and many gram and exercise treadmill test.
travel to tropical areas of the world to dive. Divers Health care workers providing travel medicine
can face a variety of medical challenges, but examinations for divers should also remind their
because dive injuries are generally rare, few clini- patients of preventive actions they can take before a
cians are trained in their diagnosis and treatment. dive. Every dive should begin with identifying poten-
Therefore, the recreational diver must be able to tial hazards (such as weather and water conditions,
assess potential risks before diving, recognize the planned depth and bottom time, environment),
signs of injury, and find qualified dive medicine assessing these hazards and the associated risk, and
help when needed. making decisions about acceptable risk. The diver
should be able to implement controls to eliminate
PREPARING FOR DIVE TRAVEL or reduce the risk (by using correct and well-main-
Planning for dive-related travel should take into tained protective equipment, for example), make
account any recent changes in health, including sure the dive is supervised, and ensure that medical
injuries or surgery, and medication use. Respiratory care is available in the event of an emergency.
diseases (such as asthma or chronic obstructive
pulmonary disease), disorders that affect central DIVING DISORDERS
nervous system higher function and conscious-
ness (such as seizures) or the peripheral nervous Barotrauma
system (such as diabetic or autonomic neuropa- EAR AND SINUS
thy), mental health dysfunction (such as anxiety, Ear barotrauma is the most common injury in
claustrophobia, or substance abuse), cardiovascu- divers. On descent, failure to equalize pressure
lar disease that limits physical exertion, and preg- changes in the middle ear space creates a pres-
nancy raise special concerns about diving fitness. sure gradient across the eardrum. This pressure
Special mention must be made regarding car- change must be controlled through proper equal-
diovascular fitness. Diving should be considered ization techniques to avoid bleeding or fluid accu-
a potentially strenuous activity that can make mulation in the middle ear and avoid stretching or
substantial demands on the cardiovascular sys- rupture of the eardrum and the membranes cov-
tem. People with known risk factors for coronary ering the windows of the inner ear. Symptoms of
artery disease, including but not limited to abnor- barotrauma include the following:
mal lipid profile, elevated blood pressure, diabe-
tes, and smoking history, who wish to either begin
• Pain
a dive program or continue diving should undergo • Tinnitus (ringing in the ears)
SCUBA DIVING 107
081
• Vertigo (dizziness or sensation of spinning) frequently tracks under the skin (subcutane-
ous emphysema) or into the tissue around the
• Sensation of fullness larynx, sometimes precipitating a change in
• Effusion ( fluid accumulation in the ear) voice characteristics.
SCUBA DIVING 109
0
1
BIBLIOGRAPHY
1. Brubakk AO, Neuman TS, Bennett PB, Elliott DH. 5. Sheffield P, Vann RD. Flying after recreational diving,
Bennett and Elliott’s Physiology and Medicine of Diving. workshop proceedings of the Divers Alert Network
5th ed. London: Saunders; 2003. 2002 May 2. Durham, NC: Divers Alert Network;
2. Dear G, Pollock NW. DAN America Dive and Travel 2004 [cited 2016 Sep. 22]; Available from: http://
Medical Guide. 5th ed. Durham, NC: Divers Alert www.diversalertnetwork.org/research/projects/fad/
Network; 2009. workshop/FADWorkshopProceedings.pdf.
3. Moon RE. Treatment of decompression illness. In: Bove 6. US Navy Diving Manual Revision 6 Change A. Publication
AA, Davis JC, editors. Bove and Davis’ Diving Medicine. Number SS521-AG-PRO-010 0910-LP-106-0957. 2011
4th ed. Philadelphia: WB Saunders; 2004. pp. 195–223. [cited 2016 Mar, 16]; Revision 6 [Available from: http://
www.alohashoredivers.com/links/DiveMan_rev6_
4. Neuman TS, Thom SR. Physiology and medicine of hyper- Frontmatter_index.pdf.
baric oxygen therapy. Philadelphia, PA: Saunders; 2008.
MEDICAL TOURISM
Duc B. Nguyen, Joanna Gaines
Medical tourism is the term commonly used to providers from a similar culture, or to receive a
describe people traveling outside their home procedure or therapy not available in their coun-
country for medical treatment. Patients may pur- try of residence. In the United States, medical
sue medical care abroad for a variety of reasons, tourism generally refers to people traveling to less-
such as decreased cost, a preference for care from developed countries for medical care. Medical
tourism is a worldwide, multibillion-dollar phe- measures to control their spread in the United
nomenon that is expected to grow substantially States.
in the next 5–10 years. Studies have estimated Several outbreaks of infectious disease have
that hundreds of thousands of medical tourists been documented among medical tourists after
travel from the United States annually. Little reli- their return to the United States. Recent examples
able epidemiologic data on medical tourism exist, include nontuberculous mycobacteria infections
but ongoing case reports and outbreaks of infec- among patients who had cosmetic surgery in the
tions serve as a reminder that medical tourism is
not without risks.
Dominican Republic and Q fever among patients
who received sheep cell injections in Germany.
2
Common categories of procedures that US Patients who experience complications after
travelers pursue during medical tourism trips receiving medical care overseas should inform
include orthopedic surgery, cosmetic surgery, their providers of their travel history and their
cardiology (cardiac surgery), oncologic care, medical history, but may lack adequate docu-
and dentistry. Common destinations include mentation of the care they received. Some may be
Thailand, Mexico, Singapore, India, Malaysia, reluctant to share such information if they have
Cuba, Brazil, Argentina, and Costa Rica. The had complications.
type of procedure and the destination need to
be considered when reviewing the risk of travel PRETRAVEL ADVICE
for medical care. FOR MEDICAL TOURISTS
Most medical tourists pay for their care at Patients who travel for medical reasons should
time of service, and rely on private companies consult a travel medicine specialist in the United
or medical concierge services to identify for- States for advice tailored to individual health
eign health care facilities. These companies may needs, preferably ≥4–6 weeks before travel. In
not require accreditation of foreign providers, addition to regular considerations for healthy
track patient outcome data, or maintain formal travel related to their destination, medical tour-
medical record security policies. Some health ists should consider the additional risks asso-
insurance companies and large employers have ciated with surgery and travel, either while
formed alliances with overseas hospitals to con- being treated or while recovering from treat-
trol health care costs, and several major medi- ment. Flying and surgery both increase the risk
cal schools in the United States have developed of blood clots and pulmonary emboli. Air pres-
joint initiatives with overseas providers, such as sure in most commercial aircraft is equivalent
the Harvard Medical School Dubai Center, the to the pressure at an altitude of approximately
Johns Hopkins Singapore International Medical 6,000–8,000 ft (1,829–2,438 m). Patients should
Center, and the Duke- National University of not travel for 10 days after chest or abdomi-
Singapore. nal surgery to avoid risks associated with this
change in pressure. The American Society of
RISKS ASSOCIATED Plastic Surgeons advises people who have had
WITH MEDICAL TOURISM cosmetic procedures of the face, eyelids, or
Medical tourism has been associated with compli- nose, or who have had laser treatments, to wait
cations, including infections caused by antibiotic- 7–10 days before flying. Patients are also advised
resistant strains of bacteria not commonly seen to avoid typical vacation activities such as sun-
in the United States. Patients who are considering bathing, drinking alcohol, swimming, and tak-
seeking medical care overseas should be aware ing long tours or engaging in strenuous activities
of this risk. It is wise for travelers to bring home or exercise after surgery. The Aerospace Medical
outer packaging and package inserts from medi- Association has published medical guidelines
cations they receive or purchase abroad. Health for airline travel that provide useful informa-
care providers should be vigilant for the possi- tion on the risks of travel with certain medical
bility of resistant infections among patients who conditions (www.asma.org/asma/media/asma/
have traveled for medical procedures and take Travel-Publications/paxguidelines.pdf ).
1
From American Medical Association. New AMA Guidelines on Medical Tourism. Chicago: AMA; 2008.
1
Excerpt from Organization for Safety and Asepsis Procedures. Traveler’s guide to safe dental care. Annapolis,
MD: Organization for Safety and Asepsis Procedures; 2001. Available from: http://www.osap.org/?page=TravelersGuide.
victims of transplant tourism, the World Health these activities to be prohibited. In view of those
Assembly Resolution 57.18 encouraged mem- events, the World Health Organization revised
ber countries to “take measures to protect the the Guiding Principles on Human Cell, Tissue
poorest and vulnerable groups [the donors] and Organ Transplantation and released those
from ‘transplant tourism’ and the sale of tis- revised principles in March 2009. These guide-
sues and organs.” A meeting in 2008 in Istanbul lines emphasize that cells, tissues, and organs
addressed the issue of transplant tourism and should only be donated freely without any form
organ trafficking, which resulted in a call for of financial incentive.
BIBLIOGRAPHY
1. Budiani-Saberi DA, Delmonico FL. Organ trafficking 3. Mathers AJ, Hazen KC, Carroll J, Yeh AJ, L. CH, Bonomo
and transplant tourism: a commentary on the RA, et al. First clinical cases of OXA-48-producing
global realities. Am J Transplant. 2008 May;8(5): carbapenem-resistant Klebsiella pneumoniae in the
925–9. United States: the "menace" arrives in the new world.
2. Chen LH, Wilson ME. The globalization of healthcare: J Clin Microbiol. 2013 Feb;51(2):680–3.
implications of medical tourism for the infectious 4. Merion RM, Barnes AD, Lin M, Ashby VB, McBride V,
disease clinician. Clin Infect Dis. 2013 Dec;57(12): Ortiz-Rios E, et al. Transplants in foreign countries
1752–9. among patients removed from the US transplant
waiting list. Am J Transplant. 2008 Apr;8(4 Pt 2): multi-resistant bacterial infection. Clin Infect Dis. 2011
988–9 6. Jul 1;53(1):49–56.
5. Organ Procurement and Transplantation Network, 9. Schnabel D, Gaines J, Nguyen DB, Esposito DH,
Scientific Registry of Transplant Recipients. United Ridpath A, Yacisin K, et al. Notes from the field:
States organ transplantation annual data report, rapidly growing nontuberculous Mycobacterium
2011. Rockville (MD): US Department of Health and wound infections among medical tourists
Human Services; 2012 [cited 2016 Sep. 22]; Available undergoing cosmetic surgeries in the Dominican
from: http://srtr.transplant.hrsa.gov/annual_reports/ Republic—multiple states, March 2013–February
2011/default.aspx.
6. Reed CM. Medical tourism. Med Clin North Am. 2008
2014. MMWR Morb Mortal Wkly Rep. 2014 Mar
7;63(9):201–2. 2
Nov;92(6):1433–46, xi. 10. US Department of Health and Human Services. 2007
7. Robyn MP, Newman AP, Amato M, Walawander M, annual report of the US Organ Procurement and
Kothe C, Nerone JD, et al. Q Fever outbreak among trav- Transplantation Network and the Scientific Registry
elers to Germany who received live cell therapy—United of Transplant Recipients: transplant data 1997–2006.
States and Canada, 2014. MMWR Morb Mortal Wkly Rockville, MD: US Department of Health and Human
Rep 2015 Oct;64(38):1071–3. Services; 2007 [cited 2016 Sep. 22]; Available from:
http://www.ustransplant.org/annual_reports/current/
8. Rogers BA, Aminzadeh Z, Hayashi Y, Paterson DL. ar_archives.htm.
Country-to-country transfer of patients and the risk of
DISCUSSING COMPLEMENTARY
& INTEGRATIVE HEALTH
APPROACHES WITH TRAVELERS
Catherine Law, Tina Adler, David Shurtleff
show it does not. The World Health Organization earth, will protect against or treat the Zika virus.
recommends against using artemisia plant mate- There is no evidence that any of these products
rial in any form (including tea) for treating or pre- can prevent or treat Zika virus infection. For more
venting malaria. The use of artemisia alone has information see Chapter 3, Zika.
contributed to the increase in malaria parasites
resistant to artemisinin. Recommended drugs Travelers’ Diarrhea Prevention
used to prevent and treat malaria are described and Treatment
in Chapter 3, Malaria. PROBIOTICS
Probiotics are often suggested to help prevent trav-
VITAMIN AND MINERAL SUPPLEMENTS elers’ diarrhea (TD). Research on their use in treat-
Limited research suggests that when children with ing acute infectious diarrhea is generally positive.
malaria are nutritionally deficient, supplements Results from studies on preventing TD are mixed
of vitamin A and zinc may help lower their fever but encouraging. Given current data, it must be
and blood levels of the malaria parasite; however, assumed that effects of probiotics in any given
there is no evidence that vitamin A or zinc prevent study are specific to the strain or strains tested.
malaria infection. Vitamin A is fat soluble, and large The US Food and Drug Administration (FDA) has
or frequent doses may accumulate in the body and not approved any health claims for probiotics.
cause acute or chronic toxicity. High intake of vita- In healthy people, probiotics usually have only
min A has been linked to birth defects. Taking beta- minor side effects, if any. For more information
carotene, a precursor of vitamin A, has been linked see “Nonantimicrobial Drugs for Prophylaxis” in
to an increased risk of lung cancer and cardiovas- the Travelers’ Diarrhea section in this chapter.
cular disease in some smokers. Zinc supplements
can interact with several types of medications. GOLDENSEAL
Anyone taking high levels of zinc should be mon- Goldenseal is an herb that has been touted as a
itored for adverse health effects. treatment for a variety of ailments. No high-qual-
ity research on goldenseal for TD has been con-
Zika Prophylaxis and Treatment ducted. Studies show that goldenseal inhibits
Consumer websites and online videos are claiming, cytochrome P450 enzymes, raising concerns that
without credible evidence, that herbs or other prod- it may increase the toxicity or alter the effects of
ucts, such as activated charcoal or diatomaceous many commonly used drugs.
recommends pyridoxine alone or in combination may help with insomnia, but it has not been
with doxylamine as a safe and effective treatment established whether they are effective for jet lag.
for nausea and vomiting associated with preg-
nancy, there is no evidence supporting claims that OTHER
pyridoxine prevents or alleviates motion sickness. There is very little evidence that aromather-
Excessive use of pyridoxine supplements can apy, chamomile, or valerian help with insomnia.
affect nerve function. None have significant side effects, but cham-
2 HOMEOPATHIC PRODUCTS
omile can cause allergic reactions. Kava is also
advertised for sleep but good research on kava
There is no evidence supporting claims that for insomnia is lacking. More importantly, kava
homeopathic products prevent or alleviate supplements have been linked to a risk of severe
motion sickness. liver damage.
For more information see the Jet Lag section
Jet Lag/Sleep Problems in this chapter.
MELATONIN
Colds and Flu
Melatonin supplements may help with sleep prob-
lems caused by jet lag. Travelers report having less ZINC
jet lag on eastward and westward flights when Zinc supplements taken orally may reduce the
given melatonin compared with placebo. In a 2007 duration of a cold. Zinc, particularly in large
clinical practice guideline, the American Academy doses, can have side effects including nausea and
of Sleep Medicine supported using melatonin to diarrhea. The intranasal use of zinc can cause
reduce jet lag symptoms and improve sleep after anosmia (loss of sense of smell), which may be
traveling across >1 time zone. A systematic litera- long-lasting or permanent. In 2009, the FDA
ture review suggested taking 0.5–5 mg of melatonin warned consumers to stop using several intrana-
appeared to be effective for easing jet lag. sal zinc products that had been linked to cases
Before recommending melatonin, consider the of anosmia.
following:
SALINE IRRIGATION
• People with epilepsy or who take an oral anti- Nasal saline irrigation, such as with neti pots, may
coagulant should never use melatonin with- be useful and safe for chronic sinusitis. However,
out medical supervision. even in places where tap water is safe to drink,
• Melatonin supplements appear to be safe for people should use only sterile or distilled water
most people when used short-term; less is for nasal irrigation to avoid the risk of introduc-
known about their long-term safety. ing waterborne pathogens. Nasal saline irrigation
may help relieve the symptoms of acute upper
• Melatonin should not be taken early in the respiratory tract infections, but the evidence is not
day, as it may cause sleepiness and delay definitive.
adaptation to local time.
VITAMIN C
• The amount of melatonin in products and
the dosages recommended on labels can vary Taking vitamin C supplements regularly may
significantly. slightly reduce the duration and severity of colds
in some people. Vitamin C supplements appear
Side effects from melatonin are uncommon but safe, even at high doses.
can include drowsiness, headache, dizziness, or
nausea. PROBIOTICS
Probiotics might reduce susceptibility to colds or
RELAXATION TECHNIQUES other upper respiratory tract infections and the
Relaxation techniques, such as progressive relax- length of the illnesses, but the quality of the evi-
ation and mindfulness- based stress reduction, dence is low or very low.
TALKING TO TRAVELERS ABOUT Federal agencies, such as the National Center for
COMPLEMENTARY HEALTH Complementary and Integrative Health (NCCIH),
APPROACHES offer evidence-based resources (nccih.nih.gov/
Given the vast number of complementary or inte- health/providers) to help you and your patients
grative interventions and the wealth of potentially have a meaningful discussion about complemen-
misleading information about them that can be tary approaches.
found on the Internet, discussing the use of these
2 approaches with patients may seem daunting.
However, it is important to be proactive, as sur-
ACKNOWLEDGMENTS
The authors thank Dr. John Williamson of
veys show that many patients are reluctant to NCCIH for his scientific review and Ms. Karen
raise the topic with their health care providers. Kaplan and Ms. Patricia Andersen of Westat for
their editorial assistance.
BIBLIOGRAPHY
1. Hao Q, Lu Z, Dong BR, Huang CQ, Wu T. Probiotics for 7. Mathie RT, Frye J, Fisher P. Homeopathic
preventing acute upper respiratory tract infections. Oscillococcinum® for preventing and treating influenza
Cochrane Database Syst Rev. 2011 Sep 7(2):CD006895. and influenza-like illness. Cochrane Database of Syst
2. Hemilä H, Chalker E. Vitamin C for preventing and Rev. 2015 (1):CD001957.
treating the common cold. Cochrane Database Syst Rev. 8. Schwenger EM, Tejani AM, Loewen PS. Probiotics
2013 Jan 31(1):CD000980. for preventing urinary tract infections in adults and
3. Karsch-Völk M, Barrett B, Kiefer D, Bauer R, Ardjomand- children. Cochrane Database of Syst Rev. 2015 Dec
Woelkart K, Linde K. Echinacea for preventing and 23(12):CD008772.
treating the common cold. Cochrane Database of Syst 9. Wang C, Lü L, Zhang A, Liu C. Repellency of selected
Rev. 2014 (2):CD000530. chemicals against the bed bug (Hemiptera:
4. King D, Mitchell B, Wlilliams CP, Spurling GK. Saline Cimicidae). J Econ Entomol. 2013 Dec;106(6):2522–9.
nasal irrigation for acute upper respiratory tract 10. World Health Organization. Global Malaria
infections. Cochrane Database Syst Rev. 2015 Apr Programme. WHO position statement:
20(4):CD006821. effectiveness of non-pharmaceutical forms of
5. Lissiman E, Bhasale AL, Cohen M. Garlic for the com- Artemisia annua L. against malaria. WHO; 2012
mon cold. Cochrane Database of Syst Rev. 2014 Nov [cited 2016 Sep. 22]; Available from: http://www.
11(11):CD006206. who.int/malaria/diagnosis_treatment/position_
statement_herbal_remedy_artemisia_annua_
6. Liu J, Manheimer E, Tsutani K, Gluud C. Medicinal herbs l.pdf ?ua=1.
for hepatitis C virus infection. Cochrane Database of
Syst Rev. 2001 Oct 23(4):CD003183.
Deep vein thrombosis (DVT) is a condition in DVT, PE, or both. VTE is often recurrent, and long-
which a blood clot develops in the deep veins, most term complications, such as postthrombotic syn-
commonly in the lower extremities. A part of the drome after a DVT or chronic thromboembolic
clot can break off and travel to the lungs, causing a pulmonary hypertension after a PE, are frequent.
pulmonary embolism (PE), which can be life threat- People traveling for extended periods of time
ening. Venous thromboembolism (VTE) refers to may be at increased risk for DVT/PE because
they have prolonged limited mobility. More than regard to duration of travel and period of observa-
300 million people travel on long-distance flights tion after travel. Estimates of travel-related VTE
each year. An association between VTE and air incidence vary because of differences between
travel was first reported in the early 1950s, and studies in duration of travel, measured outcome,
since then, long-distance air travel has become period of observation after the flight, and the pop-
more common, leading to increased concerns ulations observed.
about travel-related VTE. In general, the overall incidence of travel-
PATHOGENESIS
related VTE is low. Two studies reported that
the absolute risk of VTE for flights >4 hours is 1
2
Virchow’s classic triad for thrombus formation is in 4,656 flights and 1 in 6,000 flights. People who
venous stasis, vessel wall damage, and the hyper- travel on long-distance flights are generally health-
coagulable state. Prolonged cramped sitting ier and therefore are at lower risk for VTE than the
during long-distance travel interferes with venous general population. Five prospective studies that
flow in the legs and causes venous stasis. Seat- assessed the incidence of DVT among travelers
edge pressure on the popliteal area may contrib- at low to intermediate risk for VTE after travel
ute to vessel wall damage as well as venous stasis. >8 hours yielded an overall incidence of VTE of
Coagulation activation may result from an inter- 0.5%, while the incidence of symptomatic VTE
action between cabin conditions (such as hypo- was 0.3%.
baric hypoxia) and individual risk factors for VTE.
Studies of the pathophysiologic mechanisms ASSOCIATION WITH TRAVEL
for the increased risk of VTE after long-distance Numerous studies have examined the associa-
travel have not produced consistent results, but tion between travel, particularly air travel, and
venous stasis appears to play a major role; other VTE with varying results due to differing study
factors specific to air travel may increase coagula- methods. Outcomes ranged from asymptomatic
tion activation, particularly in travelers with pre- DVT to symptomatic DVT/PE and to severe or
existing risk factors for VTE. fatal PE. Asymptomatic DVT is estimated to be
5-to 20-fold more common than symptomatic
INCIDENCE events, is of uncertain clinical significance, and
The annual incidence of VTE in the general pop- often resolves spontaneously. Definitions of long-
ulation has been estimated at 0.1% but is higher distance travel ranged from flight duration >3
in subpopulations with risk factors for VTE (Box hours to >10 hours (most >4 hours). The period
2-10). The actual incidence of travel-related VTE of observation after the flight ranged from hours
is difficult to determine, since there is no national after landing to ≥8 weeks (most 4 weeks).
surveillance for VTE and no consensus on the Overall, these studies indicate that long-dis-
definition of travel-related VTE, particularly in tance air travel may increase a person’s risk for
VTE by 2-to 4-fold. However, published results • The most common signs or symptoms of
from these studies vary; some studies found that acute PE include unexplained shortness of
long-distance travel increased the risk of VTE, breath, pleuritic chest pain, cough or hemop-
and others either found no definitive evidence tysis, and syncope.
that it increased the risk of VTE or found that it
increased the risk only if ≥1 additional risk factors
DIAGNOSIS
were present.
2
Imaging studies are needed for diagnosis:
A similar increase in risk is also seen with other
modes of travel, such as car, bus, or train, implying • Duplex ultrasonography is the standard imag-
that the increase in risk is caused mainly by pro- ing procedure for diagnosis of DVT.
longed limited mobility rather than by the cabin
environment. The risk is the same for economy-
• Computed tomographic pulmonary angio
graphy is the standard imaging procedure for
class and business-class travel. The risk increases
diagnosis of PE. Ventilation-perfusion scan is
with increasing travel duration and with preexist-
the second-line imaging procedure.
ing risk factors for VTE. The risk decreases with
time after air travel and returns to baseline by 8
weeks; most air travel–related VTE occurs within
TREATMENT
Anticoagulants are the medications most com-
the first 1–2 weeks after the flight.
monly used to treat DVT or PE. Bleeding can be a
RISK FACTORS complication of anticoagulant therapy.
Most travel-related VTE occurs in travelers with The most frequently used injectable antico-
preexisting risk factors for VTE (Box 2-10). The agulants are unfractionated heparin, low molec-
combination of air travel with preexisting individ- ular weight heparin (LMWH), and fondaparinux.
ual risk factors may have a synergistic effect on the Oral anticoagulants include warfarin, dabigatran,
risk for VTE. Some studies have shown that 75%– rivaroxaban, apixaban, and edoxaban.
99.5% of those who developed travel-related VTE It is critical that patients who are at increased
had ≥1 preexisting risk factor; one study showed risk be evaluated with enough time prior to
that 20% had ≥5 risk factors. For travelers without departure so that travelers understand how to
preexisting risk factors, the risk of travel-related take the medication and the health provider can
VTE is low. However, a person may not be aware evaluate whether there are any potential adverse
that he or she has a risk factor such as inherited effects of the combination of these medications
thrombophilia. with others that the travel health provider has
For air travelers, height appears to be an addi- prescribed.
tional risk factor. Risk of travel- related VTE
increases with height <1.6 m (5 ft, 3 in). Airplane PREVENTIVE MEASURES
seats are higher than car seats and cannot be FOR LONG-DISTANCE
adjusted to a person’s height; therefore, shorter TRAVELERS
people who travel by air may experience seat-edge The American College of Chest Physicians pub-
pressure to the popliteal area. Risk of travel-related lished the 9th edition of their Antithrombotic
VTE also increases with height >1.9 m (6 ft, 3 in), Therapy and Prevention of Thrombosis Evidence-
possibly because taller travelers have less leg room. Based Clinical Practice Guidelines in February
2012. Recommendations for long-distance trav-
CLINICAL PRESENTATION elers (considered grade 2C: weak recommenda-
Signs and symptoms of DVT/PE are nonspecific: tion, low-or very low-quality evidence) are the
following:
• Typical signs or symptoms of DVT in the
extremities include pain or tenderness, 1. For long-distance travelers at increased risk
swelling, increased warmth in the affected of VTE (Box 2-10), frequent ambulation, calf
area, and redness or discoloration of the muscle exercise, and sitting in an aisle seat if
overlying skin. feasible are suggested.
2. For long-distance travelers at increased risk 6-fold increase in risk. Aisle seats are reported to
of VTE (Box 2- 10), use of properly fitted, have a protective effect, compared with window
below-knee graduated compression stockings or middle seats, probably because travelers are
(GCS) providing 15–30 mm Hg of pressure at freer to move around.
the ankle during travel is suggested. For all GCS are indicated for long-distance travelers
other long-distance travelers, use of GCS is at increased risk. GCS appear to reduce asymp-
not recommended. tomatic DVT in travelers and are generally well
3. For long-distance travelers, the use of aspi-
rin or anticoagulants to prevent VTE is not
tolerated.
Global use of anticoagulants for long-distance
2
recommended. travel is not indicated. Pharmacologic prophy-
laxis for long-distance travelers at particularly
There is no evidence for an association between
high risk should be decided on an individual
dehydration and travel- related VTE and no
basis. In cases where the potential benefits of
direct evidence that drinking plenty of nonalco-
pharmacologic prophylaxis outweigh the pos-
holic beverages to ensure adequate hydration
sible adverse effects, anticoagulants rather
or avoiding alcoholic beverages has a protec-
than antiplatelet drugs (such as aspirin) are
tive effect. Therefore, while maintaining hydra-
recommended.
tion is reasonable and unlikely to cause harm, it
cannot be recommended specifically to prevent
travel-related VTE.
RECOMMENDATIONS
There is evidence that immobility while fly- 1. General measures for long-distance travelers:
ing is a risk for VTE and indirect evidence that a. Calf muscle exercises
maintaining mobility may prevent VTE. In view b. Frequent ambulation
of the role of venous stasis in the pathogenesis of c. Aisle seating when feasible
travel-related VTE, it would be reasonable to rec- 2. Additional measures for long-distance travel-
ommend frequent ambulation and calf muscle ers at increased risk of VTE:
exercises for long-distance travelers. a. Properly fitted below-knee GCS
Compared with aisle seats, window seats in b. Anticoagulant prophylaxis only in partic-
one study were reported to increase the general ularly high-risk cases where the potential
risk of VTE by 2-fold, while obese travelers had a benefits outweigh the risks
BIBLIOGRAPHY
1. Aryal KR, Al-Khaffaf H. Venous thromboembolic com- of thrombosis, 9th ed: American College of Chest
plications following air travel: what’s the quantitative Physicians evidence-based clinical practice guidelines.
risk? A literature review. Eur J Vasc Endovasc Surg. 2006 Chest. 2012 Feb;141(2 Suppl):e195S–226S.
Feb;31(2):187–99. 7. Schobersberger W, Schobersberger B, Partsch H.
2. Bartholomew JR, Schaffer JL, McCormick GF. Air travel Travel-related thromboembolism: mechanisms
and venous thromboembolism: minimizing the risk. and avoidance. Expert Rev Cardiovasc Ther. 2009
Cleve Clin J Med. 2011 Feb;78(2):111–20. Dec;7(12):1559–67.
3. Chandra D, Parisini E, Mozaffarian D. Meta-analy- 8. Schreijer AJ, Cannegieter SC, Caramella M, Meijers
sis: travel and risk for venous thromboembolism. Ann JC, Krediet RT, Simons RM, et al. Fluid loss does not
Intern Med. 2009 Aug 4;151(3):180–9 0. explain coagulation activation during air travel. Thromb
4. Eklof B, Maksimovic D, Caprini JA, Glase C. Air travel- Haemost. 2008 Jun;99(6):1053–9.
related venous thromboembolism. Disease-a-month 9. Schreijer AJ, Cannegieter SC, Doggen CJ, Rosendaal
: DM. 2005 Feb-Mar;51(2-3):200–7. FR. The effect of flight-related behaviour on the risk of
5. Gavish I, Brenner B. Air travel and the risk of thrombo- venous thrombosis after air travel. Br J Haematol. 2009
embolism. Intern Emerg Med. 2011 Apr;6(2):113–6. Feb;144(3):425–9.
6. Kahn SR, Lim W, Dunn AS, Cushman M, Dentali 10. Watson HG, Baglin TP. Guidelines on travel-related
F, Akl EA, et al. Prevention of VTE in nonsurgical venous thrombosis. Br J Haematol. 2011 Jan;152(1):
patients: antithrombotic therapy and prevention 31–4.
MENTAL HEALTH
Thomas H. Valk
The practitioner can then ask about factors that is always wise to carry medications in their
might indicate a mental health problem: original containers, along with a letter from
the prescribing physician indicating that the
• Any previously treated or diagnosed psy- medications have been prescribed for medical
chiatric disorders and the type of treatment
reasons. Even with these precautions, prob-
involved (inpatient, outpatient, medications)
lems may still occur at customs.
• Current treatment for any psychiatric disor- • Psychotropic medication refills: Obtaining
ders and their nature
these medications while living overseas can 2
• Current or past use of illicit substances be problematic, as availability or even legal-
ity of the medication varies from country to
• Any diagnosis of substance use disorder, or country. Again, a check with the country’s
suggestion from medical service providers,
embassy may be helpful, as would a check
friends, or family that the traveler might be
with a reputable in-country pharmacy or
using alcohol or other substances to excess
health care provider.
• Any immediate family history of serious men- • Measuring drug levels: Locating laboratory
tal health problems
facilities for the determination of lithium lev-
In general, any history of inpatient treatment, psy- els or for other mood-stabilizing medications
chotic episode, violent or suicidal behavior, affec- may be challenging and should be investi-
tive disorder (including mania, hypomania, or gated prior to travel. High ambient tempera-
major depression), any treatment for substance tures and increased sweating could lead to
use problems, and any current treatments would lithium toxicity, even on the same dose.
warrant further evaluation by a mental health
professional, preferably one who has had some
• Mefloquine: In general, patients with mental
health issues should not be prescribed meflo-
experience in problems relating to international
quine for malarial chemoprophylaxis because
travel. On occasion, the patient’s mental status
of its potential for neuropsychiatric side
upon examination may be notably abnormal,
effects. Please see the discussion of meflo-
which would also warrant a referral.
quine in Chapter 3, Malaria.
Other issues that may be encountered and
should be addressed during the pretravel consul- • Alcoholics Anonymous (AA) and Narcotics
tation include the following: Anonymous (NA) meetings: Currently sober
patients with substance use disorders should
• Availability of culturally compatible mental consider seeking out AA and NA meetings,
health treatment in the destination country
depending upon their length of stay and sta-
for long-term travelers or expatriates.
bility of their sobriety. AA and NA maintain,
• Customs regulations: Traveling through cus- by country, lists of such meetings on their
toms with medications for personal use can websites, although availability can change.
be problematic in countries where those Language of meetings should also be checked.
medications are prohibited. What substances
are prohibited in any given country varies.
• Evacuation insurance: Travelers with mental
health problems should consider travel health
Stimulants frequently used for attention defi-
and medical evacuation insurance that does
cit disorders, such as amphetamine or meth-
not exclude psychiatric evacuations for emer-
ylphenidate, may be problematic, along with
gencies when abroad.
narcotics. This list is not exhaustive, and trav-
elers should check with the host country’s
embassy if anything is questionable. A health POST-TRAVEL MENTAL
care provider or pharmacist in the desti- HEALTH ISSUES
nation country may also be able to provide Travel health practitioners may be in a unique
guidance about medication restrictions. It position to inquire about traumatic experiences
MENTAL HEALTH 125
216
a traveler might have had that may lead to acute • Changes in mood or cognition associated
stress disorder (ASD) or posttraumatic stress dis- with the event can include diminished inter-
order (PTSD). Travelers exposed to life-threaten- est in activities, inability to experience pos-
ing events, such as disaster relief workers or war itive emotions, or an inability to remember
correspondents, may experience subclinical or significant details of the event.
outright ASD or PTSD.
If the traveler has had such experiences, clini- • Arousal symptoms can include difficulty
2 cians should inquire about possible symptoms: sleeping or concentrating, irritability, or an
exaggerated startle response.
• Reexperiencing the event can include recur-
rent, intrusive recollections, distressing As symptoms of PTSD may occur months or even
dreams of the event, and feeling as if the event years after an event, education about the pos-
is happening again. sibility of having such symptoms in the future is
worthwhile. If there is any concern about a possi-
• Avoidance symptoms can include avoiding ble reaction to a traumatic event, referral to a psy-
thoughts, feelings, activities, places, or people chiatrist is warranted.
that lead to memories of the event.
BIBLIOGRAPHY
1. American Psychiatric Association. Diagnostic and 6. Quigley RL, Copeland R. Mental health and study
Statistical Manual of Mental Disorders. 5th ed. abroad: incidence and mitigation strategies. Oral
Arlington, VA: American Psychiatric Association; 2013. presentation at: 13th Conference of the International
2. Benedek DM, Wynn GH. Clinical manual for manage- Society of Travel Medicine; 2013 May 19-23; Maastricht,
ment of PTSD. Arlington, VA: American Psychiatric The Netherlands.
Publishing, Inc.; 2011. 7. Streltzer J. Psychiatric emergencies in travelers to
3. Feinstein A, Owen J, Blair N. A hazardous profes- Hawaii. Compr Psychiatry. 1979 Sep-Oct;20(5):
sion: war, journalists, and psychopathology. Am J 463–8.
Psychiatry. 2002 Sep;159(9):1570–5. 8. Valk TH. Psychiatric medical evacuations within
4. Liese B, Mundt KA, Dell LD, Nagy L, Demure B. Medical the Foreign Service. Foreign Serv Med Bull. 1988;268:
insurance claims associated with international business 9–11.
travel. Occup Environ Med. 1997 Jul;54(7):499–5 03. 9. Valk TH. Psychiatric disorders of travel In: Keystone JS,
5. Patel D, Easmon CJ, Dow C, Snashall DC, Seed PT. Freedman DO, Kozarsky PE, Connor BA, Nothdurft HO,
Medical repatriation of British diplomats resident over- editors. Travel Medicine. 3rd ed. Philadelphia: Saunders
seas. J Travel Med. 2000 Mar-Apr;7(2):64–9. Elsevier; 2013. pp. 439–48.
TRAVEL HEALTH KITS
Kelly Winter
Regardless of the destination, all international A travel health kit can help to ensure travelers
travelers should assemble and carry a travel have supplies they need to:
health kit. The contents of a travel health kit
should be tailored to the traveler’s needs, type
• Manage preexisting medical conditions and
treat any exacerbations of these conditions.
and length of travel, and destinations. Kits can be
assembled at home or purchased at a local store, • Prevent illness and injury related to
pharmacy, or online. traveling.
• Take care of minor health problems as they exceed size limits. Exceptions are made for cer-
occur. tain medical reasons; check the Transportation
Security Administration for US outbound and
By bringing medications from home, travelers inbound travel (call toll-free at 866-289-9673 M–F
avoid having to purchase them at their destina- 8 am to 11 pm, weekends and holidays 9 am to
tion. See Perspectives: Pharmaceutical Quality & 8 pm, or e-mail TSA-[email protected]) and
Falsified Drugs later in this chapter for informa- the embassy or consulate of the destination coun-
tion about the risks associated with purchasing
medications abroad. Even when the quality of
try for their restrictions.
2
medications is reliable, medications people are SUPPLIES FOR PREEXISTING
used to taking at home may be sold under differ- MEDICAL CONDITIONS
ent names or with different ingredients and dos- Travelers with preexisting medical conditions
age units in other countries, presenting additional should carry enough medication for the dura-
challenges. tion of their trip and an extra supply, in case
the trip is extended for any reason. If additional
TRAVELING WITH MEDICATIONS supplies or medications would be needed to
All medications should be carried in their original manage exacerbations of existing medical con-
containers with clear labels, so the contents are ditions, these should be carried as well. The cli-
easily identified. The patient’s name and dosing nician managing a traveler’s preexisting medical
regimen should be on each container. Although conditions should be consulted for the best plan
many travelers prefer placing medications into of action (see Chapter 8, Travelers with Chronic
small containers or packing them in daily-dose Illnesses).
containers, officials at ports of entry may require People with preexisting conditions, such as
proper identification of medications. diabetes or allergies, should consider wearing
Travelers should carry copies of all prescrip- an alert bracelet and making sure this informa-
tions, including their generic names and pref- tion (in English and preferably translated into
erably translated into the local language of the the local language of the destination) is on a
destination. For controlled substances and card in their wallet and with their other travel
injectable medications, travelers should carry a documents.
note from the prescribing clinician or from the
travel clinic on letterhead stationery. Translating GENERAL TRAVEL HEALTH
the letter into the local language of the destina- KIT SUPPLIES
tion and attaching this translation to the original Although the following is not a comprehensive
document may prove helpful if the document is list, basic items that should be considered for a
needed during the trip. Some countries do not travel health kit are listed below. See Chapter 8
permit certain medications. If there is a question for additional suggestions that may be useful in
about these restrictions, particularly regarding planning the contents of a kit for travelers with
controlled substances, travelers should con- specific needs.
tact the embassy or consulate of the destination
country. Prescription Medications
A travel health kit is useful only when it is eas- and Supplies
ily accessible. It should be carried with the traveler
at all times (such as in a carry-on bag), although
• Medications taken on a regular basis at
home
sharp objects must remain in checked luggage.
Travelers should make sure that any liquid or gel- • Antibiotic for self-treatment of moderate to
based items packed in the carry-on bags do not severe diarrhea1
1
For factors to consider when deciding whether to use an antibiotic for self-treatment of moderate to severe travelers’ diarrhea,
see Perspectives: Antibiotics in Travelers’ Diarrhea, earlier in this chapter.
• Elastic/compression bandage wrap for translated into the local language of the
sprains and strains destination)
BIBLIOGRAPHY
1. Goodyer L. Travel medical kits. In: Keystone JS, 3. Rose SR, Keystone JS. Chapter 2, trip preparation.
Freedman DO, Kozarsky PE, Connor BA, Nothdurft HD, In: Rose SR, Keystone JS, editors. International Travel
editors. Travel Medicine. 3rd ed. Philadelphia: Saunders Health Guide. 2016 online ed. Northampton: Travel
Elsevier; 2013. pp. 63–6. Medicine, Inc; 2016.
2. Harper LA, Bettinger J, Dismukes R, Kozarsky PE.
Evaluation of the Coca-Cola company travel health kit.
…perspectives
PHARMACEUTICAL QUALITY
& FALSIFIED DRUGS
Michael D. Green
2
The quality of medicines and surveillance methods. Before international
available outside the United Recent survey studies of departure, travel health care
States should not always be antimicrobial drug quality providers should alert trav-
taken for granted. In many in Africa and Southeast elers to the dangers of coun-
countries, national drug Asia revealed that 9%–41% terfeit and substandard drugs
regulatory authorities lack failed quality specifications. and provide suggestions on
the resources to effectively Previous reports have shown how to avoid them.
monitor drug quality and that global estimates of drug
keep poor-quality pharma- counterfeiting range from 1% HOW TO AVOID
ceuticals off the market. of sales in developed coun- COUNTERFEIT
These poor-quality drugs tries to >10% in developing DRUGS WHEN
include falsified (the prod- countries. In specific regions TRAVELING
uct’s identity or source is in Africa, Asia, and Latin The best way to avoid coun-
falsely represented), coun- America, chances of pur- terfeit drugs is to reduce
terfeit (a product bearing an chasing a counterfeit drug the need to purchase medi-
unauthorized representation may be >30%. cations abroad. Anticipated
of a registered trademark), Since counterfeit drugs amounts of medications for
and substandard (a medicine are not made by the legiti- chronic conditions (such
not conforming to the spec- mate manufacturer and are as hypertension, sinusitis,
ifications set by an accepted produced under unlawful arthritis, and hay fever),
pharmacopeia) medications. circumstances, toxic con- medications for gastro-
Poor-quality medicines also taminants or lack of proper enteritis (such as travelers’
include products that are ingredients may cause diarrhea), and prophylactic
not stored correctly, such serious harm. For example, medications for infectious
that high temperature and the active pharmaceutical diseases (such as malaria)
humidity can alter the chemi- ingredient may be completely should all be purchased
cal composition. These drugs lacking, present in small before traveling. Purchasing
are an international problem quantities, or substituted by these drugs via the Internet
contributing to illness, tox- a less-effective compound. In is not recommended, since
icity, drug resistance, and addition, the wrong inactive the source of the medicines
death. Although this prob- ingredients (excipients) can is always questionable. The
lem exists on a worldwide contribute to poor drug dis- traveler should also be aware
scale, reliable global esti- solution and bioavailability. that other health-related
mates of its prevalence are As a result, a patient may not items such as medical
scarce because consensus respond to treatment or may devices, mosquito nets, and
is lacking on harmonized have adverse reactions to insect repellents could also
international definitions unknown substituted or toxic be counterfeit, falsified, or
of poor-quality medicines ingredients. substandard.
(continued)
Before departure, travel- States is available on the the brand, batch num-
ers should do the following: Department of State’s web- ber, and expiration date.
site at www.state.gov/s/cpr/ Sometimes a wary con-
• Obtain all medicines rls/dpl/32122.htm. sumer will prompt the
2 and other health-related
items needed for the trip
If travelers run out and seller into supplying qual-
require additional medica- ity medicine.
in advance. Prescriptions tions, they should take steps
written in the United to ensure the medicines they
• Be familiar with medi-
States usually cannot be cations. The size, shape,
buy are safe:
filled overseas, and over- color, and taste of coun-
the-counter medicines • Obtain medicines from terfeit medicines may
may not be available in a legitimate pharmacy. be different from the
many foreign countries. Patients should not buy authentic. Discoloration,
Checked baggage can get from open markets, street splits, cracks, spots, and
lost; therefore, travelers vendors, or suspicious- stickiness of the tablets or
should pack as much as looking pharmacies; they capsules are indications
possible in a carry-on bag should request a receipt of a possible counter-
and bring extra medicine when making the pur- feit. These defects may
in case of travel delays. chase. The US embassy also indicate improper
may be able to help find storage. Travelers should
• Make sure medicines a legitimate pharmacy in keep examples of authen-
are in their original the area. tic medications to com-
containers. If the drug pare if they purchase the
is a prescription, the • Do not buy medicines that same brand.
patient’s name and dose are substantially cheaper
regimen should be on the than the typical price. • Be familiar with the
container. Although generics are packaging. Different color
usually less expensive, inks, poor-quality print
• Bring the “patient pre- many counterfeit brand or packaging material,
scription information” names are sold at prices and misspelled words are
sheet. This sheet provides substantially lower than clues to counterfeit drugs.
information on common the normal price for that Travelers should keep an
generic and brand particular brand. example of packaging for
names, use, side effects, comparison and observe
precautions, and drug • Make sure the medicines the expiration date.
interactions. are in their original pack-
ages or containers. If trav- If the authentic packaging
Many countries have restric- elers receive medicines as is not available or if you are
tions on medicines (including loose tablets or capsules not familiar with the brand,
over-the-counter medica- supplied in a plastic bag compare the distinguishing
tions) entering their borders. or envelope, they should features of the package with
Check with the embassies ask the pharmacist to that of the insert or blister
of your destination countries see the container from pack. For example, batch/
for prohibited items. A listing which the medicine was lot numbers, manufacturing
of foreign embassies and originally dispensed. The date, and expiration date
consulates in the United traveler should record should match.
Perspectives sections are written as editorial discussions aiming to add depth and clinical perspective to the official
recommendations contained in the book. The views and opinions expressed in this section are those of the author and
do not necessarily represent the official position of CDC.
The quality and availability of medical care abroad does not usually cover emergency evacuation or
may be variable. Before departure, travelers the costs of altered itineraries. Travelers may pur-
should consider how they would access health chase specific policies to cover these expenses,
care during their trip should a medical problem or understanding that such policies often do not
emergency arise. Travelers may seek medical care cover expenses related to preexisting conditions.
for a variety of reasons, ranging from minor infec- Supplemental medical insurance plans acquired
tions and care for chronic conditions to major ill- before travel will often enable access to local pro-
ness or injury. viders in many countries through a 24-hour emer-
Some insurance plans cover emergency health gency hotline (see Travel Insurance, Travel Health
care, but travelers should check with their carri- Insurance, & Medical Evacuation Insurance sec-
ers to confirm what coverage is offered and what tion later in this chapter).
requirements exist. At a minimum, travelers may In addition to identifying quality health care,
need to provide copies of bills and invoices to ini- travelers, especially those with chronic or compli-
tiate reimbursement. Emergency health coverage cated medical issues, should know the names of
their chronic conditions and allergies, their blood Membership is free, although donations are
type, and current medications (including generic suggested. Search for clinics at www.iamat.
names), ideally in the local language. Travelers org/doctors_clinics.cfm.
should also wear medical identification jewelry
(such as a MedicAlert bracelet), if appropriate.
• The Joint Commission International (JCI) aims
to improve patient safety through accredita-
There are a number of cellular telephone appli-
tion and certification of health care facilities.
cations that enable travelers to download their
2 medical records, medications, EKG, and other
information so that it is accessible if needed.
For a list of facilities accredited through JCI,
see www.jointcommissioninternational.org/
JCI-Accredited-Organizations.
LOCATING HEALTH • Embassies and consulates in other countries,
CARE PROVIDERS AND hotel doctors, and credit card companies
FACILITIES ABROAD (especially those with special privileges) may
Before going abroad, travelers should identify also provide information.
health care providers and facilities at their destina-
tion. This is especially true for travelers with preex-
• A number of countries or national travel med-
icine societies have websites related to travel
isting or complicated medical issues. Travelers who
medicine that provide access to clinicians,
require regular dialysis need to arrange appoint-
including the following:
ments at an adequate clinical site. Similarly, preg-
nant travelers should identify reliable health
> Canada: Health Canada (www.phac-aspc.
gc.ca and travel.gc.ca)
facilities. More choices are generally available in
urban areas than in rural or remote areas.
> Great Britain: National Travel Health
Network and Centre (www.nathnac.org)
The following list of resources will help iden-
and British Global and Travel Health
tify health care providers and facilities around
Association (www.bgtha.org)
the world. CDC does not endorse any particu-
lar provider or medical insurance company, and
> South Africa: South African Society of
Travel Medicine (www.sastm.org.za)
accreditation does not necessarily ensure a good
outcome. If travelers are likely to seek health care
> Australia: Travel Medicine Alliance (www.
travelmedicine.com.au)
abroad, they should be encouraged to thoroughly
research health care facilities in the area.
> China: International Travel Healthcare
Association (http://en.itha.org.cn)
• The Department of State (www.usembassy. • Travelers also may consider contracting
gov) can help travelers locate medical services
with one of a number of private companies
and notify friends, family, or employer of an
that provide physician services abroad as
emergency.
well as medical evacuations. One example is
• The Department of State also maintains a International SOS, which operates through-
list of travel medical insurance providers at out the world. Provider locations and details
travel.state.gov/content/passports/en/go/ may be found at www.internationalsos.com.
health/insurance-providers.html.
AVOID TRAVEL WHEN SICK
• The International Society of Travel Medicine Travelers should evaluate their health before
maintains a directory of health care profes-
travel to ensure that they are healthy enough
sionals with expertise in travel medicine in
for their itinerary and should avoid travel if they
more than 80 countries. Search these clinics
become ill before or during their trip. Travelers
at www.istm.org.
may be reluctant to postpone or cancel a trip
• The International Association for Medical when ill because of their financial investment in
Assistance to Travelers maintains a network a trip, among other factors. However, some air-
of physicians, hospitals, and clinics that lines check for visibly sick passengers in the wait-
have agreed to provide care to members. ing area and during boarding. If a passenger looks
visibly ill, the airline may prohibit that person need for a blood transfusion. Not all countries
from boarding. have accurate, reliable, and systematic screening
Encouraging travelers, especially those with of blood donations for infectious agents, which
chronic or complicated health conditions, to pur- increases the risk of transfusion-related trans-
chase trip cancellation insurance, which will pro- mission of disease. Travelers in developing coun-
tect some or all of the investment in a trip, may tries should receive a blood transfusion only in
increase compliance with this recommendation. life-or-death situations. Although it is difficult to
BIBLIOGRAPHY
1. Kolars JC. Rules of the road: a consumer’s guide for from: http://www.who.int/mediacentre/factsheets/
travelers seeking health care in foreign lands. J Travel fs275/en/.
Med. 2002 Jul-Aug;9(4):198–201. 3. World Health Organization. Blood safety [ fact sheet
2. World Health Organization. Medicines: spurious/falsely- no. 279]. Geneva: World Health Organization; 2014
labelled/falsified/counterfeit (SFFC) medicines [ fact [updated July 2016 cited 2016 Sep. 22]; Available
sheet no. 275]. Geneva: World Health Organization; 2012 from: http://www.who.int/mediacentre/factsheets/
[updated January 2016 cited 2016 Sep. 22]; Available fs279/en/.
consular officer, who can assist US citizens with • Emergency medical transport to facilities that
transferring funds from the United States. are equivalent to those in the home country
or to the home country itself (repatriation)
TRAVEL INSURANCE
Travel insurance protects the financial invest- • Any specific medical services that may apply
ment in a trip, including lost baggage and trip to their circumstances, such as coverage of
cancellation. Travelers may be more likely to high-risk activities
avoid travel when sick if they know their financial
investment in the trip is protected. Depending on
Even if an insurance provider is selected carefully,
travelers should be aware that unexpected delays
2
the policy, travel insurance may or may not cover in care may still arise, especially in remote desti-
medical expenses abroad, so travelers need to nations. In special circumstances, travelers may
carefully research the coverage offered to deter- be advised to postpone or cancel international
mine if additional travel health and medical evac- trips if the health risks are too high.
uation insurance is needed.
FINDING AN INSURANCE
SUPPLEMENTAL TRAVEL PROVIDER
HEALTH AND MEDICAL The following resources, although not all-inclu-
EVACUATION INSURANCE sive, provide information about purchasing travel
Travel health insurance and medical evacuation health and medical evacuation insurance:
insurance are both short-term supplemental pol-
icies that cover health care costs on a trip and are • Department of State (www.travel.state.gov)
relatively inexpensive. Many commercial compa-
• International Association for Medical
nies offer travel health insurance, which may be Assistance to Travelers (www.iamat.org)
purchased separately or in conjunction with med-
ical evacuation insurance. Frequent travelers may • American Association of Retired Persons
consider purchasing annual policies or even poli- (www.aarp.org) ( for information about
cies that will provide coverage for repatriation to Medicare supplement plans, see below)
one’s home country.
Although travel health insurance will cover SPECIAL CONSIDERATIONS FOR
some health care costs abroad, the quality of care TRAVELERS WITH UNDERLYING
may be inadequate, and medical evacuation from MEDICAL CONDITIONS
a resource-poor area to a hospital where definitive Travelers with underlying medical conditions
care can be obtained may be necessary. The cost should discuss any concerns with the insurer
of evacuation can exceed $100,000. In such cases, before departure. In a study of international trav-
medical evacuation insurance would cover the cost elers with travel health insurance claims, only
of transportation to a facility where adequate care two-thirds of claims were fully met. Preexisting ill-
can be provided. Medical evacuation companies ness and poor documentation were the main rea-
may have better resources and experience in some sons for refusal. Travelers with medical conditions
parts of the world than others; travelers may want should choose a medical assistance company
to ask about a company’s resources in a given area, that allows them to store their medical his-
especially if planning a trip to remote destinations. tory before departure, so it can be accessed any-
The traveler should scrutinize all policies before pur- where. Travelers should carry a letter from their
chase, looking for those that provide the following: health care provider listing their medical condi-
tions and current medications (including their
• Arrangements with hospitals to guarantee generic names), written in the local language if
payments directly
possible. Those with cardiac disease should carry
• Assistance via a 24-hour physician-backed a copy (paper or electronic) of their most recent
support center (critical for medical evacua- ECG. They should also pack all medications in
tion insurance) their original bottles, checking beforehand with
TRAVEL INSURANCE, TRAVEL HEALTH INSURANCE, & MEDICAL EVACUATION INSURANCE 137
381
BIBLIOGRAPHY
1. American Association of Retired Persons, Education and 4. Leggat PA, Leggat FW. Travel insurance claims
Outreach. Overview of Medicare supplemental insur- made by travelers from Australia. J Travel Med. 2002
ance. Washington, DC: American Association of Retired Mar-Apr;9(2):59–65.
Persons; 2010 [cited 2016 Mar. 8]; Available from: http:// 5. Teichman PG, Donchin Y, Kot RJ. International
www.aarp.org/health/medicare-insurance/info-10-2008/ aeromedical evacuation. N Engl J Med. 2007 Jan
overview_medicare_supplemental_insurance.html. 18;356(3):262–70.
2. Centers for Medicare and Medicaid Services. Medicare 6. US Department of State. Insurance Providers for
coverage outside the United States. Baltimore: CMS; Overseas Coverage. Washington, DC: US Department
2016 [cited 2016 Mar. 8]; Available from: https://www. of State; 2016 [cited 2016 Sep. 22]; Available from:
medicare.gov/Pubs/pdf/11037.pdf. https://travel.state.gov/content/passports/en/go/
3. Leggat PA, Carne J, Kedjarune U. Travel insurance and health/insurance-providers.html.
health. J Travel Med. 1999 Dec;6(4):243–8.
Infectious Diseases
Related to Travel
AMEBIASIS
Jennifer R. Cope
AMEBIASIS 139
401
E. dispar, and E. moshkovskii. E. dispar and E. mos or tinidazole should be followed by treatment
hkovskii have historically been considered non- with iodoquinol or paromomycin. Asymptomatic
pathogenic, but evidence is mounting that patients infected with E. histolytica should also
E. moshkovskii can cause illness; E. bangladeshi be treated with iodoquinol or paromomycin,
has only recently been identified, so its pathogenic because they can infect others and because 4%–
potential is not well understood. More specific 10% develop disease within a year if left untreated.
tests such as EIA or PCR are needed to confirm the
diagnosis of E. histolytica. Additionally, serologic PREVENTION
tests can help diagnose extraintestinal amebiasis. Food and water precautions (see Chapter 2, Food
& Water Precautions) and hand hygiene. Avoid
3 TREATMENT
For symptomatic intestinal infection and extrain-
fecal exposure during sexual activity.
BIBLIOGRAPHY
1. Choudhuri G, Rangan M. Amebic infection 4. Lachish T, Wieder-Finesod A, Schwartz E.
in humans. Indian J Gastroenterol. 2012 Amebic Liver Abscess in Israeli Travelers: A
Jul;31(4):153–62. Retrospective Study. Am J Trop Med Hyg. 2016
2. Cordel H, Prendki V, Madec Y, Houze S, May 4;94(5):1015–9.
Paris L, Bouree P, et al. Imported amoebic 5. Shimokawa C, Kabir M, Taniuchi M, Mondal D,
liver abscess in France. PLoS Negl Trop Dis. Kobayashi S, Ali IK, et al. Entamoeba moshkovskii is
2013;7(8):e2333. associated with diarrhea in infants and causes diarrhea
3. Heredia RD, Fonseca JA, Lopez MC. Entamoeba and colitis in mice. J Infect Dis. 2012 Sep 1;206(5):744–51.
moshkovskii perspectives of a new agent to be con- 6. Ximenez C, Moran P, Rojas L, Valadez A, Gomez A,
sidered in the diagnosis of amebiasis. Acta Trop. 2012 Ramiro M, et al. Novelties on amoebiasis: a neglected
Sep;123(3):139–45. tropical disease. J Glob Infect Dis. 2011 Apr;3(2):166–74.
ANGIOSTRONGYLIASIS,
NEUROLOGIC
LeAnne M. Fox, Francisca Abanyie
INFECTIOUS AGENT EPIDEMIOLOGY
Angiostrongylus cantonensis, rat lungworm, a Most described cases have occurred in Asia and
nematode parasite. the Pacific Basin (such as in parts of Thailand,
Taiwan, mainland China, the Hawaiian Islands,
TRANSMISSION and other Pacific Islands); however, cases have
Various species of rats are the definitive hosts of been reported in many areas of the world, includ-
the parasite, known as the rat lungworm. Rats can ing the Caribbean.
infect only snails and slugs, which are the inter-
mediate hosts. Transmission to humans occurs CLINICAL PRESENTATION
by consuming infected snails or slugs or contam- Incubation period is typically 1– 3 weeks but
inated raw produce or vegetable juices. Infective ranges from 1 day to >6 weeks. A. cantonensis is
larvae have also been found in freshwater shrimp, considered the most common infectious cause
crabs, and frogs. of eosinophilic meningitis in humans. Common
BIBLIOGRAPHY
1. Chotmongkol V, Sawadpanitch K, Sawanyawisuth K, Angiostrongylus cantonensis infection in Hawaii: clinical
Louhawilai S, Limpawattana P. Treatment of eosin- characteristics and potential exposures. Am J Trop Med
ophilic meningitis with a combination of prednis- Hyg. 2011 Oct;85(4):685–9 0.
olone and mebendazole. Am J Trop Med Hyg. 2006 3. Wang QP, Lai DH, Zhu XQ, Chen XG, Lun ZR.
Jun;74(6):1122–4. Human angiostrongyliasis. Lancet Infect Dis. 2008
2. Hochberg NS, Blackburn BG, Park SY, Sejvar JJ, Effler PV, Oct;8(10):621–30.
Herwaldt BL. Eosinophilic meningitis attributable to
ANTHRAX
Kate Hendricks Walters, Rita M. Traxler, Chung K. Marston
ANTHRAX 141
412
Introducing spores through the skin can life-threatening or fatal disease is possible: cases
result in cutaneous anthrax; abrasion of the of cutaneous (4), gastrointestinal (1), and inhala-
skin increases susceptibility. Eating meat from tion (3) anthrax have been reported among peo-
infected animals can result in gastrointestinal ple who have handled, played, or made drums or
anthrax. Since 2000, injecting, and possibly smok- who have been in the same place as people partic-
ing and snorting, heroin has been associated with ipating in these activities.
B. anthracis soft-tissue infections in intravenous Severe soft tissue infections, including cases
drug users in northern Europe. Inhaling spores with sepsis and systemic infection, have been
aerosolized during work with contaminated reported in drug users in northern Europe and are
materials such as hides or wool can result in inha- suspected to be due to recreational use of heroin
3 lation anthrax.
Anthrax in humans is not generally considered
contaminated with B. anthracis spores. No asso-
ciated cases have been identified in people who
to be contagious; person-to-person transmission have not taken heroin. To date, no heroin has been
of cutaneous anthrax has rarely been reported. found to be contaminated with B. anthracis spores.
Inhalation exposure was historically associ-
EPIDEMIOLOGY ated with the industrial processing of hides or
Anthrax is a zoonotic disease that primarily affects wool (hence, “woolsorters’ disease”). However,
herbivores such as cattle, sheep, goats, antelope, in more recent decades it has also resulted from
and deer, which become infected by ingesting bioterrorism. Occasional anthrax cases have
contaminated vegetation, water, or soil; humans occurred in the United States and elsewhere in
are generally incidental hosts. Anthrax is most which the exposure source remains unidentified.
common in agricultural regions in Central and
South America, sub-Saharan Africa, Central and CLINICAL PRESENTATION
Southwestern Asia, and Southern and Eastern Cutaneous anthrax usually develops 1– 7 days
Europe. Although outbreaks occur most years in after exposure, but incubations as long as 17 days
livestock and wild herbivores in the United States have been reported. Before antimicrobial ther-
and Canada, human anthrax is now rare in both of apy, almost a quarter of patients with cutane-
these countries. ous anthrax died. The case-fatality ratio is <2%
Worldwide, the most commonly reported form with antimicrobial therapy. Cutaneous anthrax
(95%–99%) of anthrax in humans is cutaneous is characterized by localized itching followed by
anthrax. Outbreaks of cutaneous and gastrointes- the development of a painless papule, which turns
tinal anthrax have been associated with handling vesicular and enlarges, ulcerates, and develops
infected animals and butchering and consuming into a depressed black eschar within 7–10 days
meat from those animals. Most of these outbreaks of the initial lesion. The head, neck, forearms,
are reported from endemic areas of Asia and Africa. and hands are the most commonly affected sites.
A single case of travel-associated anthrax has Edema usually surrounds the lesion, sometimes
been reported. In 2006, a case of cutaneous anthrax with secondary vesicles, hyperemia, and regional
was reported in a woman who traveled with a lymphadenopathy. Patients may have malaise and
small group of tourists to Namibia, Botswana, and headache; about a third are febrile.
South Africa. Although she had no direct contact Gastrointestinal anthrax usually develops 1–
with animals, another group member handled 1 7 days after consumption of contaminated meat;
or more animal carcasses and shortly afterward however, incubations as long as 16 days have been
helped her clean an abrasion on her finger, which reported. More than half of cases die if untreated;
was later the site of the anthrax lesion. with treatment, the case- fatality ratio is <40%.
Additional cases have occurred from play- There are 2 main types, oropharyngeal and intes-
ing or handling drums made with contaminated tinal. Fever and chills are usual with either. The
goat hides that were imported from anthrax- oropharyngeal type is characterized by severe
endemic countries. Although the risk of acquir- sore throat, difficulty swallowing, swelling of the
ing anthrax from these drums appears to be low, neck, and regional lymphadenopathy; airway
compromise can occur. Symptoms of the intestinal diagnosis. Confirmatory testing, including iso-
type include nausea, vomiting, and diarrhea, which late identification, antigen detection in tissues,
may be bloody; marked ascites may develop. Shock or quantitative serology, should be performed in
and death may occur within 2–5 days of onset. the United States by the state health department
Cases of anthrax in injection drug users usually or Laboratory Response Network laboratories, or
develop within 1–4 days of exposure; more than internationally by the relevant national reference
a quarter of the confirmed cases die. Cases pres- laboratory. Guidelines for collecting and submit-
ent with severe soft tissue infection manifested ting clinical specimens for testing and algorithms
by swelling, erythema, and excessive bruising at for laboratory diagnosis can be found at www.cdc.
the injection site; pain may be less than would be gov/anthrax/lab-testing/index.html. Specimens
anticipated for the degree of swelling. In approx-
imately a third of cases, the localized symptoms
for culture should be collected before initiating
antimicrobial therapy. Anthrax is a nationally
3
are accompanied by signs of sepsis. notifiable disease.
Inhalation anthrax usually develops within a Diagnostic procedures for inhalation anthrax
week after exposure, but the incubation period include thoracic imaging studies to detect a wid-
may be prolonged (up to 2 months). Fatality ratios ened mediastinum or pleural effusion. Unless
before 2001 were 90%; since then, they have been contraindicated, lumbar puncture should be per-
45%. Initially, most patients have constitutional formed to rule out meningitis in all patients with
symptoms such as fever, chills, and fatigue, which systemic illness.
may be accompanied by cough, making inhala-
tion anthrax difficult to distinguish from influ- TREATMENT
enza and community-acquired pneumonia. This Naturally occurring localized or uncomplicated
is often described as the prodromal period. Over cutaneous anthrax can be treated with 7–10 days
the next day or so, chest pain develops in about of a single oral antimicrobial agent. First- line
half of patients, and nonthoracic complaints such agents include ciprofloxacin or an equivalent flu-
as nausea, vomiting, headache, and diaphoresis oroquinolone or doxycycline; clindamycin is an
develop in approximately one-third. Upper respi- alternative, as are penicillins if the isolate is peni-
ratory tract symptoms occur in only a quarter cillin susceptible.
of patients, and myalgias are rare. Altered men- Treatment recommendations for systemic dis-
tal status or shortness of breath generally brings ease are available at wwwnc.cdc.gov/eid/article/
patients to the attention of the medical establish- 20/2/13-0687_intro. Additional recommendations
ment and heralds the fulminant phase of illness. to prevent or treat anthrax in pregnant, post-
Anthrax meningitis may develop from hema- partum, and lactating women are available at
togenous spread of any of the clinical forms wwwnc.cdc.gov/eid/article/20/2/13-0611_intro.
of anthrax, or it may occur alone; half of all
reported cases are sequelae of cutaneous anthrax. PREVENTION
Although anthrax meningitis is usually fatal, sur- The CDC published updated recommendations
vival is significantly more likely if the patient in 2010 for preexposure use of anthrax vaccine
receives multiple antimicrobials that include a and for postexposure management of previously
bactericidal agent. unvaccinated people (www.cdc.gov/ mmwr/
preview/mmwrhtml/rr5906a1.htm). Vaccination
DIAGNOSIS against anthrax is not recommended for travelers.
Laboratory diagnosis depends on bacterial cul- To prevent anthrax, travelers should:
ture and isolation of B. anthracis; detection of bac-
terial DNA, antigens, or toxins; or detection of a
• Avoid direct or indirect contact with car-
casses of animals in anthrax-endemic regions.
host immune response to B. anthracis. Anthrax
lethal toxin can be detected in acute-phase serum, • Not eat meat from animals that were not
while serologic testing of host antibody responses inspected by health officials and found to be
requires acute-and convalescent-phase sera for healthy at the time of slaughter.
ANTHRAX 143
41
BIBLIOGRAPHY
1. Bales ME, Dannenberg AL, Brachman PS, Kaufmann 6. Hanczaruk M, Reischl U, Holzmann T, Frangoulidis
AF, Klatsky PC, Ashford DA. Epidemiologic response D, Wagner DM, Keim PS, et al. Injectional anthrax in
to anthrax outbreaks: field investigations, 1950–2001. heroin users, Europe, 2000–2012. Emerg Infect Dis. 2014
Emerg Infect Dis. 2002 Oct;8(10):1163–74. Feb;20(2):322–3.
2. CDC. Anthrax contamination of Haitian goatskin 7. Hendricks KA, Wright ME, Shadomy SV, Bradley JS,
products. MMWR Morb Mortal Wkly Rep. 1981 July Morrow MG, Pavia AT, et al. Centers for disease control
17;30(27):338. and prevention expert panel meetings on prevention
3. CDC. Gastrointestinal anthrax after an animal-hide and treatment of anthrax in adults. Emerg Infect Dis.
drumming event—New Hampshire and Massachusetts, 2014 Feb;20(2).
2009. MMWR Morb Mortal Wkly Rep. 2010 Jul 8. Meaney-Delman D, Zotti ME, Creanga AA, Misegades
23;59(28):872–7. LK, Wako E, Treadwell TA, et al. Special considerations
4. Eurosurveillance editorial team. Probable for prophylaxis for and treatment of anthrax in preg-
human anthrax death in Scotland. Euro Surveill. nant and postpartum women. Emerg Infect Dis. 2014
2006;11(8):E060817.2. Feb;20(2).
5. Griffith J, Blaney D, Shadomy S, Lehman M, Pesik 9. Van den Enden E, Van Gompel A, Van Esbroeck M.
N, Tostenson S, et al. Investigation of inhalation Cutaneous anthrax, Belgian traveler. Emerg Infect Dis.
anthrax case, United States. Emerg Infect Dis. 2014 2006 Mar;12(3):523–5.
Feb;20(2):280–3.
B VIRUS
D. Scott Schmid
occur through contact with body fluids or tissues National B Virus Resource Center at Georgia
of an infected macaque. A single case of human- State University. Detection of viral DNA by B
to-human spread has been documented, in which virus PCR from clinical specimens is the stan-
a woman became infected through direct contact dard for diagnosis of infection. Detection of
with the lesions of her infected spouse. B virus–specific antibodies in serum is also diag-
nostic. Culture is generally unsuccessful as the
EPIDEMIOLOGY virus is unlikely to remain viable during tran-
Macaques are the natural reservoir for B virus sit or after being frozen and thawed. For more
infection. No other primates are known to information, see www2.gsu.edu/ ~wwwvir/
carry any risk of B virus infection unless they index.html.
have become infected by contact with infected
macaques. Although B virus infections in TREATMENT
3
macaques are usually asymptomatic or cause For any suspected exposure, immediate first
only mild disease, approximately 70% of untreated aid is crucial. The wound should be cleansed
infections in humans are fatal. People at risk by thoroughly washing and scrubbing the area
for B virus infection are veterinarians, laboratory with soap, concentrated detergent solution,
workers, and others who have close contact with povidone-iodine, or chlorhexidine and water.
Old World macaques or monkey cell cultures, The wound should then be irrigated with
but infections in humans are rare. Since B virus running water for 15–20 minutes. For urine
was identified in 1932, fewer than 50 cases of splashes to the eyes, repeated flushes of the
human infection have been documented. eyes should be performed for 15 minutes with
sterile saline solution or water. Specimens for
CLINICAL PRESENTATION diagnostic testing should not be obtained
Disease onset typically occurs within 1 month from wound sites before washing because
of exposure, although the actual incubation doing so may force virus more deeply into
period can be as short as 3–7 days. The first the wound.
signs of disease typically include influenza- Antiviral therapy is recommended as postex-
like symptoms ( fever, headache, myalgias) and posure prophylaxis in high-risk exposures (see
sometimes vesicular lesions near the expo- www.cdc.gov/herpesbvirus/firstaid-treatment.
sure site. Localized neurologic symptoms such html). When recommended, the first choice of
as pain, numbness, or itching may occur near drug for postexposure prophylaxis is valacyclovir
the wound site. Lymphadenitis, lymphangi- and an alternative is acyclovir. If B virus infection
tis, nausea, vomiting, and abdominal pain is diagnosed, treatment consists of intravenous
may also occur. Spread of the infection to the acyclovir or ganciclovir, depending on whether
central nervous system (CNS) causes acute CNS symptoms are present.
ascending encephalomyelitis. Most patients
with CNS involvement die despite antivi- PREVENTION
ral therapy and supportive care, and those Adhering to laboratory and animal facility pro-
who survive usually suffer serious neurologic tocols will reduce the risk of B virus transmis-
sequelae. Respiratory failure associated with sion among laboratory workers. Visitors to parks
ascending paralysis is the most common cause and other tourist destinations (such as certain
of death. religious temples) with free-roaming macaques
should avoid contact with the animals (including
DIAGNOSIS feeding or petting them).
In the United States, diagnostic testing of
human specimens is performed only at the CDC website: www.cdc.gov/herpesbvirus
B VIRUS 145
416
BIBLIOGRAPHY
1. CDC. Notice to readers: occupational safety and health (Cercopithecine herpesvirus 1). Clin Infect Dis. 2002 Nov
in the care and use of nonhuman primates. MMWR 15;35(10):1191–203.
Recomm Rep. 2003;52(38):920. 4. Health NIfOSa. Hazard ID 5—C ercopithicine
2. Chosewood LC WD. Section VIII–Agent summary herpesvirus 1 (B virus) infection resulting from
statements. In: Chosewood LC WD, editor. Biosafety ocular exposure. Atlanta: CDC; 1999 [cited 2016
in microbiological and biomedical laboratories. 5th ed. Sep. 21]. Available from: http://www.cdc.gov/niosh/
Washington, DC: US Department of Health and Human docs/9 9-100/.
Services; 2009. pp. 205–8. 5. Veterinarians NAoSPH. Compendium of mea-
3. Cohen JI, Davenport DS, Stewart JA, Deitchman S, sure to prevent disease associated with animals
3
Hilliard JK, Chapman LE, et al. Recommendations in public settings, 2009. MMWR Recomm Rep.
for prevention of and therapy for exposure to B virus 2009;58(RR-0 5):1–15.
BARTONELLA INFECTIONS
Christina A. Nelson
BIBLIOGRAPHY
1. Bass JW, Freitas BC, Freitas AD, Sisler CL, Chan DS, 4. Fournier PE, Thuny F, Richet H, Lepidi H, Casalta JP,
Vincent JM, et al. Prospective randomized double blind Arzouni JP, et al. Comprehensive diagnostic strategy
placebo-controlled evaluation of azithromycin for treat- for blood culture-negative endocarditis: a prospec-
ment of cat-scratch disease. Pediatr Infect Dis J. 1998 tive study of 819 new cases. Clin Infect Dis. 2010 Jul
Jun;17(6):447–52. 15;51(2):131–4 0.
2. Eremeeva ME, Gerns HL, Lydy SL, Goo JS, Ryan ET, 5. Maguina C, Gotuzzo E. Bartonellosis. New and old.
Mathew SS, et al. Bacteremia, fever, and splenomegaly Infect Dis Clin North Am. 2000 Mar;14(1):1–22, vii.
caused by a newly recognized Bartonella species. N Engl 6. Rolain JM, Brouqui P, Koehler JE, Maguina C,
J Med. 2007 Jun 7;356(23):2381–7. Dolan MJ, Raoult D. Recommendations for treatment
3. Florin TA, Zaoutis TE, Zaoutis LB. Beyond cat scratch of human infections caused by Bartonella species.
disease: widening spectrum of Bartonella henselae infec- Antimicrob Agents Chemother. 2004 Jun;48(6):
tion. Pediatrics. 2008 May;121(5):e1413–25. 1921–33.
BRUCELLOSIS
Maria E. Negron, Rebekah Tiller, Grishma A. Kharod
BIBLIOGRAPHY
1. Al Dahouk S, Nockler K. Implications of laboratory 3. Arnow PM, Smaron M, Ormiste V. Brucellosis in a group
diagnosis on brucellosis therapy. Expert Rev Anti Infect of travelers to Spain. JAMA. 1984 Jan 27;251(4):505–7.
Ther. 2011 Jul;9(7):833–45. 4. Memish ZA, Balkhy HH. Brucellosis and international
2. Ariza J, Bosilkovski M, Cascio A, Colmenero JD, Corbel travel. J Travel Med. 2004 Jan-Feb;11(1):49–55.
MJ, Falagas ME, et al. Perspectives for the treatment of 5. Organization WH. Brucellosis. Geneva: World Health
brucellosis in the 21st century: the Ioannina recommen- Organization; 2012 [cited 2016 Sep. 21]. Available from:
dations. PLoS Med. 2007 Dec;4(12):e317. http://www.who.int/zoonoses/diseases/brucellosis/en/.
6. Pappas G, Papadimitriou P, Akritidis N, Christou L, of raw camel milk. Travel Med Infect Dis. 2016
Tsianos EV. The new global map of human brucellosis. May-Jun;14(3):255–6 0.
Lancet Infect Dis. 2006 Feb;6(2):91–9. 8. Yousefi-Nooraie R, Mortaz-Hejri S, Mehrani M,
7. Rhodes HM, Williams DN, Hansen GT. Invasive human Sadeghipour P. Antibiotics for treating human brucello-
brucellosis infection in travelers to and immigrants sis. Cochrane Database Syst Rev. 2012;10:Cd007179.
from the Horn of Africa related to the consumption
CAMPYLOBACTERIOSIS
Aimee L. Geissler, Barbara E. Mahon, Collette Fitzgerald
3
INFECTIOUS AGENT ( frequently bloody), abdominal pain, fever, and
Infection is caused by gram- negative, spiral- occasionally nausea and vomiting. More severe
shaped microaerophilic bacteria of the family illness can occur, including dehydration, blood-
Campylobacteriaceae. Most infections are caused stream infection, and symptoms mimicking acute
by Campylobacter jejuni; at least 18 other species, appendicitis or ulcerative colitis. People with cam-
including C. coli, also cause infection. C. jejuni and pylobacteriosis are at increased risk for postinfec-
C. coli are carried normally in the intestinal tracts tious complications, including reactive arthritis
of many domestic and wild animals. (2%–5% of patients), irritable bowel syndrome
(9%– 13%), and Guillain- Barré syndrome (GBS)
TRANSMISSION (0.1%). C. jejuni is the most frequently observed
The major modes of transmission include eat- antecedent bacterial infection in cases of GBS;
ing contaminated foods (especially undercooked symptoms usually begin 1–3 weeks after the onset
chicken and foods contaminated by raw chicken), of Campylobacter enteritis.
drinking contaminated water or milk (unpasteur-
ized milk, most commonly), and having contact DIAGNOSIS
with animals, particularly farm animals such as Diagnosis is traditionally based on isolation of the
cows and chickens, as well as domestic cats and organism from stool specimens or rectal swabs by
dogs. Campylobacter can also be transmitted from using selective media incubated under reduced
person to person by the fecal-oral route. oxygen tension at 42°C (107.6°F) for 72 hours.
Visualization of motile and curved, spiral, or S-
EPIDEMIOLOGY shaped rods by stool phase-contrast or dark-field
Campylobacter is a leading cause of bacterial diar- microscopy can provide rapid presumptive evi-
rheal disease worldwide; in the United States, it dence for Campylobacter enteritis. A stool specimen
is estimated to cause 1.3 million human illnesses should be collected during the acute phase of the
every year. Campylobacter is the most common diarrheal illness and before antibiotic treatment is
laboratory-confirmed enteric pathogen reported initiated. Because the organism is fastidious, a delay
in travelers returning to the United States from in transporting the specimen will affect the viabil-
every region of the world. The risk of infection is ity of Campylobacter spp. A laboratory may reject
highest in travelers to Africa and South America, stool samples without preservative that are in tran-
especially in areas with poor restaurant hygiene sit for more than 2 hours. If transport and process-
and inadequate sanitation. The infectious dose is ing are not possible within 2 hours of stool sample
small; <500 organisms can cause disease. collection, specimens should be placed in transport
medium according to standard guidelines. Only
CLINICAL PRESENTATION through culture can Campylobacter be subtyped
Incubation period is typically 2– 4 days. and tested for antimicrobial susceptibility. Rapid
Campylobacteriosis is characterized by diarrhea culture-independent diagnostic tests, including
CAMPYLOBACTERIOSIS 149
501
both antigen tests and nucleic acid–based tests, are past 20 years, and high rates of resistance are now
becoming widely available and more commonly seen in many regions. Travel abroad is a risk fac-
used. The sensitivity and specificity of stool anti- tor for infection with resistant Campylobacter.
gen tests are variable, and in settings of low prev- Clinicians should suspect resistant infection in
alence, the positive predictive value is likely to be returning travelers with campylobacteriosis in
low. Therefore, laboratories should confirm posi- whom empiric fluoroquinolone treatment has
tive results of stool antigen tests by culture. Nucleic failed. When fluoroquinolone resistance is proven
acid– based tests have recently been approved or suspected, azithromycin is usually the next
and appear to have higher sensitivity and specific- choice of treatment, although resistance to mac-
ity than the antigen tests. Campylobacteriosis is a rolides has also been reported.
3 nationally notifiable disease.
PREVENTION
TREATMENT No vaccine is available. Prevention is best
The disease is generally self-limited, lasting a week achieved by adhering to standard food and water
or less. Antibiotic therapy decreases the duration safety precautions (see Chapter 2, Food & Water
of symptoms and bacterial shedding if adminis- Precautions) and thorough handwashing after
tered early in the course of disease. Because cam- contact with animals or environments that may
pylobacteriosis generally cannot be distinguished be contaminated with animal feces. Antibiotic
from other causes of travelers’ diarrhea without a prophylaxis is not recommended.
diagnostic test, the use of empiric antibiotics in
travelers should follow the guidelines for travelers’ CDC website: www.cdc.gov/foodsafety/diseases/
diarrhea. campylobacter
Rates of antibiotic resistance, especially fluo-
roquinolone resistance, have risen sharply in the
BIBLIOGRAPHY
1. Coker AO, Isokpehi RD, Thomas BN, Amisu KO, Obi CL. 6. Kendall ME, Crim S, Fullerton K, Han PV, Cronquist AB,
Human campylobacteriosis in developing countries. Shiferaw B, et al. Travel-associated enteric infec-
Emerg Infect Dis. 2002 Mar;8(3):237–4 4. tions diagnosed after return to the United States,
2. Fitzgerald C, Nachamkin I. Campylobacter and Arcobacter. Foodborne Diseases Active Surveillance Network
In: Jorgensen JH, Pfaller MA, Carroll KC, Funke G, (FoodNet), 2004–2 009. Clin Infect Dis. 2012 Jun;54
Landry ML, Richter SS, et al., editors. Manual of Clinical Suppl 5:S480–7.
Microbiology. 11th ed. Washington, D. C.: American 7. Moore JE, Barton MD, Blair IS, Corcoran D, Dooley
Society for Microbiology Press; 2015. pp. 998–1012. JS, Fanning S, et al. The epidemiology of antibiotic
3. Friedman CR, Hoekstra RM, Samuel M, Marcus R, resistance in Campylobacter. Microbes Infect. 2006
Bender J, Shiferaw B, et al. Risk factors for sporadic Jun;8(7):1955–66.
Campylobacter infection in the United States: a case- 8. World Health Organization. The global view of
control study in FoodNet sites. Clin Infect Dis. 2004 Apr campylobacteriosis: report of an expert consultation.
15;38 Suppl 3:S285–9 6. Geneva: World Health Organization; 2012 [cited
4. Humphrey T, O'Brien S, Madsen M. Campylobacters as 2016 Sep. 21]. Available from: http://apps.who.int/
zoonotic pathogens: a food production perspective. Int J iris/bitstream/10665/80751/1/9789241564601_eng.
Food Microbiol. 2007 Jul 15;117(3):237–57. pdf ?ua=1.
5. Kassenborg HD, Smith KE, Vugia DJ, Rabatsky-Ehr T, 9. World Health Organization. WHO estimates of the
Bates MR, Carter MA, et al. Fluoroquinolone-resistant global burden of foodborne diseases. Geneva: World
Campylobacter infections: eating poultry outside of the Health Organization; 2015 [cited 2016 Sep. 22].
home and foreign travel are risk factors. Clin Infect Dis. Available from: http://www.who.int/foodsafety/
2004 Apr 15;38 Suppl 3:S279–84. areas_work/foodborne-diseases/ferg/en/.
CHIKUNGUNYA
J. Erin Staples, Susan L. Hills, Ann M. Powers
TRANSMISSION
proximity to human habitation served as vector-
breeding sites. Risk of infection exists throughout
3
Chikungunya virus is transmitted to humans via the day, as the primary vector, Ae. aegypti, aggres-
the bite of an infected mosquito of the Aedes sively bites during the daytime. Ae. aegypti mos-
spp., predominantly Aedes aegypti and Ae. albopic quitoes bite indoors or outdoors near a dwelling.
tus. Nonhuman and human primates are likely the They typically breed in domestic containers that
main reservoirs of the virus, and human-to-vector- hold water, including buckets and flower pots.
to-human transmission occurs during outbreaks of Both adults and children can become infected
the disease. Bloodborne transmission is possible; and symptomatic with the disease. From 2010
1 case was documented in a health care worker who through 2013, 110 cases of chikungunya were
was stuck with a needle after drawing blood from an identified or reported among US travelers who
infected patient. Cases have also been documented predominantly traveled to areas with known
among laboratory personnel handling infected blood ongoing outbreaks. Following the outbreaks in
and through aerosol exposure in the laboratory. the Americas, however, >3,500 chikungunya cases
The risk of a person transmitting the virus to a have been reported from US states through the
biting mosquito or through blood is highest when end of April 2016. Although most were in travel-
the patient is viremic, usually during the first ers, a few cases acquired locally in the continen-
2–6 days of illness. Maternal-fetal transmission has tal United States were reported in 2014 and 2015.
been documented during pregnancy; the highest In addition, several US territories (Puerto Rico,
risk occurs when a woman is viremic at the time of US Virgin Islands, and American Samoa) have
delivery. Studies have not found virus in breast milk. reported locally acquired cases from 2014–2016.
CHIKUNGUNYA 151
512
Abnormal laboratory findings can include nucleic acid, or virus-specific IgM and neutraliz-
thrombocytopenia, lymphopenia, and elevated ing antibodies. During the first week after onset of
creatinine and liver function tests. Rare but serious symptoms, chikungunya can often be diagnosed
complications of the disease can occur, including by performing viral culture or nucleic acid ampli-
myocarditis, ocular disease (uveitis, retinitis), hepa- fication on serum. Virus-specific IgM and neu-
titis, acute renal disease, severe bullous lesions, and tralizing antibodies normally develop toward the
neurologic disease, such as meningoencephalitis, end of the first week of illness. Therefore, to defin-
Guillain-Barré syndrome, myelitis, or cranial nerve itively rule out the diagnosis, convalescent-phase
palsies. Groups identified as having increased risk samples should be obtained from patients whose
for more severe disease include neonates exposed acute-phase samples test negative.
3 intrapartum, adults >65 years of age, and people
with underlying medical conditions, such as hyper-
Testing for chikungunya virus is performed at
CDC, several state health department laborato-
tension, diabetes, or heart disease. ries, and several commercial laboratories. Health
Acute symptoms of chikungunya typically care providers should report suspected chikun-
resolve in 7–10 days. Fatalities associated with gunya cases to their state or local health depart-
infection occur but are typically rare and most ments to facilitate diagnosis and mitigate the risk
commonly reported in older adults. Some patients of local transmission. Because chikungunya is a
will have a relapse of rheumatologic symptoms nationally notifiable disease, state health depart-
such as polyarthralgia, polyarthritis, tenosynovitis, ments should report laboratory-confirmed cases
or Raynaud syndrome in the months after acute to CDC through ArboNET, the national surveil-
illness. Studies have reported variable proportions, lance system for arboviral diseases.
ranging from 5% to 80%, of patients with persistent
joint pains for months or years after their illness. TREATMENT
Pregnant women have symptoms and out- No specific antiviral treatment is available for chiku-
comes similar to those of other people, and most ngunya. Treatment is for symptoms and can include
infections that occur during pregnancy will not rest, fluids, and use of analgesics and antipyret-
result in the virus being transmitted to the fetus. ics. Nonsteroidal anti-inflammatory drugs can be
However, when intrapartum transmission occurs, used to help with acute fever and pain. In dengue-
it can result in complications for the baby, includ- endemic areas, however, acetaminophen is the pre-
ing neurologic disease, hemorrhagic symptoms, ferred first-line treatment for fever and joint pain
and myocardial disease. There are also rare reports until dengue can be ruled out, to reduce the risk of
of spontaneous abortions after maternal infection hemorrhage. For patients with persistent joint pain,
during the first trimester. use of nonsteroidal anti-inflammatory drugs, corti-
costeroids including topical preparations, and phys-
DIAGNOSIS ical therapy may help lessen the symptoms.
The differential diagnosis of chikungunya virus
infection depends on the clinical signs and symp- PREVENTION
toms as well as where the person was suspected of No vaccine or preventive drug is available. The best
being infected. Diseases that should be considered way to prevent infection is to avoid mosquito bites
in the differential diagnosis include dengue, Zika, (see Chapter 2, Protection against Mosquitoes,
malaria, leptospirosis, parvovirus, enterovirus, Ticks, & Other Arthropods). Travelers at increased
group A Streptococcus, rubella, measles, adenovi- risk for more severe disease, including travelers
rus, postinfectious arthritis, rheumatologic condi- with underlying medical conditions and women
tions, or alphavirus infections (including Mayaro, who are late in their pregnancy (as their unborn
Ross River, Barmah Forest, O’nyong-nyong, and infants are at increased risk), may consider avoid-
Sindbis viruses). ing travel to areas with ongoing outbreaks. If travel
Preliminary diagnosis is based on the patient’s is unavoidable, emphasize the need for protective
clinical features, places and dates of travel, and measures against mosquito bites.
activities. Laboratory diagnosis is generally accom-
plished by testing serum to detect virus, viral CDC website: www.cdc.gov/chikungunya
BIBLIOGRAPHY
1. CDC. Geographic distribution of chikungunya virus. 5. Rajapakse S, Rodrigo C, Rajapakse A. Atypical manifes-
Atlanta: CDC; 2014 [cited 2016 Sep. 22]. Available from: tations of chikungunya infection. Trans R Soc Trop Med
http://www.cdc.gov/chikungunya/geo/index.html. Hyg. 2010 Feb;104(2):89–9 6.
2. Lee VJ, Chow A, Zheng X, Carrasco LR, Cook AR, 6. Simon F, Javelle E, Cabie A, Bouquillard E, Troisgros O,
Lye DC, et al. Simple clinical and laboratory predictors Gentile G, et al. French guidelines for the management
of chikungunya versus dengue infections in adults. PLoS of chikungunya (acute and persistent presentations).
Negl Trop Dis. 2012;6(9):e1786. November 2014. Med Mal Infect. 2015 Jul;45(7):243–63.
3. Lindsey NP, Prince HE, Kosoy O, Laven J, Messenger S, 7. Staples JE, Fischer M. Chikungunya virus in the
Staples JE, et al. Chikungunya virus disease in travelers – Americas—what a vectorborne pathogen can do. N Engl
3
United States, 2010–2013. Am J Trop Med Hyg. 2015 J Med. 2014 Sep 4;371(10):887–9.
Jan;92(1):82–7. 8. Thiberville SD, Moyen N, Dupuis-Maguiraga L,
4. Pan American Health Organization and CDC. Nougairede A, Gould EA, Roques P, et al. Chikungunya
Preparedness and response for chikungunya virus fever: epidemiology, clinical syndrome, pathogenesis
introduction in the Americas. Washington, DC: Pan and therapy. Antiviral Res. 2013 Sep;99(3):345–70.
American Health Organization; 2011 [cited 2016 9. World Health Organization. Chikungunya: case defini-
Sep. 22]. Available from: http://new.paho.org/hq/index. tions for acute, atypical and chronic cases. Conclusions
php?option=com_content&view=article&id=3545&Ite of an expert consultation, Managua, Nicaragua, 20-21
mid=2545&lang=en. May 2015. Wkly Epidemiol Rec. 2015 Aug 14;90(33):410–4.
CHOLERA
Karen K. Wong, Erin Burdette, Eric D. Mintz
CHOLERA 153
541
Vaccine BOOSTER DOSES
No country or territory requires vaccination The safety and efficacy of revaccination with CVD
against cholera as a condition for entry. CVD 103- 103-HgR have not been established.
HgR, a single-dose oral cholera vaccine (Vaxchora,
PaxVax), is licensed and available in the United VACCINE SAFETY AND ADVERSE
States. The vaccine was previously marketed REACTIONS
under the names Orochol and Mutacol in other Serious adverse events were rare among recip-
countries. Vaxchora was approved in June 2016 ients of Orochol and Mutacol, the previously
for use in adults ≥18 years of age. marketed formulation of the CVD 103-HgR vac-
cine. Systemic adverse events, which may include
INDICATIONS
The Advisory Committee on Immunization
diarrhea and headache, occur at similar rates in
Vaxchora recipients and nonrecipients.
3
Practices (ACIP) recommends CVD 103-HgR vac-
cine for adult travelers (age 18–64 years) to an area PRECAUTIONS AND CONTRAINDICATIONS
of active cholera transmission. An area of active Vaxchora is contraindicated in people with a
cholera transmission is defined as a province, history of severe allergic reaction to any ingre-
state, or other administrative subdivision within a dient of Vaxchora or to a previous dose of any
country with endemic or epidemic cholera caused cholera vaccine. A study with the older formu-
by toxigenic V. cholerae O1 and includes areas lation of CVD 103-HgR showed that concomi-
with cholera activity within the last year that are tant use of chloroquine decreased the immune
prone to recurrence of cholera epidemics; it does response to the vaccine; therefore, antimalar-
not include areas where rare sporadic cases have ial prophylaxis with chloroquine should begin
been reported. no sooner than 10 days after administration
The vaccine is not routinely recommended for of Vaxchora. Coadministration of mefloquine
most travelers from the United States, as most do and proguanil with CVD 103-HgR did not dimin-
not visit areas with active cholera transmission. ish the vaccine’s immunogenicity. Antibiotics
may decrease the immune response to CVD
VACCINE EFFICACY 103-HgR, so vaccine should not be administered
Adults aged 18–45 years who received Vaxchora to patients who have received antibiotics in the
were protected against severe diarrhea after previous 14 days.
oral V. cholerae O1 challenge at 10 days and at Vaxchora is not currently licensed for use
3 months after vaccination (vaccine efficacy 90% in children <18 years of age. No information is
and 80%, respectively). In adults aged 46–64 years, available on the use of Vaxchora during preg-
vibriocidal antibody seroconversion rates, the nancy or lactation. The safety and effective-
best available marker for protection against chol- ness of Vaxchora have not been established
era, were noninferior to the response seen in in immunocompromised people. There was no
adults aged 18–45 years. difference in adverse events reported among
HIV-positive recipients of an older formulation
VACCINE ADMINISTRATION of the CVD 103-HgR vaccine and those who
Vaxchora is administered in a single oral dose, received placebo.
which consists of ingestion of the entire contents Vaxchora may be shed in the stool for at least
of 1 double-chambered sachet. Vaxchora should 7 days, and the vaccine strain may be transmitted
be taken at least 10 days before potential cholera to nonvaccinated close contacts. Clinicians and
exposure. Eating or drinking should be avoided travelers should use caution when considering
for 60 minutes before and after oral ingestion whether to use the vaccine in people with immu-
of Vaxchora. Prepare and administer Vaxchora nocompromised close contacts.
in a health care setting equipped to dispose of
medical waste. CDC website: www.cdc.gov/cholera
CHOLERA 155
516
BIBLIOGRAPHY
1. Chen WH, Cohen MB, Kirkpatrick BD, Brady RC, 6. Kollaritsch H, Que JU, Kunz C, Wiedermann G, Herzog
Galloway D, Gurwith M, et al. Single-dose live oral C, Cryz SJ, Jr. Safety and immunogenicity of live oral
cholera vaccine CVD 103-HgR protects against human cholera and typhoid vaccines administered alone or
experimental infection with vibrio cholerae O1 El Tor. in combination with antimalarial drugs, oral polio
Clin Infect Dis. 2016 Jun 1;62(11):1329–35. vaccine, or yellow fever vaccine. J Infect Dis. 1997
2. Danzig L, editor. Vaxchora™ clinical data summary. Apr;175(4):871–5.
Meeting of the Advisory Committee on Immunization 7. Loharikar A, Newton AE, Stroika S, Freeman M,
Practices; 2016 February 24; Atlanta, GA. Greene KD, Parsons MB, et al. Cholera in the United
3. Gaffga NH, Tauxe RV, Mintz ED. Cholera: a new States, 2001–2011: a reflection of patterns of global
epidemiology and travel. Epidemiol Infect. 2015
3
homeland in Africa? Am J Trop Med Hyg. 2007
Oct;77(4):705–13. March;143(4):695–703.
4. Harris JB, Larocque RC, Charles RC, Mazumder RN, 8. Schilling KA, Cartwright EJ, Stamper J, Locke M,
Khan AI, Bardhan PK. Cholera's western front. Lancet. Esposito DH, Balaban V, et al. Diarrheal illness among
2010 Dec 11;376(9757):1961–5. US residents providing medical services in Haiti during
the cholera epidemic, 2010–2011. J Travel Med. 2014
5. Harris JB, LaRocque RC, Qadri F, Ryan ET, Jan-Feb;21(1):55–7.
Calderwood SB. Cholera. Lancet. 2012 Jun
30;379(9835):2466–76. 9. World Health Organization. Cholera, 2014. Wkly
Epidemiol Rec. 2015 Oct 2;90(40):517–28.
COCCIDIOIDOMYCOSIS
Tom M. Chiller, Paige A. Armstrong, Orion Z. McCotter
respiratory specimens or tissue provides a defini- risk for dissemination and people with the follow-
tive diagnosis. Microscopy of sputum or tissue can ing clinical manifestations should receive antifun-
identify Coccidioides spherules but has low sensi- gal therapy:
tivity. Coccidioidomycosis is a nationally notifi-
able disease.
• Severe acute pulmonary disease
• Chronic pulmonary disease
TREATMENT
Expert opinions differ on the proper manage-
• Disseminated disease
ment of patients with uncomplicated primary Depending on the clinical situation, azole antifun-
pulmonary disease in the absence of risk factors gal agents or amphotericin B may be used.
for severe or disseminated disease. Some experts
recommend no therapy since most illnesses are PREVENTION
3
self-limited, whereas others advise treatment to Limit exposure to outdoor dust in endemic areas.
reduce the intensity or duration of symptoms.
Treatment with antifungal agents has not been CDC website: www.cdc.gov/fungal/diseases/
proven to prevent dissemination. People at high coccidioidomycosis
BIBLIOGRAPHY
1. Ampel NM. Coccidioidomycosis. In: Kauffman of a reemerging disease. Clinical characteristics and
CA, Pappas PG, Sobel JD, Dismukes WE, editors. current controversies. Medicine (Baltimore). 2004
Essentials of Clinical Mycology. New York: Springer May;83(3):149–75.
Science+Business Media, LLC; 2011. pp. 349–66. 6. Galgiani JN, Ampel NM, Blair JE, Catanzaro A, Johnson
2. Ampel NM. Coccidioidomycosis: a review of recent RH, Stevens DA, et al. Coccidioidomycosis. Clin Infect
advances. Clin Chest Med. 2009 Jun;30(2):241–51. Dis. 2005 Nov 1;41(9):1217–23.
3. CDC. Coccidioidomycosis in travelers return- 7. Rosenstein NE, Emery KW, Werner SB, Kao A, Johnson
ing from Mexico–Pennsylvania, 2000. MMWR. R, Rogers D, et al. Risk factors for severe pulmonary
2000;49(44):1004–6. and disseminated coccidioidomycosis: Kern County,
4. Chiller TM, Galgiani JN, Stevens DA. California, 1995–1996. Clin Infect Dis. 2001 Mar
Coccidioidomycosis. Infect Dis Clin North Am. 2003 1;32(5):708–15.
Mar;17(1):41–57, viii. 8. Thompson GR, 3rd. Pulmonary coccidioidomycosis.
5. Crum NF, Lederman ER, Stafford CM, Parrish JS, Semin Respir Crit Care Med. 2011 Dec;32(6):754–63.
Wallace MR. Coccidioidomycosis: a descriptive survey
CRYPTOSPORIDIOSIS
Michele C. Hlavsa, Lihua Xiao
CRYPTOSPORIDIOSIS 157
581
or iodine). Water can be treated effectively by fil- 1 minute to allow for a margin of safety). Alcohol-
tering with an absolute 1-µm filter or heating to based hand sanitizers are not effective against the
a rolling boil (any water brought to a boil should parasite.
be adequately disinfected; however, if fuel sup-
plies are adequate, travelers may wish to boil for CDC website: www.cdc.gov/parasites/crypto
BIBLIOGRAPHY
1. Cama VA, Bern C, Roberts J, Cabrera L, Sterling CR, North American travelers to Mexico. Am J Trop Med
Ortega Y, et al. Cryptosporidium species and subtypes Hyg. 2008 Aug;79(2):210–4.
and clinical manifestations in children, Peru. Emerg
Infect Dis. 2008 Oct;14(10):1567–74.
6. Pantenburg B, Cabada MM, White AC, Jr. Treatment
of cryptosporidiosis. Expert Rev Anti Infect Ther. 2009 3
2. Cartwright RY. Food and waterborne infections associ- May;7(4):385–91.
ated with package holidays. J Appl Microbiol. 2003;94 7. Roy SL, DeLong SM, Stenzel SA, Shiferaw B,
Suppl:12S–24S. Roberts JM, Khalakdina A, et al. Risk fac-
3. Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag tors for sporadic cryptosporidiosis among
TH, Panchalingam S, et al. Burden and aetiology of diar- immunocompetent persons in the United
rhoeal disease in infants and young children in devel- States from 1999–2001. J Clin Microbiol. 2004
oping countries (the Global Enteric Multicenter Study, Jul;42(7):2944–51.
GEMS): a prospective, case-control study. Lancet. 2013 8. van Lieshout L, Roestenberg M. Clinical consequences
Jul 20;382(9888):209–22. of new diagnostic tools for intestinal parasites. Clin
4. Lalonde LF, Gajadhar AA. Effect of storage media, tem- Microbiol Infect. 2015 Jun;21(6):520–8.
perature, and time on preservation of Cryptosporidium 9. Weitzel T, Wichmann O, Muhlberger N, Reuter B,
parvum oocysts for PCR analysis. Vet Parasitol. 2009 Hoof HD, Jelinek T. Epidemiological and clinical features
Mar 23;160(3-4):185–9. of travel-associated cryptosporidiosis. Clin Microbiol
5. Nair P, Mohamed JA, DuPont HL, Figueroa JF, Carlin LG, Infect. 2006 Sep;12(9):921–4.
Jiang ZD, et al. Epidemiology of cryptosporidiosis in
TREATMENT PREVENTION
Cutaneous larva migrans is self-limiting; migrat- Reduce contact with contaminated soil by wear-
ing larvae usually die after 5–6 weeks. Albendazole ing shoes and protective clothing and using bar-
is very effective for treatment. Ivermectin is riers such as towels when seated on the ground.
effective but not approved for this indication.
Symptomatic treatment for frequent severe itch- CDC website: www.cdc.gov/parasites/
ing may be helpful. zoonotichookworm
BIBLIOGRAPHY
CYCLOSPORIASIS
Barbara L. Herwaldt
EPIDEMIOLOGY DIAGNOSIS
Most common in tropical and subtropical Diagnosed by detecting Cyclospora oocysts in
regions, where outbreaks are frequently sea- stool specimens. Stool examinations for ova and
sonal (such as during summers and rainy sea- parasites usually do not include methods for
son in Nepal); even short-term travelers can detecting Cyclospora unless testing for this par-
become infected. Outbreaks in the United States asite is specifically requested. Diagnostic assis-
and Canada have been linked to imported fresh tance for Cyclospora and other parasitic diseases
produce. is also available from CDC (www.cdc.gov/dpdx;
404-718-4745; [email protected]). Cyclosporiasis
CLINICAL PRESENTATION is a nationally notifiable disease.
Incubation period averages 1 week (range,
2 days to >2 weeks). Onset of symptoms is often TREATMENT
abrupt but can be gradual; some people have Trimethoprim-sulfamethoxazole; no highly effec-
an influenzalike prodrome. The most common tive alternatives have been identified.
BIBLIOGRAPHY
1. Abanyie F, Harvey RR, Harris JR, Wiegand RE, Gaul L, 4. Herwaldt BL. The ongoing sage of US outbreaks of cyclo-
Desvignes-Kendrick M, et al. 2013 multistate outbreaks sporiasis associated with imported fresh produce: what
of Cyclospora cayetanensis infections associated Cyclospora cayetanensis has taught us and what we have
with fresh produce: focus on the Texas investigations. yet to learn. In: Institute of Medicine, editor. Addressing
Epidemiol Infect. 2015 Dec;143(16):3451–8.
2. Hall RL, Jones JL, Herwaldt BL. Surveillance for
Foodborne Threats to Health: Policies, Practices, and
Global Coordination, Workshop Summary. Washington, 3
laboratory-confirmed sporadic cases of Cyclosporiasis— DC: National Academies Press; 2006. pp. 85–115, 33–4 0.
United States, 1997–2008. MMWR Surveill Summ. 2011 5. Ortega YR, Sanchez R. Update on Cyclospora caye
Apr 8;60(2):1–11. tanensis, a food-borne and waterborne parasite. Clin
3. Herwaldt BL. Cyclospora cayetanensis: a review, focusing Microbiol Rev. 2010 Jan;23(1):218–34.
on the outbreaks of cyclosporiasis in the 1990s. Clin 6. Shlim DR. Cyclospora cayetanensis. Clin Lab Med. 2002
Infect Dis. 2000 Oct;31(4):1040–57. Dec;22(4):927–36.
CYSTICERCOSIS
Paul T. Cantey, Susan Montgomery
CYSTICERCOSIS 161
612
3 BIBLIOGRAPHY
1. Del Brutto OH. Neurocysticercosis among international seizures during antiparasitic treatment for cysticercosis
travelers to disease-endemic areas. J Travel Med. 2012 and early after. Epilepsia. 2014 Sep;55(9):1452–9.
Mar-Apr;19(2):112–7. 4. Garcia HH, Gonzales I, Lescano AG, Bustos JA, Zimic
2. Garcia HH, Del Brutto OH, Nash TE, White AC, M, Escalante D, et al. Efficacy of combined antiparasitic
Jr., Tsang VC, Gilman RH. New concepts in the therapy with praziquantel and albendazole for neuro-
diagnosis and management of neurocysticerco- cysticercosis: a double-blind, randomised controlled
sis (Taenia solium). Am J Trop Med Hyg. 2005 trial. Lancet Infect Dis. 2014 Aug;14(8):687–95.
Jan;72(1):3–9. 5. Garcia HH, Gonzalez AE, Evans CA, Gilman RH,
3. Garcia HH, Gonzales I, Lescano AG, Bustos JA, Pretell Cysticercosis Working Group in Peru. Taenia solium
EJ, Saavedra H, et al. Enhanced steroid dosing reduces cysticercosis. Lancet. 2003 Aug 16;362(9383):547–56.
DENGUE
Tyler M. Sharp, Janice Perez-Padilla, Stephen H. Waterman
3
641
3
61
resuscitation. Patients can also develop severe a single acute-phase serum specimen obtained
hemorrhagic manifestations, including hematem- early (≤5 days after fever onset) in the illness by
esis, bloody stool, melena, or menorrhagia, espe- detecting viral genomic sequences with RT-PCR
cially if they have prolonged shock. Uncommon or dengue nonstructural protein 1 (NS1) anti-
manifestations include hepatitis, myocarditis, gen by immunoassay. Later in the illness (≥4 days
pancreatitis, and encephalitis. after fever onset), IgM against dengue virus can
As plasma leakage subsides, the patient enters be detected with ELISA. For patients presenting
the convalescent phase and begins to reabsorb during the first week after fever onset, diagnostic
extravasated intravenous fluids and pleural and testing should include a test for dengue virus (PCR
abdominal effusions. As a patient’s well- being or NS1) and IgM. For patients presenting >1 week
improves, hemodynamic status stabilizes (although
he or she may manifest bradycardia), and diure-
after fever onset, IgM is most useful, although NS1
has been reported positive up to 12 days after
3
sis ensues. The patient’s hematocrit stabilizes or fever onset (Figure 3-1). In the United States, both
may fall because of the dilutional effect of the reab- IgM ELISA and real-time RT-PCR are approved as
sorbed fluid, and the white cell count usually starts in vitro diagnostic tests.
to rise, followed by a recovery of platelet count. The Presence of virus by RT-PCR or NS1 antigen in
convalescent-phase rash may desquamate and be a single diagnostic specimen is considered labo-
pruritic. ratory confirmation of dengue in patients with a
Laboratory findings commonly include leu- compatible clinical and travel history. IgM in a sin-
copenia, thrombocytopenia, hyponatremia, ele- gle serum sample suggests a probable recent den-
vated aspartate aminotransferase and alanine gue infection and should be considered diagnostic
aminotransferase, and a normal erythrocyte for dengue if the infection most likely occurred in
sedimentation rate. a place where other potentially cross-reactive fla-
Data are limited on health outcomes of dengue viviruses (such as Zika, West Nile, yellow fever,
in pregnancy and effects of maternal infection on and Japanese encephalitis viruses) are not a risk.
the developing fetus. Perinatal transmission can If infection is likely to have occurred in a place
occur, and peripartum maternal infection may where other potentially cross-reactive flaviviruses
increase the likelihood of symptomatic infection circulate, both molecular and serologic diagnostic
in the newborn. Of the 41 perinatal transmission testing should be performed to detect evidence of
cases described in the literature, all developed infection with dengue and the other flaviviruses.
thrombocytopenia, most had evidence of plasma IgG by ELISA in a single serum sample is not
leakage evidenced by ascites or pleural effusions, useful for diagnostic testing because it remains
and fever was absent in only 2. Nearly 40% had a detectable for life after a dengue infection. In addi-
hemorrhagic manifestation, and one-fourth had tion, people infected with or vaccinated against
hypotension. Symptoms in perinatally infected other flaviviruses (such as yellow fever or Japanese
neonates typically present during the first week encephalitis) may produce cross- reactive flavi-
of life. Placental transfer of maternal IgG against virus antibodies, yielding false-positive serologic
dengue virus ( from a previous maternal infection) dengue diagnostic test results.
may increase risk for severe dengue among infants Dengue diagnostic testing (molecular and sero-
infected at 6–12 months of age, when the protec- logic) is available from several commercial refer-
tive effect of these antibodies wanes. ence diagnostic laboratories, state public health
laboratories, and CDC (www.cdc.gov/ Dengue/
DIAGNOSIS clinicalLab/index.html). Consultation on dengue
Clinicians should consider dengue in a patient diagnostic testing can be obtained from CDC at
who was in an endemic area within 2 weeks 787-706-2399.
before symptom onset. Because dengue is a
nationally notifiable disease, all suspected cases TREATMENT
should be reported to the local health depart- No specific antiviral agents exist for dengue.
ment. Laboratory confirmation can be made from Patients should be advised to stay well hydrated
DENGUE 167
681
DENV
Sensitivity
RNA
IgM*
3 NS1
0 5 6 7 8 9 90
Days After Onset of Fever
FIGURE 3-1 . Relative sensitivity of detection of dengue virus nucleic acid, antigen, and IgM1
Abbreviations: DENV, dengue virus; NS1, nonstructural protein 1.
1
DENV RNA and NS1 are detectable during the first week of illness. Anti-DENV IgM is detectable starting approximately
5 days after illness onset. Although most cases only have detectable IgM anti-DENV for 14–20 days after illness onset, in
some cases it may be detectable for up to 90 days. Detection of anti-DENV IgG is neither sensitive nor specific in identifying
patients with dengue.
and to avoid aspirin (acetylsalicylic acid), aspirin- and during epidemics). Travelers going to the trop-
containing drugs, and other nonsteroidal anti- ics for any length of time should avoid mosquito
inflammatory drugs (such as ibuprofen) because bites by taking the following preventive measures:
of their anticoagulant properties. Fever should be
controlled with acetaminophen and tepid sponge
• Select accommodations with well-screened
windows and doors or air conditioning when
baths. Febrile patients should avoid mosquito
possible. Aedes mosquitoes typically live
bites to reduce risk of further transmission. For
indoors and are often found in dark, cool
those who develop severe dengue, close obser-
places, such as in closets, under beds, behind
vation and frequent monitoring in an intensive
curtains, in bathrooms, and on porches.
care unit setting may be required. Prophylactic
Travelers should be advised to use insecti-
platelet transfusions in dengue patients are not
cides to get rid of mosquitoes in these areas.
beneficial and may contribute to fluid overload.
Similarly, administration of corticosteroids has • Wear clothing that covers the arms and legs,
no demonstrated benefit and is potentially harm- especially during the early morning and late
ful to patients; corticosteroids should not be used afternoon, when risk of being bitten is the
except in the case of autoimmune-related compli- highest.
cation (such as hemophagocytic lymphohistiocy-
tosis or immune thrombocytopenia purpura).
• Use insect repellent (see Chapter 2,
Protection against Mosquitoes, Ticks, &
Other Arthropods).
PREVENTION
No vaccine is available in the United States, • For longer-term travelers, empty and clean
although 1 has been licensed for use in Mexico, the or cover any standing water that can be
Philippines, Brazil, and Thailand. No prophylaxis mosquito-breeding sites in the local residence
is available to prevent dengue. Risk increases with (such as water storage tanks or flower pots).
duration of travel and disease incidence in the
travel destination (such as during the rainy season CDC website: www.cdc.gov/dengue
BIBLIOGRAPHY
1. Barthel A, Gourinat AC, Cazorla C, Joubert C, Dupont- and characteristics of dengue among ill returned travel-
Rouzeyrol M, Descloux E. Breast milk as a possible ers, 1997–2006. Emerg Infect Dis. 2008 Jul;14(7):1081–8.
route of vertical transmission of dengue virus? Clin 6. Simmons CP, Farrar JJ, van Vinh Chau N, Wills B.
Infect Dis. 2013 Aug;57(3):415–7. Dengue. N Engl J Med. 2012 Apr 12;366(15):1423–32.
2. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, 7. Srikiatkhachorn A, Rothman AL, Gibbons RV,
Moyes CL, et al. The global distribution and burden of Sittisombut N, Malasit P, Ennis FA, et al. Dengue—how
dengue. Nature. 2013 Apr 25;496(7446):504–7. best to classify it. Clin Infect Dis. 2011 Sep;53(6):563–7.
3. Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, 8. Streit JA, Yang M, Cavanaugh JE, Polgreen PM. Upward
Gubler DJ, et al. Dengue: a continuing global threat. Nat trend in dengue incidence among hospitalized patients,
3
Rev Microbiol. 2010 Dec;8(12 Suppl):S7–16. United States. Emerg Infect Dis. 2011 May;17(5):914–6.
4. Leder K, Torresi J, Libman MD, Cramer JP, Castelli F, 9. Tomashek KM, Margolis HS. Dengue: a potential
Schlagenhauf P, et al. GeoSentinel surveillance of illness transfusion-transmitted disease. Transfusion. 2011
in returned travelers, 2007–2011. Ann Intern Med. 2013 Aug;51(8):1654–6 0.
Mar 19;158(6):456–68.
10. World Health Organization. Dengue: guidelines
5. Schwartz E, Weld LH, Wilder-Smith A, von Sonnenburg for diagnosis, treatment, prevention and control.
F, Keystone JS, Kain KC, et al. Seasonality, annual trends, Geneva: World Health Organization; 2009.
DIPHTHERIA
Tejpratap S. P. Tiwari
DIPHTHERIA 169
701
C. diphtheriae from culture of nasal or throat required. Antimicrobial prophylaxis (erythromycin
swabs or membrane tissue. Diphtheria is a nation- or penicillin) is recommended for close contacts of
ally notifiable disease. patients.
TREATMENT PREVENTION
Patients with respiratory diphtheria require hos- All travelers should be up-to-date with diphtheria
pitalization to monitor response to treatment and toxoid vaccine before departure. After a childhood
manage complications. Equine diphtheria anti- primary series and a booster dose during ado-
toxin (DAT) is the mainstay of treatment and is lescence, routine booster doses with a diphthe-
administered after specimen testing, without ria toxoid–containing vaccine given either as Td
3 waiting for laboratory confirmation. In the United
States, DAT is available to physicians under an
(tetanus-diphtheria) or Tdap (tetanus-diphtheria-
acellular pertussis if not previously given) should
investigational new drug protocol by contacting be given to all adults every 10 years. This booster
CDC at 770-488-7100. is particularly important for travelers who will live
An antibiotic (erythromycin or penicillin) should or work with local populations in countries where
be used to eliminate the causative organisms, stop diphtheria is endemic.
exotoxin production, and reduce communicabil-
ity. Supportive care (airway, cardiac monitoring) is CDC website: www.cdc.gov/diphtheria
BIBLIOGRAPHY
1. CDC. Fatal respiratory diphtheria in a US traveler to Immunization Practices, 2010. MMWR Morb Mortal
Haiti–Pennsylvania, 2003. MMWR Morb Mortal Wkly Wkly Rep. 2011 Jan 14;60(1):13–5.
Rep. 2004 Jan 9;52(53):1285–6. 3. Galazka A. The changing epidemiology of diphtheria in
2. CDC. Updated recommendations for use of tetanus the vaccine era. J Infect Dis. 2000 Feb;181 Suppl 1:S2–9.
toxoid, reduced diphtheria toxoid and acellular per- 4. World Health Organization. Diphtheria vaccine. Wkly
tussis (Tdap) vaccine from the Advisory Committee on Epidemiol Rec. 2006 Jan 20;81(3):24–32.
INFECTIOUS AGENT TRANSMISSION
The family Filoviridae includes viruses of the Bats are the suspected reservoir species for the
Ebolavirus and Marburgvirus genuses, which can viruses within the genus Ebolavirus. Fruit bats
cause hemorrhagic fever in humans and non- (Rousettus aegypticacus) are the natural reservoirs
human primates. Five species within the genus for Marburg virus. Outbreaks occur when a per-
Ebolavirus have been identified: Tai Forest ebola son becomes infected after exposure to the reser-
virus (Taï Forest virus), Sudan ebolavirus (Sudan voir species or a secondarily infected nonhuman
virus), Zaire ebolavirus (Ebola virus), Bundibugyo primate or antelope species and then transmits
ebolavirus (Bundibugyo virus), and Reston ebola the virus to other people in the community. In the
virus (Reston virus). Marburg marburgvirus is the community, Ebola virus and Marburg virus are
single species in its genus. generally transmitted by direct physical contact
between unprotected skin or mucous membranes reported. Additional cases occurred in Nigeria,
and blood or other infected body fluids of patients Senegal, Mali, Spain, the United Kingdom, Italy,
in the acute phase of Ebola virus disease (EVD) and the United States after infected people trav-
or Marburg virus disease (MVD) or from patients eled from West Africa.
who have died from EVD or MVD. Aerosol trans- Countries with confirmed human cases of
mission of Ebola virus in humans has not been Marburg hemorrhagic fever include Uganda,
documented. Kenya, Democratic Republic of the Congo, Angola,
After recovery from acute disease, the virus and possibly Zimbabwe. Four cases of Marburg
or its RNA persists in some specific body fluids hemorrhagic fever have occurred in travelers visit-
of convalescent EVD or MVD patients. Ebola ing caves harboring bats, including Kitum cave in
virus RNA has been detected in breast milk up to
21 days after the onset of the disease and in vag-
Kenya and Python cave in Maramagambo Forest,
Uganda. Miners in the Democratic Republic of the
3
inal secretions up to 33 days after onset. Ebola Congo and Uganda have also acquired Marburg
virus has also been shown to persist in “immune- virus infection from working in underground
privileged” sites (such as the central nervous sys- mines harboring bats.
tem, eye, testes). Ebola virus and Marburg virus Reston virus is believed to be endemic in the
have been cultured from ocular aqueous humor Philippines but has not been shown to cause
at 2 and 3 months after disease onset, respectively. human disease.
Evidence suggests that Ebola and Marbug
viruses can be sexually transmitted from a male sur- CLINICAL PRESENTATION
vivor to his female partner months after onset of The incubation period for EVD and MVD ranges
disease. In pregnant women with EVD, there can be from 2–21 days, although most people develop
in utero transmission of Ebola virus to the fetus. symptoms after 7–10 days. Signs and symptoms of
EVD and MVD can vary but, in general, patients
EPIDEMIOLOGY present with an abrupt- onset fever, weakness,
People at greatest risk of EVD or MVD include fam- myalgias, arthralgias, and headache. This is often
ily members, health care workers or others who followed by gastrointestinal symptoms including
come into direct contact with infected patients anorexia, abdominal discomfort, nausea, vomiting,
or corpses without protective equipment, people and diarrhea. Conjunctival injection, rash, and hic-
who have come into contact or close proximity to cups have also been reported. In the West African
bats (visiting bat caves), and those who have han- EVD epidemic, diarrhea was severe with up to 10
dled infected primates or carcasses. Additionally, L of output reported per 24 hours. Intravascular
sexual partners of recent male EVD or MVD sur- volume depletion is common and may be asso-
vivors may be at risk if they have had contact with ciated with profound electrolyte depletion, hypo-
virus-infected semen. profusion, and shock. Coagulopathy is a late
Countries where domestically acquired EVD manifestation and can present with a petechial
cases have been reported and that should be rash, ecchymoses, and sometimes overt bleed-
considered areas where future epidemics could ing (epistaxis, melena, bloody diarrhea). Hypoxia,
occur include Republic of the Congo, Côte d’Ivo- another late manifestation, was noted in half of
ire, Democratic Republic of the Congo, Gabon, EVD patients (median oxygen saturation 84.5%).
Uganda, Guinea, Liberia, and Sierra Leone. Laboratory abnormalities include elevations in
Typically, previous Ebola outbreaks had been liver enzymes, initial drop in leukocyte count,
limited in scope and geographic extent. However, and thrombocytopenia. Because the incubation
in March of 2014, an outbreak of Ebola virus was period may be as long as 21 days, patients may not
detected in a rural area of Guinea near the bor- develop illness until returning from travel; there-
der with Liberia and Sierra Leone. By June of fore, a thorough travel and exposure history is
2014, cases were reported in all three countries critical. Fatality ratios for EVD vary, ranging from
and across many districts. The outbreak was the 19%–90% depending on Ebolavirus species and the
largest and most complex Ebola epidemic ever availability of medical care.
BIBLIOGRAPHY
1. Bah EI, Lamah MC, Fletcher T, Jacob ST, Brett-Major DM, 6. Fowler RA, Fletcher T, Fischer WA, 2nd, Lamontagne F,
Sall AA, et al. Clinical presentation of patients with Jacob S, Brett-Major D, et al. Caring for critically ill
Ebola virus disease in Conakry, Guinea. N Engl J Med. patients with Ebola virus disease. Perspectives from West
2015 Jan 1;372(1):40–7. Africa. Am J Respir Crit Care Med. 2014 Oct 1;190(7):733–7.
2. CDC. Ebola virus disease—U.S. healthcare workers 7. Osterholm MT, Moore KA, Kelley NS, Brosseau LM,
and settings—personal protective equipment. 2016 Wong G, Murphy FA, et al. Transmission of Ebola
[cited 2016 Sep. 22]. Available from: http://www.cdc. viruses: what we know and what we do not know. mBio.
gov/v hf/ebola/h ealthcare-us/ppe/index.html. 2015;6(2):e00137.
3. Ewer K, Rampling T, Venkatraman N, Bowyer G, 8. Regules JA, Beigel JH, Paolino KM, Voell J, Castellano AR,
Wright D, Lambe T, et al. A monovalent chimpanzee Munoz P, et al. A Recombinant vesicular stomatitis virus
adenovirus Ebola vaccine boosted with MVA. N Engl J Ebola vaccine—preliminary report. N Engl J Med. 2015
Med. 2016 Apr 28;374(17):1635–4 6. Apr 1. DOI: http://dx.doi.org/10.1056/NEJMoa1414216
4. Fallah M. A Cohort study of survivors of Ebola virus 9. Uyeki TM, Mehta AK, Davey RT, Jr., Liddell AM, Wolf
infection in Liberia (PREVAIL III). Conference on T, Vetter P, et al. Clinical management of Ebola virus
Retroviruses and Opportunistic Infections; February disease in the United States and Europe. N Engl J Med.
22–25, 2016; Boston, Massachusetts. 2016 Feb 18;374(7):636–46.
5. Fields BN, Knipe DM, Howley PM. Fields virology. 10. World Health Organization. Clinical care for survivors
Philadelphia: Wolters Kluwer Health/Lippincott of Ebola virus disease. 2016 [cited 2016 Apr. 11]. Available
Williams & Wilkins; 2007. from: http://www.who.int/csr/resources/publications/
ebola/guidance-survivors/en/.
ECHINOCOCCOSIS
Pedro L. Moro, Paul T. Cantey
ECHINOCOCCOSIS 173
741
BIBLIOGRAPHY
1. Brunetti E, Kern P, Vuitton DA. Expert consensus for the and therapeutic aspects. Asian Pac J Trop Med. 2012
diagnosis and treatment of cystic and alveolar echino- Apr;5(4):253–6 0.
coccosis in humans. Acta Trop. 2010 Apr;114(1):1–16. 4. McManus DP, Zhang W, Li J, Bartley PB. Echinococcosis.
2. Eckert J, Gottstein B, Heath D, Liu FJ. Prevention of echi- Lancet. 2003 Oct 18;362(9392):1295–304.
nococcosis in humans and safety precautions. In: Eckert 5. Moro PL, Schantz PM. Echinococcosis: historical land-
J, Gemmell MA, Meslin FX, Pawlowski ZS, editors. marks and progress in research and control. Ann Trop
WHO/OIE Manual on Echinococcosis in Humans and Med Parasitol. 2006 Dec;100(8):703–14.
Animals: a Public Health Problem of Global Concern.
6. Stojkovic M, Rosenberger K, Kauczor HU, Junghanss T,
Paris: World Organization for Animal Health; 2001. pp.
Hosch W. Diagnosing and staging of cystic echinococ-
238–45.
cosis: how do CT and MRI perform in comparison to
3. Mandal S, Mandal MD. Human cystic echinococ- ultrasound? PLoS Negl Trop Dis. 2012;6(10):e1880.
cosis: epidemiologic, zoonotic, clinical, diagnostic
ESCHERICHIA COLI,
DIARRHEAGENIC
Ciara E. O’Reilly, Martha Iwamoto, Patricia M. Griffin
strains capable of causing human illness, espe- period ranging from 9 hours to 3 days. The median
cially bloody diarrhea and hemolytic uremic incubation period of STEC infections is 3–4 days,
syndrome (HUS). with a range of 1–10 days. The clinical manifesta-
tions of diarrheagenic E. coli vary by pathotype
TRANSMISSION (Table 3-1).
Diarrheagenic pathotypes can be passed in the
feces of humans and other animals. Transmission DIAGNOSIS
occurs through the fecal-oral route, primarily via Many patients with travel-associated E. coli infec-
contaminated food or water and also through tions, especially those with nonbloody diarrhea, as
person-to-person contact and contact with ani- commonly occurs with ETEC infection, are likely
mals or their environment. People constitute the
main reservoir for non- STEC pathotypes that
to be managed symptomatically and are unlikely
to have the diagnosis confirmed by a laboratory.
3
cause diarrhea in humans. The intestinal tracts Most US clinical laboratories do not use tests that
of animals, especially cattle and other ruminants, can detect diarrheagenic E. coli other than STEC,
are the primary reservoirs of STEC. although recently approved nucleic acid amplifi-
cation tests that can detect ETEC are now avail-
EPIDEMIOLOGY able in some clinical laboratories. Testing for
Travel to less-developed countries is associated non-STEC pathotypes is typically done at public
with higher risk for travelers’ diarrhea, includ- health laboratories and only when an outbreak of
ing some types of E. coli infection. ETEC is the diarrheal illness of unknown origin is being inves-
most common pathotype that causes diarrhea tigated. In this situation, isolates may be sub-
among travelers returning from most regions. mitted via state health departments to CDC for
Travel-associated infections caused by non-STEC testing. These tests typically involve PCR testing
diarrheagenic E. coli are likely underrecognized or whole genome sequence analysis for the spe-
because most clinical laboratories do not use cific virulence genes of ETEC, EPEC, EAEC, EIEC,
methods that can detect them. Risk of non-STEC and DAEC.
diarrheagenic E. coli infections (primarily ETEC) When a decision is made to identify a cause of
can be divided into 3 grades, according to the des- an acute diarrheal illness, in addition to routine cul-
tination country: ture for Salmonella, Shigella, and Campylobacter,
the stool sample should be cultured for E. coli
• Low-risk countries include the United States, O157:H7 and simultaneously assayed for non-
Canada, Australia, New Zealand, Japan, and
O157 STEC with a test that detects Shiga tox-
countries in Northern and Western Europe.
ins (or the genes that encode them). For more
• Intermediate-risk countries include those in information, see www.cdc.gov/mmwr/preview/
Eastern Europe, South Africa, and some of the mmwrhtml/rr5812a1.htm. All presumptive E. coli
Caribbean islands. O157 isolates and Shiga toxin–positive specimens
should be sent to a public health laboratory for
• High-risk areas include most of Asia, the further characterization. Rapid, accurate diagno-
Middle East, Africa, Mexico, and Central and
sis of STEC infection is important, because early
South America.
clinical management decisions can affect patient
STEC infections are more commonly reported in outcomes, and early detection can help prevent
industrialized countries than in less-developed secondary spread.
countries. Additional information about travel-
ers’ diarrhea is available in Chapter 2, Travelers’ TREATMENT
Diarrhea. Patients with profuse diarrhea or vomiting
should be rehydrated. Evidence from studies
CLINICAL PRESENTATION of children with STEC O157 infection indicates
Where information is available, non-STEC diar- that early use of intravenous fluids (within the
rheagenic E. coli infections have an incubation first 4 days of diarrhea onset) may decrease the
ETEC Small bowel adherence; heat-stable Acute watery diarrhea, afebrile, occasionally severe
or heat-labile enterotoxin production
EAEC Small and large bowel adherence Watery diarrhea with mucous, occasionally bloody; can cause
mediated via various adhesions and prolonged or persistent diarrhea in children
accessory proteins; enterotoxin and
3 cytotoxin production
EPEC Small bowel adherence and epithelial Severe acute watery diarrhea; may be persistent; common
cell effacement mediated by intimin cause of infant diarrhea in developing countries
EIEC Mucosal invasion and inflammation Watery diarrhea that may progress to bloody diarrhea
of large bowel (dysenterylike syndrome), fever
DAEC Diffuse adherence to epithelial cells Watery diarrhea but pathogenicity not conclusively demonstrated
STEC Large bowel adherence mediated Watery diarrhea that progresses (often for STEC O157, less
via intimin; Shiga toxin 1, Shiga toxin often for non-O157) to bloody diarrhea in 1–3 days; abdominal
2 production cramps and tenderness; if fever present, low-grade; hemolytic
uremic syndrome complicates ≈6% of STEC O157 and ≈1% of
non-O157 infections
Abbreviations: ETEC, enterotoxigenic E. coli; EAEC, enteroaggregative E. coli; EPEC, enteropathogenic E. coli; EIEC, enteroinvasive
E. coli; DAEC, diffusely adherent E. coli; STEC, Shiga toxin–producing E. coli.
BIBLIOGRAPHY
1. CDC. Outbreak of Escherichia coli O104:H4 infections diagnosed after return to the United States, Foodborne
associated with sprout consumption—Europe and Diseases Active Surveillance Network (FoodNet),
North America, May-July 2011. MMWR Morb Mortal 2004–2009. Clin Infect Dis. 2012 Jun;54 Suppl 5:S480–7.
Wkly Rep. 2013 Dec. 20, 2013;62(50):1029–31. 7. Mintz ED. Enterotoxigenic Escherichia coli: outbreak
2. DuPont HL. Systematic review: the epidemiology surveillance and molecular testing. Clin Infect Dis.
and clinical features of travellers' diarrhoea. Aliment 2006 Jun 1;42(11):1518–20.
Pharmacol Ther. 2009 Aug;30(3):187–9 6. 8. Ouyang-Latimer J, Jafri S, VanTassel A, Jiang ZD,
3. Hedican EB, Medus C, Besser JM, Juni BA, Koziol B, Gurleen K, Rodriguez S, et al. In vitro antimicrobial
Taylor C, et al. Characteristics of O157 versus non- susceptibility of bacterial enteropathogens isolated
3
O157 Shiga toxin-producing Escherichia coli infections from international travelers to Mexico, Guatemala, and
in Minnesota, 2000–2006. Clin Infect Dis. 2009 Aug India from 2006–2008. Antimicrob Agents Chemother.
1;49(3):358–6 4. 2011 Feb;55(2):874–8.
4. Hickey CA, Beattie TJ, Cowieson J, Miyashita Y, Strife CF, 9. Shah N, DuPont HL, Ramsey DJ. Global etiology
Frem JC, et al. Early volume expansion during diarrhea of travelers' diarrhea: systematic review from 1973
and relative nephroprotection during subsequent to the present. Am J Trop Med Hyg. 2009 Apr;80(4):
hemolytic uremic syndrome. Arch Pediatr Adolesc Med. 609–14.
2011 Oct;165(10):884–9. 10. Wong CS, Mooney JC, Brandt JR, Staples AO, Jelacic S,
5. Kaper JB, Nataro JP, Mobley HL. Pathogenic Escherichia Boster DR, et al. Risk factors for the hemolytic uremic
coli. Nat Rev Microbiol. 2004 Feb;2(2):123–4 0. syndrome in children infected with Escherichia coli
6. Kendall ME, Crim S, Fullerton K, Han PV, Cronquist AB, O157:H7: a multivariable analysis. Clin Infect Dis. 2012
Shiferaw B, et al. Travel-associated enteric infections Jul;55(1):33–41.
FASCIOLIASIS
LeAnne M. Fox
FASCIOLIASIS 177
781
FILARIASIS, LYMPHATIC
LeAnne M. Fox
BIBLIOGRAPHY
1. Debrah AY, Mand S, Specht S, Marfo-Debrekyei Y, Batsa 4. Magill AJ, Ryan ET, Hill DR, Solomon T. Hunter’s
L, Pfarr K, et al. Doxycycline reduces plasma VEGF-C/
sVEGFR-3 and improves pathology in lymphatic filaria-
sis. PLoS pathogens. 2006 Sep;2(9):e92.
Tropical Medicine and Emerging Infectious Diseases.
9th ed. New York: Elsevier Inc.; 2013. 3
5. Taylor MJ, Makunde WH, McGarry HF, Turner JD,
2. Eberhard ML, Lammie PJ. Laboratory diagnosis of filari- Mand S, Hoerauf A. Macrofilaricidal activity after
asis. Clin Lab Med. 1991 Dec;11(4):977–1010. doxycycline treatment of Wuchereria bancrofti: a
3. Lipner EM, Law MA, Barnett E, Keystone JS, von double-blind, randomised placebo-controlled trial.
Sonnenburg F, Loutan L, et al. Filariasis in travelers Lancet. 2005 Jun 18-24;365(9477):2116–21.
presenting to the GeoSentinel Surveillance Network.
PLoS Negl Trop Dis. 2007;1(3):e88.
GIARDIASIS
Kathleen E. Fullerton, Jonathan S. Yoder
GIARDIASIS 179
801
DIAGNOSIS TREATMENT
Giardia cysts or trophozoites are not consistently Effective treatments include metronidazole, tini-
seen in the stools of infected patients. Diagnostic dazole, and nitazoxanide. An alternative is paro-
yield can be increased by examining up to 3 stool momycin. Because making a definitive diagnosis is
samples over several days. Direct fluorescent anti- difficult, empiric treatment can be used in patients
body testing is extremely sensitive and specific. with the appropriate history and typical symptoms.
Rapid immunochromatographic cartridge assays
also are available but should not take the place PREVENTION
of routine ova and parasite examination. Only Food and water precautions (see Chapter 2, Food
molecular testing (such as PCR) can be used to & Water Precautions and Water Disinfection for
3 identify the subtypes of Giardia. Retesting is only
recommended if symptoms persist after treat-
Travelers) and hand hygiene.
BIBLIOGRAPHY
1. Abramowicz M, editor. Drugs for Parasitic Infections. disease—GeoSentinel Surveillance System, United
New Rochelle (NY): The Medical Letter, Inc.; 2013. States, 1997–2011. MMWR Surveill Summ. 2013 Jul
2. Adam EA, Yoder JS, Gould LH, Hlavsa MC, Gargano JW. 19;62:1–23.
Giardiasis outbreaks in the United States, 1971–2011. 7. Johnston SP, Ballard MM, Beach MJ, Causer L, Wilkins
Epidemiol Infect. 2016 Oct;144(13):2790–801. PP. Evaluation of three commercial assays for detection
3. Cantey PT, Roy S, Lee B, Cronquist A, Smith K, Liang of giardia and cryptosporidium organisms in fecal speci-
J, et al. Study of nonoutbreak giardiasis: novel find- mens. J Clin Microbiol. 2003 Feb;41(2):623–6.
ings and implications for research. Am J Med. 2011 8. Ross AG, Cripps AW. Enteropathogens and chronic
Dec;124(12):1175 e1–8. illness in returning travelers. N Engl J Med. 2013 Aug
4. Escobedo AA, Cimerman S. Giardiasis: a pharma- 22;369(8):784.
cotherapy review. Expert Opin Pharmacother. 2007 9. Staat MA, Rice M, Donauer S, Mukkada S, Holloway M,
Aug;8(12):1885–9 02. Cassedy A, et al. Intestinal parasite screening in interna-
5. Hagmann SH, Han PV, Stauffer WM, Miller AO, tionally adopted children: importance of multiple stool
Connor BA, Hale DC, et al. Travel-associated disease specimens. Pediatrics. 2011 Sep;128(3):e613–22.
among US residents visiting US GeoSentinel clinics 10. Swaminathan A, Torresi J, Schlagenhauf P, Thursky K,
after return from international travel. Fam Pract. 2014 Wilder-Smith A, Connor BA, et al. A global study of
Dec;31(6):678–87. pathogens and host risk factors associated with infec-
6. Harvey K, Esposito DH, Han P, Kozarsky P, Freedman tious gastrointestinal disease in returned international
DO, Plier DA, et al. Surveillance for travel-related travellers. J Infect. 2009 Jul;59(1):19–27.
INFECTIOUS AGENT TRANSMISSION
In the United States, coxsackievirus A16 is most Person- to-
person, through contact with saliva,
commonly detected, but other enteroviruses nose and throat secretions, fluid in blisters, or
(such as coxsackievirus A10) can cause hand, stool of an infected person.
foot, and mouth disease. In the past few years,
coxsackievirus A6 has been detected in out- EPIDEMIOLOGY
breaks. Internationally, enterovirus 71 is a com- A common illness in young children, with
mon etiologic agent. worldwide distribution. Recent large outbreaks
BIBLIOGRAPHY
1. CDC. Notes from the field: severe hand, foot, and mouth management of enterovirus 71. Lancet Neurol. 2010
disease associated with coxsackievirus A6—Alabama, Nov;9(11):1097–105.
Connecticut, California, and Nevada, November 3. World Health Organization. A guide to clinical man-
2011–February 2012. MMWR Morb Mortal Wkly Rep. agement and public health response for hand, foot
2012 Mar 30;61(12):213–4. and mouth disease (HFMD). Geneva: World Health
2. Ooi MH, Wong SC, Lewthwaite P, Cardosa MJ, Organization; 2011 [cited 2016 Sep. 23]. Available
Solomon T. Clinical features, diagnosis, and from: http://www.wpro.who.int/publications/docs/
GuidancefortheclinicalmanagementofHFMD.pdf.
HELICOBACTER PYLORI
Ronnie Henry, Bradley A. Connor
HELICOBACTER PYLORI 181
812
BIBLIOGRAPHY
1. Chey WD, Wong BC. American College of 3. Peterson WL, Fendrick AM, Cave DR, Peura DA,
Gastroenterology guideline on the management of Garabedian-Ruffalo SM, Laine L. Helicobacter
HELMINTHS, SOIL-TRANSMITTED
Christine Dubray
BIBLIOGRAPHY 3
1. Bethony J, Brooker S, Albonico M, Geiger SM, Loukas Manson's Tropical Diseases. 22nd ed. London: Saunders;
A, Diemert D, et al. Soil-transmitted helminth infec- 2009. pp. 1515–48.
tions: ascariasis, trichuriasis, and hookworm. Lancet. 3. Brooker S, Clements AC, Bundy DA. Global epidemiol-
2006 May 6;367(9521):1521–32. ogy, ecology and control of soil-transmitted helminth
2. Brooker S, Bundy DAP. Soil-transmitted helminths infections. Adv Parasitol. 2006;62:221–61.
(geohelminths). In: Cook GC, Zumla A, editors.
HEPATITIS A
Noele P. Nelson
HEPATITIS A 183
841
identified risk factors for hepatitis A are interna- anti-HAV result and a negative IgM anti-HAV
tional travel and exposure to contaminated food. result indicate past infection or vaccination and
Cases of travel-related hepatitis A can occur in immunity. The presence of serum IgM anti-HAV
travelers to developing countries with “standard” usually indicates current or recent infection and
tourist itineraries, accommodations, and eating does not distinguish between immunity from
behaviors. Risk is highest for those who live in or infection and vaccination. Acute hepatitis A is a
visit rural areas, trek in backcountry areas, or fre- nationally notifiable disease.
quently eat or drink in settings of poor sanitation.
Common source food exposures are increasingly TREATMENT
recognized as a risk for hepatitis A, and sporadic Supportive care.
3 outbreaks are reported in Europe, Australia, North
America, and other regions with low levels of PREVENTION
endemic transmission. Vaccination or immune globulin (IG), food and
water precautions, maintaining standards of
CLINICAL PRESENTATION hygiene and sanitation.
The incubation period averages 28 days (range,
15–50 days). Infection can be asymptomatic or Vaccine
range in severity from a mild illness lasting 1–2 Two monovalent hepatitis A vaccines, Vaqta
weeks to a severely disabling disease lasting sev- (Merck & Co, Inc, Whitehouse Station, NJ) and
eral months. Clinical manifestations include the Havrix (GlaxoSmithKline Beecham Biologicals,
abrupt onset of fever, malaise, anorexia, nausea, Rixensart, Belgium), are approved for peo-
and abdominal discomfort, followed within a few ple ≥12 months of age in a 2-dose series, and a
days by jaundice. The likelihood of having symp- combined hepatitis A and hepatitis B (Twinrix,
toms with HAV infection is related to the age of GlaxoSmithKline) vaccine is approved for people
the infected person. In children aged <6 years, ≥18 years of age in the United States (Table 3-2).
most (70%) infections are asymptomatic; jaun- The immunogenicity of the combination vaccine
dice is uncommon in symptomatic young chil- is equivalent to that of the monovalent hepatitis
dren. Among older children and adults, the illness A and hepatitis B vaccines when tested after com-
usually lasts <2 months, although approximately pletion of the recommended schedule.
10%–15% of infected people have prolonged or
relapsing symptoms over a 6-to 9-month period. INDICATIONS FOR USE
Severe hepatic and extrahepatic complications, All susceptible people traveling for any purpose,
including fulminant hepatitis and liver failure, are frequency, or duration to countries with high or
rare but more common in older adults and peo- intermediate HAV endemicity should be vacci-
ple with underlying liver disease. Chronic infec- nated or receive IG before departure. Although
tion does not occur. The overall case-fatality ratio the Advisory Committee for Immunization Pra
is 0.3%; however, the ratio is 1.8% among adults ctices recommends hepatitis A vaccination for
aged >50 years. travelers, published maps may not be the best
guide for determining endemicity in develop-
DIAGNOSIS ing countries. Prevalence patterns of HAV infec-
HAV cannot be differentiated from other types of tion vary among regions within a country, and
viral hepatitis on the basis of clinical or epidemi- missing or obsolete data present a challenge.
ologic features. Diagnosis requires a positive test Countries where the prevalence of HAV infection
for antibody to HAV (anti-HAV) IgM in serum, is decreasing have growing numbers of suscepti-
detectable from 2 weeks before the onset of symp- ble people and risk for large outbreaks of hepati-
toms to approximately 6 months afterward. tis A. In recent years, large outbreaks of hepatitis
Serologic tests for total anti-HAV (IgG and A were reported in developed countries among
IgM) are available commercially. A positive total people who had been exposed to imported food
Hepatitis Vaqta (Merck & Co., 1–18 0.5 mL (25 U) IM 0, 6–18 mo None
A vaccine,
inactivated
Inc.) ≥19 1.0 mL (50 U) IM 0, 6–18 mo None
3
Combined Twinrix ≥18 (primary) 1.0 mL (720 IM 0, 1, 6 mo None
hepatitis (GlaxoSmithKline) ELU HAV +
A and B 20 μg HBsAg)
vaccine ≥18 (accelerated) same as above IM 0, 7, 21–30 d 12 mo
Abbreviations: ELU, ELISA units of inactivated HAV; IM, intramuscular; U, units HAV antigen; HAV, hepatitis A virus; HBsAg,
hepatitis B surface antigen.
contaminated with HAV. Taking into account single-dose hepatitis A vaccine efficacy are avail-
the complexity of interpreting hepatitis A risk able for Twinrix. An alternate, accelerated 4-dose
maps and potential risk of foodborne hepatitis schedule is available for Twinrix; doses can be
A in countries with low endemicity, some experts administered at 0, 7, and 21–30 days, followed by
advise people traveling outside the United States a dose at 12 months.
to consider hepatitis A vaccination regardless of Hepatitis A vaccine at the age- appropriate
destination. dose is preferred to IG for children and adults
Vaccination is recommended for unvacci- aged 1–40 years. For optimal protection, adults
nated household members and other people aged >40 years, immunocompromised people,
who anticipate close personal contact (such as and people with chronic liver disease or other
household contacts or regular babysitters) with chronic medical conditions planning to depart to
an international adoptee from a country of high an area in <2 weeks should receive the initial dose
or intermediate endemicity during the 60 days of vaccine along with IG (0.02 mL/kg) at a sepa-
after arrival of the child in the United States. rate injection site.
The first dose of the 2-dose hepatitis A vaccine Travelers who are aged <12 months, are aller-
series should be administered as soon as adop- gic to a vaccine component, or who otherwise
tion is planned, ideally ≥2 weeks before the arri- elect not to receive vaccine should receive a
val of the child (see Chapter 7, International single dose of IG (0.02 mL/kg), which provides
Adoption). effective protection against HAV infection for
up to 3 months. Those who do not receive vac-
VACCINE ADMINISTRATION cination and plan to travel for >3 months should
One dose of a monovalent hepatitis A vaccine receive an IG dose of 0.06 mL/kg, which must be
protects most healthy people aged 1–40 years repeated if the duration of travel is >5 months. IG
and should be administered as soon as travel can be repeated every 6 months thereafter if the
is considered. The monovalent vaccine series traveler remains in a high-risk setting, though
should be completed according to the licensed hepatitis A vaccination should be encouraged if
schedule for long-term protection. No data on not contraindicated.
HEPATITIS A 185
816
BIBLIOGRAPHY
1. Averhoff FM, Khudyakov Y, NP N. Vaccines. 7th ed. imported from Turkey: an epidemiological case study.
Philadelphia: Saunders Elsevier; 2016. Lancet Infect Dis. 2014 Oct;14(10):976–81.
2. CDC. Update: Prevention of hepatitis A after 6. Fiore AE, Wasley A, Bell BP. Prevention of hepatitis
exposure to hepatitis A virus and in interna- A through active or passive immunization: recommen-
tional travelers. Updated recommendations of the dations of the Advisory Committee on Immunization
Advisory Committee on Immunization Practices Practices (ACIP). MMWR Recomm Rep. 2006 May
(ACIP). MMWR Morb Mortal Wkly Rep. 2007 Oct 19;55(RR-7):1–23.
19;56(41):1080–4. 7. Mohd Hanafiah K, Jacobsen KH, Wiersma ST.
3. CDC. Updated recommendations from the Advisory Challenges to mapping the health risk of hepatitis
3
Committee on Immunization Practices (ACIP) for use A virus infection. Int J Health Geogr. 2011;10:57.
of hepatitis A vaccine in close contacts of newly arriving 8. Moro PL, Museru OI, Niu M, Lewis P, Broder K. Reports
international adoptees. MMWR Morb Mortal Wkly Rep. to the Vaccine Adverse Event Reporting System after
2009 Sep 18;58(36):1006–7. hepatitis A and hepatitis AB vaccines in pregnant
4. CDC. Viral Hepatitis Surveillance—United States, 2013 women. Am J Obstet Gynecol. 2014 Jun;210(6):561.e1–6.
[cited 2016 Sep. 23]. Available from: http://www.cdc. 9. Mutsch M, Spicher VM, Gut C, Steffen R. Hepatitis
gov/hepatitis/statistics/2 013surveillance/pdfs/ A virus infections in travelers, 1988–2004. Clin Infect
2013hepsurveillancerpt.pdf. Dis. 2006 Feb 15;42(4):490–7.
5. Collier MG, Khudyakov YE, Selvage D, Adams-Cameron 10. Nelson NP, Murphy TV. Hepatitis A: the changing
M, Epson E, Cronquist A, et al. Outbreak of hepatitis epidemiology of hepatitis A. Clin Liver Dis. 2013 Dec
A in the USA associated with frozen pomegranate arils 20;2(6):227–30.
HEPATITIS B
Francisco Averhoff
HEPATITIS B 187
81
Hepatitis Bprevalence
- High: ~8%
- High Intermediate: 5% • 7%
Low: <2%
Nodata
HEPATITIS B 189
901
HBSAG 2
TOTAL ANTI-HBC IGM ANTI-HBC ANTI-HBS
– – – – Never infected
+ + + – Acute infection
+ + – – Chronic infection
Abbreviations: HBsAg, hepatitis B surface antigen; anti-HBc, antibody to hepatitis B core antigen; anti-HBs, antibody to
hepatitis B surface antigen.
1
From: CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the
United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). Part II: immunization of
adults. MMWR Recomm Rep. 2006 Dec 8;55(RR-16):1–33.
2
To ensure that an HBsAg-positive test result is not a false positive, samples with reactive HBsAg results should be
tested with a licensed neutralizing confirmatory test, if recommended in the manufacturer’s prescribing information.
3
People positive only for anti-HBc are unlikely to be infectious except under unusual circumstances in which they
are the source for direct percutaneous exposure of susceptible recipients to large quantities of virus (such as blood
transfusion or organ transplant).
HEPATITIS B 191
912
192
3
INFECTIOUS DISEASES RELATED TO TRAVEL
Hepatitis B vaccine, Engerix-B (GlaxoSmithKline) 0–19 (primary) 0.5 mL (10 µg HBsAg) IM 0, 1, 6 mo None
recombinant1 0–10 (accelerated) 0.5 mL (10 µg HBsAg) IM 0, 1, 2 mo 12 mo
11–19 (accelerated) 1.0 mL (20 µg HBsAg) IM 0, 1, 2 mo 12 mo
≥20 (primary) 1.0 mL (20 µg HBsAg) IM 0, 1, 6 mo None
≥20 (accelerated) 1.0 mL (20 µg HBsAg) IM 0, 1, 2 mo 12 mo
Hepatitis B vaccine, Recombivax HB (Merck & 0–19 (primary) 0.5 mL (5 µg HBsAg) IM 0, 1, 6 mo None
recombinant1 Co., Inc.) 11–15 (adolescent accelerated) 1.0 mL (10 µg HBsAg) IM 0, 4–6 mo None
≥20 (primary) 1.0 mL (10 µg HBsAg) IM 0, 1, 6 mo None
Combined hepatitis Twinrix (GlaxoSmithKline) ≥18 (primary) 1.0 mL (720 ELU HAV + IM 0, 1, 6 mo None
A and B vaccine 20 μg HBsAg)
≥18 (accelerated) same as above IM 0, 7, 21–30 d 12 mo
Abbreviations: HBsAg, hepatitis B surface antigen; IM, intramuscular; ELU, ELISA units of inactivated HAV; HAV, hepatitis A virus.
1
Consult the prescribing information for differences in dosing for hemodialysis and other immunocompromised patients.
931
BIBLIOGRAPHY
1. CDC. A comprehensive immunization strategy to parenterally transmitted hepatitis viruses in Italy. J Med
eliminate transmission of hepatitis B virus infection in Virol. 2004 Oct;74(2):216–20.
the United States: recommendations of the Advisory 5. Pepin J, Abou Chakra CN, Pepin E, Nault V, Valiquette
Committee on Immunization Practices (ACIP) part 1: L. Evolution of the global burden of viral infections
immunization of infants, children, and adolescents. from unsafe medical injections, 2000–2010. PLoS One.
MMWR Recomm Rep. 2005 Dec 23;54(RR-16):1–31. 2014;9(6):e99677.
2. CDC. A comprehensive immunization strategy to 6. Sagliocca L, Stroffolini T, Amoroso P, Manzillo G,
eliminate transmission of hepatitis B virus infection in Ferrigno L, Converti F, et al. Risk factors for acute
the United States: recommendations of the Advisory hepatitis B: a case-control study. J Viral Hepat. 1997
Committee on Immunization Practices (ACIP) Part Jan;4(1):63–6.
II: immunization of adults. MMWR Recomm Rep. 2006
7. Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott
Dec 8;55(RR-16):1–33.
JJ. Estimations of worldwide prevalence of chronic
3. CDC. Updated US Public Health Service guidelines hepatitis B virus infection: a systematic review of data
for the management of occupational exposures to published between 1965 and 2013. Lancet. 2015 Oct
HBV, HCV, and HIV and recommendations for post- 17;386(10003):1546–55.
exposure prophylaxis. MMWR Recomm Rep. 2001 Jun
8. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas
29;50(RR-11):1–42.
MM, Murad MH. AASLD guidelines for treatment of
4. Mariano A, Mele A, Tosti ME, Parlato A, Gallo G, Ragni chronic hepatitis B. Hepatology. 2016 Jan;63(1):261–83.
P, et al. Role of beauty treatment in the spread of
HEPATITIS C
Deborah Holtzman
HEPATITIS C 193
941
Hepatitis CPrevalence
- High:~5%
- High Moderate: 2.0% • <5.0%
Low Moderate: 1.5% • <2.0%
HEPATITIS C 195
916
BIBLIOGRAPHY
1. American Association for Study of Liver Diseases hepatitis C virus infection. J Hepatol. 2014 Nov;
(AASLD), Infectious Diseases Society of America (IDSA). 61(1 Suppl):S45–57.
Recommendations for testing, managing, and treating 6. Messina JP, Humphreys I, Flaxman A, Brown A,
hepatitis C. [updated 2014 Aug 11; cited 2016 Sep. 23]. Cooke GS, Pybus OG, et al. Global distribution and
Available from: http://www.hcvguidelines.org/. prevalence of hepatitis C virus genotypes. Hepatology.
2. Averhoff FM, Glass N, Holtzman D. Global burden of 2015 Jan;61(1):77–87.
hepatitis C: considerations for healthcare providers in 7. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM,
the United States. Clin Infect Dis. 2012 Jul;55 Suppl 1: Stapleton JT, et al. Expanded classification of hepatitis
S10–5. C virus into 7 genotypes and 67 subtypes: updated crite-
3. CDC. Testing for HCV infection: an update of guidance ria and genotype assignment web resource. Hepatology.
for clinicians and laboratorians. MMWR Morb Mortal 2014 Jan;59(1):318–27.
Wkly Rep. 2013 May 10;62(18):362–5. 8. Ward JW, Mermin JH. Simple, effective, but out of reach?
4. GBD 2013 Mortality and Causes of Death Collaborators. Public health implications of HCV drugs. N Engl J Med.
Global, regional, and national age-sex specific all- 2015 Dec 31;373(27):2678–80.
cause and cause-specific mortality for 240 causes of 9. Westbrook RH, Dusheiko G. Natural history of hepatitis
death, 1990–2013: a systematic analysis for the Global C. J Hepatol. 2014 Nov;61(1 Suppl):S58–68.
Burden of Disease Study 2013. Lancet. 2015 Jan 10;
10. World Health Organization. Hepatitis C. 2015
385(9963):117–71.
[updated July 2015; cited 2016 Sep. 23]. Available
5. Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. from: http://www.who.int/mediacentre/factsheets/
Global epidemiology and genotype distribution of the fs164_apr2014/en/.
HEPATITIS C 197
981
HEPATITIS E
Eyasu H. Teshale
DIAGNOSIS TREATMENT
The diagnosis of acute hepatitis E is established by Treatment is supportive. Oral ribavirin has been
detecting anti-HEV IgM in serum. Detecting HEV used to treat chronic hepatitis E in solid-organ
RNA in serum or stools further confirms the sero- transplant recipients.
logic diagnosis but is seldom required. Longer-
term, serial detection of HEV RNA in serum or PREVENTION
stools, regardless of the HEV antibody serostatus, No vaccine is available for prevention. Travelers
suggests chronic HEV infection. No diagnostic should avoid drinking unboiled or unchlori-
test for HEV has been approved by the Food and nated water and beverages that contain unboiled
Drug Administration. water or ice. Travelers should eat only thoroughly
cooked food, including seafood, meat, offal, and
products derived from these (see Chapter 2, Food
3
& Water Precautions).
BIBLIOGRAPHY
1. Kamar N, Izopet J, Tripon S, Bismuth M, Hillaire S, 3. Krawczynski K. Hepatitis E virus. Semin Liver Dis. 2013
Dumortier J, et al. Ribavirin for chronic hepatitis E virus Feb;33(1):1–93.
infection in transplant recipients. N Engl J Med. 2014 4. Riveiro-Barciela M, Minguez B, Girones R, Rodriguez-
Mar 20;370(12):1111–20. Frias F, Quer J, Buti M. Phylogenetic demonstration
2. Khuroo MS, Khuroo MS. Hepatitis E: an emerging global of hepatitis E infection transmitted by pork meat
disease—from discovery towards control and cure. J ingestion. Journal of clinical gastroenterology. 2015
Viral Hepat. 2016 Feb;23(2):68–79. Feb;49(2):165–8.
HISTOPLASMOSIS
Brendan R. Jackson, Tom M. Chiller
HISTOPLASMOSIS 199
02
Hepatitis Eendemici~
- Highly Endemic
Endemicl
· ·ty Unknown
Not Endemic or EndemiC!
HISTOPLASMOSIS 201
0
2
BIBLIOGRAPHY
1. CDC. Outbreak of histoplasmosis among travelers 4. Morgan J, Cano MV, Feikin DR, Phelan M, Monroy OV,
returning from El Salvador—Pennsylvania and Virginia, Morales PK, et al. A large outbreak of histoplasmosis
2008. MMWR Morb Mortal Wkly Rep. 2008 Dec among American travelers associated with a hotel in
19;57(50):1349–53. Acapulco, Mexico, spring 2001. Am J Trop Med Hyg.
2. Hage CA, Azar MM, Bahr N, Loyd J, Wheat LJ. 2003 Dec;69(6):663–9.
Histoplasmosis: up-to-date evidence-based approach 5. Weinberg M, Weeks J, Lance-Parker S, Traeger M,
to diagnosis and management. Semin Respir Crit Care Wiersma S, Phan Q, et al. Severe histoplasmosis in travel-
Med. 2015 Oct;36(5):729–45. ers to Nicaragua. Emerg Infect Dis. 2003 Oct;9(10):1322–5.
3. Kauffman CA. Histoplasmosis: a clinical and laboratory 6. Wheat LJ. Histoplasmosis: a review for clinicians from
update. Clin Microbiol Rev. 2007 Jan;20(1):115–32. non-endemic areas. Mycoses. 2006 Jul;49(4):274–82.
HIV INFECTION
Philip J. Peters, John T. Brooks
injury or splash exposures to mucous mem- myalgia, malaise, lymphadenopathy, oral ulcers,
branes or nonintact skin (see Chapter 8, Health pharyngitis, and weight loss. The presence of fever
Care Workers). and rash has the best positive predictive value.
Unfortunately, acute symptomatic HIV infection
EPIDEMIOLOGY is rarely diagnosed by health care providers, as its
HIV infection occurs worldwide. As of the end symptoms are often attributed to other viral infec-
of 2014, an estimated 37 million people were liv- tions or secondary syphilis.
ing with HIV infection. Although sub- Saharan
Africa has experienced a substantial decline in the DIAGNOSIS
number of new infections annually, from 2.3 mil- Any traveler who reports risk behaviors for HIV
lion in 2000 to 1.4 million in 2014 (a 41% decline),
it remains the most affected part of the world
infection, suspects that she or he may have been
exposed to HIV, or has symptoms that could be
3
(25.8 million cases or 70% of all people living with consistent with HIV infection should be tested.
HIV infection). Although the reported adult HIV HIV can be diagnosed with laboratory-based or
prevalence in many regions of the world is low, cer- point-of-care assays that detect anti-HIV anti-
tain populations are disproportionately affected, bodies, HIV p24 antigen, or HIV-1 RNA. In the
such as sex workers, people who inject drugs, men United States, the recommended laboratory-
who have sex with men, transgender people, and based screening test for HIV is a combination
prisoners. Sex workers are particularly vulnerable; antigen/antibody assay that detects antibodies
the prevalence among sex workers is 12 times as against HIV as well as p24 antigen. The combi-
high as in the general population. nation antigen/antibody assay becomes reactive
The risk of HIV infection for international trav- approximately 2–3 weeks after HIV infection. It is
elers is generally low, although the risk is deter- estimated that 99% of people will develop a reac-
mined less by geographic destination and more by tive combination antigen/antibody result within
behaviors such as injection drug use and unpro- 6 weeks of infection, but in rare cases, it can take
tected sex. Travelers who might undergo medi- up to 6 months to develop a reactive test result.
cal procedures in low-income countries, whether Point-of-care HIV antibody tests performed on
scheduled or in an emergency, should be aware oral fluid (instead of blood) have been associ-
that the blood supply (and organs and tissues ated with a lower sensitivity during early HIV
used for transplantation) might not be adequately infection. The earliest time after exposure that
screened, increasing the risk of HIV transmission, HIV infection can be diagnosed is approximately
and that HIV can be transmitted by unsafe med- 9 days, when HIV-1 RNA becomes detectable in
ical injection practices (reusing needles, syringes, blood. Any person with unknown HIV status who
or single-dose medication vials). is diagnosed with an AIDS-defining illness, such
as Pneumocystis pneumonia, should be tested for
CLINICAL PRESENTATION HIV. For further information on HIV testing, trav-
HIV infection is a chronic disease characterized elers should talk to their health care provider, or
by ongoing viral replication and a gradual exhaus- identify an HIV testing site near them by visit-
tion and destruction of CD4 T lymphocytes. As ing the National HIV Testing Resources website
the CD4 cell count declines, an HIV-infected per- at www.hivtest.org or call CDC-INFO toll-free at
son’s susceptibility to opportunistic infections 800-CDC-INFO (800-232-4636) or 888-232-6348
and infection-related malignancies increases. An (TTY). Both of these resources are confidential.
estimated 40%–90% of people experience symp-
toms during acute HIV infection, which often TREATMENT
presents as an infectious mononucleosislike or Prompt medical care and effective treatment
influenzalike syndrome, but the clinical features with antiretrovirals can partially reverse HIV-
can be highly variable. Symptoms typically begin induced damage to the immune system and pro-
a median of 10 days after HIV infection and can long life. Effective treatment also substantially
include fever, maculopapular rash, arthralgia, reduces the risk of HIV transmission to others.
US guidelines recommend that all people diag- • Use condoms consistently and correctly, espe-
nosed with HIV infection be offered treatment cially if engaging in vaginal, anal, or oral sex
for their own health and to prevent transmis- with a person who is HIV infected or whose
sion to others. Detailed information on specific HIV status is unknown.
treatments is available from the Department
of Health and Human Services AIDSinfo (www. • Avoid injecting drugs.
aidsinfo.nih.gov). Travelers may contact AIDSinfo • Avoid sharing needles or other devices that
toll-free at 800-448-0440 (English or Spanish) or can puncture skin.
888-480-3739 (TTY).
• Avoid, if possible, blood transfusions or use of
PREVENTION
3 Although no vaccine can prevent HIV infection,
clotting factor concentrates and exposure to
nonsterile injections and other invasive medi-
travel medicine clinicians have several HIV pre- cal equipment.
vention options available.
• Ensure that if traveling for purposes of med-
Education ical treatment (see Chapter 2, Medical
Travelers should be advised that they are at risk Tourism), the blood and blood products
if they: used in the facility where the traveler will be
treated are screened for HIV, and that such
• Have sexual contact (heterosexual or homo- facilities exercise proper infection control
sexual) with an infected person or a person
practices.
whose HIV infection status is unknown.
• Use or allow the use of contaminated, Condoms
unsterilized syringes or needles for any People who are sensitive to latex should use con-
injections or other procedures that pierce doms made of polyurethane or other synthetic
the skin, including acupuncture, use of illicit materials (not lambskin) and should carry their
drugs, steroid or vitamin injections, medical own supply of male or female condoms. If no con-
or dental procedures, ear or body piercing, dom is available, travelers should abstain from
or tattooing. sex with people who are HIV-infected or whose
HIV status is unknown. Barrier methods other
• Receive infected blood, blood components, or than condoms do not prevent HIV transmis-
clotting factor concentrates. HIV infection by
sion. Spermicides alone are also not effective. The
this route is rare in facilities where donated
widely used spermicide nonoxynol-9 can increase
blood and plasma are screened for HIV.
the risk of HIV transmission and should not
• Work in a health care setting. Typically, expo- be used.
sures occur as a result of percutaneous expo-
sure to contaminated sharps, including Preexposure Prophylaxis
needles, lancets, scalpels, and broken glass Preexposure prophylaxis (or PrEP) is highly effec-
( from capillary or test tubes). See Chapter 8, tive in preventing HIV infection. PrEP consists
Health Care Workers. of 2 oral antiretroviral medications (tenofovir
and emtricitabine), coformulated as a single pill
Risk Reduction (Truvada) that is taken once daily. Daily PrEP
To reduce their risk of acquiring HIV, travelers
can lower the risk of HIV infection from sex by
should:
as much as 90% or injection drug use by as much
• Avoid sexual encounters with people who are as 70% and is indicated for people at substan-
infected with HIV, whose HIV infection status tial risk for HIV infection. Detailed information
is unknown, or who are at high risk for HIV is available from CDC (www.cdc.gov/hiv/risk/
infection, such as people who inject drugs, sex prep). Travelers who may have sex with people
workers (both male and female), and other who are infected with HIV or who are at high risk
people with multiple sexual partners. for HIV infection and travelers who may inject
drugs should discuss PrEP with their primary recommendations on postexposure prophylaxis
care and travel medicine providers. Travelers include the following:
taking PrEP should carry proper documentation
and be aware that some countries (see below
• People who have been exposed to HIV in a
nonoccupational setting (through sex or
for further information) may deny entry to peo-
needle sharing) should seek immediate med-
ple with evidence of HIV infection, which PrEP
ical consultation to consider postexposure
medications might mistakenly indicate to cus-
prophylaxis.
toms officials.
• Postexposure prophylaxis for potential expo-
Sterile Syringes and Needles sure to HIV as a result of mass-casualty events
Syringes and needles used to draw blood or
administer injections should be sterile, single
is generally not warranted, except in special
circumstances ( for example, a blast injury
3
use, disposable, and prepackaged in a sealed con- in a facility that contained a large archive of
tainer. If possible, travelers should avoid receiv- HIV-infected blood specimens).
ing medications from multidose vials, which • Clinicians seeking advice on postexposure
may have become contaminated by used nee- prophylaxis can call the US National HIV/
dles. Travelers with diabetes, hemophilia, or other AIDS Clinicians’ Consultation Center PEPline
conditions that necessitate routine or frequent toll-free at 888-448-4911 (www.nccc.ucsf.edu).
injections should be advised to carry a supply
of medication, syringes and needles, and disin- HIV TESTING REQUIREMENTS
fectant swabs sufficient to last their entire stay FOR US TRAVELERS ENTERING
abroad. These travelers should request documen- FOREIGN COUNTRIES
tation of the medical necessity for traveling with International travelers should be advised that
these items (a letter from a licensed health care some countries screen incoming travelers for HIV
provider) to avoid having them confiscated, such infection and may deny entry to people with AIDS
as by inspection personnel at ports of entry (see or evidence of HIV infection. These countries usu-
Chapter 2, Travel Health Kits for more informa- ally screen only people planning extended visits,
tion about traveling with medications). such as for work or study. People intending to visit
a country for an extended stay should review that
Postexposure Prophylaxis country’s policies and requirements. This infor-
Travelers who will be working in a medical set- mation is usually available from the consular offi-
ting (such as a nurse volunteer drawing blood or cials of the individual nations. Information about
medical missionary performing surgeries) may entry and exit requirements compiled by the
have contact with HIV-infected or potentially Department of State can be found by country at
infected biological materials. Detailed advice http://travel.state.gov/c ontent/passports/en/
regarding management of postexposure pro- country.html.
phylaxis in the occupational setting is found
in Chapter 8, Health Care Workers. General CDC website: www.cdc.gov/hiv
BIBLIOGRAPHY
1. CDC. Preexposure prophylaxis for the prevention of 3. Joint United Nations Programme on HIV/AIDS
HIV in the United States: a clinical practice guideline. (UNAIDS). Global report: UNAIDS report on the global
Atlanta 2014 [cited 216 Sep. 23]. Available from: http:// AIDS epidemic 2013. Geneva: UNAIDS; 2013 [cited 2016
www.cdc.gov/hiv/pdf/PrEPguidelines2014.pdf. Sep. 23]. Available from: http://www.unaids.org/en/
2. CDC. Preexposure prophylaxis for the preven- media/unaids/contentassets/documents/epidemiology/
tion of HIV in the United States: clinical provid- 2013/gr2013/UNAIDS_Global_Report_2013_en.pdf.
ers’ supplement. Atlanta2014 [cited 2016 Sep. 23]. 4. Kuhar DT, Henderson DK, Struble KA, Heneine W,
Available from: http://www.cdc.gov/hiv/pdf/ Thomas V, Cheever LW, et al. Updated US Public Health
PrEPProviderSupplement2014.pdf. Service guidelines for the management of occupational
exposures to human immunodeficiency virus and 6. Smith DK, Grohskopf LA, Black RJ, Auerbach JD,
recommendations for postexposure prophylaxis. Infect Veronese F, Struble KA, et al. Antiretroviral postexpo-
Control Hosp Epidemiol. 2013 Sep;34(9):875–92. sure prophylaxis after sexual, injection-drug use, or
5. Rice B, Gilbart VL, Lawrence J, Smith R, Kall other nonoccupational exposure to HIV in the United
M, Delpech V. Safe travels? HIV transmission States: recommendations from the US Department of
among Britons travelling abroad. HIV Med. 2012 Health and Human Services. MMWR Recomm Rep.
May;13(5):315–7. 2005 Jan 21;54(RR-2):1–20.
3 INFLUENZA
Grace Appiah, Joseph Bresee
Influenza is typically most common in chil- close contact with sick or dead infected poul-
dren, especially in school-aged children. Rates try. H5N1 is widespread among poultry in some
of severe illness and death are typically highest countries in Asia and the Middle East and is con-
among people aged ≥65, children <2 years, and sidered to be endemic among poultry in 6 coun-
people of any age who have underlying medi- tries: Bangladesh, China, Egypt, India (West
cal conditions that place them at increased risk Bengal), Indonesia, and Vietnam (Map 3- 7).
for complications of influenza. Children aged Egypt, Indonesia, and Cambodia have accounted
<2 years have rates of influenza- associated for 71% of reported infections in humans glob-
hospitalizations that are as high as those in ally. Instances of limited, nonsustained human-
the elderly, although with much lower death to-human transmission of H5N1 virus have been
rates. CDC estimates that from 1976 through
2006, annual influenza- associated deaths in
reported. In the United States, since December
2014, highly pathogenic avian influenza (HPAI)
3
the United States ranged from a low of approx- H5 infections have been detected in backyard and
imately 3,000 people to a high of approximately commercial poultry from 21 states. Although no
49,000 people; approximately 80%–90% of these human HPAI H5 infections have been reported in
deaths occurred among people aged ≥65 years. the United States, surveillance in domestic birds
is ongoing given the low but continued risk of
Zoonotic Influenza transmission to humans.
Influenza B viruses circulate widely only among Avian influenza A (H7N9) virus emerged in
humans, although influenza A viruses circulate China in 2013, and as of March 2016, has caused
among many animal populations. The primary 767 confirmed human illnesses. Most cases have
reservoir for influenza A viruses is wild waterfowl been identified in mainland China, but sev-
and other wild birds, but viruses are common in eral cases associated with exposure in mainland
swine populations as well. Influenza A viruses can China and subsequent travel have been identi-
also infect other animal species, such as poultry, fied in Malaysia, Taiwan, and Hong Kong. In 2014,
cats, dogs, horses, sea lions, and bats. Canada reported the first imported H7N9 case in
Human infections with animal-origin influenza North America. Most of the people with illness
A viruses are uncommon. In the United States, caused by H7N9 had exposure to infected poultry
human influenza illnesses caused by swine-origin or contaminated environments, and the virus has
influenza A viruses (called “variant” influenza been found in poultry and environmental samples
virus infections and denoted with the letter “v”) collected in China. A small proportion of human
have been sporadically identified. In 2012, 309 H7N9 illnesses has been mild, but most patients
cases (and 1 death) of human illnesses caused by have developed severe respiratory illness, and 38%
influenza A (H3N2v) viruses were identified. In the have died.
summer of 2013, 19 human cases were identified Although rare, human infections with other
in 5 states. Most illnesses caused by H3N2v have avian influenza A viruses, including H7N2, H7N3,
occurred after direct or indirect contact with an H7N7, H9N2, and H10N8, have been reported in
infected pig, often among exhibitors or visitors to recent years. In the United States, 2 infections
agricultural fairs. Limited person-to-person trans- with H7N2 virus were reported in humans in 2002
mission has occurred with this virus. The severity and 2003, both of whom recovered.
of illness has been similar to that seen with sea-
sonal influenza. CLINICAL PRESENTATION
Although avian influenza viruses do not com- Uncomplicated influenza illness is characterized
monly infect humans, disease resulting from these by the abrupt onset of signs and symptoms that
viruses has been reported. From 1997 through include fever, muscle aches, headache, malaise,
March 2016, 850 human illnesses caused by avian nonproductive cough, sore throat, vomiting, and
influenza A (H5N1) virus were reported glob- rhinitis. Less commonly, rashes have been asso-
ally, approximately 53% of which were fatal. Most ciated with influenza infection. Illness without
disease from H5N1 has occurred after direct or fever can occur, especially in the elderly. Children
INFLUENZA 207
8
02
wlf{.~
\ ..__. __
.. ,
No cases reported
INFLUENZA 209
021
are more likely than adults to also experience nau- of close contacts, including other patients,
sea, vomiting, or diarrhea when ill with influenza. such as in institutional outbreaks or other
Physical findings are predominantly localized to settings (cruise ships or tour groups, for
the respiratory tract and include nasal discharge, example)
pharyngeal inflammation without exudates, and
The sensitivity of RIDTs varies but is substantially
occasionally rales on chest auscultation. The incu-
lower than for RT-PCR or viral culture. The sen-
bation period is usually 1–4 days after exposure.
sitivity of RIDTs to detect animal-origin influenza
Influenza illness typically resolves within 1 week
viruses, including avian influenza viruses, can vary
for most previously healthy children and adults
by test type and virus subtype. Therefore, a nega-
who do not receive antiviral medication, although
3 cough and malaise can persist for >2 weeks, espe-
cially in the elderly. Complications of influenza
tive RIDT result does not rule out influenza virus
infection, and health care providers should not
rely on a negative RIDT result to make decisions
virus infection include primary influenza viral
about treatment. The decision to start antiviral
pneumonia, secondary bacterial pneumonia, par-
treatment should not be delayed while waiting for
otitis, exacerbation of underlying medical condi-
results of confirmatory laboratory testing.
tions (such as pulmonary and cardiac disease),
encephalopathy, myocarditis, myositis, and coin-
fections with other viral or bacterial pathogens.
TREATMENT
Early antiviral treatment can shorten the dura-
tion of fever and other symptoms and reduce the
DIAGNOSIS risk of complications from influenza. Antiviral
Influenza can be difficult to distinguish from respi-
treatment is recommended as early as possi-
ratory illnesses caused by other pathogens on the
ble for any patient with confirmed or suspected
basis of signs and symptoms alone. The positive
influenza who is hospitalized; has severe, compli-
predictive value of clinical signs and symptoms
cated, or progressive illness; or is at a higher risk
for influenzalike illness ( fever with either cough
for influenza- associated complications (www.
or sore throat) for laboratory-confirmed influenza
cdc.gov/f lu/professionals/antivirals/summary-
virus infection is 30%–88%, depending on the
clinicians.htm). Antiviral treatment can also be
level of influenza activity.
considered for any previously healthy patient with
Diagnostic tests available for influenza include
confirmed or suspected influenza not at high risk
viral culture, rapid influenza diagnostic tests
of complications.
(RIDTs), immunofluorescence assays, and RT-
Treatment is most effective if it can be initiated
PCR. Most patients with clinical illness consistent
within 48 hours of illness onset. For h ospitalized
with uncomplicated influenza in an area where
patients, those with severe illness, or those at
influenza viruses are circulating do not require
higher risk of complications, a ntiviral therapy may
diagnostic testing for clinical management.
still be beneficial if started >48 hours after illness
Patients who should be considered for influenza
onset. Three FDA- approved antiviral agents
diagnostic testing include the following:
are recommended for the treatment and pro-
• Hospitalized patients with suspected phylaxis of influenza: oral oseltamivir (Tamiflu,
influenza Genentech), inhaled zanamivir (Relenza,
GlaxoSmithKline), and intravenous (IV) perami-
• Patients for whom a diagnosis of influenza vir (Rapivab, BioCryst Pharmaceuticals).
will inform decisions regarding clinical care,
All 3 antiviral medications are neuraminidase
including patients who do not improve on
inhibitors that have activity against both influ-
antiviral therapy and those with medical
enza A and B viruses. Oseltamivir is approved for
conditions that place them at high risk of
treatment in children aged ≥14 days and for pro-
complications
phylaxis of patients aged ≥1 year. Oseltamivir is
• Patients for whom results of influenza testing the preferred agent to treat patients with severe
would affect infection control or management or complicated influenza illness who are able to
tolerate oral medications. Zanamivir is approved of the vaccine compared with inactivated vac-
to treat those aged ≥7 years and for prophylaxis cine. (For updates and the following season rec-
in those aged ≥5 years. Inhaled zanamivir is not ommendations, providers should access http://
recommended for use in people with under- www.cdc.gov/f lu/protect/vaccine/index.htm.)
lying chronic respiratory disease. Peramivir is For people for whom more than 1 type of vaccine
approved to treat those aged ≥18 years and is is indicated, there is no preference for any partic-
indicated for use in patients unable to tolerate ular category. During their first influenza season,
or absorb oral antiviral therapy (Table 3-5). Two children aged 6 months through 8 years require 2
other medications, amantadine and rimanta- doses of influenza vaccine (given ≥4 weeks apart)
dine, are not recommended for treatment or pro- to induce sufficient immune response.
phylaxis of influenza because of widespread viral
resistance among circulating influenza A viruses.
IIV can be administered by intramuscular
injection, transdermally via needle-free jet injec-
3
Amantadine and rimantadine are not active tor, or intradermal injection depending on the
against influenza B viruses. product. IIVs are labeled for use in people aged
For severely ill hospitalized patients, IV ≥6 months, but specific age indications vary by
peramivir or IV zanamivir (an investigational manufacturer and product; label instructions
product) should be considered for those who can- should be followed. High-dose IIV and adjuvanted
not tolerate or absorb oral oseltamivir. IV zanami- IIV vaccines, which may elicit higher levels of anti-
vir should be considered for severely ill patients bodies than standard-dose vaccines, are available
with known or suspected oseltamivir/peramivir- for people aged ≥65 years. RIV is labeled for use in
resistant virus infection. IV zanimivir is available people aged ≥18 years.
only under an approved emergency investiga- Influenza vaccine composition can be tri-
tional new drug request in hospitalized patients valent, protecting against 3 different influenza
with severe influenza. viruses (2 influenza subtype A and 1 type influ-
People at increased risk for complications of enza B), or quadrivalent, with protection against
influenza should discuss antiviral treatment and 4 different influenza viruses (2 influenza subtype
prophylaxis with their health care provider before A and 2influenza type B strains). Quadrivalent vac-
travel to areas where influenza activity is occur- cine includes a representative strain from 2 anti-
ring. CDC recommends antiviral treatment for genically distinct influenza B lineages, Yamagata
human infection with avian or swine influenza and Victoria.
viruses. Any traveler, including people at high risk for
complications of influenza, who did not receive
PREVENTION influenza vaccine during the preceding fall or
winter and wants to reduce the risk for influenza
Vaccine infection should consider influenza vaccination
AVAILABLE VACCINE PRODUCTS AND ≥2 weeks before departure if he or she plans to
INDICATIONS FOR USE travel to the tropics, with organized tourist groups
In the United States, annual influenza vaccination at any time of year, or to the Southern Hemisphere
is recommended for those aged ≥6 months and is from April through September.
the most effective way to prevent influenza and No information is available about the bene-
its complications. Several influenza vaccines are fits of revaccinating people before summer travel
approved for use in the United States (www.cdc. who were vaccinated during the preceding fall,
gov/flu/protect/vaccine/vaccines.htm) and can and revaccination is not recommended. People
be grouped into categories: inactivated influenza at higher risk for influenza complications should
vaccine (IIV), live attenuated influenza vaccine consult with their health care provider to discuss
(LAIV), and recombinant influenza vaccine (RIV). the risk for influenza or other travel-related dis-
However, for the 2016– 2017 influenza season, eases before traveling during the summer.
CDC has recommended that LAIV not be used fol- Seasonal influenza vaccines are not expected
lowing analyses that indicated lower effectiveness to provide protection against human infection
INFLUENZA 211
21
Peramivir5 Treatment No FDA approval for use in children 600 mg dose via IV infusion
(Rapivab) (1 day) for 15–30 minutes5
1
Oral oseltamivir is approved by the FDA for treatment of acute uncomplicated influenza with twice-daily dosing in people
aged ≥14 days and for prophylaxis with once-daily dosing in people aged ≥1 year. Although not part of the FDA-approved
indications, use of oral oseltamivir for treatment of influenza in infants <14 days old, and for prophylaxis in infants
3 months to 1 year of age, is recommended by CDC and the American Academy of Pediatrics.
2
This is the FDA-approved oral oseltamivir treatment dose for infants aged ≥14 days and <1 year old and provides
oseltamivir exposure in children similar to that achieved by the approved dose of 75 mg orally twice daily for adults,
as shown in 2 studies of oseltamivir pharmacokinetics in children. The American Academy of Pediatrics (AAP)
recommended an oseltamivir treatment dose of 3.5 mg/kg orally twice daily for infants aged 9–11 months for the
2015–2016 season. It is unknown whether this higher dose will improve efficacy or prevent the development of antiviral
resistance. However, there is no evidence that the 3.5 mg/kg dose is harmful or causes more adverse events to infants
in this age group. The AAP also recommended an oseltamivir treatment dose of 3 mg/kg orally twice daily for term
infants aged 0–8 months for the 2015–2016 season.
3
Current weight-based dosing recommendations are not appropriate for premature infants. Premature infants might
have slower clearance of oral oseltamivir because of immature renal function, and doses recommended for full-term
infants might lead to very high drug concentrations in this age group. CDC recommends dosing as also recommended
by the American Academy of Pediatrics: 1.0 mg/kg/dose, orally, twice daily, for those <38 weeks postmenstrual age;
1.5 mg/kg/dose, orally, twice daily, for those 38–40 weeks postmenstrual age; 3.0 mg/kg/dose, orally, twice daily, for
those >40 weeks postmenstrual age.
4
Inhaled zanamivir is approved to treat acute uncomplicated influenza with twice-daily dosing in people aged ≥7 years
and for prophylaxis with once-daily dosing in people aged ≥5 years.
5
Intravenous peramivir is FDA approved and recommended for treatment in adults ≥18 years. If used to treat
hospitalized patients, a minimum of 5 days of IV peramivir should be given (not a single dose as is recommended for
outpatients with uncomplicated illness).
INFLUENZA 213
421
safety practices and avoid contact with sources animals are sold or raised, avoid contact with
of exposure. Most human infections with avian sick or dead animals, not eat undercooked or
influenza viruses have occurred after direct or raw animal products (including eggs), and not
close contact with infected poultry. In coun- eat or drink foods or beverages that contain
tries where avian influenza virus outbreaks animal blood.
are occurring, travelers or those living abroad
should avoid markets and farms where live CDC website: www.cdc.gov/flu
BIBLIOGRAPHY
3
1. CDC. Evaluation of 11 commercially available rapid 6. Li Q, Zhou L, Zhou M, Chen Z, Li F, Wu H, et al.
influenza diagnostic tests—United States, 2011– Epidemiology of human infections with avian influ-
2012. MMWR Morb Mortal Wkly Rep. 2012 Nov enza A(H7N9) virus in China. N Engl J Med. 2014 Feb
2;61(43):873–6. 6;370(6):520–32.
2. CDC. Prevention and control of influenza with vac- 7. McGeer A, Green KA, Plevneshi A, Shigayeva A, Siddiqi
cines: recommendations of the Advisory Committee N, Raboud J, et al. Antiviral therapy and outcomes of
on Immunization Practices, United States, 2015–16 influenza requiring hospitalization in Ontario, Canada.
Influenza Season. MMWR Morb Mortal Wkly Rep. 2015 Clin Infect Dis. 2007 Dec 15;45(12):1568–75.
Aug 7;64(30):818–25. 8. Pabbaraju K, Tellier R, Wong S, Li Y, Bastien N, Tang JW,
3. Committee on Infectious Diseases AAoP. et al. Full-genome analysis of avian influenza A(H5N1)
Recommendations for prevention and control of virus from a human, North America, 2013. Emerg Infect
influenza in children, 2015–2016. Pediatrics. 2015 Dis. 2014 May;20(5):887–91.
Oct;136(4):792–808. 9. Reed C, Chaves SS, Daily Kirley P, Emerson R, Aragon D,
4. Donnelly CA, Finelli L, Cauchemez S, Olsen SJ, Doshi S, Hancock EB, et al. Estimating influenza disease burden
Jackson ML, et al. Serial intervals and the temporal from population-based surveillance data in the United
distribution of secondary infections within households States. PLoS One. 2015;10(3):e0118369.
of 2009 pandemic influenza A (H1N1): implications for 10. Siston AM, Rasmussen SA, Honein MA, Fry AM, Seib K,
influenza control recommendations. Clin Infect Dis. Callaghan WM, et al. Pandemic 2009 influenza A(H1N1)
2011 Jan 1;52 Suppl 1:S123–30. virus illness among pregnant women in the United
5. Jhung MA, Epperson S, Biggerstaff M, Allen States. JAMA. 2010 Apr 21;303(15):1517–25.
D, Balish A, Barnes N, et al. Outbreak of 11. Writing Committee of the WHO Consultation on
variant influenza A(H3N2) virus in the Clinical Aspects of Pandemic Influenza. Clinical aspects
United States. Clin Infect Dis. 2013 of pandemic 2009 influenza A (H1N1) virus infection. N
Dec;57(12):1703–12. Engl J Med. 2010 May 6;362(18):1708–19.
JAPANESE ENCEPHALITIS
Susan L. Hills, Ingrid B. Rabe, Marc Fischer
TRANSMISSION EPIDEMIOLOGY
JE virus is transmitted to humans through the JE virus is the most common vaccine-preventable
bite of an infected mosquito, primarily Culex spe- cause of encephalitis in Asia, occurring through-
cies. The virus is maintained in an enzootic cycle out most of Asia and parts of the western Pacific
(Map 3-8). Local transmission of JE virus has not develop clinical disease. Acute encephalitis is the
been detected in Africa, Europe, or the Americas. most commonly recognized clinical manifestation
Transmission principally occurs in rural agricul- of JE virus infection. Milder forms of disease, such
tural areas, often associated with rice cultivation as aseptic meningitis or undifferentiated febrile
and flood irrigation. In some areas of Asia, these illness, can also occur. The incubation period is 5–
ecologic conditions may occur near, or occasion- 15 days. Illness usually begins with sudden onset
ally within, urban centers. In temperate areas of of fever, headache, and vomiting. Mental status
Asia, transmission is seasonal, and human disease changes, focal neurologic deficits, generalized
usually peaks in summer and fall. In the subtrop- weakness, and movement disorders may develop
ics and tropics, seasonal transmission varies with over the next few days. The classical description of
monsoon rains and irrigation practices and may
be prolonged or even occur year-round.
JE includes a parkinsonian syndrome with mask-
like facies, tremor, cogwheel rigidity, and choreo-
3
In endemic countries, where adults have athetoid movements. Acute flaccid paralysis, with
acquired immunity through natural infection, JE clinical and pathological features similar to those
is primarily a disease of children. However, travel- of poliomyelitis, has also been associated with JE
associated JE can occur among people of any virus infection. Seizures are common, especially
age. For most travelers to Asia, the risk for JE is among children. The case-fatality ratio is approx-
extremely low but varies based on destination, imately 20%– 30%. Among survivors, 30%– 50%
duration, season, and activities. have serious neurologic, cognitive, or psychiatric
From 1973 through 2015, 79 JE cases among sequelae.
travelers or expatriates from nonendemic coun- Common clinical laboratory findings include
tries were published or reported to CDC. From the moderate leukocytosis, mild anemia, and hypona-
time a JE vaccine became available in the United tremia. Cerebrospinal fluid (CSF) typically has a
States in 1993, through 2015, only 10 JE cases mild to moderate pleocytosis with a lymphocytic
among US travelers were reported to CDC. predominance, slightly elevated protein, and nor-
The overall incidence of JE among people mal ratio of CSF to plasma glucose.
from nonendemic countries traveling to Asia
is estimated to be <1 case per 1 million travel- DIAGNOSIS
ers. However, expatriates and travelers who stay JE should be suspected in a patient with evi-
for prolonged periods in rural areas with active dence of a neurologic infection (such as enceph-
JE virus transmission are likely at similar risk as alitis, meningitis, or acute flaccid paralysis) who
the susceptible resident population (5–50 cases has recently traveled to or resided in an endemic
per 100,000 children per year). Travelers on even country in Asia or the western Pacific. Laboratory
brief trips might be at increased risk if they have diagnosis of JE virus infection should be per-
extensive outdoor or nighttime exposure in rural formed by using a JE virus–specific IgM-capture
areas during periods of active transmission. ELISA on CSF or serum. JE virus–specific IgM can
Short-term (<1 month) travelers whose visits are be measured in the CSF of most patients by 4 days
restricted to major urban areas are at minimal after onset of symptoms and in serum by 7 days
risk for JE. In some endemic areas, although there after onset. Plaque reduction neutralization tests
are few human cases among residents because can be performed to confirm the presence of JE
of natural immunity among older people or vac- virus– specific neutralizing antibodies and dis-
cination, JE virus is still maintained locally in an criminate between cross- reacting antibodies
enzootic cycle between animals and mosquitoes. from closely related flaviviruses (such as dengue
Therefore, susceptible visitors may be at risk for and West Nile viruses). A ≥4-fold rise in JE virus–
infection. specific neutralizing antibodies between acute-
and convalescent-phase serum specimens may be
CLINICAL PRESENTATION used to confirm recent infection. Vaccination his-
Most human infections with JE virus are asymp- tory, date of onset of symptoms, and information
tomatic; <1% of people infected with JE virus regarding other flaviviruses known to circulate in
261
3
INFECTIOUS DISEASES RELATED TO TRAVEL
RUSSIA
J'
/ 'NORTH
KOREA
r
SOUTH JAPAN
KOREA
CHINA
NEPAr
' ...... "" \' BH AN
INDIA ) PACIFIC
\BANGLADESH ~~ TAIWAN
OCEAN
ARABIAN
SEA .P BURMA PHILIPPINE
\ LAOS SEA
1/V'\.........
THAIL~ND~
BAY OF PHILIPPINES
BENGAL
SOUTH
\ CAMBODIA CHINA
I ~
SEA
SRI LANKA VIETNAM
'1..,
INDIAN BRUNEI
OCEAN MAL~Y~~~~
SINGAPORE
Japanese encephalitis risk INDONESIA VAPUA
NEW GUINEA
Known risk areas
• TIMOR·LESTE
No known risk areas CORAL
SEA
AUSTRALIA
MAP 3-8 . Distribution of Japanese encephalitis
271
the geographic area that may cross-react in sero- through 16 years. Other inactivated and live atten-
logic assays need to be considered when inter- uated JE vaccines are manufactured and used in
preting results. other countries but are not licensed for use in the
Humans have low levels of transient viremia United States.
and usually have neutralizing antibodies by the
time distinctive clinical symptoms are recognized. INDICATIONS FOR USE OF JE VACCINE
Virus isolation and nucleic-acid amplification tests FOR TRAVELERS
are insensitive in detecting JE virus or viral RNA in When making recommendations regarding the use
blood or CSF and should not be used for ruling out of JE vaccine for travelers, clinicians must weigh
a diagnosis of JE. Clinicians should contact their the overall low risk of travel-associated JE, the high
state or local health department or CDC at 970-
221-6400 for assistance with diagnostic testing.
rate of death and disability when JE occurs, the low
probability of serious adverse events after immu-
3
nization, and the cost of the vaccine. Evaluation
TREATMENT of a traveler’s risk should take into account the
There is no specific antiviral treatment for JE; ther- planned itinerary, including travel location, dura-
apy consists of supportive care and management tion, activities, and seasonal patterns of disease in
of complications. the areas to be visited (Table 3-7). The data in the
table should be interpreted cautiously, because JE
PREVENTION virus transmission activity varies within countries
and from year to year.
Personal Protection Measures The Advisory Committee on Immunization
The best way to prevent mosquitoborne dis-
Practices recommends JE vaccine for travelers
eases, including JE, is to avoid mosquito bites (see
who plan to spend ≥1 month in endemic areas
Chapter 2, Protection against Mosquitoes, Ticks,
during the JE virus transmission season. This
& Other Arthropods).
includes long-term travelers, recurrent travelers,
or expatriates who will be based in urban areas
Vaccine but are likely to visit endemic rural or agricultural
One JE vaccine is licensed and available in the
areas during a high-risk period of JE virus trans-
United States—an inactivated Vero cell culture–
mission. Vaccine should also be considered for
derived vaccine, Ixiaro (Table 3-6). Ixiaro is man-
the following:
ufactured by Valneva Scotland Limited and
distributed in the United States by VaxServe (a • Short-term (<1 month) travelers to endemic
Sanofi Pasteur company). It was approved in areas during the JE virus transmission season,
March 2009 for use in people aged ≥17 years and if they plan to travel outside an urban area
in May 2013 for use in children aged 2 months and their activities will increase the risk of JE
3
INFECTIOUS DISEASES RELATED TO TRAVEL
Australia Outer Torres Strait islands December–May; all human cases 1 human case reported from north Queensland mainland
reported February–April
Bangladesh Presumed widespread Most human cases reported Sentinel surveillance has identified human cases in Chittagong,
May–October Dhaka, Khulna, Rajshahi, Ranjpur, and Sylhet Divisions; highest
incidence reported from Rajshahi Division; outbreak reported
from Tangail District, Dhaka Division, in 1977
Bhutan Very rare reports; probably endemic in No data Proximity to other endemic areas and presence of vectors
nonmountainous areas suggests virus transmission is likely
Brunei Presumed transmission in many areas Unknown; presumed year-round Outbreak with laboratory-confirmed cases occurred in
in the country October–December 2013
Burma Limited data; presumed to be endemic Unknown; most human cases reported Outbreaks of human disease documented in Shan and Rakhine
(Myanmar) countrywide May–October States; antibodies documented in animals and humans in other
areas
Cambodia Presumed to be endemic countrywide Year-round with peak season Sentinel surveillance has identified human cases in at least
May–October 15 of 23 provinces, including Phnom Penh, Takeo, Kampong
Cham, Battambang, Svay Rieng, and Siem Reap; 1 case
reported in 2010 in a traveler who visited Phnom Penh and
Angkor Wat/Siem Reap only
China Human cases reported from all Most human cases reported Highest rates reported from Guizhou, Shaanxi, Sichuan, and
provinces except Xizang (Tibet), Xinjiang, June–October Yunnan Provinces, and Chongqing City; vaccine not routinely
and Qinghai; JE virus isolated from recommended for travel limited to Beijing, Shanghai, Hong
mosquitoes in Tibet Kong City/Kowloon, Macau, or other major cities
291
India Human cases reported from all states Most human cases reported May– Highest rates of human disease reported from the states of
except Dadra, Daman, Diu, Gujarat, October, especially in northern India; Andhra Pradesh, Assam, Bihar, Goa, Haryana, Karnataka,
Himachal Pradesh, Jammu and Kashmir, the season may be extended or year- Kerala, Tamil Nadu, Uttar Pradesh, and West Bengal
Lakshadweep, Meghalaya, Nagar Haveli, round in some areas, especially in
Punjab, Rajasthan, and Sikkim southern India
Indonesia Presumed to be endemic countrywide Year-round; peak season varies by Sentinel surveillance has identified human cases in Bali,
island Kalimantan, Java, Nusa Tenggara, Papua, and Sumatra;
several traveler cases reported in recent years from Bali
Japan2 Rare sporadic human cases on all Most human cases reported Large number of human cases reported until JE vaccination
islands except Hokkaido; enzootic July–October program introduced in late 1960s; most recent small outbreak
activity ongoing reported from Chugoku district in 2002; enzootic transmission
without human cases observed on Hokkaido; vaccine not
routinely recommended for travel limited to Tokyo or other
major cities
Korea, North Limited data; presumed to be endemic No data; proximity to South Korea
countrywide suggests peak season is likely to be
May–October
Korea, Rare sporadic human cases Most human cases reported Large number of human cases reported until routine JE
South2 countrywide; enzootic activity ongoing May–October vaccination program introduced in mid-1980s; last major
outbreak reported in 1982; vaccine not routinely recommended
for travel limited to Seoul or other major cities
JAPANESE ENCEPHALITIS
Laos Limited data; presumed to be endemic Year-round, with peak season Sentinel surveillance has identified human cases in north,
countrywide June–September central, and southern Laos
Malaysia Endemic in Sarawak; sporadic cases Year-round; in Sarawak, peak season Most human cases reported from Sarawak; vaccine not
reported from all other states October–December routinely recommended for travel limited to Kuala Lumpur or
other major cities
(continued)
219
3
0
2
220
3
INFECTIOUS DISEASES RELATED TO TRAVEL
Nepal Endemic in southern lowlands (Terai); Most human cases reported Highest rates of human disease reported from western Terai
cases also reported from hill and June–October districts, including Banke, Bardiya, Dang, and Kailali; vaccine
mountain districts, including the not routinely recommended for those trekking in high-altitude
Kathmandu valley areas
Papua New Limited data; probably widespread Unknown; probably year-round Sporadic human cases reported from Western Province;
Guinea serologic evidence of disease from Gulf and Southern Highland
Provinces; a case of JE was reported from near Port Moresby
in 2004
Philippines Human, animal, and mosquito studies Year-round with peak season Several traveler cases recently reported
have indicated transmission in 32 April–August
provinces located in all regions of the
country; presumed to be endemic
countrywide
Russia Rare human cases reported from the Most human cases reported Vaccine not routinely recommended
Far Eastern maritime areas south of July–September
Khabarovsk
Singapore Rare sporadic human cases reported Year-round Vaccine not routinely recommended
Sri Lanka Endemic countrywide except in Year-round with variable peaks based Highest rates of human disease reported from Anuradhapura,
mountainous areas on monsoon rains Gampaha, Kurunegala, Polonnaruwa, and Puttalam districts
21
Taiwan2 Rare sporadic human cases islandwide Most human cases reported Large number of human cases reported until routine
May–October JE vaccination introduced in 1968; vaccine not routinely
recommended for travel limited to Taipei or other major cities
Thailand Endemic countrywide; seasonal Year-round with peak season May– Highest rates of human disease reported from the Chiang Mai
epidemics in the northern provinces October, especially in the north Valley; several cases reported recently in travelers who visited
resort or coastal areas of southern Thailand
Vietnam Endemic countrywide; seasonal Year-round with peak season May– Highest rates of disease in the northern provinces around
epidemics in the northern provinces October, especially in the north Hanoi and northwestern and northeastern provinces bordering
China
Western Outbreaks of human disease reported in Unknown; most human cases reported Outbreaks likely followed introduction of virus, with enzootic
Pacific Guam in 1947–1948 and Saipan in 1990 October–March cycle not sustained; vaccine not recommended
Islands
1
Data are based on published reports and personal correspondence. Risk assessments should be performed cautiously, because risk can vary within areas and from year to year, and
surveillance data regarding human cases and JE virus transmission are incomplete.
2
In some endemic areas, human cases among residents are limited because of natural immunity among older people or vaccination. However, because JE virus is maintained in an
enzootic cycle between animals and mosquitoes, susceptible visitors to these areas still may be at risk for infection.
JAPANESE ENCEPHALITIS
221
3
2
virus exposure. Examples of higher-risk activ- in adults. After a booster dose administered at
ities or itineraries include 1) spending sub- 15 months, 96% of subjects were still seropro-
stantial time outdoors in rural or agricultural tected approximately 6 years later.
areas, especially during the evening or night; There are limited data on duration of seropro-
2) participating in extensive outdoor activi- tection and need for a booster dose in children.
ties (such as camping, hiking, trekking, biking, In a study conducted among children from non-
fishing, hunting, or farming); and 3) staying endemic countries, 89% were seroprotected at
in accommodations without air conditioning, 3 years after a primary 2-dose series of Ixiaro. This
screens, or bed nets. rate was higher than that in a comparative adult
study. In a study conducted among children in a
• Travelers to an area with an ongoing JE
3 outbreak.
JE-endemic country, 90% of children were sero-
protected at 36 months after the primary series.
• Travelers to endemic areas who are uncertain Seroprotection rates were variable by age group,
of specific destinations, activities, or duration but at least 81% of children in each age group were
of travel. seroprotected.
An accelerated primary series of 2 doses of
JE vaccine is not recommended for short-term
Ixiaro administered 7 days apart has been stud-
travelers whose visits will be restricted to urban
ied in adults aged 18–65 years. In the accelerated
areas or times outside a well-defined JE virus
schedule group, 99% of adults were seroprotected,
transmission season.
compared with 100% of adults in the standard
VACCINE EFFICACY AND IMMUNOGENICITY schedule group. The accelerated primary series
There are no efficacy data for Ixiaro. The vaccine was noninferior to the conventional dosing sched-
was licensed in the United States on the basis of ule. An accelerated schedule (administered on
its ability to induce JE virus neutralizing antibod- days 0 and 7) has been licensed for use in Europe.
ies as a surrogate for protection, as well as safety
evaluations in almost 5,000 adults. In pivotal VACCINE ADMINISTRATION
immunogenicity studies, 96% of adults and 100% The primary immunization schedule for Ixiaro is
of children aged 2 months through 17 years devel- 2 doses administered intramuscularly on days 0
oped protective neutralizing antibodies at 28 days and 28 (Table 3-6). For children aged 2 months
after receiving a primary immunization series of 2 through 2 years, each dose is 0.25 mL, and for
doses administered 28 days apart. Among adults adults and children aged ≥3 years, each dose is
aged ≥65 years, 65% are seroprotected at 42 days 0.5 mL. To administer a 0.25-mL dose, health care
after the 2-dose primary series. providers must expel and discard half of the vol-
A study in adults on persistence of protective ume from the 0.5-mL prefilled syringe by push-
neutralizing antibodies after a primary 2- dose ing the plunger stopper up to the edge of the red
series of Ixiaro showed that at 5 years postvac- line on the syringe barrel before injection. The 2-
cination, 82% of subjects were seroprotected. dose series should be completed ≥1 week before
However, the study was conducted in areas where travel.
tickborne encephalitis (TBE) vaccine is available.
In a subgroup analysis, seroprotection rates at 24– BOOSTER DOSES
60 months in the TBE vaccine group ranged from For adults, if the primary series of Ixiaro was
94%–100%, compared with 64%–72% in the group administered >1 year previously, a booster dose
in which TBE vaccine was not administered. TBE should be given before potential reexposure or
vaccine is not available in the United States; there- if there is a continued risk for JE virus infection.
fore, JE seroprotection rates for US travelers are Data on the response to a booster dose admin-
likely to be most similar to the rates in the group istered ≥2 years after the primary series are not
not administered TBE vaccine. available.
One observational study investigated long- There are limited data on the use of Ixiaro as
term protection following a booster dose of Ixiaro a booster dose after a primary series with the
mouse brain–derived inactivated JE vaccine. Two safety study with 1,993 adult participants who
studies have been conducted, 1 in US military per- received 2 doses of Ixiaro. Headache, myalgia,
sonnel and the other at 2 travel clinics in Europe. fatigue, and an influenzalike illness were each
Both studies demonstrated that in adults who reported at a rate of >10%. In children, fever was
had previously received at least a primary series the most commonly reported systemic reaction
of mouse brain–derived inactivated JE vaccine, a in studies.
single dose of Ixiaro adequately boosted neutral-
izing antibody levels and provided at least short- PRECAUTIONS AND CONTRAINDICATIONS
term protection. In addition, seroprotective titers A severe allergic reaction after a previous dose
against both vaccine virus strains persisted in all of Ixiaro or any other JE vaccine, or to any
participants who could be followed up at 2 years
in the European study (N = 18). However, addi-
component of Ixiaro, is a contraindication to
administration of Ixiaro. Ixiaro contains pro-
3
tional data are needed on the duration of protec- tamine sulfate, a compound known to cause
tion after a single dose of Ixiaro in prior recipients hypersensitivity reactions in some people. No
of a mouse brain–derived vaccine. Until those studies of Ixiaro in pregnant women have been
data are available, people who have received JE- conducted. Therefore, administration of Ixiaro
Vax, the mouse brain–derived vaccine formerly to pregnant women usually should be deferred.
used in the United States, and require further vac- However, pregnant women who must travel to
cination against JE virus, should receive a 2-dose an area where risk for JE virus infection is high
primary series of Ixiaro. should be vaccinated when the theoretical risk
of immunization is outweighed by the risk of
VACCINE SAFETY AND ADVERSE REACTIONS infection.
Local symptoms of pain and tenderness were
the most commonly reported symptoms in a CDC website: www.cdc.gov/japaneseencephalitis
BIBLIOGRAPHY
1. CDC. Recommendations for use of a booster dose of phase III, multicenter, observer-blind study. J Travel
inactivated Vero cell culture-derived Japanese enceph- Med. 2015 Jul-Aug;22(4):225–31.
alitis vaccine: advisory committee on immunization 6. Paulke-Korinek M, Kollaritsch H, Kundi M, Zwazl I,
practices, 2011. MMWR Morb Mortal Wkly Rep. 2011 Seidl-Friedrich C, Jelinek T. Persistence of antibodies
May 27;60(20):661–3. six years after booster vaccination with inactivated
2. CDC. Use of Japanese encephalitis vaccine in chil- vaccine against Japanese encephalitis. Vaccine. 2015 Jul
dren: recommendations of the advisory committee on 9;33(30):3600–4.
immunization practices, 2013. MMWR Morb Mortal 7. Rabe IB, Miller ER, Fischer M, Hills SL. Adverse events
Wkly Rep. 2013 Nov 15;62(45):898–9 00. following vaccination with an inactivated, Vero
3. Fischer M, Lindsey N, Staples JE, Hills S. Japanese cell culture-derived Japanese encephalitis vaccine
encephalitis vaccines: recommendations of the in the United States, 2009–2012. Vaccine. 2015 Jan
Advisory Committee on Immunization Practices 29;33(5):708–12.
(ACIP). MMWR Recomm Rep. 2010 Mar 12;59(Rr-1):1–27. 8. Schuller E, Klingler A, Dubischar-Kastner K,
4. Hills SL, Griggs AC, Fischer M. Japanese encephalitis in Dewasthaly S, Muller Z. Safety profile of the Vero cell-
travelers from non-endemic countries, 1973–2008. Am J derived Japanese encephalitis virus (JEV) vaccine
Trop Med Hyg. 2010 May;82(5):930–6. IXIARO((R)). Vaccine. 2011 Nov 3;29(47):8669–76.
5. Jelinek T, Burchard GD, Dieckmann S, Buhler S, 9. Tauber E, Kollaritsch H, von Sonnenburg F, Lademann
Paulke-Korinek M, Nothdurft HD, et al. Short-Term M, Jilma B, Firbas C, et al. Randomized, double-blind,
immunogenicity and safety of an accelerated pre- placebo-controlled phase 3 trial of the safety and tol-
exposure prophylaxis regimen with Japanese enceph- erability of IC51, an inactivated Japanese encephalitis
alitis vaccine in combination with a rabies vaccine: a vaccine. J Infect Dis. 2008 Aug 15;198(4):493–9.
LEGIONELLOSIS (LEGIONNAIRES’
DISEASE & PONTIAC FEVER)
Preeta K. Kutty, Laurel E. Garrison
titer between acute-and convalescent- phase a self-limited illness that requires supportive care
specimens also confirms the diagnosis. A sin- only; antibiotics have no benefit.
gle antibody titer of any level is not diagnostic of
legionellosis. Other diagnostic tests include direct PREVENTION
fluorescent antibody and PCR. Legionellosis is a There is no vaccine for legionellosis, and anti-
nationally notifiable disease. biotic prophylaxis is not effective. Travelers at
increased risk for infection, such as the elderly
TREATMENT or those with immunocompromising condi-
For travelers with suspected Legionnaires’ dis- tions such as cancer or diabetes, may choose to
ease, specific antibiotic treatment is necessary avoid high-risk areas, such as whirlpool spas. If
and should be administered promptly while diag-
nostic tests are being processed. Appropriate anti-
exposure cannot be avoided, travelers should be
advised to seek medical attention promptly if they
3
biotics include fluoroquinolones and macrolides. develop symptoms of Legionnaires’ disease or
Treatment may be necessary for up to 3 weeks. In Pontiac fever.
severe cases, patients may have prolonged stays in
intensive care units. Consultation with an infec- CDC website: www.cdc.gov/legionella
tious disease specialist is advised. Pontiac fever is
BIBLIOGRAPHY
1. Beer KD, Gargano JW, Roberts VA, Reses HE, Hill VR, 6. de Jong B, Payne Hallstrom L, Robesyn E, Ursut D,
Garrison LE, et al. Outbreaks associated with environ- Zucs P, Eldsnet. Travel-associated Legionnaires’ disease
mental and undetermined water exposures—United in Europe, 2010. Euro Surveill. 2013;18(23):1–8.
States, 2011–2012. MMWR Morb Mortal Wkly Rep. 2015 7. Garcia-Fulgueiras A, Navarro C, Fenoll D, Garcia J,
Aug 14;64(31):849–51. Gonzalez-Diego P, Jimenez-Bunuales T, et al.
2. Burnsed LJ, Hicks LA, Smithee LM, Fields BS, Legionnaires’ disease outbreak in Murcia, Spain. Emerg
Bradley KK, Pascoe N, et al. A large, travel-associated Infect Dis. 2003 Aug;9(8):915–21.
outbreak of legionellosis among hotel guests: utility of 8. Guyard C, Low DE. Legionella infections and travel
the urine antigen assay in confirming Pontiac fever. Clin associated legionellosis. Travel Med Infect Dis. 2011
Infect Dis. 2007 Jan 15;44(2):222–8. Jul;9(4):176–86.
3. CDC. Legionellosis—United States, 2000–2009. MMWR 9. Mouchtouri VA, Rudge JW. Legionnaires’ disease in
Morb Mortal Wkly Rep. 2011 Aug 19;60(32):1083–6. hotels and passenger ships: a systematic review of evi-
4. CDC. Surveillance for travel-associated Legionnaires dence, sources, and contributing factors. J Travel Med.
disease—United States, 2005–2006. MMWR Morb 2015 Sep-Oct;22(5):325–37.
Mortal Wkly Rep. 2007 Dec 7;56(48):1261–3. 10. Silk BJ, Moore MR, Bergtholdt M, Gorwitz RJ, Kozak NA,
5. Correia AM, Ferreira JS, Borges V, Nunes A, Gomes B, Tha MM, et al. Eight years of Legionnaires’ disease
Capucho R, et al. Probable person-to-person transmis- transmission in travellers to a condominium com-
sion of Legionnaires’ disease. N Engl J Med. 2016 Feb plex in Las Vegas, Nevada. Epidemiol Infect. 2012
4;374(5):497–8. Nov;140(11):1993–2002.
LEISHMANIASIS, CUTANEOUS
Barbara L. Herwaldt, Alan J. Magill
Leishmaniasis is a parasitic disease found in parts The risk is highest from dusk to dawn because
of the tropics, subtropics, and southern Europe. sand flies typically feed (bite) at night and during
Leishmaniasis has several different forms. This twilight hours. Although sand flies are less active
section focuses on cutaneous leishmaniasis (CL), during the hottest time of the day, they may bite
the most common form, both in general and in if they are disturbed ( for example, if hikers brush
3 travelers. against tree trunks or other sites where sand flies
are resting). Vector activity can easily be over-
INFECTIOUS AGENT looked: sand flies do not make noise, they are
Leishmaniasis is caused by obligate intracel- small (approximately one-third the size of mos-
lular protozoan parasites; approximately 20 quitoes), and their bites might not be noticed.
Leishmania species cause CL. Examples of types of travelers who might
have an increased risk for CL include ecotourists,
TRANSMISSION adventure travelers, bird watchers, Peace Corps
CL is transmitted through the bite of an infected volunteers, missionaries, military personnel, con-
female phlebotomine sand fly. CL also can occur struction workers, and people who do research
after accidental occupational (laboratory) expo- outdoors at night or twilight. However, even
sures to Leishmania parasites. short-term travelers in leishmaniasis- endemic
areas have developed CL.
EPIDEMIOLOGY
In the Old World (Eastern Hemisphere), CL is CLINICAL PRESENTATION
found in parts of the Middle East, Asia (particu- CL is characterized by skin lesions (open or closed
larly southwest and central Asia), Africa (partic- sores), which typically develop within several
ularly the tropical region and North Africa), and weeks or months after exposure. In some peo-
southern Europe. In the New World (Western ple, the sores first appear months or years later,
Hemisphere), CL is found in parts of Mexico, in the context of trauma (such as skin wounds or
Central America, and South America. Occasional surgery). The sores can change in size and appear-
cases have been reported in Texas and Oklahoma. ance over time. They typically progress from small
CL is not found in Chile, Uruguay, or Canada. papules to nodular plaques, and often lead to
Overall, CL is found in focal areas of >90 countries. open sores with a raised border and central crater
The geographic distribution of cases of CL (ulcer), which can be covered with scales or crust.
evaluated in countries such as the United States The lesions usually are painless but can be painful,
reflects travel and immigration patterns. Although particularly if open sores become infected with
Old World CL is more common overall than New bacteria. Satellite lesions, regional lymphadenop-
World CL, more than 60% of the CL cases diag- athy, and nodular lymphangitis can be noted. The
nosed in US civilians have been acquired in Latin sores usually heal eventually, even without treat-
America, including popular tourist destinations ment. However, they can last for months or years
such as Costa Rica. Cases in US service person- and typically result in scarring.
nel have reflected military activities (such as in A potential concern applies to some of
Afghanistan and Iraq). CL is usually more com- the Leishmania species in South and Central
mon in rural than urban areas, but it is found America: some parasites might spread from the
in some periurban and urban areas (such as in skin to the mucosal surfaces of the nose or mouth
Kabul, Afghanistan). The ecologic settings range and cause sores there. This form of leishmania-
from rainforests to arid regions. sis, mucosal leishmaniasis (ML), might not be
noticed until years after the original skin sores for ML caused by L. (V.) braziliensis in adults and
appear to have healed. Although ML is uncom- adolescents ≥12 years of age who weigh ≥30 kg and
mon, it has occurred in travelers and expatriates are not pregnant or breastfeeding during therapy
whose cases of CL were not treated or were inad- or for 5 months thereafter. Miltefosine is available
equately treated. The initial clinical manifesta- in the United States via www.profounda.com.
tions typically involve the nose (chronic stuffiness, Various parenteral options (such as liposo-
bleeding, and inflamed mucosa or sores) and less mal amphotericin B) are commercially avail-
often the mouth; in advanced cases, ulcerative able, although not FDA- approved to treat CL
destruction of the nose, mouth, pharynx, and lar- or ML. The pentavalent antimonial compound
ynx can be noted (such as perforation of the nasal sodium stibogluconate (Pentostam) is available
septum). to US-licensed physicians through the CDC Drug
Service (404-639-3670) for intravenous or intra-
3
DIAGNOSIS muscular administration under an investigational
Clinicians should consider CL in people with new drug protocol (see www.cdc.gov/laboratory/
chronic (nonhealing) skin lesions who have been drugservice/index.html).
in areas where leishmaniasis is found. Laboratory
confirmation of the diagnosis is achieved by PREVENTION
detecting Leishmania parasites (or DNA) in No vaccines or drugs to prevent infection are
infected tissue, through light-microscopic exam- available. Preventive measures are aimed at
ination of stained specimens, culture techniques, reducing contact with sand flies by using personal
or molecular methods. protective measures (see Chapter 2, Protection
CDC can assist in all aspects of the diagnos- against Mosquitoes, Ticks, & Other Arthropods).
tic evaluation. Identification of the Leishmania Travelers should be advised to:
species can be important, particularly if >1 spe-
cies is found where the patient traveled and if the
• Avoid outdoor activities, to the extent possi-
ble, especially from dusk to dawn, when sand
species can have different clinical and prognos- flies generally are the most active.
tic implications. Serologic testing generally is not
useful for CL but can provide supportive evidence • Wear protective clothing and apply insect
for the diagnosis of ML. repellent to exposed skin and under the edges
For consultative services, contact CDC of clothing, such as sleeves and pant legs,
Parasitic Diseases Inquiries (404-718-4745; para- according to the manufacturer’s instructions.
[email protected]).
• Sleep in air-conditioned or well-screened
areas. Spraying the quarters with insecticide
TREATMENT might provide some protection. Fans or ven-
Decisions about whether and how to treat CL tilators might inhibit the movement of sand
should be individualized, including whether to use flies, which are weak fliers.
a systemic (oral or parenteral) medication rather
than a local or topical approach. All cases of ML Sand flies are so small (approximately 2–3 mm,
should be treated with systemic therapy. Clinicians less than one-eighth of an inch) that they can pass
may consult with CDC staff about the relative mer- through the holes in ordinary bed nets. Although
its of various approaches to treat CL and ML (see closely woven nets are available, they may be
the Diagnosis section above for contact informa- uncomfortable in hot climates. The effectiveness
tion). The response to a particular regimen may of bed nets can be enhanced by treatment with
vary not only among Leishmania species but also a pyrethroid- containing insecticide. The same
for the same species in different geographic regions. treatment can be applied to window screens, cur-
The oral agent miltefosine is FDA-approved tains, bed sheets, and clothing.
to treat CL caused by 3 New World species in the
Viannia subgenus [Leishmania (V.) braziliensis, L. CDC website: www.cdc.gov/parasites/
(V.) panamensis, and L. (V.) guyanensis] as well as leishmaniasis
BIBLIOGRAPHY
1. Aronson N, Herwaldt BL, Libman M, Pearson R, 4. Hodiamont CJ, Kager PA, Bart A, de Vries HJ,
Lopez-Velez R, Weina P, et al. Diagnosis and treatment van Thiel PP, Leenstra T, et al. Species-directed therapy
of leishmaniasis: clinical practice guidelines by the for leishmaniasis in returning travellers: a comprehen-
Infectious Diseases Society of America (IDSA) and the sive guide. PLoS Negl Trop Dis. 2014 May;8(5):e2832.
American Society of Tropical Medicine and Hygiene 5. Magill AJ. Cutaneous leishmaniasis in the returning trav-
(ASTMH). Clin Infect Dis. 2016 In press. eler. Infect Dis Clin North Am. 2005 Mar;19(1):x–xi, 241–66.
2. Blum J, Buffet P, Visser L, Harms G, Bailey 6. Murray HW. Leishmaniasis in the United
MS, Caumes E, et al. LeishMan recommenda- States: treatment in 2012. Am J Trop Med Hyg. 2012
tions for treatment of cutaneous and mucosal Mar;86(3):434–4 0.
leishmaniasis in travelers, 2014. J Travel Med. 2014
3 Mar-Apr;21(2):116–29.
3. Blum J, Lockwood DN, Visser L, Harms G, Bailey MS,
7. Schwartz E, Hatz C, Blum J. New world cutaneous
leishmaniasis in travellers. Lancet Infect Dis. 2006
Jun;6(6):342–9.
Caumes E, et al. Local or systemic treatment for New
8. World Health Organization. Control of the leishma-
World cutaneous leishmaniasis? Re-evaluating the evi-
niases. Geneva: World Health Organization; 2010 [cited
dence for the risk of mucosal leishmaniasis. Int Health.
2016 Sep. 23]. Available from: http://whqlibdoc.who.int/
2012 Sep;4(3):153–63.
trs/WHO_TRS_949_eng.pdf.
LEISHMANIASIS, VISCERAL
Barbara L. Herwaldt, Alan J. Magill
Leishmaniasis is a parasitic disease found in parts southwest and central Asia), the Middle East,
of the tropics, subtropics, and southern Europe. Africa (particularly East Africa), and southern
Leishmaniasis has several different forms. This Europe. In the New World (Western Hemisphere),
section focuses on visceral leishmaniasis (VL), most cases occur in Brazil; some cases occur in
which affects some of the internal organs of the scattered foci elsewhere in Latin America. Overall,
body (such as the spleen, liver, and bone marrow). VL is found in focal areas of >60 countries. Most
(>90%) of the world’s cases of VL occur in the
INFECTIOUS AGENT Indian subcontinent (India and Bangladesh; also
VL is caused by obligate intracellular protozoan Nepal), East Africa (Sudan, South Sudan, and
parasites, particularly by the species Leishmania Ethiopia), and Brazil; none of the affected areas
donovani and L. infantum-chagasi. in these 7 countries are common destinations for
tourists from the United States.
TRANSMISSION The geographic distribution of cases of VL
VL is predominantly transmitted through the evaluated in countries such as the United States
bite of an infected female phlebotomine sand fly, reflects travel and immigration patterns. VL
although congenital and parenteral transmission is uncommon in US travelers and expatriates.
(through blood transfusions and needle sharing) Occasional cases have been diagnosed in short-
have been reported. term travelers (tourists) to southern Europe and
also in longer-term travelers (such as expatri-
EPIDEMIOLOGY ates and deployed soldiers) to the Mediterranean
VL is usually more common in rural than urban region and other areas where VL is found.
areas, but it is found in some periurban areas
(such as in northeastern Brazil). In the Old World CLINICAL PRESENTATION
(Eastern Hemisphere), VL is found in parts of Among symptomatic people, the incubation
Asia (particularly the Indian subcontinent and period typically ranges from weeks to months.
The onset of illness can be abrupt or gradual. various approaches can be discussed with CDC
Stereotypical manifestations of VL include fever, staff (see the Diagnosis section above for contact
weight loss, hepatosplenomegaly (especially sple- information).
nomegaly), and pancytopenia (anemia, leukope- Liposomal amphotericin B (AmBisome) is
nia, and thrombocytopenia). If untreated, severe approved by the Food and Drug Administration
(advanced) cases of VL typically are fatal. Latent (FDA) to treat VL and generally constitutes the
infection can become clinically manifest years to drug of choice for US patients. The oral agent
decades after exposure in people who become miltefosine is FDA approved to treat VL in patients
immunocompromised for other medical reasons who are infected with L. donovani, are ≥12 years
(such as HIV infection, immunosuppressive ther- of age, weigh ≥30 kg, and are not pregnant or
apy, or biologic immunomodulatory therapy). breastfeeding during therapy or for 5 months
thereafter; the drug is available in the United
3
DIAGNOSIS States via www.profounda.com. The pentavalent
Clinicians should consider VL in people with a antimonial compound sodium stibogluconate
relevant travel history (even in the distant past) (Pentostam) is available to US-licensed physicians
and a persistent, unexplained febrile illness, through the CDC Drug Service (404-639-3670)
especially if accompanied by other suggestive for parenteral administration under an investi-
manifestations (such as splenomegaly and pancy- gational new drug protocol (see www.cdc.gov/
topenia). Laboratory confirmation of the diagno- laboratory/drugservice/index.html).
sis is achieved by detecting Leishmania parasites
(or DNA) in infected tissue (such as in bone PREVENTION
marrow, liver, lymph node, or blood), through No vaccines or drugs to prevent infection are
light-microscopic examination of stained speci- available. Preventive measures are aimed at
mens, culture techniques, or molecular methods. reducing contact with sand flies (see Chapter 2,
Serologic testing can provide supportive evidence Protection against Mosquitoes, Ticks, & Other
for the diagnosis. Arthropods; and Prevention in the previous sec-
CDC can assist in all aspects of the diagnos- tion, Cutaneous Leishmaniasis). Preventive mea-
tic evaluation, including species identification. sures include minimizing outdoor activities, to
For consultative services, contact CDC Parasitic the extent possible, especially from dusk to dawn,
Diseases Inquiries (404-718-4745; parasites@cdc. when sand flies generally are the most active;
gov) or see www.cdc.gov/dpdx. wearing protective clothing; applying insect repel-
lent to exposed skin; using bed nets treated with
TREATMENT a pyrethroid-containing insecticide; and spraying
Infected travelers should be advised to consult dwellings with residual-action insecticides.
an infectious disease or tropical medicine spe-
cialist. Therapy for VL should be individualized CDC website: www.cdc.gov/parasites/
with expert consultation. The relative merits of leishmaniasis
BIBLIOGRAPHY
1. Aronson N, Herwaldt BL, Libman M, Pearson changing pattern at the hospital for tropical dis-
R, Lopez-Velez R, Weina P, et al. Diagnosis and eases, London. PLoS One. 2015;10(4):e0121418.
treatment of leishmaniasis: clinical practice 3. Murray HW. Leishmaniasis in the United
guidelines by the Infectious Diseases Society of States: treatment in 2012. Am J Trop Med Hyg. 2012
America (IDSA) and the American Society of Tropical Mar;86(3):434–4 0.
Medicine and Hygiene (ASTMH). Clin Infect Dis. 2016
4. Myles O, Wortmann GW, Cummings JF, Barthel RV,
In press.
Patel S, Crum-Cianflone NF, et al. Visceral leishmania-
2. Fletcher K, Issa R, Lockwood DN. Visceral leish- sis: clinical observations in 4 US army soldiers deployed
maniasis and immunocompromise as a risk factor to Afghanistan or Iraq, 2002–2004. Arch Intern Med.
for the development of visceral leishmaniasis: a 2007 Sep 24;167(17):1899–9 01.
5. Pavli A, Maltezou HC. Leishmaniasis, an emerging infec- 7. World Health Organization. Control of the leishma-
tion in travelers. Int J Infect Dis. 2010 Dec;14(12):e1032–9. niases. Geneva: World Health Organization; 2010 [cited
6. van Griensven J, Carrillo E, Lopez-Velez R, Lynen L, 2016 Sep. 23]. Available from: http://whqlibdoc.who.int/
Moreno J. Leishmaniasis in immunosuppressed individ- trs/WHO_TRS_949_eng.pdf.
uals. Clin Microbiol Infect. 2014 Apr;20(4):286–99.
LEPTOSPIROSIS
3 Renee L. Galloway, Robyn A. Stoddard, Ilana J. Schafer
altered mental status, respiratory insufficiency, or drug of choice for patients with severe leptospi-
oliguria. rosis, and ceftriaxone was shown to be equally
effective. Patients with severe leptospirosis may
DIAGNOSIS require hospitalization and supportive therapy,
Diagnosis of leptospirosis is usually based on including intravenous hydration and electrolyte
serology; microscopic agglutination test is the supplementation, dialysis in the case of oliguric
gold standard and can only be performed at cer- renal failure, and mechanical ventilation in the
tain reference laboratories. Culture is insensitive, case of respiratory failure.
but detection of the organism in blood or cerebro-
spinal fluid ( for patients with meningitis) using PREVENTION
real-time PCR can provide a more timely diagno-
sis during the acute, septicemic phase. Various
No vaccine is available in the United States.
Travelers who might be at an increased risk for
3
serologic screening tests are available, including infection should be educated on exposure risks
ELISA and multiple rapid diagnostic tests; posi- and advised to consider preventive measures such
tive screening tests should be confirmed with the as chemoprophylaxis; wearing protective clothing,
microscopic agglutination test. Leptospirosis is a especially footwear; and covering cuts and abra-
nationally notifiable disease. sions with occlusive dressings. Limited studies have
shown that chemoprophylaxis with doxycycline
TREATMENT (200 mg orally, weekly), begun 1–2 days before and
Early antimicrobial therapy can be effective in continuing through the period of exposure, might
decreasing the severity and duration of leptospi- be effective in preventing clinical disease in adults
rosis and should be initiated early, without wait- and could be considered for people at high risk and
ing for confirmatory test results, if leptospirosis with short-term exposures. The best way to pre-
is suspected. For patients with mild symptoms, vent infection is to avoid exposure: travelers should
doxycycline is a drug of choice (100 mg orally, avoid contact with potentially contaminated bodies
twice daily) but is not recommended for preg- of water, walking in flood waters, and contact with
nant women or children aged <8 years; alterna- potentially infected animals or their body fluids.
tive options include ampicillin and amoxicillin.
Intravenous penicillin (1.5 MU every 6 hours) is a CDC website: www.cdc.gov/leptospirosis
BIBLIOGRAPHY
1. Costa F, Hagan JE, Calcagno J, Kane M, Torgerson P, 6. Jensenius M, Han PV, Schlagenhauf P, Schwartz E,
Martinez-Silveira MS, et al. Global Morbidity and Parola P, Castelli F, et al. Acute and potentially life-
Mortality of Leptospirosis: A Systematic Review. PLoS threatening tropical diseases in western travelers—a
Negl Trop Dis. 2015;9(9):e0003898. GeoSentinel multicenter study, 1996–2011. Am J Trop
2. Galloway RL, Hoffmaster AR. Optimization of LipL32 Med Hyg. 2013 Feb;88(2):397–4 04.
PCR assay for increased sensitivity in diagnosing lep- 7. Pappas G, Cascio A. Optimal treatment of leptospiro-
tospirosis. Diagnostic microbiology and infectious dis- sis: queries and projections. Int J Antimicrob Agents.
ease. 2015 Jul;82(3):199–200. 2006 Dec;28(6):491–6.
3. Haake DA, Dundoo M, Cader R, Kubak BM, 8. Picardeau M, Bertherat E, Jancloes M, Skouloudis AN,
Hartskeerl RA, Sejvar JJ, et al. Leptospirosis, water Durski K, Hartskeerl RA. Rapid tests for diagnosis of
sports, and chemoprophylaxis. Clin Infect Dis. 2002 May leptospirosis: current tools and emerging technologies.
1;34(9):e40–3. Diagnostic microbiology and infectious disease. 2014
4. Haake DA, Levett PN. Leptospira Species Jan;78(1):1–8.
(Leptospirosis). In: Bennett JE, Dolin R, Blaser MJ, edi- 9. van de Werve C, Perignon A, Jaureguiberry S, Bricaire F,
tors. Principles and Practice of Infectious Diseases. 8th Bourhy P, Caumes E. Travel-related leptospiro-
ed. Philadelphia, PA: Saunders 2015. p. 2714–20. sis: a series of 15 imported cases. J Travel Med. 2013
5. Haake DA, Levett PN. Leptospirosis in humans. Jul-Aug;20(4):228–31.
Current topics in microbiology and immunology.
2015;387:65–97.
LEPTOSPIROSIS 231
3
2
LYME DISEASE
Paul S. Mead
BIBLIOGRAPHY
1. Hao Q, Hou X, Geng Z, Wan K. Distribution of Borrelia 5. Stanek G, Strle F. Lyme disease: European perspective.
burgdorferi sensu lato in China. J Clin Microbiol. 2011 Infect Dis Clin North Am. 2008 Jun;22(2):327–39.
Feb;49(2):647–5 0. 6. Steere AC. Lyme disease. N Engl J Med. 2001 Jul
2. Hubalek Z. Epidemiology of lyme borreliosis. Curr Probl 12;345(2):115–25.
Dermatol. 2009;37:31–5 0. 7. Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ,
3. Masuzawa T. Terrestrial distribution of the Lyme bor- Steere AC, Klempner MS, et al. The clinical assessment,
reliosis agent Borrelia burgdorferi sensu lato in East Asia. treatment, and prevention of Lyme disease, human
Jpn J Infect Dis. 2004 Dec;57(6):229–35. granulocytic anaplasmosis, and babesiosis: clinical
4. O’Connell S. Lyme borreliosis: current issues in diag- practice guidelines by the Infectious Diseases Society of
3
nosis and management. Curr Opin Infect Dis. 2010 America. Clin Infect Dis. 2006 Nov 1;43(9):1089–134.
Jun;23(3):231–5.
MALARIA
Paul M. Arguin, Kathrine R. Tan
MALARIA 233
3
4
2
MALARIA 235
3
26
RUS A
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3
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PHILIPPINES
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VIETNAM )
SRI LANKA
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STATES OF
MICRONESIA
MALDIVES
NEW CALEDONIA
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TASMANIA
MALARIA 237
8
32
Various test kits are available to detect anti- acutely ill travelers should be advised to seek the
gens derived from malaria parasites. Such immu- best available medical services and follow the
nologic (immunochromatographic) tests most treatment offered locally (except the use of halo-
often use a dipstick or cassette format and provide fantrine, which is not recommended; see below)
results in 2–15 minutes. These rapid diagnostic but not to stop their chemoprophylaxis regimen.
tests (RDTs) offer a useful alternative to micros-
copy in situations where reliable microscopic TREATMENT
diagnosis is not immediately available. Although Malaria can be treated effectively early in the
RDTs can detect malaria antigens within min- course of the disease, but delay of therapy can
utes, most cannot distinguish between all 5 of the have serious or even fatal consequences. Travelers
3 species that affect humans, they are less sensitive
than expert microscopy or PCR for diagnosis, they
who have symptoms of malaria should be advised
to seek medical evaluation as soon as possible.
cannot quantify parasitemia, and many will per- Specific treatment options depend on the spe-
sist with a positive result for days or weeks after cies of malaria, the likelihood of drug resistance
an infection has been treated and cleared. In addi- (based on where the infection was acquired),
tion, CDC recommends that positive and negative the age of the patient, pregnancy status, and the
RDT results always be confirmed by microscopy severity of infection.
in US health care settings. Although confirmation Detailed CDC recommendations for malaria
does not have to occur simultaneously with the treatment can be found at www.cdc.gov/malaria/
RDT, the information from microscopy, includ- diagnosis_treatment/treatment.html. Clinicians
ing the actual presence of malaria parasites, the who require assistance with the diagnosis or
species, life-cycle stages (asexual vs sexual blood- treatment of malaria should call the CDC Malaria
stage forms), and parasitemia will be most use- Hotline (770-488-7788 or toll-free at 855-856-4713)
ful if it is available as soon as possible. The Food from 9 am to 5 pm Eastern Time. After hours or on
and Drug Administration (FDA) has approved 1 weekends and holidays, clinicians requiring assis-
RDT for use in the United States by hospital and tance should call the CDC Emergency Operations
commercial laboratories, not by individual clini- Center at 770-488-7100 and ask the operator to
cians or by patients themselves. This RDT is called page the person on call for the Malaria Branch. In
BinaxNOW Malaria test. Laboratories that do not addition, it is advisable to consult with a clinician
provide in- house on- the-
spot microscopy ser- who has specialized travel or tropical medicine
vices should maintain a stock of malaria RDTs so expertise or with an infectious disease physician.
that they will be able to perform malaria diagnos- Medications that are not used in the United
tic testing when needed. States for the treatment of malaria, such as halo-
PCR tests are also available for detecting fantrine, are widely available overseas. CDC
malaria parasites. Although these tests are more does not recommend halofantrine for treat-
sensitive than routine microscopy, results are not ment because of cardiac adverse events, includ-
usually available as quickly as microscopy results ing deaths, which have been documented after
should be, thus limiting the utility of this test for treatment. These adverse events have occurred
acute diagnosis. PCR testing is most useful for in people with and without preexisting cardiac
definitively identifying the species of malaria par- problems and both in the presence and absence
asite and detecting mixed infections. Species con- of other antimalarial drugs (such as mefloquine).
firmation by PCR is available at the CDC malaria Travelers who reject the advice to take pro-
laboratory. phylaxis, who choose a suboptimal drug regimen
In sub- Saharan Africa, clinical overdiagno- (such as chloroquine in an area with chloroquine-
sis and the rate of false-positive microscopy for resistant P. falciparum), or who require a less-
malaria may be high. Travelers to this region than-optimal drug regimen for medical reasons
should be warned they may be diagnosed with are at increased risk for acquiring malaria and
malaria incorrectly, even though they are tak- needing prompt treatment while overseas. In
ing a reliable antimalarial regimen. In such cases, addition, some travelers who are taking effective
3
prophylaxis but who will be in remote areas may Preventing malaria involves striking a bal-
decide, in consultation with their travel health ance between ensuring that all people at risk
provider, to take along a reliable supply of a full for infection use the recommended prevention
course of an approved malaria treatment regimen measures, while preventing rare occurrences of
(see Box 3-3 for a definition of reliable supply). In adverse effects of these interventions among peo-
the event that they are diagnosed with malaria, ple using them unnecessarily. An individual risk
they will have immediate access to this treatment assessment should be conducted for every trav-
regimen, which if acquired in the United States is eler, taking into account not only the destination
unlikely to be counterfeit and will not deplete local country but also the detailed itinerary, including
resources. In rare instances when access to med- specific cities, types of accommodation, season,
ical care is not available and the traveler develops and style of travel. In addition, conditions such as
a febrile illness consistent with malaria, the reli- pregnancy or antimalarial drug resistance at the
able supply medication can be self-administered destination may modify the risk assessment.
presumptively. Travelers should be advised Depending on the level of risk, it may be appro-
that this self-treatment of a possible malar- priate to recommend no specific interventions,
ial infection is only a temporary measure and mosquito avoidance measures only, or mosquito
that prompt medical evaluation is imperative. avoidance measures plus chemoprophylaxis. For
Two malaria treatment regimens available in areas of intense transmission, such as West Africa,
the United States can be prescribed as a reliable exposure for even short periods of time can result
supply: atovaquone- proguanil and artemether- in transmission, so travelers to this area should
lumefantrine. The use of the same or related be considered at high risk for infection. Malaria
drugs that have been taken for prophylaxis is transmission is not distributed homogeneously
not recommended to treat malaria. For exam- throughout all countries. Some destinations have
ple, atovaquone- proguanil may be used as a malaria transmission occurring only in certain
reliable supply medication by travelers not tak- areas. If travelers are going to high-transmission
ing atovaquone- proguanil for prophylaxis. See areas during peak transmission times, even
Table 3-8 for the dosing recommendation. though the country as a whole may have relatively
low malaria transmission, they may be at high risk
PREVENTION for infection while there.
The goal of these malaria prevention guidelines is Geography is just a part of determining a trav-
to prevent malaria caused by all species, not only eler’s risk for infection. Risk can differ substan-
P. falciparum. These guidelines apply to both short- tially for different travelers as their behaviors and
term and long-term travelers. Malaria prevention circumstances differ. For example, travelers stay-
consists of a combination of mosquito avoidance ing in air-conditioned hotels may be at lower risk
measures and chemoprophylaxis. Although effi- than backpackers or adventure travelers. Similarly,
cacious, the recommended interventions are not long-term residents living in screened and air-
100% effective. conditioned housing are less likely to be exposed
MALARIA 239
4
02
3 100 mg proguanil.
The pediatric tablet
contains 62.5 mg
21–30 kg: 2 adult tablets
31–40 kg: 3 adult tablets
>41 kg: 4 adult tablets
people on atovaquone-
proguanil prophylaxis
Not recommended for
atovaquone and 25 children weighing <5 kg,
mg proguanil. pregnant women, and
women breastfeeding
infants weighing <5 kg
ARTEMETHER- A 3-day treatment schedule with a total of 6 oral doses Not for people on
LUMEFANTRINE is recommended for both adult and pediatric patients mefloquine prophylaxis
One tablet contains based on weight. The patient should receive the initial Not recommended for
20 mg artemether dose, followed by the second dose 8 hours later, then children weighing <5 kg,
and 120 mg 1 dose twice per day for the following 2 days. pregnant women, and
lumefantrine. 5 to <15 kg: 1 tablet per dose women breastfeeding
15 to <25 kg: 2 tablets per dose infants weighing <5 kg
25 to <35 kg: 3 tablets per dose
≥35 kg: 4 tablets per dose
1
If used for presumptive self-treatment, medical care should be sought as soon as possible.
than are people living without such amenities. The (preferably insecticide-treated nets), using an
highest risk is associated with first-and second- effective insecticide spray in living and sleeping
generation immigrants living in non- endemic areas during evening and nighttime hours, and
countries who return to their countries of origin wearing clothes that cover most of the body.
to visit friends and relatives (VFRs). VFR travelers All travelers should use an effective m
osquito
often consider themselves to be at no risk, because repellent (see Chapter 2, Protection against
they grew up in a malarious country and consider Mosquitoes, Ticks, & Other Arthropods). Repel
themselves immune. However, acquired immu- lents should be applied to exposed parts of the
nity is lost quickly, and VFRs should be considered skin when mosquitoes are likely to be present. If
to have the same risk as other nonimmune travel- travelers are also wearing sunscreen, sunscreen
ers (see Chapter 8, Immigrants Returning Home should be applied first and insect repellent sec-
to Visit Friends & Relatives [VFRs]). Travelers ond. In addition to using a topical insect repellent,
should also be reminded that even if a person has a permethrin-containing product may be applied
had malaria before, he or she can get it again, and to bed nets and clothing for additional protection
preventive measures are still necessary. against mosquitoes.
traveler is exposed to malaria parasites. In choos- malaria occurs and if antimalarial drug resistance
ing a chemoprophylaxis regimen before travel, the has been reported in that location (see the Yellow
traveler and the travel health provider should con- Fever & Malaria Information, by Country section
sider several factors. The travel itinerary should be later in this chapter). Additional factors to con-
reviewed in detail and compared with informa- sider are the patient’s other medical conditions,
tion on where malaria transmission occurs within medications being taken (to assess potential drug
a given country, to determine whether the trav- interactions), the cost of the medicines, and the
eler will be traveling in a part of the country where potential side effects. Table 3-9 lists some of the
Atovaquone- • Good for last-minute travelers because • Cannot be used by women who are
proguanil the drug is started 1–2 days before travel. pregnant or breastfeeding a child that
• Some people prefer to take a daily weighs <5 kg.
medicine. • Cannot be taken by people with severe
• Good choice for shorter trips because renal impairment.
the traveler takes the medicine for • Tends to be more expensive than some of
only 7 days after traveling rather than the other options (especially for long trips).
4 weeks. • Some people (including children) would
• Well tolerated—side effects uncommon. rather not take a medicine every day.
• Pediatric tablets are available and may
be more convenient.
Chloroquine • Some people would rather take medicine • Cannot be used in areas with chloroquine
weekly. or mefloquine resistance.
• Good choice for long trips because it is • May exacerbate psoriasis.
taken only weekly. • Some people would rather not take a
• Some people are already taking weekly medication.
hydroxychloroquine chronically for • For short trips, some people would rather
rheumatologic conditions; in those not take medication for 4 weeks after
instances, they may not have to take an travel.
additional medicine. • Not a good choice for last-minute travelers,
• Can be used in all trimesters of because drug needs to be started 1–2
pregnancy. weeks before travel.
Doxycycline • Some people prefer to take a daily • Cannot be used by pregnant women and
medicine. children aged <8 years.
• Good for last-minute travelers because • Some people would rather not take a
the drug is started 1–2 days before travel. medicine every day.
• Tends to be the least expensive • For short trips, some people would rather
antimalarial. not take medication for 4 weeks after
• People who are already taking travel.
doxycycline chronically to prevent • Women prone to getting vaginal yeast
acne do not have to take an additional infections when taking antibiotics may
medicine. prefer taking a different medicine.
• Doxycycline also can prevent some • People may want to avoid the increased
additional infections (such as rickettsial risk of sun sensitivity.
infections and leptospirosis), so it may • Some people are concerned about the
be preferred by people planning to hike, potential of getting an upset stomach from
camp, and swim in fresh water. doxycycline.
(continued)
MALARIA 241
4
2
Mefloquine • Some people would rather take medicine • Cannot be used in areas with mefloquine
weekly. resistance.
• Good choice for long trips because it is • Cannot be used in patients with certain
taken only weekly. psychiatric conditions.
• Can be used in all trimesters of • Cannot be used in patients with a seizure
pregnancy. disorder.
Primaquine • It is the most effective medicine for • Cannot be used in patients with G6PD
preventing P. vivax, so it is a good choice deficiency.
for travel to places with >90% P. vivax. • Cannot be used in patients who have not
• Good choice for shorter trips because the been tested for G6PD deficiency.
traveler takes the medicine for 7 days • There are costs and delays associated
after traveling rather than 4 weeks. with getting a G6PD test; however, it only
• Good for last-minute travelers because has to be done once. Once a normal G6PD
the drug is started 1–2 days before travel. level is verified and documented, the test
• Some people prefer to take a daily does not have to be repeated the next time
medicine. primaquine is considered.
• Cannot be used by pregnant women.
• Cannot be used by women who are
breastfeeding, unless the infant has also
been tested for G6PD deficiency.
• Some people (including children) would
rather not take a medicine every day.
• Some people are concerned about the
potential of getting an upset stomach from
primaquine.
benefits and limitations of medicines used for parts of Africa. Resistance to mefloquine has been
malaria chemoprophylaxis; additional informa- confirmed on the borders of Thailand with Burma
tion about choosing a malaria chemoprophylaxis (Myanmar) and Cambodia, in the western prov-
regimen can be found at www.cdc.gov/malaria/ inces of Cambodia, in the eastern states of Burma
travelers/drugs.html. on the border between Burma and China, along
The resistance of P. falciparum to chloroquine the borders of Laos and Burma, the adjacent parts
has been confirmed in all areas with P. falciparum of the Thailand–Cambodia border, and in south-
malaria except the Caribbean, Central America ern Vietnam. The resistance of P. vivax to chloro-
west of the Panama Canal, and some countries quine has been confirmed in Papua New Guinea
in the Middle East. In addition, resistance to and Indonesia.
sulfadoxine-pyrimethamine is widespread in the In addition to primary prophylaxis, presump-
Amazon River Basin area of South America, much tive antirelapse therapy (also known as terminal
of Southeast Asia, other parts of Asia, and in large prophylaxis) uses a medication toward the end of
the exposure period (or immediately thereafter) recommended for prophylaxis in children weigh-
to prevent relapses or delayed-onset clinical pre- ing <5 kg (11 lb), pregnant women, or patients
sentations of malaria caused by hypnozoites (dor- with severe renal impairment (creatinine clear-
mant liver stages) of P. vivax or P. ovale. Because ance <30 mL/min). Proguanil may increase the
most malarious areas of the world (except the effect of warfarin, so international normalized
Caribbean) have at least 1 species of relapsing ratio monitoring or dosage adjustment may be
malaria, travelers to these areas have some risk needed.
for acquiring either P. vivax or P. ovale, although
the actual risk for an individual traveler is difficult CHLOROQUINE AND HYDROXYCHLOROQUINE
to define. Presumptive antirelapse therapy is gen- Chloroquine phosphate or hydroxychloroquine
erally indicated only for people who have had pro-
longed exposure in malaria-endemic areas (such
sulfate can be used for prevention of malaria only
in destinations where chloroquine resistance is
3
as missionaries, military personnel, or Peace not present (see Maps 3-9 and 3-10 and the Yellow
Corps volunteers). Fever & Malaria Information, by Country section
The medications recommended for chemopro- later in this chapter). Prophylaxis should begin 1–
phylaxis of malaria may also be available at over- 2 weeks before travel to malarious areas. It should
seas destinations. However, combinations of these be continued by taking the drug once a week, on
medications and additional drugs that are not rec- the same day of the week, during travel in malar-
ommended may be commonly prescribed and used ious areas and for 4 weeks after a traveler leaves
in other countries. Travelers should be strongly dis- these areas (see Table 3-10 for recommended dos-
couraged from obtaining chemoprophylaxis medi- ages). Reported side effects include gastrointes-
cations while abroad. The quality of these products tinal disturbance, headache, dizziness, blurred
is not known; they may not be protective and could vision, insomnia, and pruritus, but generally these
be dangerous. These medications may have been effects do not require that the drug be discontin-
produced by substandard manufacturing prac- ued. High doses of chloroquine, such as those used
tices, may be counterfeit, or may contain contam- to treat rheumatoid arthritis, have been asso-
inants. Additional information on this topic can ciated with retinopathy; this serious side effect
be found in Chapter 2, Perspectives: Pharmaceutical appears to be extremely unlikely when chloro-
Quality & Falsified Drugs, and on the FDA quine is used for routine weekly malaria prophy-
website (www.fda.gov/Drugs/ResourcesForYou/ laxis. Chloroquine and related compounds have
Consumers/ B uyingUsingMedicineSafely/ been reported to exacerbate psoriasis. People who
BuyingMedicinefromOutsidetheUnitedStates/ experience uncomfortable side effects after taking
default.htm). chloroquine may tolerate the drug better by tak-
ing it with meals. As an alternative, the related
MEDICATIONS USED compound hydroxychloroquine sulfate may be
FOR CHEMOPROPHYLAXIS better tolerated.
ATOVAQUONE-PROGUANIL
Atovaquone-proguanil is a fixed combination of DOXYCYCLINE
the drugs atovaquone and proguanil. Prophylaxis Doxycycline prophylaxis should begin 1–2 days
should begin 1–2 days before travel to malarious before travel to malarious areas. It should be
areas and should be taken daily, at the same time continued once a day, at the same time each
each day, while in the malarious areas, and daily day, during travel in malarious areas and daily
for 7 days after leaving the areas (see Table 3-10 for for 4 weeks after the traveler leaves such areas.
recommended dosages). Atovaquone- proguanil Insufficient data exist on the antimalarial pro-
is well tolerated, and side effects are rare. The phylactic efficacy of related compounds such as
most common adverse effects reported in peo- minocycline (commonly prescribed for the treat-
ple using atovaquone-proguanil for prophylaxis ment of acne). People on a long-term regimen
or treatment are abdominal pain, nausea, vomit- of minocycline who need malaria prophylaxis
ing, and headache. Atovaquone-proguanil is not should stop taking minocycline 1–2 days before
MALARIA 243
42
244
3
INFECTIOUS DISEASES RELATED TO TRAVEL
Atovaquone- Prophylaxis in all areas Adult tablets Pediatric tablets contain 62.5 Begin 1–2 days before travel to malarious areas.
proguanil contain 250 mg mg atovaquone and 25 mg Take daily at the same time each day while in the
atovaquone and proguanil hydrochloride. malarious area and for 7 days after leaving such
100 mg proguanil • 5–8 kg: 1/2 pediatric areas. Contraindicated in people with severe renal
hydrochloride. 1 tablet daily impairment (creatinine clearance <30 mL/min).
adult tablet orally, • 8–10 kg: 3/4 pediatric Atovaquone-proguanil should be taken with food
daily tablet daily or a milky drink. Not recommended for prophylaxis
• 10–20 kg: 1 pediatric for children weighing <5 kg, pregnant women, and
tablet daily women breastfeeding infants weighing <5 kg. Partial
• 20–30 kg: 2 pediatric tablet doses may need to be prepared by a pharmacist
tablets daily and dispensed in individual capsules, as described in
• 30–40 kg: 3 pediatric the text.
tablets daily
• 40 kg: 1 adult tablet daily
Chloroquine Prophylaxis only in 300 mg base (500 5 mg/kg base (8.3 mg/kg salt) Begin 1–2 weeks before travel to malarious areas.
phosphate areas with chloroquine- mg salt) orally, once/ orally, once/week, up to a Take weekly on the same day of the week while in the
sensitive malaria week maximum adult dose of 300 malarious area and for 4 weeks after leaving such
mg base areas. May exacerbate psoriasis.
Doxycycline Prophylaxis in all areas 100 mg orally, daily ≥8 years of age: 2.2 mg/kg up Begin 1–2 days before travel to malarious areas.
to adult dose of 100 mg/day Take daily at the same time each day while in the
malarious area and for 4 weeks after leaving such
areas. Contraindicated in children aged <8 years and
pregnant women.
Hydroxychloroquine An alternative to 310 mg base (400 5 mg/kg base (6.5 mg/kg salt) Begin 1–2 weeks before travel to malarious areas.
sulfate chloroquine for mg salt) orally, once/ orally, once/week, up to a Take weekly on the same day of the week while in the
prophylaxis only in week maximum adult dose of 310 malarious area and for 4 weeks after leaving such
areas with chloroquine- mg base areas.
sensitive malaria
4
52
Mefloquine Prophylaxis in areas with 228 mg base (250 ≤9 kg: 4.6 mg/kg base (5 mg/kg Begin ≥2 weeks before travel to malarious areas.
mefloquine-sensitive mg salt) orally, once/ salt) orally, once/week Take weekly on the same day of the week while in
malaria week >9–19 kg: 1/4 tablet once/week the malarious area and for 4 weeks after leaving
>19–30 kg: 1/2 tablet once/ such areas. Contraindicated in people allergic to
week mefloquine or related compounds (quinine, quinidine)
>30–45 kg: 3/4 tablet once/ and in people with active depression, a recent
week history of depression, generalized anxiety disorder,
>45 kg: 1 tablet once/week psychosis, schizophrenia, other major psychiatric
disorders, or seizures. Use with caution in people
with psychiatric disturbances or a previous history
of depression. Not recommended for people with
cardiac conduction abnormalities.
Primaquine1 Prophylaxis for short- 30 mg base (52.6 mg 0.5 mg/kg base (0.8 mg/kg salt) Begin 1–2 days before travel to malarious areas.
duration travel to areas salt) orally, daily up to adult dose orally, daily Take daily at the same time each day while in
with principally P. vivax 30 mg base (52.6 0.5 mg/kg base (0.8 mg/kg salt) the malarious area and for 7 days after leaving
Used for presumptive mg salt) orally, daily up to adult dose orally, daily for such areas. Contraindicated in people with G6PD
antirelapse therapy for 14 days after 14 days after departure from deficiency. Also contraindicated during pregnancy
(terminal prophylaxis) departure from the the malarious area and lactation, unless the infant being breastfed has a
to decrease the risk for malarious area documented normal G6PD level.
relapses of P. vivax and Indicated for people who have had prolonged
P. ovale exposure to P. vivax, P. ovale, or both. Contraindicated
in people with G6PD deficiency. Also contraindicated
during pregnancy and lactation, unless the infant
being breastfed has a documented normal G6PD
level.
1
All people who take primaquine should have a documented normal G6PD level before starting the medication.
MALARIA
245
3
4
26
travel and start doxycycline instead. Minocycline reported to continue long after mefloquine has
can be restarted after the full course of doxy- been stopped. FDA also includes a boxed warn-
cycline is completed (see Table 3-10 for recom- ing about rare reports of persistent dizziness after
mended dosages). mefloquine use. Mefloquine is contraindicated
Doxycycline can cause photosensitivity, usu- for use by travelers with a known hypersensitiv-
ally manifested as an exaggerated sunburn reac- ity to mefloquine or related compounds (such as
tion. The risk for such a reaction can be minimized quinine or quinidine) and in people with active
by avoiding prolonged, direct exposure to the sun depression, a recent history of depression, gener-
and by using sunscreen. In addition, doxycycline alized anxiety disorder, psychosis, schizophrenia,
use is associated with an increased frequency other major psychiatric disorders, or seizures. It
3 of vaginal yeast infections. Gastrointestinal side
effects (nausea or vomiting) may be minimized
should be used with caution in people with psy-
chiatric disturbances or a history of depression.
by taking the drug with a meal or by specifically A review of available data suggests that meflo-
prescribing doxycycline monohydrate or the quine may be used safely in people concurrently
enteric-coated doxycycline hyclate, rather than on β-blockers, if they have no underlying arrhyth-
the generic doxycycline hyclate, which is often mia. However, mefloquine is not recommended
less expensive. To reduce the risk for esophagi- for people with cardiac conduction abnormal-
tis, travelers should be advised to swallow the ities. Any traveler receiving a prescription for
medicine with sufficient fluids and not to take mefloquine must also receive a copy of the FDA
doxycycline before going to bed. Doxycycline is medication guide, which can be found at www.
contraindicated in people with an allergy to tet- accessdata.fda.gov/drugsatfda_docs/label/2008/
racyclines, during pregnancy, and in infants and 019591s023lbl.pdf.
children aged <8 years. Vaccination with the oral
typhoid vaccine Ty21a should be delayed for ≥24 PRIMAQUINE
hours after taking a dose of doxycycline. Primaquine phosphate has 2 distinct uses for
malaria prevention: primary prophylaxis in areas
MEFLOQUINE with primarily P. vivax and presumptive antire-
Mefloquine prophylaxis should begin ≥2 weeks lapse therapy (terminal prophylaxis).
before travel to malarious areas. It should be con- When taken for primary prophylaxis, pri-
tinued once a week, on the same day of the week, maquine should be taken 1–2 days before travel
during travel in malarious areas and for 4 weeks to malarious areas, daily, at the same time each
after a traveler leaves such areas (see Table 3-10 day, while in the malarious areas, and daily for
for recommended dosages). Mefloquine has been 7 days after leaving the areas (see Table 3-10 for
associated with rare but serious adverse reac- recommended dosages). Primary prophylaxis
tions (such as psychoses or seizures) at prophy- with primaquine obviates the need for presump-
lactic doses; these reactions are more frequent tive antirelapse therapy.
with the higher doses used for treatment. Other When used for presumptive antirelapse ther-
side effects that have occurred in chemoprophy- apy, primaquine is administered for 14 days after
laxis studies include gastrointestinal disturbance, the traveler has left a malarious area. When chlo-
headache, insomnia, abnormal dreams, visual roquine, doxycycline, or mefloquine is used for
disturbances, depression, anxiety disorder, and primary prophylaxis, primaquine is usually taken
dizziness. Other more severe neuropsychiatric during the last 2 weeks of postexposure prophy-
disorders occasionally reported during postmar- laxis. When atovaquone-proguanil is used for pro-
keting surveillance include sensory and motor phylaxis, primaquine may be taken during the
neuropathies (including paresthesia, tremor, and final 7 days of atovaquone-proguanil, and then for
ataxia), agitation or restlessness, mood changes, an additional 7 days. Primaquine should be given
panic attacks, forgetfulness, confusion, hallucina- concurrently with the primary prophylaxis med-
tions, aggression, paranoia, and encephalopathy. ication. However, if that is not feasible, the pri-
On occasion, psychiatric symptoms have been maquine course should still be administered after
MALARIA 247
8
42
Atovaquone 2–3 days
Chloroquine 1–2 months
Hydroxychloroquine 1–2 months
malara chemoprophylaxis medicines. After 2, 4, and have comparable efficacy in that country.
and 6 half-lives, approximately 25%, 6%, and 2% No antimalarial drug is 100% protective; there-
respectively, of the drug remain in the body. fore, prophylaxis must be combined with the use
Very small amounts of antimalarial drugs are of personal protective measures (such as insect
excreted in the breast milk of lactating women. repellent, long sleeves, long pants, sleeping in a
Because the quantity of antimalarial drugs trans- mosquito- free setting or using an insecticide-
ferred in breast milk is insufficient to provide ade- treated bed net). When several different drugs are
quate protection against malaria, infants who recommended for an area, Table 3-9 may help in
require chemoprophylaxis must receive the rec- the decision-making process.
ommended dosages of antimalarial drugs listed in
Table 3-10. Because chloroquine and mefloquine
may be safely prescribed to infants, it is also safe
CHANGING MEDICATIONS AS A
RESULT OF SIDE EFFECTS
3
for infants to be exposed to the small amounts DURING CHEMOPROPHYLAXIS
excreted in breast milk. Although data are very Medications recommended for prophylaxis
limited about the use of doxycycline in lactat- against malaria have different modes of action
ing women, most experts consider the theoreti- that affect the parasites at different stages of
cal possibility of adverse events to the infant to be the life cycle. Thus, if the medication needs to
remote. be changed because of side effects before a full
Although no information is available on the course has been completed, there are some spe-
amount of primaquine that enters human breast cial considerations (see Table 3-12).
milk, the mother and infant should be tested for
G6PD deficiency before primaquine is given to a BLOOD DONATION AFTER
woman who is breastfeeding. Because data are TRAVEL TO MALARIOUS AREAS
not yet available on the safety of atovaquone- People who have been in an area where malaria
proguanil prophylaxis in infants weighing <5 kg transmission occurs should be deferred from
(11 lb), CDC does not recommend it to prevent donating blood in the United States for a period
malaria in women breastfeeding infants weigh- of time after returning from the malarious area
ing <5 kg. However, it can be used to treat women to prevent transmission of malaria through blood
who are breastfeeding infants of any weight when transfusion (Table 3-13).
the potential benefit outweighs the potential risk Risk assessments may differ between travel
to the infant (such as treating a breastfeeding health providers and blood banks. A travel health
woman who has acquired P. falciparum malaria provider advising a traveler going to a coun-
in an area of multidrug-resistant strains and who try with relatively low malaria transmission for
cannot tolerate other treatment options). a short period of time and engaging in low-risk
behaviors may choose insect avoidance only and
CHOOSING A DRUG TO PREVENT MALARIA no chemoprophylaxis for the traveler. However,
Recommendations for drugs to prevent malaria upon the traveler’s return, a blood bank may still
differ by country of travel and can be found in the choose to defer that traveler for 1 year because of
Yellow Fever & Malaria Information, by Country the travel to an area where transmission occurs.
section later in this chapter. Recommended drugs
for each country are listed in alphabetical order CDC website: www.cdc.gov/malaria
MALARIA 249
5
0
2
Mefloquine Doxycycline Begin doxycycline, continue daily while in malaria-endemic area, and
continue for 4 weeks after leaving malaria-endemic area.
Atovaquone- • If the switch occurs ≥3 weeks before departure from the endemic area,
3 proguanil atovaquone-proguanil should be taken daily for the rest of the stay in the
endemic area and for 1 week thereafter.
• If the switch occurs <3 weeks before departure from the endemic area,
atovaquone-proguanil should be taken daily for 4 weeks after the switch.
• If the switch occurs after departure from the endemic area, atovaquone-
proguanil should be taken daily until 4 weeks after the date of departure.
Chloroquine Not recommended
Atovaquone- • If the switch occurs ≥3 weeks before departure from the endemic area,
proguanil atovaquone-proguanil should be taken daily for the rest of the stay in the
endemic area and for 1 week thereafter.
• If the switch occurs <3 weeks before departure from the endemic area,
atovaquone-proguanil should be taken daily for 4 weeks after the switch.
• If the switch occurs after departure from the endemic area, atovaquone-
proguanil should be taken daily until 4 weeks after the date of departure.
Chloroquine Not recommended
Atovaquone- Doxycycline Begin doxycycline, continue daily while in malaria-endemic area, and
proguanil continue for 4 weeks after leaving malaria-endemic area.
Mefloquine Not recommended
Chloroquine Doxycycline Begin doxycycline, continue daily while in malaria-endemic area, and
continue for 4 weeks after leaving malaria-endemic area.
Atovaquone- • If the switch occurs ≥3 weeks before departure from the endemic area,
proguanil atovaquone-proguanil should be taken daily for the rest of the stay in the
endemic area and for 1 week thereafter. 3
• If the switch occurs <3 weeks before departure from the endemic area,
atovaquone-proguanil should be taken daily for 4 weeks after the switch.
• If the switch occurs following departure from the endemic area,
atovaquone-proguanil should be taken daily until 4 weeks after the date
of departure.
Mefloquine Not recommended
Primaquine Doxycycline Begin doxycycline, continue daily while in malaria-endemic area, and
continue for 4 weeks after leaving malaria-endemic area.
Atovaquone- Begin atovaquone-proguanil, continue daily while in malaria-endemic area,
proguanil and continue for 7 days after leaving malaria-endemic area.
Chloroquine Not recommended
Travelers to malaria-endemic areas May not donate blood for 1 year after travel.
Former residents of malaria- May not donate blood for 3 years after departing. If they return to a
endemic areas malaria-endemic area within that 3-year period, they are deferred for
an additional 3 years.
People diagnosed with malaria May not donate for 3 years after treatment.
MALARIA 251
5
2
BIBLIOGRAPHY
1. Boggild AK, Parise ME, Lewis LS, Kain KC. Atovaquone- 5. Leder K, Black J, O’Brien D, Greenwood Z, Kain KC,
proguanil: report from the CDC expert meeting on Schwartz E, et al. Malaria in travelers: a review of the
malaria chemoprophylaxis (II). Am J Trop Med Hyg. GeoSentinel surveillance network. Clin Infect Dis. 2004
2007 Feb;76(2):208–23. Oct 15;39(8):1104–12.
2. CDC. Malaria Surveillance—United States, 2013. 6. Newman RD, Parise ME, Barber AM, Steketee RW.
MMWR Surveill Summ. 2016 Mar 4;65(2):1–22. Malaria-related deaths among US travelers, 1963–2001.
3. Fradin MS, Day JF. Comparative efficacy of insect repel- Ann Intern Med. 2004 Oct 5;141(7):547–55.
lents against mosquito bites. N Engl J Med. 2002 Jul 7. Steinhardt LC, Magill AJ, Arguin PM. Review: Malaria
4;347(1):13–8. chemoprophylaxis for travelers to Latin America. Am J
3 4. Hill DR, Baird JK, Parise ME, Lewis LS, Trop Med Hyg. 2011 Dec;85(6):1015–24.
Ryan ET, Magill AJ. Primaquine: report 8. Tan KR, Magill AJ, Parise ME, Arguin PM. Doxycycline
from CDC expert meeting on malaria for malaria chemoprophylaxis and treatment: report
chemoprophylaxis I. Am J Trop Med Hyg. 2006 from the CDC expert meeting on malaria chemopro-
Sep;75(3):402–15. phylaxis. Am J Trop Med Hyg. 2011 Apr;84(4):517–31.
3
on Java, cutting off
forces. P. falciparum malaria
the supply of quinine
as monotherapy were
and leaving the Allies • 1967: A second mas-
disappointing, with early
with no source for sive US government–
treatment failures due
antimalarial drugs. sponsored antimalarial
to the emergence of
drug discovery effort
• 1943: American scien- atovaquone-resistant
centered at the Walter
tists quickly devised a parasites. However,
Reed Army Institute of
manufacturing process combining atovaquone
Research began and
for mepacrine, and with proguanil led to an
led to the discovery of
the drug was given as efficacious combination
mefloquine.
a treatment and as therapy.
a prophylactic under • 1971: During studies
• 1982: The fixed com-
the name Atabrine. of volunteers with
bination of pyrimeth-
Meanwhile, the experimentally induced
amine and sulfadoxine
Allies, especially the malaria infections, it
(Fansidar) became
Americans, launched was observed that tetra-
available in the United
the largest antimalar- cycline, administered to
States. CDC recom-
ial drug discovery and treat intercurrent bacte-
mended a combined
development program rial infections, appeared
regimen of chloroquine
the world had seen. to exert blood schizon-
and Fansidar to prevent
By 1945, several new tocidal activity against
chloroquine-resistant
antimalarial drugs chloroquine-resistant
P. falciparum.
had been introduced, P. falciparum. A few
including chloro- additional studies were • 1985: CDC added cau-
quine and proguanil. performed with tetra- tionary language to
Chloroquine went on cycline, doxycycline, the recommendation
to assume a role both and minocycline, but for pyrimethamine-
in prophylaxis for no formal develop- sulfadoxine use as
travelers and as a ment of the drug as weekly malaria chemo-
treatment drug for an antimalarial was prophylaxis resulted in
endemic areas. pursued. fatal cases of Stevens-
• 1959: Chloroquine- Johnson syndrome.
• 1977: Although it was
resistant Plasmodium CDC added doxycycline
not yet available in the
falciparum malaria was as an alternative reg-
United States, CDC rec-
first reported. imen for antimalarial
ommended sulfadoxine-
prophylaxis.
• 1965: Large-scale pyrimethamine as an
American military alternative for primary • 1986: CDC removed
involvement began in prophylaxis. amodiaquine as a
recommended alter- new drug application for and the Vietnam War. The
native for malaria doxycycline for malaria modern history of develop-
prevention. chemoprophylaxis. ing drugs to prevent malaria
grew almost entirely from
• Late 1980s: The US • 2000: Combination of
the need to protect military
Army conducted sev- fixed dose atovaquone-
personnel and keep them
eral field and human proguanil (Malarone)
healthy to conduct combat
challenge clinical trials was approved by FDA.
operations in malaria-
demonstrating the effi-
cacy of doxycycline as
malaria prophylaxis.
• 2001–2002: CDC added
atovaquone-proguanil
endemic areas. Those mas-
sive government-funded 3
as an alternative reg- efforts produced the drugs
• 1987: CDC added imen for malaria che- now used to keep modern
chloroquine-proguanil moprophylaxis and civilian travelers safe from
as an alternative removed chloroquine- the sickness and death
regimen for malaria progaunil as a recom- that mark malaria’s march
prevention. mended alternative. through time.
MEASLES (RUBEOLA)
Paul A. Gastañaduy, James L. Goodson
• Preschool and school-age children (aged that generally persist for 1 day to 3 weeks and
≥12 months) should be given 2 MMR or rarely recur. Chronic joint symptoms are rare,
MMRV doses separated by ≥28 days. if they occur at all.)
• Adults born in or after 1957 should be given 2 Evidence does not support a causal link between
MMR or MMRV doses separated by ≥28 days. MMR vaccination and any of the following: hear-
ing loss, retinopathy, optic neuritis, ocular pal-
One dose of MMR or MMRV is approximately 85% sies, Guillain-Barré syndrome, cerebellar ataxia,
effective when administered at age 9 months and Crohn’s disease, or autism. A published report
93% effective when administered at age ≥1 year. on MMR vaccination and inflammatory bowel
Vaccine effectiveness of 2 doses is 97%.
3 Measles-containing vaccine and immune glob-
ulin (IG) may be effective as postexposure pro-
disease and pervasive developmental disorders
(such as autism) has never been replicated by
other studies and has subsequently been widely
phylaxis. MMR or MMRV, if administered within discredited and retracted by the journal.
72 hours after initial exposure to measles virus,
may provide some protection. If the exposure
CONTRAINDICATIONS AND PRECAUTIONS
does not result in infection, the vaccine should
CONTRAINDICATIONS
induce protection against subsequent measles
Allergy—People with severe allergy (hives, swell-
virus infection. IG can be used to prevent or miti-
ing of the mouth or throat, difficulty breathing,
gate measles in a susceptible person when admin-
hypotension, and shock) to gelatin or neomycin,
istered within 6 days of exposure. However, any
or who have had a severe allergic reaction to a
immunity conferred is temporary unless modified
prior dose of MMR or MMRV vaccine, should not
or typical measles occurs, and the person should
be revaccinated. MMR or MMRV vaccine may be
receive MMR or MMRV 6 months after intramus-
administered to people who are allergic to eggs
cularly administered IG or 8 months after intra-
without prior routine skin testing or the use of
venously administered IG, provided the person is
special protocols.
then aged ≥12 months and the vaccine is not oth-
erwise contraindicated. Pregnancy—MMR vaccines should not be admin-
istered to pregnant women or those attempting to
become pregnant. Because of the theoretical risk
VACCINE SAFETY AND ADVERSE REACTIONS
to the fetus when the mother receives a live virus
In rare circumstances, MMR vaccination has been
vaccine, women should be counseled to avoid
associated with the following adverse events:
becoming pregnant for 28 days after receipt of
• Anaphylaxis (approximately 1–3.5 occur- MMR vaccine.
rences per million doses administered) Immunosuppression—Enhanced replication of
live vaccine viruses can occur in people who have
• Thrombocytopenia (a rate of 1 case in
every 25,000 doses during the 6 weeks after immune deficiency disorders. Death related to
immunization) vaccine-associated measles virus infection has
been reported among severely immunocompro-
• Febrile seizures (The risk of febrile sei- mised people. Therefore, severely immunosup-
zures is approximately 25–33 cases for every pressed people should not be vaccinated with
100,000 doses of MMR vaccine administered, MMR or MMRV vaccine ( for a thorough discussion
but overall, the rate of febrile seizure after of recommendations for immunocompromised
measles-containing vaccine is much lower travelers, see Chapter 8, Immunocompromised
than the rate with measles disease.) Travelers):
• Joint symptoms (Arthralgia develops among • People with leukemia in remission, and
approximately 25% of nonimmune postpu- off chemotherapy, who were not immune
bertal women from the rubella component to measles when diagnosed with leuke-
of the MMR vaccination. Approximately 10% mia, may receive MMR vaccine. At least
have acute arthritislike signs and symptoms 3 months should elapse after termination of
BIBLIOGRVAPHY
1. American Academy of Pediatrics. Measles. In: 5. Measles & Rubella Initiative [Internet]. Washington, DC:
Pickering LK, editor. Red Book: 2015 Report of the Amercian Red Cross; 2014 [cited 2016 Sep. 25]. Available
Committee on Infectious Diseases. 30th ed. Elk Grove from: http://www.measlesrubellainitiative.org.
Village, IL: American Academy of Pediatrics; 2015. pp. 6. National Notifiable Diseases Surveillance System.
535–47. Measles (rubeola): 2013 case definition. Atlanta: CDC;
2. Bellini WJ, Rota JS, Lowe LE, Katz RS, Dyken PR, Zaki 2013 [cited 2016 Sep. 25]. Available from: http://wwwn.
SR, et al. Subacute sclerosing panencephalitis: more cdc.gov/NNDSS/script/casedef.aspx?CondYrID=908&-
cases of this fatal disease are prevented by measles DatePub=1/1/2013.
immunization than was previously recognized. J Infect 7. Perry RT, Halsey NA. The clinical significance of mea-
Dis. 2005 Nov 15;192(10):1686–93. sles: a review. J Infect Dis. 2004 May 1;189 Suppl 1:S4–16.
3. CDC. General recommendations on immunization— 8. Perry RT, Murray JS, Gacic-Dobo M, Dabbagh A,
recommendations of the Advisory Committee on Mulders MN, Strebel PM, et al. Progress toward regional
Immunization Practices (ACIP). MMWR Recomm Rep. measles elimination—worldwide, 2000–2014. MMWR
2011;60(RR-02):1–6 0. Morb Mortal Wkly Rep. 2015 Nov 13;64(44):1246–51.
4. CDC. Prevention of measles, rubella, congenital rubella 9. World Health Organization. Measles [ fact sheet
syndrome, and mumps, 2013: summary recommen- no. 286]. Geneva: World Health Organization; 2014
dations of the Advisory Committee on Immunization [cited 2016 Sep. 25]. Available from: http://www.who.
Practices (ACIP). MMWR Recomm Rep. 2013 Jun int/mediacentre/factsheets/fs286/en.
14;62(RR-0 4):1–34.
MELIOIDOSIS
David D. Blaney, Jay E. Gee
protect against contact with soil and water lacerations, abrasions, or burns that have been
in endemic areas and thoroughly clean skin contaminated with soil or surface water.
BIBLIOGRAPHY
1. Benoit TJ, Blaney DD, Doker TJ, Gee JE, Elrod MG, Rolim of Burkholderia pseudomallei and burden of melioidosis.
DB, et al. A review of melioidosis cases in the Americas. Nat Microbiol. 2016;1:15008.
Am J Trop Med Hyg. 2015 Dec;93(6):1134–9. 5. Limmathurotsakul D, Kanoksil M, Wuthiekanun V,
2. Currie BJ. Melioidosis: evolving concepts in epidemi-
ology, pathogenesis, and treatment. Semin Respir Crit
Care Med. 2015 Feb;36(1):111–25.
Kitphati R, deStavola B, Day NP, et al. Activities of daily
living associated with acquisition of melioidosis in
northeast Thailand: a matched case-control study. PLoS
3
3. Currie BJ, Dance DA, Cheng AC. The global distribu- Negl Trop Dis. 2013;7(2):e2072.
tion of Burkholderia pseudomallei and melioidosis: an 6. O’Sullivan BP, Torres B, Conidi G, Smole S, Gauthier C,
update. Trans R Soc Trop Med Hyg. 2008 Dec;102 Suppl Stauffer KE, et al. Burkholderia pseudomallei infection in
1:S1–4. a child with cystic fibrosis: acquisition in the Western
4. Limmathurotsakul D, Golding N, Dance DA, Messina JP, Hemisphere. Chest. 2011 Jul;140(1):239–42.
Pigott DM, Moyes CL, et al. Predicted global distribution 7. Wiersinga WJ, Currie BJ, Peacock SJ. Melioidosis. N Engl
J Med. 2012 Sep 13;367(11):1035–4 4.
MENINGOCOCCAL DISEASE
Jessica R. MacNeil, Sarah A. Meyer
Diagnosis is generally made by isolating N. men- people who have functional or anatomic asple-
ingitidis from blood or CSF through culture, by nia, or people with HIV. Vaccine, product, num-
detecting meningococcal antigen in CSF by latex ber of doses, and booster dose recommendations
agglutination, or by evidence of N. meningitidis are based on age and risk factor and are described
DNA by PCR. in detail for each risk group in the 2013 ACIP
The signs and symptoms of meningococcal Meningococcal Disease Recommendations (www.
meningitis are similar to those of other causes of cdc.gov/mmwr/preview/mmwrhtml/rr6202a1.
bacterial meningitis, such as Haemophilus influ- htm).
enzae and Streptococcus pneumoniae. The caus- Adolescents and young adults aged 16–23 years
ative organism should be identified so that the may also be vaccinated with a serogroup B menin-
correct antibiotics can be used for treatment and
prophylaxis. Meningococcal disease is nationally
gococcal (MenB) vaccine to provide short-term
protection against most strains of serogroup B
3
notifiable. meningococcal disease. The preferred age for
MenB vaccination is 16 through 18 years. ACIP
TREATMENT also recommends routine use of MenB vaccine for
Meningococcal disease is potentially fatal and people aged ≥10 years who are at increased risk
should always be viewed as a medical emergency. for meningococcal disease, including people who
Antibiotic treatment must be started early in have persistent complement component defi-
the course of the disease, and empirically prior ciency and people who have functional or ana-
to the diagnostic test results. Several antibiotic tomic asplenia.
choices are available, including third-generation
cephalosporins. IMMUNIZATION FOR TRAVELERS
ACIP recommends that travelers who visit or
reside in parts of sub-Saharan Africa known as
PREVENTION the “meningitis belt” (see Map 3-11) during the
Vaccine dry season (December–June) receive vaccina-
Six meningococcal vaccines are licensed in the tion with a quadrivalent (serogroup A, C, W, or Y)
United States. Refer to Table 3-14 for more infor- meningococcal vaccine before travel. The pre-
mation about available meningococcal vaccines. ferred vaccine for people aged 2 months through
Approximately 7–10 days are required after vac- 55 years and meningococcal vaccine-nonnaïve
cination for the development of protective anti- people aged ≥56 years is MenACWY, and MPSV4
body levels. is preferred for meningococcal vaccine- naïve
people aged ≥56 years. Advisories for travelers
ROUTINE IMMUNIZATION to other countries are issued when outbreaks of
The Advisory Committee on Immunization meningococcal disease are recognized (see the
Practices (ACIP) recommends routine admin- CDC Travelers’ Health website at www.cdc.gov/
istration of a quadrivalent meningococcal con- travel).
jugate vaccine (MenACWY) for all people aged For infants aged <9 months, MenACWY-CRM
11–18 years. A single dose of vaccine should be (Menveo) is the only licensed vaccine that pro-
administered at age 11 or 12 years, and a booster tects against serogroups A and W and therefore
dose should be administered at age 16 years. should be used for travelers in this age group. In
Routine immunization with MenACWY is not children initiating vaccination at 2 months of age,
recommended for other age groups in the United MenACWY-CRM should be administered as a 4-
States, with the exception of people at increased dose series at 2, 4, 6, and 12 months of age. In chil-
risk for meningococcal disease. Those at increased dren initiating vaccination at 7–23 months of age,
risk for meningococcal disease include people MenACWY-CRM should be administered as a 2-
who have a persistent complement component dose series, with the second dose administered at
deficiency (C3, C5-9, properdin, factor D, or factor ≥12 months of age and ≥3 months after the first
H or people who are taking eculizumab [Soliris]), dose, although it can be administered as early as
8 weeks after the first dose before travel. For trav- a quadrivalent vaccine should receive a booster
elers initiating vaccination at ≥9 months, either dose: for children who received their last dose
MenACWY- CRM or MenACWY- D (Menactra) at <7 years of age, a booster dose of MenACWY
may be used. For travelers 9–23 months of age should be administered after 3 years and repeated
who receive MenACWY- D, 2 doses should be every 5 years thereafter if they live in or travel to
administered, with the second dose adminis- a hyperendemic areas. For people who received
tered at ≥3 months after the first dose, although it their last dose at ≥7 years of age, a booster dose
can be administered as early as 8 weeks after the should be administered after 5 years and every
first dose before travel. Infants and children who 5 years thereafter if they live in or travel to a
received Hib-MenCY-TT (MenHibrix) are not pro- hyperendemic area.
tected against serogroups A and W and should
receive a quadrivalent vaccine before travel.
A monovalent serogroup A meningococcal
conjugate vaccine (MenAfriVac) has progressively
3
For most people aged 2– 55 years, 1 dose been introduced into meningitis belt countries
of a MenACWY vaccine (MenACWY- CRM or since 2010 through mass vaccination campaigns.
MenACWY- D) is recommended before travel. This vaccine is not available in the United States
Additional dosing instructions for people with for travelers and is not recommended instead of
HIV, asplenia, or persistent complement com- the quadrivalent vaccines (MenACWY or MPSV4)
ponent deficiencies are available in the 2013 for travelers who will be living in meningitis belt
ACIP Meningococcal Disease Recommendations countries as it does not protect against sero-
(www.cdc.gov/ m mwr/ p review/ m mwrhtml/ groups C, W, and Y.
rr6202a1.htm). MenB vaccine is not recommended for peo-
Because MenACWY vaccine is not licensed ple who live in or travel to meningitis belt coun-
for use in adults aged ≥56 years, MPSV4 is recom- tries, as serogroup B disease is extremely rare in
mended for people aged ≥56 years who have never this region. MenB vaccine is not routinely recom-
previously been vaccinated with MenACWY. mended for travel to other regions of the world
However, for people aged ≥56 years who were pre- unless an outbreak of serogroup B disease has
viously vaccinated with MenACWY or for whom been reported. Although MenB vaccine is not
multiple doses are anticipated, MenACWY is pre- licensed in the United States for children <10 years
ferred. Additionally, in the event that MPSV4 is of age. Some European countries have recently
not available, MenACWY may be administered to introduced MenB vaccine as a routine immu-
any person aged ≥56 years. nization for infants. Infants who will be living in
Travelers to the Kingdom of Saudi Arabia these countries may consider MenB vaccination
(KSA) for Umrah or Hajj are required to provide according to the routine infant immunization rec-
documentation of quadrivalent vaccine at least ommendations of that country.
10 days and no more than 3 years before arrival for
polysaccharide vaccine and no more than 8 years VACCINE SAFETY AND ADVERSE REACTIONS
before arrival for conjugate vaccine (see www. Low-grade fevers and local reactions, such as injec-
moh.gov.sa/en/Hajj/Pages/HealthRegulations. tion site pain, arm swelling, and pain that limits
aspx). ACIP recommendations for adult travelers movement of the injected arm, are side effects seen
are to receive a booster dose if it has been ≥5 years after both conjugate and polysaccharide quadri-
since the previous MenACWY dose. Current visa valent meningococcal vaccines but occur more
requirements should be confirmed with the KSA commonly after conjugate vaccine. Symptoms are
embassy. Although the KSA Ministry of Health generally mild to moderate and resolve within 48–
currently advises against travel to Hajj for preg- 72 hours. Severe adverse events, such as high fever,
nant women or children, these groups should chills, joint pain, rash, or seizures are rare (<5% of
receive meningococcal vaccination according to vaccinees) with either type of vaccine.
licensed indications for their age if they travel. Although no clinical trials of meningococ-
International travelers at risk for meningococ- cal vaccines have been conducted in pregnant or
cal disease who were previously vaccinated with lactating women, postlicensure safety data have
BIBLIOGRAPHY
1. American Academy of Pediatrics. Meningococcal infec- epidemiology of meningococcal disease. Vaccine. 2012
tions. In: Kimberlin DW, Brady MT, Jackson M, Long SS, May 30;30 Suppl 2:B26–36.
editors. Red Book: 2015 Report of the Committee 6. MacNeil JR, Rubin L, Folaranmi T, Ortega-Sanchez IR,
on Infectious Diseases. 30th ed. Elk Grove Village, Patel M, Martin SW. Use of serogroup B meningococcal
IL: American Academy of Pediatrics; 2015. pp. 547–58. vaccines in adolescents and young adults: recommen-
2. CDC. Prevention and control of meningococcal dis- dations of the Advisory Committee on Immunization
ease: recommendations of the Advisory Committee on Practices, 2015. MMWR Morb Mortal Wkly Rep. 2015
Immunization Practices (ACIP). MMWR Morb Mortal Oct 23;64(41):1171–6.
Wkly Rep. 2013;62(2):1–28. 7. Rosenstein NE, Perkins BA, Stephens DS, Popovic T,
3. Folaranmi T, Rubin L, Martin SW, Patel M, MacNeil JR. Hughes JM. Meningococcal disease. N Engl J Med. 2001
Use of serogroup B meningococcal vaccines in per- May 3;344(18):1378–88.
sons aged >/=10 years at increased risk for serogroup 8. Stephens DS, Greenwood B, Brandtzaeg P. Epidemic
B meningococcal disease: recommendations of the meningitis, meningococcaemia, and Neisseria meningiti-
Advisory Committee on Immunization Practices, dis. Lancet. 2007 Jun 30;369(9580):2196–210.
2015. MMWR Morb Mortal Wkly Rep. 2015 Jun
9. Wilder-Smith A. Meningococcal disease: risk for inter-
12;64(22):608–12.
national travellers and vaccine strategies. Travel Med
4. Greenwood B. Manson Lecture. Meningococcal Infect Dis. 2008 Jul;6(4):182–6.
meningitis in Africa. Trans R Soc Trop Med Hyg. 1999
10. World Health Organization. Meningitis control in
Jul-Aug;93(4):341–53.
countries of the African meningitis belt, 2015. Wkly
5. Halperin SA, Bettinger JA, Greenwood B, Harrison LH, Epidemiol Rec. 2016 Apr 22;91(16):209–16.
Jelfs J, Ladhani SN, et al. The changing and dynamic
BIBLIOGRAPHY
1. Arabi YM, Arifi AA, Balkhy HH, Najm H, Aldawood syndrome coronavirus infections. N Engl J Med. 2013
AS, Ghabashi A, et al. Clinical course and outcomes of Jun 27;368(26):2487–94.
critically ill patients with Middle East respiratory syn- 4. Oboho IK, Tomczyk SM, Al-Asmari AM, Banjar AA,
drome coronavirus infection. Ann Intern Med. 2014 Mar Al-Mugti H, Aloraini MS, et al. 2014 MERS-CoV outbreak
18;160(6):389–97. in Jeddah—a link to health care facilities. N Engl J Med.
2. CDC. Interim infection prevention and control rec- 2015 Feb 26;372(9):846–54.
ommendations for hospitalized patients with Middle 5. World Health Organization. Coronavirus infections.
East respiratory syndrome coronavirus (MERS-CoV). [cited 2016 Sep. 25]. Available from: http://www.who.
[updated 2015 June; cited 2016 Sep. 25]. Available int/csr/disease/coronavirus_infections/en/.
from: http://www.cdc.gov/coronavirus/mers/infection-
6. Zumla A, Hui DS, Perlman S. Middle East respiratory
prevention-control.html.
syndrome. Lancet. 2015 Sep 5;386(9997):995–1007.
3. Memish ZA, Zumla AI, Al-Hakeem RF, Al-Rabeeah AA,
Stephens GM. Family cluster of Middle East respiratory
MUMPS
Cristina V. Cardemil, Nakia S. Clemmons
swelling of the parotid glands, other salivary evidence of mumps immunity (as documented by
glands, or both, lasting ≥2 days, and without 2 doses of live mumps virus vaccine, laboratory
other apparent cause. Laboratory confirmation evidence of immunity, laboratory confirmation
of mumps involves detection of nucleic acid by of disease, or birth before 1957) should be vacci-
RT-PCR or virus isolation by culture. For further nated with 2 doses of measles-mumps-rubella
information on laboratory testing, see www.cdc. (MMR) vaccine ≥28 days apart. There is no rec-
gov/mumps/lab/index.html. Mumps is a nation- ommendation for vaccination against mumps
ally notifiable disease. for infants aged <12 months before international
travel; however, infants aged 6–11 months should
TREATMENT receive 1 dose of MMR vaccine before departure
Supportive care is the mainstay of treatment. to protect against measles.
3
PREVENTION CDC website: www.cdc.gov/mumps
Before departure from the United States, travel-
ers aged ≥12 months who do not have acceptable
BIBLIOGRAPHY
1. CDC. Manual for the surveillance of vaccine- 4. Dayan GH, Quinlisk MP, Parker AA, Barskey AE,
preventable diseases. Atlanta: CDC; 2012 [cited 2016 Harris ML, Schwartz JM, et al. Recent resurgence of
Sep. 25]. Available from: http://www.cdc.gov/vaccines/ mumps in the United States. N Engl J Med. 2008 Apr
pubs/surv-manual/index.html. 10;358(15):1580–9.
2. CDC. Prevention of measles, rubella, congenital rubella 5. World Health Organization. Immunization, vaccines
syndrome, and mumps, 2013: summary recommen- and biologicals: mumps. 2015 [updated 5 Aug 2015;
dations of the Advisory Committee on Immunization cited 2016 Sep. 25]. Available from: http://www.who.int/
Practices (ACIP). MMWR Recomm Rep. 2013 Jun immunization/monitoring_surveillance/burden/vpd/
14;62(RR-0 4):1–34. surveillance_type/passive/mumps/en/.
3. CDC. Update: mumps outbreak—New York and New
Jersey, June 2009–January 2010. MMWR Morb Mortal
Wkly Rep. 2010 Feb 12;59(5):125–9.
NOROVIRUS
Aron J. Hall, Ben Lopman
NOROVIRUS 269
0
72
a solution of domestic bleach (5–25 tablespoons To help prevent the spread of noroviruses, ill
bleach per gallon of water) may be used. Soiled people may be isolated on cruise ships and in
articles of clothing should be washed at the maxi- institutional settings.
mum available cycle length and machine-dried at
high heat. CDC website: www.cdc.gov/norovirus
BIBLIOGRAPHY
1. Ajami NJ, Kavanagh OV, Ramani S, Crawford SE, Atmar 6. Hall AJ, Lopman BA, Payne DC, Patel MM, Gastanaduy
RL, Jiang ZD, et al. Seroepidemiology of norovirus- PA, Vinje J, et al. Norovirus disease in the United States.
associated travelers’ diarrhea. J Travel Med. 2014
Jan-Feb;21(1):6–11.
Emerg Infect Dis. 2013 Aug;19(8):1198–205.
7. Hall AJ, Vinjé J, Lopman B, Park GW, Yen C, Gregoricus 3
2. Aliabadi N, Lopman BA, Parashar UD, Hall AJ. Progress N, et al. Updated norovirus outbreak management and
toward norovirus vaccines: considerations for further disease prevention guidelines. MMWR Recomm Rep.
development and implementation in potential target 2011 Mar 4;60(RR-3):1–18.
populations. Expert Rev Vaccines. 2015;14(9):1241–53. 8. Koo HL, Ajami NJ, Jiang ZD, Neill FH, Atmar RL,
3. Apelt N, Hartberger C, Campe H, Loscher T. The prev- Ericsson CD, et al. Noroviruses as a cause of diarrhea
alence of norovirus in returning international travelers in travelers to Guatemala, India, and Mexico. J Clin
with diarrhea. BMC Infect Dis. 2010;10:131. Microbiol. 2010 May;48(5):1673–6.
4. Atmar RL, Bernstein DI, Harro CD, Al-Ibrahim MS, Chen 9. Patel MM, Widdowson MA, Glass RI, Akazawa K, Vinje
WH, Ferreira J, et al. Norovirus vaccine against experi- J, Parashar UD. Systematic literature review of role of
mental human Norwalk virus illness. N Engl J Med. 2011 noroviruses in sporadic gastroenteritis. Emerg Infect
Dec 8;365(23):2178–87. Dis. 2008 Aug;14(8):1224–31.
5. Hall AJ, Eisenbart VG, Etingue AL, Gould LH, Lopman 10. Thornley CN, Emslie NA, Sprott TW, Greening GE,
BA, Parashar UD. Epidemiology of foodborne norovirus Rapana JP. Recurring norovirus transmission on an
outbreaks, United States, 2001–2008. Emerg Infect Dis. airplane. Clin Infect Dis. 2011 Sep;53(6):515–20.
2012 Oct;18(10):1566–73.
ONCHOCERCIASIS (RIVER
BLINDNESS)
Paul T. Cantey
travelers are primarily dermatologic (rash and but not the adult worms. Some experts recom-
pruritus) and may occur years after departure mend treating patients with 1 dose of ivermec-
from endemic areas. Nodules are more common tin followed by 6 weeks of doxycycline to kill
in endemic populations. Wolbachia, an endosymbiotic rickettsialike bacte-
rium that appears to be required for the survival
DIAGNOSIS of the O. volvulus adult worm and for embryo-
Presence of microfilariae in superficial skin shav- genesis. Diethylcarbamazine is contraindicated
ings or punch biopsy, adult worms in histologic in onchocerciasis, because it has been associated
sections of excised nodules, or characteristic eye with severe and fatal posttreatment reactions. An
lesions. Serologic testing is most useful for detect- expert in tropical medicine should be consulted
3 ing infection when microfilariae are not identifi-
able. Determination of serum antifilarial antibody
to help manage these patients.
BIBLIOGRAPHY
1. Hoerauf A. Filariasis: new drugs and new opportunities 4. McCarthy JS, Ottesen EA, Nutman TB. Onchocerciasis
for lymphatic filariasis and onchocerciasis. Curr Opin in endemic and nonendemic populations: differences in
Infect Dis. 2008 Dec;21(6):673–81. clinical presentation and immunologic findings. J Infect
2. Klion AD. Filarial infections in travelers and immigrants. Dis. 1994 Sep;170(3):736–41.
Curr Infect Dis Rep. 2008 Mar;10(1):50–7. 5. Tielsch JM, Beeche A. Impact of ivermectin on illness
3. Lipner EM, Law MA, Barnett E, Keystone and disability associated with onchocerciasis. Trop Med
JS, von Sonnenburg F, Loutan L, et al. Int Health. 2004 Apr;9(4):A45–56.
Filariasis in travelers presenting to the 6. WHO Expert Committee. Onchocerciasis and its
GeoSentinel Surveillance Network. PLoS Negl Trop Dis. control. Report of a WHO Expert Committee on
2007;1(3):e88. Onchocerciasis Control. World Health Organ Tech Rep
Ser. 1995;852:1–104.
PERTUSSIS
Tami H. Skoff, Jennifer L. Liang
INFECTIOUS AGENT EPIDEMIOLOGY
Fastidious gram-negative coccobacillus Bordetella Pertussis is endemic worldwide, even in areas
pertussis. with high vaccination rates. In recent years, per-
tussis has resurged in a number of countries with
TRANSMISSION successful vaccination programs, especially coun-
Person-to-
person transmission via aerosolized tries that have transitioned from whole-cell per-
respiratory droplets or by direct contact with tussis vaccine formulations to acellular pertussis
respiratory secretions. preparations, including the United States. In 2012,
>48,000 cases of pertussis were reported nation- is met); serology and direct fluorescent antibody
ally, the largest number in the United States since tests are not confirmatory tests included in the
1955. Disease rates are highest among young chil- current case definition for reporting purposes.
dren in countries where vaccination coverage is Pertussis is a nationally notifiable disease.
low, which is primarily in the developing world.
In developed countries, the reported incidence of TREATMENT
pertussis is highest among infants too young to be Macrolide antibiotics (azithromycin, clarithro-
vaccinated. mycin, and erythromycin) are recommended
Immunity from childhood vaccination and to treat pertussis in people aged ≥1 month; for
natural disease wanes with time; therefore, ado- infants aged <1 month, azithromycin is the pre-
lescents and adults who have not received a
tetanus-diphtheria-pertussis (Tdap) booster vac-
ferred antibiotic. Antimicrobial therapy with a
macrolide antibiotic administered <3 weeks after
3
cination can become infected or reinfected. US cough onset can limit transmission to others.
travelers are not at increased risk for disease spe- Postexposure prophylaxis is recommended for all
cifically because of international travel, but they household contacts of cases and for people at high
are at risk if they come in close contact with risk of developing severe disease (such as infants
infected people. Infants, especially those who are and women in the third trimester of pregnancy) or
too young to be protected by a complete vaccina- those who will have contact with a person at high
tion series, are at highest risk for severe illness and risk of severe illness. The recommended agents
death from pertussis. and dosing regimens for prophylaxis are the same
as for the treatment of pertussis.
CLINICAL PRESENTATION
In classic disease, mild upper respiratory tract
PREVENTION
symptoms begin 7–10 days (range, 6–21 days)
after exposure, followed by a cough that becomes Vaccine
paroxysmal. Coughing paroxysms can vary in fre- Travelers should be up- to-
date with pertussis
quency and are often followed by vomiting. Fever vaccinations before departure. Multiple pertus-
is absent or minimal. The clinical case definition sis vaccines are available in the United States for
for pertussis includes cough for ≥2 weeks with infants and children, and 2 vaccines are availa-
paroxysms, whoop, or posttussive vomiting. ble for adolescents and adults. A complete list-
Disease in infants aged <6 months can be atyp- ing of licensed vaccines can be found at www.
ical, with a short catarrhal stage, gagging, gasp- fda.gov/ B iologicsBloodVaccines/ Vaccines/
ing, or apnea as early manifestations. Among ApprovedProducts/ucm093833.htm.
infants aged <2 months, the case-fatality ratio is
approximately 1%. Recently immunized children INFANTS AND CHILDREN
who develop disease may have mild cough illness; In the United States, all infants and children
older children and adults may have prolonged should receive 5 doses of acellular pertussis vac-
cough with or without paroxysms. The cough cine in combination with diphtheria and tetanus
gradually wanes over several weeks to months. toxoids (DTaP) at ages 2, 4, 6, and 15–18 months
and 4–6 years. An accelerated schedule of doses
DIAGNOSIS may be used to complete the DTaP series.
Factors such as prior vaccination status, stage of Children aged 7–10 years who are not fully vac-
disease, antibiotic use, specimen collection and cinated against pertussis and for whom no con-
transport conditions, and use of nonstandard- traindication to pertussis vaccine exists should
ized tests may affect the sensitivity, specificity, receive a single dose of tetanus toxoid, reduced
and interpretation of available diagnostic tests diphtheria toxoid, and acellular pertussis vaccine
for B. pertussis. CDC guidelines for the laboratory (Tdap) to provide protection against pertussis. If
confirmation of pertussis cases include culture additional doses of tetanus and diphtheria toxoid-
and PCR (when the above clinical case definition containing vaccines are needed, then they should
PERTUSSIS 273
4
72
be vaccinated according to catch-up guidance, previously received Tdap. Adolescents and adults
with Tdap preferred as the first dose (www.cdc. who have never been immunized against pertus-
gov/vaccines/schedules/hcp/imz/catchup.html). sis, tetanus, or diphtheria; who have incomplete
immunization; or whose immunity is uncertain
ADOLESCENTS AND ADULTS should follow the catch-up schedule established
Adolescents aged 11–18 years who have com- for Td/Tdap.
pleted the recommended childhood DTwP/DTaP
vaccination series and who have not previously PREGNANT WOMEN
received Tdap and adults aged ≥19 years who have Women should have a dose of Tdap during each
not previously received Tdap should receive a sin- pregnancy, irrespective of her history of receiving
3 gle dose of Tdap instead of tetanus and diphthe-
ria toxoids (Td) vaccine for booster immunization
Tdap. Although Tdap may be given at any time
during pregnancy, to maximize the maternal anti-
against tetanus, diphtheria, and pertussis. To pro- body response and passive antibody transfer to
vide pertussis protection before travel, Tdap can the infant, optimal timing for Tdap administration
be given regardless of the interval from the last is at 27–36 weeks’ gestation.
Td, except to people for whom pertussis vacci-
nation is contraindicated or for people who have CDC website: www.cdc.gov/pertussis
BIBLIOGRAPHY
1. Acosta AM, DeBolt C, Tasslimi A, Lewis M, Stewart 6. CDC. Updated recommendations for use of tetanus
LK, Misegades LK, et al. Tdap vaccine effectiveness in toxoid, reduced diphtheria toxoid, and acellular per-
adolescents during the 2012 Washington State pertussis tussis vaccine (Tdap) in pregnant women--Advisory
epidemic. Pediatrics. 2015 Jun;135(6):981–9. Committee on Immunization Practices (ACIP), 2012.
2. American Academy of Pediatrics. Pertussis (whooping MMWR Morb Mortal Wkly Rep. 2013;62(7):131–5.
cough). In: Pickering LK, editor. Red Book: 2012 Report 7. Edwards KM, Decker MD. Pertussis vaccines.
of the Committee on Infectious Diseases. 29th ed. Elk In: Plotkin SA, Orenstein WA, Offit PA, editors.
Grove Village, IL: American Academy of Pediatrics; 2012. Vaccines. 6th ed. Philadelphia: Saunders Elsevier;
pp. 553–66. 2012. p. 447–92.
3. Broder KR, Cortese MM, Iskander JK, Kretsinger K, 8. Misegades LK, Winter K, Harriman K, Talarico J,
Slade BA, Brown KH, et al. Preventing tetanus, diph- Messonnier NE, Clark TA, et al. Association of child-
theria, and pertussis among adolescents: use of tet- hood pertussis with receipt of 5 doses of pertussis
anus toxoid, reduced diphtheria toxoid and acellular vaccine by time since last vaccine dose, California, 2010.
pertussis vaccines. Recommendations of the Advisory Jama. 2012 Nov 28;308(20):2126–32.
Committee on Immunization Practices (ACIP). MMWR 9. Tan T, Dalby T, Forsyth K, Halperin SA, Heininger U,
Recomm Rep. 2006 Dec 15;55(RR-17):1–33. Hozbor D, et al. Pertussis across the globe: recent epide-
4. CDC. Pertussis (whooping cough) postexposure anti- miologic trends from 2000 to 2013. Pediatr Infect Dis J.
microbial prophylaxis. [cited 2016 Sep. 25]. Available 2015 Sep;34(9):e222–32.
from: http://www.cdc.gov/pertussis/outbreaks/pep. 10. Tiwari T, Murphy TV, Moran J. Recommended anti-
html. microbial agents for the treatment and postexposure
5. CDC. Updated recommendations for use of tetanus prophylaxis of pertussis: 2005 CDC Guidelines. MMWR
toxoid, reduced diphtheria toxoid and acellular per- Recomm Rep. 2005 Dec 9;54(RR-14):1–16.
tussis (Tdap) vaccine from the Advisory Committee on
Immunization Practices, 2010. MMWR Morb Mortal
Wkly Rep. 2011 Jan 14;60(1):13–5.
PINWORM (ENTEROBIASIS,
OXYURIASIS, THREADWORM)
Christine Dubray
BIBLIOGRAPHY
1. American Academy of Pediatrics. Pinworm infection 2. American Public Health Association. Enterobiasis.
(Enterobius vermicularis). In: Kimberlin DW, editor. In: Heyman DL, editor. Control of Communicable
Red Book: 2015 Report of the Committee on Infectious Diseases Manual. 19th ed. Washington, DC: American
Diseases. 30h ed. Elk Grove Village, IL: American Public Health Association; 2008. pp. 223–5.
Academy of Pediatrics; 2015. pp. 621–2. 3. Kucik CJ, Martin GL, Sortor BV. Common intestinal
parasites. Am Fam Physician. 2004 Mar 1;69(5):1161–8.
BIBLIOGRAPHY
1. Neerinckx S, Bertherat E, Leirs H. Human plague occur- 3. World Health Organization. Human plague: review of
rences in Africa: an overview from 1877 to 2008. Trans R regional morbidity and mortality, 2004–2009. Wkly
Soc Trop Med Hyg. 2010 Feb;104(2):97–103. Epidemiol Rec. 2009 Feb 5;85(6):40–5.
2. Perry RD, Fetherston JD. Yersinia pestis--etiologic agent
of plague. Clin Microbiol Rev. 1997 Jan;10(1):35–66.
PNEUMOCOCCAL DISEASE 3
Fernanda C. Lessa
BIBLIOGRAPHY
1. CDC. Intervals between PCV13 and PPSV23 vaccines: (ACIP). MMWR Morb Mortal Wkly Rep. 2014 Sep
recommendations of the Advisory Committee on 19;63(37):822–5.
Immunization Practices (ACIP). MMWR Morb Mortal 4. CDC. Use of 13-valent pneumococcal conjugate vaccine
Wkly Rep. 2015 Sep 4;64(34):944–7. and 23-valent pneumococcal polysaccharide vaccine
2. CDC. Licensure of a 13-valent pneumococcal conjugate among children aged 6-18 years with immunocompro-
vaccine (PCV13) and recommendations for use among mising conditions: recommendations of the Advisory
children--Advisory Committee on Immunization Committee on Immunization Practices (ACIP). MMWR
Practices (ACIP), 2010. MMWR Morb Mortal Wkly Rep. Morb Mortal Wkly Rep. 2013 June 28, 2013;62(25):521–4.
2010 Mar 12;59(9):258–61. 5. Rudan I, O’Brien KL, Nair H, Liu L, Theodoratou E, Qazi S,
3. CDC. Use of 13-valent pneumococcal conjugate vaccine et al. Epidemiology and etiology of childhood pneumonia
and 23-valent pneumococcal polysaccharide vaccine in 2010: estimates of incidence, severe morbidity, mortal-
among adults aged >/=65 years: recommendations of ity, underlying risk factors and causative pathogens for
the Advisory Committee on Immunization Practices 192 countries. J Glob Health. 2013 Jun;3(1):010401.
POLIOMYELITIS
James P. Alexander, Manisha Patel, Steven G. F. Wassilak
GPEI has built upon the success in the symptomatic, including acute flaccid paralysis of
Americas and made great progress in eradicat- a single limb to quadriplegia, respiratory failure,
ing WPVs, reducing the number of reported polio and rarely, death.
cases worldwide by more than 99% since the mid-
1980s. As of April 2016, WPV circulation has never
been interrupted in only 2 countries: Afghanistan
DIAGNOSIS
The diagnosis is made by identifying poliovirus
and Pakistan. Because of polio eradication efforts,
in clinical specimens (usually stool) obtained
the number of countries where travelers are at
from an acutely ill patient. Poliovirus may be
risk for polio has decreased dramatically. The last
detected by cell culture followed by identifica-
documented case of WPV-associated paralysis in
a US resident traveling abroad occurred in 1986
in a 29-year-old vaccinated adult who had been
tion using plaque reduction neutralization tests
or PCR. Poliovirus may also be identified by direct 3
nucleic acid amplification from stool specimens
traveling in South and Southeast Asia. In 2005, an
followed by genomic sequencing to confirm the
unvaccinated US adult traveling abroad acquired
genotype and determine the likely geographic
VAPP after contact with an infant recently vacci-
origin. Shedding in fecal specimens can be inter-
nated with OPV.
mittent, but usually poliovirus can be detected
In spite of progress made in eradicating WPVs
for up to 4 weeks after onset of illness. During
globally, polio-free countries remain at risk for
the first 3–10 days of the illness, poliovirus can
imported WPV cases and outbreaks, and travelers
also be detected from oropharyngeal specimens.
to some countries are at risk for exposure to WPV.
Poliovirus is rarely detected in the blood or cere-
During 2003–2013, northern Nigeria served as a
brospinal fluid. Polio is a nationally notifiable
reservoir for the spread of WPV into 26 previously
disease.
polio-free countries, many of which were part of
a “WPV importation belt” extending across sub-
Saharan Africa from the west coast to the Horn TREATMENT
of Africa in the east. With the intensification of Only treatment for symptoms is available, rang-
polio eradication activities in Nigeria and neigh- ing from pain and fever relief to intubation and
boring countries during 2012– 2014, outbreaks mechanical ventilation for patients with respira-
were controlled and endemic transmission in tory insufficiency.
Nigeria was interrupted. From 2012 through early
2014, imported WPV from Pakistan was found in
PREVENTION
some sewage samples taken in Egypt, Israel, and
the West Bank and Gaza (without any identified Vaccine
polio cases) and caused outbreaks in Iraq and RECOMMENDATIONS FOR HEALTH
Syria—all of which were controlled by July 2015. PROTECTION
In addition to these risks, travelers are also at risk In the United States, infants and children should
for contracting polio from cases and outbreaks be vaccinated against polio as part of a routine
of vaccine-derived poliovirus (VDPV), which can immunization series (see Infants and Children
develop and circulate in areas with low vaccina- below). Polio vaccination is recommended for all
tion coverage where OPV is used. travelers to countries with WPV or VDPV circu-
For additional information on the status of polio lation. Countries are considered to have WPV or
eradication efforts, countries or areas with active VDPV circulation if they have evidence during
WPV or VDPV circulation, and vaccine recom- the previous 12 months of ongoing endemic cir-
mendations, consult the travel notices on the CDC culation (WPV only), a polio outbreak, or environ-
Travelers’ Health website (www.cdc.gov/travel) or mental evidence (through sewage sampling) of
the GPEI website (www.polioeradication.org). WPV or VDPV circulation. For additional infor-
mation on countries with WPV or VDPV circu-
CLINICAL PRESENTATION lation and vaccine recommendations, consult
Clinical manifestations of poliovirus infection the travel notices on the CDC Travelers’ Health
range from asymptomatic (most infections) to website (www.cdc.gov/ travel) or the weekly
POLIOMYELITIS 279
8
02
update of reported WPV and VDPV cases at residents departing from countries with VDPV
the GPEI website (www.polioeradication.org/ transmission (“infected with VDPV”). Clinicians
Dataandmonitoring/Poliothisweek.aspx). should be aware that long- term travelers and
Before traveling to areas that have WPV or residents may be required to show proof of polio
VDPV circulation, travelers should ensure that vaccination when departing from these coun-
they have completed the recommended age- tries. All polio vaccination administration should
appropriate polio vaccine series and that adults be documented on an International Certificate
have received a single lifetime IPV booster dose. In of Vaccination or Prophylaxis (ICVP). The polio
addition, CDC recommends a single lifetime IPV vaccine must be received between 4 weeks and
booster dose for certain adult travelers to some 12 months before the date of departure from the
3 countries that border areas with WPV circulation.
These recommendations are based on evidence of
polio-affected country. Country requirements may
change, so clinicians should check for updates
historical cross-border transmission. These rec- on the CDC Travelers’ Health website. Refer to
ommendations apply only to travelers with a high the Clinical Update: Interim CDC Guidance for
risk of exposure to someone with imported WPV Travel to and from Countries Affected by the New
infection. These travelers would include those Polio Vaccine Requirements (wwwnc.cdc.gov/
working in health care settings, refugee camps, or travel/n ews-announcements/p olio-guidance-
other humanitarian aid settings. Since the situa- new-requirements) for a list of affected countries,
tion is dynamic, refer to the CDC Travelers’ Health guidance on meeting the vaccination require-
website destination pages for the most up-to-date ments, and instructions on how to order and fill
polio vaccine recommendations (wwwnc.cdc. out the ICVP.
gov/travel/destinations/list).
To eliminate the risk for VAPP, IPV has been the INFANTS AND CHILDREN
only polio vaccine available in the United States In the United States, all infants and children
since 2000; however, OPV continues to be used in should receive 4 doses of IPV at ages 2, 4, and 6–
many countries and for global polio eradication 18 months and 4–6 years. The final dose should
activities. For complete information on recom- be administered at age ≥4 years, regardless of the
mendations for poliomyelitis vaccination, con- number of previous doses, and should be given
sult the Advisory Committee on Immunization ≥6 months after the previous dose. A fourth dose
Practices recommendations website (www.cdc. in the routine IPV series is not necessary if the
gov/vaccines/hcp/acip-recs/vacc-specific/polio. third dose was administered at age ≥4 years and
html) and the World Health Organization position ≥6 months after the previous dose. If the routine
paper on poliovirus vaccines (www.who.int/wer/ series cannot be administered within the recom-
2016/wer9112/en). mended intervals before protection is needed, the
following alternatives are recommended:
COUNTRY REQUIREMENTS
• The first dose should be given to infants at age
In May 2014, the World Health Organization ≥6 weeks.
(WHO) declared the international spread of polio
to be a public health emergency of international • The second and third doses should
concern under the authority of the International be administered ≥4 weeks after the
Health Regulations (2005). To prevent further previous doses.
spread of disease, WHO issued temporary polio • The minimum interval between the third and
vaccine recommendations for long-term travel- fourth doses is 6 months.
ers (staying >4 weeks) and residents departing
from countries with WPV transmission (“export- If the age-appropriate series is not completed
ing WPV” or “infected with WPV”). In November before departure, the remaining IPV doses to com-
2015, these recommendations were extended plete a full series should be administered when
to long-term travelers (staying >4 weeks) and feasible, at the intervals recommended above.
POLIOMYELITIS 281
8
2
primary immunodeficiency diseases should not be situation no longer occurs in the United States
given OPV and should avoid contact with excreted unless a child receives OPV overseas.
OPV virus (such as exposure to a child vaccinated
with OPV in the previous 6 weeks); however, this CDC website: www.cdc.gov/polio
BIBLIOGRAPHY
1. CDC. Immunization schedules. Atlanta: CDC; 2016 Immunization Practices (ACIP). MMWR Recomm Rep.
[cited 2016 Sep. 25]. Available from: http://www.cdc. 2000 May 9;49(RR-5):1–22.
gov/vaccines/schedules/index.html. 7. Sutter RW, Kew OM, Cochi SL, Aylward RB. Poliovirus
next decade due to major could be eradicated any- The World Health
programmatic challenges where. However, in the Assembly declaration
including conflict, political 3 remaining countries of polio eradication as a
instability, hard-to-reach where endemic wild polio- public health emergency
populations, and poor virus transmission had in 2012 initiated a new era
infrastructure. Determined never been interrupted— in which emergency oper-
3 programmatic innovation
was needed to overcome
Nigeria, Pakistan, and
Afghanistan—case counts
ations were established in
GPEI partner agencies and
these challenges. In India, were increasing, and polio- at national and subnational
for example, a series of virus importations from levels in the last remaining
operational innovations the polio-endemic coun- polio-endemic countries
were developed and tries caused multiple out- of Nigeria, Pakistan, and
implemented to improve breaks in many countries Afghanistan to complete
vaccination service deliv- that had previously been eradication. Substantial
ery and reach chronically polio free. In October 2011, progress has been
undervaccinated groups— GPEI’s independent moni- achieved with the renewed
groups that were often toring board issued a crit- efforts. WPV type 3 was
outside the reach of the ical report, stating bluntly last detected in 2012, and
formal health care delivery that the program was polio-free certification in
system. In addition, vaccine “not on track to interrupt the Southeast Asia Region
innovations were brought to poliovirus transmission” was announced in 2014.
fruition, most importantly and that “polio eradication Four WPV cases were
the division of OPV into needs to be treated as a reported in Nigeria in
monovalent components global health emergency” August 2016; these are the
(mOPV1 and mOPV3) for if the ultimate goal of first cases reported in the
the first time since they the program was ever to country since July 2014.
had been combined into be achieved. This report No WPV cases have been
the trivalent vaccine in the led to the World Health detected elsewhere in
1960s. These monovalent Assembly declaring global Africa since August 2014.
vaccines and, later on, polio eradication “a pro- As of September 14, 2016,
the bivalent (types 1 and grammatic emergency Afghanistan, Pakistan, and
3) vaccine greatly increased for global public health” Nigeria were the last three
immunogenicity, because in 2012. In addition, the countries with endemic
interference by the World Health Organization WPV type 1 transmis-
more robust type 2 compo- declared the international sion, and 26 cases had
nent was removed. spread of WPV to previ- been reported worldwide
By 2011, the GPEI ously polio-free countries in 2016.
was at a crossroads. to be “a public health In May 2013, the 66th
The last WPV case in emergency of international World Health Assembly
India was reported in concern” in 2014, trigger- endorsed the Polio
early 2011. This success ing oversight by an emer- Eradication and Endgame
answered the question of gency committee under Strategic Plan 2013–2018.
feasibility—if polio could the International Health This plan provides a time-
be eradicated in India, it Regulations. line for completion of polio
3
inal strain contained in after polio eradication [cited 2016 Sep. 25].
Available from: http://
OPV, which can emerge is certified, so that polio
www.polioeradication.
in locations where child- eradication assets in high org/Portals/0/Document/
hood vaccination coverage priority countries can be Aboutus/Governance/
is low. To prevent type 2 leveraged and transitioned IMB/4IMBMeeting/
VDPV emergence, which to improve global health as IMBReportOctober2011.pdf.
accounted for 79% of the part of polio eradication’s 6. Jenkins HE, Aylward RB,
Gasasira A, Donnelly CA,
circulating VDPVs in 2014– legacy.
Abanida EA, Koleosho-
2015, a coordinated global Adelekan T, et al. Effectiveness
switch in all countries from BIBLIOGRAPHY of immunization against
use of trivalent (types 1, 2 paralytic poliomyelitis in
1. Dowdle WR, Cochi SL. Nigeria. N Engl J Med. 2008
and 3) OPV to bivalent OPV
Global eradication of polio- Oct 16;359(16):1666–74.
(types 1 and 3) was imple- virus: history and rationale.
mented in April 2016. To 7. Snider CJ, Diop OM, Burns
In: Selmer BL, Wimmer E,
CC, Tangermann RH,
mitigate risks by increas- editors. Molecular Biology of
Wassilak SG. Surveillance
ing population immunity Picornaviruses. Washington,
systems to track progress
DC: ASM Press; 2002. pp.
to poliovirus type 2, inac- toward polio eradication—
473–80.
tivated poliovirus vaccine worldwide, 2014–2015.
2. el-Sayed N, el-Gamal Y, MMWR Morb Mortal Wkly
(IPV) is being introduced
Abbassy AA, Seoud I, Rep. 2016 Apr 8;65(13):346–51.
in all countries where it Salama M, Kandeel A, et al.
has not been in use. The 8. Sutter RW, John TJ, Jain H,
Monovalent type 1 oral polio-
Agarkhedkar S, Ramanan
plan also has an objective virus vaccine in newborns.
PV, Verma H, et al.
to contain poliovirus and N Engl J Med. 2008 Oct
Immunogenicity of bivalent
16;359(16):1655–65.
certify interruption of types 1 and 3 oral poliovirus
poliovirus transmission. In 3. Global Polio Eradication vaccine: a randomised, double-
Initiative. Polio eradication blind, controlled trial. Lancet.
order to contain poliovirus, and endgame strategic plan, 2010 Nov 13;376(9753):1682–8.
laboratories with samples 2013–2018. Geneva: World
9. World Health Organization.
containing poliovirus will Health Organization; 2013
List of innovations in the
need to destroy or consoli- [cited 2016 Sep. 25]. Available
India Polio Eradication
date and safely store those from: http://www.polioerad-
Program. 2013 [cited 2016
ication.org/resourcelibrary/
samples. Requirements strategyandwork.aspx.
Sep. 25]. Available from:
for certifying a WHO region http://www.polioeradication.
4. Hagan JE, Wassilak SG, org/Portals/0/Document/
as free of WPV include Craig AS, Tangermann Resources/StrategyWork/
the absence of any WPV RH, Diop OM, Burns CC, EAP/EAP_annex1.pdf.
Q FEVER
Gilbert J. Kersh
3 TRANSMISSION
Most commonly through inhalation of aerosols
DIAGNOSIS
Serologic evidence of a 4-fold rise in phase II IgG
or dust contaminated with dried birth fluids or by indirect fluorescent antibody test between
excreta from infected animals (usually cattle, paired sera taken 3–4 weeks apart is the gold stan-
sheep, or goats). C. burnetii is highly infectious dard for diagnosis of acute infection. A single high
and persists in the environment. Infections via serum phase II IgG titer (>1:128) in conjunction
ingestion of contaminated, unpasteurized dairy with clinical evidence of infection may be con-
products and human-to-human transmission via sidered evidence of probable Q fever. PCR assays
sexual contact have been rarely reported. may be used on whole blood or serum samples
in the early stages of illness and before initiation
EPIDEMIOLOGY of antibiotic therapy. C. burnetii may be detected
Distributed worldwide; the prevalence is highest in infected tissues by using immunohistochem-
in African and Middle Eastern countries. Reported ical staining or DNA detection methods or by
rates of human infection are higher in France and direct isolation of the agent via culture. Q fever is
Australia than in the United States. The largest a nationally notifiable disease.
known Q fever outbreak reported to date involved
approximately 4,000 human cases and occurred TREATMENT
during 2007–2010 in the Netherlands. Travelers Doxycycline is the treatment of choice for acute
who visit rural areas or farms with cattle, sheep, Q fever. Pregnant women, children aged <8 years
goats, or other livestock may be exposed to Q with mild illness, and patients allergic to doxy-
fever. Occupational exposure to infected animals cycline may be treated with alternative antibi-
(such as in farmers, veterinarians, butchers, meat otics such as trimethoprim- sulfamethoxazole.
packers, and seasonal or migrant farm workers), Treatment for acute Q fever is not recommended
particularly during parturition, poses a high risk for asymptomatic people or for those whose
for disease transmission. symptoms have resolved. Chronic C. burnetii
infections require long-term combination therapy
CLINICAL PRESENTATION with agents such as doxycycline, hydroxychloro-
It is estimated that more than half of acute infec- quine, trimethoprim- sulfamethoxazole, fluoro-
tions are mild or asymptomatic. Incubation quinolones, and rifampin.
period is typically 2–3 weeks but may be shorter
after exposure to large numbers of organisms. The PREVENTION
most common presentation of acute infection is Avoid areas where potentially infected animals
a self-limiting influenzalike illness, with pneumo- are kept, and avoid consumption of unpasteur-
nia or hepatitis in more severe acute infections. ized dairy products. A human vaccine for Q fever
Chronic infections occur primarily in patients has been developed and used in Australia, but it is
with preexisting cardiac valvulopathies, vascular not available in the United States.
abnormalities, or immunosuppression. Women
infected during pregnancy are at risk for adverse CDC website: www.cdc.gov/qfever
BIBLIOGRAPHY
1. Anderson A, Bijlmer H, Fournier PE, Graves S, Hartzell J, 5. Kobbe R, Kramme S, Gocht A, Werner M, Lippert U,
Kersh GJ, et al. Diagnosis and management of Q fever— May J, et al. Travel-associated Coxiella burnetii infec-
United States, 2013: recommendations from CDC and tions: three cases of Q fever with different clinical mani-
the Q Fever Working Group. MMWR Recomm Rep. 2013 festation. Travel Med Infect Dis. 2007 Nov;5(6):374–9.
Mar 29;62(RR-03):1–30. 6. Million M, Thuny F, Richet H, Raoult D. Long-term out-
2. Cohen NJ, Papernik M, Singleton J, Segreti J, Eremeeva come of Q fever endocarditis: a 26-year personal survey.
ME. Q fever in an American tourist returned from Lancet Infect Dis. 2010 Aug;10(8):527–35.
Australia. Travel Med Infect Dis. 2007 May;5(3):194–5. 7. Roest HI, Tilburg JJ, van der Hoek W, Vellema P, van
3. Delord M, Socolovschi C, Parola P. Rickettsioses and Q Zijderveld FG, Klaassen CH, et al. The Q fever epidemic
3
fever in travelers (2004–2013). Travel Med Infect Dis. in The Netherlands: history, onset, response and reflec-
2014 Sep-Oct;12(5):443–58. tion. Epidemiol Infect. 2011 Jan;139(1):1–12.
4. Jensenius M, Davis X, von Sonnenburg F, Schwartz E, 8. Ta TH, Jimenez B, Navarro M, Meije Y, Gonzalez FJ,
Keystone JS, Leder K, et al. Multicenter GeoSentinel Lopez-Velez R. Q Fever in returned febrile travelers. J
analysis of rickettsial diseases in international Travel Med. 2008 Mar-Apr;15(2):126–9.
travelers, 1996–2 008. Emerg Infect Dis. 2009
Nov;15(11):1791–8.
RABIES
Brett W. Petersen, Ryan M. Wallace, David R. Shlim
RABIES 287
82
rabies virus variants based on the reservoir spe- death. Once clinical signs manifest, patients die
cies in which they circulate. Regionally, different quickly in the absence of intensive supportive care.
viral variants are adapted to various mammalian
hosts and perpetuate in dogs and wildlife, such DIAGNOSIS
as bats, foxes, jackals, mongooses, raccoons, and The diagnosis may be relatively simple in a patient
skunks. Canine rabies remains enzootic in many with a compatible history and a classic clinical
areas of the world, including Africa, Asia, and presentation (Box 3-4). However, clinical suspi-
parts of Central and South America. cion and prioritization of differential diagnoses
Timely and specific information about the may be complicated by variations in clinical pre-
global occurrence of rabies is often difficult to sentation and a lack of exposure history. The
3 find. Surveillance levels vary, and reporting status
can change suddenly as a result of disease rein-
exposure history is difficult to elicit if the risk of
exposure to rabies was not recognized, the expo-
troduction or emergence. The rate of rabies expo- sure was not discussed with friends and family,
sures in travelers is at best an estimate and may and several weeks to months have elapsed since
range from 16 to 200 per 100,000 travelers. the exposure.
Definitive antemortem diagnosis requires
CLINICAL PRESENTATION high-complexity experimental test methods on
Clinical illness in humans begins following inva- multiple samples (such as serum, cerebrospi-
sion of the peripheral and then central nervous nal fluid [CSF], saliva, and skin biopsy from the
system and culminates in acute fatal encephali- nape of the neck), which can be collected sequen-
tis. After infection the asymptomatic incubation tially if initial testing is negative and clinical sus-
period is variable, but signs and symptoms most picion is high. Additional detailed information
commonly develop within several weeks to several on diagnostic testing may be obtained from CDC
months after exposure. Pain and paresthesia at the (www.cdc.gov/rabies/specific_groups/doctors/
site of exposure are often the first symptoms of ante_mortem.html). Rising levels of rabies virus–
disease. The disease then progresses rapidly from neutralizing antibodies, particularly in the CSF,
a nonspecific, prodromal phase with fever and is diagnostic in an unvaccinated, encephalitic
vague symptoms to an acute, progressive enceph- patient. Rabies is a nationally notifiable disease.
alitis. The neurologic phase may be characterized
by anxiety, paresis, paralysis, and other signs of TREATMENT
encephalitis; spasms of swallowing muscles can There is not yet an evidence-based “best prac-
be stimulated by the sight, sound, or perception tices” medical approach to treating patients
of water (hydrophobia); and delirium and convul- with rabies; most patients are managed with
sions can develop, followed rapidly by coma and symptomatic and palliative supportive care. An
experimental approach, known as the Milwaukee tiny teeth, and wounds may not be readily appar-
protocol, involves inducing coma and treating ent. Any suspected or documented bite or wound
with antiviral drugs, but it remains controversial. from a bat should be grounds for seeking PEP.
Rabies is still considered universally fatal for prac- Children are at higher risk for rabies exposure
tical purposes, and preventive measures are the and subsequent illness because of their inquisi-
only way to optimize survival after a bite from a tive nature and inability to read behavioral cues
rabid animal. from dogs and other animals. The smaller stature
of children makes them more likely to experience
PREVENTION severe bites to high-risk areas, such as the face
Rabies in travelers is best prevented by having a and head. Also contributing to the higher risk is
comprehensive strategy. This consists of (1) edu-
cation about risks and the need to avoid bites
their attraction to animals and the possibility that
they may not report an exposure.
3
from mammals, especially high-risk rabies reser-
voir species; (2) consultation with travel health Preexposure Vaccination
professionals to determine if preexposure vacci- Preexposure rabies vaccination may be recom-
nation is recommended; (3) knowing how to pre- mended for certain international travelers based
vent rabies after a bite; and (4) knowing how to on the occurrence of animal rabies in the coun-
obtain postexposure prophylaxis (PEP). The last try of destination; the availability of antirabies
may involve urgent importation of rabies biolog- biologics; the intended activities of the traveler,
ics or international travel to where PEP is avail- especially in remote areas; and the traveler’s dura-
able. Travelers who have died of rabies either did tion of stay. A decision to receive preexposure
not seek PEP or received inadequate care when rabies immunization may also be based on the
they did. likelihood of repeat travel to at-risk destinations
or long-term travel to a high- risk destination.
Avoiding Animal Bites Preexposure vaccination may be recommended
Travelers to rabies-enzootic countries should be for veterinarians, animal handlers, field biologists,
warned about the risk of rabies exposure and edu- cavers, missionaries, and certain laboratory work-
cated as to how to avoid animal bites. Travelers ers. Table 3-15 provides criteria for preexposure
should avoid free-roaming mammals, avoid pro- vaccination. Regardless of whether preexposure
voking domestic animals, and avoid contact with vaccine is administered, travelers going to areas
bats and other wildlife. Although nonhuman pri- where the risk of rabies is high should be encour-
mates are rarely rabid, they are a common source aged to purchase medical evacuation insurance
of bites, mainly on the Indian subcontinent. In (see Chapter 2, Travel Insurance, Travel Health
most instances these nonhuman primates can- Insurance, & Medical Evacuation Insurance).
not be followed up for rabies assessments, and In the United States, preexposure vaccination
the bite victims are recommended to receive PEP. consists of a series of 3 intramuscular injections
Awareness of this risk and simple prevention is given on days 0, 7, and 21 or 28 in the deltoid with
particularly effective. Travelers should be advised human diploid cell rabies vaccine (HDCV) or puri-
to not approach or otherwise interact with mon- fied chick embryo cell (PCEC) vaccine (Table 3-16).
keys or carry food while monkeys are near, espe- Travelers should receive all 3 preexposure immu-
cially around monkeys that are habituated to nizations before travel. If 3 doses of rabies vaccine
tourists. Travelers should be educated to not han- cannot be completed before travel, the traveler
dle bats or other wildlife and consider the need should not start the series, as few data exist to
for personal protective equipment before enter- guide PEP after a partial immunization series.
ing caves where bats may be found, given the Preexposure vaccination does not eliminate
risk for exposures to rabies virus, histoplasmo- the need for additional medical attention after a
sis, Marburg virus (see Ebola Virus Disease and rabies exposure, but it simplifies PEP. Preexposure
Marburg Virus Disease section this chapter), or vaccination may also provide some protection
other bat-associated pathogens. Many bats have when an exposure to rabies virus is unrecognized
RABIES 289
0
92
Infrequent (greater Exposure nearly always Veterinarians and animal Primary course; no
than general episodic with source control staff working with serologic testing or booster
population) recognized terrestrial carnivores vaccination
Bite or nonbite exposure in areas where rabies
is uncommon to rare;
veterinary students; and
travelers visiting areas
where rabies is enzootic
and immediate access to
medical care, including
biologics, is limited
1
Judgment of relative risk and extra monitoring of vaccination status of laboratory workers are the responsibility of the
laboratory supervisor (see www.cdc.gov/biosafety/publications/bmbl5 for more information).
2
Preexposure booster immunization consists of 1 dose of human diploid cell (rabies) vaccine or purified chick
embryo cell vaccine, 1.0-mL dose, intramuscular (deltoid area). Per Advisory Committee on Immunization Practices
recommendations, minimum acceptable antibody level is complete virus neutralization at a 1:5 serum dilution by
the rapid fluorescent focus inhibition test, which is equivalent to approximately 0.1 IU/mL. A booster dose should be
administered if titer falls below this level in populations that remain at risk.
Abbreviations: HDCV, human diploid cell vaccine; IM, intramuscular; PCEC, purified chick embryo cell.
1
Patients who are immunosuppressed by disease or medications should postpone preexposure
vaccinations and consider avoiding activities for which rabies preexposure prophylaxis is indicated
during the period of expected immunosuppression. If this is not possible, immunosuppressed people
who are at risk for rabies should have their antibody titers checked after vaccination.
2
Every attempt should be made to adhere to recommended schedules; however, for most minor
3
deviations (delays of a few days for individual doses), vaccination can be resumed as though the
traveler were on schedule. If 3 doses of rabies vaccine cannot be completed before travel, the traveler
should not start the series, as few data exist to guide PEP after a partial immunization series.
wounds that might require suturing should have remaining dose should be administered intra-
the suturing delayed for a few days. If suturing is muscularly at a site distant from the site of vac-
necessary to control bleeding or for functional or cine administration. If the wounds are extensive,
cosmetic reasons, rabies immune globulin (RIG) the dose-appropriate volume of RIG must not be
should be injected into all wounded tissues before exceeded. If the volume is inadequate to inject all
suturing. The use of local anesthetic is not contra- the wounds, the RIG may be diluted with normal
indicated in wound management. saline to ensure sufficient volume to inject in all of
the wounds. This is a particular issue in children
Postexposure Prophylaxis whose body weight may be small in relation to the
IN TRAVELERS WHO RECEIVED size and number of wounds.
PREEXPOSURE VACCINATION RIG is difficult to access in many countries. If
PEP for someone previously vaccinated consists modern cell culture vaccine is available but access
of 2 doses of modern cell culture vaccine given on to RIG is delayed, the vaccine series should be
days 0 and 3 after the exposure. The booster doses started as soon as possible, and RIG may be added
do not have to be the same brand as the one in the to the regimen up to and including day 7. After
original preexposure immunization series. day 7, RIG is unlikely to provide benefit, as anti-
bodies would be expected to be present from the
IN TRAVELERS WHO DID NOT RECEIVE patient’s own vaccine-derived immune response.
PREEXPOSURE VACCINATION Because rabies virus can persist in tissue for
PEP for an unvaccinated patient consists of a long time before invading a peripheral nerve,
administration of RIG (20 IU/kg for human RIG a traveler who has sustained a bite that is suspi-
and 40 IU/kg for equine RIG) and a series of 4 cious for rabies should receive full PEP, includ-
injections of rabies vaccine over 14 days, or 5 ing RIG, even if a considerable length of time
doses over a 1- month period in immunosup- has passed since the initial exposure. If there is
pressed patients (Table 3-17). After wound cleans- a scar, or the patient remembers where the bite
ing, as much of the dose-appropriate volume of occurred, an appropriate amount of RIG should
RIG (Table 3-17) as is anatomically feasible should be injected in that area.
be injected at the wound site. The intent is to put Human RIG is manufactured by plasmapher-
the RIG in the areas where saliva may have con- esis of blood from hyperimmunized volunteers.
taminated wounded tissue. If the wound is small The total quantity of commercially produced
and on a distal extremity such as a finger or toe, human RIG falls short of worldwide demand, and
the health care provider must use clinical judg- it is not available in many developing countries.
ment to decide how much RIG to inject to avoid Equine RIG or purified fractions of equine RIG
local tissue compression and complications. Any may be available in some developing countries
RABIES 291
29
Abbreviations: RIG, rabies immune globulin; IM, intramuscular; HDCV, human diploid cell vaccine; PCEC, purified chick
embryo cell.
1
All postexposure prophylaxis should begin with immediate, thorough cleansing of all wounds with soap and water,
povidone iodine, or other substances with virucidal activity.
2
Every attempt should be made to adhere to recommended schedules; however, for most minor deviations (delays of a
few days for individual doses), vaccination can be resumed as though the traveler were on schedule. When substantial
deviations occur, immune status should be assessed by serologic testing 7–14 days after the final dose is administered.
3
Five vaccine doses for the immunosuppressed patient. The first 4 vaccine doses are given on the same schedule as
for an immunocompetent patient, and the fifth dose is given on day 28; patient follow-up should include monitoring
antibody response. See www.cdc.gov/mmwr/preview/mmwrhtml/rr5902a1.htm for more information.
4
CDC recommends 4 postexposure vaccine doses, on days 0, 3, 7, and 14, unless the patient is immunocompromised in
some way, in which case a fifth dose is given at day 28.
5
Preexposure immunization with HDCV or PCEC, prior postexposure prophylaxis with HDCV or PCEC, or people
previously vaccinated with any other type of rabies vaccine and a documented history of positive rabies virus
neutralizing antibody response to the prior vaccination.
6
RIG is not recommended.
where human RIG might not be available. Such antibody titers. Assistance in managing compli-
products are preferable to no RIG. cated PEP scenarios can be obtained from expe-
The incidence of adverse events after the use rienced travel medicine professionals, health
of modern equine- derived RIG is low (0.8%– departments, and CDC.
6.0%), and most reactions are minor. However, Rabies vaccine was once manufactured from
such products are not regulated by the Food and viruses grown in animal brains, and some of these
Drug Administration, and their use cannot be rec- vaccines are still in use in developing countries.
ommended unequivocally. In addition, unpuri- Typically, the brain-derived vaccines, also known
fied antirabies serum of equine origin might still as nerve tissue vaccines, can be identified if the
be used in some countries where neither human traveler is offered a large-volume injection (5 mL)
nor equine RIG is available. The use of this antira- daily for approximately 14–21 days. Because of
bies serum is associated with higher rates of seri- variability of potency in these preparations, which
ous adverse reactions, including anaphylaxis and may limit effectiveness, and the risk of adverse
serum sickness. reactions, the traveler should not accept these
Different PEP schedules, alternative routes of vaccines but travel to a location where acceptable
administration, and other rabies vaccines besides vaccines and RIG are available.
HDCV and PCEC may be used abroad. For exam-
ple, commercially available purified Vero cell Rabies Vaccine
rabies vaccine and purified duck embryo cell VACCINE SAFETY AND ADVERSE REACTIONS
vaccine are acceptable alternatives if available. Travelers should be advised that they may expe-
However, other rabies vaccines or PEP regimens rience local reactions after vaccination such as
might require additional prophylaxis or con- pain, erythema, swelling, or itching at the injection
firmation of adequate rabies virus neutralizing site, or mild systemic reactions such as headache,
nausea, abdominal pain, muscle aches, and diz- consider switching to the alternative vaccine for
ziness. Approximately 6% of people receiving the remainder of the series.
booster vaccinations with HDCV may experience
systemic hypersensitivity reactions character- PRECAUTIONS AND CONTRAINDICATIONS
ized by urticaria, pruritus, and malaise. The like- Pregnancy is not a contraindication to PEP. In
lihood of these reactions may be less with PCEC. infants and children, the dose of HDCV or PCEC
Once initiated, rabies PEP should not be inter- for preexposure or PEP is the same as that rec-
rupted or discontinued because of local or mild ommended for adults. The dose of RIG for PEP is
systemic reactions to rabies vaccine. If an adverse based on body weight (Table 3-17).
event occurs with one of the vaccine types,
CDC website: www.cdc.gov/rabies
3
BIBLIOGRAPHY
1. Gautret P, Parola P. Rabies vaccination for international 6. Rupprecht CE, Gibbons RV. Clinical practice.
travelers. Vaccine. 2012 Jan 5;30(2):126–33. Prophylaxis against rabies. N Engl J Med. 2004 Dec
2. Gautret P, Tantawichien T, Vu Hai V, Piyaphanee W. 16;351(25):2626–35.
Determinants of pre-exposure rabies vaccination 7. Smith A, Petrovic M, Solomon T, Fooks A. Death from
among foreign backpackers in Bangkok, Thailand. rabies in a UK traveller returning from India. Euro
Vaccine. 2011 May 23;29(23):3931–4. Surveill. 2005 Jul;10(30):E050728 5.
3. Malerczyk C, Detora L, Gniel D. Imported human rabies 8. van Thiel PP, de Bie RM, Eftimov F, Tepaske R, Zaaijer
cases in Europe, the United States, and Japan, 1990 to HL, van Doornum GJ, et al. Fatal human rabies due to
2010. J Travel Med. 2011 Nov-Dec;18(6):402–7. Duvenhage virus from a bat in Kenya: failure of treat-
4. Mills DJ, Lau CL, Weinstein P. Animal bites and rabies ment with coma-induction, ketamine, and antiviral
exposure in Australian travellers. Med J Aust. 2011 Dec drugs. PLoS Negl Trop Dis. 2009;3(7):e428.
19;195(11-12):673–5. 9. Warrell MJ, Warrell DA. Rabies and other lyssavirus
5. Rupprecht CE, Briggs D, Brown CM, Franka R, Katz SL, diseases. Lancet. 2004 Mar 20;363(9413):959–69.
Kerr HD, et al. Use of a reduced (4-dose) vaccine sched- 10. World Health Organization. WHO expert consul-
ule for postexposure prophylaxis to prevent human tation on rabies. World Health Organ Tech Rep Ser.
rabies: recommendations of the Advisory Committee 2005;931:1–88.
on Immunization Practices. MMWR Recomm Rep. 2010
Mar 19;59(RR-2):1–9.
RABIES 293
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…perspectives
INTRADERMAL RABIES
PREEXPOSURE IMMUNIZATION
David R. Shlim
(continued)
*Perspectives sections are written as editorial discussions aiming to add depth and clinical perspective to the official
recommendations contained in the book. The views and opinions expressed in this section are those of the author and do
not necessarily represent the official position of CDC.
3
INFECTIOUS AGENTS occur throughout the year. Because of the 5-to
Rickettsial infections are caused by various 14-day incubation period for most rickettsial dis-
bacterial species from the genera Rickettsia, eases, tourists often do not experience symptoms
Orientia, Ehrlichia, Neorickettsia, Neoehrlichia, and during their trip, and disease onset may coincide
Anaplasma (Table 3-18). Rickettsia spp. are classi- with their return home or develop within a week
cally divided into the typhus group and spotted after returning. Although the most commonly
fever group (SFG). Orientia spp. make up the scrub diagnosed rickettsial diseases in travelers are usu-
typhus group. The rickettsial pathogens most ally in the spotted fever or typhus groups, trav-
likely to be encountered during travel outside the elers may acquire a wide range of rickettsioses,
United States include R. africae (African tick-bite including emerging and newly recognized species
fever), R. conorii (Mediterranean spotted fever), (Table 3-18).
R. rickettsii (known as both Rocky Mountain spot- Tickborne spotted fever rickettsioses are the
ted fever and Brazilian spotted fever), O. tsut- most frequently reported travel-associated rickett-
sugamushi (scrub typhus), and R. typhi (murine or sial infections. Those who go on safari—especially
fleaborne typhus). those walking in the bush, game hunters, and
ecotourists in southern Africa—are at risk for
TRANSMISSION African tick-bite fever, which consistently remains
Most rickettsial pathogens are transmitted by the most commonly reported rickettsial infec-
ectoparasites such as fleas, lice, mites, and ticks. tion acquired during travel. Mediterranean spot-
Organisms can be transmitted by bites from these ted fever is less commonly reported but occurs
ectoparasites or by inoculating infectious flu- over an even larger region, including much of
ids or feces from the ectoparasites into the skin. Europe, Africa, India, and the Middle East. Rocky
Inhaling or inoculating conjunctiva with infec- Mountain spotted fever (also known as Brazilian
tious material may also cause infection for some spotted fever and other local names) is reported
of these organisms. The specific vectors that throughout much of the Western Hemisphere,
transmit each rickettsial pathogen are listed in including Canada, the United States, Mexico, and
Table 3-18. Transmission of some rickettsial dis- several countries in Central and South America
eases after transfusion or organ transplantation is including Argentina, Brazil, Colombia, Costa Rica,
rare but has been reported. and Panama. Clusters of illness may be reported in
families or in geographic areas. Contact with dogs
EPIDEMIOLOGY in rural and urban settings and outdoor activi-
All age groups are at risk for rickettsial infec- ties such as hiking, hunting, fishing, and camping
tions during travel to endemic areas. Both short increase the risk of infection.
and long-term travelers are at risk for infection. Scrub typhus, which is transmitted by trom-
Transmission is increased during outdoor activi- biculid mites encountered in high grass and brush,
ties in the spring and summer months when ticks is endemic in northern Japan, Southeast Asia, the
and fleas are most active; however, infection can western Pacific Islands, northern Australia, China,
RICKETTSIAL (SPOTTED & TYPHUS FEVERS) & RELATED INFECTIONS, INCLUDING ANAPLASMOSIS & EHRLICHIOSIS 297
8
92
298
3
INFECTIOUS DISEASES RELATED TO TRAVEL
Anaplasma Human anaplasmosis Anaplasma Tick Small mammals, Primarily United States, worldwide
phagocytophilum rodents, deer
A. platys Dogs Venezuela
A. ovis Sheep Cyprus, Iran
“A. capra” Goats China
Ehrlichia Human ehrlichiosis Ehrlichia chaffeensis Tick Deer, wild and domestic Common in United States, possibly
E. muris dogs, domestic worldwide
E. ewingii ruminants, rodents
E. canis Dogs Venezuela
Neorickettsia Sennetsu fever, neorickettsiosis Neorickettsia Trematode Fish Japan, Malaysia, possibly other
sennetsu (ingestion) parts of Asia
Scrub typhus Scrub typhus Orientia Larval mite Rodents Asia-Pacific region from maritime
tsutsugamushi (chigger) Russia and China to Indonesia and
North Australia to Afghanistan
African tick-bite fever R. africae Tick Ruminants Sub-Saharan Africa, West Indies
Rickettsialpox R. akari Mite House mice, wild Countries of the former Soviet Union,
rodents South Africa, Korea, Turkey, Balkan
countries, United States
29
Queensland tick typhus R. australis Tick Rodents Australia, Tasmania
RICKETTSIAL (SPOTTED & TYPHUS FEVERS) & RELATED INFECTIONS, INCLUDING ANAPLASMOSIS & EHRLICHIOSIS
Mediterranean spotted fever or R. conorii Tick Dogs, rodents Southern Europe, southern and
Boutonneuse fever western Asia, Africa, India
Cat flea rickettsiosis R. felis Flea Domestic cats, rodents, Europe, North and South America,
opossums Africa, Asia
Far Eastern spotted fever R. heilongjiangensis Tick Rodents Far East of Russia, Northern China,
eastern Asia
Aneruptive fever R. helvetica Tick Rodents Central and northern Europe, Asia
Flinders Island spotted fever, Thai tick R. honei, including Tick Rodents, reptiles Australia, Thailand
typhus strain “marmionii”
Mediterranean spotted fever–like R. massiliae Tick Unknown France, Greece, Spain, Portugal,
disease Switzerland, Sicily, central Africa,
Mali, and Argentina
Mediterranean spotted fever–like illness R. monacensis Tick Lizards, possibly birds Europe, North Africa
Maculatum infection; Tidewater spotted R. parkeri Tick Rodents North and South America
fever; American boutonneuse fever
Rocky Mountain spotted fever Brazilian R. rickettsia Tick Rodents North, Central, and South America
spotted fever
North Asian tick typhus, Siberian tick R. sibirica Tick Rodents Russia, China, Mongolia
typhus
(continued)
299
3
03
300
3
INFECTIOUS DISEASES RELATED TO TRAVEL
Tickborne lymphadenopathy (TIBOLA), R. slovaca Tick Lagomorphs, rodents Southern and eastern Europe, Asia
Dermacentor-borne necrosis and
lymphadenopathy (DEBONEL)
Typhus fever Epidemic typhus, sylvatic typhus R. prowazekii Human body louse, Humans, flying Central Africa; Asia; Central, North,
flying squirrel squirrels and South America
ectoparasites,
possibly some ticks
Murine typhus, fleaborne typhus R. typhi Flea Rodents Tropical and subtropical areas
worldwide
301
maritime areas, and several parts of south-central Brazil, but the role of ticks in the natural transmis-
Russia, India, and Sri Lanka. More than 1 million sion of R. prowazekii has not been characterized.
cases occur annually. Most travel-acquired cases Ehrlichiosis and anaplasmosis are tickborne
of scrub typhus occur during visits to rural areas infections most commonly reported in the United
in endemic countries for activities such as camp- States. A variety of species are implicated in infec-
ing, hiking, or rafting, but urban cases have also tion, but E. chaffeensis and A. phagocytophilum are
been described. most common. Infections with various Ehrlichia
R. typhi and R. felis, which are transmitted by and Anaplasma spp. have also been reported in
fleas, are widely distributed, especially throughout Europe, Asia, and South America. Neoehrlichia
the tropics and subtropics and in port cities and mikurensis is a tickborne pathogen that occurs in
coastal regions with rodents. Humans exposed to
flea-infested cats, dogs, and peridomestic animals
Europe and Asia and perhaps in Africa. Sennetsu
fever, caused by Neorickettsia sennetsu, occurs in
3
while traveling in endemic regions, or who enter Japan, Malaysia, and possibly other parts of Asia.
or sleep in areas infested with rodents, are at most This disease can be contracted from eating raw
risk for fleaborne rickettsioses. Murine typhus has infected fish.
been reported among travelers returning from
southeastern Asia, Africa, and the Mediterranean CLINICAL PRESENTATION
Basin. In the United States, most cases are Rickettsioses are difficult to diagnose, even by
reported from Hawaii, California, and Texas. health care providers experienced with these
R. akari, the causative agent of rickettsialpox, is diseases. Most symptomatic rickettsial diseases
transmitted by house-mouse mites, and circulates cause a moderately severe illness, but some, such
in mainly urban centers in Ukraine, South Africa, as Rocky Mountain spotted fever, Mediterranean
Korea, the Balkan states, and the United States. spotted fever, scrub typhus, and epidemic typhus,
Outbreaks of rickettsialpox most often occur after may be life threatening and can be fatal in 20%–
contact with infected rodents and their mites, 60% of untreated cases, so prompt treatment is
especially during natural die-offs or extermina- essential.
tions of infected rodents that cause the mites to Clinical presentations vary with the causative
seek out new hosts, including humans. The agent agent and patient; however, common symptoms
may spill over and occasionally be found in other that typically develop within 1–2 weeks of infec-
wild rodent populations. tion include fever, headache, malaise, rash, nausea,
Epidemic typhus caused by R. prowazekii and vomiting. Many rickettsioses are accompa-
infection is rarely reported among tourists but nied by a maculopapular, vesicular, or petechial
can occur in impoverished communities and ref- rash or sometimes an eschar at the site of the
ugee populations where body lice are prevalent. tick bite. African tick-bite fever is typically milder
Outbreaks often occur during colder months. than some other rickettsioses, but recovery is
Travelers at most risk for epidemic typhus improved with treatment. It should be suspected
include those who may visit areas with large in a patient who presents with fever, headache,
homeless populations, impoverished areas, refu- myalgia, and an eschar (tache noir) after recent
gee camps, and regions that have recently expe- travel to southern Africa. Mediterranean spotted
rienced war or natural disasters. Active foci of fever is a potentially life-threatening rickettsial
epidemic typhus are known in the Andes regions infection and should be suspected in patients with
of South America and some parts of Africa rash, fever, and eschar after recent travel to north-
(including but not limited to Burundi, Ethiopia, ern Africa or the Mediterranean. Rocky Mountain
and Rwanda). Louseborne epidemic typhus does spotted fever is frequently characterized by fever,
not regularly occur in the United States, but a headache, nausea, and abdominal pain; a rash is
zoonotic reservoir occurs in the southern flying commonly reported, but eschars are not. Scrub
squirrel, and sporadic sylvatic typhus cases are typhus should be suspected in patients with a
reported. Tick-associated reservoirs of R. prowaze- fever, headache, and myalgia after recent travel
kii have been described in Ethiopia, Mexico, and to Asia; eschar, lymphadenopathy, cough, and
RICKETTSIAL (SPOTTED & TYPHUS FEVERS) & RELATED INFECTIONS, INCLUDING ANAPLASMOSIS & EHRLICHIOSIS 301
3
0
2
encephalitis may be present. Patients with murine Immediate empiric treatment with a tetracycline,
or epidemic typhus usually present with a severe most commonly doxycycline, is recommended for
but nonspecific febrile illness, and approximately all ages. Almost all other broad-spectrum antibi-
half will also present with a rash. Ehrlichiosis otics are not helpful. Chloramphenicol may be an
and anaplasmosis should be suspected in febrile alternative in some cases, but its use is associated
patients with leukopenia and thrombocytopenia with more deaths, particularly for R. rickettsii. In
and mild to moderately elevated levels of hepatic some areas, tetracycline-resistant scrub typhus
transaminases. has been reported. Azithromycin may be an effec-
tive alternative. Anaplasma phagocytophilum
DIAGNOSIS infections may respond to rifampin, which may
3 Diagnosis is usually based on clinical recognition
and serology. Serologic testing provides stronger
be an alternate drug for pregnant patients. Expert
advice should be sought if alternative agents are
evidence when acute-and convalescent- phase being considered.
serum samples are compared; a ≥4-fold rise in
titer is diagnostic. PCR assays and immunohisto- PREVENTION
chemical analyses may also be helpful, but useful No vaccine is available for preventing rickettsial
results are highly dependent upon the specimen infections. Antibiotics are not recommended for
submitted. If an eschar is present, a swab or biopsy prophylaxis of rickettsial diseases and should not
sample of the lesion can be evaluated by PCR and be given to asymptomatic people.
provides a species-specific diagnosis. If ehrlichio- Travelers should be instructed to minimize
sis or anaplasmosis is suspected, PCR of a whole- exposure to biting arthropods during travel
blood specimen provides the best diagnostic test. (including lice, fleas, ticks, mites) and to animal
A buffy coat may provide presumptive evidence reservoirs (particularly dogs) when traveling in
of infection if examined to identify characteris- endemic areas. The proper use of insect or tick
tic intraleukocytic morulae. Contact the CDC repellents on skin or clothing, self-examination
Rickettsial Zoonoses Branch at 404-639-1075 for after visits to vector-infested areas, and wearing
further information. Ehrlichiosis, anaplasmosis, protective clothing are ways to reduce risk. These
and spotted fever rickettsiosis are nationally noti- precautions are especially important for people
fiable diseases. with underlying conditions that may compro-
mise their immune systems, as these people may
TREATMENT be more susceptible to severe disease. For more
Treatment of patients with possible rickettsioses detailed information, see Chapter 2, Protection
should be started when disease is suspected against Mosquitoes, Ticks, & Other Arthropods.
and should never await confirmatory testing,
as certain infections can be rapidly progressive. CDC website: www.cdc.gov/ticks
BIBLIOGRAPHY
1. Biggs HM, Behravesh CB, Bradley KK, Dahlgren FS, 4. Jensenius M, Davis X, von Sonnenburg F, Schwartz E,
Drexler NA, Dumler JS, et al. Diagnosis and manage- Keystone JS, Leder K, et al. Multicenter GeoSentinel
ment of tickborne rickettsial diseases: Rocky Mountain analysis of rickettsial diseases in international
spotted fever and other spotted fever group rickett- travelers, 1996–2008. Emerg Infect Dis. 2009
sioses, ehrlichioses, and anaplasmosisUnited States. Nov;15(11):1791–8.
MMWR Recomm Rep. 2016;65(2):1–4 4. 5. Li H, Zheng YC, Ma L, Jia N, Jiang BG, Jiang RR, et al.
2. Demeester R, Claus M, Hildebrand M, Vlieghe E, Human infection with a novel tick-borne Anaplasma
Bottieau E. Diversity of life-threatening complications species in China: a surveillance study. Lancet Infect Dis.
due to Mediterranean spotted fever in returning travel- 2015 Jun;15(6):663–70.
ers. J Travel Med. 2010 Mar-Apr;17(2):100–4.
6. Nachega JB, Bottieau E, Zech F, Van Gompel A. Travel-
3. Hendershot EF, Sexton DJ. Scrub typhus and rickettsial acquired scrub typhus: emphasis on the differential
diseases in international travelers: a review. Curr Infect diagnosis, treatment, and prevention strategies. J Travel
Dis Rep. 2009 Jan;11(1):66–72. Med. 2007 Sep-Oct;14(5):352–5.
7. Paddock CD, Fernandez S, Echenique GA, 9. Roch N, Epaulard O, Pelloux I, Pavese P, Brion JP, Raoult D,
Sumner JW, Reeves WK, Zaki SR, et al. et al. African tick bite fever in elderly patients: 8 cases in
Rocky Mountain spotted fever in French tourists returning from South Africa. Clin Infect
Argentina. Am J Trop Med Hyg. 2008 Dis. 2008 Aug 1;47(3):e28–35.
Apr;78(4):687–92. 10. Silaghi C, Beck R, Oteo JA, Pfeffer M, Sprong H.
8. Raoult D, Parola P, editors. Rickettsial Neoehrlichiosis: an emerging tick-borne zoonosis
Diseases. New York: Informa Healthcare caused by Candidatus Neoehrlichia mikurensis. Exp
USA, Inc; 2007. Appl Acarol. 2016 Mar;68(3):279–97.
3
RUBELLA
Emmaculate J. Lebo, Cristina V. Cardemil, Susan E. Reef
RUBELLA 303
4
0
3
vaccinated with measles-mumps-rubella (MMR) outbreaks, especially during the first 20 weeks of
vaccine. Before departure from the United States, pregnancy, and should be vaccinated immedi-
infants aged 6–11 months should receive 1 dose of ately postpartum. Health care providers should
MMR vaccine ( for measles protection), and chil- also ensure that all women of childbearing age
dren aged ≥12 months and adults should receive and recent immigrants are up-to-date on their
2 doses of MMR vaccine ≥28 days apart on or immunization against rubella or have evidence of
after the first birthday. MMR vaccine is contra- immunity to rubella, because these groups are at
indicated during pregnancy. Pregnant women the highest risk for maternal-fetal transmission of
who do not have acceptable evidence of rubella rubella virus.
immunity should not travel to countries where
3 rubella is endemic or areas with known rubella CDC website: www.cdc.gov/rubella
BIBLIOGRAPHY
1. CDC. Rubella. In: Hamborsky J, Kroger A, Wolfe S, 5. Reef SE, Redd SB, Abernathy E, Kutty P, Icenogle JP.
editors. Epidemiology and Prevention of Vaccine- Evidence used to support the achievement and mainte-
Preventable Diseases. 13th ed. Washington, DC: Public nance of elimination of rubella and congenital rubella
Health Foundation; 2015. pp. 275–89. syndrome in the United States. J Infect Dis. 2011 Sep
2. CDC. Summary of notifiable infectious diseases and 1;204 Suppl 2:S593–7.
conditions—United States, 2013. MMWR Morb Mortal 6. Vynnycky E, Adams EJ, Cutts FT, Reef SE, Navar AM,
Wkly Rep. 2015 Oct 23;62(53):1–122. Simons E, et al. Using seroprevalence and immunisation
3. Papania MJ, Wallace GS, Rota PA, Icenogle JP, coverage data to estimate the global burden of congen-
Fiebelkorn AP, Armstrong GL, et al. Elimination of ital rubella syndrome, 1996–2010: a systematic review.
endemic measles, rubella, and congenital rubella PLoS One. 2016;11(3):e0149160.
syndrome from the Western hemisphere: the 7. World Health Organization. Rubella vaccines: WHO
US experience. JAMA Pediatr. 2014 Feb;168(2):148–55. position paper. Wkly Epidemiol Rec. 2011 July 15,
4. Reef SE, Plotkin SA. Rubella vaccine. In: Plotkin SA, 2011;86(29):301–16.
Orenstein WA, Offit PA, editors. Vaccines. 6th ed.
Philadelphia: Saunders Elsevier; 2012. pp. 688–717.
SALMONELLOSIS (NONTYPHOIDAL)
Jennifer C. Hunter, Louise K. Francois Watkins
Latin America and the Caribbean, 5.8 cases per isolates are also obtained from blood, urine,
100,000 among travelers to Asia, and 25.8 cases abscesses, cerebrospinal fluid, and other sites of
per 100,000 among travelers to Africa. The true infection. Although culture-independent diagnos-
number of illnesses is much higher, because most tic tests are increasingly used by clinical labora-
ill people do not have a stool specimen tested. tories to diagnose Salmonella infection, isolates
US travelers with salmonellosis were most likely are needed for serotyping and antimicrobial sus-
to report visiting the following countries: Mexico ceptibility testing. Salmonella isolate submission
(38% of travel- associated salmonellosis), India requirements vary by state, but most states man-
(9%), Jamaica (7%), the Dominican Republic (4%), date that Salmonella isolates or clinical material
China (3%), and the Bahamas (2%); these findings be submitted to the local or state public health
are influenced by the number of travelers to dif-
ferent destinations. A systematic review of travel-
laboratory. To understand submission require-
ments in a particular state, clinical laboratories are
3
ers’ diarrhea etiology studies published from 2002 advised to review the disease reporting and man-
through 2011 found that Salmonella was detected datory isolate submission regulations of that state.
in <5% of patients who had traveled to Latin Salmonellosis is a nationally notifiable disease.
America, the Caribbean, and South Asia and in
5%–15% of patients who had traveled to Africa TREATMENT
or Southeast Asia. Salmonella infection and car- Current recommendations are to treat most
riage have been reported among internationally patients with uncomplicated Salmonella infec-
adopted children. tion with oral rehydration therapy but not
with antimicrobial agents. Antimicrobial ther-
CLINICAL PRESENTATION apy should be considered for patients who are
Gastroenteritis is the most common clinical pre- severely ill ( for example, those with severe diar-
sentation of nontyphoidal Salmonella infection. rhea, high fever, or manifestations of extrain-
The incubation period is typically 6–72 hours; testinal infection) and for people at increased
while atypical, illness has been documented even risk of invasive disease (infants, older adults,
14 days after exposure. Illness is commonly man- and the debilitated or immunosuppressed).
ifested as acute diarrhea, abdominal pain, fever, When antimicrobial therapy is indicated,
and sometimes vomiting. The illness usually lasts empiric treatment is usually required until
4–7 days, and most people recover without treat- susceptibility data are available. Resistance to
ment. Approximately 5% of people develop bac- antimicrobial agents varies by serotype and
teremia or focal infection (such as meningitis or geographic region. Fluoroquinolones are con-
osteomyelitis). Salmonellosis outcomes differ by sidered first- line treatment in adult travel-
serotype. Infections with some serotypes, includ- ers. However, resistance to fluoroquinolones
ing Dublin and Choleraesuis, are more likely to among Salmonella strains is rising globally. In
result in invasive infections. Rates of invasive a study of international travelers diagnosed
infections and death are generally higher among with S. enterica serotype Enteritidis infection
infants, older adults, and people with immuno- in the United States, 24% of isolates showed
suppressive conditions (including HIV), hemoglo- decreased susceptibility to fluoroquinolo-
binopathies, and malignant neoplasms. Infection nes compared with only 3% of isolates from
with antibiotic-resistant organisms has been asso- patients with no history of international travel.
ciated with a higher risk of bloodstream infection Azithromycin can be used for children and is
and hospitalization. an alternative agent for adults returning from
Latin America or Asia, where resistance in
DIAGNOSIS this organism to fluoroquinolones may exceed
Culturing organisms continues to be the main- 10%. Azithromycin resistance has been docu-
stay of clinical diagnostic testing for nontyphoidal mented in multiple settings globally but is not
Salmonella infection. Approximately 90% of iso- commonly reported. Resistance to older anti-
lates are obtained from routine stool culture, but microbial agents (chloramphenicol, ampicillin,
and trimethoprim-sulfamethoxazole) has been aimed at avoiding foods and drinks at high risk
present for many years; these should not be for contamination; frequent handwashing, espe-
considered first-line empiric agents in returning cially after contacting animals or their environ-
travelers (see Chapter 2, Travelers’ Diarrhea). ment; and taking food and water precautions (see
Chapter 2, Food & Water Precautions).
PREVENTION
No vaccine is available against nontyphoidal CDC website: www.cdc.gov/salmonella
Salmonella infection. Preventive measures are
BIBLIOGRAPHY
3 1. American Public Health Association. Salmonellosis.
In: Heymann DL, editor. Control of Communicable
Diseases Active Surveillance Network (FoodNet) study.
Foodborne Pathog Dis. 2011 Sep;8(9):1031–7.
Diseases Manual. 19th ed. Washington, DC: American 6. Jones TF, Ingram LA, Cieslak PR, Vugia DJ, Tobin-
Public Health Association; 2008. pp. 534–4 0. D’Angelo M, Hurd S, et al. Salmonellosis outcomes
2. Association of Public Health Laboratories. State legal differ substantially by serotype. J Infect Dis. 2008 Jul 1;
requirements for submission of isolates and other 198(1):109–14.
clinical materials by clinical laboratories: a review 7. Kendall ME, Crim S, Fullerton K, Han PV, Cronquist AB,
of state approaches 2015 [cited 2016 Sep. 26]. Shiferaw B, et al. Travel-associated enteric infections
Available from: https://www.aphl.org/aboutAPHL/ diagnosed after return to the United States, Foodborne
publications/Documents/StateRequirements_ Diseases Active Surveillance Network (FoodNet),
Appendix_v6.pdf. 2004–2009. Clin Infect Dis. 2012 Jun;54 Suppl 5:S480–7.
3. Brooks JT, Matyas BT, Fontana J, DeGroot MA, Beuchat LR, 8. Kirk MD, Pires SM, Black RE, Caipo M, Crump JA,
Hoekstra M, et al. An outbreak of Salmonella serotype Devleesschauwer B, et al. World Health Organization
Typhimurium infections with an unusually long incuba- estimates of the global and regional disease bur-
tion period. Foodborne Pathog Dis. 2012 Mar;9(3):245–8. den of 22 foodborne bacterial, protozoal, and viral
4. Iwamoto M, Huang JY, Cronquist AB, Medus C, Hurd S, diseases, 2010: a data synthesis. PLoS Med. 2015
Zansky S, et al. Bacterial enteric infections detected by Dec;12(12):e1001921.
culture-independent diagnostic tests—FoodNet, United 9. O’Donnell AT, Vieira AR, Huang JY, Whichard J, Cole D,
States, 2012–2014. MMWR Morb Mortal Wkly Rep. 2015 Karp BE. Quinolone-resistant Salmonella enterica sero-
Mar 13;64(9):252–7. type Enteritidis infections associated with international
5. Johnson LR, Gould LH, Dunn JR, Berkelman R, Mahon BE, travel. Clin Infect Dis. 2014 Nov 1;59(9):e139–41.
FoodNet Travel Working Group. Salmonella infections 10. Steffen R, Hill DR, DuPont HL. Traveler’s diarrhea: a
associated with international travel: a Foodborne clinical review. JAMA. 2015 Jan 6;313(1):71–80.
SARCOCYSTOSIS
Douglas H. Esposito
BIBLIOGRAPHY
1. Arness MK, Brown JD, Dubey JP, Neafie RC, Granstrom Tioman Island, Malaysia, 2011–2012. Clin Infect Dis. 2014
DE. An outbreak of acute eosinophilic myositis Nov 15;59(10):1401–10.
attributed to human Sarcocystis parasitism. Am J Trop 3. Fayer R, Esposito DH, Dubey JP. Human infections
Med Hyg. 1999 Oct;61(4):548–53. with Sarcocystis species. Clin Microbiol Rev. 2015
2. Esposito DH, Stich A, Epelboin L, Malvy D, Han PV, Apr;28(2):295–311.
Bottieau E, et al. Acute muscular sarcocystosis: an inter- 4. Italiano CM, Wong KT, AbuBakar S, Lau YL, Ramli
national investigation among ill travelers returning from N, Syed Omar SF, et al. Sarcocystis nesbitti causes
SARCOCYSTOSIS 307
8
03
acute, relapsing febrile myositis with a high attack Tioman Island, Malaysia, 2011–2014. Clin Infect Dis. 2015
rate: description of a large outbreak of muscular sarco- Jan 15;60(2):329.
cystosis in Pangkor Island, Malaysia, 2012. PLoS Negl 6. Tappe D, Stich A, Langeheinecke A, von Sonnenburg F,
Trop Dis. 2014 May;8(5):e2876. Muntau B, Schafer J, et al. Suspected new wave of mus-
5. Slesak G, Schafer J, Langeheinecke A, Tappe D. cular sarcocystosis in travellers returning from Tioman
Prolonged clinical course of muscular sarcocystosis Island, Malaysia, May 2014. Euro Surveill. 2014;19(21).
and effectiveness of cotrimoxazole among travelers to
3 SCABIES
Diana Martin
as clothing and bed linens that have been used CDC website: www.cdc.gov/parasites/scabies
by an infested person should be avoided, espe-
cially if the person has crusted scabies.
BIBLIOGRAPHY
1. Ansart S, Perez L, Jaureguiberry S, Danis M, Bricaire management of crusted scabies. PLoS Negl Trop Dis.
F, Caumes E. Spectrum of dermatoses in 165 travelers 2013;7(9):e2387.
returning from the tropics with skin diseases. Am J Trop 6. Davis RF, Johnston GA, Sladden MJ. Recognition and
Med Hyg. 2007 Jan;76(1):184–6. management of common ectoparasitic diseases in trav-
3
2. Bouvresse S, Chosidow O. Scabies in healthcare settings. elers. Am J Clin Dermatol. 2009;10(1):1–8.
Curr Opin Infect Dis. 2010 Apr;23(2):111–8. 7. Hengge UR, Currie BJ, Jager G, Lupi O, Schwartz RA.
3. Chosidow O. Clinical practices. Scabies. N Engl J Med. Scabies: a ubiquitous neglected skin disease. Lancet
2006 Apr 20;354(16):1718–27. Infect Dis. 2006 Dec;6(12):769–79.
4. Currie BJ, McCarthy JS. Permethrin and 8. Heukelbach J, Feldmeier H. Scabies. Lancet. 2006 May
ivermectin for scabies. N Engl J Med. 2010 Feb 27;367(9524):1767–74.
25;362(8):717–25. 9. O’Brien BM. A practical approach to common skin
5. Davis JS, McGloughlin S, Tong SY, Walton SF, Currie problems in returning travellers. Travel Med Infect Dis.
BJ. A novel clinical grading scale to guide the 2009 May;7(3):125–46.
SCHISTOSOMIASIS
Susan Montgomery
SCHISTOSOMIASIS 309
031
Types of schistosomiasis
- Low Risk for Hepatic-Intestinal - Hepatic-Intestinal
Low Risk for both Hepatic-Intestinal and Urinary - Both Hepatic-Intestinal and Urinary
SCHISTOSOMIASIS 311
3
21
infected humans. The specific snail vectors can polyposis and, with heavy infections, to peripor-
be difficult to identify, and whether snails are tal liver fibrosis. S. haematobium eggs typically
infected with human schistosome species can lodge in the urinary tract and can cause dysuria
only be determined in the laboratory. and hematuria. Calcifications in the bladder may
The geographic distribution of cases of schis- appear late in the disease. S. haematobium infec-
tosomiasis acquired by travelers reflects travel tion can also cause genital symptoms and has
and immigration patterns. Most travel-associated been associated with increased risk of bladder
cases of schistosomiasis are acquired in sub- cancer. As with acute schistosomiasis, eosino-
Saharan Africa. Sites in Africa frequently vis- philia may be present during chronic infection
ited by travelers are common sites of infection. with any species.
3 These sites include rivers and water sources in
the Banfora region (Burkina Faso) and areas pop-
Rarely, central nervous system manifestations
of schistosomiasis may develop; this is thought to
ulated by the Dogon people (Mali), Lake Malawi, result from aberrant migration of adult worms or
Lake Tanganyika, Lake Victoria, the Omo River eggs depositing in the spinal cord or brain. Signs
(Ethiopia), the Zambezi River, and the Nile River. and symptoms are related to ectopic granulomas
However, as visitors travel to more remote sites, in the central nervous system and can present as
it is important to remember that most freshwa- transverse myelitis.
ter surface water sources in Africa are potentially
contaminated and can be sources of infection. DIAGNOSIS
A local claim that there is no schistosomiasis in a Diagnosis is made by microscopic identification
body of freshwater is not necessarily reliable. of parasite eggs in stool (S. mansoni or S. japoni-
The types of travelers and expatriates poten- cum) or urine (S. haematobium). Serologic tests
tially at increased risk for infection include are useful to diagnose light infections because egg
adventure travelers, Peace Corps volunteers, mis- shedding may not be consistent such as in travel-
sionaries, soldiers, and ecotourists. Outbreaks of ers and in others who have not had schistosomi-
schistosomiasis have occurred among adventure asis previously. Antibody tests do not distinguish
travelers on river trips in Africa. between past and current infection. Immunologic
test sensitivity and specificity vary, depending on
CLINICAL PRESENTATION the antigen preparation used and how the test is
The incubation period is typically 14–84 days for performed. Health care providers should consider
acute schistosomiasis (Katayama syndrome), but screening asymptomatic people who may have
chronic infection can remain asymptomatic for been exposed during travel and may benefit from
years. Penetration of cercariae can be associated treatment.
with a rash that develops within hours or up to a More detailed information and assistance with
week after contaminated water exposures. Acute diagnosis may be obtained from CDC (www.cdc.
schistosomiasis is characterized by fever, head- gov/parasites/schistosomiasis or CDC Parasitic
ache, myalgia, diarrhea, and respiratory symp- Diseases Inquiries, 404-718-4745).
toms. Eosinophilia is often present, as well as
painful hepatomegaly or splenomegaly. TREATMENT
The clinical manifestations of chronic schisto- Schistosomiasis is uncommon in the United
somiasis are the result of host immune responses States, and clinicians unfamiliar with manage-
to schistosome eggs. Eggs, secreted by adult worm ment of schistosomiasis should consult an infec-
pairs living in the bloodstream, become lodged in tious disease or tropical medicine specialist for
the capillaries of organs and cause granulomatous diagnosis and treatment. Praziquantel is used
reactions. S. mansoni and S. japonicum eggs most to treat schistosomiasis. Praziquantel is most
commonly lodge in the blood vessels of the liver effective against adult forms of the parasite and
or intestine and can cause diarrhea, constipation, requires an immune response to the adult worm
and blood in the stool. Chronic inflammation can to be fully effective. Host immune response differ-
lead to bowel wall ulceration, hyperplasia, and ences may affect individual response to treatment
BIBLIOGRAPHY
1. Berry A, Mone H, Iriart X, Mouahid G, Aboo O, Boissier aspects of an old disease. Emerg Infect Dis. 2006
J, et al. Schistosomiasis haematobium, Corsica, France. Nov;12(11):1696–700.
Emerg Infect Dis. 2014 Sep;20(9):1595–7. 7. Nicolls DJ, Weld LH, Schwartz E, Reed C, von
2. Bierman WF, Wetsteyn JC, van Gool T. Presentation Sonnenburg F, Freedman DO, et al. Characteristics of
and diagnosis of imported schistosomiasis: relevance of schistosomiasis in travelers reported to the GeoSentinel
eosinophilia, microscopy for ova, and serology. J Travel Surveillance Network 1997–2008. Am J Trop Med Hyg.
Med. 2005 Jan-Feb;12(1):9–13. 2008 Nov;79(5):729–34.
3. Clerinx J, Van Gompel A. Schistosomiasis in travellers 8. Ross AG, Bartley PB, Sleigh AC, Olds GR, Li Y, Williams
and migrants. Travel Med Infect Dis. 2011 Jan;9(1):6–24. GM, et al. Schistosomiasis. N Engl J Med. 2002 Apr
4. Corachan M. Schistosomiasis and international travel. 18;346(16):1212–20.
Clin Infect Dis. 2002 Aug 15;35(4):446–5 0. 9. Ross AG, Vickers D, Olds GR, Shah SM, McManus
5. Grobusch MP, Muhlberger N, Jelinek T, Bisoffi Z, DP. Katayama syndrome. Lancet Infect Dis. 2007
Corachan M, Harms G, et al. Imported schistoso- Mar;7(3):218–24.
miasis in Europe: sentinel surveillance data from 10. World Health Organization Expert Committee.
TropNetEurop. J Travel Med. 2003 May-Jun;10(3):164–9. Prevention and control of schistosomiasis and soil-
6. Meltzer E, Artom G, Marva E, Assous MV, Rahav G, transmitted helminthiasis. World Health Organ Tech
Schwartzt E. Schistosomiasis among travelers: new Rep Ser. 2002;912:1–57.
SCHISTOSOMIASIS 313
431
SEXUALLY TRANSMITTED
DISEASES
Emily J. Weston, Kimberly Workowski
ulcers are detected on anoscopy, presumptive STDs can often result in serious and long-term
therapy should include a regimen for anogenital complications, including pelvic inflammatory dis-
herpes. LGV should be suspected in a traveler with ease, infertility, stillbirths and neonatal infections,
tender unilateral inguinal or femoral lymphade- anogenital and other cancers, and an increased
nopathy or proctocolitis. Presumptive treatment risk for HIV acquisition and transmission.
for LGV should be considered for men who have
sex with men and who have proctitis and perianal PREVENTION
or mucosal ulcers, after obtaining specific testing The prevention and control of STDs are based
for Chlamydia trachomatis (culture, direct immu- on accurate risk assessment, education, coun-
nofluorescence, or nucleic acid testing) from rel- seling, early identification of asymptomatic
evant specimens (genital lesions, rectal, or lymph
node). Of note, for patients presenting with procti-
infection, and effective treatment of patients
and their sex partners. Pretravel advice should
3
tis, C. trachomatis nucleic acid amplification test- include specific messages with strategies to avoid
ing of a rectal specimen is recommended. While acquiring or transmitting STDs. Abstinence or
a positive result is not a definitive diagnosis of mutual monogamy with an uninfected partner
LGV, the results might aid in the presumptive is the most reliable way to avoid acquiring and
clinical diagnosis of LGV proctitis. Donovanosis transmitting STDs.
is endemic in India, Papua New Guinea, central For people whose sexual behaviors place
Australia, and southern Africa and is diagnosed them at risk for STDs, correct and consistent
with a crush tissue preparation from the lesion. use of the male latex condom can reduce the
Testing specimens from the anatomic site of risk of HIV infection and other STDs, includ-
exposure with nucleic acid amplification tests ing chlamydia, gonorrhea, and trichomoniasis.
can detect C. trachomatis and Neisseria gonor- Preventing lower genital tract infections might
rhoeae. Culture and antibiotic susceptibility test- reduce the risk of pelvic inflammatory disease
ing should be considered when gonorrhea is in women. Correct and consistent use of male
suspected, because of geographic differences in latex condoms also reduces the risk of HPV
antimicrobial susceptibility. Various diagnos- infection, genital herpes, syphilis, and chan-
tic methods are available to identify the cause of croid, although data are limited. Only water-
an abnormal vaginal discharge, including micro- based lubricants (such as K-Y Jelly or glycerin)
scopic evaluation and pH testing of vaginal secre- should be used with latex condoms because
tions, DNA probe- based testing, nucleic acid oil-based lubricants (such as petroleum jelly,
amplification testing, and culture. shortening, mineral oil, or massage oil) can
Diagnosis of anogenital warts is made by weaken latex condoms. Spermicides contain-
visual inspection, with confirmation by biopsy if ing nonoxynol- 9 are not recommended for
clinically indicated. STD/HIV prevention, as nonoxynol-9 may dis-
Anyone who seeks evaluation for STDs, or is rupt genital or rectal epithelium and has been
diagnosed with an STD, should be screened for associated with an increased risk of HIV trans-
HIV infection. People seeking STD care known mission. Contraceptive methods that are not
to be HIV-infected should be provided linkage to mechanical barriers do not protect against HIV
HIV care and treatment services. or other STDs.
Prompt evaluation of sexual partners is nec-
TREATMENT essary to prevent reinfection and disrupt trans-
Evaluation, management, and follow-up of STDs mission of many STDs. Preexposure vaccination
should be based on standard guidelines (CDC is among the most effective methods for prevent-
and the World Health Organization). The prev- ing some STDs. Two HPV vaccines are available
alence of antimicrobial resistance in different and licensed for girls and women aged 9–26 years
areas should be considered when selecting treat- to prevent cervical precancers and cancers: the
ment regimens. Early detection and treatment quadrivalent HPV and the bivalent HPV vaccine.
are important, as many STDs are asymptomatic. The quadrivalent vaccine also prevents genital
warts and is recommended for boys and men men who have sex with men and injection drug
aged 9–26 years as well as girls and women. All users. Travelers, particularly those at high risk for
travelers should be considered candidates for acquiring HIV infection, may consider discussing
both hepatitis A and hepatitis B vaccines, as these preexposure prophylaxis with their health care
infections can be sexually transmitted. Hepatitis B providers (see www.cdc.gov/ hiv/
prep and HIV
vaccine is recommended for all people being eval- section in this chapter).
uated or treated for an STD. In addition, hepatitis
A and hepatitis B vaccines are recommended for CDC website: www.cdc.gov/std
3 BIBLIOGRAPHY
1. CDC. Human papillomavirus vaccination: recommen- treatment. Clin Infect Dis. 2015 Dec 15;61 Suppl 8:
dations of the Advisory Committee on Immunization S865–73.
Practices (ACIP). MMWR Recomm Rep. 2014 Aug 8. Unemo M, Nicholas RA. Emergence of multidrug-
29;63(RR-05):1–30. resistant, extensively drug-resistant and untreatable
2. CDC. Recommendations for the laboratory-based gonorrhea. Future Microbiol. 2012 Dec;7(12):1401–22.
detection of Chlamydia trachomatis and Neisseria 9. Vivancos R, Abubakar I, Hunter PR. Foreign travel,
gonorrhoeae—2014. MMWR Recomm Rep. 2014 Mar casual sex, and sexually transmitted infections: sys-
14;63(RR-02):1–19. tematic review and meta-analysis. Int J Infect Dis. 2010
3. CDC. Sexually transmitted diseases treatment Oct;14(10):e842–51.
guidelines, 2015. MMWR Recomm Rep. 2015 Jun 10. World Health Organization. Baseline report on
5;64(RR-03):1–137. global sexually transmitted infection surveillance
4. CDC. Supplemental information and guidance for vacci- 2012. 2013 [cited 2016 Sep. 26]. Available from: http://
nation providers regarding use of 9-valent HPV vaccine. www.who.int/reproductivehealth/publications/rtis/
2015 [cited 2016 Sep. 26]. Available from: http://www. 9789241505895/en/.
cdc.gov/hpv/downloads/9vhpv-guidance.pdf. 11. World Health Organization. Global incidence and
5. Korzeniewski K, Juszczak D. Travel-related sex- prevalence of selected curable sexually transmitted
ually transmitted infections. Int Marit Health. infections–2008. Geneva 2012 [cited 2016 Sep. 26].
2015;66(4):238–46. Available from: http://www.who.int/reproductive-
6. Lahra MM, Lo YR, Whiley DM. Gonococcal antimi- health/publications/rtis/stisestimates/en/.
crobial resistance in the Western Pacific Region. Sex 12. World Health Organization. Report on global sexually
Transm Infect. 2013 Dec;89 Suppl 4:iv19–23. transmitted infection surveillance 2013. 2014 [cited 2016
7. Stoner BP, Cohen SE. Lymphogranuloma Sep. 26]. Available from: www.who.int/reproductivehealth/
Venereum 2015: clinical presentation, diagnosis, and publications/rtis/stis-surveillance-2013/en/.
. . .perspectives
SEX & TOURISM
Kimberly A. Workowski, Elissa Meites
SEXUAL ABUSE purpose of having sex with If you suspect child sex-
AND THE LAW a minor. In addition, child ual exploitation occurring
Although commercial sex pornography, including sex- overseas, you can report tips
work may be legal in some ual photographs or videos of anonymously by using the
countries, sex trafficking, minors in foreign countries, Operation Predator smart-
sex with a minor, and child is illegal in the United States. phone app (https://itunes.
pornography are always These crimes are subject to apple.com/us/app/operation-
criminal activities according prosecution with penalties of predator/id695130859), call-
to US law and can be pros- up to 30 years in prison. ing the Homeland Security
ecuted in the United States Nearly 2 million chil- Investigations Tip Line
even if the behavior occurred dren around the world toll-free at 866-347-2423, or
abroad. The Trafficking are victims of commercial submitting the information
Victims Protection Act sexual exploitation, and online at www.ice.gov/tips.
makes it illegal to recruit, roughly 1 million children In the United States, the
entice, or obtain a person of are victims of trafficking. National Center for Missing
any age to engage in com- Children abused by sex & Exploited Children’s
mercial sex acts or to benefit tourists suffer not only Cybertipline collects reports
from such activities. Federal sexual abuse but also pov- of child prostitution and
law also bars US residents erty, homelessness, and other crimes against children
from engaging in sexual or physical, emotional, and (toll-free at 800-843-5678,
pornographic activities with psychological abuse, as well www.cybertipline.com). At
a child aged <18 years any- as health problems includ- least 8,000 Americans have
where in the world, regard- ing illnesses, addictions, been arrested for child sex
less of local age of consent, malnourishment, infections, exploitation and 99 Americans
or to travel abroad for the physical injuries, and STDs. have been convicted for child
sex tourism since 2003, when To combat child sexual transmitted infections in travel-
the federal PROTECT Act was abuse, some international ers: implications for prevention
and control. Clin Infect Dis.
passed to strengthen the US hotels and other tourism
2004 Aug 15;39(4):533–8.
government’s prosecution of services have voluntarily
2. CDC. Sexually transmitted
crimes related to sex tourism. adopted a code of conduct
diseases treatment guidelines,
Americans and US per- that includes training and 2015. MMWR Recomm Rep.
manent residents account reporting suspicious activi- 2015 Jun 5;64(RR-03):1–137.
for an estimated 25% of ties. Tourist establishments 3. Marrazzo JM. Sexual tourism:
child sex tourists world-
wide and up to 80% in Latin
supporting this initiative to
protect children from sex
implications for travelers and
the destination culture. Infect 3
Dis Clin North Am. 2005
America. These are typically tourism are listed online
Mar;19(1):103–20.
Caucasian men aged ≥40 (www.thecode.org). For more
4. Newman WJ, Holt BW, Rabun JS,
and have been traced visiting ways you can help, see the
Phillips G, Scott CL. Child sex
Mexico, Central and South Department of State list of tourism: extending the borders
America (Brazil, Colombia, 15 ways to fight human traf- of sexual offender legislation.
Costa Rica, Dominican ficking (www.state.gov/j/tip/ Int J Law Psychiatry. 2011
Republic), Southeast Asia id/help). Mar-Apr;34(2):116–21.
(Cambodia, India, Laos, 5. Vivancos R, Abubakar I, Hunter
PR. Foreign travel, casual sex,
Philippines, Thailand), and sexually transmitted infec-
Eastern Europe (Estonia, BIBLIOGRAPHY tions: systematic review and
Latvia, Lithuania, Russia), 1. Abdullah AS, Ebrahim SH, meta-analysis. Int J Infect Dis.
2010 Oct;14(10):e842–51.
and other regions. Fielding R, Morisky DE. Sexually
Perspectives sections are written as editorial discussions aiming to add depth and clinical perspective to the official
recommendations contained in the book. The views and opinions expressed in this section are those of the authors and do
not necessarily represent the official position of CDC.
SHIGELLOSIS
Anna Bowen
SHIGELLOSIS 319
03
2
handwashing, strict adherence to standard food washing hands with soap and water or when soap
and water safety precautions (see Chapter 2, Food and water are not available.
& Water Precautions), and minimizing fecal-
oral exposures during sexual contact. Alcohol- CDC website: www.cdc.gov/shigella
based hand sanitizers may be a useful adjunct to
BIBLIOGRAPHY
1. American Academy of Pediatrics. Shigella infec- international implications. Clin Microbiol Infect. 2015
tions. In: Kimberlin DW, Brady MT, Jackson MA, Aug;21(8):765.e9–.e14.
Long SS, editors. Red Book: 2015 Report of the
Committee on Infectious Diseases. 30th ed. Elk Grove
Village, IL: American Academy of Pediatrics; 2015.
6. Hoffmann C, Sahly H, Jessen A, Ingiliz P, Stellbrink HJ,
Neifer S, et al. High rates of quinolone-resistant strains 3
of Shigella sonnei in HIV-infected MSM. Infection. 2013
pp. 706–9. Oct;41(5):999–1003.
2. Baker KS, Dallman TJ, Ashton PM, Day M, Hughes 7. Kendall ME, Crim S, Fullerton K, Han PV, Cronquist AB,
G, Crook PD, et al. Intercontinental dissemination of Shiferaw B, et al. Travel-associated enteric infections
azithromycin-resistant shigellosis through sexual trans- diagnosed after return to the United States, Foodborne
mission: a cross-sectional study. Lancet Infect Dis. 2015 Diseases Active Surveillance Network (FoodNet), 2004–
Aug;15(8):913–21. 2009. Clin Infect Dis. 2012 Jun;54 Suppl 5:S480–7.
3. Bardhan P, Faruque AS, Naheed A, Sack DA. Decrease 8. Lane CR, Sutton B, Valcanis M, Kirk M, Walker C, Lalor
in shigellosis-related deaths without Shigella spp.- K, et al. Travel destinations and sexual behavior as indi-
specific interventions, Asia. Emerg Infect Dis. 2010 cators of antibiotic resistant shigella strains—Victoria,
Nov;16(11):1718–23. Australia. Clin Infect Dis. 2016 Mar 15;62(6):722–9.
4. CDC. Importation and domestic transmission of 9. Nygren BL, Schilling KA, Blanton EM, Silk BJ, Cole
Shigella sonnei resistant to ciprofloxacin—United DJ, Mintz ED. Foodborne outbreaks of shigello-
States, May 2014–February 2015. MMWR Morb Mortal sis in the USA, 1998–2008. Epidemiol Infect. 2013
Wkly Rep. 2015 Apr 3;64(12):318–20. Feb;141(2):233–41.
5. Gray MD, Lacher DW, Leonard SR, Abbott J, Zhao S, 10. Wong MR, Reddy V, Hanson H, Johnson KM, Tsoi
Lampel KA, et al. Prevalence of Shiga toxin-producing B, Cokes C, et al. Antimicrobial resistance trends of
Shigella species isolated from French travellers return- Shigella serotypes in New York City, 2006–2009. Microb
ing from the Caribbean: an emerging pathogen with Drug Resist. 2010 Jun;16(2):155–61.
INFECTIOUS AGENT TRANSMISSION
Smallpox is caused by variola virus, genus
Smallpox
Orthopoxvirus. Other members of this genus that
Person to person, principally respiratory; less
cause infection in humans are vaccinia virus,
commonly through contact with infectious skin
monkeypox virus, and cowpox virus. In 1980, the
lesions or scabs.
World Health Organization officially declared
smallpox to be eradicated.
Vaccinia DIAGNOSIS
Infections with wild vaccinialike viruses have Orthopoxvirus infection is confirmed by PCR or
been reported among cattle and buffalo herders in virus isolation. Health care providers can refer
BIBLIOGRAPHY
1. Baxby D, Bennett M, Getty B. Human cowpox 1969- 4. Reynolds MG, Emerson GL, Pukuta E, Karhemere S,
93: a review based on 54 cases. Br J Dermatol. 1994 Muyembe JJ, Bikindou A, et al. Detection of human
Nov;131(5):598–6 07. monkeypox in the Republic of the Congo following
2. Levine RS, Peterson AT, Yorita KL, Carroll D, Damon intensive community education. Am J Trop Med Hyg.
IK, Reynolds MG. Ecological niche and geographic 2013 May;88(5):982–5.
distribution of human monkeypox in Africa. PLoS One. 5. Trindade GS, Guedes MI, Drumond BP, Mota BE,
2007;2(1):e176. Abrahao JS, Lobato ZI, et al. Zoonotic vaccinia
3. Nakazawa Y, Emerson GL, Carroll DS, Zhao H, Li Y, virus: clinical and immunological characteristics in
Reynolds MG, et al. Phylogenetic and ecologic perspec- a naturally infected patient. Clin Infect Dis. 2009 Feb
tives of a monkeypox outbreak, southern Sudan, 2005. 1;48(3):e37–4 0.
Emerg Infect Dis. 2013 Feb;19(2):237–45.
STRONGYLOIDIASIS
Francisca Abanyie
INFECTIOUS AGENT EPIDEMIOLOGY
An intestinal nematode, Strongyloides stercoralis. Endemic in the tropics and subtropics and in lim-
ited foci elsewhere, including in Appalachia and
TRANSMISSION the southeastern United States. Estimates of
Filariform larvae found in contaminated soil pen- global prevalence exceed 100 million. Most doc-
etrate human skin. Person-to-person transmis- umented infections in the United States occur
sion is rare but documented. in immigrants, refugees, and military veterans
STRONGYLOIDIASIS 323
4
3
2
who have lived in endemic areas for long periods which typically contain high numbers of filariform
of time. Risk for short-term travelers is low, but larvae. Serologic testing is available through com-
infections can occur. mercial laboratories and through the National
Institutes of Health and CDC (www.cdc.gov/dpdx;
CLINICAL PRESENTATION 404-718-4745; [email protected]).
Most infections are asymptomatic. With acute
infections, a localized, pruritic, erythematous TREATMENT
papular rash can develop at the site of skin pen- Treatment of choice for acute, chronic, and dis-
etration, followed by pulmonary symptoms (a seminated disease or hyperinfection is ivermec-
Löffler-
like pneumonitis), diarrhea, abdominal tin. The alternative is albendazole, although it is
3 pain, and eosinophilia. Migrating larvae in the skin
cause larva currens, a serpiginous urticarial rash.
associated with lower cure rates. Prolonged or
repeated treatment may be necessary in patients
Immunocompromised people, especially those with hyperinfection, disseminated disease, or
receiving systemic corticosteroids, those with coinfection with human T cell lymphotropic virus
human T cell lymphotropic virus type 1 infection, 1, as relapse can occur.
those with hematologic malignancies, or who
have had organ transplants, are at risk for hyper- PREVENTION
infection or disseminated disease, characterized No vaccine or preventative drugs are available.
by abdominal pain, diffuse pulmonary infiltrates, Protective measures include wearing shoes when
and septicemia or meningitis from enteric bacte- walking in areas where humans may have defe-
ria. The death rate from untreated hyperinfection cated. It may be reasonable to perform serologic
and disseminated strongyloidiasis is high. testing on patients who have been at high risk
for Strongyloides infection and who will either be
DIAGNOSIS placed on glucocorticosteroids, other immuno-
Peripheral blood eosinophilia is common in suppressive drug regimens, or who will undergo
intestinal strongyloidiasis but often absent in procedures such as transplantation that involve
disseminated strongyloidiasis. Rhabditiform lar- immunosuppression. If indicated, these patients
vae can be visualized on microscopic examina- should be treated before immunosuppression.
tion of stool, either directly or by culture on agar Empiric treatment may be considered in people
plates. Repeated stool examinations or exam- deemed at high risk of strongyloidiasis in whom
ination of duodenal contents may be necessary. immediate immunosuppression is required.
Hyperinfection and disseminated strongyloidiasis
are diagnosed by examining stool, sputum, cere- CDC website: www.cdc.gov/parasites/
brospinal fluid, and other body fluids and tissues, strongyloides
BIBLIOGRAPHY
1. Keiser PB, Nutman TB. Strongyloides stercoralis in the prevalence and management. PLoS Negl Trop Dis. 2014
immunocompromised population. Clin Microbiol Rev. Aug;8(8):e3018.
2004 Jan;17(1):208–17. 4. Seybolt LM, Christiansen D, Barnett ED. Diagnostic
2. Olsen A, van Lieshout L, Marti H, Polderman T, Polman evaluation of newly arrived asymptomatic refu-
K, Steinmann P, et al. Strongyloidiasis—the most gees with eosinophilia. Clin Infect Dis. 2006 Feb
neglected of the neglected tropical diseases? Trans R 1;42(3):363–7.
Soc Trop Med Hyg. 2009 Oct;103(10):967–72. 5. Siddiqui AA, Berk SL. Diagnosis of Strongyloides
3. Puthiyakunnon S, Boddu S, Li Y, Zhou X, Wang C, Li stercoralis infection. Clin Infect Dis. 2001 Oct
J, et al. Strongyloidiasis—an insight into its global 1;33(7):1040–7.
TAENIASIS
Paul T. Cantey, Jeffrey L. Jones
BIBLIOGRAPHY
1. Cantey PT, Coyle CM, Sorvillo FJ, Wilkins PP, Starr 3. Wittner M, White ACJ, Tanowitz HB. Taenia and
MC, Nash TE. Neglected parasitic infections in the other tapeworm infections. In: Guerrant R.L.,
United States: cysticercosis. Am J Trop Med Hyg. 2014 Walker D.H., Weller P.F., editors. Tropical Infectious
May;90(5):805–9. Diseases: Principles, Pathogens and Practice. 3rd ed.
2. Garcia HH, Gonzalez AE, Evans CA, Gilman RH, Philadelphia: Saunders Elsevier; 2011. pp. 839–47.
Cysticercosis Working Group in Peru. Taenia solium
cysticercosis. Lancet. 2003 Aug 16;362(9383):547–56.
TETANUS
Tejpratap S. P. Tiwari
TRANSMISSION EPIDEMIOLOGY
Contact with nonintact skin, usually via inju- Distributed worldwide; more common in rural
ries from contaminated objects. “Tetanus-prone” and agricultural regions, areas where contact with
TETANUS 325
3
62
BIBLIOGRAPHY
1. CDC. Updated recommendations for use of tetanus 2. Farrar JJ, Yen LM, Cook T, Fairweather N, Binh N, Parry
toxoid, reduced diphtheria toxoid and acellular per- J, et al. Tetanus. J Neurol Neurosurg Psychiatry. 2000
tussis (Tdap) vaccine from the Advisory Committee on Sep;69(3):292–301.
Immunization Practices, 2010. MMWR Morb Mortal 3. World Health Organization. Tetanus vaccine. Wkly
Wkly Rep. 2011 Jan 14;60(1):13–5. Epidemiol Rec. 2006 May 19;81(20):198–208.
TICKBORNE ENCEPHALITIS
Marc Fischer, Ingrid B. Rabe, Pierre E. Rollin
infrequently been reported through laboratory military training. The risk is negligible for peo-
exposure and slaughtering viremic animals. ple who remain in urban or unforested areas
Direct person-to-person spread of TBE virus and who do not consume unpasteurized dairy
occurs only rarely, through blood transfusion or products.
breastfeeding. Vector tick population density and infec-
tion rates in TBE virus-endemic foci are highly
EPIDEMIOLOGY variable. For example, TBE virus infection
TBE is endemic in focal areas of Europe and rates in I. ricinus in central Europe vary from
Asia, extending from eastern France to north- <0.1% to approximately 5%, depending on geo-
ern Japan and from northern Russia to Albania. graphic location and time of year, while rates
Approximately 5,000–13,000 TBE cases are
reported each year, with large annual fluctua-
of up to 40% have been reported in I. persulca-
tus in Siberia. The number of TBE cases reported
3
tions. Russia has the largest number of reported from a country depends on the ecology and geo-
cases. The highest disease incidence has been graphic distribution of TBE virus, the intensity of
reported from western Siberia, Slovenia, and diagnosis and surveillance, and the vaccine cov-
the Baltic States (Estonia, Latvia, Lithuania). erage in the population. Therefore, the number
Other European countries with reported cases of human TBE cases reported from an area may
or known endemic areas include Albania, not be a reliable predictor of a traveler’s risk for
Austria, Belarus, Bosnia, Croatia, Czech infection. The same ticks that transmit TBE virus
Republic, Denmark, Finland, France, Germany, can also transmit other pathogens, including
Hungary, Italy, Norway, Poland, Romania, Borrelia burgdorferi (the agent for Lyme disease),
Serbia, Slovakia, Sweden, Switzerland, and Anaplasma phagocytophilum (anaplasmosis),
Ukraine. Asian countries with reported TBE and Babesia spp. (babesiosis), and simultane-
cases or virus activity include China, Japan, ous infection with multiple organisms has been
Kazakhstan, Kyrgyzstan, Mongolia, and described.
South Korea. From 2000 through 2015, 7 cases of TBE among
Most cases occur from April through US travelers to Europe and China were reported.
November, with peaks in early and late sum- TBE is not a nationally notifiable disease in the
mer when ticks are active. The incidence and United States, and additional cases may have
severity of disease are highest in people aged occurred.
≥50 years. Most cases occur in areas <2,500
ft (750 m). In the last 30 years, the geographic
range of TBE virus appears to have expanded to
CLINICAL PRESENTATION
Approximately two- thirds of infections are
new areas, and the virus has been found at alti-
asymptomatic. The median incubation period for
tudes up to and above 5,000 ft (1,500 m). These
TBE is 8 days (range, 4–28 days). The incubation
trends are likely due to a complex combination
period for milkborne exposure is usually shorter
of changes in diagnosis and surveillance, human
(3–4 days). Acute neuroinvasive disease is the
activities and socioeconomic factors, and ecol-
most commonly recognized clinical manifesta-
ogy and climate.
tion of TBE virus infection. However, TBE disease
The overall risk of acquiring TBE for an unvac-
often presents with milder forms of the disease or
cinated visitor to a highly endemic area during
a biphasic course:
the TBE virus transmission season has been esti-
mated at 1 case per 10,000 person-months of • First phase: nonspecific febrile illness with
exposure. Most TBE virus infections result from headache, myalgia, and fatigue. Usually lasts
tick bites acquired in forested areas through for several days and may be followed by an
activities such as camping; hiking; fishing; bicy- afebrile and relatively asymptomatic period.
cling; collecting mushrooms, berries, or flow- Up to two-thirds of patients recover without
ers; and outdoor occupations such as forestry or any further illness.
• Second phase: central nervous system isolation and RT-PCR should not be used to rule
involvement resulting in aseptic meningi- out a diagnosis of TBE. Clinicians should contact
tis, encephalitis, or myelitis. Findings include their state or local health department, the CDC
meningeal signs, altered mental status, cog- Viral Special Pathogens Branch (404-639-1115), or
nitive dysfunction, ataxia, rigidity, seizures, CDC Division of Vector-Borne Diseases (970-221-
tremors, cranial nerve palsies, and limb 6400) for assistance with diagnostic testing.
paresis.
TREATMENT
Disease severity increases with age. Although TBE There is no specific antiviral treatment for TBE;
tends to be less severe in children, residual symp- therapy consists of supportive care and manage-
3 toms and neurologic deficits have been described.
Clinical course and long-term outcome also vary
ment of complications.
Abbreviation: IM, intramuscular.
1
No TBE vaccines are licensed or available in the United States. FSME-IMMUN, FSME-IMMUN Junior, Encepur-Adults,
and Encepur-Children are licensed in Europe and EnceVir and TBE-Moscow are licensed in Russia.
2
If a rapid immune response is required, the second dose can be administered 2 weeks after the first dose.
3
Booster doses recommended every 3 years for people aged ≥50 years.
4
An accelerated schedule has been used with 3 doses given on days 0, 7, and 21. After the primary series, the first
booster dose is administered at 12–18 months.
5
For emergency situations, there is a rapid primary series schedule of 0 and 1–2 months.
been evaluated for both European vaccines, and adventure travel, or living in TBE-endemic coun-
results in seroconversion rates are similar to those tries for an extended period of time, may wish to
observed with the standard vaccination schedule. be vaccinated in Europe.
Travelers anticipating high-risk exposures, such as
working or camping in forested areas or farmland, CDC website: www.cdc.gov/vhf/tbe
BIBLIOGRAPHY
1. Amicizia D, Domnich A, Panatto D, Lai PL, Cristina ML, 5. Kollaritsch H, Paulke-Korinek M, Holzmann H,
Avio U, et al. Epidemiology of tick-borne encephalitis Hombach J, Bjorvatn B, Barrett A. Vaccines and vac-
(TBE) in Europe and its prevention by available vac- cination against tick-borne encephalitis. Expert Rev
cines. Hum Vaccin Immunother. 2013 May;9(5):1163–71. Vaccines. 2012 Sep;11(9):1103–19.
2. CDC. Tick-borne encephalitis among US travelers to 6. Kunze U. The International Scientific Working Group on
Europe and Asia—2000-2009. MMWR Morb Mortal Tick-Borne Encephalitis (ISW TBE): Review of 17 years
Wkly Rep. 2010 Mar 26;59(11):335–8. of activity and commitment. Ticks Tick Borne Dis. 2016
3. Committee to Advise on Tropical Medicine and Travel Apr;7(3):399–4 04.
(CATMAT). Statement on tick-borne encephalitis. An 7. Ruzek D, Dobler G, Donoso Mantke O. Tick-borne
Advisory Committee Statement (ACS). Can Commun encephalitis: pathogenesis and clinical implications.
Dis Rep. 2006 Apr 1;32(ACS-3):1–18. Travel Med Infect Dis. 2010 Jul;8(4):223–32.
4. Donoso Mantke O, Escadafal C, Niedrig M, Pfeffer M, 8. Steffen R. Epidemiology of tick-borne encephalitis
Working Group for Tick-Borne Encephalitis Virus. (TBE) in international travellers to Western/Central
Tick-borne encephalitis in Europe, 2007 to 2009. Euro Europe and conclusions on vaccination recommenda-
Surveill. 2011;16(39). tions. J Travel Med. 2016 Apr;23(4).
9. Suss J. Tick-borne encephalitis 2010: epidemiology, risk 10. World Health Organization. Vaccines against tick-borne
areas, and virus strains in Europe and Asia—an over- encephalitis: WHO position paper. Wkly Epidemiol Rec.
view. Ticks Tick Borne Dis. 2011 Mar;2(1):2–15. 2011 Jun 10;86(24):241–56.
TOXOPLASMOSIS
Jeffrey L. Jones
3
INFECTIOUS AGENT occur, and learning disabilities, cognitive deficits,
Toxoplasma gondii, an intracellular coccidian pro- or visual impairments may develop later in life.
tozoan parasite.
DIAGNOSIS
TRANSMISSION Serologic testing for T. gondii antibodies. Eye
Ingestion of soil, water, or food contaminated disease is diagnosed by ocular examination.
with cat feces, ingestion of undercooked meat, Diagnosis of toxoplasmic encephalitis in immu-
congenital transmission when a woman becomes nocompromised people (most often seen in peo-
infected during pregnancy, and contaminated ple with AIDS) can be based on typical clinical
blood transfusion and organ transplantation. course and identification of ≥1 mass lesion by CT,
MRI, or other radiographic testing. Biopsy may be
EPIDEMIOLOGY needed to make a definitive diagnosis.
T. gondii is endemic throughout most of the world.
Risk is higher in developing and tropical coun- TREATMENT
tries, especially when people eat undercooked Treatment is reserved for those with severe dis-
meat, drink untreated water, or are extensively ease or who are immunocompromised. A number
exposed to soil. of regimens are available, including pyrimeth-
amine, sulfadiazine, and leukovorin. Alternative
CLINICAL PRESENTATION treatment regimens include clindamycin, atova-
Incubation period is 5–23 days. Symptoms may quone, and azithromycin.
include influenzalike symptoms or a mononucle-
osis syndrome with prolonged fever, lymphade- PREVENTION
nopathy, elevated liver enzymes, lymphocytosis, Food and water precautions (see Chapter 2, Food
and weakness. Rarely, chorioretinitis or dissem- & Water Precautions). Avoid direct contact with
inated disease can occur in immunocompetent soil or sand that may be contaminated with cat
people. In severely immunocompromised peo- feces. If caring for a cat, change the litter box
ple, severe and even fatal toxoplasmic encephali- daily. If pregnant or immunocompromised, avoid
tis, pneumonitis, and other systemic illnesses can changing cat litter if possible, and do not adopt or
occur, most often from reactivation of a previous handle stray cats.
infection. Infants with congenital toxoplasmo-
sis are often asymptomatic, but eye disease, neu- CDC website: www.cdc.gov/parasites/
rologic disease, or other systemic symptoms can toxoplasmosis
BIBLIOGRAPHY
1. Anand R, Jones CW, Ricks JH, Sofarelli TA, Hale DC. 2. Bottieau E, Clerinx J, Van den Enden E, Van
Acute primary toxoplasmosis in travelers returning from Esbroeck M, Colebunders R, Van Gompel A, et al.
endemic countries. J Travel Med. 2012 Jan-Feb;19(1):57–60. Infectious mononucleosis-like syndromes in febrile
travelers returning from the tropics. J Travel Med. 2006 HIV-infected adults and adolescents: recommendations
Jul-Aug;13(4):191–7. from the Centers for Disease Control and Prevention,
3. Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet. 2004 the National Institutes of Health, and the HIV Medicine
Jun 12;363(9425):1965–76. Association of the Infectious Diseases Society of
America. [updated Aug 17 2016; cited 2016 Sep. 26].
4. Montoya JG, Remington JS. Management of Toxoplasma Available from: https://aidsinfo.nih.gov/contentfiles/
gondii infection during pregnancy. Clin Infect Dis. 2008 lvguidelines/adult_oi.pdf.
Aug 15;47(4):554–66.
6. Sepulveda-Arias JC, Gomez-Marin JE, Bobic B, Naranjo-
5. Panel on Opportunistic Infections in HIV-Infected Galvis CA, Djurkovic-Djakovic O. Toxoplasmosis as a
Adults and Adolescents. Guidelines for the preven- travel risk. Travel Med Infect Dis. 2014 Nov-Dec;12(6 Pt
tion and treatment of opportunistic infections in A):592–6 01.
3
TRYPANOSOMIASIS, AFRICAN
(SLEEPING SICKNESS)
Francisca Abanyie
INFECTIOUS AGENT are not at risk. Flies bite during the day, and <1%
Two subspecies of the protozoan parasite are infected. Risk of infection increases with the
Trypanosoma brucei (T. b. rhodesiense and number of fly bites, which is not always directly
T. b. gambiense). correlated with duration of travel. Cases imported
into the United States are rare.
TRANSMISSION
The bite of an infected tsetse fly (Glossina CLINICAL PRESENTATION
spp.). Bloodborne and congenital transmission
are rare. T. b. rhodesiense
Clinical manifestations generally appear within
EPIDEMIOLOGY 1–3 weeks of the infective bite and may include
Endemic in rural sub-Saharan Africa. T. b. rhode- high fever, a chancre at the bite site, skin rash,
siense is found in eastern and southeastern Africa, headache, myalgia, thrombocytopenia, and
mainly Tanzania, Uganda, Malawi, Zambia, and less commonly, splenomegaly, renal failure,
Zimbabwe. T. b. gambiense is found in central Africa or cardiac dysfunction. Central nervous sys-
and in limited areas of West Africa, primarily in tem involvement can occur within a month of
Democratic Republic of the Congo, Central African infection and results in sleep cycle disturbance,
Republic, Angola, South Sudan, Guinea, Cameroon, mental deterioration, and eventually death.
Gabon, Côte d’Ivoire, Congo, Chad, and north-
ern Uganda. World Health Organization (WHO) T. b. gambiense
maps of African trypanosomiasis cases, by country, Clinical manifestations generally appear months
are available at www.who.int/trypanosomiasis_ to years after infection and are nonspecific. Signs
african/country/foci_AFRO/en. and symptoms may include intermittent fever,
In 2014, 3,796 sleeping sickness cases were headache, malaise, myalgia, arthralgia, facial
reported to the World Health Organization; edema, pruritus, lymphadenopathy, and weight
T. b. gambiense accounted for >98% of cases. Many loss. Central nervous system involvement occurs
cases, however, are probably not recognized nor after several months to years of infection and is
reported. Tsetse flies inhabit rural, densely vege- characterized by daytime somnolence and night-
tated areas; people who only travel to urban areas time sleep disturbance, severe headache, and
BIBLIOGRAPHY
1. Brun R, Blum J, Chappuis F, Burri C. Human African 3. Simarro PP, Franco JR, Cecchi G, Paone M, Diarra A,
trypanosomiasis. Lancet. 2010 Jan 9;375(9709):148–59. Ruiz Postigo JA, et al. Human African trypanosomiasis
2. Franco JR, Simarro PP, Diarra A, Jannin JG. in non-endemic countries (2000–2010). J Travel Med.
Epidemiology of human African trypanosomiasis. 2012 Jan-Feb;19(1):44–53.
Clinical epidemiology. 2014;6:257–75.
TRYPANOSOMIASIS, AMERICAN
(CHAGAS DISEASE)
Susan Montgomery
TRANSMISSION EPIDEMIOLOGY
Typically through feces of an infected triatom- Endemic in many parts of Mexico and Central
ine insect (reduviid bug), may occur when a bug and South America. In the United States, Chagas
bite is scratched or by consuming food or bever- disease is primarily a disease of immigrants
ages contaminated with infected bug feces; may from endemic areas of Latin America. The risk
to travelers is extremely low, but they could be commonly, ELISA, immunoblot, and immunoflu-
at risk if staying in poor-quality housing or from orescent antibody test) to detect T. cruzi–specific
consuming contaminated food or beverages in antibodies. PCR is not a useful diagnostic test
endemic areas. for chronic-phase infections since parasites are
not detectable in the peripheral blood during
CLINICAL PRESENTATION this phase.
Acute illness typically develops ≥1 week after
exposure and lasts up to 60 days. A chagoma TREATMENT
may develop at the site of infection; for example, Antitrypanosomal drug treatment is always rec-
the Romaña sign (edema of the eyelid and ocu- ommended for acute, early congenital, and reac-
lar tissues). Most infected people never develop
symptoms but remain infected throughout their
tivated T. cruzi infection and for chronic T. cruzi
infection in children aged <18 years old. In adults,
3
lives. Approximately 20%– 30% of patients will treatment is usually recommended. In the United
develop chronic manifestations of Chagas dis- States, treatment drugs (benznidazole and nifur-
ease after a prolonged period without any clinical timox) are provided by CDC under investiga-
disease. Chronic Chagas disease usually affects tional protocols. Contact CDC (chagas@cdc.
the heart; clinical signs include conduction sys- gov; 404- 718-4745) for assistance with clinical
tem abnormalities, ventricular arrhythmias, and management.
in late-stage disease, congestive cardiomyopa-
thy. Less common chronic gastrointestinal prob- PREVENTION
lems (such as megaesophagus or megacolon) may Insect precautions (see Chapter 2, Protection
develop with or without cardiac manifestations. against Mosquitoes, Ticks, & Other Arthropods)
Reactivation disease can occur in immunocom- and food and water precautions (see Chapter 2,
promised patients. Food & Water Precautions). Avoid sleeping in
thatch, mud, and adobe housing in endemic areas;
DIAGNOSIS using insecticides in and around such homes is
During the acute phase, parasites may be detect- also protective. Impregnated bed nets are help-
able in fresh preparations of buffy coat or stained ful. Screening blood and organs for Chagas dis-
peripheral blood specimens; PCR testing may also ease prevents transmission via transfusion or
help detect acute infection. After the acute phase, transplantation.
diagnosis requires 2 or more serologic tests (most
CDC website: www.cdc.gov/parasites/chagas
BIBLIOGRAPHY
1. Bern C. Antitrypanosomal therapy for chronic Chagas’ 3. Carter YL, Juliano JJ, Montgomery SP, Qvarnstrom Y.
disease. N Engl J Med. 2011 Jun 30;364(26):2527–34. Acute Chagas disease in a returning traveler. Am J Trop
2. Bern C, Montgomery SP, Herwaldt BL, Rassi A Jr, Marin- Med Hyg. 2012 Dec;87(6):1038–4 0.
Neto JA, Dantas RO, et al. Evaluation and treatment 4. Rassi A Jr, Rassi A, Marin-Neto JA. Chagas disease.
of Chagas disease in the United States: a systematic Lancet. 2010 Apr 17;375(9723):1388–4 02.
review. JAMA. 2007 Nov 14;298(18):2171–81.
TUBERCULOSIS
Philip LoBue
nodes, pleura, bones and joints, brain and spinal are pending. Culture-based susceptibility testing
cord lining (meningitis), kidneys, bladder, and is recommended for all patients with a positive
genitalia. culture, regardless of the availability of molecu-
Infection is manifested by a positive TST or lar testing, to make a final determination on the
IGRA result 8–10 weeks after exposure. Overall, appropriate drug regimen. LTBI is diagnosed by a
only 5%–10% of otherwise healthy people have an positive TST or IGRA after further examinations
infection that progresses to disease during their (such as chest radiograph, symptom review) have
lifetime. Progression to disease can occur weeks excluded TB disease. Tuberculosis is a nationally
to decades after initial infection. People with notifiable disease.
TB disease have symptoms or other manifesta-
tions of illness such as an abnormal chest radio-
graph. In the remainder, the infection remains
TREATMENT
People with LTBI can be treated to prevent pro-
3
in a latent state (latent TB infection or LTBI) in gression to TB disease. American Thoracic Society
which the infected person has no symptoms and (ATS)/CDC guidelines for treatment of LTBI rec-
cannot spread TB to others. The risk of progres- ommend 9 months of isoniazid as the preferred
sion is much higher in immunosuppressed peo- treatment. The combination regimen of isoniazid
ple (8%–10% per year in HIV-infected people not and rifapentine given as 12 weekly doses using
receiving antiretroviral therapy). People who directly observed therapy is recommended as
are receiving tumor necrosis factor inhibitors equivalent to 9 months of isoniazid for treating
to treat rheumatoid arthritis and other chronic LTBI in otherwise healthy patients aged ≥12 years
inflammatory conditions are also at increased who are at higher risk of developing active TB, for
risk for disease progression. example after recent exposure to contagious TB.
For people who have been exposed to isoniazid-
DIAGNOSIS resistant, rifampin-susceptible TB or who can-
Diagnosis of TB disease is confirmed by cultur- not tolerate isoniazid, 4 months of rifampin is
ing M. tuberculosis from sputum or other respira- a reasonable alternative. Travelers who suspect
tory specimens for pulmonary TB and from other that they have been exposed to TB should inform
affected body tissues or fluids for extrapulmonary their health care provider of the possible expo-
TB. On average, it takes about 2 weeks to culture sure and receive medical evaluation. CDC and
and identify M. tuberculosis, even with rapid cul- ATS have published guidelines for targeted test-
ture techniques. A preliminary diagnosis of TB ing and treatment of LTBI. Because drug resis-
can be made when acid-fast bacilli are seen by tance is relatively common in some parts of the
microscope on sputum smear or in other body world, travelers who have TST or IGRA conver-
tissues or fluids. However, microscopy cannot sion associated with international travel should
distinguish between M. tuberculosis and nontu- consult experts in infectious diseases or pulmo-
berculous mycobacteria. This is particularly prob- nary medicine.
lematic in countries such as the United States TB disease is treated with a multiple-drug reg-
where TB incidence is low. Nucleic acid amplifica- imen administered by directly observed therapy
tion tests are more rapid than culture and specific for 6–9 months (usually isoniazid, rifampin, eth-
for M. tuberculosis. They are also more sensitive ambutol, and pyrazinamide for 2 months, fol-
than the acid-fast bacillus smear but less sensi- lowed by isoniazid and rifampin for an additional
tive than culture. A diagnosis of TB disease can be 4 months) if the TB is not MDR TB. MDR TB
made by using clinical criteria in the absence of treatment is more difficult, requiring 4–6 drugs
microbiologic confirmation. However, laboratory for 18–24 months; it should be managed by an
testing should be performed when feasible to con- expert in MDR TB. ATS/CDC/Infectious Diseases
firm the diagnosis. Molecular tests for drug resis- Society of America have published guidelines on
tance can be performed directly on specimens and TB treatment (www.cdc.gov/mmwr/preview/
can guide initial treatment while culture results mmwrhtml/rr5211a1.htm).
TUBERCULOSIS 335
3
6
- 201-582
- 101-200
- 26-100
1-25
No estimate
TUBERCULOSIS 337
8
3
Armenia 9.4 43
Azerbaijan 13 28
Bangladesh 1.4 29
Belarus 34 69
3 Bulgaria 2.3 23
Burma 5.0 27
China 5.7 26
Estonia 19 62
Ethiopia 1.6 12
Georgia 12 39
India 2.2 15
Indonesia 1.9 12
Kazakhstan 26 58
Kyrgyzstan 26 55
Latvia 8.2 30
Lithuania 14 49
Moldova 24 62
Nigeria 2.9 14
Pakistan 3.7 18
Philippines 2.0 21
Russia 19 49
Tajikistan 8.1 52
Ukraine 22 56
Uzbekistan 23 62
Vietnam 4.0 23
BIBLIOGRAPHY
1. American Thoracic Society and CDC. Diagnostic stan- 7. Jensen PA, Lambert LA, Iademarco MF, Ridzon R.
dards and classification of tuberculosis in adults and Guidelines for preventing the transmission of
children. Am J Respir Crit Care Med. 2000 Apr;161(4 Mycobacterium tuberculosis in health-care
Pt 1):1376–95. settings, 2005. MMWR Recomm Rep. 2005 Dec
2. American Thoracic Society and CDC. Targeted tubercu- 30;54(RR-17):1–141.
lin testing and treatment of latent tuberculosis infection. 8. Seaworth BJ, Armitige LY, Aronson NE, Hoft
Am J Respir Crit Care Med. 2000 Apr;161(4 Pt 2):S221–47. DF, Fleenor ME, Gardner AF, et al. Multidrug-
3. CDC. Availability of an assay for detecting resistant tuberculosis. Recommendations for
Mycobacterium tuberculosis, including rifampin- reducing risk during travel for healthcare and
resistant strains, and considerations for its use—United humanitarian work. Ann Am Thorac Soc. 2014
States, 2013. MMWR Morb Mortal Wkly Rep. 2013 Oct Mar;11(3):286–95.
18;62(41):821–7. 9. World Health Organization. Global tuberculosis report
4. CDC. Recommendations for use of an isoniazid- 2015. 20th ed. Geneva: World Health Organization; 2015
rifapentine regimen with direct observation to treat [cited 2016 Sep. 26]. Available from: http://www.who.
latent Mycobacterium tuberculosis infection. MMWR int/tb/publications/global_report/en/.
Morb Mortal Wkly Rep. 2011 Dec 9;60(48):1650–3. 10. World Health Organization. Tuberculosis and air
5. CDC. Treatment of tuberculosis. MMWR Recomm Rep. travel: guidelines for prevention and control. 3rd ed.
2003 Jun 20;52(RR-11):1–77. Geneva: World Health Organization; 2008 [cited
2016 Sep. 26]. Available from: http://www.who.int/tb/
6. CDC. Updated guidelines for using interferon gamma publications/tb-airtravel-guidance/en/.
release assays to detect Mycobacterium tuberculosis
infection, United States. MMWR Recomm Rep. 2010.
TUBERCULOSIS 339
0
4
3
...perspectives
TUBERCULIN SKIN TESTING
OF TRAVELERS
Philip LoBue
Screening for asymptomatic yield a negative result are have potential prolonged or
Perspectives sections are written as editorial discussions aiming to add depth and clinical perspective to the official
recommendations contained in the book. The views and opinions expressed in this section are those of the author and do not
necessarily represent the official position of CDC.
to make the diagnosis. Bone marrow culture Patients treated with an antibiotic may con-
increases the diagnostic yield to approximately tinue to have fever for 3–5 days, although the
80% of cases and is relatively unaffected by prior height of the fever generally decreases each day.
or concurrent antibiotic use. Stool culture is not Patients may actually feel worse during the sev-
usually positive during the first week of illness, eral days it takes for the fever to end. If fever in a
so blood culture is preferred. Urine culture has person with culture-confirmed typhoid or para-
no higher diagnostic yield than stool culture for typhoid fever does not subside within 5 days,
acute cases. alternative antimicrobial agents or other foci of
The Widal test is unreliable but is widely used infection such as abscesses, bone or joint infec-
in developing countries because of its low cost. It tions, and other extraintestinal sites should be
is a serologic assay that may react in patients with
typhoid or paratyphoid fever, but is not specific
considered.
3
and false positives may occur. Serologic assays PREVENTION
are not an adequate substitute for blood, stool, or
Food and Water
bone marrow culture.
Safe food and water precautions and frequent
Because there is no definitive serologic test for
handwashing (especially before meals) are
typhoid or paratyphoid fever, the initial diagno-
important in preventing typhoid and paratyphoid
sis often has to be made clinically. The combina-
fever (see Chapter 2, Food & Water Precautions).
tion of a history of risk for infection and a gradual
Although vaccines are recommended to prevent
onset of fever that increases in severity over sev-
typhoid fever, they are not 100% effective; there-
eral days should raise suspicion of typhoid or
fore, even vaccinated travelers should follow rec-
paratyphoid fever. Typhoid fever is a nationally
ommended food and water precautions. For
notifiable disease.
paratyphoid fever, food and water precautions are
the only prevention method, as no vaccines are
TREATMENT available.
Specific antimicrobial therapy shortens the clin-
ical course of enteric fever and reduces the risk
Vaccine
for death. Fluoroquinolones are recommended
for empiric treatment of enteric fever in adults, INDICATIONS FOR USE
but quinolone resistance is >80% for Typhi and CDC recommends typhoid vaccine for travelers
Paratyphi A infections in travelers to South and to areas where there is an increased risk of expo-
Southeast Asia, which suggests that treatment fail- sure to S. enterica serotype Typhi. Destination-
ures will occur. Injectable third-generation ceph- specific vaccine recommendations are available
alosporins are often the empiric drug of choice at the CDC Travelers’ Health website (www.cdc.
when the possibility of fluoroquinolone resistance gov/travel).
is high. Azithromycin and ceftriaxone are increas- Two typhoid vaccines are available in the
ingly used to treat typhoid fever or paratyphoid United States:
fever because of the emergence of multidrug-resis- • Vi capsular polysaccharide vaccine (ViCPS)
tant strains, although increasing resistance to azi- (Typhim Vi, manufactured by Sanofi Pasteur)
thromycin in Typhi strains has been documented for intramuscular use
outside the United States. In contrast, no cases of
ceftriaxone resistance have been reported among
• Oral live attenuated vaccine (Vivotif, manu-
factured from the Ty21a strain of serotypeTy-
Typhi and Paratyphi A isolates tested by the
phi by PaxVax)
CDC National Antimicrobial Monitoring System
through 2013. Additional data on antimicrobial Both typhoid vaccines protect 50%–80% of recip-
resistance among enteric fever cases in the United ients; travelers should be reminded that typhoid
States can be found at www.cdc.gov/narmsnow. immunization is not 100% effective, and typhoid
fever could still occur. Available typhoid vaccines may not have a large effect on how well the vac-
offer no protection against paratyphoid fever. cine works. However, we are unaware of any
studies showing the effect of such deviations;
VACCINE ADMINISTRATION thus, if 4 doses are not completed as directed,
Table 3-21 provides information on vaccine dos- optimal immune response may not be achieved.
age, administration, and revaccination. The time The vaccine manufacturer recommends that
required for primary vaccination differs for the 2 Ty21a not be administered to infants or to chil-
vaccines, as do the lower age limits. dren aged <6 years. A booster dose is recom-
Primary vaccination with ViCPS consists of one mended every 5 years for people who remain
0.5 mL (25 mg) dose administered intramuscu- at risk.
3 larly. One dose should be given ≥2 weeks before
travel. The manufacturer does not recommend VACCINE SAFETY AND ADVERSE REACTIONS
the vaccine for infants and for children <2 years Adverse reactions to Ty21a vaccine are rare and
old. A booster dose is recommended every 2 years mainly consist of abdominal discomfort, nau-
for people who remain at risk. sea, vomiting, and rash. ViCPS vaccine is most
Primary vaccination with oral Ty21a vac- often associated with headache (16%–20%) and
cine consists of 4 capsules, 1 taken every other injection-site reactions (7%). Adverse reactions
day. The capsules should be kept refrigerated should be reported to the Vaccine Adverse Event
(not frozen), and all 4 doses must be taken to Reporting System by visiting https:// vaers.hhs.
achieve maximum efficacy. Each capsule should gov/index or calling 1-800-822-7967.
be taken with cool liquid no warmer than 98.6°F
(37°C), approximately 1 hour before a meal and PRECAUTIONS AND CONTRAINDICATIONS
≥2 hours after a previous meal. This regimen No information is available on the safety of these
should be completed ≥1 week before poten- vaccines in pregnancy; it is prudent on theo-
tial exposure. What to do when a dose of the retical grounds to avoid vaccinating pregnant
oral vaccine is missed or taken late is unclear. women. However, the benefits of vaccinating
Some suggest that minor deviations in the dos- pregnant women may outweigh potential risks
ing schedule, such as taking a dose one day late, when the likelihood of typhoid exposure is high;
1
The vaccine must be kept refrigerated (35.6°F–46.4°F, 2°C–8°C).
2
Administer with cool liquid no warmer than 98.6°F (37°C).
the inactivated vaccine (ViCPS) may be consid- Theoretical concerns have been raised about
ered in these situations. Live attenuated Ty21a the immunogenicity of live, attenuated Ty21a vac-
vaccine should not be given to pregnant women cine in people concurrently receiving antimicrobial
or immunocompromised travelers, including agents (including antimalarial chemoprophylaxis),
those infected with HIV. The intramuscular vac- viral vaccines, or immune globulin. The growth of
cine presents a theoretically safer alternative for the live Ty21a strain is inhibited in vitro by various
immunocompromised travelers. (The Advisory antibacterial agents, and vaccination with Ty21a
Committee on Immunization Practices does not should be delayed for >72 hours after the admin-
recommend against vaccinating household con- istration of any antibacterial agent. Available data
tacts of immunocompromised people with Ty21a; do not suggest that simultaneous administration
although vaccine organisms can be shed tran-
siently in the stool of vaccine recipients, second-
of oral polio or yellow fever vaccine decreases the
immunogenicity of Ty21a. If typhoid vaccination
3
ary transmission of vaccine organisms has not is warranted, it should not be delayed because of
been documented.) The only contraindication administration of viral vaccines. Simultaneous
to vaccination with ViCPS vaccine is a history of administration of Ty21a and immune globulin
severe local or systemic reactions after a previous does not appear to pose a problem.
dose. Neither vaccine should be given to people
with an acute febrile illness. CDC website: www.cdc.gov/typhoid-fever
BIBLIOGRAPHY
1. Beeching NJ, Clarke PD, Kitchin NR, Pirmohamed J, 6. Gupta SK, Medalla F, Omondi MW, Whichard JM, Fields
Veitch K, Weber F. Comparison of two combined vac- PI, Gerner-Smidt P, et al. Laboratory-based surveil-
cines against typhoid fever and hepatitis A in healthy lance of paratyphoid fever in the United States: travel
adults. Vaccine. 2004 Nov 15;23(1):29–35. and antimicrobial resistance. Clin Infect Dis. 2008 Jun
2. Buckle GC, Walker CL, Black RE. Typhoid fever and 1;46(11):1656–63.
paratyphoid fever: systematic review to estimate global 7. Lynch MF, Blanton EM, Bulens S, Polyak C, Vojdani J,
morbidity and mortality for 2010. J Glob Health. 2012 Stevenson J, et al. Typhoid fever in the United States,
Jun;2(1):010401. 1999–2006. JAMA. 2009 Aug 26;302(8):859–65.
3. Crump JA, Mintz ED. Global trends in typhoid 8. Parry CM, Hien TT, Dougan G, White NJ,
and paratyphoid fever. Clin Infect Dis. 2010 Jan Farrar JJ. Typhoid fever. N Engl J Med. 2002 Nov
15;50(2):241–6. 28;347(22):1770–82.
4. Date KA, Newton AE, Medalla F, Blackstock A, 9. Steinberg EB, Bishop R, Haber P, Dempsey AF, Hoekstra
Richardson L, McCullough A, et al. Changing patterns RM, Nelson JM, et al. Typhoid fever in travelers: who
in enteric fever incidence and increasing antibiotic should be targeted for prevention? Clin Infect Dis. 2004
resistance of enteric fever isolates in the United States, Jul 15;39(2):186–91.
2008–2012. Clin Infect Dis. 2016 Aug 1;63(3):322–9. 10. Wain J, Pham VB, Ha V, Nguyen NM, To SD, Walsh AL,
5. Effa EE, Bukirwa H. Azithromycin for treating et al. Quantitation of bacteria in bone marrow from
uncomplicated typhoid and paratyphoid fever patients with typhoid fever: relationship between
(enteric fever). Cochrane Database Syst Rev. counts and clinical features. J Clin Microbiol. 2001
2008(4):CD006083. Apr;39(4):1571–6.
VARICELLA (CHICKENPOX)
Mona Marin, Adriana S. Lopez
hemorrhagic conditions; rarely (about 1 case in varicella. Treatment with oral acyclovir should
40,000), these complications may result in death. be considered for people at increased risk for
Modified varicella, also known as break- moderate to severe disease, such as people aged
through varicella, can occur in vaccinated peo- >12 years, people with chronic cutaneous or pul-
ple. Breakthrough varicella is usually mild, with monary disorders, people who are receiving
<50 lesions, low or no fever, and shorter dura- long-term salicylate therapy, and people who
tion of rash. The rash may be atypical in appear- are receiving short, intermittent, or aerosolized
ance with fewer vesicles and predominance of courses of corticosteroids. Intravenous acyclovir
maculopapular lesions. Breakthrough varicella is recommended for immunocompromised peo-
is contagious, although less so than varicella in ple, including patients being treated with high-
unvaccinated people. dose corticosteroids for ≥2 weeks, and people
with serious, virally mediated complications (such
3
DIAGNOSIS as pneumonia). Therapy initiated within 24 hours
Varicella is often diagnosed clinically on the basis of onset maximizes efficacy.
of a generalized maculopapulovesicular rash. The
clinical diagnosis of varicella in the United States PREVENTION
has become increasingly challenging as a grow- Vaccine
ing proportion of cases occur in vaccinated peo- All people, including those traveling or living
ple in whom disease is mild and rash is atypical. abroad, should be assessed for varicella immunity,
Although not routinely recommended, laboratory and those who do not have evidence of immu-
diagnosis is likely to become increasingly useful. nity or contraindications to vaccination should
Varicella is a nationally notifiable disease. receive age-appropriate vaccination. Vaccination
For laboratory confirmation, skin lesions are against varicella is not a requirement for entry
the preferred specimen. Vesicular swabs or scrap- into any country (including the United States),
ings and scabs from crusted lesions can be used to but people who do not have evidence of immunity
identify varicella-zoster virus DNA by PCR (pre- should be considered at risk for varicella during
ferred method as it is the most sensitive and spe- international travel. Evidence of immunity to var-
cific) or direct fluorescent antibody. In the absence icella includes any of the following:
of vesicles or scabs, scrapings of maculopapular
lesions can be collected for testing. Serologic tests • Documentation of age-appropriate
may also be used to confirm disease but are less vaccination:
reliable than PCR or direct fluorescent antibody > Preschool-aged children (≥12 months
methods for virus identification. through 3 years of age): 1 dose
> School-aged children (≥4 years of age),
• A significant rise in serum varicella IgG titers adolescents, and adults: 2 doses
from acute-and convalescent-phase samples
by any standard serologic assay can confirm a • Laboratory evidence of immunity or labora-
diagnosis retrospectively; these antibody tests tory confirmation of disease
may not be reliable in immunocompromised • Birth in the United States before 1980 (not a
people. criterion for health care personnel, pregnant
• Of note, testing for varicella-zoster IgM by women, and immunocompromised people)
using commercial kits is not recommended, • A health care provider’s diagnosis of varicella
because available methods lack sensitivity or verification of a history of varicella
and specificity; false-positive IgM results are
common in the presence of high IgG levels. • A health care provider’s diagnosis of herpes
zoster or verification of a history of herpes
zoster
TREATMENT
Treatment with antivirals is not routinely rec- Varicella vaccine contains live, attenuated
ommended for otherwise healthy children with varicella-
zoster virus. Single-
antigen varicella
vaccine is licensed for people aged ≥12 months, vaccine should be administered as soon as possi-
and the combination measles- mumps- rubella- ble within 5 days after exposure to rash, if there
varicella (MMRV) vaccine is licensed only for are no contraindications to use. Among children,
children 1–12 years. CDC recommends varicella protective efficacy was reported as ≥90% when
vaccination for all people aged ≥12 months with- vaccination occurred within 3 days of exposure.
out evidence of immunity to varicella who do not No data are available regarding a potential benefit
have contraindications to the vaccine: 1 dose for of administering a second dose to 1-dose vaccine
children aged 1–3 years and 2 doses for people aged recipients after exposure. However, adminis-
≥4 years. The minimum interval between doses is tration of the second dose is recommended for
3 months for children aged <13 years and 4 weeks exposed people to bring them up-to-date on vac-
3 for people aged ≥13 years. Contraindications for
vaccination include allergy to vaccine compo-
cination and for best protection against future
exposures.
nents, immune- compromising conditions or
treatments, and pregnancy. When evidence of Varicella Zoster Immune Globulin
immunity is uncertain, a possible history of vari- People without evidence of immunity who have
cella is not a contraindication to varicella vaccina- contraindications for vaccination and who are at
tion. Vaccine effectiveness is approximately 80% risk for severe varicella and complications are rec-
after 1 dose and 95% after 2 doses. ommended to receive postexposure prophylaxis
with varicella zoster immune globulin. The vari-
VACCINE SAFETY AND ADVERSE REACTIONS cella zoster immune globulin product licensed in
The varicella vaccine is generally well tolerated. the United States is VariZIG.
The most common adverse events after vaccina- People who should receive VariZIG after
tion are self-limited injection-site reactions (pain, exposure include immunocompromised peo-
soreness, redness, and swelling). Fever or a vari- ple, pregnant women without evidence of
cellalike rash, usually consisting of a few lesions at immunity, and some infants. VariZIG provides
the injection site or generalized rash with a small maximum benefit when administered as soon
number of lesions, are reported less frequently. as possible after exposure but may be effective
Compared with use of MMR and varicella if administered as late as 10 days after exposure.
vaccines at the same visit, use of MMRV vac- In the United States, VariZIG can be obtained
cine is associated with a higher risk for fever from FFF Enterprises, Temecula, California,
and febrile seizures 5–12 days after the first by calling 800-843-7477 or visiting www.fffen-
dose among children aged 12–23 months and terprises.com or from ASD Healthcare, Frisco,
approximately 1 additional febrile seizure for Texas, by calling 800-746-6273 or visiting www.
every 2,300–2,600 MMRV vaccine doses admin- asdhealthcare.com.
istered. Use of separate MMR and varicella vac- If VariZIG is not available, intravenous immune
cines avoids this increased risk for fever and globulin (IVIG) can be considered (also within
febrile seizures in this age group. For detailed 10 days of exposure). Additionally, in the absence
information regarding the varicella vaccine, of both VariZIG and IVIG, some experts recom-
visit www.cdc.gov/vaccines/vpd-vac/varicella/ mend prophylaxis with acyclovir (80 mg/kg/day in
default.htm. 4 divided doses for 7 days; maximum dose, 800 mg,
4 times per day), beginning 7–10 days after expo-
POSTEXPOSURE PROPHYLAXIS sure for people without evidence of immunity and
with contraindications for varicella vaccination.
Vaccine Published data on the benefit of acyclovir as post-
Varicella vaccine is recommended for postexpo- exposure prophylaxis among immunocompro-
sure administration for unvaccinated healthy peo- mised people are limited.
ple aged ≥12 months and without other evidence
of immunity, to prevent or modify the disease. The CDC website: www.cdc.gov/chickenpox
BIBLIOGRAPHY
1. American Academy of Pediatrics. Varicella-zoster infec- Committee on Immunization Practices (ACIP). MMWR
tions. In: Kimberlin DW, Brady MT, Jackson MA, Long Recomm Rep. 2008 Jun 6;57(RR-5):1–30.
SS, editors. Red Book: 2015 Report of the Committee 6. Marin M, Broder KR, Temte JL, Snider DE, Seward
on Infectious Diseases. 30th ed. Elk Grove Village, JF. Use of combination measles, mumps, rubella, and
IL: American Academy of Pediatrics; 2015. pp. 846–59. varicella vaccine: recommendations of the Advisory
2. Bialek SR, Perella D, Zhang J, Mascola L, Viner K, Committee on Immunization Practices (ACIP). MMWR
Jackson C, et al. Impact of a routine two-dose vari- Recomm Rep. 2010 May 7;59(RR-3):1–12.
cella vaccination program on varicella epidemiology. 7. Marin M, Guris D, Chaves SS, Schmid S, Seward
Pediatrics. 2013 Nov;132(5):e1134–4 0. JF. Prevention of varicella: recommendations
3
3. CDC. Updated recommendations for use of VariZIG— of the Advisory Committee on Immunization
United States, 2013. MMWR Morb Mortal Wkly Rep. Practices (ACIP). MMWR Recomm Rep. 2007 Jun
2013 Jul 19;62(28):574–6. 22;56(RR-4):1–4 0.
4. Gershon AA, Takahasi M, Seward JF. Varicella vaccine. 8. World Health Organization. WHO vaccine-preventable
In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. diseases: monitoring system. 2016 global summary
6th ed. Philadelphia: Saunders Elsevier; 2012. pp. 2016 [cited 2016 Sep. 26]. Available from: http://apps.
837–69. who.int/immunization_monitoring/globalsummary/
5. Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention schedules?sc%5Bd%5D=&sc%5Bv%5D%5B%5D=
of herpes zoster: recommendations of the Advisory VARICELLA&sc%5BOK%5D=OK.
VIRAL HEMORRHAGIC FEVERS
Barbara Knust, Mary Choi
BIBLIOGRAPHY
1. Ergonul O, Holbrook MR. Crimean-Congo hemorrhagic 7. Peters CJ, Makino S, Morrill JC. Rift valley fever.
fever. In: Guerrant RL, Walker DH, Weller PF, editors. In: Guerrant RL, Walker DH, Weller PF, editors.
Tropical Infectious Diseases: Principles, Pathogens and Tropical Infectious Diseases: Principles, Pathogens
Practice. 3rd ed. Philadelphia: Elsevier; 2011. pp. 466–9. and Practice. 3rd ed. Philadelphia: Saunders Elsevier;
2. Gunther S, Lenz O. Lassa virus. Crit Rev Clin Lab Sci. 2011. pp. 462–5.
2004;41(4):339–9 0. 8. Peters CJ, Zaki SR. Overview of viral hemorrhagic
3. Heyman P, Vaheri A, Lundkvist A, Avsic-Zupanc T. fevers. In: Guerrant RL, Walker DH, Weller PF, editors.
Hantavirus infections in Europe: from virus carriers to Tropical Infectious Diseases: Principles, Pathogens
a major public-health problem. Expert Rev Anti Infect and Practice. 3rd ed. Philadelphia: Elsevier; 2011.
pp. 441–8.
3
Ther. 2009 Mar;7(2):205–17.
4. Marty AM, Jahrling PB, Geisbert TW. Viral hemorrhagic 9. Rollin PE, Nichol ST, Zaki S, Ksiazek TG. Arenaviruses
fevers. Clin Lab Med. 2006 Jun;26(2):345–86, viii. and filoviruses. In: Jorgensen JH, Pfaller MA, Carroll KC,
Funke G, Landry ML, Richter SS, et al., editors. Manual
5. Ozkurt Z, Kiki I, Erol S, Erdem F, Yilmaz N, Parlak M, of Clinical Microbiology. 11th ed. Washington, DC: ASM
et al. Crimean-Congo hemorrhagic fever in eastern Press; 2015. pp. 1669–86.
Turkey: clinical features, risk factors and efficacy of
ribavirin therapy. J Infect. 2006 Mar;52(3):207–15. 10. Wahl-Jensen V, Peters CJ, Jahrling PB, Feldman
H, Kuhn JH. Filovirus infections. In: Guerrant RL,
6. Paweska JT, Sewlall NH, Ksiazek TG, Blumberg LH, Walker DH, Weller PF, editors. Tropical Infectious
Hale MJ, Lipkin WI, et al. Nosocomial outbreak of novel Diseases: Principles, Pathogens and Practice. 3rd ed.
arenavirus infection, southern Africa. Emerg Infect Dis. Philadelphia: Elsevier; 2011. pp. 483–91.
2009 Oct;15(10):1598–6 02.
YELLOW FEVER
Mark D. Gershman, J. Erin Staples
1
Countries or areas where “a risk of YFV transmission is present,” as defined by the World Health Organization, are
countries or areas where “yellow fever has been reported currently or in the past, plus vectors and animal reservoirs
currently exist” (see the current country list within the International Travel and Health publication (Annex 1) at www.who.
int/ith/en/index.html).
2
These countries are not holoendemic (only a portion of the country has risk of yellow fever transmission). See Maps 3-14
and 3-15 and yellow fever vaccine recommendations (Yellow Fever & Malaria Information, by Country) for details.
YELLOW FEVER 353
4
5
3
Eritrea2
Rwanda3
São Tomé and Príncipe3
Somalia2
Tanzania3
3 1
Zambia2
Countries listed in this table are not contained on the official World Health Organization list of countries with risk
of YFV transmission (Table 3-22). Therefore, proof of yellow fever vaccination should not be required if traveling from
any of these countries to another country with a vaccination entry requirement (unless that country requires proof of
yellow fever vaccination from all arriving travelers; see Table 3-26). An exception is Bolivia, which requires yellow fever
vaccination for people traveling from or transiting through any of the 6 countries with low potential for exposure, in
addition to those with risk of YFV transmission.
2
These countries are classified as “low potential for exposure to YFV” in only some areas; the remaining areas of these
countries are classified as having no risk of exposure to YFV.
3
The entire area of these countries is classified as “low potential for exposure to YFV.”
a vaccinated traveler. This nonfatal case occurred monkeys in the forest canopy in South America
in a traveler from Spain who visited several West do not often come in contact with humans.
African countries in 1988. In early 2016, >15 long- Additionally, there is a relatively high level of
term travelers from Africa and Asia developed immunity in local residents because of vaccine
yellow fever disease after visiting Angola, where use, which might reduce the risk of transmission.
one of the largest urban outbreaks was occurring.
Reportedly, none of the ill travelers was vaccinated. CLINICAL PRESENTATION
The risk of acquiring yellow fever is difficult to Asymptomatic or clinically inapparent infection
predict because of variations in ecologic determi- is believed to occur in most people infected with
nants of virus transmission. For a 2-week stay, the YFV. For people who develop symptomatic illness,
estimated risks for illness and death due to yel- the incubation period is typically 3–6 days. The ini-
low fever for an unvaccinated traveler visiting an tial illness presents as a nonspecific influenzalike
endemic area in: syndrome with sudden onset of fever, chills, head-
ache, backache, myalgia, prostration, nausea, and
• West Africa are 50 per 100,000 and 10 per vomiting. Most patients improve after the initial
100,000, respectively presentation. After a brief remission of hours to a
• South America are 5 per 100,000 and 1 per day, approximately 15% of patients progress to a
100,000, respectively more serious or toxic form of the disease, charac-
terized by jaundice, hemorrhagic symptoms, and
The risk of illness during outbreaks of the disease is eventually shock and multisystem organ failure.
likely higher. These estimates are a rough guideline The case-fatality ratio for severe cases with hepa-
based on the risk to indigenous populations, often torenal dysfunction is 20%–50%.
during peak transmission season. Thus, these
risk estimates may not accurately reflect the risk DIAGNOSIS
to travelers, who may have a different immunity The preliminary diagnosis is based on the patient’s
profile, take precautions against getting bitten by clinical features, places and dates of travel, and activ-
mosquitoes, and have less outdoor exposure. ities. Laboratory diagnosis is best performed by:
The risk of acquiring yellow fever in South
America is lower than that in Africa, because • Virus isolation or nucleic acid amplification
tests performed early in the illness for YFV
the mosquitoes that transmit the virus between
or yellow fever viral RNA. However, by the
time more overt symptoms are recognized, (see Chapter 2, Protection against Mosquitoes,
the virus or viral RNA might be undetectable. Ticks, & Other Arthropods).
Therefore, virus isolation and nucleic acid
amplification should not be used to rule out a Vaccine
diagnosis of yellow fever. Yellow fever is preventable by a relatively safe,
effective vaccine. All yellow fever vaccines cur-
• Serologic assays to detect virus-specific rently manufactured are live-attenuated viral vac-
IgM and IgG antibodies. Because of cross-
cines. Only one yellow fever vaccine is licensed for
reactivity between antibodies raised against
use in the United States (Table 3-24). Studies com-
other flaviviruses, more specific antibody test-
paring the reactogenicity and immunogenicity
ing, such as a plaque reduction neutralization
test, should be done to confirm the infection.
of various yellow fever vaccines, including those
manufactured outside the United States, suggest
3
Clinicians should contact their state or local health that there is no substantial difference in the reac-
department or call the CDC Arboviral Diseases togenicity or immune response generated by the
Branch at 970-221-6400 for assistance with diag- various vaccines. Thus, people who receive yellow
nostic testing for yellow fever infections and for fever vaccines in other countries should be con-
questions about antibody response to vaccination. sidered protected against yellow fever.
Yellow fever is a nationally notifiable disease.
INDICATIONS FOR USE
TREATMENT Yellow fever vaccine is recommended for peo-
There are no specific medications to treat YFV ple aged ≥9 months who are traveling to or living
infections; treatment is directed at symptom- in areas with risk for YFV transmission in South
atic relief or life-saving interventions. Rest, flu- America and Africa. In addition, some countries
ids, and use of analgesics and antipyretics may require proof of yellow fever vaccination for entry.
relieve symptoms of fever and aching. Care should See the Yellow Fever & Malaria Information, by
be taken to avoid medications, such as aspirin Country section at the end of this chapter for
or nonsteroidal anti-inflammatory drugs, which more detailed information on the requirements
may increase the risk for bleeding. Infected people and recommendations for yellow fever vaccina-
should be protected from further mosquito expo- tion for specific countries.
sure (staying indoors or under a mosquito net) Because of the risk of serious adverse events
during the first few days of illness, so they do not after yellow fever vaccination, clinicians should
contribute to the transmission cycle. only vaccinate people who (1) are at risk of expo-
sure to YFV or (2) require proof of vaccination to
PREVENTION enter a country. To further minimize the risk of
Personal Protection Measures serious adverse events, clinicians should carefully
The best way to prevent mosquitoborne diseases, observe the contraindications and consider the
including yellow fever, is to avoid mosquito bites precautions to vaccination before administering
17D yellow YF-Vax (Sanofi ≥9 months1 0.5 mL2 SC 1 dose Not recommended
fever vaccine Pasteur) for most3
Abbreviation: SC, subcutaneous.
1
Ages 6–8 months and ≥60 years are precautions and age <6 months is a contraindication to the use of yellow fever
vaccine.
2
YF-Vax is available in single-dose and multiple-dose (5-dose) vials.
3
For further details regarding revaccination, see “Vaccine Administration” in this section.
YELLOW FEVER 355
3
5
6
3 function
• Primary immunodeficiencies
<6 years)2
• Pregnancy
• Malignant neoplasms • Breastfeeding
• Transplantation
• Immunosuppressive and immunomodulatory therapies
1
If vaccination is considered essential because of a high risk for acquiring yellow fever, desensitization can be performed
under direct supervision of a physician experienced in the management of anaphylaxis.
2
Symptoms of HIV are classified in 1) Adults and Adolescents, Table 1. CDC. 1993 Revised classification system for
HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep
1992;41(RR-17). Available from: www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm and 2) Panel on Antiretroviral
Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric
HIV infection. 2010. Available from http://aidsinfo.nih.gov/ContentFiles/PediatricGuidelines.pdf. pp. 20–2.
yellow fever vaccine (Table 3-25). For additional The Advisory Committee on Immunization
information, refer to the yellow fever vaccine rec- Practices (ACIP) also stated that a single dose of
ommendations of the Advisory Committee on yellow fever vaccine provides long-lasting protec-
Immunization Practices (ACIP) at www.cdc.gov/ tion and is adequate for most travelers. However,
vaccines/hcp/acip-recs/vacc-specific/yf.html. these guidelines specify that additional doses of
yellow fever vaccine are recommended for the fol-
VACCINE ADMINISTRATION
lowing groups of travelers:
For all eligible people, a single injection of recon-
stituted vaccine should be administered subcu- • Women who were pregnant when they
taneously. Until recently, revaccination has been received their initial dose of vaccine: they
required by certain countries at 10-year intervals should receive 1 additional dose of yellow
to comply with International Health Regulations fever vaccine before their next travel that puts
(IHR) of the World Health Organization (WHO). them at risk for yellow fever.
However, in 2014, the WHO Strategic Advisory • People who received a hematopoietic stem
Group of Experts on Immunization concluded cell transplant after receiving a dose of yellow
that a single primary dose of yellow fever vaccine fever vaccine: they should be revaccinated
provides sustained immunity and lifelong pro- before their next travel that puts them at risk
tection against yellow fever disease and that a for yellow fever as long as they are sufficiently
booster dose is not needed. That year the World immunocompetent to be safely vaccinated.
Health Organization adopted the recommenda-
tion to remove the 10-year booster dose require- • People who were infected with HIV when
ment from the IHR after a 2-year transition period. they received their last dose of yellow fever
As of July 11, 2016, a completed International vaccine: they should receive a dose every
Certificate of Vaccination or Prophylaxis is valid 10 years if they continue to be at risk for yel-
for the lifetime of the vaccinee and countries low fever virus infection.
cannot require proof of revaccination (booster) The updated recommendations also note that a
against yellow fever as a condition of entry, even if booster dose may be considered for travelers who
the last vaccination was more than 10 years prior. received their last dose of yellow fever vaccine
≥10 years previously and who will be in a higher- recent reports have been among people of all ages.
risk setting based on season, location, activities, YEL-AND is rarely fatal.
and duration of their travel. This would include Among all cases of YEL-AND reported globally,
travelers who plan to spend a prolonged period almost all occurred in first-time vaccine recipi-
in endemic areas, or those traveling to highly ents. The onset of illness for documented cases in
endemic areas such as rural West Africa during the United States is 2–56 days after vaccination.
peak transmission season or an area with an The incidence of YEL-AND in the United States
ongoing outbreak. All current ACIP yellow fever is 0.8 per 100,000 doses administered. The rate is
vaccine recommendations can be found on the higher in people aged ≥60 years, with a rate of 2.2
ACIP website at www.cdc.gov/ vaccines/
hcp/ per 100,000 doses.
acip-recs/vacc-specific/yf.html.
Although booster doses of yellow fever vac- Yellow Fever Vaccine–Associated Viscerotropic
3
cine are not recommended for most travelers, and Disease (YEL-AVD)—YEL-AVD is a severe illness
despite the recent changes to the IHR, clinicians similar to wild-type disease, with vaccine virus
and travelers should review the entry require- proliferating in multiple organs and often leading
ments for destination countries. At the time this to multiple organ dysfunction syndrome or mul-
edition goes to press it is uncertain when and if all tiorgan failure and death. Since the initial cases
countries with yellow fever vaccination require- of YEL-AVD were published in 2001, >100 con-
ments will adopt and fully implement this change firmed and suspected cases have been reported
that is stipulated by the IHR. See the yellow fever throughout the world.
vaccination requirements on the CDC Travelers’ YEL- AVD has been reported to occur only
Health website (wwwnc.cdc.gov/travel/desti- after the first dose of yellow fever vaccine; world-
nations/list) for more information on country- wide, there have been no laboratory-confirmed
specific recommendations and requirements. reports of YEL-AVD following booster doses. For
YEL-AVD cases reported in the United States, the
VACCINE SAFETY AND ADVERSE REACTIONS median time from yellow fever vaccination until
COMMON ADVERSE REACTIONS symptom onset is 4 days (range, 1–18 days). The
Reactions to yellow fever vaccine are gener- case-fatality ratio for all reported YEL-AVD cases
ally mild; 10%–30% of vaccinees report mild sys- in the United States is approximately 46%. The
temic adverse events. Reported events typically incidence of YEL-AVD in the United States is 0.3
include low-grade fever, headache, and myalgia cases per 100,000 doses of vaccine administered.
that begin within days after vaccination and last The rate is higher for people aged ≥60 years, with
5–10 days. Approximately 1% of vaccinees tem- a rate of 1.2 per 100,000 doses. The rate is even
porarily curtail their regular activities because of higher for people aged ≥70 years.
these reactions.
CONTRAINDICATIONS
SEVERE ADVERSE REACTIONS INFANTS YOUNGER THAN 6 MONTHS
Hypersensitivity—Immediate hypersensitivity reac- Yellow fever vaccine is contraindicated for infants
tions, characterized by rash, urticaria, or broncho- aged <6 months. This contraindication was insti-
spasm are uncommon. Anaphylaxis after yellow tuted in the late 1960s in response to a high rate
fever vaccine is reported to occur at a rate of 1.3 of YEL-AND documented in vaccinated young
cases per 100,000 doses administered. infants (50–400 per 100,000). The mechanism of
increased neurovirulence in infants is unknown
Yellow Fever Vaccine– Associated Neurologic but may be due to the immaturity of the blood-
Disease (YEL-AND)—YEL-AND represents a con- brain barrier, higher or more prolonged viremia,
glomerate of clinical syndromes, including menin- or immune system immaturity.
goencephalitis, Guillain-Barré syndrome, acute
disseminated encephalomyelitis, and rarely, cra- HYPERSENSITIVITY
nial nerve palsies. Historically, YEL-AND was seen Yellow fever vaccine is contraindicated for people
primarily among infants as encephalitis, but more with a history of acute hypersensitivity reaction to
YELLOW FEVER 357
8
53
a previous dose of the vaccine, as well as those who provided, and counseling on protective measures
have a history of an allergic reaction to any of the against mosquito bites should be emphasized. See
vaccine components, including eggs, egg products, the following section, Precautions, for other HIV-
chicken proteins, or gelatin. The stopper used in infected people not meeting the above criteria.
vials of vaccine also contains dry natural latex rub-
ber, which may cause an allergic reaction. Immunodeficiencies (other than thymus disorder
If vaccination of a person with a questionable or HIV infection)—Yellow fever vaccine is contrain-
history of hypersensitivity to any of the vaccine dicated for people with primary immunodeficien-
components is considered essential because of a cies, as well as those with malignant neoplasms
high risk for acquiring yellow fever, skin testing, or transplantation that might be associated with
3 as described in the vaccine package insert, should
be performed under close medical supervision. If
immunosuppression caused either by treatment or
the underlying condition. While there are no data
a person has a positive skin test to the vaccine or on the use of yellow fever vaccine in these people,
has severe egg sensitivity and the vaccination is they presumably are at increased risk for yellow
recommended, desensitization, as described in fever vaccine–associated serious adverse events
the package insert, can be performed under direct (see Chapter 8, Immunocompromised Travelers).
supervision of a physician experienced in the If someone with an immunodeficiency cannot
management of anaphylaxis. avoid travel to a yellow fever–endemic area, a
medical waiver should be provided, and counsel-
ALTERED IMMUNE STATUS ing on protective measures against mosquito bites
Thymus Disorder—Yellow fever vaccine is contra- should be emphasized.
indicated for people with a thymus disorder that is
associated with abnormal immune cell function, Immunosuppressive and Immunomodulatory
such as thymoma or myasthenia gravis. If travel to Therapies—Yellow fever vaccine is contraindi-
a yellow fever–endemic area cannot be avoided in cated for people whose immunologic response
a person with such a thymus disorder, a medical is either suppressed or modulated by current or
waiver should be provided and counseling on pro- recent radiation therapies or drugs. Drugs with
tective measures against mosquito bites should known immunosuppressive or immunomodu-
be emphasized. Because there is no evidence of latory properties include, but are not limited to,
immune dysfunction or increased risk of yellow high-dose systemic corticosteroids, alkylating
fever vaccine–associated serious adverse events drugs, antimetabolites, tumor necrosis factor-α
in people who have undergone incidental surgical inhibitors (such as etanercept), interleukin-1 and
removal of their thymus or have had indirect radi- interleukin-6 blocking agents (such as anakinra and
ation therapy in the distant past, these people can tocilizumab), or other monoclonal antibodies tar-
be given yellow fever vaccine if recommended or geting immune cells (such as rituximab or alemtu-
required. zumab). There are no specific data on the use of
yellow fever vaccine in people receiving these ther-
HIV Infection—Yellow fever vaccine is contra- apies. However, these people are presumed to be at
indicated for people with AIDS or other clinical increased risk for yellow fever vaccine–associated
manifestations of HIV, including people with CD4 serious adverse events, and the use of live atten-
T lymphocyte values <200/mm3 or <15% of total uated vaccines is contraindicated in the package
lymphocytes for children aged <6 years. This rec- insert for most of these therapies (see Chapter 8,
ommendation is based on a potential increased Immunocompromised Travelers).
risk of encephalitis in this population. Live viral vaccines should be deferred in peo-
If travel to a yellow fever–endemic area cannot ple who have discontinued these therapies until
be avoided by a person with severe immune sup- immune function has improved. If travel to a yellow
pression based on CD4 counts (<200/mm3 or <15% fever–endemic area cannot be avoided for some-
total lymphocytes for children aged <6 years) or one receiving immunosuppressive or immuno-
symptomatic HIV, a medical waiver should be modulatory therapies, a medical waiver should be
provided and counseling on protective measures of HIV infection in the Contraindications section
against mosquito bites should be emphasized. above). Large prospective, randomized trials have
Family members of people with altered not been performed to adequately address the
immune status, who themselves have no contra- safety and efficacy of yellow fever vaccine among
indications, can receive yellow fever vaccine. this group. Retrospective and prospective studies
that combined included >500 HIV-infected people
PRECAUTIONS reported no serious adverse events among patients
INFANTS AGED 6–8 MONTHS considered moderately immunosuppressed based
Age 6–8 months is a precaution for yellow fever on their CD4 counts. However, HIV infection has
vaccination. Two cases of YEL-AND have been been associated with a reduced immunologic
reported among infants aged 6– 8 months. In
infants <6 months of age, the rates of YEL-AND
response to a number of inactivated and live atten-
uated vaccines, including yellow fever vaccine. The
3
are elevated (50–400 per 100,000). By 9 months of mechanisms for the diminished immune response
age, risk for YEL-AND is believed to be substan- in HIV-infected people are uncertain but appear to
tially lower. ACIP generally recommends that, be correlated with HIV RNA levels and CD4 T cell
whenever possible, travel to yellow fever–endemic counts.
countries should be postponed or avoided for If an asymptomatic HIV- infected person
children aged 6–8 months. If travel is unavoidable, with moderate immune suppression (CD4 T
the decision of whether to vaccinate these infants lymphocyte values 200–499/mm3 or 15%–24%
needs to balance the risks of YFV exposure with of total lymphocytes for children aged <6 years)
the risk for adverse events after vaccination. is traveling to a yellow fever– endemic area,
vaccination may be considered. Vaccinated
ADULTS 60 YEARS OF AGE OR OLDER people should be monitored closely after vac-
Age ≥60 years is a precaution for yellow fever vac- cination; if an adverse event occurs, the state
cination, particularly if this is the first dose of the health department or CDC should be notified
yellow fever vaccine given. From adverse events and a report made to VAERS. However, if inter-
passively reported to the Vaccine Adverse Events national travel requirements—not risk of yel-
Reporting System (VAERS), the rate of serious low fever— are the only reason to vaccinate
adverse events in people aged ≥60 years was 7.7 an HIV-infected person, the person should be
per 100,000 doses distributed, compared with 3.8 excused from immunization and issued a medi-
per 100,000 for all vaccine recipients. The risk of cal waiver to fulfill health regulations.
YEL-AND and YEL-AVD is also increased in this If an asymptomatic HIV-infected person has
age group, at 2.2 and 1.2 per 100,000 doses, respec- no evidence of immune suppression based on
tively, compared with 0.8 and 0.3 per 100,000 for CD4 counts (CD4 T lymphocyte values ≥500/mm3
all vaccine recipients. Given that YEL-AVD has or ≥25% of total lymphocytes for children aged
been reported exclusively, and YEL-AND almost <6 years), yellow fever vaccine can be adminis-
exclusively, in primary vaccine recipients, caution tered if recommended.
should be exercised with older travelers who may Because vaccinating asymptomatic HIV-
be receiving yellow fever vaccine for the first time. infected people might be less effective than vac-
If travel is unavoidable, the decision to vaccinate cinating people not infected with HIV, measuring
travelers aged ≥60 years needs to weigh the risks their neutralizing antibody response to vaccina-
and benefits of the vaccination in the context of tion should be considered before travel. Contact
their destination-specific risk for exposure to YFV. the state health department or the CDC Arboviral
Diseases Branch (970-221-6400) to discuss sero-
HIV INFECTION logic testing.
Asymptomatic HIV infection with CD4 T lympho-
cyte values 200–499/mm3 or 15%–24% of total lym- PREGNANCY
phocytes for children aged <6 years is a precaution Pregnancy is a precaution for yellow fever vac-
for yellow fever vaccination (see also the discussion cine administration. The safety of yellow fever
YELLOW FEVER 359
03
6
vaccination during pregnancy has not been stud- (such as renal disease, hepatitis C virus infection,
ied in a large prospective trial. However, a study other liver disease, or diabetes mellitus). Caution
of women who were vaccinated with yellow should be used if considering vaccination of such
fever vaccine early in their pregnancies found patients. Factors to consider in assessing patients’
no major malformations in their infants. A slight general level of immune competence include dis-
increased risk was noted for minor, mostly skin, ease severity, duration, clinical stability, complica-
malformations in infants. A higher rate of spon- tions, and comorbidities.
taneous abortions in pregnant women receiving
the vaccine was reported but not substantiated SIMULTANEOUS ADMINISTRATION
in a subsequent study. The proportion of women OF OTHER VACCINES AND DRUGS
3 vaccinated during pregnancy who develop YFV-
specific IgG antibodies is variable depending on
No evidence exists that inactivated vaccines inter-
fere with the immune response to yellow fever
the study (39% or 98%) and may be correlated vaccine. Therefore, inactivated vaccines can be
with the trimester in which they received the vac- administered either simultaneously or at any time
cine. Because pregnancy may affect immunologic before or after yellow fever vaccination. ACIP rec-
function, serologic testing can be considered to ommends that yellow fever vaccine be given at the
document a protective immune response to the same time as other live viral vaccines. Otherwise,
vaccine. the clinician should wait 30 days between vacci-
If travel is unavoidable and the vaccination nations, as the immune response to a live viral
risks are felt to outweigh the risks of YFV expo- vaccine might be impaired if administered within
sure, pregnant women should be excused from 30 days of another live viral vaccine. One study
immunization and issued a medical waiver to involving the simultaneous administration of yel-
fulfill health regulations. Pregnant women who low fever and measles- mumps- rubella (MMR)
must travel to areas where YFV exposure is likely vaccines in children found a decrease in the
should be vaccinated. Although there are no spe- immune response against yellow fever, mumps,
cific data, ACIP recommends that a woman wait and rubella when the vaccines were given on the
4 weeks after receiving the yellow fever vaccine same day versus 30 days apart. Additional stud-
before conceiving. ies are needed to confirm these findings, but they
suggest that if possible, yellow fever and MMR
BREASTFEEDING should be given 30 days apart. Limited data sug-
Breastfeeding is a precaution for yellow fever vac- gest oral Ty21a typhoid vaccine, a live bacterial
cine administration. Three YEL-AND cases have vaccine, can be administered simultaneously or at
been reported in exclusively breastfed infants any interval before or after yellow fever vaccine.
whose mothers were vaccinated with yellow fever There are no data on the immune response to live
vaccine. All 3 infants were diagnosed with enceph- attenuated influenza and yellow fever vaccines
alitis and aged <1 month at the time of exposure. administered simultaneously. However, data from
Further research is needed to document the risk live attenuated influenza and MMR found no evi-
of potential vaccine exposure through breastfeed- dence of interference.
ing. Until more information is available, yellow
fever vaccine should be avoided in breastfeeding INTERNATIONAL CERTIFICATE
women. However, when travel of nursing mothers OF VACCINATION OR
to a yellow fever–endemic area cannot be avoided PROPHYLAXIS (ICVP)
or postponed, these women should be vaccinated. The IHR allow countries to require proof of yel-
low fever vaccination documented on an ICVP
OTHER CONSIDERATIONS as a condition of entry for travelers arriving from
There are no data regarding possible increased certain countries, even if only in transit, to pre-
adverse events or decreased vaccine efficacy vent importation and indigenous transmission
after administration of yellow fever vaccine to of YFV. Some countries require evidence of vacci-
patients with other chronic medical conditions nation from all entering travelers, which includes
direct travel from the United States (Table 3-26). of entry to a country. Revaccination at the point
Some countries do not require an ICVP for infants of entry is not a recommended option for the
younger than a certain age (see Yellow Fever & traveler.
Malaria Information, by Country section at the Clinics may purchase ICVPs, CDC 731 ( formerly
end of this chapter for specific age requirements). PHS 731), from the US Government Printing Office
A traveler who has a specific contraindication to (http://bookstore.gpo.gov, 866-512-1800). This cer-
yellow fever vaccine and who cannot avoid travel tificate of vaccination (ICVP) is valid beginning
to a country requiring vaccination should request 10 days after the date of primary vaccination. As of
a waiver from a physician before embarking on July 2016, the yellow fever vaccine booster require-
travel (see the Medical Waivers [Exemptions] ment was eliminated in the IHR and a completed
section below). Travelers who arrive in a country ICVP is considered valid for the lifetime of the
that has a yellow fever vaccination entry require- vaccinee.
ment without proof of yellow fever vaccination or
a medical waiver may be quarantined for up to PEOPLE AUTHORIZED TO SIGN
6 days, refused entry, or vaccinated on site. THE ICVP AND DESIGNATED
YELLOW FEVER VACCINATION
AUTHORIZATION TO PROVIDE CENTERS
VACCINATIONS AND The ICVP must be signed by a medical provider,
TO VALIDATE THE ICVP who may be a licensed physician or a health care
People who received a yellow fever vaccination worker designated by the physician, supervising
after December 15, 2007, must provide proof of the administration of the vaccine (Figure 3-2).
vaccination on the new ICVP. If the person received A signature stamp is not acceptable. Yellow fever
the vaccine before December 15, 2007, their orig- vaccination must be given at a certified center in
inal International Certificate of Vaccination possession of an official “uniform stamp,” which
against Yellow Fever (ICV) card is still valid as can be used to validate the ICVP.
proof of vaccination. Vaccinees should receive a State health departments are responsible for
completed ICVP (Figure 3-2), validated (stamped designating nonfederal yellow fever vaccination
and signed) with the stamp of the center where centers and issuing uniform stamps to clinicians.
the vaccine was given (see below). An incomplete Information about the location and hours of yel-
or inaccurate ICVP is not valid. Failure to secure low fever vaccination centers may be obtained by
validations can cause a traveler to be quarantined, visiting CDC’s website at wwwnc.cdc.gov/travel/
denied entry, or possibly revaccinated at the point yellow-fever-vaccination-clinics-search.aspx.
YELLOW FEVER 361
3
26
Medical Waivers (Exemptions) • Give the traveler a signed and dated exemp-
For medical contraindications, a clinician who has tion letter on letterhead stationery, clearly
decided to issue a waiver should fill out and sign stating the contraindications to vaccina-
the Medical Contraindications to Vaccination sec- tion and bearing the stamp used by the yel-
tion of the ICVP (Figure 3-3). The clinician should low fever vaccination center to validate
also do the following: the ICVP.
for
(Name of disease – Nom de la maladie) pour
3
is medically
(Name of traveler – Nom du voyageur) est médicalement
YELLOW FEVER 363
43
364
6
3
INFECTIOUS DISEASES RELATED TO TRAVEL
YELLOW FEVER 365
3
6
The information in the section on yellow Countries that only contain areas with low
fever vaccine recommendations is advice given potential for exposure to YFV (Table 3-23) are not
by CDC to prevent YFV infections among travel- included on the official WHO list of countries with
ers. Recommendations are subject to change at risk of YFV transmission (Table 3-22). Therefore,
any time because of changes in YFV circulation; proof of yellow fever vaccination should not be
therefore, CDC encourages travelers to check the required if traveling from a country with low
destination pages for up-to-date vaccine informa- potential for exposure to YFV to a country with a
tion and to check for relevant travel notices on vaccination entry requirement (unless that coun-
the CDC website before departure (www.cdc.gov/ try requires proof of yellow fever vaccination from
travel). all arriving travelers; see Table 3-26). An exception
3 Yellow fever vaccine recommendations
for travelers going to specific destinations are
is Bolivia, which requires yellow fever vaccination
for people traveling from or transiting through any
based on the risk classification for YFV trans- of the 6 countries with low potential for exposure,
mission: endemic, transitional, low potential for in addition to those with risk of YFV transmission.
exposure, and no risk. Yellow fever vaccination is
recommended for travel to endemic and transi- VACCINATION FOR TRAVEL
tional areas (Maps 3-14 and 3-15). Although vacci- ON MILITARY ORDERS
nation is generally not recommended for travel to Because military requirements may exceed those
areas with low potential for exposure, it might be indicated in this publication, any person who
considered for a small subset of travelers whose plans to travel on military orders (civilians and
itinerary could place them at increased risk for military personnel) should contact the nearest
exposure to YFV (such as prolonged travel, heavy military medical facility to determine the require-
exposure to mosquitoes, or inability to avoid mos- ments for his or her trip (see also Chapter 8, Special
quito bites). Yellow fever vaccination is not recom- Considerations for US Military Deployments).
mended in areas with no risk.
CDC website: www.cdc.gov/yellowfever
BIBLIOGRAPHY
1. Gershman MD, Staples JE, Bentsi-Enchill AD, the Advisory Committee on Immunization Practices,
Breugelmans JG, Brito GS, Camacho LA, et al. 2015. MMWR Morb Mortal Wkly Rep. 2015 Jun
Viscerotropic disease: case definition and guidelines for 19;64(23):647–5 0.
collection, analysis, and presentation of immunization 6. Staples JE, Gershman M, Fischer M. Yellow fever vac-
safety data. Vaccine. 2012 Jul 13;30(33):5038–58. cine: recommendations of the Advisory Committee on
2. Jentes ES, Poumerol G, Gershman MD, Hill DR, Immunization Practices (ACIP). MMWR Recomm Rep.
Lemarchand J, Lewis RF, et al. The revised global yellow 2010 Jul 30;59(RR-7):1–27.
fever risk map and recommendations for vaccination, 7. Staples JE, Monath TP, Gershman MD, Barrett ADT.
2010: consensus of the Informal WHO Working Group Yellow fever vaccine. In: Plotkin SA, Orenstein WA, Offit
on Geographic Risk for Yellow Fever. Lancet Infect Dis. PA, editors. Vaccines. 7th ed. Philadelphia: Elsevier;
2011 Aug;11(8):622–32. In press.
3. Lindsey NP, Rabe IB, Miller ER, Fischer M, Staples JE. 8. World Health Organization. International
Adverse event reports following yellow fever vaccina- Health Regulations, 2005. Geneva: World Health
tion, 2007-13. J Travel Med. 2016 May;23(5). Organization; 2008 [cited 2016 Sep. 27]. Available
4. Monath TP, Cetron MS. Prevention of yellow fever in from: http://whqlibdoc.who.int/publications/2008/
persons traveling to the tropics. Clin Infect Dis. 2002 9789241580410_eng.pdf.
May 15;34(10):1369–78. 9. World Health Organization. Vaccines and vaccination
5. Staples JE, Bocchini JA, Jr., Rubin L, Fischer M. Yellow against yellow fever. WHO position paper—June 2013.
fever vaccine booster doses: recommendations of Wkly Epidemiol Rec. 2013 Jul 5;88(27):269–83.
The history of yellow fever vac- Allies in 1943 to provide eco- the Expert Commission on
cination requirements is best nomic assistance to war-rav- Quarantine. This commission
understood in the larger con- aged European nations, assist created the first official map 3
text of the history of interna- refugees, and conduct public of yellow fever–endemic areas
tional measures to prevent the health functions. (The UNRRA in 1945. Soon after the end
spread of infectious diseases. is unrelated to the more of World War II, the respon-
The first international dis- familiar United Nations orga- sibilities of the UNRRA were
ease control measures were nization, founded in 1945.) The assumed by the newly formed
instituted in Europe in the public health responsibilities World Health Organization
14th century in an attempt to included the oversight of inter- (WHO), which appointed the
prevent the spread of bubonic national quarantine activities, Yellow Fever Panel. In 1949,
plague. Subsequently, chol- particularly those delineated the Yellow Fever Panel modi-
era became the next major in the updated International fied the original UNRRA map
target of international disease Sanitary Conventions of 1944, and issued its first report,
control efforts. The lack of which contained yellow fever which recommended that
agreement between countries control measures. (The live “measures may be applied
on the most effective means attenuated 17D yellow fever permanently against arrivals
of disease prevention and lack vaccine had been developed from endemic areas.”
of consistency in quarantine and put into use by the late The International
regulations eventually led 1930s.) Specific provisions Sanitary Regulations (ISR),
to a series of International for national governments drafted by WHO to replace
Sanitary Conferences. included quarantining a trav- the previous International
The first International eler from an endemic area Sanitary Conventions, were
Sanitary Conference was held who did not possess a valid adopted by the World Health
in Paris in 1851, and others vaccination certificate. This Assembly in 1951. The ISR
were held periodically until provision, which directed stipulated that “vaccination
1944. Several international countries how to deal with against yellow fever shall be
health organizations, including unvaccinated travelers who required of any person leav-
the Health Organization of may have been exposed to yel- ing an infected local area on
the League of Nations, were low fever virus, was the pre- an international voyage and
established to oversee the cursor to formal yellow fever proceeding to a yellow fever
various international regula- vaccination requirements. receptive area.” Although
tions on disease control. The In order for the provisions only alluded to in previ-
onset of World War II in 1939 of the Sanitary Conventions ous International Sanitary
severely disrupted the inter- of 1944 to be carried out, Conventions, this was the
national public health func- areas where yellow fever was first regulatory language that
tions of these organizations. endemic had to be delineated. overtly mandated yellow fever
The United Nations Relief and The conventions delegated vaccination requirements
Rehabilitation Administration this responsibility to the for country entry. The ISR
(UNRRA) was created by the UNRRA, which appointed were modified and renamed
(continued)
YERSINIOSIS
L. Hannah Gould, Cindy R Friedman
BIBLIOGRAPHY
1. Cover TL, Aber RC. Yersinia enterocolitica. N Engl J Med. 3. Mead PS. Yersinia species, including plague. In: Bennett
1989 Jul 6;321(1):16–24. JE, Dolin R, Blaser MJ, editors. Mandell, Douglas, and
2. Kendall ME, Crim S, Fullerton K, Han PV, Cronquist Bennett’s Principles and Practice of Infectious Diseases.
AB, Shiferaw B, et al. Travel-associated enteric infec- 8th ed. Philadelphia: Saunders Elsevier; 2015. pp. 2615–7.
tions diagnosed after return to the United States, 4. Perdikogianni C, Galanakis E, Michalakis M, Giannoussi
Foodborne Diseases Active Surveillance Network E, Maraki S, Tselentis Y, et al. Yersinia enterocolitica
(FoodNet), 2004–2009. Clin Infect Dis. 2012 Jun;54 infection mimicking surgical conditions. Pediatr Surg
Suppl 5:S480–7. Int. 2006 Jul;22(7):589–92.
ZIKA
Tai-Ho Chen, J. Erin Staples, Marc Fischer
INFECTIOUS AGENT EPIDEMIOLOGY
Zika virus is a single-stranded RNA virus of the Zika virus was first identified in Uganda in 1947.
Flaviviridae family, genus Flavivirus. Before 2007, only sporadic human cases were
reported from countries in Africa and Asia. In 2007,
TRANSMISSION the first documented Zika virus disease outbreak
Transmission occurs through the bite of an was reported in the Federated States of Micronesia.
infected Aedes species mosquito. Intrauterine, In subsequent years, outbreaks of Zika virus dis-
perinatal, sexual, laboratory, and possible ease were identified in countries in Southeast Asia
transfusion-
associated transmission also have and the Western Pacific. Zika virus was identified
been reported. Although Zika viral particles were for the first time in the Western hemisphere in
found in the breast milk of 1 woman, and virus 2015, when large outbreaks were reported in Brazil.
RNA has been detected in breast milk of 2 addi- Since then, the virus spread throughout much of
tional women, transmission of Zika virus through the Americas. (See www.cdc.gov/travel for current
breastfeeding has not been documented. CDC travel notices for Zika virus.)
ZIKA 369
0
3
7
BIBLIOGRAPHY
1. Besnard M, Lastere S, Teissier A, Cao-Lormeau V, Musso non-vector-borne transmission of Zika virus, Colorado,
D. Evidence of perinatal transmission of Zika virus, USA. Emerg Infect Dis. 2011 May;17(5):880–2.
French Polynesia, December 2013 and February 2014. 5. Hayes EB. Zika virus outside Africa. Emerg Infect Dis.
Euro Surveill. 2014;19(13). 2009 Sep;15(9):1347–5 0.
2. Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, 6. Petersen EE, Polen KN, Meaney-Delman D, Ellington
Lanciotti RS, et al. Zika virus outbreak on Yap Island, SR, Oduyebo T, Cohn A, et al. Update: interim guid-
Federated States of Micronesia. N Engl J Med. 2009 Jun ance for health care providers caring for women of
11;360(24):2536–43. reproductive age with possible Zika virus exposure—
3. Food and Drug Administration. Recommendations United States, 2016. MMWR Morb Mortal Wkly Rep.
for donor screening, deferral, and product man- 2016;65(12):315–22.
agement to reduce the risk of transfusion— 7. Petersen LR, Jamieson DJ, Powers AM, Honein MA. Zika
transmission of Zika virus. 2016 [cited 2016 Virus. N Engl J Med. 2016 Apr 21;374(16):1552–63.
Sep. 27]. Available from: http://www.fda.
8. Staples JE, Dziuban EJ, Fischer M, Cragan JD,
gov/downloads/BiologicsBloodVaccines/
Rasmussen SA, Cannon MJ, et al. Interim guidelines
GuidanceComplianceRegulatoryInformation/
for the evaluation and testing of infants with possible
Guidances/Blood/UCM486360.pdf.
congenital Zika virus infection –United States, 2016.
4. Foy BD, Kobylinski KC, Chilson Foy JL, Blitvich BJ, MMWR Morb Mortal Wkly Rep. 2016;65(3):63–7.
Travassos da Rosa A, Haddow AD, et al. Probable
ZIKA 371
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27
The following pages present country- specific Assembly (of WHO) adopted the recommenda-
3 information on yellow fever vaccine require-
ments and recommendations (see Table 3- 27)
tion to amend the IHR by removing the 10-year
booster dose requirement, and stipulated a 2-year
and malaria transmission information and pro- transition period for this change. Consequently,
phylaxis recommendations. Fourteen country- as of July 11, 2016, a completed International
specific maps of malaria transmission areas, 11 Certificate of Vaccination or Prophylaxis (ICVP)
country-specific maps depicting yellow fever is valid for the lifetime of the vaccinee. Moreover,
vaccine recommendations, and a reference map countries cannot require proof of revaccination
of China are included to aid in interpreting the (booster) against yellow fever as a condition of
information. The information was accurate at entry, even if the last vaccination was more than
the time of publication; however, this informa- 10 years prior.
tion is subject to change at any time as a result In the United States, the Advisory Committee
of changes in disease transmission or, in the case on Immunization Practices (ACIP) published a
of yellow fever, changing country entry require- new recommendation in 2015 that one dose of
ments. Updated information reflecting changes yellow fever vaccine provides long-lasting protec-
since publication can be found in the online ver- tion and is adequate for most travelers. The rec-
sion of this book (www.cdc.gov/yellowbook) and ommendation also identifies specific groups of
on the CDC Travelers’ Health website (www.cdc. travelers who should receive additional doses and
gov/travel). General recommendations for other others for whom additional doses may be con-
vaccines to consider during the pretravel consul- sidered. For details, see the Yellow Fever section
tation can be found on the CDC Travelers’ Health earlier in this chapter. For the most up-to-date
website (www.cdc.gov/travel). information about yellow fever vaccine boosters,
consult the CDC Travelers’ Health website or the
YELLOW FEVER specific publication posted on the ACIP website
Since publication of the 2016 edition of CDC (www.cdc.gov/mmwr/pdf/wk/mm6423.pdf).
Health Information for International Travel, addi- Ultimately, the clinician’s decision whether
tional country-specific data has been made or not to vaccinate any traveler must take into
available on the geographic risk of yellow fever account the traveler’s risk of being infected with
virus (YFV) transmission. Based on a review of YFV, country entry requirements, and individual
these data by the WHO Scientific and Technical risk factors for serious adverse events after yellow
Advisory Group on Geographical Yellow Fever fever vaccination (such as age and immune sta-
Risk Mapping (in which CDC participates), an tus). For a thorough discussion of yellow fever and
updated yellow fever vaccination recommenda- guidance for vaccination, see the Yellow Fever sec-
tion was made for Rwanda. tion earlier in this chapter.
Revaccination against yellow fever was pre- NOTE: Despite the recent changes to the
viously required by certain countries at 10-year IHR regarding yellow fever vaccine boost-
intervals to comply with International Health ers, it is uncertain when and if all countries
Regulations (IHR). In 2014, the World Health with current yellow fever vaccination entry
requirements will adopt this change. Even if Health website (www.cdc.gov/travel) for any
countries do modify their official policies to reported updates to country entry require-
extend the validity period of the ICVP from ments since publication of this edition.
10 years to the lifetime of the vaccinee, there is
no guarantee that all national border officials MALARIA
will be aware of such policy change or be able The following recommendations to protect trav-
to enforce it appropriately. CDC obtains infor- elers from malaria were developed using the best
mation yearly from WHO about official coun- available data from multiple sources. Countries
try entry requirements. WHO likely will not be are not required to submit malaria surveillance
asking countries about yellow fever vaccine data to CDC. On an ongoing basis, CDC actively
booster entry requirements in the yearly ques-
tionnaires, because it will be assumed that
solicits data from multiple sources, including
World Health Organization (main and regional 3
countries are complying with the amended offices); national malaria control programs; inter-
IHR. This could leave a gap in the foresee- national organizations, such as the International
able future in accurate published information Society of Travel Medicine; CDC overseas staff;
about entry requirements for yellow fever vac- US military; academic, research, and aid organi-
cine boosters for certain countries. Past expe- zations; and published records from the medical
rience has demonstrated that information literature. The reliability and accuracy of those
given by consulates and embassies about vac- data are also assessed. If the information is avail-
cination requirements is often not accurate. able, trends in malaria incidence and other data
Therefore, providers and travelers should not are considered in the context of malaria control
rely solely on such information when deter- activities within a given country, or other miti-
mining current yellow fever vaccination entry gating factors such as natural disasters, wars, and
requirements for specific destinations. With other events that may affect the ability to control
the caveats described above, readers should malaria or accurately count and report it. Factors
refer to the online version of this book (www. such as the volume of travel to that country and
cdc.gov/yellowbook) and the CDC Travelers’ the number of acquired cases reported in the US
Generally not recommended Vaccination generally not recommended in areas where the potential
for YFV exposure is low, as determined by absence of reports of human
yellow fever and past evidence suggestive of only low levels of YFV
transmission. However, vaccination might be considered for a small
subset of travelers who are at increased risk for exposure to YFV because
of prolonged travel, heavy exposure to mosquitoes, or inability to avoid
mosquito bites.
Not recommended Vaccination not recommended in areas where there is no risk of YFV
transmission, as determined by absence of past or present evidence of
YFV circulation in the area or environmental conditions not conducive to
YFV transmission.
surveillance system are also examined. Based on These recommendations should be used in
all those considerations, recommendations are conjunction with an individual risk assessment,
developed to try to accurately describe areas of taking into account not only the destination
the country where transmission occurs, substan- country but also the detailed itinerary including
tial occurrences of antimalarial drug resistance, specific cities, types of accommodation, season,
the proportions of species present, and the rec- and style of travel, as well as special health condi-
ommended chemoprophylaxis options. tions such as pregnancy.
The recommendations for malaria prevention Several medications are available for malaria
include estimates of relative risk for US travelers. chemoprophylaxis. When deciding on which drug
This means that compared to a hypothetical aver- to use, clinicians should consider the specific itin-
COUNTRY-SPECIFIC INFORMATION
Recommendations: Recommended for all travelers
AFGHANISTAN ≥9 months of age.
YELLOW FEVER
MALARIA
Requirements: Required if traveling from a country
Areas with malaria: All.
with risk of YFV transmission.1
Estimated relative risk of malaria for US
Recommendations: None.
travelers: High.
MALARIA Drug resistance4: Chloroquine.
Areas with malaria: April–December in all areas Malaria species: P. falciparum 90%, P. ovale 5%,
<2,500 m (8,202 ft).
Estimated relative risk of malaria for US travelers:
P. vivax 5%.
Recommended chemoprophylaxis: Atovaquone-
3
Moderate.3 proguanil, doxycycline, or mefloquine.
Drug resistance4: Chloroquine.
Malaria species: P. vivax 80%–90%, P. falciparum ANGUILLA (UK)
10%–20%.
YELLOW FEVER
Recommended chemoprophylaxis: Atovaquone-
No requirements or recommendations.
proguanil, doxycycline, or mefloquine.
MALARIA
ALBANIA No malaria transmission.
YELLOW FEVER
Requirements: Required if traveling from a country
ANTARCTICA
with risk of YFV transmission and ≥1 year of age.1 YELLOW FEVER
Recommendations: None. No requirements or recommendations.
MALARIA MALARIA
No malaria transmission. No malaria transmission.
ARUBA Recommendations: None.
MALARIA
YELLOW FEVER
No malaria transmission.
No requirements or recommendations.
MALARIA BANGLADESH
No malaria transmission.
YELLOW FEVER
Requirements: Required if traveling from a country
AUSTRALIA with risk of YFV transmission and ≥1 year of age.1
YELLOW FEVER Recommendations: None.
Requirements: Required if traveling from a country
MALARIA
with risk of YFV transmission and ≥1 year of age,
Areas with malaria: All areas, except in the city
including transit >12 hours in an airport located in a
of Dhaka.
country with risk of YFV transmission.1 This requirement
excludes Galápagos Islands in Ecuador and the island of
Estimated relative risk of malaria for US
travelers: Low.
3
Tobago and is limited to Misiones Province in Argentina.
Drug resistance4: Chloroquine.
Recommendations: None.
Malaria species: P. falciparum 90%, P. vivax 10%,
MALARIA P. malariae rare.
No malaria transmission. Recommended chemoprophylaxis: Atovaquone-
proguanil, doxycycline, or mefloquine.
AUSTRIA
YELLOW FEVER BARBADOS
No requirements or recommendations. YELLOW FEVER
MALARIA Requirements: Required if traveling from a country
No malaria transmission. with risk of YFV transmission and ≥1 year of age,
including transit >12 hours in an airport located in a
AZERBAIJAN country with risk of YFV transmission.1 This requirement
YELLOW FEVER excludes Guyana and Trinidad and Tobago.
No requirements or recommendations. Recommendations: None.
MALARIA MALARIA
No malaria transmission. No malaria transmission.
BAHAMAS, THE BELGIUM
YELLOW FEVER YELLOW FEVER
Requirements: Required if traveling from a country No requirements or recommendations.
with risk of YFV transmission and ≥1 year of age, MALARIA
including transit >12 hours in an airport located in a No malaria transmission.
country with risk of YFV transmission.1 This requirement
excludes Guyana, Suriname, and Trinidad and Tobago. BELIZE
Recommendations: None. YELLOW FEVER
MALARIA Requirements: Required if traveling from a country
No malaria transmission. with risk of YFV transmission and ≥1 year of age,
including transit in an airport located in a country with
BAHRAIN risk of YFV transmission.1
YELLOW FEVER Recommendations: None.
Requirements: Required if traveling from a country MALARIA
with risk of YFV transmission and ≥9 months of age, Areas with malaria: Rare locally transmitted cases.
including transit >12 hours in an airport located in a None in Belize City and islands frequented by tourists,
country with risk of YFV transmission.1 such as Ambergris Caye.
Estimated relative risk of malaria for US travelers: São Tomé and Príncipe, Rwanda, Somalia, Tanzania,
Very low. Zambia, and designated areas of Eritrea.1
Drug resistance4: None. Recommendations:
Malaria species: P. vivax 100%. Recommended for all travelers ≥9 months of
Recommended chemoprophylaxis: Mosquito age traveling to the following areas <2,300 m in
avoidance only. elevation2 and east of the Andes Mountains: the
entire departments of Beni, Pando, Santa Cruz, and
BENIN designated areas (see Map 3-17) of Chuquisaca,
YELLOW FEVER Cochabamba, La Paz, and Tarija departments.
Requirements: Required if traveling from a country with Not recommended for travelers whose itineraries are
risk of YFV transmission and ≥1 year of age, including limited to areas >2,300 m in elevation2 and all areas not
transit in an airport located in a country with risk of YFV listed above, including the cities of La Paz and Sucre.
3 transmission.1
Recommendations: Recommended for all travelers
≥9 months of age.
MALARIA
Areas with malaria: All areas <2,500 m (8,202 ft).
None in the city of La Paz (see Map 3-18).
MALARIA Estimated relative risk of malaria for US travelers: Low.
Areas with malaria: All. Drug resistance4: Chloroquine.
Estimated relative risk of malaria for US Malaria species: P. vivax 93%, P. falciparum 7%.
travelers: High. Recommended chemoprophylaxis: Atovaquone-
Drug resistance4: Chloroquine. proguanil, doxycycline, mefloquine, or primaquine5.
Malaria species: P. falciparum >85%, P. ovale 5%–10%,
P. vivax rare. BONAIRE
Recommended chemoprophylaxis: Atovaquone- YELLOW FEVER
proguanil, doxycycline, or mefloquine. Requirements: Required if traveling from a country
with risk of YFV transmission and ≥6 months of age.1
BERMUDA (UK) This requirement applies only to travelers going to
YELLOW FEVER Bonaire, Saba, or Sint Eustatius.
No requirements or recommendations. Recommendations: None.
MALARIA MALARIA
No malaria transmission. No malaria transmission.
8
32
3
INFECTIOUS DISEASES RELATED TO TRAVEL
Lima*
YELLOW FEVER AND MALARIA INFORMATION, BY COUNTRY
PACIFIC
OCEAN
Malaria transmission
Malaria transmission is ATLANTIC
known to occur
OCEAN
Malaria transmission is not
ARGENTINA I
~
known to occur
r-_-_1-
- T Tourist destination
c'
250 500 1.000 1,500mi
3
8
43
MALARIA
Areas with malaria: Present at altitudes <1,000 m
CAMEROON
(3,281 ft), including Bagan. Rare transmission above YELLOW FEVER
1,000 m. Requirements: Required for arriving travelers from all
Estimated relative risk of malaria for US travelers: countries if traveler is ≥9 months of age.
Moderate. Recommendations: Recommended for all travelers
Drug resistance4: Chloroquine and mefloquine. ≥9 months of age.
Malaria species: P. falciparum 60%, P. vivax 35%; MALARIA
P. malariae, P. ovale, P. knowlesi rare. Areas with malaria: All.
Recommended chemoprophylaxis: Estimated relative risk of malaria for US travelers: High.
In the provinces of Bago, Kachin, Kayah, Kayin, Shan, Drug resistance4: Chloroquine.
and Tanintharyi below 1,000m (3,281 ft): Atovaquone- Malaria species: P. falciparum >85%, P. ovale 5%–10%,
BURUNDI CANADA
YELLOW FEVER YELLOW FEVER
Requirements: Required for arriving travelers from No requirements or recommendations.
all countries if traveler is ≥1 year of age. MALARIA
Recommendations: Recommended for all travelers No malaria transmission.
≥9 months of age.
MALARIA CANARY ISLANDS (SPAIN)
Areas with malaria: All. YELLOW FEVER
Estimated relative risk of malaria for US travelers: No requirements or recommendations.
Moderate.
MALARIA
Drug resistance4: Chloroquine.
No malaria transmission.
Malaria species: P. falciparum 86%; P. malariae, P. ovale,
P. vivax 14% combined.
Recommended chemoprophylaxis: Atovaquone-
CAPE VERDE
proguanil, doxycycline, or mefloquine. YELLOW FEVER
Requirements: Required if traveling from a country
CAMBODIA with risk of YFV transmission and ≥1 year of age,
including transit >12 hours in an airport located in a
YELLOW FEVER
country with risk of YFV transmission.1
Requirements: Required if traveling from a country
Recommendations: None.
with risk of YFV transmission and ≥1 year of age,
including transit >12 hours in an airport located in a MALARIA
country with risk of YFV transmission.1 Areas with malaria: Limited cases in São Tiago Island.
Recommendations: None. Estimated relative risk of malaria for US travelers:
Very low.
MALARIA
Drug resistance4: Chloroquine.
Areas with malaria: Present throughout the
Malaria species: Primarily P. falciparum.
country, including Siem Reap city. None in the
Recommended chemoprophylaxis: Mosquito
city of Phnom Penh or at the temple complex at
avoidance only.
Angkor Wat.
Estimated relative risk of malaria for US
travelers: Low. CAYMAN ISLANDS (UK)
Drug resistance4: Chloroquine and mefloquine. YELLOW FEVER
Malaria species: P. falciparum 86%, P. vivax 12%, No requirements or recommendations.
P. malariae 2%, P. knowlesi rare. MALARIA
Recommended chemoprophylaxis: No malaria transmission.
In the provinces of Banteay Meanchey,
Battambang, Kampot, Koh Kong, Odder CENTRAL AFRICAN
Meanchey, Pailin, Preah Vihear, Pursat, and
Siem Reap bordering Thailand: Atovaquone-proguanil REPUBLIC
or doxycycline. YELLOW FEVER
All other areas with malaria: Atovaquone-proguanil, Requirements: Required for arriving travelers from all
doxycycline, or mefloquine. countries if traveler is ≥9 months of age.
YELLOW FEVER
country with risk of YFV transmission.1 This requirement
excludes Galápagos Islands in Ecuador and the island of
3
Requirements: Required if traveling from a country Tobago and is limited to Misiones Province in Argentina.
with risk of YFV transmission.1 Recommendations: None.
Recommendations:
MALARIA
Recommended for all travelers ≥9 months of age traveling
No malaria transmission.
to areas south of the Sahara Desert (see Map 3-14).
Not recommended for travelers whose itineraries are
limited to areas in the Sahara Desert (see Map 3-14).
COCOS (KEELING) ISLANDS
MALARIA (AUSTRALIA)
Areas with malaria: All. YELLOW FEVER
Estimated relative risk of malaria for US Requirements: Required if traveling from a country
travelers: High. with risk of YFV transmission and ≥1 year of age,
Drug resistance4: Chloroquine. including transit >12 hours in an airport located
Malaria species: P. falciparum 85%; P. malariae, P. ovale, in a country with risk of YFV transmission.1 This
P. vivax 15% combined. requirement excludes Galápagos Islands in Ecuador
Recommended chemoprophylaxis: Atovaquone- and the island of Tobago and is limited to Misiones
proguanil, doxycycline, or mefloquine. Province in Argentina.
Recommendations: None.
CHILE MALARIA
YELLOW FEVER No malaria transmission.
No requirements or recommendations.
MALARIA COLOMBIA (see Maps 3-23
No malaria transmission. and 3-24.)
CHINA (see Map 3-22.) YELLOW FEVER
Requirements: None.
YELLOW FEVER Recommendations:
Requirements: Required if traveling from a country with Recommended for all travelers ≥9 months of age except
risk of YFV transmission and ≥1 year of age, including as mentioned below.
transit in an airport located in a country with risk of Generally not recommended for travelers to the cities
YFV transmission.1 This requirement does not apply to of Barranquilla, Cali, Cartagena, and Medellín (see
travelers whose itineraries are limited to Hong Kong Map 3-23).
Special Administrative Region (SAR) and Macao SAR. Not recommended for travelers whose itineraries are
Recommendations: None. limited to all areas >2,300 m in elevation,2 the department
MALARIA of San Andrès y Providencia, and the capital city of Bogotá.
Areas with malaria: Present in the counties along the MALARIA
China-Burma (Myanmar) border in Yunnan Province. Areas with malaria: All areas <1,700 m (5,577 ft). None
Limited transmission in Motuo County in Tibet. No in Bogotá, Cartagena, and Medellín (see Map 3-24).
malaria in areas where most major river cruises pass. Estimated relative risk of malaria for US
Estimated relative risk of malaria for US travelers: travelers: Low.
Very low. Drug resistance4: Chloroquine.
Drug resistance4: Chloroquine and mefloquine. Malaria species: P. falciparum 50%, P. vivax 50%.
Malaria species: Primarily P. vivax; P. falciparum in Recommended chemoprophylaxis: Atovaquone-
Yunnan Province. proguanil, doxycycline, or mefloquine.
8
3
6
3
INFECTIOUS DISEASES RELATED TO TRAVEL
·..·..... RUSSIA
..... . . . .
KAZAKHSTAN .·. ..... ·..... .· .
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·.... : *
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T~IKISTAN: •• •• ••• • ••••
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XINJIANG UYGUR JAPAN
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*
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SEA
PHILIPPINES
SEA
Recommendations:
Generally not recommended for travelers going to the
ETHIOPIA (see Maps 3-27 and 3-28.)
following states: Anseba, Debub, Gash Barka, Mae Kel, YELLOW FEVER
and Semenawi Keih Bahri. Requirements: Required if traveling from a country
Not recommended for all areas not listed above, with risk of YFV transmission and ≥9 months of age,
including the Dahlak Archipelago (see Map 3-14). including transit >12 hours in an airport located in a
country with risk of YFV transmission.1
MALARIA
Recommendations:
Areas with malaria: All areas <2,200 m (7,218 ft). None
Recommended for all travelers ≥9 months of age, except
in Asmara.
as mentioned below.
Estimated relative risk of malaria for US
Generally not recommended for travelers whose
travelers: High.
itinerary is limited to the Afar and Somali Provinces (see
Drug resistance4: Chloroquine.
Map 3-27).
Malaria species: P. falciparum 85%, P. vivax 10%–15%,
P. ovale rare. MALARIA
Recommended chemoprophylaxis: Atovaquone- Areas with malaria: All areas <2,500 m (8,202 ft),
proguanil, doxycycline, or mefloquine. except none in the city of Addis Ababa (see Map 3-28).
Estimated relative risk of malaria for US travelers:
ESTONIA Moderate.
Drug resistance4: Chloroquine.
YELLOW FEVER
Malaria species: P. falciparum 60%–70%, P. vivax
No requirements or recommendations.
30%–40%, P. malariae and P. ovale rare.
MALARIA Recommended chemoprophylaxis: Atovaquone-
No malaria transmission. proguanil, doxycycline, or mefloquine.
MALARIA YELLOW FEVER
Areas with malaria: All areas, including Matoury, Requirements: Required if traveling from a
Macouria, and Kourou, except none in coastal areas country with risk of YFV transmission and
west of Kourou and Cayenne City. ≥1 year of age, including transit >12 hours in
Estimated relative risk of malaria for US an airport located in a country with risk of YFV
travelers: Low. transmission.1
Drug resistance4: Chloroquine. Recommendations: None.
Malaria species: P. vivax >70%, P. falciparum 20%–30%, MALARIA
P. malariae rare No malaria transmission.
Recommended chemoprophylaxis: Atovaquone-
proguanil, doxycycline, or mefloquine. GABON
FRENCH POLYNESIA, YELLOW FEVER
Requirements: Required for arriving travelers from
INCLUDING THE ISLAND all countries if traveler is ≥1 year of age.
GROUPS OF SOCIETY Recommendations: Recommended for all travelers
≥9 months of age.
ISLANDS (TAHITI, MOOREA, MALARIA
AND BORA-BORA), Areas with malaria: All.
Estimated relative risk of malaria for US
MARQUESAS ISLANDS travelers: High.
(HIVA OA AND UA HUKA), Drug resistance4: Chloroquine.
Malaria species: P. falciparum 90%; P. malariae, P. ovale,
AND AUSTRAL ISLANDS P. vivax 10% combined.
(TUBUAI AND RURUTU)
*All footnotes are located on page 424.
3
Recommended chemoprophylaxis: None.
Estimated relative risk of malaria for US
travelers: High.
Drug resistance4: Chloroquine.
GREENLAND (DENMARK)
Malaria species: P. falciparum ≥85%, P. ovale 5%–10%, YELLOW FEVER
P. malariae and P. vivax rare. No requirements or recommendations.
Recommended chemoprophylaxis: Atovaquone- MALARIA
proguanil, doxycycline, or mefloquine. No malaria transmission.
GEORGIA GRENADA
YELLOW FEVER YELLOW FEVER
No requirements or recommendations. Requirements: Required if traveling from a country
MALARIA with risk of YFV transmission and ≥1 year of age,
No malaria transmission. including transit >12 hours in an airport located in a
country with risk of YFV transmission.1
GERMANY Recommendations: None.
YELLOW FEVER MALARIA
No requirements or recommendations. No malaria transmission.
MALARIA
No malaria transmission.
GUADELOUPE (FRANCE)
YELLOW FEVER
GHANA Requirements: Required if traveling from a country
with risk of YFV transmission and ≥1 year of age,
YELLOW FEVER
including transit >12 hours in a country with risk
Requirements: Required for arriving travelers from all
of YFV transmission.1
countries if traveler is ≥9 months of age.
Recommendations: None.
Recommendations: Recommended for all travelers
≥9 months of age. MALARIA
No malaria transmission.
MALARIA
Areas with malaria: All.
Estimated relative risk of malaria for US
GUAM (US)
travelers: High. YELLOW FEVER
Drug resistance4: Chloroquine. No requirements or recommendations.
Malaria species: P. falciparum 90%, P. ovale 5%–10%, MALARIA
P. vivax rare. No malaria transmission.
Recommended chemoprophylaxis: Atovaquone-
proguanil, doxycycline, or mefloquine. GUATEMALA
YELLOW FEVER
GIBRALTAR (UK) Requirements: Required if traveling from a country
YELLOW FEVER with risk of YFV transmission and ≥1 year of age,
No requirements or recommendations. including transit >12 hours in an airport located in a
MALARIA country with risk of YFV transmission.1
No malaria transmission. Recommendations: None.
GUINEA
YELLOW FEVER
No requirements or recommendations.
MALARIA
YELLOW FEVER Areas with malaria: All (including Port Labadee).
Requirements: Required if traveling from a country Estimated relative risk of malaria for US travelers:
with risk of YFV transmission and ≥1 year of age.1 Moderate.
Recommendations: Recommended for all travelers Drug resistance4: None.
≥9 months of age. Malaria species: P. falciparum 99%, P. malariae rare.
MALARIA Recommended chemoprophylaxis: Atovaquone-
Areas with malaria: All. proguanil, chloroquine, doxycycline, or mefloquine.
Estimated relative risk of malaria for US travelers: High.
Drug resistance4: Chloroquine. HONDURAS
Malaria species: P. falciparum >85%, P. ovale 5%–10%, YELLOW FEVER
P. vivax rare. Requirements: Required if traveling from a country with
Recommended chemoprophylaxis: Atovaquone- risk of YFV transmission and ≥1 year of age, including
proguanil, doxycycline, or mefloquine. transit >12 hours in an airport located in a country with
risk of YFV transmission.1 This requirement excludes the
GUINEA-BISSAU Central African Republic, Panama, and South Sudan.
YELLOW FEVER Recommendations: None.
Requirements: Required for arriving travelers from all MALARIA
countries if traveler is ≥1 year of age. Areas with malaria: Present throughout the country
Recommendations: Recommended for all travelers and in Roatán and other Bay Islands. None in San Pedro
≥9 months of age. Sula and Tegucigalpa.
MALARIA Estimated relative risk of malaria for US travelers:
Areas with malaria: All. Moderate.
Estimated relative risk of malaria for US travelers: Drug resistance4: None.
Moderate. Malaria species: P. vivax 93%, P. falciparum 7%.
Drug resistance4: Chloroquine. Recommended chemoprophylaxis: Atovaquone-
Malaria species: P. falciparum >85%, P. ovale 5%–10%, proguanil, chloroquine, doxycycline, mefloquine, or
P. vivax rare. primaquine5.
Recommended chemoprophylaxis: Atovaquone-
proguanil, doxycycline, or mefloquine. HONG KONG SAR
GUYANA (CHINA)
YELLOW FEVER
YELLOW FEVER
No requirements or recommendations.
Requirements: Required if traveling from a country
with risk of YFV transmission and ≥1 year of age, MALARIA
including transit in an airport located in a country with No malaria transmission.
risk of YFV transmission.1
Recommendations: Recommended for all travelers HUNGARY
≥9 months of age. YELLOW FEVER
MALARIA No requirements or recommendations.
Areas with malaria: All areas <900 m (2,953 ft). Rare MALARIA
cases in the cities of Amsterdam and Georgetown. No malaria transmission.
MALARIA
No malaria transmission.
KENYA (see Maps 3-30 and 3-31.)
YELLOW FEVER
IRELAND Requirements: Required if traveling from a
country with risk of YFV transmission and ≥1 year
YELLOW FEVER
of age.1
No requirements or recommendations.
Recommendations:
MALARIA Recommended for all travelers ≥9 months of age,
No malaria transmission. except as mentioned below.
Generally not recommended for travelers whose
ISRAEL itinerary is limited to the following areas: the
YELLOW FEVER entire North Eastern Province; the states of Kilifi,
No requirements or recommendations. Kwale, Lamu, Malindi, and Tanariver in the Coast
MALARIA
No malaria transmission.
Province; and the cities of Mombasa and Nairobi
(see Map 3-30).
3
MALARIA
ITALY, INCLUDING HOLY Areas with malaria: Present in all areas (including
SEE (VATICAN CITY) game parks) <2,500 m (8,202 ft) including the city of
Nairobi (see Map 3-31).
YELLOW FEVER
Estimated relative risk of malaria for US travelers:
No requirements or recommendations.
Moderate.
MALARIA Drug resistance4: Chloroquine.
No malaria transmission. Malaria species: P. falciparum >85%, P. vivax 5%–10%,
P. ovale up to 5%.
JAMAICA Recommended chemoprophylaxis: Atovaquone-
YELLOW FEVER proguanil, doxycycline, or mefloquine.
Requirements: Required if traveling from a country
with risk of YFV transmission and ≥1 year of age, KIRIBATI (FORMERLY
including transit in an airport located in a country with
risk of YFV transmission.1
GILBERT ISLANDS),
Recommendations: None. INCLUDES TARAWA,
MALARIA
No malaria transmission.
TABUAERAN (FANNING
ISLAND), AND BANABA
JAPAN (OCEAN ISLAND)
YELLOW FEVER
YELLOW FEVER
No requirements or recommendations.
Requirements: Required if traveling from a
MALARIA country with risk of YFV transmission and ≥1 year
No malaria transmission. of age.1
Recommendations: None.
JORDAN MALARIA
YELLOW FEVER No malaria transmission.
Requirements: Required if traveling from a country
with risk of YFV transmission and ≥1 year of age,
including transit >12 hours in an airport located in a
KOSOVO
YELLOW FEVER
country with risk of YFV transmission.1
Requirements: This country has not stated its yellow
Recommendations: None.
fever vaccination certificate requirements.
MALARIA Recommendations: None.
No malaria transmission.
MALARIA
KAZAKHSTAN No malaria transmission.
YELLOW FEVER
Requirements: Required if traveling from a country
KUWAIT
with risk of YFV transmission.1 YELLOW FEVER
Recommendations: None. No requirements or recommendations.
MALARIA MALARIA
No malaria transmission. No malaria transmission.
LAOS LATVIA
YELLOW FEVER YELLOW FEVER
Requirements: Required if traveling from a country No requirements or recommendations.
with risk of YFV transmission.1 MALARIA
Recommendations: None. No malaria transmission.
MALARIA
Areas with malaria: All, except none in the city of LEBANON
Vientiane. YELLOW FEVER
Estimated relative risk of malaria for US travelers: No requirements or recommendations.
Very low. MALARIA
Drug resistance4: Chloroquine and mefloquine. No malaria transmission.
3 MACEDONIA
including transit >12 hours in an airport located in a
country with risk of YFV transmission.1
Recommendations: None.
YELLOW FEVER
No requirements or recommendations. MALARIA
Areas with malaria: Present in rural areas. None in
MALARIA
Georgetown, Kuala Lampur, and Penang State (includes
No malaria transmission.
Penang Island).
MADAGASCAR Estimated relative risk of malaria for US
travelers: Low.
YELLOW FEVER Drug resistance4: Chloroquine.
Requirements: Required if traveling from a country Malaria species: P. falciparum, P. vivax, P. knowlesi,
with risk of YFV transmission and ≥9 months of age, P. malariae, P. ovale.
including transit >12 hours in an airport located in a Recommended chemoprophylaxis: Rural
country with risk of YFV transmission.1 areas: Atovaquone-proguanil, doxycycline, or
Recommendations: None. mefloquine.
MALARIA
Areas with malaria: All areas, except rare cases in the MALDIVES
city of Antananarivo. YELLOW FEVER
Estimated relative risk of malaria for US travelers: Requirements: Required if traveling from a country
Moderate. with risk of YFV transmission and ≥1 year of age,
Drug resistance4: Chloroquine. including transit >12 hours in an airport located in a
Malaria species: P. falciparum 85%, P. vivax 5%–10%, country with risk of YFV transmission.1
P. ovale 5%. Recommendations: None.
Recommended chemoprophylaxis: All areas except
MALARIA
the city of Antananarivo: Atovaquone-proguanil,
No malaria transmission.
doxycycline, or mefloquine.
Antananarivo: Mosquito avoidance only.
MALI
MADEIRA ISLANDS YELLOW FEVER
Requirements: Required for arriving travelers from all
(PORTUGAL) countries if traveler is ≥1 year of age.
YELLOW FEVER Recommendations:
No requirements or recommendations. Recommended for all travelers ≥9 months of age going
MALARIA to areas south of the Sahara Desert (see Map 3-14).
No malaria transmission. Not recommended for travelers whose itineraries are
limited to areas in the Sahara Desert (see Map 3-14).
MALAWI MALARIA
YELLOW FEVER Areas with malaria: All.
Requirements: Required if traveling from a country Estimated relative risk of malaria for US
with risk of YFV transmission and ≥1 year of age, travelers: High.
including transit >12 hours in an airport located in a Drug resistance4: Chloroquine.
country with risk of YFV transmission.1 Malaria species: P. falciparum >85%, P. ovale 5%–10%,
Recommendations: None. P. vivax rare.
Recommended chemoprophylaxis: Atovaquone-
MALARIA
proguanil, doxycycline, or mefloquine.
Areas with malaria: All.
3
No malaria transmission.
Recommendations: None.
MARSHALL ISLANDS MALARIA
Areas with malaria: Rare cases.
YELLOW FEVER
Estimated relative risk of malaria for US travelers:
No requirements or recommendations.
No data.
MALARIA Drug resistance4: Chloroquine.
No malaria transmission. Malaria species: P. falciparum 93%, P. vivax 5%,
P. malariae and P. ovale 2%.
MARTINIQUE (FRANCE) Recommended chemoprophylaxis: Mosquito
YELLOW FEVER avoidance only.
Requirements: Required if traveling from a country
with risk of YFV transmission and ≥1 year of age, MEXICO (see Map 3-32.)
including transit >12 hours in an airport located in a YELLOW FEVER
country with risk of YFV transmission.1 No requirements or recommendations.
Recommendations: None.
MALARIA
MALARIA Areas with malaria: Present in Campeche,
No malaria transmission. Chiapas, Chihuahua, Nayarit, and Sinaloa. Rare
cases in Durango, Jalisco, Oaxaca, Sonora, and
MAURITANIA Tabasco. Rare cases in the municipality of Othón
YELLOW FEVER P. Blanco in the southern part of Quintana Roo
Requirements: Required if traveling from a country bordering Belize. No malaria along the US-Mexico
with risk of YFV transmission and ≥1 year of age.1 border (see Map 3-32).
Recommendations: Estimated relative risk of malaria for US travelers:
Recommended for all travelers ≥9 months of age Very low.
traveling to areas south of the Sahara Desert (see Drug resistance4: None.
Map 3-14). Malaria species: P. vivax 100%.
Not recommended for travelers whose itineraries Recommended chemoprophylaxis:
are limited to areas in the Sahara Desert (see States of Campeche, Chiapas, Chihuahua, Nayarit,
Map 3-14). and Sinaloa: Atovaquone-proguanil, chloroquine,
MALARIA doxycycline, mefloquine, or primaquine5.
Areas with malaria: All areas, including the city of States of Durango, Jalisco, Oaxaca, Sonora, Tabasco,
Nouakchott. and Othón P. Blanco municipality of Quintana
Estimated relative risk of malaria for US Roo: Mosquito avoidance only.
travelers: High.
Drug resistance4: Chloroquine. MICRONESIA, FEDERATED
Malaria species: P. falciparum >85%, P. ovale 5%–10%,
P. vivax rare.
STATES OF; INCLUDES
Recommended chemoprophylaxis: Atovaquone- YAP, POHNPEI, CHUUK,
proguanil, doxycycline, or mefloquine. AND KOSRAE ISLANDS
MAURITIUS YELLOW FEVER
No requirements or recommendations.
YELLOW FEVER
MALARIA
Requirements: Required if traveling from a country
No malaria transmission.
with risk of YFV transmission and ≥1 year of age,
MONGOLIA
that originated outside the countries with risk of YFV
transmission, but who have been in transit through 3
these areas, are not required to possess a certificate
YELLOW FEVER
provided that they remained at the airport or in the
No requirements or recommendations.
adjacent town during transit. All travelers whose flights
MALARIA originated in countries with risk of YFV transmission
No malaria transmission. or who have been in transit through these countries on
unscheduled flights are required to possess a certificate.
MONTENEGRO The certificate is not required for children <1 year of age,
YELLOW FEVER but such infants may be subject to surveillance.
No requirements or recommendations. Recommendations: None.
MALARIA MALARIA
No malaria transmission. Areas with malaria: Present in the provinces of
Kavango (East and West), Kunene, Ohangwena,
MONTSERRAT (UK) Omusati, Oshana, Oshikoto, Otjozondjupa and Zambezi.
YELLOW FEVER Rare cases in other parts of the country. No malaria in
Requirements: Required if traveling from a country the city of Windhoek.
with risk of YFV transmission and ≥1 year of age.1 Estimated relative risk of malaria for US
Recommendations: None. travelers: Low.
Drug resistance4: Chloroquine.
MALARIA
Malaria species: P. falciparum >90%; P. malariae,
No malaria transmission.
P. ovale, P. vivax rare.
MOROCCO Recommended chemoprophylaxis:
Kavango (East and West), Kunene, Ohangwena,
YELLOW FEVER Omusati, Oshana, Oshikoto, Otjozondjupa, and
No requirements or recommendations. Zambezi: Atovaquone-proguanil, doxycycline, or
MALARIA mefloquine.
No malaria transmission. Other parts of the country with rare cases: Mosquito
avoidance only.
MOZAMBIQUE
YELLOW FEVER NAURU
Requirements: Required if traveling from a country with YELLOW FEVER
risk of YFV transmission and ≥9 months of age, including Requirements: Required if traveling from a country
transit >12 hours in an airport located in a country with with risk of YFV transmission and ≥1 year of age.1
risk of YFV transmission.1 This requirement includes São Recommendations: None.
Tomé and Príncipe, Somalia, and Tanzania and excludes MALARIA
Argentina, French Guiana, Paraguay, and South Sudan. No malaria transmission.
Recommendations: None.
MALARIA NEPAL
Areas with malaria: All. YELLOW FEVER
Estimated relative risk of malaria for US travelers: Requirements: Required if traveling from a country
Moderate. with risk of YFV transmission and ≥1 year of age,
Drug resistance4: Chloroquine. including transit >12 hours in an airport located in a
Malaria species: P. falciparum >90%, P. malariae, country with risk of YFV transmission.1
P. ovale, P. vivax rare. Recommendations: None.
3 YELLOW FEVER
No requirements or recommendations.
NICARAGUA (see Map 3-33.)
YELLOW FEVER
MALARIA
No requirements or recommendations.
No malaria transmission.
MALARIA
NEW CALEDONIA (FRANCE) Areas with malaria: Present in Región Autónoma
Atlántico Norte (RAAN) and Región Autónoma
YELLOW FEVER
Atlántico Sur (RAAS). Rare cases in Boaco,
Requirements: Required if traveling from a country
Chinandega, Esteli, Jinotega, Leon, Matagalpa, and
with risk of YFV transmission and ≥1 year of age,
Nueva Segovia. No malaria in the city of Managua
including transit >12 hours in an airport located in a
(see Map 3-33).
country with risk of YFV transmission.1 Note: In the
PAKISTAN MALARIA
No malaria transmission.
YELLOW FEVER
Requirements: Required if traveling from a PANAMA (see Maps 3-34 and 3-35.)
country with risk of YFV transmission and
YELLOW FEVER
≥1 year of age, including transit >12 hours in an
Requirements: No requirements.
3 airport located in a country with risk of YFV
transmission.1
Recommendations:
Recommended for all travelers ≥9 months of age
Recommendations: None.
traveling to all mainland areas east of the area
MALARIA surrounding the canal (the entire provinces of
Areas with malaria: All areas (including all cities) Darién, Emberá, and Kuna Yala [also spelled Guna
<2,500 m (8,202 ft). Yala] and areas of the provinces of Colón and Panamá
Estimated relative risk of malaria for US travelers: that are east of the canal) (see Map 3-34).
Moderate. Not recommended for travelers whose itineraries
Drug resistance4: Chloroquine. are limited to areas west of the canal, the city
Malaria species: P. vivax 70%, P. falciparum 30%. of Panama, the canal area itself, and the Balboa
PERU (see Maps 3-36 and 3-37.) Estimated relative risk of malaria for US
travelers: Low.
YELLOW FEVER Drug resistance4: Chloroquine.
Requirements: None. Malaria species: P. falciparum 70%–80%, P. vivax 20%–
Recommendations: 30%, P. knowlesi rare.
Recommended for all travelers ≥9 months of age Recommended chemoprophylaxis: Atovaquone-
going to the following areas at elevations below proguanil, doxycycline, or mefloquine.
2,300 m: the regions of Amazonas, Loreto, Madre
de Dios, San Martin, Ucayali, Puno, Cusco, Junín,
Pasco, and Huánuco, and designated areas (see Map
PITCAIRN ISLANDS (UK)
YELLOW FEVER
3-36) of the following regions: far north of Apurimac,
Requirements: Required if traveling from a
far northern Huancavelica, far northeastern
country with risk of YFV transmission and ≥1 year
Ancash, eastern La Libertad, northern and eastern
3 Cajamarca, northern and northeastern Ayacucho,
and eastern Piura.
of age.1
Recommendations: None.
Generally not recommended for travelers whose MALARIA
itineraries are limited to the following areas west of the No malaria transmission.
Andes: regions of Lambayeque and Tumbes and the
designated areas (see Map 3-36) of western Piura and POLAND
south, west, and central Cajamarca. YELLOW FEVER
Not recommended for travelers whose itineraries are No requirements or recommendations.
limited to the following areas: all areas above 2,300 m MALARIA
elevation, areas west of the Andes not listed above, the No malaria transmission.
city of Cusco, the capital city of Lima, Machu Picchu,
and the Inca Trail (see Map 3-36). PORTUGAL
MALARIA YELLOW FEVER
Areas with malaria: All departments <2,000 m No requirements or recommendations.
(6,562 ft), including the cities of Iquitos and Puerto
MALARIA
Maldonado and only the remote eastern regions of
No malaria transmission.
La Libertad and Lambayeque. None in the following
areas: Lima Province; the cities of Arequipa, Ica,
Moquegua, Nazca, Puno, and Tacna; the highland
PUERTO RICO (US)
tourist areas (Cusco, Machu Picchu, and Lake YELLOW FEVER
Titicaca); and along the Pacific Coast (see Map 3-37). No requirements or recommendations.
Estimated relative risk of malaria for US travelers: MALARIA
Moderate. No malaria transmission.
Drug resistance4: Chloroquine.
Malaria species: P. vivax 85%, P. falciparum 15%. QATAR
Recommended chemoprophylaxis: Atovaquone- YELLOW FEVER
proguanil, doxycycline, or mefloquine. No requirements or recommendations.
PHILIPPINES MALARIA
No malaria transmission.
YELLOW FEVER
Requirements: Required if traveling from a country
with risk of YFV transmission and ≥1 year of age,
RÉUNION (FRANCE)
YELLOW FEVER
including transit in an airport located in a country with
Requirements: Required if traveling from a country
risk of YFV transmission.1
with risk of YFV transmission and ≥1 year of age,
Recommendations: None.
including transit >12 hours in an airport located in a
MALARIA country with risk of YFV transmission.1
Areas with malaria: Present in rural areas <600 m Recommendations: None.
(1,969 ft) except none in the 22 provinces of Aklan, Albay,
MALARIA
Benguet, Biliran, Bohol, Camiguin, Capiz, Catanduanes,
No malaria transmission.
Cavite, Cebu, Guimaras, Iloilo, Northern Leyte, Southern
Leyte, Marinduque, Masbate, Eastern Samar, Northern
Samar, Western Samar, Siquijor, Sorsogon, and Surigao
ROMANIA
Del Norte. None in metropolitan Manila and other YELLOW FEVER
urban areas. No requirements or recommendations.
MALARIA
No malaria transmission.
SAINT KITTS (SAINT
CHRISTOPHER) AND
RUSSIA NEVIS (UK)
YELLOW FEVER
YELLOW FEVER
No requirements or recommendations.
Requirements: Required if traveling from a country
MALARIA with risk of YFV transmission and ≥1 year of age,
No malaria transmission. including transit >12 hours in an airport located in a
country with risk of YFV transmission.1
RWANDA Recommendations: None.
YELLOW FEVER MALARIA
Requirements: Required if traveling from a
3
No malaria transmission.
country with risk of YFV transmission and ≥1 year
of age. Also required if traveling from a country SAINT LUCIA
with an active yellow fever outbreak. Further
YELLOW FEVER
details available at http://moh.gov.rw/index.php?
Requirements: Required if traveling from a country
id=34&tx_ttnews%5btt_news%5d=633&cHash=
with risk of YFV transmission and ≥1 year of age.1
31c90fd13b953240c27d812275643392.
Recommendations: None.
Recommendations: Generally not recommended for
travelers to Rwanda. MALARIA
No malaria transmission.
MALARIA
Areas with malaria: All.
Estimated relative risk of malaria for US travelers:
SAINT MARTIN
Moderate. YELLOW FEVER
Drug resistance4: Chloroquine. Requirements: Required if traveling from a country
Malaria species: P. falciparum 90%, P. vivax 5%, with risk of YFV transmission and ≥1 year of age,
P. ovale 5%. including transit >12 hours in an airport located in a
Recommended chemoprophylaxis: Atovaquone- country with risk of YFV transmission.1
proguanil, doxycycline, or mefloquine. Recommendations: None.
MALARIA
SABA No malaria transmission.
YELLOW FEVER
Requirements: Required if traveling from a SAINT PIERRE AND
country with risk of YFV transmission and ≥6 months MIQUELON (FRANCE)
of age.1
YELLOW FEVER
Recommendations: None.
No requirements or recommendations.
MALARIA
MALARIA
No malaria transmission.
No malaria transmission.
SAINT BARTHÉLEMY SAINT VINCENT AND
YELLOW FEVER
Requirements: Required if traveling from a country THE GRENADINES
with risk of YFV transmission and ≥1 year of age, YELLOW FEVER
including transit >12 hours in an airport located in a Requirements: Required if traveling from a country
country with risk of YFV transmission.1 with risk of YFV transmission and ≥1 year of age.1
Recommendations: None. Recommendations: None.
MALARIA MALARIA
No malaria transmission. No malaria transmission.
including transit >12 hours in an airport located in a Recommendations: Recommended for all travelers
country with risk of YFV transmission.1 ≥9 months of age.
Recommendations: None. MALARIA
MALARIA Areas with malaria: All.
No malaria transmission. Estimated relative risk of malaria for US
travelers: High.
SAN MARINO Drug resistance4: Chloroquine.
YELLOW FEVER Malaria species: P. falciparum >85%, P. ovale 5%–10%,
No requirements or recommendations. P. vivax rare.
Recommended chemoprophylaxis: Atovaquone-
MALARIA
proguanil, doxycycline, or mefloquine.
No malaria transmission.
SERBIA
3 SÃO TOMÉ AND PRÍNCIPE
YELLOW FEVER
YELLOW FEVER
No requirements or recommendations.
Requirements: Required if traveling from a country
with risk of YFV transmission and ≥1 year of age, MALARIA
including transit in an airport located in a country with No malaria transmission.
risk of YFV transmission.1
Recommendations: Generally not recommended for SEYCHELLES
travelers to São Tomé and Príncipe. YELLOW FEVER
MALARIA Requirements: Required if traveling from a
Areas with malaria: All. country with risk of YFV transmission and
Estimated relative risk of malaria for US travelers: ≥1 year of age, including transit >12 hours in an
Very low. airport located in a country with risk of YFV
Drug resistance4: Chloroquine. transmission.1
Malaria species: P. falciparum 85%; P. malariae, P. ovale, Recommendations: None.
P. vivax 15% combined. MALARIA
Recommended chemoprophylaxis: Atovaquone- No malaria transmission.
proguanil, doxycycline, or mefloquine.
SIERRA LEONE
SAUDI ARABIA YELLOW FEVER
YELLOW FEVER Requirements: Required for arriving travelers from all
Requirements: Required if traveling from a country countries.
with risk of YFV transmission and ≥1 year of age, Recommendations: Recommended for all travelers
including transit >12 hours in an airport located in a ≥9 months of age.
country with risk of YFV transmission.1 MALARIA
Recommendations: None. Areas with malaria: All.
MALARIA Estimated relative risk of malaria for US
Areas with malaria: Rare cases in Asir and Jazan travelers: High.
emirates by border with Yemen. None in the cities of Drug resistance4: Chloroquine.
Jeddah, Mecca, Medina, Riyadh, and Ta’if. Malaria species: P. falciparum >85%, P. ovale 5%–10%,
Estimated relative risk of malaria for US travelers: P. malariae and P. vivax rare.
Very low. Recommended chemoprophylaxis: Atovaquone-
Drug resistance4: Chloroquine. proguanil, doxycycline, or mefloquine.
Malaria species: P. falciparum predominantly,
remainder P. vivax. SINGAPORE
Recommended chemoprophylaxis: Mosquito YELLOW FEVER
avoidance only. Requirements: Required for travelers who are
≥1 year of age who, within the preceding 6 days,
SENEGAL have been in or have been in transit >12 hours
YELLOW FEVER in an airport located in a country with risk of YFV
Requirements: Required if traveling from a country transmission.1
with risk of YFV transmission and ≥9 months of age, Recommendations: None.
including transit in an airport located in a country with MALARIA
risk of YFV transmission.1 No malaria transmission.
SURINAME SYRIA 3
YELLOW FEVER YELLOW FEVER
Requirements: Required if traveling from a No requirements or recommendations.
country with risk of YFV transmission and
MALARIA
≥1 year of age, including transit >12 hours in an
No malaria transmission.
airport located in a country with risk of YFV
transmission.1
Recommendations: Recommended for all travelers
TAIWAN
≥9 months of age. YELLOW FEVER
No requirements or recommendations.
MALARIA
Areas with malaria: Present in the municipality MALARIA
of Tapanahony in Sipaliwini Province. Rare cases No malaria transmission.
in Brokopondo Province and Boven Saramacca
municipality in Sipaliwini Province. No malaria in TAJIKISTAN
Paramaribo. YELLOW FEVER
Estimated relative risk of malaria for US No requirements or recommendations.
travelers: Low. MALARIA
Drug resistance4: Chloroquine. Areas with malaria: Rare indigenous cases.
Malaria species: P. falciparum >70%, P. vivax Estimated relative risk of malaria for US travelers:
15%–20%. Very low.
Recommended chemoprophylaxis: Drug resistance4: Chloroquine.
Tapanohony municipality in Sipaliwini Malaria species: P. vivax 90%, P. falciparum 10%.
Province: Atovaquone-proguanil, doxycycline, or Recommended chemoprophylaxis: Mosquito
mefloquine. avoidance only.
Other areas with malaria: Mosquito avoidance only.
TANZANIA
SWAZILAND YELLOW FEVER
YELLOW FEVER Requirements: Required if traveling from a
Requirements: Required if traveling from a country country with risk of YFV transmission and
with risk of YFV transmission.1 ≥1 year of age, including transit >12 hours in an
Recommendations: None. airport located in a country with risk of YFV
MALARIA transmission.1
Areas with malaria: Present in eastern areas Recommendations: Generally not recommended for
bordering Mozambique and South Africa, including all travelers to Tanzania.
of Lubombo district and the eastern half of Hhohho, MALARIA
Manzini, and Shiselweni districts. Areas with malaria: All areas <1,800 m (5,906 ft).
Estimated relative risk of malaria for US travelers: Estimated relative risk of malaria for US
Very low. travelers: High.
Drug resistance4: Chloroquine. Drug resistance4: Chloroquine.
Malaria species: P. falciparum 99%, P. ovale and Malaria species: P. falciparum >85%, P. ovale >10%,
P. vivax 1%. P. malariae and P. vivax rare.
Recommended chemoprophylaxis: Atovaquone- Recommended chemoprophylaxis: Atovaquone-
proguanil, doxycycline, or mefloquine. proguanil, doxycycline, or mefloquine.
THAILAND TOGO
YELLOW FEVER YELLOW FEVER
Requirements: Required if traveling from a country Requirements: Required for arriving travelers from all
with risk of YFV transmission and ≥9 months of age, countries if traveler is ≥9 months of age.
including transit >12 hours in an airport located in a Recommendations: Recommended for all travelers
country with risk of YFV transmission.1 ≥9 months of age.
Recommendations: None. MALARIA
MALARIA Areas with malaria: All.
Areas with malaria: Primarily in provinces that Estimated relative risk of malaria for US
border Burma (Myanmar), Cambodia, and Laos and travelers: High.
the provinces of Kalasin, Krabi (Plai Phraya district), Drug resistance4: Chloroquine.
3
Nakhon Si Thammarat, Narathiwat, Pattani, Phang Malaria species: P. falciparum 85%, P. ovale 5%–10%,
Nga (including Phang Nga City), Rayong, Sakon remainder P. vivax.
Nakhon, Songkhla, Surat Thani, and Yala, especially Recommended chemoprophylaxis: Atovaquone-
the forest and forest fringe areas of these provinces. proguanil, doxycycline, or mefloquine.
Rare to few cases in other parts of Thailand, including
other parts of Krabi Province and the cities of TOKELAU (NEW ZEALAND)
Bangkok, Chiang Mai, Chiang Rai, Koh Phangan, YELLOW FEVER
Koh Samui, and Phuket. None in the islands of Krabi No requirements or recommendations.
Province (Koh Phi Phi, Koh Yao Noi, Koh Yao Yai, and
MALARIA
Ko Lanta) and Pattaya City.
No malaria transmission.
Estimated relative risk of malaria for US
travelers: Low.
Drug resistance4: Chloroquine and mefloquine. TONGA
Malaria species: P. falciparum 50% (up to 75% in some YELLOW FEVER
areas), P. vivax 50% (up to 60% in some areas), P. ovale No requirements or recommendations.
and P. knowlesi rare. MALARIA
Recommended chemoprophylaxis: No malaria transmission.
Provinces that border Burma (Myanmar), Cambodia,
and Laos, the provinces of Kalasin, Plai Phraya district
of Krabi, Nakhon Si Thammarat, Narathiwat, Pattani,
TRINIDAD AND TOBAGO
YELLOW FEVER
Phang Nga (including Phang Nga City), Rayong, Sakon
Requirements: Required if traveling from a country
Nakhon, Songkhla, Surat Thani, and Yala: Atovaquone-
with risk of YFV transmission and ≥1 year of age,
proguanil or doxycycline.
including transit in an airport located in a country with
All other areas of Thailand with malaria including
risk of YFV transmission.1
the cities of Bangkok, Chiang Mai, Chiang Rai,
Recommendations:
Koh Phangan, Koh Samui, and Phuket: Mosquito
Recommended for all travelers ≥9 months of
avoidance only.
age traveling to the island of Trinidad, except as
TIMOR-LESTE mentioned below.
Generally not recommended for travelers whose
YELLOW FEVER itinerary is limited to the urban areas of the capital city
Requirements: Required if traveling from a country of Port of Spain, cruise ship passengers who do not
with risk of YFV transmission and ≥1 year of age, disembark from the ship, and airplane passengers in
including transit in an airport located in a country with transit.
risk of YFV transmission.1 Not recommended for travelers whose itineraries are
Recommendations: None. limited to the island of Tobago.
MALARIA MALARIA
Areas with malaria: All. No malaria transmission.
Estimated relative risk of malaria for US travelers:
Moderate.
Drug resistance4: Chloroquine.
TUNISIA
Malaria Species: P. falciparum 50%, P. vivax 50%, YELLOW FEVER
P. ovale <1%, P. malariae <1%. No requirements or recommendations.
Recommended chemoprophylaxis: Atovaquone- MALARIA
proguanil, doxycycline, or mefloquine. No malaria transmission.
YELLOW FEVER URUGUAY
No requirements or recommendations.
YELLOW FEVER
MALARIA No requirements or recommendations.
No malaria transmission.
MALARIA
TUVALU No malaria transmission.
YELLOW FEVER UZBEKISTAN
No requirements or recommendations.
YELLOW FEVER
MALARIA No requirements or recommendations.
No malaria transmission.
MALARIA
UGANDA No malaria transmission.
YELLOW FEVER VANUATU
Requirements: Required for arriving travelers from
YELLOW FEVER
all countries. Also, proof of yellow fever vaccination
No requirements or recommendations.
required of all travelers leaving Uganda.
Recommendations: Recommended for all travelers MALARIA
≥9 months of age. Areas with malaria: All.
Estimated relative risk of malaria for US travelers:
MALARIA
Moderate.
Areas with malaria: All.
Drug resistance4: Chloroquine.
Estimated relative risk of malaria for US
Malaria species: P. falciparum 60%, P. vivax 35%–40%,
travelers: High.
P. ovale <1%.
Drug resistance4: Chloroquine.
Recommended chemoprophylaxis: Atovaquone-
Malaria species: P. falciparum >85%; remainder
proguanil, doxycycline, or mefloquine.
P. malariae, P. ovale, and P. vivax.
Recommended chemoprophylaxis: Atovaquone-
proguanil, doxycycline, or mefloquine.
VENEZUELA (see Maps 3-39
and 3-40.)
UKRAINE YELLOW FEVER
YELLOW FEVER Requirements: None.
No requirements or recommendations. Recommendations:
MALARIA Recommended for all travelers ≥9 months of age, except
No malaria transmission. as mentioned below.
Generally not recommended for travelers whose
UNITED ARAB EMIRATES itinerary is limited to the following areas: the states of
Aragua, Carabobo, Miranda, Vargas, and Yaracuy, and
YELLOW FEVER
the Distrito Federal (see Map 3-39).
No requirements or recommendations.
Not recommended for travelers whose itineraries are
MALARIA limited to the following areas: all areas >2,300m in
No malaria transmission. elevation in the states of Merida, Tachira, and Trujillo;
2
3
INFECTIOUS DISEASES RELATED TO TRAVEL
.. ··.. ATLANTIC
OCEAN
Malllhma
APUII£
YELLOW FEVER AND MALARIA INFORMATION, BY COUNTRY
BCILIVAR
G Ul n
H ghlands
COLOMBIA
...
. . .· .... . ...
Malaria transmission .
la Esnaalda :.
Malaria transmission is
known to occur BRAZIL
Malaria transmission is not
known to occur ...·
~ - -1 ..,
-... _ ~ Tourist destination
111
3
4
2
3 VIETNAM
WESTERN SAHARA
YELLOW FEVER
YELLOW FEVER Requirements: This territory has not stated its yellow
Requirements: Required if traveling from a country fever vaccination certificate requirements.
with risk of YFV transmission and ≥1 year of age.1 Recommendations: None.
Recommendations: None.
MALARIA
MALARIA Areas with malaria: Rare cases.
Areas with malaria: Rural areas only. Rare cases in the Estimated relative risk of malaria for US travelers:
Mekong and Red River Deltas. None in the cities of Da No data.
Nang, Haiphong, Hanoi, Ho Chi Minh City (Saigon), Nha Drug resistance4: Chloroquine.
Trang, and Qui Nhon. Malaria species: Unknown.
Estimated relative risk of malaria for US Recommended chemoprophylaxis: Mosquito
travelers: Low. avoidance only.
Drug resistance4: Chloroquine and mefloquine.
Malaria species: P. falciparum 50%–90%, P. vivax 10%– YEMEN
50%, P. knowlesi rare.
YELLOW FEVER
Recommended chemoprophylaxis:
No requirements or recommendations.
Southern part of the country in the provinces of Dac
Lac, Gia Lai, Khanh Hoa, Kon Tum, Lam Dong, Ninh MALARIA
Thuan, Song Be, Tay Ninh: Atovaquone-proguanil or Areas with malaria: All areas <2,000 m (6,562 ft). None
doxycycline. in Sana’a.
Other areas with malaria except Mekong and Estimated relative risk of malaria for US
Red River Deltas: Atovaquone-proguanil, doxycycline, travelers: Low.
or mefloquine. Drug resistance4: Chloroquine.
Mekong and Red River Deltas: Mosquito avoidance only. Malaria species: P. falciparum 95%; P. malariae, P. vivax,
P. ovale 5% combined.
VIRGIN ISLANDS, BRITISH Recommended chemoprophylaxis: Atovaquone-
proguanil, doxycycline, or mefloquine.
YELLOW FEVER
No requirements or recommendations.
ZAMBIA (see Map 3-41.)
MALARIA
YELLOW FEVER
No malaria transmission.
Requirements: Required if traveling from a country
with risk of YFV transmission and ≥9 months of age,
VIRGIN ISLANDS, US including transit >12 hours in an airport located in a
YELLOW FEVER country with risk of YFV transmission.1
No requirements or recommendations. Recommendations:
MALARIA Generally not recommended for travelers going to the
No malaria transmission. North West and Western Provinces (see Map 3-41).
Not recommended in all other areas not listed above.
WAKE ISLAND, US MALARIA
YELLOW FEVER Areas with malaria: All.
No requirements or recommendations. Estimated relative risk of malaria for US travelers:
MALARIA Moderate.
No malaria transmission. Drug resistance4: Chloroquine.
FOOTNOTES
Yellow Fever
1
The official WHO list of countries with risk of YFV transmission can be found in Table 3-22. Proof of yellow fever vaccination
should be required only if traveling from a country on the WHO list, unless otherwise specified. The following countries,
containing only areas with low potential for exposure to YFV, are not on the WHO list: Eritrea, Rwanda, São Tomé and
Príncipe, Somalia, Tanzania, Zambia.
2
An elevation of 2,300 m is equivalent to 7,546 ft.
Malaria
3
This risk estimate is based largely on cases occurring in US military personnel who travel for extended periods of time with
3 4
5
unique itineraries that likely do not reflect the risk for the average US traveler.
Refers to P. falciparum malaria unless otherwise noted.
Primaquine can cause hemolytic anemia in people with G6PD deficiency. Patients must be screened for G6PD deficiency
before starting primaquine.
Select Destinations
RATIONALE FOR SELECT
DESTINATIONS
Ronnie Henry
This chapter of the Yellow Book was created to limitations prevent us from including all tour-
allow experts who have lived in or have frequently ist destinations in this chapter, and the deci-
visited particular destinations to share their sion of what destinations to add or remove is
insider’s knowledge of these places. Each of these guided by volume of US travel, uniqueness of
sections should be considered a personal per- health risks, and other factors. In this edition,
spective on the area discussed. They are editorial we have added Cuba (reflecting the loosening
in nature, containing the author’s expressed opin- of US travel restrictions) and Burma (reflect-
ions; they should not be taken as a prescription ing its emergence as a tourist destination). To
for pretravel care. These sections are intended to accommodate these new sections, we have
help a travel health provider feel more comfort- removed Cambodia and Egypt & Nile River
able giving advice about destinations that he or Cruises. Because these destinations remain
she may have never visited and to provide a level relevant, these sections will continue to exist
of detail about the attractions and risks that has in the Yellow Book online (www.cdc.gov/
not been provided elsewhere in this book. yellowbook), along with other online-only sec-
The destination sections are among the tions: Guatemala and Belize, Iguaçu Falls, and
most popular features of the Yellow Book. Space Jamaica.
when a giant volcano, perhaps the size of Mount avoidable. The best insurance for carefree trips is
Kilimanjaro, exploded and collapsed on itself mil- a pretravel consultation with a travel health care
lions of years ago. The crater has most of the same provider, choosing an experienced and sophis-
animals as the Masai Mara reserve. The major ticated tour operator, and taking along a small,
East African game parks are shown on Map 4-1. personalized medical kit (see Chapter 2, Travel
Travelers should research the optimum time Health Kits).
of the year for their safari. The wildebeest migra- Experienced tour operators generally require
tion in the Serengeti is a seasonal event, for exam- that clients buy medical evacuation insurance,
ple, although the precise time of the migration supply clients with ample literature relating to
may vary from year to year. Some parks have a local conditions, and employ knowledgeable
dry season, offering better views of the animals, guides who carry first aid kits and communica-
as the vegetation is sparser and animals gather tion equipment to summon help, if necessary
where water is present, but roads are dustier. And (see Chapter 2, Travel Insurance, Travel Health
many areas of Africa have times of the year that
are more comfortable for visitors, with cooler
Insurance, & Medical Evacuation Insurance).
Health advice must be itinerary-and game
4
weather, lower humidity, and less chance of rain. park–specific. Immunizations and preventive
medications necessary for one park may not be
HEALTH ISSUES necessary for others. Parks may be long distances
Health and safety issues that safari-goers are likely apart and located in countries with different
to encounter are mostly predictable and largely health standards and dissimilar climates. Some
Travelers must check the requirements of each clothing left to dry outdoors, and the larvae enter
country on their itinerary, including countries the skin when the clothing is worn. Clothing
they only transit through on the way to their des- should be dried indoors or ironed before wearing.
tination. Some countries may require a valid ICVP Tungiasis is caused by direct penetration of skin
even if there is no yellow fever in the country by sand fleas, resulting in small, painful nodules,
travelers are leaving or entering. often on the foot adjacent to toenails. Prevention
includes wearing closed-toed footwear and not
Other Health Risks walking barefoot.
African trypanosomiasis (sleeping sickness), a dis- Symptoms of many diseases acquired in Africa
ease only rarely seen among travelers, is transmit- may surface weeks and occasionally months after
ted by day-biting tsetse flies (Glossina). Wearing exposure, sometimes long after the traveler has
light-colored clothing (and avoiding wearing blue) returned home. Patients should mention all travel
seems to deter the flies. Insect repellents are only to their health care provider if they become ill
partially effective. Symptoms include fever, eschar
at the site of the bite, headache, and signs of cen-
after a trip.
4
tral nervous system involvement. Several cases Other Safety Risks
of trypanosomiasis (rhodesiense) have recently Although being a crime victim is an unusual
been reported in European tourists visiting the occurrence for those on safari, robberies, mug-
Masai Mara National Reserve in Kenya and wild- gings, and carjackings may occur in major urban
life reserves in Tanzania. centers, notably Nairobi and Mombasa. Street
Dengue, filariasis, leishmaniasis, and oncho- muggings during the day and night are com-
cerciasis (river blindness) are other diseases mon. The rates of fatal motor vehicle crashes
carried by insects that occur in East Africa. in sub-Saharan Africa are among the highest
Swimming in freshwater ponds, lakes, and riv- in the world. Travelers should fasten seat belts
ers can result in schistosomiasis (bilharzia), a when riding in cars and wear a helmet when rid-
parasite found in freshwater snails and trans- ing bicycles or motorbikes. Within game parks,
mitted by exposure to water. All freshwater serious motor vehicle crashes are rare, as the
sources should be considered contaminated. poor roads discourage speeding. However, travel
Swimming in the ocean or well- chlorinated in rural areas between parks is high risk, espe-
pools is safe. cially after dark. If at all possible, nighttime driv-
Myiasis and tungiasis are rare skin diseases ing in sub-Saharan Africa should be avoided, and
among travelers. Myiasis is caused by fly larvae pedestrians should take extra care for speeding
penetrating the skin and causing a boil-like lesion vehicles. Boarding an overcrowded bus should
with a central aperture. Eggs are usually laid on be avoided.
BIBLIOGRAPHY
1. Gobbi F, Bisoffi Z. Human African trypanosomiasis aspects of an old disease. Emerg Infect Dis. 2006
in travellers to Kenya. Eurosurveillance. 2012 Mar Nov;12(11):1696–700.
8;17(10):pii=20109. 4. Thrower Y, Goodyer LI. Application of insect repellents
2. CDC. Yellow fever vaccine: recommendations of the by travelers to malaria endemic areas. J Travel Med.
Advisory Committee on Immunization Practices 2006 Jul-Aug;13(4):198–202.
(ACIP). MMWR Recomm Rep. 2010 Jun 30;59(RR-7): 5. Warne B, Weld LH, Cramer JP, Field VK, Grobusch MP,
1–27. Caumes E, et al. Travel-related infection in European
3. Meltzer E, Artom G, Marva E, Assous MV, Rahav G, travelers, EuroTravNet 2011. J Travel Med 2014
Schwartzt E. Schistosomiasis among travelers: new Jul-Aug;21(4):248–54.
may visit farms where they either sacrifice an ani- of visas to travelers from countries experiencing
mal themselves or have it done by an appointed infectious disease outbreaks. In 2012, Uganda was
representative. The World Health Organization not permitted to send pilgrims due to an Ebola
recommends travelers visiting farms or other outbreak in that country, and the same restriction
areas where animals are present practice general applied to Liberia, Guinea, and Sierra Leone in
hygiene measures, including regular handwashing 2015. Multiple medical facilities are located in and
before and after touching animals and avoiding around the holy sites; medical services are offered
contact with sick animals. Travelers should avoid free of charge to pilgrims. An estimated 20,000
the consumption of raw or undercooked animal health care workers were in attendance during
products (including milk and meat). the 2012 Hajj.
After returning to Mecca, pilgrims go imme-
diately to the Grand Mosque, which contains Vaccine-Preventable Diseases
the Ka’aba, and perform a tawaf, which involves CDC recommends all travelers to Saudi Arabia
4 circling the Ka’aba 7 times counterclockwise.
Because of the vast number of people (each floor
be up-to-date with routine immunizations. In
addition, hepatitis A vaccine is recommended
of the 3-level mosque has a capacity of 750,000 for most travelers, and hepatitis B vaccine
people), performing a tawaf can take hours. In is recommended for travelers who might be
addition to tawaf, pilgrims may perform sa’i, walk- exposed to blood or other body fluids. Travelers
ing (and running during certain parts) 7 times from yellow fever–endemic countries, or those
between the hills of Safa and Marwah, and then who travel via these areas, must provide proof
drinking water from the Well of Zamzam. This of yellow fever vaccination. Although a require-
route is enclosed by the Grand Mosque and can ment for polio vaccine does not include adult
be traversed via air-conditioned tunnels, with sep- pilgrims from the United States, it is best to
arate sections for walkers, runners, and disabled ensure full vaccination against polio before
pilgrims. Pilgrims then return to Mina and pelt all travel. All pilgrims who travel from countries
three columns at the Jamaraat on the 11th and where polio is reported are required to show
12th of the month, with the option of repeating it proof of polio vaccination at least 6 weeks prior
on the 13th. to arrival in Saudi Arabia. In addition, a single
After performing a final tawaf, pilgrims leave dose of the polio vaccine is administered to all
Mecca, ending Hajj. Although it is not required pilgrims in Saudi Arabia from countries where
as part of Hajj, many pilgrims extend their trips polio has been reported irrespective of previous
to travel to Medina. In Medina, pilgrims visit the immunization against the disease. The number
Mosque of the Prophet, which contains the tomb of polio doses administered at ports of entry is
of Mohammed. Physicians should query patients about 500,000, representing more than 90% of
about their itineraries to ensure they have ade- eligible pilgrims.
quate medication and supplies for the length of
their trip. MENINGOCOCCAL VACCINE
The Kingdom of Saudi Arabia will not issue Hajj
HEALTH ISSUES or Umrah visas without proof of meningococcal
The Kingdom of Saudi Arabia (KSA) sets medi- vaccination at least 10 days and no more than
cal requirements such as proof of vaccination as 3 years before arrival for polysaccharide vac-
part of the visa application process for Hajj pil- cine and no more than 8 years before arrival for
grims. These vaccinations may include seasonal conjugate vaccine. (CDC recommends revacci-
influenza, H1N1, and meningitis. Health experts nation with conjugate vaccine after 5 years for
in KSA currently advise that the elderly, the ter- people at continued risk.) All pilgrims must have
minally ill, pregnant women, and children post- received a single dose of quadrivalent ACWY vac-
pone their plans for Hajj and Umrah for safety cine and must show proof of vaccination on a
reasons. KSA may also choose to limit issuance valid International Certificate of Vaccination or
Prophylaxis. Although the KSA Ministry of Health active pulmonary disease. Pilgrims are advised
currently advises against travel to the Hajj for to see their doctors if they develop signs of active
pregnant women or children, if they choose to tuberculosis.
travel these groups should receive meningococ- Middle East respiratory syndrome (MERS)
cal vaccination according to licensed indications is caused by the MERS coronavirus, which was
for their age. These requirements are regularly first identified in Saudi Arabia in 2012. Cases
updated on the Saudi Ministry of Hajj website and have been identified in and around the Arabian
should be consulted before travel. Peninsula, and cases have also been exported to
Current Hajj vaccination requirements are other countries, including the United States. The
available from the following sources: most common symptoms include fever, cough,
and shortness of breath. However, myalgia, diar-
• Saudi Arabian Embassy (http://embassies. rhea, vomiting, abdominal pain, thrombocyto-
mofa.gov.sa/sites/usa/AR/Pages/default.
penia, and leukopenia have also been reported.
aspx)
• Saudi Arabian Ministry of Hajj (http://haj.
The severity of illness has ranged from mild to
severe, and approximately 40% of reported cases
4
gov.sa/english/pages/default.aspx) have been fatal. The role of animal-to-human
transmission is unclear, but the virus has been
• Saudi Arabian Ministry of Health (www. found in camels in this region. The diagnosis can
moh.gov.sa/en/Hajj/HealthGuidelines/
be suspected on clinical grounds and confirmed
HealthGuidelinesBeforeHajj/Pages/
by PCR testing. More information is available in
default.aspx)
Chapter 3, Middle East Respiratory Syndrome
(MERS).
Respiratory Infections
Respiratory tract infections are common during
Hajj, with pneumonia being the most common Other Health and Safety Risks
cause of hospital admission. These risks under- COMMUNICABLE DISEASES
score the need to follow recommendations Diarrheal disease is common during Hajj, and
from the Advisory Committee on Immuni travelers should be educated on usual preven-
zation Practices for pneumococcal conju- tion measures and self-treatment. A pretravel visit
gate and polysaccharide vaccines for pilgrims should include discussions about prevention, oral
aged ≥65 years and for younger travelers with rehydration strategies, antimotility agents, and
comorbidities. emergency antibiotic use for treatment of travel-
Seasonal influenza vaccine is strongly rec- ers’ diarrhea. More information can be found in
ommended for all pilgrims. Behavioral inter- Chapter 2, Travelers’ Diarrhea.
ventions such as hand hygiene, wearing a face Chafing caused by long periods of stand-
mask, cough etiquette, social distancing, and ing and walking in the heat can lead to fungal
contact avoidance may mitigate respiratory ill- or bacterial skin infections. Clothing should
ness among pilgrims. Pretravel advice about be light, not restrictive, and changed often to
common respiratory conditions should include maintain hygiene. Travelers should be advised
a general assessment for respiratory fitness, to keep skin dry, use talcum powder, and be
necessary vaccinations, and prescription of aware of any pain or soreness caused by gar-
adequate supplies of portable respiratory med- ments. Any sores or blisters that develop should
ications (inhalers are easier to transport than be disinfected and kept covered. Special atten-
nebulizers). tion should be paid to protect the feet, which
The crowded conditions during Hajj increase are bare when inside the Grand Mosque. People
the probability of tuberculosis transmission. Risk with diabetes are at increased risk of skin
is estimated to be about 10% in those with high infections.
level of exposure. Many pilgrims come from highly Nasal ablution, called istinshaaq, is the practice
endemic areas and some arrive for Hajj with of rinsing your nose with water before performing
some rituals during the Hajj. Medical literature Heat exhaustion and heatstroke are a threat
has identified cases of primary amebic menin- to the health and well-being of travelers, can
goencephalitis (PAM) caused by Naegleria fowl- exacerbate chronic conditions, and are a lead-
eri transmitted as a result of nasal ablution. Nasal ing cause of death, particularly when Hajj occurs
ablution is common during Hajj, and pilgrims are during the summer months. Pilgrims should stay
advised to use safe water to protect themselves hydrated, wear sunscreen, and seek shade when
from this potential risk (see Chapter 2, Water possible. Umbrellas are frequently used to pro-
Disinfection for Travelers). vide portable sun protection. Travelers should
At the end of Hajj, Muslim men must shave be counseled on minimizing the risk of heat-
their heads. The use of unclean blades can trans- related injuries, as well as sun avoidance. Some
mit bloodborne pathogens, such as hepatitis B rituals may also be performed at night to avoid
virus, hepatitis C virus, and HIV. Licensed bar- daytime heat. Pilgrims can be reassured that reli-
bers are tested for these bloodborne pathogens gious leaders have deemed night rituals as legiti-
4 and are required to use disposable, single-use
blades. Unfortunately, unlicensed barbers con-
mate. Except for the absolute presence on Arafat
on the ninth of Dhul Hijah, most compulsory rit-
tinue to operate by the roadside, where they use uals can be postponed or done by proxy, or a pen-
nonsterile blades on multiple men. Male trav- alty can be paid.
elers should be advised to be shaved only at Fire is a potential risk at Hajj. In 1997, open
officially designated centers, which are clearly stoves set tents on fire, and the resulting blaze
marked. killed 343 pilgrims and injured more than 1,500.
Aedes and Anopheles mosquitoes, which trans- As a result, makeshift tents were replaced with
mit dengue and malaria, respectively, are present permanent fiberglass structures; pilgrims are not
in Saudi Arabia, and mosquito bite prevention allowed to set up their own tents or prepare their
measures are advisable. Dengue has been docu- own food. Cooking in the tents is also prohibited.
mented in Mecca but not during Hajj. Intensive In 2015, a hotel caught fire, leading to the evacua-
insecticide spraying campaigns are undertaken tion of more than 1,000 pilgrims.
before Hajj, and the housing units of pilgrims
arriving from endemic areas are especially tar- TRAUMA
geted before their arrival. Prophylaxis against Trauma is a major cause of injury and death
malaria is not required. during Hajj. Motor vehicle crashes are the pri-
mary risk for US travelers overseas, and pilgrims
NONCOMMUNICABLE DISEASES may walk long distances through or near dense
AND OTHER HAZARDS traffic. In such dense crowds, crush disasters (or
Hajj is arduous even for young, healthy pilgrims, “stampedes”) are also a risk. In 2004, after 251
and many Muslims may wait until they are older pilgrims were killed and another 244 injured,
before making Hajj. Travelers who are caught the Saudi government replaced the round
up in the experience of Hajj or Umrah may for- pillars with wide, elliptical columns to reduce
get to take their usual medications. People with crowd densities. After another crowd crush in
chronic medical conditions should undergo a 2006 that killed 280 pilgrims and injured 289,
functional assessment before leaving for Hajj. the single- tiered Jamaraat pedestrian bridge
The medical provider should identify each trav- was demolished and replaced with a wider,
eler’s unique risks and tailor a plan for how to multilevel bridge. In 2015, thousands of pilgrims
reduce them. The provider should make any were killed during a crush at Mina, making it
adjustments to the usual medical regimen, the deadliest Hajj disaster on record. Death usu-
ensure that the traveler has an adequate supply ally results from asphyxiation or head trauma,
of medications, and educate the traveler about and large crowds limit the movement of emer-
symptoms that should prompt urgent medical gency medical services, making prompt treat-
attention. ment difficult.
BIBLIOGRAPHY
1. Alsafadi H, Goodwin W, Syed A. Diabetes care during 6. Memish ZA. The Hajj: communicable and non-
Hajj. Clin Med. 2011 Jun;11(3):218–21. communicable health hazards and current
2. Alzahrani AG, Choudhry AJ, Al Mazroa MA, Turkistani guidance for pilgrims. Euro Surveill. 2010 Sep
AH, Nouman GS, Memish ZA. Pattern of diseases 30;15(39):19671.
among visitors to Mina health centers during the Hajj 7. Memish ZA. Saudi Arabia has several strategies to care
season, 1429 H (2008 G). J Infect Public Health. 2012 for pilgrims on the Hajj. BMJ. 2011;343:d7731.
Mar;5(1):22–34. 8. Memish ZA, Al-Rabeeah AA. Health conditions of
3. Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, travellers to Saudi Arabia for the pilgrimage to Mecca
Al-Hajjar S, Al-Barrak A, et al. Epidemiological, (Hajj and Umra) for 1434 (2013). J Epidemiol Glob
demographic, and clinical characteristics of 47 cases Health. 2013 Jun;3(2):59–61.
of Middle East respiratory syndrome coronavirus 9. Shibl A, Tufenkeji H, Khalil M, Memish Z,
disease from Saudi Arabia: a descriptive study. Lancet Meningococcal Leadership Forum (MLF) Expert
Infect Dis. 2013 Sep;13(9):752–61. Group. Consensus recommendation for menin-
4. Balaban V, Stauffer WM, Hammad A, Afgarshe M, gococcal disease prevention for Hajj and Umra
Abd-Alla M, Ahmed Q, et al. Protective practices and pilgrimage/travel medicine. East Mediterr Health J
respiratory illness among US travelers to the 2009 Hajj. 2013 Apr;19(4):389–9 2.
J Travel Med. 2012 May-Jun;19(3):163–8. 10. World Health Organization. Health conditions
5. Memish Z, Zumla A, Alhakeem R, Assiri A, Turkestani A, for travellers to Saudi Arabia pilgrimage to Mecca
Al Harby KD, et al. Hajj: infectious disease surveillance (Hajj). Wkly Epidemiol Rec. 2005 Dec 9;80(49-5 0):
and control. Lancet. 2014 Jun 14;383(9934):2073–82. 431–2.
4 DESTINATION OVERVIEW
South Africa has been called “a world in one
of the old gold-╉mining towns in Mpumalanga,
many of which are in near-╉original condition;
country.” The epithet refers, in part, to the diver- spectacular drives and fascinating tours of
sity in the geography, which includes lush sub- the old wineries along the wine routes in the
tropical regions, old hardwood forests, sweeping Western Cape; or visits to the southernmost
Highveld vistas, and the deep desert of the point of Africa at Cape Agulhas or Cape Point,
Kalahari; the splendor of the animal species where the Indian and Atlantic Oceans meet in
found throughout the country and protected a roar of foam.
in expansive game reserves; the diverse origins South Africa is also a common destination
of the locals ( from Africa, Europe, India, and for humanitarian workers, missionaries, and stu-
Southeast Asia); the cultural, artistic, and culi- dents. A sizable number of South Africans live
nary variety; and access to the conveniences of outside the country and would be considered
a developed infrastructure amid the challenges VFR travelers (visiting friends and relatives) when
of Africa. returning to the country for a visit (see Chapter 8,
South Africa has experienced a surge in tour- Immigrants Returning Home to Visit Friends &
ism in the past 2 decades, with visitors from Relatives).
within the African continent as well as those While there is a wide range of living stan-
from Europe and North America. Business trav- dards in South Africa, most visitors experience
elers typically head to the commercial cen- standards comparable to those in developed
ters of Johannesburg, Cape Town, and Durban. countries. A smaller number of visitors may
Tourists may be attracted by the game reserves, go to less developed areas, either the lower-╉
the largest of which is Kruger National Park, income townships outside most towns and cit-
located along the Mozambique border in the ies or to rural areas. Hikers, adventure-╉seekers,
northeast (see Map 4-╉3). Kwa-╉Zulu Natal has and missionaries will experience a wider range
a number of game parks (Hluhluwe-╉Umfolozi of living standards. Similarly, the quality and
and Saint Lucia) set inland from Durban, and availability of health care are variable. Middle-╉
the Eastern Cape has parks (Addo Elephant and upper-╉income South Africans live in low-╉
Park and Shamwari) easily accessed from Port risk environments, have a standard of health
Elizabeth on the southern coast. Many smaller comparable to that of North Americans, and
luxury reserves have emerged to cater to the have access to world-╉class medical facilities.
high-╉end traveler. Visitors may be attracted to Poorer South Africans live in areas with few
itineraries that include a trip from Cape Town amenities, are exposed to a wide range of dis-
along the south coast through the small scenic eases, and have limited access to adequate
towns of Knysna and Plettenberg Bay; a tour health care.
world. The prevalence of HIV infection is approx- against tick-bite fever, but no studies exist to sup-
imately 19% among people aged 15–49 years, and port or refute this viewpoint. Taking doxycycline
the prevalence among sex workers is even higher. only as prophylaxis for tick-bite fever (as opposed
Other sexually transmitted diseases (STDs) are to taking it for malaria chemoprophylaxis) is not
also present at high rates in this population. recommended.
Travelers should be aware of STD risks and use
condoms if they have sex with someone whose Travelers’ Diarrhea
HIV or STD status is unknown. As with most destinations, the risk of travelers’
diarrhea depends on style of traveling and food
Vectorborne Diseases choices. A fluoroquinolone, such as ciprofloxacin,
Malaria transmission only occurs along the can be considered for self-treatment of moderate
border with Zimbabwe and Mozambique, spe- to severe diarrhea.
cifically in Vembe and Mopane district munici-
4 palities of Limpopo Province, Ehlanzeni district
municipality in Mpumalanga Province, and
Waterborne Diseases
Schistosomiasis, a common parasite through-
Umkhanyakude in Kwazulu- Natal Province. out Africa, may be present in any body of
This area includes Kruger National Park (see freshwater, such as lakes, streams, and ponds.
Map 3-38). Plasmodium falciparum is the pre- Travelers should avoid swimming in fresh, unch-
dominant species and is universally resistant lorinated water.
to chloroquine. Visitors to these areas should
be on a malaria chemoprophylaxis regimen and Animal Avoidance
should be advised to take mosquito precau- Although most travelers avoid wild animals in
tions. Malaria in the northeastern game reserves game reserves, rabies is common in dogs and
occurs throughout the year but is seasonally other mammals throughout the country. The
variable; the highest transmission occurs from KwaZulu-Natal Province has the highest inci-
September through May, peaking from February dence of rabies. Travelers have no way of telling if
to early May. The risk to visiting travelers is a given animal is rabid and should avoid all con-
low. Preventing mosquito bites is the first line tact with animals. Any bite or scratch from an
of defense against malaria. The South African animal should be washed with soap and water
Department of Health recommends malaria che- immediately and be evaluated as soon as pos-
moprophylaxis for all travelers visiting malaria sible by a clinician. Postexposure prophylaxis
risk areas from September through May and and medical care for rabies exposures can be
mosquito-avoidance measures for the rest of the obtained in South Africa. Rabies vaccine is avail-
year. CDC recommends chemoprophylaxis at all able throughout South Africa, and human rabies
times of the year (see Chapter 3, Yellow Fever & immune globulin is available in major urban
Malaria Information, by Country). medical centers.
Tick-bite fever caused by rickettsial species
is common in South Africa. The incidence rate Safety and Security
for visitors from Europe is estimated to be 4%– South Africa has experienced a rise in violent
5%. The disease is characterized by an eschar at crime, which includes armed robberies, car-
the bite site, regional adenopathy, and a macu- jackings, home invasions, and rape. Most of
lopapular to petechial rash. Hikers and camp- these incidents occur in lower income residen-
ers in rural areas who are exposed to ticks are tial areas and, as such, most visitors will not be
especially at risk. Measures should be taken to affected. However, awareness of personal safety
prevent tick bites (see Chapter 2, Protection and security should be stressed to all visitors.
against Mosquitoes, Ticks, & Other Arthropods). Travelers should rely on local guidance about
Travelers who are taking doxycycline for malaria the security precautions to take in specific
chemoprophylaxis may have some protection areas.
Although South Africa has a modern road sys- remote rural areas. Travelers should fasten seat
tem, drivers should be alert for dangerous driv- belts when riding in cars and wear a helmet when
ing practices, stray animals, and poor roads in riding bicycles or motorbikes.
BIBLIOGRAPHY
1. Blumberg LH, de Frey A, Frean J, Mendelson M. The Africa: from control to elimination. S Afr Med J. 2013
2010 FIFA World Cup: communicable disease risks and Oct;103(10 Pt2):779–╉83.
advice for visitors to South Africa. J Travel Med. 2010 5. Probst C, Parry CD, Rehm J. Socio-╉economic differences
May-╉Jun;17(3):150–╉2. in HIV/╉AIDS mortality in South Africa. Trop Med Int
2. Durrheim DN, Braack LE, Waner S, Gammon S. Risk of Health. 2016 Jul;21(7):846–╉55.
malaria in visitors to the Kruger National Park, South 6. South African National Travel Health Network.
Africa. J Travel Med. 1998 Dec;5(4):173–╉7. SaNTHNet [homepage on the Internet]. Dunvegan
3. Frean J, Blumberg L, Ogunbanjo GA. Tick bite fever in (South Africa): South African National Travel Health
South Africa. SA Fam Pract. 2008 Mar-╉Apr;50(2):33–╉5.
4. Maharaj R, Raman J, Morris N, Moonasar D, Durrheim
Network; c2013 [cited 2016 Sep. 23]; Available
from: http://╉www.santhnet.co.za/╉.
4
DN, Seocharan I, et al. Epidemiology of malaria in South
TANZANIA: KILIMANJARO
Shutterstock
Kevin C. Kain
The classic route up Kilimanjaro is the Marangu Machame route (the so-called “whiskey” route,
route (40 miles; 64 km), usually sold as a 5-day, since the days are generally longer with tougher
4-night trip. Marangu is frequently nicknamed climbs). Machame and other routes involve
the “Coca-Cola” route, since accommodation and camping but are usually sold as 6-to 9-day pack-
food are provided in bunkhouses, and the trail ages, providing more opportunity to acclimatize
is wide and relatively easy compared with other and a greater chance to successfully summit.
routes. There are at least 9 alternative routes Kilimanjaro can be climbed throughout the year
(Map 4- 4), including the stunningly beautiful (March–April are often the wettest months), but
the weather is unpredictable, and the climber it. People with certain underlying medical condi-
must be prepared for extreme weather and rain tions, including pregnancy, significant underlying
at any time of the year. A 2011 review of UK com- lung or cardiac disease, and ocular and neurologic
panies arranging high-altitude trekking reported conditions, may be more susceptible to altitude-
that only 16 of 93 (17%) companies offering associated problems or may be taking medica-
Kilimanjaro treks complied with Wilderness tions that may interact with altitude medications,
Medical Society guidelines on ascending to alti- and should consult a travel health provider with
tude, compared with 92% of treks to Everest base knowledge of altitude illness before travel.
camp. Moreover, fewer than half of these compa- Enjoying the experience and successfully
nies carry medications to prevent or treat alti- reaching the summit can be enhanced by allow-
tude illness, so trekkers should be prepared to ing more time to acclimatize:
carry and understand how and when to use these
medications.
• If Ngorongoro crater is part of the planned
Climbing Kilimanjaro is a dream for many who
visit Africa. However, a large number of travelers
combined safari/Kilimanjaro hike itiner-
ary, try to spend the last few nights of the 4
safari there, because its elevation (7,500 ft;
are ill-prepared, ascend too quickly, and conse-
2,286 m) will aid acclimatization for the
quently fail to summit. With due preparation and
Kilimanjaro trek.
more reasonable ascent rates, climbing “Kili” is
an aspiration that can be successfully and safely • It is strongly encouraged to add at least an
accomplished by many. extra day or two to the ascent of Kilimanjaro,
regardless of the route, but especially on
HEALTH ISSUES routes normally promoted as 4-to 6-day
The main medical issues for those attempting trips.
to climb Kilimanjaro include the prevention
and treatment of altitude illness and the poten-
• If possible, before attempting Kilimanjaro
travelers may acclimatize by hiking nearby
tial for drug interactions between medications
Mount Meru (14,978 ft; 4,565 m) or Mount
used for altitude illness and antimalarial or anti-
Kenya (to Point Lenana, 16,355 ft; 4,895
diarrheal agents commonly used by travelers to
m). A number of combined climbing trips
Tanzania.
for Mount Kenya and Kilimanjaro are now
offered commercially.
Altitude and Acute Mountain
Sickness (AMS) For those with a past history of susceptibility
Altitude illness is a problem on Kilimanjaro to AMS and for those in whom adequate accli-
and a major contributor to the reason that only matization is not possible (most “Kili” clients),
50% of those attempting the standard 4-to 5- the use of medications such as acetazolamide
day Marangu route reach the crater rim, known to prevent altitude illness is recommended.
as Gilman’s Point (18,652 ft; 5,685 m), and as Acetazolamide accelerates acclimatization,
few as 10% reach the summit, known as Uhuru is effective in preventing (beginning the day
(Freedom) Peak (19,341 ft; 5,895 m). Prevalence before ascent) and treating AMS, and is safe in
rates of AMS were 75%–77% in recent studies of children.
4-and 5-day ascents on the Marangu route. Those For those who are intolerant of or allergic to
using acetazolamide were significantly less likely acetazolamide, dexamethasone is an alternative
to develop AMS on the 5-day ascents, but 40%– for prevention of AMS, but there are cautions
50% of those taking acetazolamide may still involved in using dexamethasone for ascent.
report AMS symptoms. Consideration should be given to carrying a
Every hiker on Kilimanjaro should receive treatment course of dexamethasone for high-
pretravel advice on AMS, be able to recognize altitude cerebral edema (HACE). Travelers with
symptoms, and know how to prevent and treat symptoms of altitude illness must not continue
to ascend and need to descend if symptoms concurrent use of CYP3A4 inhibitors such as
are worsening at the same altitude. A flexible doxycycline could lead to elevated plasma lev-
itinerary and having an extra guide who can els of nifedipine and potentially lower blood
accompany any member of the group down the pressure. Therefore, it would not be advised to
mountain if he or she becomes ill are consider- take nifedipine for altitude illness prophylaxis
ations. See Chapter 2, Altitude Illness, for more concurrently with doxycycline.
information about prevention and treatment of
altitude illness. Treatment of Travelers’ Diarrhea
There are no reported drug interactions between
Malaria acetazolamide and the fluoroquinolones (cipro-
Kilimanjaro is unique in that its tropical malaria- floxacin, levofloxacin) or macrolides (azithromy-
endemic location means that many trekkers will cin) commonly used to treat travelers’ diarrhea.
be on antimalarial drugs and may need to con- There is a potential increased risk of tendon rup-
4 tinue them after their climb, particularly if they
are also visiting game parks and staying over-
ture when dexamethasone is used with fluoro-
quinolones. Avoid concurrent use of macrolides
night at altitudes <5,906 ft (1,800 m). Malaria and nifedipine.
prophylaxis is recommended for Tanzania (even
if only for a short trip). If a traveler flew directly Remote Travel
into Kilimanjaro International Airport (2,932 ft; Kilimanjaro treks are physically demanding and
894 m) and went the same day to an altitude require a good level of fitness and preparation for
above 1,800 m, there would be no risk of malaria. the elements. Kilimanjaro weather is character-
However, most people will be on safari or trav- ized by extremes; travelers should be prepared for
eling before or after their Kilimanjaro trip and tropical heat, heavy rains, and bitter cold. Gear,
therefore will be on prophylaxis. especially sleeping bags, should be kept in water-
Kilimanjaro is also a unique destination proof bags. Travelers should have adequate health
in that high altitude will affect everyone, and insurance, including medical evacuation insur-
possible interactions should be considered ance, and make sure their medical care and med-
between drugs commonly used for malaria pro- ical evacuation policies will cover any potential
phylaxis or treatment of AMS, high- altitude costs for a rescue or evacuation from the top of
pulmonary edema, or HACE, such as acet- the mountain.
azolamide, dexamethasone, and nifedipine. Travelers should carry a first aid kit that
Fortunately, there are few reported clinically includes bandages, tape, blister kit, antibacterial
significant drug interactions between com- and antifungal cream, antibiotics for travelers’
mon malaria prophylaxis agents (atovaquone- diarrhea, antimalarials, antiemetics, oral rehydra-
proguanil, doxycycline, or mefloquine) and tion salts, antihistamines, analgesics, throat loz-
acetazolamide or dexamethasone. Nifedipine enges, and medications for altitude illness (see
is metabolized by the CYP3A4 enzyme, and Chapter 2, Travel Health Kits).
BIBLIOGRAPHY
1. Bartsch P, Gibbs JS. Effect of altitude on the heart Kilimanjaro (5895 m). Wilderness Environ Med. 2009
and the lungs. Circulation. 2007 Nov 6;116(19): Winter;20(4):311–7.
2191–202. 4. Jackson SJ, Varley J, Sellers C, Josephs K, Codrington L,
2. Baumgartner RW, Siegel AM, Hackett PH. Going high Duke G, et al. Incidence and predictors of acute moun-
with preexisting neurological conditions. High Alt Med tain sickness among trekkers on Mount Kilimanjaro.
Biol. 2007 Summer;8(2):108–16. High Alt Med Biol. 2010 Fall;11(3):217–22.
3. Davies AJ, Kalson NS, Stokes S, Earl MD, Whitehead 5. Low EV, Avery AJ, Gupta V, Schedlbauer A, Grocott
AG, Frost H, et al. Determinants of summiting MP. Identifying the lowest effective dose of acet-
success and acute mountain sickness on Mt azolamide for the prophylaxis of acute mountain
sickness: systematic review and meta-analysis. BMJ. practical recommendations. Prog Cardiovasc Dis. 2010
2012 Oct;345:e6779. May-Jun;52(6):512–24.
6. Luks AM, Swenson ER. Travel to high altitude 9. Ritchie ND, Baggott AV, Andrew Todd WT.
with pre-existing lung disease. Eur Respir J. 2007 Acetazolamide for the prevention of acute mountain
Apr;29(4):770–92. sickness—a systematic review and meta-analysis.
7. Luks AM, Swenson ER. Medication and dosage J Travel Med. 2012 Sep-Oct;19(5):298–307.
considerations in the prophylaxis and treatment of 10. Shah NM, Windsor JS, Meijer H, Hillebrandt D. Are UK
high-altitude illness. Chest. 2008 Mar;133(3):744–55. commercial expeditions complying with wilderness
8. Rimoldi SF, Sartori C, Seiler C, Delacretaz E, Mattle HP, medical society guidelines on ascent rates to altitude?
Scherrer U, et al. High-altitude exposure in patients J Travel Med. 2011 May-Jun;18(3):214–6.
with cardiovascular disease: risk assessment and
T Tourist destination
B 250 500 1.000 1,500mi
MAP 4-5 . Brazil destination map
445
4
4
6
contact. Typhoid vaccine is recommended for Arthropods). Because of the risks associated with
most travelers, especially those more likely to Zika virus infection during pregnancy, travelers
be exposed to potentially contaminated food or should consult the CDC Travelers’ Health web-
water, such as those staying with friends or rela- site (www.cdc.gov/travel) for the most current
tives; visiting smaller cities, villages, or rural areas; recommendations for Zika.
or prone to “adventurous eating.” Yellow fever
vaccine is recommended for travelers to certain Malaria
areas, and it is therefore critical that clinicians Almost all malaria in Brazil occurs in the Amazon
ask patients about their itineraries and potential Basin, although the mosquito vector is present in
travel within the country. much of Brazil. Plasmodium vivax is the main spe-
cies of malaria parasite, although approximately 15%
Travelers’ Diarrhea and of cases are caused by P. falciparum. Prophylactic
Foodborne Infections treatment with antimalarial medication is recom-
4 Travelers should take food and water precautions
throughout Brazil (see Chapter 2, Food & Water
mended for travelers to malaria- endemic areas
in Brazil (see Chapter 3, Yellow Fever & Malaria
Precautions). Travelers’ diarrhea is the most com- Information, by Country, and Map 3-21).
mon travel- related ailment, and travelers who
consume foods or beverages from street vendors, Yellow Fever
raw fruits or vegetables, or unpasteurized dairy Yellow fever virus circulates in monkeys and
products are at increased risk for foodborne infec- is transmitted by mosquitoes throughout the
tions. Oral rehydration salts are available from Amazon Basin and in forested regions along all
public health clinics and in almost all pharma- major river basins in Brazil, including Iguaçu Falls
cies in Brazil. Clinicians may wish to prescribe an and as far south as Rio Grande do Sul. Vaccination
antibiotic for self-treatment of moderate to severe against yellow fever is recommended for all
diarrhea (see Chapter 2, Travelers’ Diarrhea). travelers aged >9 months going to areas at risk
of yellow fever. (See Chapter 3, Yellow Fever &
Vectorborne Diseases Malaria Information, by Country, and Map 3-20.)
CHIKUNGUNYA, DENGUE, AND ZIKA
Vectorborne diseases, including mosquitoborne Rickettsial Disease
diseases, are present in many areas in Brazil; these Several tickborne rickettsial diseases have been
infections are the leading causes of febrile illness identified in Brazil, including febre maculosa
among travelers returning from South America. and Brazilian spotted fever, caused by the eti-
Chikungunya, dengue, and Zika are all transmit- ologic agent of Rocky Mountain spotted fever,
ted by Aedes mosquitoes, and risk is considered Rickettsia rickettsii. Travelers should take precau-
high in many Brazilian states because of high tions to avoid flea and tick bites both indoors
indices of Aedes infestation. Some of these vec- and outdoors. For more detailed information,
torborne diseases are new to Brazil: chikungunya see Chapter 2, Protection against Mosquitoes,
was first detected in Brazil in 2014, and Zika was Ticks, & Other Arthropods.
first detected in Brazil in 2015.
From 2000 through 2010, cases of dengue Other Infections
increased throughout Brazil, and epidemics were SEXUALLY TRANSMITTED DISEASES (STDS)
reported from large Brazilian cities, including Rio In Brazil, condoms are distributed free of charge
de Janeiro and Salvador. In 2015, Brazil recorded by the government and are available in health
1.6 million probable cases of dengue and approx- clinics, tourist service centers, and other distri-
imately 21,000 cases of chikungunya. Travelers bution points in many cities. Male condoms are
to Brazil should take measures to protect them- available throughout Brazil in pharmacies, con-
selves from mosquito bites (see Chapter 2, venience stores, and large supermarkets; female
Protection against Mosquitoes, Ticks, & Other condoms are also available in some locations.
Travelers, particularly those at high risk for Schistosomiasis is not acquired by contact with
acquiring HIV infection (such as men who have saltwater (oceans or seas).
sex with men), may consider discussing preexpo- Both cutaneous and visceral leishmania-
sure prophylaxis with their health care provider sis occur in Brazil and are most common in the
(www.cdc.gov/hiv/prep). Amazon and northeast regions. The risk is high-
est from dusk to dawn because sand flies typi-
RESPIRATORY DISEASES cally feed (bite) at night and during twilight hours.
Peak influenza circulation occurs from April Ecotourists and adventure travelers might have
through September in most of Brazil but may an increased risk, but even short-term travelers in
occur throughout the year in tropical areas. endemic areas have developed leishmaniasis.
Seasonal influenza vaccination is recommended
at least 2 weeks before travel. Pneumococcal RABIES
vaccination is recommended for the elderly and Preexposure rabies vaccination is recommended
younger adults with chronic medical conditions
to prevent pneumonia complications.
for prolonged stays, particularly for children and
those planning rural travel. For shorter stays,
4
A number of fungal diseases endemic to parts rabies vaccination is recommended for adven-
of Brazil, including coccidioidomycosis, histo- ture travelers, those who may be occupationally
plasmosis, paracoccidioidomycosis, and cryp- exposed to animals, and those staying in locations
tococcosis, are caused by inhalation of fungal >24 hours from access to rabies immune globulin.
spores typically present in soil, resulting in respi-
ratory illness and occasionally more severe dis- TUBERCULOSIS (TB)
ease such as meningitis or bone infection. Tuberculosis is prevalent in Brazil, but short-term
Travelers should exercise caution before disturb- travelers are not considered at high risk for infec-
ing soil, particularly if it is contaminated by bird tion unless they will be spending time in specific
or bat feces, and should beware of bat guano crowded environments. Travelers who antici-
in caves. pate possible prolonged exposure to people with
TB because they will routinely come into contact
LEPTOSPIROSIS with clinic, hospital, prison, or homeless shelter
Outbreaks of leptospirosis have occurred in urban populations should have a tuberculin skin test
areas in Brazil following heavy flooding. Travelers or TB blood test before leaving the United States.
participating in recreational water activities are at If the test is negative, the traveler should have a
increased risk, particularly after heavy rainfall or repeat test 8–10 weeks after returning from Brazil.
flooding.
Other Health and Safety Risks
PARASITIC INFECTIONS As in many foreign countries, motor vehicle acci-
Chagas’ disease has been eliminated in most dents are among the leading causes of injury and
Brazilian states through insecticide spraying. death of US citizens in Brazil. Road conditions in
Although risk to travelers is extremely low, out- Brazil differ significantly from those in the United
breaks associated with contaminated food or States, and driving at night can be dangerous. The
drink have been reported, including locally pre- national toll-free number for emergency roadside
pared juice containing açái, an Amazonian fruit assistance is 193 (in Portuguese only). It is ille-
eaten throughout Brazil. Travelers and ecotour- gal to drive after drinking alcohol, even in small
ists staying in poor-quality housing may be at quantities. Seat belt use is mandatory in vehicles,
higher risk. and children aged ≤10 years must be seated in the
Schistosomiasis is found in freshwater lakes back seat. Brazilian federal law requires car seats
and rivers in many states of Brazil, especially in for all children under the age of 7.5 years. Travelers
the northeast. Swimming, bathing, and wading in with small children (weighing <40 lb) should travel
fresh, unchlorinated water can result in infection. with car or booster seats, since safety seats may
BRAZIL 447
8
4
BIBLIOGRAPHY
1. Gaines J, Sotir MJ, Cunningham TJ, Harvey KA, 4. Nobrega AA, Garcia MH, Tatto E, Obara MT, Costa E,
Lee CV, Stoney RJ, et al. Health and safety issues Sobel J, et al. Oral transmission of Chagas disease by
for travelers attending the World Cup and Summer consumption of acai palm fruit, Brazil. Emerg Infect Dis.
Olympic and Paralympic Games in Brazil, 2014 2009 Apr;15(4):653–5.
to 2016. JAMA Intern Med. 2014 Aug;174(8): 5. Oliveira-Ferreira J, Lacerda MV, Brasil P, Ladislau JL,
1383–9 0. Tauil PL, Daniel-Ribeiro CT. Malaria in Brazil: an over-
2. Jentes ES, Poumerol G, Gershman MD, Hill DR, view. Malar J. 2010 Apr 30;9:115.
Lemarchand J, Lewis RF, et al. The revised global 6. Teixeira MG, Siqueira JB Jr, Ferreira GL, Bricks L, Joint
yellow fever risk map and recommendations for G. Epidemiological trends of dengue disease in Brazil
vaccination, 2010: consensus of the Informal WHO (2000–2010): a systematic literature search and analysis.
Working Group on Geographic Risk for Yellow Fever. PLoS Negl Trop Dis. 2013 Dec 19;7(12):e2520.
Lancet Infect Dis. 2011 Aug;11(8):622–32.
7. Wilson ME, Chen LH, Han PV, Keystone JS, Cramer
3. Malaria Atlas Project. The spatial limits of JP, Segurado A, et al. Illness in travelers returned from
Plasmodium vivax malaria transmission map in Brazil: the GeoSentinel experience and implications
2010 in Brazil. [cited 2016 Sep. 23]; Available from: for the 2014 FIFA World Cup and the 2016 Summer
http://www.map.ox.ac.uk/explore/countries/BRA/. Olympics. Clin Infect Dis 2014 May;58(10):1347–56.
CUBA
Linda R. Taggart,
Andrea K. Boggild
Jonatan Brandt/Personal Collection
DESTINATION OVERVIEW Vieja (Old Havana) or walk along the sea wall, 4
The Republic of Cuba is a Caribbean island the Malecon. Another popular destination
located between the Caribbean Sea and the is Trinidad, a colonial city known for its cob-
North Atlantic Ocean, approximately 90 miles blestone streets (see Map 4-╉ 6). Throughout
(145 km) south of Key West, Florida. It is the the country, tourists can enjoy the sight of
largest country in the Caribbean and has a pop- vintage cars and sample Cuban cigars, rum,
ulation of 11 million people. The official lan- and mojitos.
guage is Spanish. The climate is tropical, with
a dry season from November to April and a
rainy season from May to October. Originally
HEALTH ISSUES
inhabited by a native Amerindian population, Vaccine-╉Preventable Diseases
it was colonized by the Spanish in the 15th Travelers should confirm that routine vac-
century. In 1898, Cuba gained independence cinations are up-╉ to-╉
date, including sea-
from Spain, with the assistance of the United sonal influenza vaccine. Hepatitis A vaccine
States, and then gained independence from the is recommended for non-╉ immune travelers.
United States in 1902. In 1959, a revolutionary Vaccination against hepatitis B should also be
army under Fidel Castro overthrew the govern- considered for most travelers, especially those
ment and established a communist state. A US who may be exposed to blood or body fluids,
embargo has been in place since 1961; however, including those intending to do medical work
since December 2014, efforts have been made by or those who may seek medical treatment,
the United States to reestablish diplomatic rela- obtain tattoos or piercings, use injection drugs,
tions with Cuba. Although tourist travel to Cuba or have sex. Typhoid vaccination is recom-
is still prohibited under US law, 12 categories mended for most travelers, especially visitors
of travel are now authorized, including family of friends and relatives, those traveling to rural
visits, professional research and meetings, and areas, and those likely to partake in “adventur-
humanitarian projects. ous eating.” Rabies vaccine is recommended
Although out of reach of most US citizens for travelers who may be in contact with dogs,
for years, Cuba has long been a popular travel bats, or other mammals; travelers who expect
destination for Canadians and Europeans. to have occupational exposure to animals; and
The largest and most popular resort area is long-╉term travelers. Although extremely rare
in Varadero, a peninsula with a vast, 13-╉mile in travelers, cholera is a possible risk in parts
stretch of sandy beach and more than 50 of Cuba. Cholera vaccine is recommended for
hotels. Those seeking to experience Cuban adult travelers visiting areas with cholera activ-
culture often travel to the nearby capital city ity within the last year that are prone to recur-
of Havana to explore the streets of La Habana rence of cholera epidemics.
CUBA 449
0
5
4
SUN, SAND, AND WATER HAZARDS turn signals. Tourist company buses and radio-
Care should be taken to avoid excess sun expo- dispatched taxis are generally safe and reliable.
sure. Visitors should apply sunscreen of SPF ≥15 Travelers should fasten seat belts when riding
that protects against both UVA and UVB, wear in cars and wear a helmet when riding bicycles
protective clothing, and seek shade when possi- or motorbikes. Unlicensed taxis and yellow 3-
ble. Travelers to the Caribbean are at risk of cuta- wheeled “coco taxis” should be avoided. Thefts
neous larva migrans from lying or walking on soil, may occur, especially in crowded locations such
including sandy beaches. Risk can be minimized as beaches, markets, Old Town Havana, and the
by wearing shoes and avoiding lying directly on Prado neighborhood. These are usually nonvi-
sand. Marine envenomations by jellyfish, micro- olent, but there is some concern that violent
scopic cnidarians causing sea bather’s eruption, crime is increasing, and travelers should not
sea urchins, and stingrays can occur in the warm resist if confronted.
shallow waters surrounding many resort areas.
BIBLIOGRAPHY
1. Boggild AK, Geduld J, Libman M, Ward BJ, McCarthy AE, social–ecological resilience. EcoHealth. 2008
Doyle PW, et al. Travel-acquired infections and illnesses Sep;5(3):346–59.
in Canadians: surveillance report from CanTravNet 4. The World Factbook. Central Intelligence Agency;
surveillance data, 2009–2011. Open Med. 2014 Feb 2016 [updated Feb. 2016; cited 2016 Feb. 13]; Available
11;8(1):e20–32. from: https://www.cia.gov/library/publications/the-
2. Fillion K, Mileno MD. Cholera in travelers: shifting tides world-factbook/.
in epidemiology, management, and prevention. Curr 5. U.S. Department of State. US passport and
Infect Dis Rep. 2015 Jan;17(1):455. international travel: Cuba. 2015 [updated Oct.
3. Morrison K, Aguiar Prieto P, Castro Domínguez A, 2015; cited 2016 Jan. 31]; Available from: https://
Waltner-Toews D, FitzGibbon J. Ciguatera fish travel.state.gov/content/passports/en/country/
poisoning in La Habana, Cuba: a study of local cuba.html.
CUBA 451
4
5
2
rare in travelers, cholera is a possible risk in use condoms with any partner whose HIV or
parts of the Dominican Republic. Cholera vac- sexually transmitted disease status is unknown.
cine is recommended for adult travelers vis-
iting an area with cholera activity within the Vectorborne Diseases
last year that is prone to recurrence of cholera Zika, chikungunya, dengue, and malaria are
epidemics. potential concerns for travelers to the Dominican
Republic. All travelers should take precautions
HIV and Other Sexually to prevent mosquito bites by wearing long-
Transmitted Diseases sleeved shirts and long pants and using insect
Commercial sex work occurs throughout the repellent. See Chapter 2, Protection against
Dominican Republic, and some locations, such as Mosquitoes, Ticks, & Other Arthropods for more
Sosua and Puerto Plata, are known as sex tour- information.
ism destinations. HIV prevalence among female The malaria in the Dominican Republic is not
commercial sex workers is as high as 6% in some drug-resistant. CDC recommends that travelers
areas; syphilis (12%), hepatitis B virus (2.4%), to the Dominican Republic take malaria chemo-
and hepatitis C virus (0.9%) are also concerns. prophylaxis unless they are only visiting the urban
Among men who have sex with men, HIV preva- areas of Santiago or Santo Domingo. Dengue is
lence is as high as 6.9% and active syphilis as high widespread throughout the Dominican Republic;
as 13.9%. Travelers should avoid sexual inter- 16,871 cases were reported in 2015, of which 103
course with commercial sex workers and always were fatal (case-fatality ratio, 0.61). Although cases
of dengue are reported year-round, transmission or helmets. The Dominican Republic has among
frequently increases during the rainy season from the highest number of traffic deaths per cap-
May through November. The mosquito vector for ita in the world (41.7 per 100,000 population).
dengue is found in urban as well as rural areas. Many fatal or serious traffic crashes involve
Chikungunya was introduced to the Dominican motorcycles and pedestrians. Motorcycle taxis,
Republic in 2014. which are used throughout the country, includ-
The first cases of local vectorborne Zika virus ing in tourist areas, frequently carry 2 or more
transmission were reported in the Dominican passengers without helmets. Visitors should
Republic in 2016, which emphasizes the need avoid motorcycle taxis, use only licensed taxis,
for mosquito precautions. Because of the risks and always wear a seatbelt.
to pregnancy, travelers should consult the Foreign tourists may become victims of crime
CDC Travelers’ Health website (www.cdc.gov/ in the Dominican Republic. The risks are similar
travel) for the most current recommendations to most major US cities. Although much crime
4 for Zika. affecting tourists involves robbery or pickpock-
eting, more serious assaults occasionally occur,
Food and Water Safety and criminals may react violently if resisted.
Travelers should only drink water that is puri- Visitors to the Dominican Republic should
fied or bottled. Ice served in well-established follow normal precautions such as going out in
tourist locations is usually made from puri- groups, especially at night; using only licensed
fied water and safe to consume. However, ice taxi drivers; drinking alcohol in moderation; and
may not be safe in remote or nontourist areas. being cautious of strangers. Criminal activity is
Food hygiene at large, all-inclusive, and popu- often higher in the Christmas and New Year sea-
lar tourist locations has improved over the last son, and additional caution is advised during
few years. However, travelers’ diarrhea contin- those months.
ues to be the most common problem for visitors
to the Dominican Republic. Food purchased on MEDICAL TOURISM
the street or sold on beaches by informal sell- The market for medical tourism, including plas-
ers presents a higher risk of illness. Tourists are tic surgery and dental care, is growing in the
advised not to eat raw or undercooked seafood Dominican Republic and attracts thousands of
in the Dominican Republic. patients each year to access medical services
that cost a fraction of what they do in the United
Sun and Heat Safety States. Several companies and clinics offer
Visitors to the Dominican Republic often under- package deals that include postsurgical recov-
estimate the strength of the sun and the dehy- ery at a tourist resort. Most health care facilities
drating effect of the humid environment. Visitors catering to medical tourists in the Dominican
should take precautions to avoid sunburn by Republic have not met the standards required
wearing hats and suitable clothing, along with by international accreditation organizations.
proper application of a broad- spectrum sun- Outbreaks of health care–associated infections,
screen with an SPF ≥15 that protects against both medical malpractice, and even deaths have
UVA and UVB. Travelers should also drink plenty been reported among foreign visitors traveling
of fluids throughout the day. to the Dominican Republic for medical tourism.
People considering traveling to the Dominican
Safety and Security Republic for medical procedures, including
Driving in the Dominican Republic is hazard- plastic surgery or dental care, should consult
ous. Traffic laws are rarely enforced, and drivers with a health care provider before travel and
commonly drive while intoxicated, text while consider whether foreign health care providers
driving, exceed speed limits, do not respect red meet quality standards of care (see Chapter 2,
lights or stop signs, and drive without seatbelts Medical Tourism).
BIBLIOGRAPHY
1. Banco Central de la República Dominicana [Internet]. poblaciones claves. Gais, trans y hombres que
Estadísticas económicas: sector turismo. Santo tienen sexo con hombres (GTH) trabajadoras sex-
Domingo (Dominican Republic): Banco Central de uales (TRSX) usuarios de drogas (UD), 2012. Santo
la República Dominicana.; c2012 [cited 2016 Sep. 23]; Domingo (Dominican Republic): CONAVIHSIDA;
Available from: http://╉www.bancentral.gov.do/╉ 2014 [cited 2016 Sep. 23]; Available from: http://╉
estadisticas_╉economicas/╉turismo/. countryoffice.unfpa.org/╉dominicanrepublic/╉drive/╉
2. CDC. Dengue fever among US travelers returning CONAVIHSIDASegundaEncuestaVigiliancia.pdf.
from the Dominican Republic –╉Minnesota and Spanish.
Iowa, 2008. MMWR Morb Mortal Wkly Rep. 2010 Jun 5. Dirección General de Epidemiología [Internet]. Sistema
4;59(21):654–╉6. nacional de vigilancia epidemiológica, boletín sema-
3. CDC. Notes from the field: rapidly growing nontu- nal 2013. Santo Domingo (Dominican Republic)2014
berculous Mycobacterium wound infections among [updated Sep. 2014 ; cited 2016 Sep. 23]; Available
medical tourists undergoing cosmetic surgeries in the from: http://╉digepisalud.gob.do/╉boletines/╉boletines-╉
4
Dominican Republic—╉multiple states, March 2013–╉ semanales/╉cat_╉view/╉34-╉boletines-╉semanales/╉108-╉2013.
February 2014. MMWR Morb Mortal Wkly Rep. 2014 html. Spanish.
Mar 7;63(9):201–╉2. 6. World Health Organization. Global status report on road
4. CONAVIHSIDA (Consejo Nacional para el VIH safety 2013: supporting a decade of action. Geneva: 2013
y sida). Segunda encuesta de vigilancia de com- Sep 22. Available from: http://╉www.who.int/╉violence_╉
portamiento con vinculación serológica en injury_╉prevention/╉road_╉safety_╉status/╉2013/╉en/.╉
HAITI
J. Nadine Gracia, Clive M. Brown, Dana M. Sampson,
Lacreisha Ejike-╉King
Gary W. Brunette/Personal Collection
HAITI 455
4
5
6
wood, and lumber, Haiti has experienced consid- waterfalls, caves, and the most mountains of any
erable environmental degradation due to deforesta- nation in the Caribbean. The people of Haiti are
tion, poor agricultural practices, and soil erosion. It known for their resilience, strength, and warm
is reported to be the poorest country in the Western and kind spirit, leaving travelers to often say after
Hemisphere, having suffered from political and eco- a visit to Haiti that they have fallen in love with
nomic instability for most of its history. the country and its people.
French and Creole are the official languages
of the country. French is the principal written HEALTH ISSUES
and administratively authorized language. It is Haiti has suffered significant environmental degra-
the medium of instruction in most schools. Most dation, contributing to poor sanitation and water
(approximately 90%) of Haiti’s 10.3 million people, quality. As a result, various public health risks exist
however, use Creole as their primary language. for Haitians and for people traveling to Haiti.
Because of the mix of indigenous, African, and
European influences, Haiti possesses a “mosaic cul- Vaccine-Preventable Diseases
ture” that is reflected in local art, music, and cuisine. All people traveling to Haiti should be up-to-
Once called the Pearl of the Antilles because date on routine vaccinations, including seasonal
of its natural beauty, Haiti is home to a vibrant influenza and booster doses to protect against
and diverse landscape that includes beaches, tetanus and diphtheria. Diphtheria is endemic
in Haiti, and the number of reported cases has Local transmission of Zika virus was con-
increased in recent years. Additionally, hep- firmed in January 2016. Because of the seri-
atitis A vaccine and typhoid are strongly rec- ous consequences of Zika infection during
ommended, especially if travelers are staying pregnancy, travelers should consult the CDC
with friends or relatives or visiting smaller cit- Travelers’ Health website (www.cdc.gov/travel)
ies or rural areas. Providers should also con- to obtain the most current recommendations
sider administering hepatitis B vaccine. Rabies for travel to Haiti.
affects Haiti more than any other nation in the
Americas. Prevention efforts have decreased the Travelers’ Diarrhea and Food-or
number of human cases of rabies transmitted by Water-Related Diseases
dogs, but deaths continue to be reported in Haiti. Travelers to Haiti will want to experience the
Rabies vaccination is recommended for travelers local, flavorful cuisine, such as rice with red
anticipating contact with animals. Yellow fever beans, plantains, griot (seasoned, fried pork),
vaccination is required for people traveling from
countries where the disease is endemic. Although
and a variety of fish and shellfish, including
conch. While enjoying the incredible Haitian
4
extremely rare in travelers, cholera is a possible cuisine, travelers should select food and bev-
risk in parts of Haiti. Cholera vaccine is recom- erages carefully (see Chapter 2, Food & Water
mended for adult travelers visiting areas with Precautions). Travelers’ diarrhea is a significant
cholera activity within the last year that are prone risk in Haiti, and travelers are at additional risk
to recurrence of cholera epidemics. of contracting hepatitis A and typhoid fever.
HAITI 457
8
54
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may appear on roads (such as carts, animals, and
NATURAL DISASTERS
vendors), and roads may be unpaved or have large
Natural disasters common to Haiti include tropical
potholes. The main roads have been cleared of
storms, flooding, hurricanes, and earthquakes. Haiti
rubble from the 2010 earthquake, although some
experiences 2 rainy seasons, from April through June
rubble remains in certain areas. Traffic is usually
and from October through November. Hurricane
chaotic and congested in urban areas. Tap taps
season lasts from June through November. In 2008,
(vibrantly painted buses or pick-up trucks that
Haiti experienced a series of 4 hurricanes and tropi-
serve as share taxis in Haiti but are open-air vehi-
cal storms within 2 months.
cles that are often overloaded with passengers and
In January 2010, Haiti experienced a 7.0 magni-
not mechanically sound) are a common form of
tude earthquake. More than 220,000 people died,
public transportation for Haitians but are not rec-
and 1.5 million people were displaced from their
ommended for visitors to the country because of
homes. Multiple powerful aftershocks added to
safety concerns (such as crashes, robbery, or kid-
the widespread devastation and destruction. As a
napping). Travelers can exercise safety while trav-
result, the health, emergency response, and safety
eling in Haiti by keeping alert when traveling on
infrastructure in the nation was significantly
foot, choosing safe vehicles, and observing safety
weakened; the country’s infrastructure remains
practices when operating vehicles. Travelers
largely underdeveloped after the earthquake.
should fasten seat belts when riding in cars and
wear a helmet when riding bicycles or motorbikes.
DISCLOSURE
CRIME Lacreisha Ejike-King is an employee of the US
Food and Drug Administration (FDA); views
The crime rate in Haiti is high, particularly in the
expressed in this chapter are those of the authors
capital of Port-
au-
Prince, which presents per-
and do not necessarily reflect the official policy or
sistent safety concerns for travelers. Although
position of the FDA.
BIBLIOGRAPHY
1. Brown C, Ripp J, Kazura J. Perspectives on Haiti two 2010. MMWR Morb Mortal Wkly Rep. 2011 Jul
years after the earthquake. Am J Trop Med Hyg. 2012 15;60(27):914–7.
Jan;86(1):5–6. 4. Dowell SF, Tappero JW, Frieden TR. Public health in
2. CDC. Malaria in post-earthquake Haiti: CDC’s Haiti—challenges and progress. N Engl J Med. 2011 Jan
recommendations for prevention and treatment. 27;364(4):300–1.
Atlanta: CDC; 2010 [cited 2016 Sep. 23]; Available 5. Institute for Health Metrics and Evaluation. Country
from: http://www.cdc.gov/malaria/resources/pdf/new_ Profile: Haiti. IHME; [cited 2016 Mar. 10]; Available
info/2010/malaria-1-pager_dec3v1_5 08.pdf. from: http://www.healthdata.org/haiti.
3. CDC. Dengue virus infections among travelers return- 6. Pan American Health Organization/World Health
ing from Haiti—Georgia and Nebraska, October Organization (PAHO/WHO), Epidemiological Week/
EW 52. Number of reported cases of chikungunya fever 8. United Nations Development Programme (UNDP)
in the Americas, by country or territory 2013–╉2014. Human Development Report Office. Human develop-
Washington, DC: 2014 Dec 29. Available from: http://╉ ment report 2013. The rise of the South: human progress
www.paho.org/╉h q/╉index.php?option=com_╉topics& in a diverse world. New York: 2013 Sep 22. Available
view=readall&cid=5927&Itemid=40931&lang=en. from: http://╉hdr.undp.org/╉en/╉2013-╉report.
7. Pan American Health Organization/╉World Health 9. World Food Programme [Internet]. Haiti overview. Port
Organization (PAHO/╉WHO), Health Information au Prince (Haiti): World Food Programme; c2014 [cited
and Analysis Project (HSD/╉HA). Health situation in 2016 Sep. 23]; Available from: http://╉www.wfp.org/╉
the Americas: basic indicators, 2014. Washington, countries/╉haiti/╉overview.
DC: 2014. Available from: http://╉www.paho.org/╉ 10. World Health Organization. Countries: Haiti
hq/╉index.php?option=com_╉docman&task=doc_╉ Country Profile. WHO; [cited 2016 Sep. 23]; Available
view&gid=27299&Itemid=721. from: http://╉www.who.int/╉countries/╉hti/╉en/╉.
MEXICO
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portion of tourism to Mexico. Also common should be considered for travelers who are likely
are day trips to northern border cities and to come into contact with these animals or those
longer cultural trips to historical and World who will be traveling to areas with limited access
Heritage sites. Popular pre-Columbian anthro- to medical care.
pologic destinations include Teotihuacan out-
side Mexico City, Great Pyramid of Cholula Travelers’ Diarrhea and Other
in Puebla, Tulum and Cobá in Quintana Roo, Foodborne and Waterborne
El Tajín in Veracruz, Chichen Itzá in Yucatán, Infections
Monte Alban in Oaxaca, and Palenque in Travelers’ diarrhea is common among visitors to
Chiapas. Baja California offers whale watching Mexico. In addition to practicing food and water
on the Pacific Coast and sports fishing in the precautions, travelers should consider bringing
Gulf of California. an antibiotic for self-treatment of diarrhea (see
A large number of US residents travel to the Food & Water Precautions and Travelers’
Mexico to receive health services (medical tour-
ism). Only Thailand sees a higher number of US
Diarrhea sections in Chapter 2). Travelers should
keep in mind that tap water is not potable and
4
travelers for this purpose. The main services should avoid consuming raw dairy products,
sought are dental services, eye care, and cosmetic undercooked meat or fish, leafy greens, or raw
surgery in the border cities. Increasingly, a com- vegetables. Foodborne infections that are a risk in
plete range of services and specialized procedures Mexico include amebiasis, cysticercosis, brucello-
are offered in cities with large medical services sis, listeriosis, and infections with Mycobacterium
infrastructure, such as Mexico City, Monterrey, bovis. Cholera is considered a low risk in Mexico;
Mérida, Cancún, and Guadalajara (see Chapter 2, however, travelers should adhere to food and
Medical Tourism). water precautions.
RABIES MALARIA
Travelers should be educated on how to avoid Malaria incidence has decreased dramatically
animal bites to reduce the risk of rabies. In in recent decades in Mexico, and risk of infec-
Mexico, the most common animal species that tion with Plasmodium vivax among US travel-
carry rabies are unvaccinated dogs or cats and ers is considered very low. Major resorts are free
wild animals such as bats, coatis, coyotes, foxes, of malaria, as is the US–Mexico border region.
and skunks. Preexposure rabies vaccination Malaria prophylaxis is recommended for travelers
MEXICO 461
4
26
to Campeche, Chiapas, Chihuahua, Nayarit, and reported worldwide, CDC has investigated travel-
Sinaloa. Mosquito avoidance but not chemo- associated clusters of legionellosis in association
prophylaxis is recommended for travelers to with hotels and resorts in Mexico. Legionellosis
Durango, Jalisco, Oaxaca, Sonora, Tabasco, and should be considered in elderly and immuno-
Othón P. Blanco municipality of Quintana Roo. compromised travelers who develop pneumonia
within 14 days of travel.
RICKETTSIAL DISEASE
Rickettsial diseases found in Mexico include TUBERCULOSIS (TB)
Rocky Mountain spotted fever, which is poten- Mexico’s TB incidence is lower than rates in Asia,
tially fatal unless treated promptly with antibiot- Africa, and Eastern Europe, but is 5 times that of
ics, and fleaborne typhus, which usually causes the United States. The potential risk of exposure
symptoms that are similar to dengue. Travelers and infection with M. tuberculosis should be dis-
should take precautions to avoid flea and tick cussed with travelers planning long-term stays
4 bites both indoors and outside. Rocky Mountain
spotted fever associated with Rhipicephalus san-
(≥6 months) or those who may be exposed to
patients with untreated TB (such as those work-
guineus, the brown dog tick, has been identified ing in health care settings, homeless shelters, or
recently in northern Mexico in urban and rural prisons).
areas with large stray dog populations.
Other Health and Safety Risks
PARASITIC INFECTIONS Good health care is available in most Mexican
Cutaneous leishmaniasis, transmitted by sand cities, and hotels in tourist resorts usually have
flies, is found in focal areas of coastal and south- well-trained physicians available. Travelers
ern Mexico. The risk is higher for ecotourists, should be aware that payment up front (cash
field biologists, and long-term travelers. Travelers or credit card) may be required before receiv-
should prevent fly bites, which includes avoid- ing any care. Also, most providers do not accept
ing outdoor activities at night. Travelers to beach US domestic health insurance or Medicare/
areas may be at risk for cutaneous larva migrans Medicaid plans. Injuries, rather than infectious
(CLM), a creeping skin eruption most commonly diseases, pose the largest risk of death among
associated with dog hookworm infection. CLM healthy travelers to Mexico. In one review, the
can be prevented by wearing shoes and avoiding leading cause of death to all US travelers to
direct skin contact with sand. Chagas disease is Mexico was injuries (51%), and 18% of deaths
endemic throughout Mexico. resulted from motor vehicle crashes.
Mexico’s highway system and roads have
Other Infections become increasingly modernized over the years.
RESPIRATORY DISEASES Toll highways are often of high quality. Never
Influenza virus strains similar to those in the theless, driving in traffic in cities and at night
United States circulate in Mexico, as was demon- through the countryside can be dangerous.
strated by the emergence of pandemic influ- Travelers should fasten seat belts when riding in
enza A (H1N1) in North America in the spring of cars and wear a helmet when riding bicycles or
2009. Coccidioidomycosis, a fungal respiratory motorbikes. Although travel in Mexico is gener-
disease caused by inhaling spores in the soil, is ally safe, drug-related violence has continued to
endemic in northwestern Mexico. Several out- increase in parts of the country. Department of
breaks of coccidioidomycosis have been reported State advisories should be monitored for relevant
among missionary groups from the United safety and security alerts.
States doing construction projects in this region. Air pollution in Mexico City, while decreased in
Histoplasmosis, another fungal respiratory dis- recent years, can be particularly severe during the
ease agent found in soil, is endemic in other dry winter months and can exacerbate asthma
regions of Mexico, mainly the central and south- and chronic lung and heart conditions. Both
east regions. Although cases of legionellosis are healthy travelers from lower elevations and people
with lung and heart conditions should cautiously Oaxaca) and in the center states of Morelos, State
acclimate to Mexico City’s altitude. of Mexico, Guanajuato, and Durango. Travelers
Most injuries and deaths caused by poison- should exercise caution when visiting Mexico’s
ous Centruroides genus scorpions are reported rural areas and when participating in outdoor
from states in the Pacific Coast (from Sonora to activities, especially during spring and summer.
BIBLIOGRAPHY
1. Brathwaite DO, San Martin JL, Montoya RH, del Diego 6. Flores-Figueroa J, Okhuysen PC, von Sonnenburg F,
J, Zambrano B, Dayan GH. The history of dengue DuPont HL, Libman MD, Keystone JS, et al. Patterns
outbreaks in the Americas. Am J Trop Med Hyg. 2012 of illness in travelers visiting Mexico and Central
Oct;87(4):584–93. America: the GeoSentinel experience. Clin Infect Dis.
2. CDC. Update: novel influenza A (H1N1) virus infection – 2011 Sep;53(6):523–31.
Mexico, March–May, 2009. MMWR Morb Mortal Wkly 7. Laniado-Laborin R. Coccidioidomycosis and other
Rep. 2009 Jun 5;58(21):585–9.
3. CDC. Human rabies from exposure to a vampire bat in
endemic mycoses in Mexico. Rev Iberoam Micol. 2007
Dec 31;24(4):249–58.
4
Mexico—Louisiana, 2010. MMWR Morb Mortal Wkly 8. Leparc-Goffart I, Nougairede A, Cassadou S, Prat C, de
Rep. 2011 Aug 12;60(31):1050–2. Lamballerie X. Chikungunya in the Americas. Lancet.
4. CDC. Notes from the field: outbreak of Vibrio cholerae 2014 Feb 8;383(9916):514.
Serogroup O1, Serotype Ogawa, Biotype El Tor Strain – 9. Spradling PR, Xing J, Phippard A, Fonseca-Ford M,
La Huasteca Region, Mexico, 2013. MMWR Morb Mortal Montiel S, Guzman NL, et al. Acute viral hepatitis in
Wkly Rep. 2013;63(25):552–3. the United States-Mexico border region: data from
5. Fitchett JR, Vallecillo AJ, Espitia C. Tuberculosis trans- the Border Infectious Disease Surveillance (BIDS)
mission across the United States–Mexico border. Rev Project, 2000–2009. J Immigr Minor Health. 2013
Panam Salud Publica. 2011 Jan;29(1):57–6 0. Apr;15(2):390–7.
Mark J. Sotir/Personal Collection
2007. Machu Picchu is located in southern Peru Other popular tourist destinations in Peru
and stands in the middle of a tropical mountain include the northern Amazon rainforest in Loreto,
forest, in an extraordinarily picturesque setting. It which can be visited by traveling to the lodges
was probably the most amazing urban creation of around Iquitos or by journeying on the increas-
the Inca Empire at its height; its giant walls, ter- ingly popular Amazon River cruises that go both
races, and ramps seem as if they have been cut upstream and downstream from Iquitos. Also,
naturally in the continuous rock escarpments. Peru is home to the Cordillera Blanca, a hundred-
The natural setting, on the eastern slopes of the mile range of spectacular snow-covered peaks
Andes, is in the upper Amazon Basin, with its rich that form the backbone of the Andes Mountains
diversity of flora and fauna. in Peru. The Cordillera Blanca boasts 33 peaks
A visit to Peru will likely begin in the capital >18,040 ft (5,500 m) and has an international repu-
city of Lima, a sprawling megacity that is home tation for its spectacular trekking and world-class
to approximately one-third of Peru’s population. mountaineering. Puno and Lake Titicaca, which
4 Interestingly, many people think Lima is a high-
altitude Incan city, but it is actually located on
has been called the highest navigable lake in the
world, in southern Peru near the Bolivian border
the Pacific coast at sea level (Map 4-10). From are also popular with tourists, with itineraries that
Lima, one can take an hour-long flight to Cusco, include visitations to islands on the lake. Another
the gateway to Machu Picchu and a worthwhile tourist destination south of Lima is the Nazca
destination of its own. Tourists can visit multiple Desert, home of the ancient geoglyphs known as
Inca-era ruins, both in Cusco and mountain vil- the Nazca Lines.
lages and markets in the Valle Sagrado (Sacred
Valley), before taking the train to Machu Picchu. HEALTH ISSUES
From the train there are multiple ways to reach Important pretravel information for Peru includes
the actual site, varying from buses up the moun- advice on preventing high- altitude illness, the
tain to Machu Picchu from the nearby town of risk for cutaneous leishmaniasis in certain jun-
Aguas Calientes to multiple- day hikes across gle areas, the risk of vectorborne illnesses, includ-
Andean mountain trails. One of the world’s ing malaria, and the use of yellow fever vaccine in
most popular and best-known treks, the Inca some areas.
Trail, begins at an elevation of more than 8,000
ft (>2,500 meters) on the Cusco–Machu Picchu Altitude and Acute
railway. This moderate 26-mile (43-km) trek is Mountain Sickness
usually done in 4 days and 3 nights, and most Travelers to Machu Picchu will arrive and tran-
fit people should be able to complete the hike. sit through Cusco, which is 11,200 ft (3,400 m)
Nevertheless, it is quite challenging, with 3 high above sea level. A recent study of travelers to
mountain passes; the highest is Warmiwañusca Cusco found that three-quarters flew directly
at 13,796 ft (4,205 m), before ending at the ruins from sea level. Most will quickly note shortness
of Machu Picchu (7,970 ft; 2,430 m). of breath on gathering luggage and making their
Many people also wish to add a tropical way to local hotels on the hilly streets. Many
rainforest experience to their Cusco trip and arriving travelers, maybe as many as half, will
take the 30-minute flight from Cusco to Puerto find that Cusco’s elevation leads to some degree
Maldonado, 34 miles (55 km) west of the Bolivian of acute mountain sickness (AMS), with the ini-
border, at the confluence of the Rio Tambopata tial symptoms of headache, nausea, and loss of
with the Madre de Dios River, a major tribu- appetite beginning 4–8 hours after arrival. The
tary of the Amazon River. Most travelers take a hypoxemia of high altitude can also affect the
boat up the Rio Tambopata to one of several rus- quality of sleep in the first few nights in Cusco,
tic lodges. Visitors wanting to see the Amazon causing restless sleep, frequent awakening, and
rainforest may also go to the more remote periodic breathing (irregular breathing patterns,
Manu National Park in the south, also reached often alternating periods of deep breathing and
via Cusco. shallow breathing), even in those who appear
to be doing well during the day. Some travelers visit Cusco on the return from Machu Picchu,
may progress to severe forms of altitude illness, when people are better acclimatized. The train
including high-altitude pulmonary edema and follows the Rio Urubamba north and north-
high-altitude cerebral edema. The symptoms of west (downstream) to Aguas Calientes (6,693 ft;
AMS can markedly impair the traveler and pre- 2,040 m). Machu Picchu (7,972 ft; 2,430 m) is
vent enjoyment of the sights of Cusco. People located on a ridge above the town.
with underlying lung disease may not be the best
candidates for travel to this destination. Expert Cutaneous Leishmaniasis
pretravel medical consultation is advised. (See Many areas in the Pacific valleys of the Andes
Chapter 2, Altitude Illness) and the Amazon tropical rainforest are endemic
Surveys have shown that most travelers arrive for cutaneous leishmaniasis (CL), a parasitic
in Cusco with limited or no knowledge of AMS infection transmitted by bites of sand flies (see
or the fact that AMS can be prevented to a large Chapter 3, Leishmaniasis, Cutaneous). While this
4 degree by prophylactic use of acetazolamide.
Every traveler to Cusco should be counseled about
disease is widespread in southeastern Peru, the
highest risk for travelers seems to be in the Manu
AMS before travel and be prepared to prevent or Park area in Madre de Dios. In Manu, CL is most
self-treat AMS with acetazolamide. Travelers to often caused by Leishmania braziliensis, and there
other parts of Peru may also require counseling is a risk of both localized ulcerative CL and muco-
about AMS; other common travel destinations sal leishmaniasis. There is no visceral leishmani-
at high elevation include the Cordillera Blanca asis in Peru. Travelers should be counseled to be
(peaks >18,040 ft; 5,500 m), Puno (12,556 ft; meticulous about vector precautions, as there is
3,830 m) and Lake Titicaca. (More information no vaccine or prophylaxis to prevent leishmania-
about prevention and treatment of altitude illness sis. Any person with a skin lesion persisting more
can be found in Chapter 2, Altitude Illness.) Locals than a few weeks after return from Peru should be
refer to AMS as soroche and will almost always evaluated for CL.
offer the new arrival a cup of hot coca tea (mate
de coca) when checking in to the hotel. Although Yellow Fever
many believe mate de coca can prevent and treat Proof of yellow fever vaccination is not required
soroche, no data support its use in the prevention for entry into Peru. Travelers who are limiting
or treatment of AMS. Perhaps of concern to some their itineraries to Lima, Cusco, Machu Picchu,
who may experience random drug screening as a and the Inca Trail do not need yellow fever vac-
condition of employment, people who drink a sin- cination. Peru recommends vaccination for all
gle cup of coca tea will test positive for cocaine travelers >9 months of age who intend to visit any
metabolites in standard drug toxicology screens jungle areas of the country <7,546 ft (2,300 m). For
for several days. However, sitting quietly and rest- complete CDC yellow fever vaccination recom-
ing while enjoying a cup of tea is a most civilized mendations for Peru, see Chapter 3, Yellow Fever
activity and a pleasant memory. & Malaria Information, by Country.
New arrivals may also find it helpful to tran-
sit directly from Cusco to the Valle Sagrado of the Malaria
Rio Urubamba (Sacred Valley) to spend the first Both Plasmodium vivax malaria and P. falciparum
few days and nights at a somewhat lower alti- malaria are found in the Peruvian Amazon, as
tude. This spectacular river valley begins 15 miles well as the central jungle and northern coastal
(24 km) northeast of Cusco in the town of Pisac regions. Among people with severe malaria hos-
(9,751 ft; 2,972 m), known for its colorful Sunday pitalized at a tertiary referral center in Lima,
markets, and continues downstream toward the most were P. vivax infections, and almost half
northwest for another 37 miles (60 km) to reach the were infected in Amazonia. There is no malaria
town of Ollantaytambo (9,160 ft; 2,792 m). One can risk for travelers visiting only Lima and its vicin-
board the train to Machu Picchu in Ollantaytambo, ity, coastal areas south of Lima, or the popular
at the northwest end of the Valle Sagrado and then highland tourist areas (Cusco, Machu Picchu,
and Lake Titicaca). The malaria-endemic areas to clinically improve in 12–24 hours after initial
for most tourists are the neotropical rainforests empiric fluoroquinolone treatment. Azithromycin
of the Amazon (see Map 3-37). Malaria in the can be used for people who do not respond to
Peruvian Amazon is unpredictable from season empiric treatment of acute gastroenteritis with a
to season; P. falciparum epidemics occasionally fluoroquinolone. Cyclosporiasis, an intestinal ill-
occur in the Loreto region. The city of Iquitos ness caused by the parasite Cyclospora cayetanen-
in the northern rainforest is a frequent arrival sis, is also common in Peru. This diagnosis should
destination for those traveling to jungle lodges be considered in people with watery diarrhea, loss
around the city or for boarding river cruise boats of appetite, weight loss, cramping, and bloating
for rainforest travel. Malaria transmission occurs that persist for days to weeks. Treatment is with
in the areas in and around Iquitos. Malaria trans- trimethoprim-sulfamethoxazole.
mission occurs throughout the year but is sea- Dengue is common in the neotropical areas
sonally variable, with peak activity between of Peru and the northern coast. Mayaro virus,
January and May that correlates with the rainy
season. Prophylaxis is recommended for most
an alphavirus found in the Amazon Basin and
transmitted by mosquitoes, causes a dengue-
4
travelers. like illness. As with other alphaviruses, Mayaro
The city of Puerto Maldonado is a 30-minute can result in lengthy and debilitating arthralgia.
flight from Cusco and a popular arrival destination Chikungunya, another alphavirus that can cause
for those visiting the rainforest lodges on the Rio arthralgia, has also been reported in Peru. The
Tambopata. Newly arrived travelers usually tran- first cases of local vectorborne Zika virus trans-
sit directly from the airport to the boats that take mission were reported in Peru in 2016. Because
them up the river to numerous lodges. Peruvian of the risks to pregnancy, travelers should consult
Ministry of Health data document that malaria the CDC Travelers’ Health website (www.cdc.gov/
transmission occurs in Puerto Maldonado. Most travel) for the most current recommendations for
cases reported in the region occur in local loggers Zika. Travelers to Peru should take measures to
and gold miners in the forests. protect themselves from daytime mosquito bites
to prevent vectorborne illnesses (see Chapter 2,
Other Infectious Diseases Protection against Mosquitoes, Ticks, & Other
Typical travelers’ diarrhea is relatively common. Arthropods). Physicians treating patients with
Fluoroquinolone-resistant Campylobacter gastro- signs and symptoms of a denguelike illness and a
intestinal infections can occur and should be sus- recent history of travel to the Amazon should con-
pected in anyone with a gastrointestinal illness sider Mayaro, chikungunya, and Zika in the differ-
with fever and systemic symptoms and failure ential diagnosis.
BIBLIOGRAPHY
1. Cabada MM, Maldonado F, Quispe W, Serrano E, Mozo 4. Neumayr A, Gabriel M, Fritz J, Gunther S, Hatz C,
K, Gonzales E, et al. Pretravel health advice among Schmidt-Chanasit J, et al. Mayaro virus infection in
international travelers visiting Cuzco, Peru. J Travel traveler returning from Amazon Basin, northern Peru.
Med. 2005 Mar-Apr;12(2):61–5. Emerg Infect Dis. 2012 Apr;18(4):695–6.
2. Llanos-Chea F, Martínez D, Rosas A, Samalvides F, 5. Salazar H, Swanson J, Mozo K, White ACJ, Cabada MM.
Vinetz JM, Llanos-Cuentas A. Characteristics of travel- Acute mountain sickness impact among travelers to
related severe Plasmodium vivax and Plasmodium falci- Cusco, Peru. J Travel Med 2012 Jul;19(4):220–5.
parum malaria in individuals hospitalized at a tertiary 6. Shaw MT, Harding E, Leggat PA. Illness and injury to
referral center in Lima, Peru. Am J Trop Med Hyg. 2015 students on a school excursion to Peru. J Travel Med.
Dec;93(6):1249–53. 2014 May-Jun;21(3):183–8.
3. Mazor SS, Mycyk MB, Wills BK, Brace LD, Gussow L, 7. Steinhardt LC, Magill AJ, Arguin PM. Review: Malaria
Erickson T. Coca tea consumption causes positive urine chemoprophylaxis for travelers to Latin America. Am J
cocaine assay. Eur J Emerg Med. 2006 Dec;13(6):340–1. Trop Med Hyg. 2011 Dec;85(6):1015–24.
ASIA
do well to attempt an understanding of the coun- staying in accommodations without air condition-
try’s society, human rights, and environment, and ing, window or door screens, or bed nets.
tourism’s potential impact on them.
Malaria and Other
HEALTH ISSUES Vectorborne Diseases
Malaria is present in all areas of Burma below
Vaccine-Preventable Diseases altitudes of 3,281 ft (1,000 m), including Bagan,
ROUTINE IMMUNIZATIONS and the risk to travelers is considered mod-
Travelers to Burma should be up-to-date on rou- erate. The incidence of malaria in Burma is
tine vaccines, including vaccines for tetanus and higher than that of neighboring countries in the
influenza. Influenza exhibits a seasonal pattern Greater Mekong Subregion and is concentrated
with peaks occurring from June through September, in and around forested areas. Drug- resistant
overlapping with the typical rainy season. malaria has been and continues to be a concern
4 OTHER VACCINATIONS
in Burma, and chemoprophylaxis recommen-
dations vary accordingly. For travelers to Bago,
Hepatitis A is transmitted by contaminated food Kachin, Kayah, Kayin, Shan, and Tanintharyi,
or water and is endemic in Burma; all nonimmune atovaquone-proguanil or doxycycline is recom-
travelers should be vaccinated. Travelers can also mended but not mefloquine; for other malaria
reduce the risk of hepatitis A infection by follow- risk areas, atovaquone- proguanil, doxycycline,
ing recommendations for safe food and water (see or mefloquine can be used. Other vectorborne
Chapter 2, Food & Water Precautions). Based on infections endemic in Burma include dengue
data from US-bound refugees, the prevalence of and chikungunya.
hepatitis B infection in Burma is high. Hepatitis B Zika is endemic in Burma; the risk to travel-
vaccination is recommended for most travelers ers is unknown but believed to be low. Because
before departure, especially those who might of the risk of birth defects in babies born to
engage in activities that increase risk to body fluid women who were infected with Zika while preg-
exposure, such as unprotected sexual contact, injec- nant, women who are pregnant or planning to
tion drug use, tattooing, or providing medical care. become pregnant should not travel to Burma. If
Typhoid and other diseases transmitted by they decide to travel, they should strictly follow
contaminated food and water are common, and steps to prevent mosquito bites. Travelers should
typhoid vaccine is recommended. consult the CDC Travelers’ Health website (www.
Rabies vaccination is recommended for trav- cdc.gov/travel) for the most current recommen-
elers participating in extensive outdoor activities, dations for Zika.
such as camping or caving, that could increase
their risk of animal bites. Vaccination is also rec- Leptospirosis
ommended for travelers working with animals, Leptospirosis is a bacterial disease usually trans-
such as veterinarians, and for young children, for mitted through contact with water contaminated
whom it can be difficult to prevent interaction with the urine of infected animals (see Chapter 3,
with dogs or other animals. Leptospirosis). It occurs most commonly during
Japanese encephalitis (JE) is presumed to be the rainy season. Travelers should avoid contact
endemic throughout Burma, so travelers should with soil and water that could be contaminated,
take precautions to avoid mosquito bites (see and cover any open wounds to prevent exposure.
Chapter 2, Protection against Mosquitoes, Ticks, Skin wounds that have been contaminated with
& Other Arthropods). Travelers should consider soil or water should be immediately and thor-
obtaining JE vaccine if they will be in Burma for oughly cleaned.
>1 month or if their itineraries include higher-risk
activities such as spending substantial time in rural Travelers’ Diarrhea
areas, especially in the evening or at night; outdoor Travelers’ diarrhea is common among visitors
activities (such as camping, hiking, or farming); or to Burma (see Chapter 2, Travelers’ Diarrhea).
Travelers should follow safe food and water recom- parts of Burma, including popular tourist desti-
mendations, including eating food that is cooked nations such as Rangoon, Mandalay, and Bagan.
and served hot and drinking only bottled water. Prolonged heat exposure, especially for travelers
Oral rehydration solution is helpful in severe cases in poor physical condition, elderly or very young
of diarrhea and is usually available in pharmacies. travelers, and those not accustomed to heat,
poses a risk for heat-related illnesses such as heat
Other Health and Safety Risks exhaustion or heat stroke. During periods of high
ROAD TRAFFIC INJURIES heat, travelers should take precautions to reduce
Vehicular crashes are a leading cause of injury and risk of heat-related illnesses, including drinking
death among travelers to Burma. Visitors should ample water and wearing lightweight, loose, and
use only reputable taxi or public transportation light-colored clothing (see Chapter 2, Problems
companies and always wear seat belts. Motor with Heat & Cold).
cycles account for a high percentage of road traf-
fic deaths and should be avoided. Pedestrians and
bicyclists are also commonly victims of road traffic
HEALTH CARE ACCESS
Travelers with chronic medical conditions
4
deaths and should exercise caution; right-of-way should not rely on being able to purchase or refill
rules and infrastructure improvements (such as medications in Burma; counterfeit and substan-
crosswalks or bike lanes) to protect these groups dard medications are common. International-
are often not followed or not in place. standard medical care is rarely available, so
treatment of chronic disease exacerbations or
HEAT-RELATED ILLNESSES severe injuries can be suboptimal. Travelers
Average high temperatures in the hot season should strongly consider medical evacuation
(March to June) can exceed 95°F (35°C) in many insurance.
BIBLIOGRAPHY
1. Agency CI. The World FactBook: Burma. Central 7. Lo E, Nguyen J, Oo W, Hemming-Schroeder E, Zhou
Intelligence Agency; 2016 [updated 2016 Sep.; G, Yang Z, et al. Examining Plasmodium falciparum
cited 2016 Sep. 23]; Available from: https://www.cia. and P. vivax clearance subsequent to antimalarial drug
gov/library/publications/the-world-factbook/geos/ treatment in the Myanmar-China border area based on
bm.html. quantitative real-time polymerase chain reaction. BMC
2. Cheng AC, Currie BJ. Melioidosis: epidemiology, patho- Infect Dis 2016 Apr 16;16(1):154.
physiology, and management. Clin Microbiol Rev. 2005 8. Mixson-Hayden T, Lee D, Ganova-Raeva L, Drobeniuc
Apr;18(2):383–416. J, Stauffer WM, Teshale E, et al. Hepatitis B virus and
3. Cui L, Yan G, Sattabongkot J, Cao Y, Chen B, Chen hepatitis C virus infections in United States-bound
X, et al. Malaria in the Greater Mekong Subregion: refugees from Asia and Africa. Am J Trop Med Hyg 2014
heterogeneity and complexity. Acta Trop. 2012 Jun;90(6):1014–20.
Mar;121(3):227–39. 9. Republic of the Union of Myanmar. The 2014 Myanmar
4. Dapat C, Saito R, Kyaw Y, Naito M, Hasegawa G, Suzuki population and housing census: highlights of the main
Y, et al. Epidemiology of human influenza A and B results. Census Report. Nay Pyi Taw: Department of
viruses in Myanmar from 2005 to 2007. Intervirology Population MoIaP; 2015 May. Available from: http://
2009;52(6):310–20. myanmar.unfpa.org/sites/asiapacific/files/
pub-pdf/C ensus%20Highlights%20Report%20-
5. Hills SL, Rabe BR, Fischer M. Infectious diseases %20ENGLISH%20(1).pdf.
related to travel. Atlanta, GA: CDC; 2016 [updated 2015
July; cited 2016 Sep. 24]; Available from: http://wwwnc. 10. U.S. Department of State. U.S. Passport & International
cdc.gov/travel/yellowbook/2016/infectious-diseases- Travel: Burma (Myanmar). USDS; [cited 2016 May 7];
related-to-travel/japanese-encephalitis. Available from: https://travel.state.gov/content/passports/
en/country/burma.html.
6. Hotez PJ, Bottazzi ME, Strych U, Chang LY, Lim YA,
Goodenow MM, et al. Neglected tropical diseases 11. World Health Organization. Global status report
among the Association of Southeast Asian Nations on road safety 2013. WHO; 2013 [cited 2016 May 7 ];
(ASEAN): overview and update. PLoS Negl Trop Dis Available from: http://www.who.int/violence_injury_
2015;9(4):e0003575. prevention/road_safety_status/2013/en/.
DESTINATION OVERVIEW
4 China, with >1.3 billion people, is the world’s
inventions of Ancient China”: paper, the com-
pass, gunpowder, and printing. Today, China is
most populous country and the fourth largest considerably more advanced (with the ability to
geographically, behind Russia, Canada, and the put people in space, for example) and wealth-
United States. It shares a border with 14 other ier than many other developing countries, yet
countries and has approximately 11,000 miles rural poverty and underdevelopment are still
(18,000 km) of coastline. China is divided into 23 problems, particularly in the western part of the
provinces, 5 autonomous regions, and 4 munic- country.
ipalities (Map 4-╉12). This large landmass is home Approximately 700 million Chinese people
to diverse topography, languages, and customs. live in rural areas. Urban areas are growing rap-
The climate varies from tropical in the south idly, however, and China is now home to many
to subarctic in the north, with wide variations of the world’s largest megacities. Shanghai and
between regions and seasons. Natural hazards Beijing each have close to 20 million inhabitants,
include typhoons along the southern and east- and Chongqing, with a metropolitan population
ern seaboards, dust storms in the north, floods, of more than 30 million, is among the fastest-╉
earthquakes, and landslides. Six of the 10 deadli- growing urban centers in the world. Rivers play a
est natural disasters in history occurred in China, central role in China’s economy, history, and cul-
including the 1556 Shaanxi earthquake, which is ture. The Yangtze River Basin, stretching 4,000
thought to have killed more than 800,000 people, miles (6,400 km) from the Tibetan plateau to the
making it the most lethal earthquake in history. East China Sea near Shanghai, is home to more
Chinese superstition holds that natural disasters than 5% of the world’s population.
foretell the death of a ruler or the end of a dynasty, In 2015, more than 120 million tourists visited
and indeed Mao Tse-╉ tung died only 6 weeks China. Tourism to China has grown at an extraor-
after the 1976 Tangshan earthquake, the death dinary pace over the past decade, although num-
toll of which was also in the hundreds of thou- bers have leveled off slightly in the past few years.
sands. More recently, devastating earthquakes What is even more striking is the rapid growth
have struck the western provinces of Sichuan in in Chinese outbound tourism, from 29 million in
2008 and Qinghai in 2010. Torrential rain, floods, 2004 to 120 million in 2015.
and landslides plagued large areas of China in China’s long history and varied natural
the summer of 2010, as well as drought and dust beauty can be traced through its 48 UNESCO
storms in the north. World Heritage sites, from the imperial gran-
China has one of the world’s oldest contin- deur of the Forbidden City and the Temple of
uous civilizations, dating back >5,000 years. It Heaven to the marvel of the Great Wall, the
has the world’s longest continuously used writ- Terracotta Warriors in Xi’an, and the spec-
ten language system and is the source of many tacular mountainous sanctuaries of the west.
major inventions, including the “four great The most recent additions are the Tusi tribal
KAZAKHSTAN
·.· .. :
. .·..
.' •
.. : .....
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MONGOLIA
... ..,
·. .·
..... . . . ..
.. . ....
......... •/N.ORTH SEA OF
. ·.
.. .
.-- -·~
..... ••Gingdao
~
..DaUan
~
YELLOW
* Seoul
SOUTH
KOREA
JAPAN
:.
·..
~
. ...~
be
....... .........
........t
SEA
...... .......
... ·--
\
Delhi *
EAST
CHINA
* ......
Kathmandu •• •••• •
.
. ••• BH.UTAN
....... SEA
...:
~.
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Taipei
TAIWAN
OCEAN
. --+...... ct'
,
:: _. / ••.• • .· • · ·: ........ . . . . .+ Hong Kong + Kaohsiung
BURMA ••• •. · VIETNAM · .••
BAY .. *
CHINA
4
47
domains in Western China and the Grand village tours, the Silk Road, and other more remote
Canal, the oldest (468 bce) and longest regions. Aside from tourism, increasing numbers
(1,115 miles; 1,794 km) man-made canal in the of people travel to China to visit friends and rela-
world, linking Beijing and Hangzhou. Popular tives, to study, or to adopt children. These groups
itineraries often include Beijing and the may be at particularly high risk of illness because
Great Wall, Xi’an, and the Yangtze River (see they underestimate their risks, are less likely to
Box 4- 1 for information specifically about seek pretravel advice, and stay in more local or
Yangtze River cruises). Other tourist destina- rural accommodations. People traveling to China
tions include the following: to adopt children often worry about the health of
the child but neglect their own health.
• Shanghai and Hong Kong, with their futuristic
architecture and East-meets-West mystique
HEALTH ISSUES
• Lijiang in the province of Yunnan, where Although China is now the world’s second-largest
4 many ethnic minorities are concentrated economy, per capita income is still below the
world average, with wide disparity in wealth and
• Sichuan Province, home to China’s iconic development between rural and urban as well as
symbol, the panda
east and west. Health risks vary accordingly.
• Guilin, famous for its uniquely shaped lime-
stone karst mountains that are often featured Air Pollution
in Chinese paintings China’s rapid economic expansion has resulted
in tremendous increases in emissions of air pol-
• Tibet, accessible now by the world’s highest lutants, particularly in the megacities. Although
railroad directly to Lhasa, with a maximum
aggressive efforts are underway to control pollu-
altitude of 16,640 ft (5,072 m)
tion, 16 of the 20 most polluted cities in the world
Specialized itineraries are increasingly being are in China, and Beijing regularly tops the list.
offered, including hiking, mountain climbing, On peak pollution days, the levels of particulate
matter in the air can exceed 40 times the limit and improperly stored vaccines. In addition, vac-
considered safe by the World Health Organization. cine shortages are frequent; adult tetanus vaccines
Short-term exposure to these levels of air pollu- were out of stock from 2014 through the time of
tion can irritate the eyes and throat, and those writing. Travelers are unlikely to be able to com-
with underlying cardiorespiratory illness, includ- plete unfinished vaccination series once in China
ing asthma, chronic obstructive pulmonary dis- and may be unable to access tetanus vaccine if
ease, or congestive heart failure, may find their injured while there. All travelers should have an up-
condition exacerbated. In addition, exposure to to-date tetanus-containing vaccine before going to
high levels of air pollution significantly increases China. Hong Kong functions under different rules,
the risk of respiratory tract infections, includ- and international vaccines are in use there.
ing sinusitis, otitis, bronchitis, and pneumonia.
Children and the elderly are the most vulnerable HEPATITIS B
to these effects. Hepatitis B infection is endemic in China. Nearly
Although surgical- style face masks have
become increasingly fashionable in the big cit-
one-third of the 350 million people worldwide
infected with the hepatitis B virus (HBV) reside
4
ies of China, especially Beijing and Shanghai, in China. Hepatitis B vaccination and other pre-
they provide no protection from air pollution ventive measures should be discussed with non-
and are not recommended. Properly fitted N95 immune travelers.
masks can filter out particulates but not gaseous
pollutants and can sometimes actually com- JAPANESE ENCEPHALITIS
pound breathing problems, so are not routinely Japanese encephalitis (JE) occurs in all regions
recommended. except Qinghai, Xinjiang, and Xizang (Tibet) (see
Map 3-8 and Table 3-7). China has greatly reduced
Vaccine-Preventable Diseases the incidence of JE through vaccination and, as of
Routine vaccinations should be up- to-
date, 2008, included JE in its expanded national immu-
including seasonal influenza. In addition, hepa- nization program; however, the disease remains
titis A and B and typhoid vaccinations are usu- a threat to unimmunized travelers. Although
ally recommended. Since the Xinjiang Uygur the JE season varies by region, most cases in
Autonomous Region borders Pakistan, a polio- local residents are reported from June through
endemic country, adults traveling to this region October. The risk of JE for most travelers to China
who will be working in health care settings, ref- is low but varies based on season, destination,
ugee camps, or humanitarian aid settings should duration, and activities. Risk is highest among
be vaccinated against polio, including a single life- travelers to rural areas during the transmission
time booster dose of polio vaccine (IPV). Measles season. JE vaccine is recommended for travelers
and rubella immunity is particularly important, who plan to spend ≥1 month in endemic areas
and although a massive vaccination campaign during June through October. It should be con-
begun in September 2010 has decreased the num- sidered for shorter-term travelers if they plan to
ber of reported measles cases, there were still travel to rural areas and will have an increased
more than 100,000 cases reported in 2014. A few risk for JE virus exposure based on their activities
travelers have made news headlines by triggering or itineraries, such as spending substantial time
outbreaks in their home countries after return- outdoors or staying in accommodations without
ing from China. Although limited data exist on air conditioning, screens, or bed nets. However,
rubella in China, it was not part of the national rare sporadic cases have occurred on an unpre-
immunization program until 2008, and incidence dictable basis in short-term travelers, including
is believed to be high. in periurban Beijing and Shanghai.
China is making considerable advances in vac-
cination, with the objective of developing their RABIES
own locally made vaccines. There have, however, Rabies is a serious problem in China, as in much
been many well-publicized issues with counterfeit of Asia, with more than 3,000 reported human
CHINA 475
4
67
deaths per year. Mammal bites in any area of to drink even in major cities. Most hotels provide
China, including urban areas, must be consid- bottled or boiled water, and bottled water is eas-
ered high risk for rabies. As rabies immune globu- ily available. In addition, there have been several
lin is generally unavailable, animal bites are often well-publicized episodes of contamination of food
trip-enders, requiring evacuation to Hong Kong, with pesticides and other substances. Travelers
Bangkok, or home for postexposure prophylaxis. should strictly avoid undercooked fish and shell-
Bites are surprisingly common in tourists. For fish and unpasteurized milk.
example, dog bites were the most common der-
matologic problem seen after China travel in an SEXUALLY TRANSMITTED DISEASES
analysis of data from the GeoSentinel Surveillance Sexually transmitted diseases, including syphi-
Network. Rabies risk and prevention should be lis, HIV, gonorrhea, and chlamydia, are a grow-
discussed in pretravel consultations, and a strat- ing problem in China, particularly along the
egy for dealing with a possible exposure should booming eastern seaboard. Travel is associated
4 be developed. Long-term travelers and expatri-
ates living in China should consider the preexpo-
with loosened inhibitions and increased casual
sexual liaisons. Travelers should be aware of
sure vaccination series. Travel health insurance, STD risks and use condoms if they have sex with
including medical evacuation insurance, should someone whose HIV or STD status is unknown.
be encouraged (see Chapter 2, Travel Insurance, Hepatitis B vaccination before travel should be
Travel Health Insurance, & Medical Evacuation considered.
Insurance).
ROAD TRAFFIC INJURIES
Vectorborne Diseases Traffic in China is often chaotic, and the rate of
traffic crashes, including fatal ones, is among the
MALARIA
highest in the world. Driving is on the right side
Malaria risk is very low for travelers to China,
of the road in mainland China but on the left in
with the exception of those visiting rural parts of
Hong Kong and Macau. In practice, many people
southern Yunnan Province. For this area, chemo-
drive down the middle of the road. Child safety
prophylaxis should be considered. Mefloquine
seats, rear seat belts, and bicycle or motorcy-
resistance in southern Yunnan means that trav-
cle helmets are rarely seen and not widely avail-
elers should be given doxycycline or atovaquone-
able. Electronic bicycles (E-bikes) are popular and
proguanil for travel in this area.
do not have to be registered. They often travel in
pedestrian and bicycle lanes as well as with traffic.
DENGUE Because E-bikes are quiet (no engine noise), they
In 2014, southern China experienced its worst can be hard to avoid. Motor vehicles and E-bikes
dengue outbreak in decades; Guangdong province often drive with no lights, making night travel
reported more than 40,000 cases in just 2 months. dangerous. Traffic crashes, even minor ones, can
Travelers should practice daytime mosquito pre- create major traffic jams and sometimes turn into
cautions in the summer months. violent altercations, particularly when foreigners
are involved. China has not signed the conven-
Other Health Risks tion that created the International Driving Permit,
FOODBORNE ILLNESSES and travelers require a Chinese license to drive in
The risk for travelers’ diarrhea appears to be low China. For all of these reasons, it is often simpler
in deluxe accommodations in China but moder- and safer to hire a local driver than to drive one-
ate elsewhere. Usual food and water precautions self. It is also advisable to avoid driving at night
should apply, and travelers should consider bring- or when weather conditions are bad, and not to
ing an antibiotic for self-treatment of moderate to assume that traffic rules or right-of-way will be
severe diarrhea. Since highly quinolone-resistant respected. Travelers should fasten seat belts when
Campylobacter is a problem in China, azithromy- riding in cars and wear a helmet when riding bicy-
cin may be a good choice. Tap water is not safe cles or motorbikes.
BIBLIOGRAPHY
1. Custer B, Sullivan S, Hazlet TK, Iloeje U, Veenstra DL, Available from: http://mkt.unwto.org/en/publication/
Kowdley KV. Global epidemiology of hepatitis B virus. J unwto-tourism-highlights-2012-edition.
Clin Gastroenterol. 2005 Nov-Dec;38(10 Suppl):S158–68. 7. World Health Organization. Hepatitis B Surveillance
2. Cutfield NJ, Anderson NE, Brickell K, Hueston L, Pikholz and control. WHO; [updated 2016 July; cited 2016
C, Roxburgh RH. Japanese encephalitis acquired during Sep. 24]; Available from: www.who.int/mediacentre/
travel in China. Intern Med J. 2005 Aug;35(8):497–8. factsheets/fs204/en/.
3. Davis XM, MacDonald S, Borwein S, Freedman DO, 8. World Health Organization. Measles bulletin: Western
Kozarsky PE, von Sonnenburg F, et al. Health risks in Pacific region. Geneva: World Health Organization;
travelers to China: the GeoSentinel experience and 2010 [cited 2016 Sep. 24]; Available from: http://www.
implications for the 2008 Beijing Olympics. Am J Trop wpro.who.int/entity/immunization/documents/docs/
Med Hyg. 2008 Jul;79(1):4–8. MeasBulletinVol4Issue1_F840.pdf.
4. Hills SL, Griggs AC, Fischer M. Japanese encephalitis in 9. Xia J, Min L, Shu J. Dengue fever in China: an emerging
travelers from non-endemic countries, 1973–2008. Am J problem demands attention. Emerg Microbes Infect.
Trop Med Hyg. 2010 May;82(5):930–6. 2015 Jan;4(1):e3
5. Shaw MT, Leggat PA, Borwein S. Travelling to China for 10. Zhang J, Jin Z, Sun GQ, Zhou T, Ruan S. Analysis of
the Beijing 2008 Olympic and Paralympic games. Travel rabies in China: transmission dynamics and control.
Med Infect Dis. 2007 Nov;5(6):365–73. PLoS One. 2011;6(7):e20891.
6. United Nations World Tourism Organization. UNWTO 11. Zhang YZ, Xiong CL, Xiao DL, Jiang RJ, Wang ZX, Zhang
tourism highlights. Madrid: United Nations World LZ, et al. Human rabies in China. Emerg Infect Dis. 2005
Tourism Organization; 2012 [cited 2016 Sep. 24]. Dec;11(12):1983–4.
CHINA 477
84
7
DESTINATION OVERVIEW
4 India is approximately one-╉third the size of the
Varanasi, and cities in Rajasthan, such as Jaipur
(the Pink City) and Udaipur. Agra is the home of the
United States and has 4 times the population Taj Mahal, a breathtaking monument to lost love.
(almost 1.3 billion people). This makes it the Along the northern travel circle, one can stop to
second most populous country in the world, enjoy the magnificent bird sanctuary at Keoladeo
behind China. Rich in history, vibrant culture, Ghana and the tiger reserve at Ran Thambore (see
and diversity, India is the birthplace of 4 world Map 4-╉13). Varanasi, sacred to Hindus, Buddhists,
religions: Hinduism, Buddhism, Jainism, and and Jains, welcomes Hindu pilgrimages and boasts
Sikhism. Despite the growth of megacities such extraordinary experiences along the Ganges.
as Mumbai and Delhi (both more than 20 million A more southern route might swing through Goa
people), India’s rural population is still twice that and its beautiful beaches along the western coast,
of its urban population. Although India is one a destination in the past forming the backdrop
of the fastest-╉growing economies in the world, for great parties and old-╉time hippies, which has
the literacy rate varies by state (64%–╉94%), the now become a haven for writers and artists boast-
level of poverty is high, and the life expectancy is ing a chic new culture. Mumbai, a common entry
about 66 years. The topography is varied, ranging point to India, hosts Bollywood, the largest film
from tropical beaches to foothills, deserts, and industry in the world. Kolkata (Calcutta) is consid-
the Himalayan mountains. The north has a more ered the cultural capital of the country. Bengaluru
temperate climate, while the south is more tropi- (Bangalore) in the south-╉central region is both the
cal year-╉round. Many travelers prefer India during garden city and India’s Silicon Valley. The old sea-
the winter—╉ November through March, when side town of Kochi (Cochin) shows evidence of
the temperatures are more agreeable—╉although its Portuguese heritage, and Hyderabad shows off
some, particularly families with children, must its old granite fort, many mosques, and bazaars.
travel during the summer vacation time. Despite the many and varied itineraries, most
India is becoming more popular for US travel- health recommendations for travelers to India are
ers, and rates of travel from the United States are similar. The incidences of some illnesses, such as
increasing. International businesses are flourish- those transmitted by mosquitoes, increase during
ing in India; tourists are flocking to the temples, the monsoon season (May–╉October) with the high
beaches, and the Taj Mahal. For some new US temperatures, heavy rains, and the risk of flooding.
residents, India remains their homeland, and they Some of the most important health consid-
make frequent visits to family and friends. In addi- erations of travel to India are those for travel-
tion, India has a large and growing medical tour- ers who are visiting friends and relatives (VFRs).
ism sector. These travelers often do not seek pretravel health
Because tourists could not possibly visit all the advice, since they are returning to their land of
sites in India during a 2-╉week holiday, they usually origin. Such travelers may stay in rural areas often
select a part of India for any given trip. A typical not visited by tourists or business people, live in
itinerary in the north of India includes Delhi, Agra, homes, and eat and drink with their families, and
INDIA 479
0
8
4
thus are at higher risk of many travel-related ill- India, the disease is present in many parts of the
nesses (see Chapter 8, Immigrants Returning country. Risk is highest during the monsoon sea-
Home to Visit Friends and Relatives [VFRs]). son from May through October; however, the sea-
son may be extended or year-round in some areas,
HEALTH ISSUES especially in the south. Vaccination is not recom-
mended for the typical 2-week trip most travelers
Vaccine-Preventable Diseases
take to see the major tourist sites in urban areas.
All travelers to India should be up-to-date with
However, vaccination is recommended for trav-
their routine immunizations and are advised to
elers who plan to spend ≥1 month in endemic
consider hepatitis B vaccine. Particularly import-
areas during the JE virus transmission season and
ant is making sure that the traveler is immune to
should be considered for short-term travelers as
measles. India has not had a case of wild poliovirus
well, if they plan repeated travel or travel to peri-
since early 2011, obtained its polio-free certification
urban areas and have an increased risk for JE virus
4
from the World Health Organization in March 2014,
exposures (see Chapter 3, Japanese Encephalitis).
and celebrated 5 years of being polio-free in January
Publicized outbreaks in recent years have not
2016. Polio vaccine is no longer recommended for
been in typical tourist destinations.
US travelers. However, all travelers (residents and
nationals) from countries reporting cases of polio
RABIES
should check to see if there is a requirement for a
dose of polio vaccine prior to entry into India. India has the highest burden of rabies in the
world, with estimates of 18,000– 20,000 human
HEPATITIS A cases per year. Dogs roam in packs in many areas
All travelers to India should be protected against of the country. Unfortunately, human rabies
hepatitis A. Although some assume that those immune globulin is not readily available except
born in India would have been exposed to hepati- in some clinics in major cities. Information about
tis A in childhood and thus be immune, this may such clinics can be obtained from the website
no longer be true, particularly for younger people. of the International Society of Travel Medicine
Providers should consider serologic testing for (www.istm.org). Otherwise, if a traveler has not
hepatitis A IgG in VFR travelers, or they should be received preexposure rabies vaccination, a bite
immunized. may result in having to leave the country for post-
exposure prophylaxis. Even so, a preexposure
TYPHOID series is not recommended for all travelers to India.
More than 80% of typhoid fever cases in the However, education about bite avoidance and
United States are in people who traveled to India management should be a part of every pretravel
or other countries in south Asia. Thus, even for consultation. Cost is a consideration for many.
short-term travel, a typhoid vaccine should be Long- term travelers, expatriates, missionaries,
recommended. Patients who are hesitant to be and volunteers may want to obtain preexposure
vaccinated may find it even more compelling that immunization for themselves and their children.
typhoid fever acquired in south Asia is becoming Travelers may want to purchase a medical evac-
increasingly resistant to quinolone antibiotics, uation insurance policy that will cover travel for
sometimes requiring parenteral therapy. recommended rabies postexposure prophylaxis.
Paratyphoid fever, a similar disease caused by
Salmonella enterica serovar Paratyphi A, B, and C, CHOLERA
has become increasingly prevalent in south Asia, Although extremely rare in travelers, cholera is a
but typhoid vaccines are not protective against possible risk in parts of India. Cholera vaccine is
this infection. not routinely recommended for most travelers on
typical tourist itineraries, but it may be consid-
JAPANESE ENCEPHALITIS ered for those at higher risk, such as those who
Although there has never been a published case of are visiting friends and relatives or traveling for
a traveler acquiring Japanese encephalitis (JE) in humanitarian aid work in disaster areas.
INDIA 481
8
4
2
and testing before and after travel. Use of bacil- Fasten seat belts when riding in cars and wear
lus Calmette-Guérin (BCG) vaccine in health care a helmet when riding bicycles or motorbikes.
workers who will have increased risk of tubercu- Avoid overcrowded buses, travel by bus into the
losis during travel has recently been proposed, interior or on curving, mountainous roads, and
although this recommendation remains contro- long-distance travel at night. Rural nighttime
versial (see Chapter 3, Tuberculosis). Access to driving should be discouraged, even when a paid
vaccine and lack of expertise in administering the driver has been hired. Air pollution is a problem
vaccine are also barriers. in the major cities, so those with chronic lung
disease or asthma may consider spending time
Other Issues outdoors when there is less traffic or staying in
Arrival in India for the first time may be shock- facilities outside major cities.
ing to travelers who have never ventured into Medical tourism is a growing industry in
the developing world. The crowds, the intense India. Many newer medical facilities have recently
4 colors, heat, and smells are striking and invade
all the senses at once. It is difficult to enjoy the
opened for travelers desiring cardiac, orthopedic,
dental, or plastic surgery or transplantations at a
beauty without being touched by the enormity substantially lower cost than in the United States.
of the poverty. The close juxtaposition of the The benefits and hazards require careful exam-
old and new is noteworthy. At times this can be ination (see Chapter 2, Medical Tourism). Health
overwhelming. care is quite variable in India and dependent on
Transportation in India remains problematic. the location.
While traveling through India, travelers should In general, travelers feel safe while in India.
be advised to carry food and beverages with Peddlers and promoters are aggressive with
them in the event of delays, which are almost tourists, however, and may require a firm “no.”
inevitable no matter the mode of transport. Travelers may want to avoid making eye contact
Traveling by train can be harrowing, particu- with a peddler or his goods, or they may risk hav-
larly having to force one’s way through the crowd ing someone follow them down the street trying
and onto the train. Travelers should make sure to sell them something. The stress of negotiating
to keep passports and valuables safe while in a one’s way through India makes this destination a
crowd. Roadways are some of the most hazard- place where having a close traveling companion
ous in the world, and India has a large number is important.
of traffic-
related deaths, including pedestrian It is always wise to pay attention to Department
deaths. Animals, rickshaws, motor scooters, of State advisories in case of issues that arise at
people, bicycles, trucks, and overcrowded buses some borders, or occasional increases in religious
compete for space in an unregulated free-for-all. tensions or terrorist activities.
BIBLIOGRAPHY
1. Baggett HC, Graham S, Kozarsky PE, Gallagher N, 4. Jensenius M, Han PV, Schlagenhauf P, Schwartz E, Parola
Blumensaadt S, Bateman J, et al. Pretravel health P, Castelli F, et al. Acute and potentially life-threatening
preparation among US residents traveling to India to tropical diseases in western travelers—a GeoSentinel
VFRs: importance of ethnicity in defining VFRs. J Travel multicenter study, 1996–2011. Am J Trop Med Hyg. 2013
Med. 2009 Mar-Apr;16(2):112–8. Feb;88(2):397–4 04.
2. Buhl MR, Lindquist L. Japanese encephalitis in travel- 5. Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J,
ers: review of cases and seasonal risk. J Travel Med. 2009 Butt F, Balakrishnan R, et al. Emergence of a new anti-
May;16:217–9. biotic resistance mechanism in India, Pakistan, and the
3. Epelboin L, Robert J, Tsyrina-Kouyoumdjian E, Laouira S, UK: a molecular, biological, and epidemiological study.
Meyssonnier V, Caumes E, et al. High rate of multidrug- Lancet Infect Dis. 2010 Sep;10(9):597–6 02.
resistant gram-negative bacilli carriage and infection in 6. Laxminarayan R, Chaudhury RR. Antibiotic Resistance
hospitalized returning travelers: a cross-sectional cohort in India: Drivers and Opportunities for Action. PLoS
study. J Travel Med. 2015 Sep-Oct;22(5):292–9. Med. 2016 Mar 2;13(3):e1001974.
7. Leder K, Torresi J, Brownstein JS, Wilson ME, Keystone JS, United States, 1999–╉2006. JAMA. 2009 Aug 26;302(8):
Barnett E, et al. Travel-╉associated illness trends and clus- 859–╉65.
ters, 2000–╉2010. Emerg Infect Dis. 2013 Jul;19(7):1049–╉73. 9. Shaw MT, Leggat PA, Chatterjee S. Travelling to India
8. Lynch MF, Blanton EM, Bulens S, Polyak C, for the Delhi XIX Commonwealth Games 2010. Travel
Vojdani J, Stevenson J, et al. Typhoid fever in the Med Infect Dis. 2010 May;8(3):129–╉38.
NEPAL
David R. Shlim
4
Gregg Taliaferro/Personal Collection
NEPAL 483
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NEPAL 485
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winds in the mountains. Helicopter rescue is democratic revolution led to a multiparty par-
billed at $4,000 per hour, with an average total liamentary system under a constitutional
cost of $8,000 to $10,000. monarch. Frustration with the rate of prog-
Two main clinics in Kathmandu specialize in ress in rural areas led to a Maoist insurrection
the care of foreigners in Nepal. Contact informa- and 10 years of low-╉grade but violent civil war.
tion is available on the International Society of A peace agreement was reached and the mon-
Travel Medicine website (www.istm.org). Hospital archy abolished in 2008, but an effective gov-
facilities have improved steadily over the years, ernment has yet to remain in place. The main
and general and orthopedic emergency surgery effect on tourists can be disruptions to their
are reliable and available in Kathmandu. The clos- schedule by demonstrations and strikes, but
est evacuation point for definitive care is Bangkok. none of the political tension has been aimed
at foreigners; Nepal remains a safe destina-
THE POLITICAL SITUATION tion to visit. However, visitors should moni-
4 The political situation in Nepal has been in
transition since 1990, when a mainly peaceful
tor the political situation while planning their
journey.
BIBLIOGRAPHY
1. Cave W, Pandey P, Osrin D, Shlim DR. Chemoprophylaxis 3. Schwartz E, Shlim DR, Eaton M, Jenks N, Houston R.
use and the risk of malaria in travelers to Nepal. J Travel The effect of oral and parenteral typhoid vaccination
Med. 2003 Mar-╉Apr;10(2):100–╉5. on the rate of infection with Salmonella typhi and
2. Hoge CW, Shlim DR, Echeverria P, Rajah R, Herrmann Salmonella paratyphi A among foreigners in Nepal.
JE, Cross JH. Epidemiology of diarrhea among expatriate Arch Intern Med. 1990 Feb;150(2):349–╉51.
residents living in a highly endemic environment. JAMA.
1996 Feb 21;275(7):533–╉8.
THAILAND
Gabrielle A. Benenson, Michael W. Benenson
1 night in Thailand, and the number of visitors Over the years, medical tourism to Thailand
continues to grow. Thai is a melodic, tonal lan- has increased, as the costs for treatment are much
guage that can be difficult to learn. Luckily, English lower and the quality of care is generally good. In
is commonly spoken at most popular destinations addition, Thailand has a large expatriate com-
in Thailand. Road signs, maps, and tourist guides munity and has also become a popular destina-
provide information in English and Thai. tion for retirees from around the world. The warm
With close to 68 million people and 76 politi- climate and low cost of living make Thailand an
cal provinces, Thailand is a geographically diverse attractive place to live.
country a little smaller than the state of Texas
(Map 4- 15). Because Thailand is close to the HEALTH ISSUES
equator, the climate is tropical and often hot
and humid. Flooding is always a possibility in Vaccine-Preventable Diseases
Thailand, and various regions are prone to flash All travelers should be up-to-date on their routine
floods. Monsoon rains fall from July through
October and can last until cooler, drier weather
vaccinations. In addition, travelers to Thailand
should also be vaccinated against hepatitis A 4
comes in November, making November through and hepatitis B. Typhoid and Japanese enceph-
February a popular time of year to visit. Thailand’s alitis vaccines should be considered based on
central location and major international airport potential risk.
in Bangkok make it an easy access point for other
destinations in Asia. RABIES
More than 9 million people live in the capi- Government-sponsored mass vaccination cam-
tal city of Bangkok, a major metropolis and cen- paigns for dogs and cats have reduced the prev-
ter of commerce. Bangkok is a mix of old and alence of rabies in Thailand, but rabies is still a
new—skyscrapers and waterways, bustling city small risk. Preexposure vaccination is only rec-
streets full of people, vendors, dogs, uneven ommended for travelers who have an occupation
sidewalks, and lots of traffic, in contrast to the that puts them at risk for exposure (such as veter-
fast, quiet, and modern monorail and subway inarians) or who will be traveling in areas where
systems. Tourists visit historic sites of glitter- it will be difficult to get immediate access to
ing grandeur such as one of Bangkok’s many care, including biologics (see Chapter 3, Rabies).
Buddhist temples or the Grand Palace to catch Hospitals and clinics in Bangkok cater to the
a glimpse of the Emerald Buddha. The main expatriate community and medical tourists, and
artery of Bangkok is the Chao Phraya River and rabies vaccine is readily available for preexposure
its canals, which provide access to tourist sites, and postexposure prophylaxis, although not all
boat tours, the floating market, and restaurants. hospitals in Thailand carry human rabies immune
Bangkok is a paradise of culinary delights, from globulin.
local fare at a sidewalk noodle stand to a fancy
5-star meal in a restaurant. Rounding off a visit JAPANESE ENCEPHALITIS
to Bangkok, many tourists will enjoy the plea- Japanese encephalitis ( JE) is endemic through-
sures of Thai nightlife, which includes a variety out Thailand (see Chapter 3, Japanese Ence
of bars and pubs, dance clubs, drag shows, and phalitis). Transmission occurs year-round, with
the famous red-light districts of Soi Cowboy, seasonal epidemics from May through October
Nana, and Patpong. in the northern provinces. JE vaccine is recom-
Visitors to Thailand will also likely visit Chiang mended for travelers who plan to visit Thailand
Mai in northern Thailand. The city, surrounded for ≥1 month and should be considered for
by a moat and defensive wall, has more than 300 those visiting for a shorter period but who have
temples, a popular night bazaar for great shop- an increased risk of JE virus exposure due to
ping, and easy access to the handicraft villages, their itineraries or activities. The highest rates
elephant nature parks, and outdoor adventures of human disease have been reported from the
that are popular in the region. Chiang Mai Valley. Several cases have been
THAILAND 487
84
reported among travelers who visited resort or If they decide to travel to Thailand, they should
coastal areas of southern Thailand. strictly follow steps to prevent mosquito bites.
Travelers should consult the CDC Travelers’
CHOLERA Health website (www.cdc.gov/travel) for the
Although extremely rare in travelers, cholera is a most current recommendations for Zika. See
possible risk in parts of Thailand. Cholera vaccine Chapter 3, Zika.
is not routinely recommended for most travel-
ers on typical tourist itineraries, but it is recom- Travelers’ Diarrhea
mended for adult travelers visiting an area with Although the Thai government and several non-
cholera activity within the last year that are prone governmental organizations are leading proj-
to recurrence of cholera epidemics. ects to provide clean water across Thailand,
and some hotels use their own filtration sys-
Vectorborne Diseases tems, water and food may still contain harm-
MALARIA
Malaria is endemic in specific areas of Thailand,
ful bacteria and other contaminants. Travelers
should practice food and water precautions
4
particularly the rural, forested areas that bor- and bring an antibiotic for self-treatment of
der Burma (Myanmar), Cambodia, and Laos and moderate to severe diarrhea. Because fluoro-
the provinces of Kalasin, Krabi (Plai Phraya dis- quinolone resistance is widespread in Thailand
trict), Nakhon Si Thammarat, Narathiwat, Pattani, and other areas of Southeast Asia, azithromy-
Phang Nga (including Phang Nga City), Rayong, cin may be preferred (see Chapter 2, Travelers’
Sakon Nakhon, Songkhla, Surat Thani, and Yala, Diarrhea).
especially the forest and forest fringe areas of
these provinces. Prophylaxis is recommended for Water and Soil Diseases
travelers visiting any of these areas (see Chapter 3, Melioidosis is highly endemic in northeast
Malaria). Transmission in Thailand occurs year- Thailand, and the highest number of leptospi-
round, and most cases are due to Plasmodium rosis cases can be found in the southern and
falciparum, with the rest due to P. vivax or mixed northeastern regions of the country. For both
infection. Atovaquone-proguanil or doxycycline diseases, most cases occur during the rainy sea-
are the recommended antimalarial drugs for trav- son from July through October. Adventure trav-
elers in Thailand. elers may be at increased risk because of their
exposure to water and soil. Travelers who visit
DENGUE endemic areas should avoid contact with soil
Dengue is endemic throughout Thailand (see and water that could be contaminated and
Chapter 3, Dengue) with large epidemics that ensure that any open wounds are covered to
occur every several years. Peak transmis- prevent exposure. When contact cannot be
sion occurs during the rainy season, although avoided, travelers should wear protective cloth-
cases occur year-round even in non-epidemic ing and footwear to reduce the risk of expo-
years. Travelers to Thailand should take mea- sure. Skin lacerations, abrasions, or burns that
sures to protect themselves from daytime mos- have been contaminated with soil or surface
quito bites to prevent dengue (see Chapter 2, water should be immediately and thoroughly
Protection against Mosquitoes, Ticks, & Other cleaned.
Arthropods).
Other Health and Safety Risks
ZIKA MEDICAL TOURISM
Zika is endemic in Thailand, but the risk to trav- Thailand is among the top medical tourist des-
elers is believed to be low. Because of the risk tinations worldwide. Travelers who plan to seek
of birth defects in babies born to women who medical care in Thailand should be advised to
were infected with Zika while pregnant, women research facilities and develop a plan before
who are pregnant should not travel to Thailand. departure, learn about health insurance coverage,
THAILAND 489
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and evaluate their health before making the trip crashes. Motorcycles are a cheap, easy, and pop-
(see Chapter 2, Medical Tourism). ular mode of transportation, but they are also
the most vulnerable vehicles on the road (see
SEXUALLY TRANSMITTED DISEASES AND Chapter 2, Injury Prevention). Travelers should
HIV/AIDS avoid riding motorcycles. If they must ride, they
Thailand is a popular destination for sex tour- should wear a helmet. Travelers should fasten seat
ism (see Chapter 3, Perspectives: Sex & Tourism) belts when riding in cars.
and, although illegal, sex work is practiced openly Thailand has experienced intermittent
across the country. A 100% condom program periods of political unrest throughout the coun-
with sex workers helped slow the spread of HIV try and ethnonationalist violence in the south-
and other sexually transmitted diseases; how- ern provinces. In 2014, a caretaker military
ever, approximately 450,000 people were living government was established to maintain peace,
with HIV/AIDS in Thailand in 2014. Although the develop a constitution, and facilitate democratic
4 number of new HIV infections has been decreas-
ing, HIV remains concentrated in key popula-
elections. However, the country remains polit-
ically divided, and travelers should be aware of
tions. Travelers should be aware of these risks the possibility of demonstrations, pay attention
and always use condoms during sex with partners to the local news, and monitor the US embassy
whose HIV status is unknown. website (http://bangkok.usembassy.gov) and
social media outlets to find out if and where pro-
SAFETY AND SECURITY tests and demonstrations may occur. Travelers
Approximately 14,000 people are killed on the should avoid these locations, since no one can
roads in Thailand each year, and a substantial predict whether protests will stay peaceful or
proportion (73% in 2012) are killed in motorcycle turn violent.
BIBLIOGRAPHY
1. Bureau of Epidemiology, Ministry of Public Health, 2015 [cited 2016 Apr. 2]; Available from: http://www.
Thailand. National disease surveillance (report tourism.go.th/home/details/11/221/24710.
506): Leptospirosis. Bangkok: 2014 2014 Sep 22. Available 5. Gongal G, Wright AE. Human rabies in the WHO
from: http://www.boe.moph.go.th/boedb/surdata/ Southeast Asia Region: forward steps for elimination.
506wk/y57/en/d43_0 957_en.pdf Adv Prev Med. 2011;Article ID 383870:1–5.
2. Central Intelligence Agency. The World Fact Book 6. Joint Commission International (JCI) [Internet].
2013-14. Washington, DC: CIA; 2013 [updated 2016 JCI-accredited organizations. Oak Brook (IL): JCI;
Sep; cited 2016 Apr. 9]; Available from: https://www.cia. 2016 [cited 2016 Sep. 25]; Available from: www.
gov/library/publications/the-world-factbook/geos/ jointcommissioninternational.org/about-jci/jci-
th.html. accredited-organizations/.
3. Chanlett-Avery E, Dolven B. Thailand: background and 7. National AIDS Committee, Royal Thai Government.
US relations. Washington, DC: 2014 2014 Sep 22. Report Thailand ending AIDS: Thailand AIDS response progress
No.: RL32593. report 2015. Geneva: UNAIDS, 2015 Apr 2.
4. Department of Tourism, Ministry of Tourism and 8. World Health Organization. Global status report on
Sports. International tourist arrivals to Thailand in 2015. road safety 2015. Geneva: 2015 2016 Apr 9. Report No.
Bangkok, Thailand: Ministry of Tourism and Sports; 978 92 4 156506 6.
VIETNAM
Caroline Uribe/Personal Collection
Sheryl Lyss, Jeffrey McFarland, Anthony Mounts
DESTINATION OVERVIEW
Vietnam has a population of approximately
Dalat, the Cu Chi tunnels, and floating markets of
the Mekong Delta are easy trips (see Map 4-╉16). 4
94 million people, of whom about two-╉thirds live in
rural areas. The total size of Vietnam is 127,243 mi2
(331,114 km2), slightly larger than New Mexico. It
HEALTH ISSUES
is located in Southeast Asia and borders China, Vaccine-╉Preventable Diseases
Laos, and Cambodia. Vietnam is divided into 63 Travelers to Vietnam should be up-╉to-╉date on rou-
provinces. The terrain and climate vary, partic- tine vaccines, including seasonal influenza. Travelers
ularly between the north and the south and the should also protect themselves by getting vacci-
mountainous and coastal areas. Once among the nated against typhoid and hepatitis A. Hepatitis B
poorest countries in the world, Vietnam has since protection is advised, especially for long-╉term trav-
achieved lower-╉middle income status. elers and expatriates, given the high prevalence of
Vietnam is an increasingly popular travel des- chronic HBV infection in the population.
tination for business and tourism. Travelers often
try to get a flavor for the entire country with a JAPANESE ENCEPHALITIS
trip of at least 10 days or combine their Vietnam Because Japanese encephalitis (JE) is endemic
travels with other nearby Southeast Asia destina- throughout Vietnam, JE vaccination is recom-
tions such as Angkor Wat in Cambodia or Luang mended for all travelers who spend ≥1 month in
Prabang in Laos. There is no shortage of attractions the country and should be considered for short-╉
in Vietnam, regardless of whether a traveler is inter- term travelers who plan on spending time out-
ested in touring historical sites, shopping in ethnic side urban areas and may be involved in activities
markets or traditional trade villages, trekking or bik- that expose them to the mosquitoes that trans-
ing in hills or valleys, seeing native wildlife, cruising mit JE virus. Such activities may include camping,
on the Mekong River or Ha Long Bay, scuba diving hiking, biking or other outdoor activities, or stay-
in the sea, relaxing at a spa resort, visiting art gal- ing in accommodations without air condition-
leries, or taking cooking lessons to understand the ing, screens, or bed nets (see Chapter 3, Japanese
regional variations of Vietnam’s cuisine. Encephalitis). JE has seasonal peaks from May
A typical itinerary might start in the north through October, and the highest rates of JE disease
and include visiting the capital, Hanoi; touring occur in the northern provinces around Hanoi and
the UNESCO World Heritage site, Ha Long Bay, the northwestern and northeastern provinces bor-
aboard a junk boat; and exploring the rice fields dering China. Personalized advice during a thor-
in Sapa or Mai Chau. In the coastal region, trav- ough pretravel consultation is important.
elers often go to Hue, Hoi An, Da Nang, and Nha
Trang, each with its own charms and unique per- Malaria
sonality. In the south, travelers often choose to see Malaria in Vietnam is caused by Plasmodium
Vietnam’s largest, busiest, and most modern city, falciparum and P. vivax. Cases and deaths have
Ho Chi Minh City. From there, Phu Quoc Island, decreased substantially in the past 15 years, and
VIETNAM 491
4
29
ongoing local transmission is primarily a concern poultry (such as chickens and ducks) and wild
in rural, forested areas that are not included in birds; avoid touching surfaces that have bird drop-
most tourist itineraries. There are rare cases in pings ( feces) or other bird fluids on them; and
the Mekong Delta and Red River Delta. There are avoid places where live birds are raised, kept, or
no cases in cities of Da Nang, Haiphong, Hanoi, sold, such as live bird markets.
Ho Chi Minh City (Saigon), Nha Tran, and Qui Travelers should eat only bird meat or products
Nhon. Travelers to the Mekong Delta should that have been thoroughly cooked. Any dishes that
take precautions to avoid mosquito bites, such contain uncooked (raw) or undercooked bird meat
as wearing loose-fitting clothing (long pants and or products such as eggs and poultry blood should
long-sleeved shirts) and using insect repellent be avoided. For example, egg yolks should not
(see Chapter 2, Protection against Mosquitoes, be runny or liquid. Travelers should also practice
Ticks, & Other Arthropods) but do not need to healthy habits to help stop the spread of germs by
take antimalarial drugs. Travelers the south- washing hands often with soap and clean water or
4 ern part of the country in the provinces of Dac
Lac, Gia Lai, Khanh Hoa, Kon Tum, Lam Dong,
using an alcohol-based hand sanitizer (containing
at least 60% alcohol) when soap and clean water are
Ninh Thuan, Song Be, and Tay Ninh should take not available and hands are not visibly dirty.
atovaquone-proguanil or doxycycline. Travelers
to other areas with malaria should take atova- Other Health and Safety Risks
quone-proguanil, doxycycline, or mefloquine (see FOODBORNE ILLNESSES
Chapter 3, Malaria). Drinking tap water should be avoided, as should
beverages with ice. Travelers should avoid eating
Dengue and Zika raw or undercooked meat or seafood, uncooked
Dengue is endemic in Vietnam and, although peak vegetables, and raw fruits that cannot be peeled by
transmission occurs during the summer rainy the traveler. Travelers should be cautious about eat-
season, dengue virus transmission occurs year- ing food or drinking beverages from street vendors.
round. Zika is also endemic in Vietnam, but the Travelers with seafood allergies should be particu-
risk to travelers is believed to be low. Because of larly cautious in Vietnam, given the common use of
the risk of birth defects in babies born to women fish and other seafood sauces in many dishes.
infected with Zika while pregnant, women who Travelers should be particularly careful not to
are pregnant should not travel to Vietnam. If they consume dishes containing uncooked blood of pigs
decide to travel to Vietnam, they should strictly or other animals because of the risk of trichinellosis
follow steps to prevent mosquito bites. Travelers and Streptococcus suis infections (meningitis or sep-
should consult the CDC Travelers’ Health website ticemia). One popular traditional Vietnamese dish,
(www.cdc.gov/travel) for the most current recom- tiet canh, is made of coagulated, fresh, raw blood
mendations for Zika. mixed with cooked pieces of meat. It can be difficult
to know just by looking if a dish contains uncooked
Avian Influenza blood. Ask, and when in doubt do not eat it.
Vietnam has reported sporadic cases of human
infection with avian influenza A (H5N1) virus. ENVIRONMENTAL EXPOSURES
H5N1 is endemic in domestic poultry in Vietnam, Skin rashes may result from fungal infections or
with continued sporadic and geographically dis- the combination of heat and humidity. Sunstroke,
persed poultry outbreaks. sunburn, and dehydration can be problems for
A novel avian influenza A (H7N9) virus was travelers. Efforts should be made to keep clothes,
identified in China in 2013, including in a prov- shoes, and linens clean and dry. Use of a broad-
ince bordering Vietnam. To date, no animals or spectrum sunscreen with SPF ≥15 that protects
humans have been identified in Vietnam with this against both UVA and UVB is recommended; trav-
strain of avian influenza virus. elers should keep well hydrated and minimize sun
To avoid infection with avian influenza viruses, exposure by using clothing, hats, and umbrellas.
travelers to an area affected by avian influenza Travelers with allergies or asthma may find
should avoid direct contact with birds, including their conditions are exacerbated because of high
VIETNAM 493
49
levels of particulate matter and indoor air pollu- turning back. Pedestrians will observe that motor-
tion, especially in Hanoi and Ho Chi Minh City. The bikes and cars will go around them much like a
US Department of State in partnership with the school of fish will part when it encounters an
US Environmental Protection Agency monitors object, and then regroup. Note that motorbikes
air quality in Vietnam (https://airnow.gov/index. and sometimes cars will travel on the wrong side
cfm?action=airnow.global_summary#Vietnam). of the street (against oncoming traffic) as well
Short-term exposure to these levels of air pollu- as on sidewalks, so travelers should be urged to
tion can irritate the eyes and throat, and those always look in both directions and be particularly
with underlying cardiorespiratory illness, includ- cautious when crossing at corners.
ing asthma, chronic obstructive pulmonary dis-
ease, or coronary heart failure, may find their Medical Care in Vietnam
condition exacerbated. In addition, exposure to Several private medical practices, clinics, and hos-
high levels of air pollution significantly increases pitals that serve foreigners are available in Hanoi
4 the risk of respiratory tract infections, includ-
ing sinusitis, otitis, bronchitis, and pneumonia.
and Ho Chi Minh City. However, blood transfusion
services, inpatient care, and specialty services are
Children and the elderly are the most vulnerable. generally not of high quality. Thus, travelers should
ensure that they have adequate medical evacua-
ROAD SAFETY tion insurance in case they need to be evacuated
To avoid motor vehicle–related injuries, travelers to Singapore or Bangkok where high-quality spe-
should fasten seat belts when riding in cars and cialty services are provided (see Chapter 2, Travel
wear a safety helmet when riding bicycles and Insurance, Travel Health Insurance, & Medical
motorbikes. Pedestrians may find road conditions Evacuation Insurance). To ensure the quality of any
in Vietnam to be challenging because of an appar- needed medications, travelers may want to con-
ent lack of rules and the large number of vehicles sider purchasing them through an expatriate or
and motorcycles sharing the road. Travelers are international travel clinic, even if the price is higher.
advised to walk facing traffic and, when crossing If a traveler is taking prescription medicine, he or
the street, to proceed at a consistent walking pace she should bring enough medication for the entire
with no sudden direction changes, such as quickly trip, in the original bottle, and with the prescription.
BIBLIOGRAPHY
1. Carrique-Mas JJ, Bryant JE. A review of foodborne bacte- 6. Manabe T, Yamaoka K, Tango T, Binh NG, Co DX, Tuan
rial and parasitic zoonoses in Vietnam. EcoHealth. 2013 ND, et al. Chronological, geographical, and seasonal
Dec;10(4):465–89. trends of human cases of avian influenza A (H5N1) in
2. Central Intelligence Agency. The World Fact Book: Vietnam, 2003–2014: a spatial analysis. BMC Infect Dis
Vietnam. CIA; 2016 [updated 2016 Sep.; cited 2016 Apr. 12]; 2016 Feb 4;16(64):1391–8.
Available from: https://www.cia.gov/library/publications/ 7. Phung D, Hien TT, Linh HN, Luong LM, Morawska
resources/the-world-factbook/geos/vm.html. L, Chu C, et al. Air pollution and risk of respiratory
3. Cuong HQ, Vu NT, Cazelles B, Boni MF, Thai KT, and cardiovascular hospitalizations in the most
Rabaa MA, et al. Spatiotemporal dynamics of dengue populous city in Vietnam. Sci Total Environ 2016 Jul
epidemics, southern Vietnam. Emerg Infect Dis. 2013 1;557-558(2016):322–30.
Jun;19(6):945–53. 8. Roberts L. In Vietnam, an anatomy of a measles out-
4. Hsu A, Emerson J, Levy M, de Sherbinin A, Johnson L, break. Science. 2015 May 29;348(6238):962.
Malik O, et al. The 2014 Environmental Performance 9. World Health Organization Western Pacific Region
Index: country profiles, Viet Nam. New Haven (CT): Yale [Internet]. WHO representative office in Vietnam.
Center for Environmental Law and Policy; 2014 [cited Hanoi: World Health Organization; 2014 [cited 2016
2016 Sep. 25]; Available from: http://epi2012.yale.edu/ Sep. 25]; Available from: http://www.wpro.who.int/
epi/country-profile/viet-nam. vietnam/en.
5. Huong VT, Hoa NT, Horby P, Bryant JE, Van Kinh N, 10. Yen NT, Duffy MR, Hong NM, Hien NT, Fischer M,
Toan TK, et al. Raw pig blood consumption and poten- Hills SL. Surveillance for Japanese encephalitis
tial risk for Streptococcus suis infection, Vietnam. in Vietnam, 1998–2007. Am J Trop Med Hyg. 2010
Emerg Infect Dis. 2014 Nov;20(11):1895–8. Oct;83(4):816–9.
Post-Travel Evaluation
GENERAL APPROACH TO THE
RETURNED TRAVELER
Jessica K. Fairley
5
to sub- Saharan Africa presenting with fever, Underlying Medical Illness
malaria was the most common specific diag- Comorbidities can affect the susceptibility to
nosis. On the other hand, febrile patients after infection, as well as the clinical manifestations
travel to Latin America or Southeast Asia were and severity of illness. An increasing number of
much more likely to have dengue. The duration immunosuppressed people (due to organ trans-
of travel is also important, since the risk of a plants, immune- modulating medications, HIV
travel-related illness increases with the length infection, or other primary or acquired immu-
of the trip. A tropical medicine specialist can nodeficiencies) are international travelers (see
assist with the differential diagnosis and may be Chapter 8, Immunocompromised Travelers).
aware of outbreaks or the current prevalence of
an infectious disease in an area. The 2014–2015 Vaccines Received and
Ebola virus epidemic in West Africa highlighted Prophylaxis Used
the importance of epidemiologic factors and The history of vaccinations and malaria chemo-
travel itineraries in managing patients and pro- prophylaxis should be reviewed when evaluating
tecting staff and the community. an ill returned traveler. Less than half of US trav-
elers to developing countries seek pretravel med-
Timing of Illness in Relation ical advice and may not have received vaccines
to Travel or taken antimalarial drugs. Although adherence
Most ill travelers will seek medical attention to malaria chemoprophylaxis does not rule out
within 1 month of return from their destination, the possibility of malaria, it reduces the risk and
because most common travel-related infections increases the likelihood of an alternative diagno-
have short incubation periods. Occasionally, how- sis. Fever and a rash in a traveler without measles
ever, infections such as schistosomiasis, leishman- vaccination would raise concern about mea-
iasis, or tuberculosis can manifest months or even sles. The most common vaccine-preventable dis-
years later. Therefore, in unusual cases, a detailed eases found in a large 2010 GeoSentinel study of
history that extends beyond a few months before returned travelers included enteric fever (typhoid
presentation can be helpful. The most common and paratyphoid), viral hepatitis, and influenza.
travel-related infections with short incubation More than half of these patients with vaccine-
periods are listed in Table 5-1. preventable diseases were hospitalized.
Freshwater swimming or other water contact can sections in Chapter 3 for more information on
put the patient at risk for schistosomiasis, lepto- these emerging infections.
spirosis, and other diseases. Delayed onset and chronic cough after travel
The activities during a trip and the type of could be tuberculosis, especially in a long-term
accommodations can also influence the risk for traveler or health care worker. Other uncom-
acquiring certain diseases. Travelers who visit mon infections causing respiratory illness after
friends and relatives are at higher risk of malaria, travel to specific regions are histoplasmosis, coc-
typhoid fever, and certain other diseases, often cidioidomycosis, Q fever, plague, tularemia, and
because they stay longer, travel to more remote melioidosis. Helminth infections that produce
destinations, have more contact with local water pulmonary disease include strongyloidiasis, para-
sources, and do not seek pretravel advice (see gonimiasis, and schistosomiasis.
Chapter 8, Immigrants Returning Home to Visit
Friends & Relatives [VFRs]). Someone backpack- Eosinophilia
ing and camping in rural areas will also have a Eosinophilia in a returning traveler suggests a pos-
higher risk of certain diseases than those staying sible helminth infection. Allergic diseases, hema-
in luxury, air-conditioned hotels. tologic disorders, and a few other viral, fungal, and
5 COMMON SYNDROMES
protozoan infections can also cause eosinophilia.
Fever and eosinophilia can be present during
The most common clinical presentations after pulmonary migration of parasites, such as hook-
travel to developing countries include systemic worm, Ascaris, and Strongyloides. Acute schistoso-
febrile illness, diarrheal illness, and dermato- miasis, or Katayama syndrome, is also a cause of
logic conditions. These are described in more fever and eosinophilia and can be associated with
detail in the following sections of this chapter pulmonary infiltrates. Other parasitic infections
(Fever in Returned Travelers, Persistent Travelers’ associated with eosinophilia include chronic
Diarrhea, and Skin & Soft Tissue Infections in strongyloidiasis, visceral larval migrans, lym-
Returned Travelers). Fever in a traveler return- phatic filariasis, and acute trichinellosis. Findings
ing from a malaria-endemic country needs to be in an outbreak of sarcocystosis in travelers return-
evaluated immediately. ing from Tioman Island, Malaysia, included myal-
gia and eosinophilia. The affected travelers had
Respiratory Complaints eosinophilic myositis on muscle biopsy.
Respiratory complaints are frequent among
returned travelers and are typically associated MANAGEMENT
with common respiratory viruses (see Chapter 2, Most post-travel illnesses can be managed on an
Respiratory Infections). Influenza is among the outpatient basis, but some patients, especially
most common vaccine-preventable diseases asso- those with systemic febrile illnesses, may need to
ciated with international travel. Severe respiratory be hospitalized. Furthermore, potentially severe,
symptoms— especially associated with fever— transmissible infections such as Ebola or MERS
in a returned traveler should alert the physician require enhanced infection control measures and
to common infectious diseases such as seasonal may require higher levels of care. Severe presen-
influenza, bacterial pneumonia, and malaria but tations, such as acute respiratory distress, men-
could also suggest more unusual entities, such as tal status change, and hemodynamic instability,
Legionnaires’ disease. Emerging respiratory infec- require inpatient care. Clinicians should have
tions such as Middle East respiratory syndrome a low threshold for admitting febrile patients if
(MERS) and H7N9 avian influenza from China malaria is suspected. Confirmation of diagno-
should be in the differential if the travel history sis can be delayed, and complications can occur
is appropriate and respiratory symptoms do not rapidly. Management in an inpatient setting is
have a clear alternative diagnosis. In these sus- especially important if the patient may not reli-
pected cases, local public health authorities and ably follow up or when no one is at home to
CDC should be alerted immediately. See relevant assist if symptoms worsen quickly. Consultation
with an infectious diseases physician is recom- may need to be involved for transmissible, high-╉
mended in severe travel-╉related infections, when consequence infections. CDC provides on-╉ call
management is complicated, or when the diag- assistance with the diagnosis and management
nosis remains unclear. A tropical medicine or of parasitic infections at 404-╉718-╉4745 for par-
infectious disease specialist should be involved asitic infections other than malaria or 770-╉488-╉
in cases that require specialized treatment, such 7788 (toll-╉free at 855-╉856-╉4713) for malaria, during
as neurocysticercosis, severe malaria, and leish- business hours. After business hours, call the CDC
maniasis, among others. Public health authorities Emergency Operations Center at 770-╉488-╉7100.
BIBLIOGRAPHY
1. Boggild AK, Castelli F, Gautret P, Torresi J, von 6. Hendel-╉Paterson B, Swanson SJ. Pediatric travelers vis-
Sonnenburg F, Barnett ED, et al. Vaccine preventable iting friends and relatives (VFR) abroad: illnesses, barri-
diseases in returned international travelers: results from ers and pre-╉travel recommendations. Travel Med Infect
the GeoSentinel Surveillance Network. Vaccine. 2010 Dis. 2011 Jul;9(4):192–╉203.
Oct 28;28(46):7389–╉95. 7. Leder K, Torresi J, Libman MD, Cramer JP, Castelli F,
2. CDC. Notes from the field: acute muscular sarcocystosis
among returning travelers—╉Tioman Island, Malaysia, 2011.
MMWR Morb Mortal Wkly Rep. 2012 Jan 20;61(2):37–╉8.
Schlagenhauf P, et al. GeoSentinel surveillance of illness
in returned travelers, 2007–╉2011. Ann Intern Med. 2013
Mar 19;158(6):456–╉68.
5
3. Chen LH, Wilson ME, Davis X, Loutan L, Schwartz E, 8. Ryan ET, Wilson ME, Kain KC. Illness after international
Keystone J, et al. Illness in long-╉term travelers vis- travel. N Engl J Med. 2002 Aug 15;347(7):505–╉16.
iting GeoSentinel clinics. Emerg Infect Dis. 2009 9. Schulte C, Krebs B, Jelinek T, Nothdurft HD, von
Nov;15(11):1773–╉82. Sonnenburg F, Loscher T. Diagnostic significance of
4. Fairley JK, Kozarsky PE, Kraft CS, Guarner J, Steinberg JP, blood eosinophilia in returning travelers. Clin Infect Dis.
Anderson E, et al. Ebola or Not? Evaluating the ill trav- 2002 Feb 1;34(3):407–╉11.
eler from Ebola-╉affected countries in West Africa. Open 10. Wilson ME, Weld LH, Boggild A, Keystone JS,
Forum Infect Dis. 2016 Jan 18;3(1ofw005). Kain KC, von Sonnenburg F, et al. Fever in returned
5. Hamer DH, Connor BA. Travel health knowledge, travelers: results from the GeoSentinel Surveillance
attitudes and practices among United States travelers. Network. Clin Infect Dis. 2007 Jun 15;44(12):1560–╉8.
J Travel Med. 2004 Jan–╉Feb;11(1):23–╉6.
common diagnoses. A large proportion of ill- differential diagnosis. Most serious febrile infec-
nesses in returned travelers is caused by com- tions manifest within the first month after return
mon, cosmopolitan infections (such as bacterial from tropical travel, yet infections related to travel
pneumonia or pyelonephritis), so these must exposures can occasionally occur months or even
be considered along with unusual infections. >1 year after return. In the United States, >90% of
Because the geographic area of travel deter- reported cases of Plasmodium falciparum malaria
mines the relative likelihood of major causes of manifest within 30 days of return, but almost half
fever, it is essential to identify where the febrile of cases of P. vivax malaria manifest >30 days after
patient has traveled and lived (Table 5-2). Details return.
about activities (such as freshwater exposure in
schistosomiasis-endemic areas, animal bites, sex-
ual activities, tattoos, or local medical care with FINDINGS REQUIRING URGENT
injections) and accommodations in areas with ATTENTION
malaria (bed nets, window screens, air condi- Presence of associated signs, symptoms, or labora-
tioning) during travel may provide useful clues. tory findings can focus attention on specific infec-
Preparation before travel (such as hepatitis tions (Table 5-4). Findings that should prompt
A vaccine or yellow fever vaccine) will markedly urgent attention include hemorrhage, neurologic
reduce the likelihood of some infections, so this impairment, and acute respiratory distress. Even
is a relevant part of the history. A history of travel if an initial physical examination is unremarkable,
and residence should be an integral part of every it is worth repeating the examination, as new
medical history. findings may appear that will help in the diagnos-
Because each infection has a characteristic tic process (such as skin lesions or tender liver).
incubation period (although the range is extremely Although most febrile illnesses in returned trav-
wide with some infections), the time of expo- elers are related to infections, the clinician should
sures needs to be defined in different geographic bear in mind that other problems, including pul-
areas (Table 5-3). This knowledge will allow the monary emboli and drug hypersensitivity reac-
clinician to exclude some infections from the tions, can be associated with fever.
Spotted fever rickettsiosis Few days to 2–3 weeks Causative species vary by region
Encephalitis, arboviral; enteric fever; See above incubation periods for See above distribution for relevant
acute HIV; leptospirosis; malaria relevant diseases diseases
(continued)
Amebic liver abscess, hepatitis E, See above incubation periods for See above distribution for relevant
malaria, acute schistosomiasis relevant diseases diseases
Leishmaniasis, visceral 2–10 months (10 days to years) Asia, Africa, Latin America, southern
Europe, and the Middle East
5
Table 5-4. Common clinical findings and associated infections
COMMON CLINICAL FINDINGS INFECTIONS TO CONSIDER AFTER TROPICAL TRAVEL
Fever and rash Dengue, chikungunya, Zika, rickettsial infections, enteric fever (skin lesions
may be sparse or absent), acute HIV infection, measles
Undifferentiated fever and normal Dengue, malaria, rickettsial infection, enteric fever, chikungunya, Zika
or low white blood cell count
Fever and hemorrhage Viral hemorrhagic fevers (dengue and others), meningococcemia,
leptospirosis, rickettsial infections
Fever and eosinophilia Acute schistosomiasis, drug hypersensitivity reaction, fascioliasis and
other parasitic infections (rare)
Fever and pulmonary infiltrates Common bacterial and viral pathogens, legionellosis, acute
schistosomiasis, Q fever, leptospirosis
Fever and altered mental status Cerebral malaria, viral or bacterial meningoencephalitis, African
trypanosomiasis, scrub typhus
Fever persisting >2 weeks Malaria, enteric fever, Epstein-Barr virus infection, cytomegalovirus
infection, toxoplasmosis, acute HIV infection, acute schistosomiasis,
brucellosis, tuberculosis, Q fever, visceral leishmaniasis (rare)
Fever with onset >6 weeks after Plasmodium vivax or ovale malaria, acute hepatitis (B, C, or E), tuberculosis,
travel amebic liver abscess
Fever accompanied by any of the following Travelers may acquire infections caused by
syndromes deserves further scrutiny, because it common bacteria that are unusually resistant.
may indicate a disease of public health importance: Bacteria that produce extended- spectrum β-
lactamases and carbapenem- resistant Entero
• Skin rash with or without conjunctivitis bacteriaceae, including bacteria expressing the
• Difficulty breathing metalloprotease NDM-1, which confers resistance
to many available antibiotics, have been found
• Shortness of breath in infections acquired during travel, most often
• Persistent cough related to medical care (both elective and emer-
gency). Enteric fever, the term used to describe
• Decreased consciousness either typhoid or paratyphoid fever, has also
• Bruising or unusual bleeding (without previ- become increasingly resistant to fluoroquinolo-
ous injury) nes (see Chapter 3, Typhoid & Paratyphoid Fever).
The tables in this section identify some com-
• Persistent diarrhea mon infections by presenting findings or other
• Persistent vomiting (other than air or motion characteristics, by area of travel and by incu-
sickness) bation periods. These highlight only the most
common infections. The listed references and
5
• Jaundice websites should be consulted for more detailed
• Paralysis of recent onset information. In most studies, a specific cause for
fever is not identified in about 25% of returned
People who travel to visit friends and relatives
travelers.
(VFRs) often do not seek pretravel medical advice
and are at higher risk for some diseases than other
travelers. A review of GeoSentinel Surveillance KEEP IN MIND
Network data showed that a larger proportion of
• Initial symptoms of life-threatening and self-
immigrant VFRs than tourist travelers presented limited infections can be identical.
with serious (requiring hospitalization), poten-
tially preventable travel-related illnesses. • Fever in returned travelers is often caused by
common, cosmopolitan infections, such as
CHANGE OVER TIME pneumonia and pyelonephritis, which should
Clinicians have access to resources on the Internet not be overlooked in the search for exotic
that provide information about geographic- diagnoses.
specific risks, disease activity, and other useful • Travelers may be infected with highly drug-
information, such as drug-susceptibility patterns resistant pathogens.
for pathogens. Infectious diseases are dynamic, as
demonstrated by the introduction and spread of • Patients with malaria may be afebrile at the
chikungunya virus in the Americas beginning in time of evaluation but typically give a history
late 2013 and the rapid spread of Zika virus in the of fever or chills.
Americas in 2015 and 2016. In contrast, because • Malaria is the most common cause of
of the wide use of vaccine, hepatitis A infection is acute undifferentiated fever after travel
now infrequently seen in travelers. to sub-Saharan Africa and to some other
Common infections in returned travelers may tropical areas.
be seen at unexpected times of the year. Because
influenza transmission can occur throughout the
• Malaria, especially P. falciparum, can prog-
ress rapidly. Diagnostic studies should be done
year in tropical areas, and the peak season in the
promptly and treatment instituted immediately
Southern Hemisphere is May to August, clini-
if malaria is diagnosed (see Chapter 3, Malaria).
cians in the Northern Hemisphere must be alert
to the possibility of influenza outside the usual • A history of taking malaria chemoprophylaxis
US influenza season. does not exclude the possibility of malaria.
5 BIBLIOGRAPHY
1. Bottieau E, Clerinx J, Schrooten W, Van den Enden E, 5. Leder K, Torresi J, Libman MD, Cramer JP, Castelli F,
Wouters R, Van Esbroeck M, et al. Etiology and out- Schlagenhauf P, et al. GeoSentinel surveillance of illness
come of fever after a stay in the tropics. Arch Intern in returned travelers, 2007–╉2011. Ann Intern Med. 2013
Med. 2006 Aug 14-╉28;166(15):1642–╉8. Mar 19;158(6):456–╉68.
2. Hassing RJ, Alsma J, Arcilla MS, van Genderen PJ, 6. Mendelson M, Han PV, Vincent P, von
Stricker BH, Verbon A. International travel and acqui- Sonnenburg F, Cramer JP, Loutan L, et al. Regional
sition of multidrug-╉resistant Enterobacteriaceae: a �variation in travel-╉related illness acquired in Africa,
systematic review. Euro Surveill 2015;20(47):pii=30074. March 1997–╉May 2011. Emerg Infect Dis. 2014
DOI: http://╉dx.doi.org/╉10.2807/╉1560-╉7917. Apr;20(4):532–╉41.
ES.2015.20.47.30074. 7. Ryan ET. Troubling news from Asia about treating
3. Jensenius M, Davis X, von Sonnenburg F, Schwartz E, enteric fever: a coming storm. Lancet Infect Dis 2016
Keystone JS, Leder K, et al. Multicenter GeoSentinel May;16(5):508–╉9.
analysis of rickettsial diseases in international travelers, 8. Ryan ET, Wilson ME, Kain KC. Illness after international
1996–╉2008. Emerg Infect Dis. 2009 Nov;15(11):1791–╉8. travel. N Engl J Med. 2002 Aug 15;347(7):505–╉16.
4. Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, 9. Wilson ME, Weld LH, Boggild A, Keystone JS, Kain
Butt F, Balakrishnan R, et al. Emergence of a new anti- KC, von Sonnenburg F, et al. Fever in returned travel-
biotic resistance mechanism in India, Pakistan, and the ers: results from the GeoSentinel Surveillance Network.
UK: a molecular, biological, and epidemiological study. Clin Infect Dis. 2007 Jun 15;44(12):1560–╉8.
Lancet Infect Dis. 2010 Sep;10(9):597–╉602.
Although most cases of travelers’ diarrhea are of the following broad categories: 1) persistent
acute and self-╉ limited, a certain percentage �infection or coinfection with a second organ-
of travelers will develop persistent (>14 days) ism not �targeted by initial therapy, 2) previously
gastrointestinal symptoms (see Chapter 2, undiagnosed gastrointestinal disease unmasked
Travelers’ Diarrhea). The pathogenesis of per- by the enteric infection, or 3) a postinfectious
sistent travelers’ diarrhea generally falls into one phenomenon.
of chronic diarrhea. Colorectal cancer should be parasitic, and viral enteropathogens. This may be
considered, particularly in patients passing occult particularly helpful when persistent diarrhea is
or gross blood rectally or with the onset of a new caused by a parasite or C. difficile.
iron-deficiency anemia. Overall, these assays have high sensitivity and
specificity; however, the clinical and financial
POSTINFECTIOUS effect of these molecular panels has not yet been
PHENOMENA fully assessed, and molecular testing may, in some
In a certain percentage of patients who pres- cases, detect colonization rather than infection,
ent with persistent gastrointestinal symptoms, making it difficult for clinicians to interpret the
no specific source will be found. Patients may results.
experience temporary enteropathy following an Traditional methods of microbial diagno-
acute diarrheal infection, with villous atrophy, sis have relied on the use of microscopy; 3 or
decreased absorptive surface area, and disaccha- more stool specimens should be examined for
ridase deficiencies. This can lead to osmotic diar- ova and parasites, including acid-fast stains for
rhea, particularly when large amounts of lactose, Cryptosporidium, Cyclospora, and Cystoisospora,
sucrose, sorbitol, or fructose are consumed. Use of as well as Giardia antigen testing; C. difficile toxin
5 antimicrobial medications during the initial days
of diarrhea may also lead to alterations in intesti-
assay; and a D-xylose absorption test to deter-
mine if nutrients are being properly absorbed. If
nal flora and diarrhea symptoms. underlying gastrointestinal disease is suspected,
Occasionally, the onset of symptoms of irri- an initial evaluation should include serologic
table bowel syndrome (IBS) can be traced to an tests for celiac and inflammatory bowel disease.
acute bout of gastroenteritis. IBS that develops Subsequently, other studies to visualize both the
after acute enteritis has been termed postinfec- upper and lower gastrointestinal tracts, with biop-
tious (PI)-IBS. To be labeled PI-IBS, symptoms sies, may be indicated.
should follow an episode of gastroenteritis or trav-
elers’ diarrhea if the work-up for microbial patho- MANAGEMENT
gens and underlying gastrointestinal disease is Dietary modifications may help those with mal-
negative. Whether the use of antibiotics to treat absorption. If stools are bloody or when disease
acute TD decreases or increases the likelihood of is caused by C. difficile, antidiarrheal medica-
PI-IBS is unknown. tions such as loperamide or diphenoxylate should
not be used in children and should be used cau-
EVALUATION tiously, if at all, in adults. Probiotic medications
Diagnostics to determine specific microbial have been shown to reduce the duration of per-
etiologies in cases of persistent diarrhea have sistent diarrhea among children in some set-
advanced in the past number of years. Among tings. Antimicrobial medications may be useful
the most useful tools in microbial diagnosis is in treating persistent diarrhea caused by para-
the high-throughput multiplex DNA extraction sites. Nonabsorbable antibiotics may help if small
PCR. This technology uses a single stool speci- intestinal bacterial overgrowth accompanies the
men to simultaneously detect multiple bacterial, symptom complex.
BIBLIOGRAPHY
1. Connor BA. Sequelae of traveler’s diarrhea: focus on 4. Libman MD, Gyorkos TW, Kokoskin E, Maclean JD.
postinfectious irritable bowel syndrome. Clin Infect Dis. Detection of pathogenic protozoa in the diagnostic
2005 Dec 1;41 (Suppl 8):S577–86. laboratory: result reproducibility, specimen pooling,
2. Connor BA. Chronic diarrhea in travelers. Curr Infect and competency assessment. J Clin MIcrobiol. 2008
Dis Rep. 2013 Jun;15(3):203–10. Jul;76(7):2200–5.
3. Hanevik K, Dizdar V, Langeland N, Hausken T. 5. Mintz ED, Weber JT, Guris D, Puhr N, Wells JG,
Development of functional gastrointestinal Yashuk JC, et al. An outbreak of Brainerd diar-
disorders after Giardia lamblia infection. BMC rhea among travelers to the Galapagos Islands.
Gastroenterol 2009 Apr. 21;9:27. J Infect Dis. 1998 Apr;177(4):1041–5.
6. Norman FF, Perez-Molina J, Perez de Ayala A, Jimenez BC, of developing inflammatory bowel disease.
Navarro M, Lopez-Velez R. Clostridium difficile-associated Gastroenterology. 2008 Sep;135(3):781–6.
diarrhea after antibiotic treatment for traveler’s diarrhea. 9. Schwille-Kiuntke J, Mazurak N, Enck P. Systematic
Clin Infect Dis. 2008 Apr 1;46(7):1060–3. review with meta-analysis: post-infectious irritable
7. Platts-Mills JA, Operario DJ, Houpt ER. Molecular diag- bowel syndrome after travellers’ diarrhoea. Aliment
nosis of diarrhea: current status and future potential. Pharmacol Ther 2015 Jul;41(11):1029–37.
Curr Infect Dis Rep. 2012 Feb;14(1):41–6. 10. Spiller R, Garsed K. Postinfectious irrita-
8. Porter CK, Tribble DR, Aliaga PA, Halvorson HA, ble bowel syndrome. Gastroenterology. 2009
Riddle MS. Infectious gastroenteritis and risk May;136(6):1979–88.
Dengue 3.4
Leishmaniasis 3.3
Myiasis 2.7
Scabies 1.5
Cellulitis 1.5
1
Modified from Lederman ER, Weld LH, Elyazar IR, et al. Dermatologic conditions of the ill returned
traveler: an analysis from the GeoSentinel Surveillance Network. Int J Infect Dis. 2008;12(6):593–602.
tropics, particularly when good hygiene cannot In addition to pyoderma, cellulitis or erysip-
be maintained. Organisms responsible are com- elas may complicate excoriated insect bites or
monly Staphylococcus aureus or Streptococcus any trauma to the skin. Cellulitis and erysipelas
pyogenes. Drug-resistant organisms are frequently manifest as areas of skin erythema, edema, and
acquired in the tropics. The presentations can warmth in the absence of an underlying suppu-
include pyoderma or impetigo, abscess forma- rative focus. Unlike cellulitis, erysipelas lesions
tion, erysipelas, cellulitis, lymphangitis, or ulcer- are raised, there is a clear line of demarcation at
ation. Furunculosis, or recurrent pyoderma, may the edge of the lesion, and the lesions are more
be the result of colonization of the skin and nasal likely to be associated with fever. Cellulitis, on
mucosa with S. aureus. Boils may continue to the other hand, is more likely to be associated
occur weeks or months after a traveler returns with lymphangitis. Cellulitis and erysipelas are
and, if associated with S. aureus, definitive treat- usually caused by β-hemolytic streptococci
ment usually involves decolonization with nasal (such as groups A, B, C, G, and F Streptococcus).
mupirocin, a skin wash with an antimicrobial skin S. aureus (including methicillin-resistant strains)
cleanser, and less often, an oral antibiotic combi- and gram- negative aerobic bacteria may also
nation including rifampin. cause cellulitis.
Another common bacterial skin infection, system may be involved. Eosinophilia is common,
especially in children in the tropics, is impetigo and a definitive diagnosis is often difficult.
due to S. aureus or S. pyogenes. Impetigo is a highly
contagious superficial skin infection that gener- MACULAR LESIONS
ally appears on the arms, legs, or face as “honey- Macular lesions are common and often nonspe-
colored” or golden crusting formed from dried cific and may be due to drug reactions or viral
serum. Local care and a topical antibiotic such exanthems. Superficial mycoses, such as tinea
as mupirocin may be used, although a systemic versicolor and tinea corporis, may also present as
antibiotic may be required. Emerging antibiotic macular lesions.
resistance among staphylococci and streptococci Tinea versicolor, due to Malassezia furfur
complicates antimicrobial options. (previously Pityrosporum ovale), is characterized
Myiasis presents as a painful lesion simi- by asymptomatic hypopigmented or hyperpig-
lar to a boil. It is caused by infestation with the mented oval, slightly scaly patches measuring
larval stage of the African tumbu fly (Cordylobia 1–3 cm that are found on the upper chest, neck,
anthropophaga) or the Latin American bot fly and back. Diagnosis may be made by examina-
(Dermatobia hominis). At the center of the lesion tion with a Wood’s lamp or by placing a drop of
is a small punctum that allows the larva to
breathe. Extraction of the fly larva can be difficult,
methylene blue on a slide onto which clear cellu-
lose acetate tape is placed sticky side down, after
5
especially of the bot fly; extraction may be facili- it has been touched briefly to the skin lesions to
tated by first asphyxiating the larva, usually with pick up superficial scales. Detection of hyphae
an occlusive dressing or covering (such as a bottle (“spaghetti”) and spores (“meatballs”) suggest the
cap filled with petroleum jelly) for several hours diagnosis. Treatment with topical or systemic
and then squeezing the larva out. azoles (ketoconazole, fluconazole), terbinafine, or
Tungiasis is caused by a sand flea (Tunga pen- selenium sulfide (present in some shampoos) is
etrans). The female burrows into the skin, usually recommended.
the foot, and produces a nodular, pale, subcuta- Tinea corporis (ringworm) may be caused
neous lesion with a central dark spot. The painful by a number of different superficial fungi. The
or pruritic lesion expands as the female produces lesion is often a single lesion with an expanding
eggs in her uterus. Treatment involves extraction. red, raised ring, with a central area of clearing in
Loa loa filariasis occurs rarely in long-term the middle. Treatment is usually several weeks’
travelers living in rural sub-Saharan Africa. The application of a topical antifungal agent or a short
traveler may present with transient, migratory, sub- course of an oral antifungal agent.
cutaneous, painful, or pruritic swellings produced Lyme disease, a tickborne infection with
by the adult nematode migration (Calabar swell- Borrelia burgdorferi, is common in North America,
ing). Rarely, the worm can be visualized crossing Europe, and Russia (see Chapter 3, Lyme Disease).
the conjunctiva of the eye or eyelid. Eosinophilia An infected traveler may present with ≥1 large
is common. Loiasis can be diagnosed by finding erythematous patches, with or without central
microfilariae in blood collected during daytime; clearing, often surrounding a prior tick bite. The
however, since microfilaremia may be absent, filar- patient may not have noticed the tick bite.
ial serologic tests may be helpful. Leprosy (Hansen disease) frequently presents
Gnathostomiasis is a nematode infection with hypopigmented or erythematous patches
found primarily in Southeast Asia and less com- that are frequently hypoesthetic to pin prick and
monly in Africa and Latin America. Infection associated with peripheral nerve enlargement.
results from eating undercooked or raw freshwater This condition is almost exclusively found in
fish. Infected travelers may experience transient, immigrants from developing countries.
migratory, subcutaneous, pruritic, or painful swell-
ings that may occur weeks or even years after expo- LINEAR LESIONS
sure. The symptoms are due to migration of the Cutaneous larva migrans, a skin infection
worm through the body, and the central nervous with the larval stage of dog or cat hookworm
fever. The condition is self-limited in 2–12 days; found in classical dengue, as well as in severe
typically no antibiotic therapy is required. dengue. Antigen and antibody detection tests, as
well as PCR assays, are available to diagnose den-
Skin Infections Associated with Bites gue; detecting IgM in the appropriate clinical sce-
Wound infections after dog and cat bites are nario would support the diagnosis. Treatment is
caused by a variety of microorganisms. S. aureus; supportive.
α-, β-, and γ-hemolytic streptococci; several gen- Chikungunya, a virus transmitted by a pri-
era of gram-negative organisms; and a number of marily Aedes mosquito, has caused major out-
anaerobic microorganisms have been isolated. breaks of illness in southeast Africa, South Asia,
The prevalence of Pasteurella multocida iso- the Americas, and the Caribbean (see Chapter 3,
lates from dog bite wounds is 20%–50%; P. mul- Chikungunya). Chikungunya is similar to den-
tocida is a major pathogen in cat bite infections. gue clinically, including the rash, although hem-
Splenectomized patients are at particular risk of orrhage, shock, and death are not typical of
severe cellulitis and sepsis due to Capnocytophaga chikungunya. A major distinguishing feature is
canimorsus after a dog bite. Management of dog that arthritis or arthralgia is common with chi-
and cat bites includes consideration of rabies post- kungunya (and may persist for months), whereas
exposure prophylaxis, tetanus immunization, and
antibiotic prophylaxis. Primary closure of punc-
in dengue, myalgia is the major clinical feature.
Similar to dengue, serologic tests are available.
5
ture wounds and dog bites to the hand should Treatment of the arthritis is with nonsteroidal
be avoided. Antibiotic prophylaxis for dog bites anti-inflammatory drugs.
is controversial, although most experts would Zika, a virus also transmitted by Aedes mosq
treat splenectomized patients with amoxicillin- uitoes has caused a major outbreak in the Western
clavulanate prophylactically. Since P. multocida Hemisphere since May 2015 (see Chapter 3, Zika).
is a common accompaniment of cat bites, pro- Sexual transmission has been documented as well.
phylaxis with amoxicillin-clavulanate or a fluo- The infection is characterized by fever, arthralgia,
roquinolone for 3–5 days should be considered. lymphadenopathy, maculopapular rash, and con-
Management of monkey bites includes wound junctivitis. Microcephaly, brain and eye damage,
care, tetanus immunization, rabies postexposure and fetal loss have occurred as a result of fetal
prophylaxis, and consideration of antimicrobial infection. An increased risk of Guillain-Barré syn-
prophylaxis. Bites and scratches from Old World drome has also been documented. Diagnosis is
macaque monkeys have also been associated with by molecular diagnostics and serologic testing.
fatal encephalomyelitis due to B virus infection Treatment is supportive.
in humans (see Chapter 3, B virus). Valacyclovir South African tick typhus, or African tick-
postexposure prophylaxis is recommended after bite fever (Rickettsia africae), is the most fre-
a high-risk macaque exposure. quent cause of fever and rash in southern Africa.
Transmitted by ticks, the disease is characterized
FEVER AND RASH by fever and a papular or vesicular rash associated
Fever and rash in returned travelers are most with localized lymphadenopathy and the pres-
often due to a viral infection. ence of an eschar (a mildly painful 1 to 2 cm black
Dengue is caused by 1 of 4 strains of den- necrotic lesion with an erythematous margin).
gue viruses (see Chapter 3, Dengue). The dis- Satellite lesions may be present. Diagnosis is usu-
ease is transmitted by an Aedes mosquito often ally through clinical recognition and is confirmed
found in urban areas, and its incidence contin- by serologic testing. Treatment is with doxycy-
ues to increase. The disease is characterized by cline. Other rickettsial infections such as rickettsi-
the abrupt onset of high fever, frontal headache alpox and scrub typhus may present with eschars
(often accompanied by retro-orbital pain), myal- or maculopapular, vesicular, and petechial rashes.
gia, and a faint macular rash (containing islands Rocky Mountain spotted fever (RMSF),
of pallor) that becomes evident on the second although uncommon in travelers, is an import-
to fourth day of illness. A petechial rash may be ant cause of fever and rash because of its potential
severity and the need for early treatment. This patients it begins with petechiae. Doxycycline is
tickborne infection is found in the United States, the treatment of choice.
Mexico, and parts of Central and South America. The category of fever with rash is large, and
Most patients with RMSF develop a rash between providers caring for ill travelers should also
the 3rd and 5th days of illness. The typical rash of consider the following diagnoses: enteroviruses,
RMSF begins on the ankles and wrists and spreads such as echovirus and coxsackievirus; hepatitis B
both centrally and to the palms and soles. The rash virus; measles; Epstein-Barr virus; cytomegalovi-
commonly begins as a maculopapular eruption rus; typhus; leptospirosis; syphilis; and HIV.
and then becomes petechial, although in some
BIBLIOGRAPHY
1. Aronson N, Herwaldt B, Libman M, Pearson R, 6. Lederman ER, Weld LH, Elyazar IR, von Sonnenburg
Lopez-Velez R, Weina P, et al. Diagnosis and treatment F, Loutan L, Schwartz E, et al. Dermatologic condi-
of leishmaniasis: clinical practice guidelines by the tions of the ill returned traveler: an analysis from the
Infectious Diseases Society of America (IDSA) and the GeoSentinel Surveillance Network. Int J Infect Dis. 2008
American Society of Tropical Medicine and Hygiene Nov;12(6):593–6 02.
SCREENING ASYMPTOMATIC
RETURNED TRAVELERS
Michael Libman
diseases, and specific diagnostic tests may not be well studied. Travelers are often concerned about
readily available or may have poorly defined oper- “worms,” by which they mean intestinal nem-
ating characteristics. The decision to screen for atodes. However, probably because of hygiene
particular pathogens will depend on the type of and short duration of exposure for most travel-
travel, itinerary, and exposure history. However, ers, infections with large numbers of the com-
exposure history is often unreliable and poorly mon nematodes, such as Ascaris, Trichuris, or
predictive of infection, the value of a detailed itin- hookworm, are rare. Questioning returning expa-
erary is limited by incomplete information on triates infected with intestinal helminths has dis-
where pathogens are endemic, and the type of closed no attributable symptoms compared with
travel often does not provide a practical assess- uninfected controls, although there have been
ment of risk. case reports of complications, such as migration
Screening traditionally has been viewed as a of Ascaris into the biliary system. The life cycles
secondary prevention intervention, that is, an of almost all helminths preclude any real risk of
attempt to identify existing occult illnesses or ongoing transmission from asymptomatic hosts
health risks. The cost effectiveness of screening in developed countries. Helminths generally have
involves a consideration of the natural history of a natural lifespan of months to a few years, which
the problem, the predictive value of the test, the
direct and indirect costs of the test, and the effec-
ensures eventual spontaneous clearance and are
of limited clinical importance when present in
5
tiveness of prevention or therapy. Because of con- low intensity infection, though in rare cases aber-
venience and the susceptibility to suggestion at rant migration of Ascaris might result in clinical
the time of screening, the screening visit may also disease. The exception to this rule is Strongyloides.
offer an opportunity to promote primary preven- For this helminth, serious complications are well
tion by discussing behavioral or other risk fac- known, nonspecific symptoms may easily be
tors predisposing to ill health. These may include, overlooked, duration of carriage after infection
for example, counseling on sexual health or the is unlimited, and the original burden of infection
avoidance of schistosomiasis or malaria. is irrelevant. Unfortunately, diagnosis by stool
examination is notoriously insensitive, and sero-
PARASITIC INFECTION logic methods are often required, as discussed
Travelers are often most concerned with the pos- below. Molecular panels for helminths are at the
sibility of occult parasitic infection. Unfortunately, research stage of development.
when screening for parasitic disease, the literature The finding of pathogenic protozoa in asymp-
shows that patient questionnaires and common tomatic patients is of questionable significance
laboratory testing have poor sensitivity and spec- (with the possible exception of Entamoeba his-
ificity. Studies have shown that even an exhaus- tolytica, a rare finding in these travelers). History
tive risk-factor history in asymptomatic patients of exposure to contaminated food or water has
is unable to reliably detect those who would or poor predictive value. There is no evidence to sug-
would not have evidence of parasitic infection. gest that these asymptomatic carriers are likely to
Physical examination is equally unrewarding. develop symptoms at a later time. Certainly, the
Most commonly, a stool examination is per- medications used to treat pathogens have their
formed, typically microscopy. Several molecular own adverse effects. In theory, these carriers pose
assays are commercially available; these detect a public health risk, although transmission by
a panel of viral, bacterial, and parasitic (proto- asymptomatic travelers appears to be rare. This is
zoal) pathogens. In some cases these panels are further complicated by the fact that stool micros-
more sensitive than traditional testing meth- copy for protozoa is expensive, not very sensitive,
ods, and even asymptomatic people are often and not highly reproducible, and many laborato-
found to harbor pathogens. The clinical implica- ries have limited expertise. Entamoeba histolytica
tions of asymptomatic carriage, sometimes at a cannot be distinguished from E. dispar by micros-
low level, are unknown for most of these agents, copy, requiring further specimen collection and
and the risks and benefits of treatment are not testing. Studies reveal that most travelers with
Entamoeba on microscopy are carrying E. dis- and effective. The common antihelminthic agents,
par. Antigen testing for E. histolytica and Giardia such as ivermectin, albendazole, and praziquan-
(among others) is fairly reliable but lacks the tel, have excellent safety profiles. Nevertheless,
potential to screen for all intestinal parasites with rare but severe adverse events can occur when
a single test. Commercial molecular methods to certain occult, unsuspected parasitoses are pres-
screen stool specimens for multiple pathogens ent, such as ivermectin and loiasis or albendazole
simultaneously typically include several proto- and neurocysticercosis. While it is not clear who
zoa, generally with sensitivity at least as good as should be screened, it is logical to at least perform
microscopy, and offer rapid turnaround times serologic tests on travelers with a high duration
of several hours, although costs remain high. and risk of exposure and to treat all those found to
Some of these panels are sensitive for question- be positive. Since asymptomatic filarial infections
ably pathogenic organisms, such as Blastocystis appear least likely to have sequelae, and treat-
and Dientamoeba. Identifying these may lead to ment is often neither very effective nor easy, the
patient anxiety and unnecessary treatment. threshold for filarial serology (or antigen testing in
Among the helminths capable of causing the case of Wuchereria bancrofti) should be higher.
eventual illness in asymptomatic travelers, most Serology usually only becomes positive after
5 emphasis has been given to Strongyloides and the
parasites that cause schistosomiasis and filariasis.
adult forms have matured, which means waiting
for 3 months or so after exposure. Serology for
There is no evidence that the low-burden schisto- these pathogens are available at the parasitic dis-
somal infections typically found in travelers are eases laboratory at CDC (www.dpd.cdc.gov/dpdx;
likely to lead to the types of complications com- 404-718-4745; [email protected]). Serology for
monly found in endemic areas, such as liver fibro- filarial infection is available as well through the
sis or malignancy. Nevertheless, this possibility NIH laboratory (301-496-5398).
cannot be entirely ruled out, particularly in those Screening for eosinophilia is a common test,
who may have more intense exposures. Even brief since it is quick, universally available, and theo-
exposures to freshwater lakes and rivers in known retically of value in detecting invasive helminths,
endemic foci in Africa are associated with sub- if not protozoa. However, multiple studies have
stantial seroconversion rates. In addition, com- shown eosinophilia to have poor sensitivity.
plications due to ectopic egg migration can occur Specificity can be high; however, the low prev-
in light infections and without warning. On the alence of infection in asymptomatic travelers
other hand, reports of travelers with late compli- means positive predictive value is low. In addi-
cations from asymptomatic filarial infections are tion, the finding of eosinophilia may lead to an
virtually nonexistent. Traditional tests for the par- extensive and often fruitless search for a cause,
asites that cause these infections, including stool generating high costs. Many cases of eosinophilia
examination for Strongyloides and Schistosoma resolve spontaneously, possibly because of infec-
spp., urine for S. haematobium, and blood or skin tion with nonpathogenic organisms or a nonin-
snips for microfilaria, all lack sensitivity, par- fectious cause, such as allergy or drug reaction.
ticularly in low-burden infection. For this rea- Eosinophil counts may be repeated after several
son, serologic testing has been advocated as the weeks or months before embarking on an exten-
best screening tool. The problems with serologic sive investigation. Counts may be highly variable,
screening include expense, lack of easy availabil- even within a single day, and are suppressed by
ity, and lack of standardization. Serologic tests are endogenous or exogenous steroids. Evaluation of
often designed to maximize sensitivity, typically absolute counts, rather than by percentage of leu-
at the expense of specificity. Unfortunately, speci- kocytes, is more reproducible and predictive.
ficity is almost impossible to define. Seropositivity Immigrants with frequent and regular expo-
in the absence of direct pathogen detection is sure to malaria may gradually develop partial
common, and its clinical significance can be dif- immunity. This may result in low-level parasitemia
ficult to determine. Fortunately, for strongyloidia- with few or no symptoms. They may later recru-
sis and schistosomiasis, treatment is cheap, easy, desce with more severe illness. This phenomenon
is rare in other travelers. There is no justifica- release assay (IGRA), which also is less subject
tion for screening most asymptomatic travelers, to false-positive results related to BCG vaccina-
whether by blood film, serologic tests, or molec- tion. Unfortunately, recent data suggest that IGRA
ular methods. No available tests can detect latent results show inadequate reproducibility, lead-
infections with Plasmodium vivax or P. ovale. ing to false “conversions” on follow-up testing. In
Travelers should be reminded to seek evaluation most patients born and raised in low-prevalence
for unexplained fever and notify practitioners of countries, a case can be made for omitting the
any recent travel. pretravel test, because results are rarely positive.
Occult trypanosomiasis in asymptomatic trav- For many long-term travelers, such as expatri-
elers (as opposed to immigrants) appears to be ate workers and some missionary and aid work-
extremely rare. Screening tests, such as serology ers, the visits for asymptomatic screening may
and molecular diagnostics, are of unknown value. also be their only interludes from a continuing
For travelers to endemic areas of Latin America, assignment abroad allowing for a general health
testing might be considered in cases of prolonged evaluation. The usual recommendations for the
residence in primitive housing, such as mud walls periodic health exam, which may include screen-
and thatched roofs, especially if reduviid bugs ing for hypertension, diabetes, and malignancy,
have been seen. East African trypanosomiasis has
affected travelers but typically causes symptoms.
would apply. These visits also provide an oppor-
tune time to review vaccination status, malaria
5
West African disease is generally not reported in prophylaxis, and health behaviors.
travelers. Other parasitic infections rarely seen
in returning travelers include neurocysticercosis, SUMMARY
fascioliasis, paragonimiasis, and others. Primary Recommendations for screening the asympto-
care providers should refer patients suspected of matic traveler are necessarily based on opin-
having these infections to an infectious diseases ion and common sense, rather than convincing
specialist. evidence. The following may serve as a general
guideline.
NONPARASITIC ILLNESS For the asymptomatic short stay (<3–6
Sexual activity and travel seem to be linked. High months) traveler, the yield of screening is low and
rates of contact with new partners, including sex should be directed by specific risk factors revealed
workers, have been documented in volunteers, in the history. A history of prolonged (>2 weeks)
expatriate workers, backpackers, and military per- digestive symptoms during travel can suggest
sonnel. Of concern are the low rates of reported protozoal infection. Exposure to fresh water in a
condom use. Returning travelers with acute HIV region endemic for schistosomiasis, especially in
or hepatitis B infection pose public health risks. Africa, merits serologic screening, with the addi-
Travelers may be hesitant to volunteer a relevant tion of stool and urine examination in the case of
history. Screening for sexually transmitted infec- high-intensity exposure. Serology for Strongyloides
tions should always be considered. should be considered in those who have a high risk
The incidence of tuberculosis related to travel of skin exposure to soil likely to be contaminated
is difficult to estimate. Estimates of exposure with human feces, usually those with a history
based on skin test (Mantoux) conversions suggest of frequently walking barefoot outdoors. A sex-
rates of exposure of the same general magnitude ual history should be obtained, and screening for
as the local population. Work in high-prevalence sexually transmitted and bloodborne infections is
settings such as health care institutions or refu- often warranted. Work in a health care setting or
gee camps merits screening. Traditionally, this other area at high risk for TB may merit screening.
has been done using pre-and post-travel skin For longer-stay travelers, as the overall yield
tests. This is cumbersome, requiring as many of screening increases it becomes less useful to
as 4 pretravel visits for a 2-step test and 2 vis- rely on history for selective testing. The emphasis
its after potential exposure. This number can be should be on those with the longest stays and the
reduced by using the more expensive interferon-γ most problematic sanitary conditions. In some
cases, employers may require certain tests, partly and bloodborne infections including HIV, hep-
for reasons of liability. Stool examinations are atitis B and C, gonorrhea, chlamydia, and syphi-
usually done, although they serve mostly to pro- lis should be offered to all except those with the
vide a psychological reassurance. Serologic test- most convincing absence of risk. Mantoux or
ing for schistosomiasis and strongyloidiasis IGRA tests should be limited to those who have
should be done in those with recent or remote worked in a health care or similar setting, or who
travel histories to endemic areas and reporting have had intimate and prolonged contact with
some level of risk. Eosinophil counts are usu- residents of an endemic area for ≥6 months. Any
ally done, although results should be interpreted other screening should be guided by exceptional
cautiously. Screening for sexually transmitted exposures or knowledge about local outbreaks.
BIBLIOGRAPHY
1. Baaten GG, Sonder GJ, van Gool T, Kint JA, van den 3. Soonawala D, van Lieshout L, den Boer MA, Claas EC,
Hoek A. Travel-related schistosomiasis, strongyloidiasis, Verweij JJ, Godkewitsch A, et al. Post-travel screening
filariasis, and toxocariasis: the risk of infection and the of asymptomatic long-term travelers to the tropics
5
diagnostic relevance of blood eosinophilia. BMC Infect for intestinal parasites using molecular diagnostics.
Dis. 2011 Apr 5;11:84. Am J Trop Med Hyg. 2014 May;90(5):835–9.
2. MacLean JD, Libman M. Screening r eturning 4. Yansouni CP, Merckx J, Libman MD, Ndao M. Recent
travelers. Infect Dis Clin North Am. 1998 advances in clinical parasitology diagnostics. Curr
Jun;12(2):431–43. Infect Dis Rep 2014 Nov;16(11):434.
Conveyance &
Transportation Issues
AIR TRAVEL
Susan A. Lippold, Tina Objio, Phyllis E. Kozarsky
AIR TRAVEL 517
851
a series of filters 20–30 times per hour. In most Flight attendants are trained in basic first
newer-model airplanes, the recycled air passes aid procedures such as CPR, and use of AED
through high- efficiency particulate air (HEPA) machines but are generally not certified in emer-
filters, which capture 99.9% of particles (bac-
gency medical response. Many airlines use
teria, fungi, and larger viruses or virus clumps) ground-based medical consultants to assist flight
0.1–0.3 µm in diameter. Furthermore, air gener- crew and volunteer passenger responders in man-
ally circulates in defined areas within the aircraft, aging medical cases. In nearly one-half of in-flight
thus limiting the distribution of pathogens spread emergencies, physician volunteers have provided
by small-particle aerosols beyond a small num- assistance. The Aviation Medical Assistance Act,
ber of rows. As a result, the cabin air environment passed in 1998, provides some protection from lia-
is not conducive to the spread of most infectious bility to providers who respond to in-flight medi-
diseases. cal emergencies.
Some diseases may be spread by contact with The goal of managing in-flight medical emer-
infected secretions, such as when an ill person gencies is to stabilize the passenger until ground-
sneezes or coughs and the secretions or drop- based medical care can safely be reached. When
lets land on someone’s face (mouth, nose, eyes), considering diversion to a closer airport, the cap-
or by touching a contaminated surface and then tain must consider the needs of the ill passenger,
touching one’s face with contaminated hands. as well as other safety concerns such as weather,
Practicing good handwashing and respiratory landing conditions, and terrain. Certain routes,
hygiene (covering mouth when coughing or
sneezing) decreases the risk of disease spread by
such as transoceanic flights, and availability of
definitive medical care may restrict diversion
6
direct or indirect contact. options.
AIR TRAVEL 519
0
5
2
health authorities for possible screening or pro- had direct contact with respiratory secretions
phylaxis. When necessary, public health author- or vomitus.
ities will obtain contact information from the
airline for potentially exposed travelers so they
Measles (Rubeola)
may be contacted and offered an intervention.
Measles is a viral illness transmitted by respira-
For information regarding CDC’s travel restric-
tory droplets, direct contact, or airborne routes.
tions, see www.cdc.gov/quarantine/qas-frn-travel-
Most measles cases diagnosed in the United
restriction.html. To request a consultation, pub-
States are imported from countries where mea-
lic health authorities may contact the CDC quar-
sles is endemic. An ill traveler is considered infec-
antine station of jurisdiction (see www.cdc.gov/
tious during a flight of any duration if he or she
quarantine/ q uarantinestationcontactlistfull.
traveled during the 4 days before rash onset
html) or the CDC Emergency Operations Center
through 4 days after rash onset. Flight-related
by calling 770-488-7100.
contact investigations are initiated as quickly as
possible so postexposure prophylaxis may be pro-
Tuberculosis (Mycobacterium vided to susceptible travelers. If indicated, MMR
tuberculosis) (measles, mumps, and rubella) vaccine given
Tuberculosis (TB) is transmitted from person to
within 72 hours of exposure or immune globulin,
person via airborne respiratory droplet nuclei.
given within 6 days of exposure, may prevent mea-
Although the risk of transmission onboard air-
6 craft is low, CDC recommends conducting pas-
senger contact investigations for flights ≥8 hours
sles or decrease its severity in people who are not
immune.
if the person with TB has sputum that is smear-
DISINSECTION
positive for acid-fast bacilli and cavitation on
To reduce the accidental spread of mosquitoes
chest radiograph or has multidrug-resistant TB.
and other vectors via airline cabins and luggage
People known to have active TB disease should
compartments, a number of countries require
not travel by commercial air (or any other com-
disinsection of all inbound flights or flights from
mercial means) until they are determined to
certain areas. Although disinsection, when done
be noninfectious. State health department TB
appropriately, was declared safe by the World
controllers are valuable resources for advice to
Health Organization (WHO) in 1995, there is still
determine when a person can be considered non-
much debate about the safety of the agents and
infectious (www.tbcontrollers.org/community/
the effectiveness of disinsection as a public health
statecityterritory).
measure to prevent the spread of vectorborne dis-
eases. Although CDC reserves the right to require
Meningococcal disease (Neisseria disinsection to control importation and spread of
meningitidis) a vectorborne infectious disease, it is not currently
Meningococcal disease caused by N. meningitidis
required for aircraft arriving at US airports. WHO
is transmitted by direct contact with respiratory
information on aircraft disinsection, including
droplets and secretions and can be rapidly fatal.
available procedures, can be found at www.who.
Therefore, close contacts of ill travelers need to be
int/ith/mode_of_travel/aircraft_disinsection/en.
quickly identified and provided with prophylactic
An updated list of countries that require disinsec-
antimicrobial agents. Antimicrobial prophylaxis
tion, and the types of methods used, is available at
should be considered for any of the following:
the Department of Transportation website: www.
• Household members traveling with the ill transportation.gov/office-policy/aviation-policy/
traveler aircraft-disinsection-requirements.
• Travel companions with prolonged close INFORMATION FOR
contact
AIR CREW
• Travelers seated directly next to the ill traveler In preparation for a healthy journey, flight crew
on flights ≥8 hours (gate to gate) or who have can refer to Chapter 8, Advice for Air Crews and
to the CDC Travelers’ Health website (www. the CDC Airline Guidance webpage: www.cdc.
cdc.gov/╉travel). If flight crew encounter pas- gov/╉quarantine/╉air. Requirements and tools for
sengers with potentially infectious diseases, see reporting are also provided.
BIBLIOGRAPHY
1. Aerospace Medical Association Air Transport Medicine economic analysis of alternate protocols. Travel Med
Committee. Medical guidelines for airline travel. Infect Dis. 2014 Jan-╉Feb;12(1):54–╉62.
Alexandria, VA: Aerospace Medical Association; 2014 6. Nable JV, Tupe CL, Gehle BD, Brady WJ. In-╉Flight medi-
[cited 2016 Mar. 24]; Available from: https://╉www.asma. cal emergencies during commercial travel. N Engl J Med
org/╉publications/╉medical-╉publications-╉for-╉airline-╉ 2015 Sep 3;375(10):939–╉45.
travel/╉medical-╉considerations-╉for-╉airline-╉travel.
7. Neatherlin J, Cramer EH, Dubray C, Marienau KJ,
2. Bagshaw M, Barbeau DN. The aircraft cabin Russell M, Sun H, et al. Influenza A(H1N1)pdm09 during
Â�environment. In: Keystone JS, Freedman DO, Kozarsky air travel. Travel Med Infect Dis. 2013 Mar-╉Apr;11(2):110–╉8.
PE, Connor BA, Nothdurft HO, editors. Travel Medicine.
8. Nelson K, Marienau K, Schembri C, Redd S. Measles
3rd ed. Philadelphia: Saunders Elsevier; 2013. pp.
transmission during air travel, United States, December
405–╉12.
1, 2008–╉December 31, 2011. Travel Med Infect Dis. 2013
3. Huizer YL, Swaanm CM, Leitmeyer KC, Timen A. Mar-╉Apr;11(2):81–╉9.
Usefulness and applicability of infectious disease con-
9. Peterson DC, Martin-╉Gill C, Guyette FX, Tobias AZ,
trol measures in air travel: a review. Travel Med Infect
McCarthy CE, Harrington ST, et al. Outcomes of medi-
Dis. 2015 Jan-╉Feb;13(1):19–╉30.
6
cal emergencies on commercial airline flights. N Engl J
4. Illig PA. Passenger health. In: Curdt-╉Christiansen C, Med. 2013 May 5;368(22):2075–╉83.
Draeger J, Kriebel J, Antunano M, editors. Principles and
10. World Health Organization. Tuberculosis and
Practice of Aviation Medicine. Hackensack, NJ: World
air travel: guidelines for prevention and control.
Scientific; 2009. pp. 667–╉708.
Geneva: World Health Organization; 2008 [cited 2016
5. Marienau KJ, Cramer EH, Coleman MS, Marano N, Sep 26]; 3rd ed. Available from: http://╉www.who.int/╉tb/╉
Cetron MS. Flight related tuberculosis contact inves- publications/╉2008/╉WHO_╉HTM_╉TB_╉2008.399_╉eng.pdf.
tigations in the United States: comparative risk and
CRUISE SHIP TRAVEL
Joanna J. Regan, Kara Tardivel, Susan A. Lippold, Krista Kornylo Duong
Although no agency officially regulates medical The following measures should be encouraged
practice aboard cruise ships, consensus- based to limit the introduction and spread of communi-
guidelines for cruise ship medical facilities were cable diseases on cruise ships:
published by the American College of Emergency
Physicians (ACEP) in 1995 and most recently
• Passengers and their clinicians should consult
CDC’s Travelers’ Health website (www.cdc.
updated in 2013. ACEP guidelines (www.acep.
gov/travel) before travel for updates on out-
org/content.aspx?id=29500), which are followed
breaks and travel health notices.
by most major cruise lines, state that the cruise
ship medical facilities should maintain the follow- • Passengers ill with communicable diseases
ing minimum capabilities: before a voyage should delay travel until they
are no longer contagious.
• Provide emergency medical care for passen-
gers and crew • Passengers who become ill during the voy-
age should seek care in the ship’s infirmary to
• Stabilize patients and initiate receive clinical management, facilitate infec-
r easonable diagnostic and therapeutic
tion control measures, and maximize report-
interventions
ing of potential public health events.
• Facilitate the evacuation of seriously ill or
injured patients
SPECIFIC HEALTH RISKS
6 ILLNESSES AND INJURY GI Illness
From 2008 through 2014, rates of GI illness
ABOARD CRUISE SHIPS among passengers on voyages lasting 3–21 days
Cruise ship medical clinics deal with a wide variety
decreased from 27.2 to 22.3 cases per 100,000
of illnesses and injuries. Approximately 3%–11%
travel days. Despite this decrease, GI illness out-
of conditions reported to cruise ship infirmaries
breaks continue to occur. Updates on these out-
are urgent or an emergency. Approximately 95%
breaks involving ships with US ports of call can be
of illnesses are treated or managed onboard, and
found at www.cdc.gov/nceh/vsp/surv/gilist.htm.
5% require evacuation and shoreside consultation
More than 90% of GI outbreaks with a con-
for medical, surgical, or dental problems. Roughly
firmed cause are due to norovirus. Characteristics
half of passengers who seek medical care are older
of norovirus that facilitate outbreaks are a low
than 65 years of age. Most infirmary visits are due
infective dose, easy person-to-person transmis-
to acute illnesses, of which respiratory illnesses
sibility, prolonged viral shedding, no long-term
(19%–29%); seasickness (10%–25%); injuries from
immunity, and the organism’s ability to survive
slips, trips, or falls (12%–18%); and gastrointesti-
routine cleaning procedures. From 2010 through
nal (GI) illness (9%–10%) are the most frequently
2015, 8– 16 outbreaks of norovirus infections
reported diagnoses. Death rates for cruise ship
occurred on cruise ships each year. GI outbreaks
passengers, most often from cardiovascular
on cruise ships from food and water sources have
events, range from 0.6 to 9.8 deaths per million
also been associated with Salmonella spp., entero-
passenger-nights.
toxigenic Escherichia coli, Shigella spp., Vibrio spp.,
The most frequently reported cruise ship out-
Staphylococcus aureus, Clostridium perfringens,
breaks involve respiratory infections, GI infections
Cyclospora cayetanensis, and hepatitis A and E
(norovirus), and vaccine- preventable diseases
viruses.
other than influenza, such as varicella (chicken-
To protect themselves from infections and
pox). To reduce the risk of onboard introduction
reduce the spread of GI illnesses on cruise ships,
of communicable diseases by embarking passen-
passengers should be counseled on the following:
gers, ships may conduct medical screening during
embarkation to identify ill passengers, preventing • Passengers should wash their hands with
them from boarding or requiring isolation if they soap and water often, especially before eating
are allowed to board. and after using the restroom.
• Inform CDC of any travel-associated subsequently spread across the Caribbean and
Legionnaires’ disease cases by sending an Latin America. See Chapter 3 for additional infor-
email to [email protected]. Cases mation on specific vectorborne diseases.
of Legionnaires’ disease should be quickly Passengers should follow recommendations
reported to public health officials in order for avoiding mosquito bites and vectorborne
to determine if there are links to previously infections:
reported clusters and to stop potential clus- • Use an effective insect repellent (see
ters and new outbreaks. Chapter 2, Protection against Mosquitoes,
Ticks, & Other Arthropods).
Vaccine-Preventable
Diseases (VPDs) • Treat clothing and gear with permethrin or
purchase permethrin-treated items.
Although most cruise ship passengers are from
countries with routine vaccination programs • While indoors, remain in well-screened or
(such as the United States and Canada), many air-conditioned areas.
crew members originate from developing coun-
tries with low immunization rates. Outbreaks
• When outdoors, wear long-sleeved shirts,
long pants, boots, and hats.
of measles, rubella, meningococcal disease and,
most commonly, varicella have been reported on • Obtain yellow fever vaccination if recom-
6 cruise ships. Preventive measures to reduce the
spread of VPDs onboard cruise ships should be
mended or required.
• Take antimalarial chemoprophylaxis if
followed:
needed (see Chapter 3, Yellow Fever & Malaria
• Crew members should have documented Information, by Country).
proof of immunity to VPDs (see Chapter 2,
General Recommendations for Vaccination &
Other Health Concerns
Immunoprophylaxis).
Stresses of cruise ship travel include varying
• Passengers, especially older passengers weather and environmental conditions, as well
(>65 years of age) and immunocompro- as unaccustomed changes in diet and physical
mised people, should be up-to-date with rou- activity. Foreign travel may increase the likelihood
tine vaccinations before travel, as well as any of risk-taking behaviors such as alcohol misuse,
required or recommended vaccinations spe- drug use, and unsafe sex. In spite of modern sta-
cific for their destinations. bilizer systems, seasickness is a common com-
plaint (affecting up to one-fourth of travelers) (see
• Women of childbearing age should be Chapter 2, Motion Sickness). Cruise lines may not
immune to varicella and rubella before cruise
allow women to board after the 24th week of preg-
ship travel.
nancy, and pregnant women should contact the
cruise line for specific policies and recommenda-
Vectorborne Diseases tions before booking ( for additional information,
Cruise ship port visits may include countries see Chapter 8, Pregnant Travelers).
where vectorborne diseases such as malaria,
dengue, yellow fever, Japanese encephalitis, and PREVENTIVE MEASURES
Zika are endemic. New diseases might surface in FOR CRUISE SHIP TRAVELERS
unexpected locations. For example, chikungunya Cruise ship travelers often have complex itiner-
was reported in late 2013 for the first time in the aries due to multiple, short port visits. Although
Caribbean (with subsequent spread through- most of these port visits do not include overnight
out the Caribbean and numerous North, Central, stays off the cruise ship, some trips have options
and South American countries and territories). for travelers to venture off the ship for ≥1 night.
Zika virus was first reported in Brazil in 2015 and Therefore, cruise ship travelers may be uncertain
about potential exposures and which antimicro- with health conditions should carry a written
bial prophylaxis, immunizations, and preventive summary of essential health information (electro-
measures should be considered. Box 6-1 summa- cardiogram, chest radiograph, if abnormal, blood
rizes recommendations for cruise travelers and type, chronic conditions, allergies, treating phy-
clinicians advising cruise travelers in pretravel sician contact information, and medication list)
preparation and healthy behaviors during travel. that would facilitate their care during a medi-
Travelers with special medical needs, such as cal emergency. In addition, all prospective cruise
wheelchairs, oxygen tanks, or dialysis, should travelers should verify coverage with their health
inform their cruise line before traveling. Travelers insurance carriers and, if not included, consider
BIBLIOGRAPHY
DEATH DURING TRAVEL
Nicole J. Cohen, Megan R. Reynolds, G. Gale Galland
A hermetically sealed casket is one that is air- accompanied by a permit issued by the CDC
tight and secured against the escape of micro- director.
organisms. It should be accompanied by valid 2. The remains are shipped in a leakproof con-
documentation certifying that it is hermetically tainer. A leakproof container is one that is
sealed. puncture resistant and sealed so that there
If a CDC permit is obtained to allow importa- is no leakage of fluids outside the container
tion of human remains, CDC may impose addi- during handling, storage, transport, or
tional conditions for importation. Permits for shipping.
the importation of human remains of a person
CDC may also require additional measures,
known or suspected to have died from a quaran-
including detention, disinfection, disinfestation,
tinable communicable disease may be obtained
fumigation, or other related measures, if there is
from CDC’s Division of Global Migration and
evidence that the human remains are or may be
Quarantine by calling the CDC Emergency
infected or contaminated with a communicable
Operations Center at 770-488-7100. A copy of the
disease and that such measures are necessary to
CDC permit must accompany the human remains
prevent the introduction, transmission, or spread
at all times during shipment.
of communicable diseases into the United States.
Remains of a Person Who Died EXPORTATION OF HUMAN
of Any Cause Other than a REMAINS
6 Quarantinable Communicable
Disease
CDC does not regulate the exportation of human
remains outside the United States, although other
When the cause of death is anything other than a
state and local regulations may apply. Exporters
quarantinable communicable disease, the remains
of human remains and travelers taking human
may be cleared, released, and authorized for entry
remains out of the United States should be aware
into the United States if 1 of the following condi-
that the importation requirements of the desti-
tions is met:
nation country and the air carrier must be met.
1. The remains meet the standards for impor- Information regarding these requirements may be
tation found in 42 CFR 71.55: the remains obtained from the appropriate foreign embassy or
are cremated or properly embalmed and consulate (www.state.gov/s/cpr/rls) and the air
placed in a hermetically sealed casket or are carrier.
BIBLIOGRAPHY
1. Bureau of Consular Affairs, U.S. State Department. Available from: http://www.cdc.gov/quarantine/
Death abroad. Washington, DC: US Department of human-remains.html.
State; 2014 [cited 2016 Apr. 11]; Available from: https:// 5. CDC. Specific laws and regulations governing the
travel.state.gov/content/passports/en/abroad/events- control of communicable diseases. Atlanta: CDC; 2014
and-records/death.html. [cited 2016 Apr. 11]; Available from: http://www.cdc.gov/
2. Bureau of Consular Affairs, U.S. State Department. quarantine/SpecificLawsRegulations.html.
Return of remains of deceased US citizens. Washington, 6. National Funeral Directors Association. Shipping remains
DC: US Department of State; 2014 [cited 2016 Apr. 11]; from the United States to a foreign country. Brookfield,
Available from: http://travel.state.gov/content/ WI: National Funeral Directors Association; c2014 [cited
passports/english/abroad/events-and-records/death/ 2016 Apr. 11]; Available from: http://nfda.org/additional-
return-remains.html. tools-shipping/2257-shipping-remains-from-the%20
3. CDC. Quarantine station contact list, map, and fact united-states%20to%20a%20foreign-country.html.
sheets. Atlanta: CDC; 2013 [cited 2016 Apr. 11]; 7. US Customs and Border Protection. Requirements for
Available from: http://www.cdc.gov/quarantine/ importing bodies in coffins/ashes in urns. Washington,
quarantinestationcontactlistfull.html. DC: US Department of Homeland Security; 2015 [cited
4. CDC. Guidance for importation of human remains 2016 Apr. 11]; Available from: https://help.cbp.gov/app/
into the United States for interment or subsequent answers/detail/a_id/237/kw/importation%20of%20
cremation. Atlanta: CDC; 2014 [cited 2016 Apr. 11]; human%20remains.
TRAVELING ABROAD WITH A PET destination state for specific rules about impor-
Travelers planning to take a companion animal tation. Importers should research applicable
to a foreign country must meet the entry require- requirements as soon as they know they will be
ments of the destination country and transporta- importing an animal or animal product into the
tion guidelines of the airline. To obtain destination United States. Veterinary exams or certifications,
country information, travelers should contact the vaccinations, or permits may be needed.
country’s embassy in Washington, DC or the near-
est consulate (see www.state.gov/s/cpr/rls/fco). ANIMAL HEALTH
Airline guidelines may be obtained from specific CERTIFICATES
companies. Travelers should be aware that long
flights can be hard on pets, particularly older ani-
CDC regulations do not require general health
certificates for animals entering the United
6
mals with chronic health conditions, very young States. However, some states may require health
dogs, or breeds such as bulldogs that may be pre- certificates for entry, and some airlines may
disposed to respiratory stress. Additionally, upon require these certificates for transport. Before
reentering the United States, pets that traveled departure, travelers should check with the depart-
abroad are subject to the same import require- ments of health and of agriculture in their destina-
ments as animals that have never lived in the tion states and with the airline for any certificate
United States. requirements. The department of environmental
protection or department of natural resources
REQUIREMENTS of some states and local governments may have
FOR ENTERING THE additional requirements.
UNITED STATES
CDC restricts the importation of animals and INTERNATIONAL PET
animal products that might pose an infectious RESCUE AND ADOPTION
disease threat to humans. Any animal or animal Although done with the best of intentions, res-
product can be restricted from entry if there is cuing and importing stray animals from for-
reasonable knowledge or suspicion that it poses eign countries can create human health risks.
a human health risk. However, CDC has explicit Travelers are at an increased risk for possible bites
restrictions for specific animals such as dogs, cats, and scratches from fearful and stressed animals,
turtles, nonhuman primates, African rodents, which may result in injury or exposure to infec-
civets, and bats, as well as products made from tious disease. Animals that are infected with zoo-
them. Importers must meet stringent require- notic diseases might not show any outward signs
ments in order to import these animals and items of being ill. Therefore, all rescued animals should
into the United States. Many of these animals are be examined by a licensed veterinarian both
also regulated by other federal agencies or by indi- before departure and after arrival in the United
vidual state governments. Travelers should check States. If the intent of travel is to rescue animals,
with the Department of Agriculture (USDA), participants should discuss rabies preexposure
the Fish and Wildlife Service (FWS), and their prophylaxis with their health care providers.
more information on CDC’s importation require- of introducing these viruses, the importation of
ments, see www.cdc.gov/importation/bringing- all live bats requires a CDC permit. Many bats
an-animal-into-the-united-states/monkeys.html. require additional permits issued by FWS. The
application for a CDC import permit for bats can
Turtles be found at www.cdc.gov/importation/bringing-
Although often kept as pets, turtles can trans- an-animal-into-the-united-states/bats.html.
mit Salmonella to humans. For this reason, CDC In some circumstances, known vectors of
restricts the importation of some turtles. A person human disease such as ticks or mosquitoes may
may import up to 6 viable turtle eggs or live turtles be imported into the United States with a permit
with a shell length of <4 in (10 cm) for noncom- from CDC for science, education, or exhibition.
mercial purposes. More live turtles or viable turtle For additional information, see www.cdc.gov/
eggs may be imported with CDC permission but phpr/ipp/index.htm.
only for science, education, or exhibition. CDC
does not restrict the importation of live turtles Other Animals
with a shell length >4 inches. Check with USDA or Travelers planning to import horses, ruminants,
FWS regarding additional requirements to import swine, poultry or other birds, or dogs used for han-
turtles. More information is available at www.cdc. dling livestock should contact National Import
gov/importation/bringing-an-animal-into-the- Export Services, a part of USDA’s Animal Plant
united-states/turtles.html. Health Inspection Service, at 301-851-3300 or visit
African Rodents
www.aphis.usda.gov to learn about additional
requirements.
6
African rodents are a known source of commu- Travelers planning to import fish, reptiles, spi-
nicable diseases, such as monkeypox. Thus, CDC ders, wild birds, rabbits, bears, wild members of
does not allow the importation of these animals. the cat family, or other wild or endangered ani-
Exceptions may be made for animals imported mals should contact FWS at 800-344-9453 (toll-
for science, education, or exhibition purposes, free general number), 703-358-1949 (FWS Office
with permission from CDC. Check with USDA or of Law Enforcement), or visit www.fws.gov/le/
FWS regarding additional requirements to import travelers.html.
African rodents. For additional information, see
www.cdc.gov/importation/bringing-an-animal-
IMPORTATION OF ANIMAL
into-the-united-states/african-rodents.html.
PRODUCTS
Civets and Related Animals Trophies and Animal Products
To reduce the risk of introducing severe acute Travelers often want to import animal skins, hunt-
respiratory syndrome (SARS) coronavirus, civets ing trophies, or other items made from a nimals
and related animals ( family Viverridae) may not when returning from a trip. Many of these items
be imported into the United States. Exceptions must either be rendered noninfectious (see www.
may be made for animals imported for science, cdc.gov/ a nimalimportation/ a nimalproducts.
education, or exhibition purposes, with permis- html) or be accompanied by an import permit.
sion from CDC. Check with USDA or FWS regard- CDC restricts products made from nonhuman
ing additional requirements to import civets and primates, African rodents, civets, and bats. These
related animals. For more information, see www. products may also be regulated by other US fed-
cdc.gov/importation/bringing-an-animal-into- eral agencies. CDC has the right to restrict other
the-united-states/civets.html. items known to carry infectious diseases. For
example, CDC restricts goatskin souvenirs, such
Bats and Other Vectors as Haitian goatskin drums, from entry into the
Bats are reservoirs of many viruses that can United States because they have been associ-
infect humans, including rabies virus, Nipah ated with cases of anthrax in humans. Travelers
virus, and SARS coronavirus. To reduce the risk who want to import hunting trophies or other
products made from animals should check with global wildlife trade. CDC prohibits the impor-
CDC, USDA, and FWS to make sure they are com- tation of bushmeat into the United States from
plying with federal regulations. CDC-restricted species. Bushmeat importa-
tion may also be restricted under USDA or FWS
Bushmeat regulations. In addition to the human and ani-
Animal products may also include items intended mal health risks, many of the wild animals com-
for human consumption. Bushmeat, for example, monly hunted for bushmeat are threatened or
is an animal product that is an important aspect endangered species protected by international
of West and Central African culture. This prod- wildlife laws and treaties such as the Convention
uct, generally raw, smoked, or partially processed on International Trade of Endangered Species
meat from wild animals, might harbor infectious (CITES).
and zoonotic agents that can cause human and For additional information about importing
animal disease. Bushmeat has been linked to animals and animal products into the United States
deadly diseases including Ebola. Recent stud- and for permit applications, travelers should visit
ies have found evidence of simian foamy viruses, www.cdc.gov/importation/index.html or contact
which are known to cause infections in humans 1-800-CDC INFO (1-800-232-4636). To request CDC
but have not been associated with human dis- permission to import a CDC-regulated animal or
ease. As people migrate around the world, bush- product, send a message to CDCAnimalImports@
meat has become a growing commodity in the cdc.gov.
6
BIBLIOGRAPHY
1. Bair-Brake H, Bell T, Higgins A, Bailey N, Duda M, 6. Editorial: bongo-drum disease. Lancet. 1974 Jun
Shapiro S, et al. Is that a rodent in your luggage? 8;1(7867):1152.
A mixed method approach to describe bushmeat 7. McQuiston JH, Wilson T, Harris S, Bacon RM, Shapiro
importation into the United States. Zoonoses Public S, Trevino I, et al. Importation of dogs into the United
Health. 2014 Mar;61(2):97–104. States: risks from rabies and other zoonotic diseases.
2. CDC. Multistate outbreak of monkeypox—Illinois, Zoonoses Public Health. 2008 Oct;55(8-10):421–6.
Indiana, and Wisconsin, 2003. MMWR Morb Mortal 8. National Association of State Public Health Veterinarians,
Wkly Rep. 2003 Jun 13;52(23):537–4 0. Inc. Compendium of animal rabies prevention and con-
3. CDC. Rabies in a dog imported from Iraq—New Jersey, trol, 2009. MMWR Recomm Rep. 2009;58(RR-1):1–15.
June 2008. MMWR Morb Mortal Wkly Rep. 2008 Oct 9. Stam F, Romkens TE, Hekker TA, Smulders YM. Turtle-
3;57(40):1076–8. associated human salmonellosis. Clin Infect Dis. 2003
4. DeMarcus TA, Tipple MA, Ostrowski SR. US policy for Dec 1;37(11):e167–9.
disease control among imported nonhuman primates. 10. Wu D, Tu C, Xin C, Xuan H, Meng Q, Liu Y, et al. Civets
J Infect Dis. 1999 Feb;179 Suppl 1:S281–2. are equally susceptible to experimental infection by two
5. Dobson AP. What links bats to emerging infectious different severe acute respiratory syndrome coronavirus
diseases? Science. 2005 Oct 28;310(5748):628–9. isolates. J Virol. 2005 Feb;79(4):2620–5.
International Travel
with Infants & Children
TRAVELING SAFELY WITH
INFANTS & CHILDREN
Nicholas Weinberg, Michelle S. Weinberg, Susan A. Maloney
assessing a child who is planning international parents feeding their child formula should consider
travel, clinicians should: whether they need to bring formula from home.
Water served to young children, including
• Review routine childhood and travel-related water used to prepare infant formula, should be
vaccinations. The pretravel visit is an oppor-
disinfected (see Chapter 2, Water Disinfection
tunity to ensure that children are up-to-date
for Travelers). In some parts of the world, bottled
on routine vaccinations.
water may also be contaminated and should be
• Assess all anticipated travel-related activities. disinfected before consumption.
Similarly, food precautions should be fol-
• Provide preventive counseling and inter- lowed diligently. Foods served to children should
ventions tailored to specific risks, including
be thoroughly cooked and eaten while still hot;
special travel preparations and treatment
fruits eaten raw should be peeled by the caregiver
that may be required for infants and chil-
immediately before consumption. Additionally,
dren with underlying conditions, chronic dis-
caution should be used with fresh dairy products,
eases, or immunocompromising conditions.
which may not be pasteurized and may be diluted
Adolescents traveling in a student group or
with untreated water. For short trips, parents may
program may require counseling about dis-
want to bring a supply of safe snacks from home
ease prevention and the risks of sexually
for times when the children are hungry and the
transmitted infections, empiric treatment and
available food may not be appealing or safe. See
management of common travel-related ill-
Chapter 2, Food & Water Precautions for more
nesses, sexual assault, and drug and alcohol
information.
use during international travel (see Chapter 8,
Scrupulous attention should be paid to hand-
7 Study Abroad & Other International Student
Travel).
washing and cleaning bottles, pacifiers, teething
rings, and toys that fall to the floor or are handled
• Give special consideration to the risks of chil- by others; water used to clean these items should
dren who are VFR travelers in developing be potable. Parents should be particularly care-
countries. Conditions may include increased ful to wash hands well after diaper changes, espe-
risk of malaria, intestinal parasites, and cially for infants with diarrhea, to avoid spreading
tuberculosis. infection to themselves and other family mem-
bers. When proper handwashing facilities are not
• Consider counseling adults traveling with available, an alcohol-based hand sanitizer (con-
children and older children to take a course in
taining ≥60% alcohol) can be used as a disinfect-
basic first aid before travel.
ing agent. However, because alcohol-based hand
sanitizers are not effective against certain patho-
DIARRHEA gens, hands should be washed with soap and
Diarrhea and associated gastrointestinal illness water as soon as possible. Additionally, alcohol
are among the most common travel-related prob- does not remove organic material; visibly soiled
lems affecting children. Infants and children with hands should be washed with soap and water.
diarrhea can become dehydrated more quickly Chemoprophylaxis with antibiotics is not gen-
than adults. The etiology of travelers’ diarrhea erally used in children.
(TD) in children is similar to that in adults (see
Chapter 2, Travelers’ Diarrhea). Treatment
ANTIEMETICS AND ANTIMOTILITY DRUGS
Prevention Because of potential side effects, antiemetics are
For infants, breastfeeding is the best way to reduce generally not recommended for self-or family-
the risk of foodborne and waterborne illness. administered treatment of children with vomiting
Infant formulas available abroad may not have and TD. Because of the association between salic-
the same nutritional composition or be held to ylates and Reye syndrome, bismuth subsalicylate
the same safety standards as in the United States; (BSS), the active ingredient in both Pepto-Bismol
and Kaopectate, is not generally recommended to they are not approved by the Food and Drug
treat diarrhea in children aged <12 years. However, Administration for this purpose among children
some clinicians use it off-label with caution in aged <18 years because of cartilage damage seen
certain circumstances. Caution should be taken in animal studies. The American Academy of
in administering BSS to children with viral infec- Pediatrics suggests that fluoroquinolones be con-
tions, such as varicella or influenza, because of the sidered for the treatment of children with severe
risk for Reye syndrome. BSS is not recommended infections caused by multidrug-resistant strains
for children aged <3 years. A recent Cochrane of Shigella species, Salmonella species, Vibrio chol-
Collaboration Review of the use of antiemetics for erae, or Campylobacter jejuni. Clinicians should
reducing vomiting related to acute gastroenteri- be aware that fluoroquinolone resistance in gas-
tis in children and adolescents showed some trointestinal organisms has been reported from
benefits with ondansetron, metoclopramide, some countries, particularly in Asia. Routine use
or dimenhydrinate. However, the routine use of of fluoroquinolones for chemoprophylaxis or
these medications for emesis associated with TD empiric treatment for TD among children is not
has not yet been determined and is not generally recommended.
recommended.
Antimotility drugs, such as loperamide and Fluid and Nutrition Management
diphenoxylate, are rarely given to small children. The biggest threat to the infant with diarrhea
Loperamide is not recommended for children and vomiting is dehydration. Fever or increased
aged <6 years. Diphenoxylate and atropine com- ambient temperature increases fluid loss and
bination tablets are not recommended for chil- speeds dehydration. Adults traveling with children
dren aged <2 years. These drugs should be used should be counseled about the signs and symp-
with caution in children because of potential side
effects (see Chapter 2, Travelers’ Diarrhea).
toms of dehydration and the proper use of oral
rehydration salts (ORS). Medical attention may be
7
required for an infant or young child with diarrhea
ANTIBIOTICS who has the following:
Few data are available regarding empiric treat- • Signs of moderate to severe dehydration
ment of TD in children. The antimicrobial options
for empiric treatment of TD in children are lim- • Bloody diarrhea
ited. In practice, when an antibiotic is indicated • Temperature >101.5°F (38.6°C)
for moderate to severe diarrhea, some clinicians
prescribe azithromycin as a single daily dose (10 • Persistent vomiting (unable to maintain oral
mg/kg) for 3 days. Clinicians can prescribe unre- hydration)
constituted azithromycin powder before travel, The mainstay of management of TD is adequate
with instructions from the pharmacist for mix- hydration.
ing it into an oral suspension if it becomes nec-
essary to use it. Although resistance breakpoints ORS USE AND AVAILABILITY
have not yet been determined, elevated minimum Parents should be advised that dehydration is best
inhibitory concentrations for azithromycin have prevented and treated by use of ORS in addition
been reported for some gastrointestinal patho- to the infant’s usual food. ORS should be provided
gens. Therefore, parents should be counseled to to the infant by bottle, cup, oral syringe (often
seek medical attention for their children if they do available in pharmacies), or spoon while medical
not improve after empiric treatment. Clinicians attention is being obtained. Low-osmolarity ORS
should review possible contraindications, such is the most effective in preventing dehydration,
as QT prolongation and cardiac arrhythmias with although other formulations are available and
azithromycin, before prescribing medications for may be used if they are more acceptable to young
empiric treatment of TD. children. Homemade sugar-salt solutions are not
Although fluoroquinolones are frequently recommended. Adults traveling with children
used for the empiric treatment of TD in adults, should be counseled that sports drinks, which are
shock, seizures, coma, and death. Initial symp- Personal Protective Measures
toms of malaria in children may mimic many and Repellent Use
other common causes of pediatric febrile illness Children should sleep in rooms with air condi-
and therefore may result in delayed diagnosis tioning or screened windows, or sleep under bed
and treatment. Among 33 children with imported nets when available. Mosquito netting should be
malaria diagnosed at 11 medical centers in used over infant carriers. Children can reduce
New York City, 11 (32%) had severe malaria and skin exposed to mosquitoes by wearing long
14 (43%) were initially misdiagnosed. Clinicians pants and long sleeves while outdoors in areas
should counsel adults traveling with children in where malaria is transmitted. Clothing and mos-
malaria-endemic areas to use preventive mea- quito nets can be treated with insect repellents
sures, be aware of the signs and symptoms of such as permethrin, a repellent and insecti-
malaria, and seek prompt medical attention if cide that repels and kills ticks, mosquitoes, and
they develop. other arthropods. Permethrin remains effective
through multiple washings. Clothing and bed
Antimalarial Drugs nets should be retreated according to the prod-
Pediatric doses for malaria chemoprophylaxis are uct label. Permethrin should not be applied to
provided in Table 3-10. All dosing should be cal- the skin. Although permethrin provides longer
culated on the basis of body weight. Medications duration of protection, recommended repel-
used for infants and young children are the same lents that can be applied to skin can also be used
as those recommended for adults, except under on clothing and mosquito nets. See Chapter 2,
the following circumstances: Protection against Mosquitoes, Ticks, & Other
Arthropods for more details about these protec-
• Doxycycline should not be given to children
aged <8 years because of the risk of teeth tive measures.
CDC recommends the use of repellents con-
7
staining.
taining one of the following active ingredients,
• Atovaquone-proguanil should not be used which are registered with the Environmental
for prophylaxis in children weighing <11 lb Protection Agency, according to the product
(<5 kg) because of lack of data on safety and labels: DEET [N,N-diethyl-m-toluamide], picari-
efficacy. din, oil of lemon eucalyptus [OLE] or PMD [para-
Chloroquine, mefloquine, and atovaquone- menthane-3,8-diol], and IR3535 (http://cfpub.epa.
proguanil have a bitter taste. Before departure, gov/oppref/insect). Most repellents can be used
pharmacists can be asked to pulverize tablets and on children aged >2 months, with the following
prepare gelatin capsules with calculated pediat- considerations:
ric doses. Mixing the powder in a small amount • Products containing OLE specify that
of food or drink can facilitate the administra- they should not be used on children aged
tion of antimalarial drugs to infants and chil- <3 years.
dren. Additionally, any compounding pharmacy
can alter the flavoring of malaria medication • Repellent products must state any age restric-
tablets so that children are more willing to take tion. If none is stated, the Environmental
them. Assistance with finding a compound- Protection Agency has not required a restric-
ing pharmacy is available on the Compounder tion on the use of the product.
Connect section of the International Academy of • Many repellents contain DEET as the active
Compounding Pharmacists’ website (www.iacprx. ingredient. The concentration of DEET varies
org; 800-927-4227). Because overdose of antima- considerably among products. The duration
larial drugs, particularly chloroquine, can be fatal, of protection varies with the DEET concen-
medication should be stored in childproof con- tration; higher concentrations protect lon-
tainers and kept out of the reach of infants and ger. Products with DEET concentration
children. above 50% do not offer a marked increase in
protection time. The American Academy of living in areas where dengue or other arbovi-
Pediatrics recommends that ruses (such as chikungunya, Japanese encephali-
tis, yellow fever, or Zika viruses) are endemic or
> ≤30% DEET should be used on children
epidemic. Among 8 children who were diagnosed
aged >2 months.
with acute dengue infection after visiting friends
> Repellents with DEET should not be used and relatives in the Caribbean, 3 developed severe
on infants aged <2 months.
dengue. Children traveling to areas with dengue
or other arboviruses should use the same mos-
Repellents can be applied to exposed skin and
quito protection measures described for malaria.
clothing; however, they should not be applied
However, families should be counseled that,
under clothing. Repellents should never be used
unlike the mosquitoes that transmit malaria, the
over cuts, wounds, or irritated skin. Young chil-
Aedes mosquitoes that transmit dengue, chikun-
dren should not be allowed to handle the product.
gunya, yellow fever, and Zika are aggressive day-
When using repellent on a child, an adult should
time biters and can also bite at night. Clinicians
apply it to his or her own hands and then rub them
should consider dengue or other arboviral infec-
on the child, with the following considerations:
tions in children with fever if they have recently
• Avoid the child’s eyes and mouth, and apply been in an endemic or epidemic area.
sparingly around the ears.
INFECTION AND INFESTATION
• Do not apply repellent to children’s hands, FROM SOIL CONTACT
since children tend to put their hands in their
Children are more likely than adults to have
mouths.
contact with soil or sand and therefore may be
7 • Heavy application and saturation are gener-
ally unnecessary for effectiveness. If biting
exposed to diseases caused by infectious stages
of parasites present in soil, including ascaria-
insects do not respond to a thin film of repel- sis, hookworm infestation, cutaneous or visceral
lent, then apply a bit more. larva migrans, trichuriasis, and strongyloidia-
sis. Children and infants should wear protective
• After returning indoors, wash treated footwear and play on a sheet or towel rather than
skin with soap and water or bathe. This
directly on the ground. Clothing should not be
is particularly important when repel-
dried on the ground. In countries with a tropical
lents are used repeatedly in a day or on
climate, clothing or diapers dried in the open air
consecutive days.
should be ironed before use to prevent infestation
Products that contain both repellents and sun- with fly larvae.
screen are generally not recommended, because
instructions for use are different and sunscreen ANIMAL EXPOSURES
may need to be reapplied more often and in larger AND RABIES
amounts than repellent alone. In general, apply Worldwide, rabies is more common in chil-
sunscreen first, and then apply repellent. dren than adults. In addition to the potential for
Mosquito coils should be used with caution in increased contact with animals, children are also
the presence of children to avoid burns and inad- more likely to be bitten on the head or neck, leading
vertent ingestion. For more information about to more severe injuries. Children and their families
repellent use and other protective measures, see should be counseled to avoid all stray or unfamil-
Chapter 2, Protection against Mosquitoes, Ticks, iar animals and to inform adults of any contact or
& Other Arthropods. bites. Bats throughout the world are considered to
have the potential to transmit rabies virus. Animal
DENGUE AND OTHER bites and scratches should be washed thoroughly
ARBOVIRUSES with water and soap (and povidone iodine if avail-
Pediatric VFR travelers who may have frequent and able); for mammal bites and scratches, the child
prolonged travel may have risk similar to children should be evaluated promptly to assess the need
for rabies postexposure prophylaxis. Because automobiles and other vehicles, children weigh-
rabies vaccine and rabies immune globulin may ing ≤40 lb (18 kg) should be restrained in age-
not be available in certain destinations, families appropriate car seats or booster seats, as described
should seriously consider purchasing medical above. These seats often must be carried from
evacuation insurance. home, since availability of well-maintained and
approved seats may be limited abroad. In gen-
AIR TRAVEL eral, children are safest traveling in the rear seat;
Although air travel is safe for healthy newborns, no one should ever travel in the bed of a pickup
infants, and children, a few issues should be con- truck. Families should be counseled that in many
sidered in preparation for travel. Children with developing countries, cars may lack front or rear
chronic heart or lung problems may be at risk for seatbelts. They should attempt to arrange trans-
hypoxia during flight, and a clinician should be portation in vehicles or rent vehicles with seat-
consulted before travel. Making sure that children belts and other safety features.
can be safely restrained during a flight is a safety
consideration. Severe turbulence or a crash can Drowning and Water-Related Illness
create enough momentum that a parent cannot and Injuries
hold onto a child: Drowning is the second leading cause of death
in young travelers. Children may not be familiar
• Children should be placed in a rear-facing with hazards in the ocean or in rivers. Swimming
Federal Aviation Authority–approved child- pools may not have protective fencing to keep
safety seat until they are aged ≥1 year and toddlers from falling into the pool. Close supervi-
weigh ≥20 lb (9 kg). sion of children around water is essential. Water
• Children aged ≥1 year and 20–40 lb (9–18 kg)
should use a forward-facing Federal Aviation
safety devices such as life vests may not be availa-
ble abroad, and families should consider bringing
7
Authority–approved child-safety seat. these from home. Protective footwear is import-
ant to avoid injury in many marine environments.
• Children who weigh >40 lb (18 kg) can be Schistosomiasis is a risk to children and adults
secured in the aircraft seat belt. in endemic areas. While in schistosomiasis-
Ear pain can be troublesome for infants and chil- endemic areas (Map 3-12), children should not
dren during descent. Pressure in the middle ear swim in fresh, unchlorinated water such as lakes
can be equalized by swallowing or chewing: or ponds.
descend to see if they improve. Acetazolamide is be diminished by one-third, and covering cloth-
not approved for pediatric use for altitude illness, ing should be worn or time in the sun decreased
but it is generally safe in children when used for accordingly.
other indications.
OTHER CONSIDERATIONS
SUN EXPOSURE Travel Stress
Sun exposure, and particularly sunburn before age Changes in schedule, activities, and environ-
15 years, is strongly associated with melanoma ment can be stressful for children. Including chil-
and other forms of skin cancer (see Chapter 2, dren in planning for the trip and bringing along
Sun Exposure). Exposure to UV light is highest familiar toys or other objects can decrease these
near the equator, at high altitudes, during mid- stresses. For children with chronic illnesses, deci-
day (10 am–4 pm), and where light is reflected sions regarding timing and itinerary should be
off water or snow. Sunscreens are generally rec- made in consultation with the child’s health care
ommended for use in children aged >6 months. providers.
Sunscreens (or sun blocks), either physical (such
as titanium or zinc oxides) or chemical (sun pro- Insurance
tection factor [SPF] ≥15 and providing protec- As for any traveler, insurance coverage for ill-
tion from both UVA and UVB), should be applied nesses and injuries while abroad should be ver-
as directed, and reapplied as needed after sweat- ified before departure. Consideration should be
ing and water exposure. Babies aged <6 months given to purchasing special medical evacuation
require extra protection from the sun because of insurance for airlifting or air ambulance to an area
their thinner and more sensitive skin; severe sun- with adequate medical care (see Chapter 2, Travel
7 burn for this age group is considered a medical
emergency. Babies should be kept in the shade
Insurance, Travel Health Insurance, & Medical
Evacuation Insurance).
and wear clothing that covers the entire body.
A minimal amount of sunscreen can be applied Identification
to small exposed areas, including the infant’s face In case family members become separated, each
and hands. infant or child should carry identifying informa-
Sun-blocking shirts are available that are made tion and contact numbers in his or her own cloth-
for swimming and preclude having to rub sun- ing or pockets. Because of concerns about illegal
screen over the entire trunk. Hats and sunglasses transport of children across international borders,
also reduce sun injury to skin and eyes. If both if only 1 parent is traveling with the child, he or she
sunscreen and a DEET-containing insect repel- may need to carry relevant custody papers or a
lent are applied, the SPF of the sunscreen may notarized permission letter from the other parent.
BIBLIOGRAPHY
1. Ashkenazi S, Schwartz E, Ryan M. Travelers’ diarrhea in versus adults hospitalized with imported malaria.
children: what have we learnt? Pediatr Infect Dis J. 2016 Pediatr Emerg Care. 2016 Apr;32(4):227–31.
Jun;35(6):698–700. 5. Hagmann S, Neugebauer R, Schwartz E, Perret
2. Bradley JS, Jackson MA, Committee on Infectious C, Castelli F, Barnett ED, et al. Illness in chil-
Diseases. The use of systemic and topical fluoroquinolo- dren after international travel: analysis from the
nes. Pediatrics. 2011 Oct;128(4):e1034–45. GeoSentinel Surveillance Network. Pediatrics. 2010
3. Fedorowicz Z, Jagannath VA, Carter B. Antiemetics for May;125(5):e1072–80.
reducing vomiting related to acute gastroenteritis in 6. Herbinger KH, Drerup L, Alberer M, Nothdurft HD,
children and adolescents. Cochrane Database Syst Rev. Sonnenburg F, Loscher T. Spectrum of imported infec-
2011 Sep 7(9):1–71. tious diseases among children and adolescents return-
4. Goldman-Yassen AE, Mony VK, Arguin PM, Daily JP. ing from the tropics and subtropics. J Travel Med. 2012
Higher Rates of misdiagnosis in pediatric patients May-Jun;19(3):150–7.
7. Hunziker T, Berger C, Staubli G, Tschopp A, Weber 9. Krishnan N, Purswani M, Hagmann S. Severe dengue
R, Nadal D, et al. Profile of travel-associated illness virus infection in pediatric travelers visiting friends and
in children, Zurich, Switzerland. J Travel Med. 2012 relatives after travel to the Caribbean. Am J Trop Med
May-Jun;19(3):158–62. Hyg. 2012 Mar;86(3):474–6.
8. Kamimura-Nishimura K, Rudikoff D, Purswani M, 10. van Rijn SF, Driessen G, Overbosch D, van Genderen
Hagmann S. Dermatological conditions in inter- PJ. Travel-related morbidity in children: a pro-
national pediatric travelers: epidemiology, preven- spective observational study. J Travel Med. 2012
tion and management. Travel Med Infect Dis. 2013 May-Jun;19(3):144–9.
Nov-Dec;11(6):350–6.
VACCINE RECOMMENDATIONS
FOR INFANTS & CHILDREN
Michelle S. Weinberg
Vaccinating children for travel requires careful the CDC website for up-to-date requirements and
evaluation. Whenever possible, children should recommendations (www.cdc.gov/travel).
complete the routine immunizations of childhood Additional information about diseases and
on a normal schedule. However, travel at an ear-
lier age may require accelerated schedules. Not all
routine vaccination is available in the disease-
specific sections in Chapter 3. Interactive tools for
7
travel-related vaccines are effective in infants, determining routine and catch-up childhood vac-
and some are specifically contraindicated. cination are available at www.cdc.gov/vaccines/
The recommended childhood and adoles- schedules/hcp/child-adolescent.html.
cent immunization schedule is available at www.
cdc.gov/vaccines/schedules/downloads/child/ MODIFYING THE IMMUNIZATION
0-18yrs-schedule.pdf. The catch-up schedule for SCHEDULE FOR INADEQUATELY
children and adolescents who start their vacci- IMMUNIZED INFANTS AND
nation schedule late or who are >1 month behind YOUNGER CHILDREN BEFORE
can also be accessed at www.cdc.gov/vaccines/ INTERNATIONAL TRAVEL
schedules/downloads/child/catchup-schedule- Several factors influence recommendations
pr.pdf. This table also describes the recommended for the age at which a vaccine is administered,
minimum intervals between doses for children including age-specific risks of the disease and
who need to be vaccinated on an accelerated its complications, the ability of people of a given
schedule, which may be necessary before interna- age to develop an adequate immune response to
tional travel. the vaccine, and potential interference with the
Country- specific vaccination recommenda- immune response by passively transferred mater-
tions and requirements for departure and entry nal antibodies.
vary over time. For example, proof of yellow fever The routine immunization schedules for
vaccination is required for entry into certain coun- infants and children in the United States do
tries. Meningococcal vaccination is required for not provide specific guidelines for those trav-
travelers entering Saudi Arabia for the annual Hajj. eling internationally before the age when
The World Health Organization issued tempo- specific vaccines and toxoids are routinely rec-
rary vaccination requirements for residents of and ommended. Recommended age limitations are
long-term visitors to countries with active wild based on potential adverse events (yellow fever
poliovirus transmission. Clinicians should check vaccine), lack of efficacy data or inadequate
immune response (polysaccharide vaccines and The second dose is necessary for long-term
influenza vaccine), maternal antibody interfer- protection.
ence (measles-mumps-rubella [MMR] vaccine),
or lack of safety data. In deciding when to travel
• Immune globulin (IG) for hepatitis A pro-
tection: Children aged <1 year or who are
with a young infant or child, parents should be
allergic to a vaccine component and who are
advised that the earliest opportunity to receive
traveling to high-risk areas can receive IG.
routinely recommended immunizations in the
One dose of 0.02 mL/kg intramuscularly pro-
United States (except for the dose of hepatitis
vides protection for up to 3 months, and 1
B vaccine at birth and age 1 month) is at age
dose of 0.06 mL/kg IM provides protection for
6 weeks. In general, live-virus vaccines (MMR,
3–5 months. Children should receive a sec-
varicella, yellow fever) should be administered
ond dose after 5 months if travel continues.
on the same day or spaced ≥28 days apart.
For optimal protection, children aged ≥1 year
who are immunocompromised or have
Routine Infant and Childhood chronic medical conditions and who are plan-
Vaccinations ning to depart to a high-risk area in <2 weeks
Children should receive routine vaccination
should receive the initial dose of vaccine
for hepatitis A virus; hepatitis B virus; diphthe-
along with IG at a separate anatomic injection
ria, tetanus, pertussis; Haemophilus influenzae
site. IG does not interfere with the response
type b (Hib); human papillomavirus; influenza;
to yellow fever vaccine but can interfere
MMR; Neisseria meningitidis; polio; rotavirus;
with the response to other live injected vac-
Streptococcus pneumoniae; and varicella. In order
cines (such as MMR and varicella vaccines).
to complete vaccine series before travel, vaccine
7 doses can be administered at the minimum inter-
vals. Parents should be informed that infants and
Administration of MMR and varicella vaccines
should be delayed for >3 months after admin-
istration of IG for hepatitis A prophylaxis. IG
children who have not received all recommended
should not be administered <2 weeks after
doses might not be fully protected. Rotavirus vac-
MMR or varicella vaccines unless the bene-
cine is unique among the routine vaccines given
fits exceed those of vaccination. If IG is given
to US infants because it has maximum ages for
during this time, the child should be revacci-
the first and last doses; specific consideration
nated with the live MMR or varicella vaccines
should be given to the timing of an infant’s travel
but not sooner than 3 months after IG admin-
so that the infant will still be able to receive the
istration. When travel plans do not allow ade-
vaccine series, if at all possible.
quate time to administer live vaccines and IG
Travel-specific vaccine considerations include
before travel, the severity of the diseases and
the following:
their epidemiology at the destination will help
• Hepatitis A vaccine: Although hepatitis determine the course of preparation.
A is usually mild or asymptomatic in infants
and children aged <5 years, infected children
• Hepatitis B vaccine: Vaccine can be
administered with an accelerated sched-
may transmit the infection to older children
ule of 4 doses of vaccine given at 0, 1, 2, and
and adults, who are at risk for severe disease.
12 months; the last dose may be given on
Vaccination should be ensured for all children
return from travel.
traveling to areas where there is an intermedi-
ate or high risk of hepatitis A. Because of the • Influenza vaccine: Influenza viruses cir-
potential interference by maternal antibod- culate predominantly in the winter months
ies, the hepatitis A vaccine is not approved for in temperate regions (typically November–
children aged <1 year. The vaccine series con- April in the Northern Hemisphere and April–
sists of 2 doses ≥6 months apart. One dose of September in the Southern Hemisphere) but
monovalent hepatitis A vaccine administered can occur year-round in tropical climates.
at any time before departure can provide ade- Since influenza viruses may be circulating at
quate protection for most healthy children. any time of the year, travelers aged ≥6 months
who were not vaccinated during the influenza Immunization Schedules website at www.
season of their country of residence should cdc.gov/vaccines/schedules for additional
be vaccinated ≥2 weeks before departure if information).
vaccine is available. Children aged 6 months
Adolescents and young adults aged 16 through
through 8 years who are receiving influenza
23 years may also be vaccinated with a sero-
vaccine for the first time require 2 doses
group B meningococcal (MenB) vaccine to pro-
administered ≥4 weeks apart. Check the CDC
vide short-term protection against most strains of
website annually for updated recommenda-
serogroup B meningococcal disease. The preferred
tions about seasonal influenza vaccination.
age for MenB vaccination is 16–18 years. ACIP
• MMR or MMRV vaccine: Children travel- also recommends routine use of MenB vaccine
ing abroad may need to be vaccinated at an for people aged ≥10 years who are at increased
earlier age than is routinely recommended. risk for meningococcal disease, including peo-
Infants aged 6–11 months should receive ple who have persistent complement compo-
1 dose of MMR vaccine before departure, nent deficiency and people who have functional
then be vaccinated with MMR or MMRV or anatomic asplenia. MenB vaccine is not recom-
(measles-mumps-rubella-varicella) vaccine at mended for people who travel to or reside in men-
12–15 months (≥28 days after the initial dose) ingitis belt countries, as serogroup B disease is
and again at 4–6 years, according to the rou- rare in this region. MenB vaccine is not routinely
tinely recommended schedule. Children aged recommended for travel to other regions of the
≥12 months should have 2 doses of MMR vac- world unless an outbreak of serogroup B disease
cine before traveling overseas. Children who has been reported. Although MenB vaccine is not
have received 1 dose should receive their
second dose before departure, provided the
licensed in the United States for children <10 years
of age, some European countries have recently 7
2 doses are separated by ≥28 days. introduced MenB vaccine as a routine immuni-
zation for infants. Infants who will be residing in
• Meningococcal vaccine: Epidemics of these countries may consider MenB vaccination
meningococcal disease, caused by the bac-
according to the routine infant immunization rec-
terium Neisseria meningitidis, occur in
ommendations of that country.
sub-Saharan Africa during the dry sea-
son, December through June (see Map 3- • Polio vaccine: Polio vaccine is recom-
11). CDC recommends that travelers be mended for travelers to countries with evi-
vaccinated before traveling to this region. dence of wild poliovirus (WPV) circulation
Meningococcal vaccination is a require- (during the last 12 months) and for travelers
ment to enter Saudi Arabia when traveling to with a high risk of exposure to someone
Mecca during the annual Hajj. Health require- with imported WPV infection when traveling
ments and recommendations for US travel- to some countries that border areas with
ers to the Hajj are available each year on the WPV circulation. Refer to the CDC Travelers’
CDC Travelers’ Health website (www.cdc.gov/ Health website destination pages for the
travel). Meningococcal vaccine is also recom- most up-to-date polio vaccine recommenda-
mended for children aged 2 months through tions (wwwnc.cdc.gov/travel/destinations/
18 years who travel to or reside in areas list). Clinicians should ensure that travelers
where N. meningitidis is hyperendemic or epi- have completed the recommended age-
demic; for these children, providers should appropriate polio vaccine series and have
take care to use a meningococcal vaccine received a single lifetime booster dose, if nec-
that is licensed for the child’s age group and essary. See Chapter 3, Poliomyelitis and CDC’s
contains all 4 serotypes (A, C, Y, W-135). The Immunization Schedules website (www.cdc.
schedule for the primary series and booster gov/vaccines/schedules) for information
doses varies depending on which meningo- about accelerated schedules for completing
coccal vaccine is administered (see CDC’s the routine series. Young adults (≥18 years of
age) who are traveling to areas where polio be seasonal in temperate climates and year-round
vaccine is recommended and who have in more tropical climates. The risk to short-term
received a routine series with either inacti- travelers and those who confine their travel to
vated polio vaccine (IPV) or live oral polio urban centers is low. JE vaccine is recommended
vaccine in childhood should receive a single for travelers who plan to spend a month or lon-
lifetime booster dose of IPV before departure. ger in endemic areas during the JE virus transmis-
Available data do not indicate the need for sion season. JE vaccine should be considered for
more than a single lifetime booster dose with short-term (<1 month) travelers whose itinerary
IPV. However, requirements for long-term or activities might increase their risk for expo-
travelers may apply when departing certain sure to JE virus. The decision to vaccinate a child
countries. should follow the more detailed recommenda-
tions in Chapter 3, Japanese Encephalitis.
• In May 2014, the World Health Organization An inactivated Vero cell culture–derived JE
(WHO) declared the international spread
vaccine (Ixiaro [Valneva]) was licensed by the
of polio to be a Public Health Emergency
Food and Drug Administration in 2009 for use in
of International Concern (PHEIC) under
the United States for travelers aged ≥17 years. In
the authority of the International Health
2013, the recommendations were expanded and
Regulations (2005). To prevent further spread
the vaccine was licensed for use in children start-
of disease, WHO issued temporary polio vac-
ing at age 2 months.
cine recommendations for long-term travel-
The primary series is 2 intramuscular doses
ers (staying >4 weeks) and residents departing
administered 28 days apart. Information on age-
from countries with WPV transmission
appropriate dosing is available at www.cdc.gov/
7 (“exporting WPV” or “infected with WPV”).
Clinicians should be aware that long-term
japaneseencephalitis/vaccine/vaccineChildren.
html. For people aged ≥17 years, ACIP recom-
travelers and residents may be required to
mends that if the primary series was administered
show proof of polio vaccination when depart-
>1 year previously, a booster dose may be given
ing from these countries. All polio vaccina-
before potential JE virus exposures. Although
tion administration should be documented
studies are being conducted on the need for a
on an International Certificate of Vaccination
booster dose following a primary series of Ixiaro
or Prophylaxis (ICVP). The polio vaccine must
in children, data are not yet available.
be received between 4 weeks and 12 months
before the date of departure from the polio- RABIES VACCINE
infected country. Country requirements
Rabies virus causes an acute viral encephalitis
may change, so clinicians should check for
that is virtually 100% fatal. Traveling children may
updates on the CDC Travelers’ Health web-
be at increased risk of rabies exposure, mainly
site. Refer to the Clinical Update: Interim
from dogs that roam the streets in developing
CDC Guidance for Travel to and from
countries. Bat bites carry a potential risk of rabies
Countries Affected by the New Polio Vaccine
throughout the world. There are 2 strategies to
Requirements (wwwnc.cdc.gov/travel/
prevent rabies in humans:
news-announcements/polio-guidance-new-
requirements) for a list of affected countries, • Avoiding animal bites or scratches.
guidance on meeting the vaccination require-
ments, and instructions on how to order and
• Use of preexposure and postexposure pro-
phylaxis. A 3-dose preexposure immunization
fill out the ICVP.
series may be given on days 0, 7, and 21 or 28.
In the event of a subsequent possible rabies
Other Vaccines virus exposure, the child will require 2 more
JAPANESE ENCEPHALITIS VACCINE doses of rabies vaccine on days 0 and 3. The
Japanese encephalitis (JE) virus is transmitted by decision whether to obtain preexposure
mosquitoes and is endemic throughout most of immunization for children should follow
Asia and parts of the western Pacific. The risk can the recommendations in Chapter 3, Rabies.
Children who have not received preexposure countries within the yellow fever–endemic zone.
immunization and may have been exposed to In February 2015, the CDC Advisory Committee
rabies require a weight-based dose of human on Immunization Practices (ACIP) approved a
rabies immune globulin and a series of 4 new recommendation that a single dose of yel-
rabies vaccine doses on days 0, 3, 7, and 14. low fever vaccine provides long-lasting protection
and is adequate for most travelers. The updated
TYPHOID VACCINE recommendations also identify specific groups of
Typhoid fever is caused by the bacterium travelers who should receive additional doses and
Salmonella enterica serotype Typhi. Vaccination is others for whom additional doses may be consid-
recommended for travelers to areas where there is ered. More information, including how to access
a recognized risk of exposure to Salmonella Typhi. yellow fever vaccine in the United States, is avail-
Two typhoid vaccines are available: Vi capsu- able in Chapter 3, Yellow Fever.
lar polysaccharide vaccine (ViCPS) administered Infants aged <9 months are at higher risk
intramuscularly, and oral live attenuated vac- for developing encephalitis from yellow fever
cine (Ty21a). Both vaccines induce a protective vaccine, which is a live virus vaccine. Studies con-
response in 50%–80% of recipients. The ViCPS ducted during the early 1950s identified 4 cases of
vaccine can be administered to children who are encephalitis out of 1,000 children aged <6 months
aged ≥2 years, with a booster dose 2 years later vaccinated with yellow fever vaccine. An addi-
if continued protection is needed. The Ty21a tional 10 cases of encephalitis associated with yel-
vaccine, which consists of a series of 4 capsules low fever vaccine administered to infants aged
(1 taken every other day) can be administered to <4 months were reported worldwide during the
children aged ≥6 years. A booster series for Ty21a 1950s.
should be taken every 5 years, if indicated. The
capsule cannot be opened for administration but
Travelers with infants aged <9 months should
be advised against traveling to areas within the
7
must be swallowed whole. All 4 doses should be yellow fever–endemic zone. ACIP recommends
taken ≥1 week before potential exposure. that yellow fever vaccine never be given to infants
aged <6 months. Infants aged 6–8 months should
YELLOW FEVER VACCINE be vaccinated only if they must travel to areas of
Yellow fever, a disease transmitted by mosquitoes, ongoing epidemic yellow fever and if a high level
is endemic in certain areas of Africa and South of protection against mosquito bites is not pos-
America (see Maps 3-14 and 3-15). Proof of yellow sible. Clinicians considering vaccinating infants
fever vaccination is required for entry into some aged 6–8 months may contact their respective
countries (see Chapter 3, Yellow Fever & Malaria state health departments or CDC toll-free at 800-
Information, by Country). Infants and children CDC-INFO (800-232-4636) or wwwn.cdc.gov/dcs/
aged ≥9 months can be vaccinated if they travel to ContactUs/Form.
BIBLIOGRAPHY
1. CDC. General recommendations on immunization— 4. CDC. Interim CDC guidance for polio vaccination
recommendations of the Advisory Committee on for travel to and from countries affected by wild
Immunization Practices (ACIP). MMWR Recomm Rep. poliovirus. MMWR Morb Mortal Wkly Rep. 2014 Jul
2011 Jan 28;60(2):1–6 4. 11;63(27):591–4.
2. CDC. Use of Japanese encephalitis vaccine in 5. CDC. Yellow fever vaccine: recommendations of the
children: recommendations of the Advisory Advisory Committee on Immunization Practices (ACIP).
Committee on Immunization Practices, 2013. MMWR Recomm Rep. 2015 Jun 19;64(23):647–50.
MMWR Morb Mortal Wkly Rep. 2013 Nov 6. Global Polio Eradication Initiative. Polio public health
15;62(45):898–9 00. emergency: temporary recommendations to reduce
3. CDC. Prevention and control of meningococcal dis- international spread of poliovirus. Geneva: Global Polio
ease: recommendations of the Advisory Committee on Eradication Initiative; 2016 [cited 2016 Apr. 18]; Available
Immunization Practices (ACIP). MMWR Recomm Rep. from: http://www.polioeradication.org/Keycountries/
2013 Mar 22;62(RR-2):1–28. PolioEmergency.aspx.
7. Jackson BR, Iqbal S, Mahon B, Centers for Disease meningococcal vaccines in adolescents and young
Control and Prevention (CDC). Updated recommen- adults: recommendations of the Advisory Committee
dations for the use of typhoid vaccine—╉Advisory on Immunization Practices, 2015. MMWR Morb Mortal
Committee on Immunization Practices, United Wkly Rep. 2015 Oct 23;64(41):1171–╉6.
States, 2015. MMWR Morb Mortal Wkly Rep. 2015 Mar 9. Red Book. 2015 Report of the Committee on Infectious
27;64(11):305–╉8. Diseases. 30th ed. Kimberlin DW, Brady MT, Jackson
8. MacNeil JR, Rubin L, Folaranmi T, Ortega-╉Sanchez IR, MA, editors. Elk Grove Village, IL: American Academy of
Patel M, Martin SW, et al. Use of serogroup B Pediatrics; 2015.
The medical preparation of a traveler who is during travel. For the first 6 months of life, exclu-
breastfeeding differs only slightly from that of sive breastfeeding is recommended. This is espe-
other travelers and depends in part on whether cially important during travel because exclusive
the mother and child will be separated or together breastfeeding means feeding only breast milk,
during travel. Most mothers should be advised no other foods or drinks, which potentially pro-
to continue breastfeeding their infants through- tects infants from exposure to contamination and
out travel. Before departure, mothers may wish pathogens via foods or liquids. Additionally, feed-
7 to compile a list of local breastfeeding resources
at their destination to have on hand. Clinicians
ing only at the breast protects infants from poten-
tial exposure to contamination from containers
and travelers can use the Find a Lactation (bottles, cups, utensils).
Consultant Tool (www.ilca.org/╉why-╉ibclc/╉falc) to Breastfeeding infants require no water supple-
find contact information for experts at their desti- mentation, even in extreme heat environments.
nation. Map 7-╉1 shows destinations with English-╉ Breastfeeding protects children from eustachian
language breastfeeding support groups facilitated tube pain and collapse during air travel, especially
by accredited volunteer mothers. Clinicians and during ascent and descent, by allowing them
travelers can use La Leche League International’s to stabilize and gradually equalize internal and
interactive map (www.llli.org/╉search/╉groups) to external air pressure.
find specific location and contact information for Clinicians should offer information to
breastfeeding support group leaders and groups breastfeeding mothers so that they are better
worldwide. able to continue breastfeeding during travel.
Mothers who plan to use an electric breast Frequent, unrestricted breastfeeding opportu-
pump while traveling may need an electrical cur- nities ensure the mother’s milk supply remains
rent adapter and converter and should have a ample and the child’s nutrition and hydration
back-╉up option available, including information are ideal. Mothers who are concerned about
on hand expression techniques (detailed hand breastfeeding away from home may feel more
expression instructions are available at www. comfortable breastfeeding the child in a fabric
workandpump.com/╉handexpression.htm). carrier. In many countries around the world,
breastfeeding in public places is more widely
TRAVELING WITH A practiced than in the United States. US fed-
BREASTFEEDING CHILD eral legislation protects mothers’ and children’s
Breastfeeding provides unique benefits to moth- right to breastfeed anywhere they are other-
ers and children traveling together. Health care wise authorized to be while on federal property,
providers should explain clearly to breastfeeding which includes US Customs areas, embassies,
mothers the value of continuing breastfeeding and consulates overseas.
7
MAP 7-1 . Breastfeeding support group locations1
1
La Leche League Groups facilitated by accredited volunteer breastfeeding mothers. Country-and group-specific information
available at www.llli.org/search/groups.
protect milk during travel. Expressed milk is not Further research is needed to document the risk of
considered a biohazard. International Air Transport potential vaccine exposure through breastfeeding.
Authority regulations for shipping category B bio- Data about possible excretion of vaccine virus and
logical substances (UN 3373) do not apply to duration of excretion in breast milk are insufficient
expressed milk; it is considered a food for individ- to make a recommendation about temporary sus-
ual use. Travelers shipping frozen milk should fol- pension of breastfeeding, pumping, and discarding
low guidelines for shipping other frozen foods and pumped milk. Until more information is available,
liquids. Expressed milk does not need to be declared yellow fever vaccine should be avoided in breast-
at US Customs upon return to the United States. feeding women. However, when nursing moth-
ers must travel to a yellow fever–endemic area,
IMMUNIZATIONS AND these women should be vaccinated (see Chapter 3,
MEDICATIONS Yellow Fever, for more information).
In almost all situations, clinicians can and should
select immunizations and medications for the Medications
nursing mother that are compatible with breast- According to the American Academy of Pediat
feeding. In most circumstances, it is inappropriate rics (AAP) 2013 Clinical Report: The Transfer of
to counsel mothers to wean in order to be vacci- Drugs and Therapeutics into Human Breast Milk,
nated or to withhold vaccination due to breast- many mothers are inappropriately advised to
feeding status. discontinue breastfeeding or avoid taking essen-
Breastfeeding and lactation do not affect tial medications because of fears of adverse
maternal or infant dosage guidelines for any effects on their infants. The AAP’s Tips for Giving
immunization or medication; children always Accurate Information to Mothers (www2.aap.org/
7 require their own immunization or medication,
regardless of maternal dose. In the absence of doc-
breastfeeding/files/pdf/Lactmed.pdf) advises that
this is usually unnecessary because only a small
umented risk to the breastfeeding child of a par- proportion of medications are contraindicated in
ticular maternal medication, the known risks of breastfeeding mothers or associated with adverse
stopping breastfeeding generally outweigh a theo- effects on their infants. The National Institutes
retical risk of exposure via breastfeeding. for Health’s database of information on drugs and
lactation (LactMed) is an online database of clin-
Immunizations ical information about drugs and breastfeeding
Breastfeeding mothers and children should be (http://toxnet.nlm.nih.gov/newtoxnet/lactmed.
vaccinated according to routine, recommended htm). It provides information about maternal lev-
schedules. Administration of most live and inac- els of drugs in breast milk, infant levels in blood,
tivated vaccines does not affect breastfeeding, potential effects in breastfeeding infants and on
breast milk, or the process of lactation. Only 2 lactation itself, the AAP category indicating the
vaccines, vaccinia (smallpox) and yellow fever, level of compatibility of the drug with breastfeed-
require special consideration. Preventive vaccinia ing, and alternate drugs to consider. The phar-
(smallpox) vaccine is contraindicated for use in maceutical reference guide, Medications and
breastfeeding mothers. Mothers’ Milk, is updated every 2 years and pro-
vides a comprehensive review of the compatibil-
SPECIAL CONSIDERATION: YELLOW FEVER ity or effects on breastfeeding of approximately
VACCINATION 1,000 drugs, including concerns such as risk cat-
Breastfeeding is a precaution for yellow fever vac- egories, pharmacologic properties, interactions
cine administration. Three cases of yellow fever with other drugs, and suitable alternatives.
vaccine–associated neurologic disease (YEL-AND)
have been reported in exclusively breastfed infants SPECIAL CONSIDERATION: ANTIMALARIAL
whose mothers were vaccinated with yellow fever MEDICATIONS
vaccine. All 3 infants were diagnosed with enceph- Since chloroquine and mefloquine may be
alitis and aged <1 month at the time of exposure. safely prescribed to infants, both are considered
BIBLIOGRAPHY
1. Academy of Breastfeeding Medicine (ABM) Protocol February 2016. MMWR Morb Mortal Wkly Rep 2016
Committee. ABM clinical protocol #8: human milk Feb 26;65(7):182–7.
storage information for home use for full-term infants. 3. Hale TW, Rowe HE. Medications and Mothers’ Milk
Breastfeed Med. 2010 Jun;5(3):127–30. 2016: A Manual of Lactational Pharmacology. 17th ed.
2. Fleming-Dutra KE, Nelson JM, Fischer M, Staples JE, Plane, TX: Hale Pub; 2016.
Karwowski MP, Mead P, et al. Update: interim guidelines 4. Kuhn S, Twele-Montecinos L, MacDonald J,
for health care providers caring for infants and chil- Webster P, Law B. Case report: probable transmission
dren with possible Zika virus infection—United States,
of vaccine strain of yellow fever virus to an infant via 6. Section on Breastfeeding. Breastfeeding and the use of
breast milk. CMAJ. 2011 Mar 8;183(4):e243–╉5. human milk. Pediatrics. 2012 Mar;129(3):e827–╉41.
5. Sachdev HP, Krishna J, Puri RK, Satyanarayana L, Kumar 7. Staples JE, Gershman M, Fischer M. Yellow fever vac-
S. Water supplementation in exclusively breastfed cine: recommendations of the Advisory Committee on
infants during summer in the tropics. Lancet. 1991 Apr Immunization Practices (ACIP). MMWR Recomm Rep.
20;337(8747):929–╉33. 2010 Jul 30;59(RR-╉7):1–╉27.
INTERNATIONAL ADOPTION
Mary Allen Staat, Heather Burke
7
at risk for acquiring infectious diseases second- sles, varicella, tetanus, diphtheria, pertussis, hep-
ary to travel or resulting from contact with the atitis A, hepatitis B, and polio must be ensured
newly arrived child. International adoptees may for everyone who will be in the household or in
be underimmunized and are at increased risk for close contact by providing care for the adopted
infections such as measles, hepatitis A, and hep- child. Measles immunity or 2 doses of measles-╉
atitis B because of crowded living conditions, mumps-╉ rubella (MMR) vaccine separated by
malnutrition, lack of clean water, lack of immu- ≥28 days should be documented for all people
nizations, and exposure to endemic diseases born in or after 1957. Varicella vaccine should be
that are not commonly seen in the United States. given to those without a history of varicella disease
Challenges in providing care to internationally or documentation of 2 doses of varicella vaccine
adopted children include the absence of a com- ≥3 months apart. Adults who have not received the
plete medical history, lack of availability of a bio- tetanus-╉diphtheria-╉acellular pertussis (Tdap) vac-
logical family history, questionable reliability of cine, including adults >65 years old, should receive
immunization records, variation in preadoption a single dose of Tdap to protect against Bordetella
living standards, varying disease epidemiology pertussis in addition to tetanus and diphtheria.
in the countries of origin, the presence of pre- Unprotected family members and close contacts
viously unidentified medical problems, and the of the adopted child should be immunized against
increased risk for developmental delays and psy- hepatitis A virus (HAV) before the child’s arrival.
chological issues in these children. Most adult family members and caretakers will
need to be immunized with hepatitis B vaccine,
TRAVEL PREPARATION since it has only been routinely given since 1990.
FOR ADOPTIVE PARENTS If the adopted child is from a polio-╉endemic
AND THEIR FAMILIES area, family members and caretakers should
A pretravel clinic visit is strongly recommended ensure they have completed the recommended
for prospective adoptive parents. In preparation, age-╉appropriate polio vaccine series. A one-╉time
the travel health provider must know the disease inactivated polio booster for adults who have
risks in the adopted child’s country of origin and completed the primary series in the past is rec-
the medical and social histories of the adoptee (if ommended if they are traveling to these areas
and can be considered for adults who remain at States or earlier if the child has fever, anorexia,
home but who will be in close contact caring for diarrhea, vomiting, or other medical concerns.
the child. Additional polio vaccination require- Items to consider during medical examination of
ments for long-term travelers (staying >4 weeks) an adopted child include the following:
and residents departing from countries with polio
transmission may affect travel (see Chapter 3,
• Temperature (fever requires further
investigation)
Poliomyelitis).
Prospective adoptive parents and any children • General appearance: alert, interactive
traveling with them should receive advice on travel
safety, food safety, immunization, malaria chemo-
• Anthropometric measurements: weight/age,
height/age, weight/height, head circumfer-
prophylaxis, diarrhea prevention and treatment,
ence/age, body mass index
and other travel-related health issues, as outlined
elsewhere in this book. Instructions on car seats, • Facial features: length of palpebral fissures,
injury prevention, food safety, and air travel apply philtrum, upper lip (fetal alcohol syndrome:
equally to the adoptive child, so the travel health short palpebral fissures, thin upper lip, indis-
provider should also be familiar with and provide tinct philtrum), other facial features sugges-
information on these child-specific issues. tive of a genetic syndrome
of newly arrived adoptees. Because of widespread (antibiotic type and treatment duration), and
use of the HBV vaccine, the prevalence of HBV follow-up testing are rarely available; therefore,
infection has decreased over the years. Children a full evaluation for disease must be undertaken
found to be positive for HBsAg should be retested and antitreponemal treatment given dependent
6 months later to determine if the child has a upon the results.
chronic infection. Results of a positive HBsAg test
should be reported to the state health depart- HIV
ment. HBV is highly transmissible within the HIV screening is recommended for all interna-
household. All members of households adopt- tionally adopted children. Positive HIV antibodies
ing children with chronic HBV infection must be in children aged <18 months may reflect maternal
immunized and should have follow-up antibody antibody and not infection. Assaying for HIV DNA
titers to determine whether levels consistent with PCR will confirm the diagnosis of HIV in
with immunity have been achieved. Children with the infant or child. Standard screening for HIV
chronic HBV infection should receive additional is with ELISA antibody testing, but some experts
tests for HBV e antigen, HBV e antibody, hepati- recommend PCR for any infant aged <6 months
tis D virus antibody, viral load, and liver function. on arrival. If PCR testing is done, 2 negative results
They should be vaccinated for hepatitis A if they from assays administered 1 month apart, at least
are not immune. They should also have a consul- one of which is done after the age of 4 months, are
tation with a pediatric gastroenterologist. Repeat necessary to exclude infection. Children with HIV
screening at 6 months after arrival should be done infection should be referred to a specialist. Some
on all children who initially test negative for HBV experts recommend repeating the screen for HIV
surface antibody. antibodies 6 months after arrival if the initial test-
Hepatitis C
ing is negative.
7
Routine screening for hepatitis C virus (HCV) Chagas Disease
should be done, since most children with HCV Screening for Chagas disease should be consid-
infection are asymptomatic, screening for risk ered for children arriving from a country endemic
factors is not possible, effective treatments are for Chagas disease. Chagas disease is endemic
available, and close follow-up of infected patients throughout much of Mexico, Central America, and
is needed to identify long-term complications. South America (see Chapter 3, Trypanosomiasis,
Antibody testing with an EIA should be done for American [Chagas Disease]). The risk of Chagas
screening. Since maternal antibody may be pres- disease varies by region within endemic countries.
ent in children <18 months of age, PCR testing Although the risk of Chagas disease is likely low in
should be done if the EIA is positive. Children with adopted children from endemic countries, treat-
HCV infection should be referred to a gastroenter- ment of infected children is effective. Serologic
ologist for further evaluation, management, and testing when the child is aged 9–12 months will
treatment. avoid possible false-positive results from mater-
nal antibody. Testing by PCR can be done in chil-
Syphilis dren <9 months of age. If a child tests positive for
Screening for Treponema pallidum is recom- Chagas disease, the child should be referred to a
mended for all internationally adopted children. specialist for further evaluation and management.
Initial screening is done with both nontreponemal
and treponemal tests. Treponemal tests remain Malaria
positive for life in most cases even after success- Routine screening for malaria is not recom-
ful treatment and are specific for treponemal dis- mended for internationally adopted children.
eases, which include syphilis and other diseases However, thick and thin malaria smears should
(such as yaws, pinta, and bejel) that can be seen be obtained immediately for any febrile child
in some countries. In children with a history of newly arrived from a malaria-endemic area (see
syphilis, the child’s initial evaluation, treatment Chapter 3, Malaria).
immunization schedule of the United Nations to the vaccines reportedly administered and
Expanded Programme of Immunizations (begun reimmunize only for those diseases to which
in 1974). In many developing countries, HBV, the child has no protective titers. Immunity to
Haemophilus influenzae type b (Hib), and rotavi- B. pertussis is an exception; antibody titers do
rus vaccines have become more widely available. not correlate with immune status to B. pertussis.
Upon arrival in the United States, >90% of newly However, protective antibody levels to diph-
arrived internationally adopted children need theria and tetanus imply protective antibody
catch-up immunizations to meet ACIP guidelines. levels to B. pertussis. For children ≥6 months of
Hepatitis A, Hib, human papillomavirus, mumps, age, testing can be done for diphtheria (IgG),
pneumococcal conjugate, rotavirus, rubella, and tetanus (IgG), polio (neutralizing antibody to
varicella vaccines are often not available in devel- each serotype), hepatitis B (surface antibody),
oping countries. Reliability of vaccine records and Hib. Reimmunization for pneumococcus
appears to differ by, and even within, country of is recommended given that there are 13 sero-
origin. Some children may have an immuniza- types in the vaccine. Most experts recommend
tion record with documentation of the vaccines serologic testing for infants and children aged
and dates they were given, and others may have ≥6 months. For children ≥12 months of age, test-
incomplete documentation or no record at all. ing can be done for measles, mumps, rubella,
In addition, some children may be immune to hepatitis A, and varicella. MMR is not given in
vaccine-preventable diseases such as hepatitis A, most countries of origin; measles vaccine is
measles, mumps, rubella, or varicella. A clinical often administered as a single antigen.
diagnosis of any of these diseases should not be Immunizations should be given according to
accepted as evidence of immunity. the current ACIP schedule for catch-up vacci-
Providers can choose 1 of 2 approaches for
vaccination of internationally adopted children.
nation. If the infant is <6 months old and there
is uncertainty regarding immunization status
7
The first is to reimmunize regardless of immu- or validity of the immunization record, the child
nization record. The second, applicable to chil- should be reimmunized according to the ACIP
dren aged ≥6 months, is to test antibody titers schedule.
BIBLIOGRAPHY
1. American Academy of Pediatrics. Medical evaluation of 2014. MMWR Morb Mortal Wkly Rep. 2014 Feb. 7,
internationally adopted children for infectious diseases. 2014;63(5):108–9.
In: Pickering LK, editor. Red Book: 2015 Report of the 6. CDC, ACIP. Updated recommendations from the
Committee on Infectious Diseases. 30th ed. Elk Grove Advisory Committee on Immunization Practices (ACIP)
Village, IL: American Academy of Pediatrics; 2015. for use of hepatitis A vaccine in close contacts of newly
2. American Academy of Pediatrics Committee on arriving international adoption. MMWR Morb Mortal
Infectious Diseases. Recommendations for adminis- Wkly Rep. 2009;58(36):1006–7.
tering hepatitis A vaccine to contacts of international 7. Immigrant visas issued to orphans coming into
adoptees. Pediatrics. 2011 Oct;128(4):803–4. the US. [database on the Internet]. US Department
3. CDC. Measles among adults associated with adop- of State. 1999–2015 [cited 2016 Apr. 17]. Available
tion of children in China—California, Missouri, and from: http://adoption.state.gov/about_us/statistics.
Washington, July–August 2006. MMWR Morb Mortal php.
Wkly Rep. 2007 Feb 23;56(7):144–6. 8. Mandalakas AM, Kirchner HL, Iverson S, Chesney M,
4. CDC. CDC immigration requirements: technical Spencer MJ, Sidler A, et al. Predictors of Mycobacterium
instructions for tuberculosis screening and treat- tuberculosis infection in international adoptees.
ment: using cultures and directly observed therapy. Pediatrics. 2007 Sep;120(3):e610–6.
2009 [cited 2016 June 20]. Available from: http://www. 9. Staat MA, Rice M, Donauer S, Mukkada S,
cdc.gov/immigrantrefugeehealth/pdf/tuberculosis-ti- Holloway M, Cassedy A, et al. Intestinal parasite
2009.pdf. screening in internationally adopted children: impor-
5. CDC. Recommended immunization schedules for tance of multiple stool specimens. Pediatrics. 2011
persons aged 0 through 18 years—United States, Sep;128(3):e613–22.
10. Staat MA, Stadler LP, Donauer S, Trehan I, Rice M, 11. Stadler LP, Donauer S, Rice M, Trehan I, Salisbury
Salisbury S. Serologic testing to verify the immune S, Staat MA. Factors associated with protective
status of internationally adopted children against antibody levels to vaccine preventable diseases in
vaccine preventable diseases. Vaccine. 2010 Nov internationally adopted children. Vaccine. 2010 Dec
23;28(50):7947–55. 10;29(1):95–103.
Advising Travelers
with Specific Needs
IMMUNOCOMPROMISED
TRAVELERS
Camille Nelson Kotton, Andrew T. Kroger, David O. Freedman
and discuss whether any of the disease- immune suppression. Vaccine recommendations
prevention measures recommended for the for different categories of immunocompromised
proposed trip could destabilize the under- adults are shown in Table 8-1.
lying medical condition, directly or through
drug interactions.
MEDICAL CONDITIONS WITHOUT
• Do the conditions, medications, and treat- SIGNIFICANT IMMUNOLOGIC
ments of the traveler constitute contraindi- COMPROMISE
cations to, decrease the effectiveness of, or With regard to travel immunizations, travelers
increase the risk for adverse events of any whose health status places them in one of the
of the disease-prevention measures recom- following groups are not considered significantly
mended for the proposed trip? Depending on immunocompromised and should be prepared
the destination, such measures may include as any other traveler, although the nature of the
immunizations and drugs used for malaria underlying disease needs to be kept in mind.
chemoprophylaxis and management of trav-
elers’ diarrhea. Are there specific health haz- 1. Travelers receiving corticosteroid therapy
ards at the destination that would exacerbate under any of the following circumstances:
the underlying condition or be more severe in > Short-or long-term daily or alternate-day
an immunocompromised traveler? If so, can therapy with <20 mg of prednisone or
specific interventions be recommended to equivalent.
mitigate these risks? > Long-term, alternate-day treatment with
short-acting preparations.
• If an immunocompromised traveler were to > Maintenance steroids at physiologic doses
become ill while traveling, what are the health
(replacement therapy).
care options (see Chapter 2, Obtaining Health
> Steroid inhalers or topical steroids (skin,
Care Abroad)? What would the traveler do
8 should medical evacuation be required? An
immunocompromised traveler should have a
ears, or eyes).
> Intraarticular, bursal, or tendon injection
of steroids.
plan for when and how to seek care overseas
> If >1 month has passed since high-dose
and how to pay for it.
steroids (≥20 mg per day of prednisone or
The traveler’s immune status is particularly rel- equivalent for >2 weeks) have been used.
evant to immunizations. Overall considerations After short-term (<2 weeks) therapy with
for vaccine recommendations, such as destina- daily or alternate-day dosing of ≥20 mg of
tion and the likely risk of exposure to disease, are prednisone or equivalent, some experts
the same for immunocompromised travelers as will still wait 2 weeks or more before
for other travelers. The risk of severe illness or administering live vaccines.
death from a vaccine-preventable disease must 2. HIV patients without severe immunosup-
be weighed against potential adverse events pression ( for definitions of severe immuno
from administering a live vaccine to an immu- suppression, see www.cdc.gov/mmwr/
nocompromised patient. In some complex cases preview/mmwrhtml/rr6002a1.htm).
when travelers cannot tolerate recommended 3. Travelers with a history of cancer who
immunizations or prophylaxis, the traveler received their last chemotherapy treatment
should consider changing the itinerary, altering ≥3 months previously and whose malignancy
the activities planned during travel, or deferring is in remission.
the trip. 4. Hematopoietic stem cell transplant recipi-
For purposes of clinical assessment and ents who are >2 years posttransplant, not on
approach to immunizations, immunocompro- immunosuppressive drugs, with no evidence
mised travelers may be thought of as falling into of ongoing malignancy, and without graft-
1 of 4 groups, based on mechanism and level of versus-host disease.
Live Vaccines
Measles-mumps-rubella (MMR) R3 X3 X3 U U U
Typhoid, Ty21a X X X U U U
Varicella (adults)4 C4 X4 X4 U U U
Zoster OC7 X7 X U U U
Inactivated Vaccines
IMMUNOCOMPROMISED TRAVELERS
Tdap, DTaP U U U U U U
(continued)
559
8
05
560
6
8
ADVISING TRAVELERS WITH SPECIFIC NEEDS
Influenza (inactivated) R R R R R R
Japanese encephalitis15 ND ND ND ND ND ND
Meningococcal group B C C C R C C
Polio (IPV) U U U U U U
Td or Tdap U U U U U U
Typhoid, Vi U U U U U U
Abbreviations: X, Contraindicated (per the Advisory Committee on Immunization Practices [ACIP]); U, Use as indicated for normal hosts; R, Recommended for all in this patient category;
P, Precaution (per ACIP); OC, Other considerations; C, Consider; ND, No data; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.
1
No safety or efficacy data exist regarding use of the current formulation of CVD 103-HgR vaccine in HIV-positive adults or people with severe immunosuppression. Limited data from an
older formulation of the CVD 103-HgR suggest no association between the vaccine and serious or systemic adverse events, and slightly lower immunogenicity of the vaccine in HIV-positive
versus HIV-negative adults.
2
CDC did not recommend use of LAIV in the 2016–2017 season due to questions about LAIV effectiveness. Readers should consult the most recent guideline for recommendations in
subsequent years.
3
MMR vaccination is recommended for all HIV-infected patients aged ≥12 months with (for patients aged <6 years) CD4 percentage ≥15% or (for patients aged ≥6 years) CD4 percentage
≥15% and CD4 counts ≥200/mm3 for ≥6 months if they are without evidence of measles immunity. Immune globulin may be administered for short-term protection of those facing high risk
of measles and for whom MMR vaccine is contraindicated. Additional guidance is available at www.cdc.gov/mmwr/preview/mmwrhtml/rr6204a1.htm.
4
Varicella vaccine should not be administered to people who have cellular immunodeficiencies, but people with impaired humoral immunity (including congenital or acquired
hypoglobulinemia or dysglobulinemia) may be vaccinated. HIV-positive adults with CD4 counts ≥200 cells/mm3 should be considered to receive 2 doses of vaccine spaced at 3-month
intervals. VariZIG (varicella-zoster–specific immune globulin) is recommended for those exposed to varicella or herpes zoster if they do not have evidence of varicella immunity and have
contraindications to vaccination.
5
See details in Chapter 3, Yellow Fever. Yellow fever (YF) vaccination is a precaution for asymptomatic HIV-infected people with CD4 cell counts of 200–499/mm3. YF vaccination is not a
precaution for people with asymptomatic HIV infection and CD4 cell counts ≥500/mm3. YF vaccine is also considered contraindicated by ACIP for symptomatic HIV patients without AIDS
and with CD4 counts <200/mm3.
561
6
No data suggest increased risk of serious adverse events after use of YF vaccine in people with these conditions; however, varying degrees of immune deficit might be present, and
providers should carefully weigh vaccine risks and benefits before deciding to vaccinate people with these conditions.
7
Also contraindicated by ACIP for symptomatic HIV patients without AIDS and with CD4 counts <200/mm3. No recommendation for asymptomatic HIV patients without AIDS and with CD4
counts ≥200/mm3.
8
Recipients of a hematopoietic stem cell transplant should be vaccinated with a 3-dose regimen 6–12 months after a successful transplant, regardless of vaccination history; at least 4
weeks should separate doses.
9
Only recommended for asplenic adults who have not previously received Hib vaccine.
10
Routinely indicated for all men who have sex with men, people with multiple sexual partners, hemophiliacs, patients with chronic hepatitis, injection drug users, and others.
11
Hepatitis B vaccination is indicated for people at risk for infection by sexual exposure, including sex partners of hepatitis B surface antigen (HBsAg)-positive people, sexually active
people who are not in a long-term mutually monogamous relationship, people seeking evaluation or treatment for a sexually transmitted disease, men who have sex with men, people at
risk for infection by percutaneous or mucosal exposure to blood, current or recent injection-drug users, household contacts of HBsAg-positive people, residents and staff of facilities for
developmentally disabled people, health care and public safety workers with reasonably anticipated risk for exposure to blood or blood-contaminated body fluids, people with end-stage
renal disease, international travelers to regions with high or intermediate levels (HBsAg prevalence >2%) of endemic HBV infection (see Map 3-4), people with chronic liver disease, and
people with HIV infection.
12
Adult patients receiving hemodialysis or with other immunocompromising conditions should receive 1 dose of 40 μg/mL Recombivax HB administered on a 3-dose schedule at 0, 1, and
6 months or 2 doses of 20 μg/mL (Engerix-B) administered simultaneously on a 4-dose schedule at 0, 1, 2, and 6 months. Test for antibodies to hepatitis B virus surface antigen serum
after vaccination and revaccinate if initial antibody response is absent or suboptimal (<10 mIU/mL). HIV-infected nonresponders may react to a subsequent vaccine course if CD4 cell
counts rise to 500/mm3 after institution of highly active antiretroviral therapy. See text for discussion of other immunocompromised groups.
13
People with diabetes who are younger than 60 years as soon as feasible after diagnosis; people with diabetes who are age 60 years or older at the discretion of the treating clinician
based on the likelihood of acquiring HBV infection, including the risk posed by an increased need for assisted blood glucose monitoring in long-term care facilities, the likelihood of
experiencing chronic sequelae if infected with HBV, and the likelihood of immune response to vaccination; all people with chronic liver disease not caused by hepatitis B. At present,
routine testing of antibody response after vaccination in people with diabetes or chronic liver disease is not recommended.
14
HPV vaccine should be administered as indicated for males and females but is additionally recommended for all in this patient category for men 22 through 26 years of age (otherwise
male indication is through age 21 years). Female indication in each category is through 26 years of age.
15
No safety or efficacy data exist regarding the use of Ixiaro in immunocompromised people. In general, inactivated vaccines can be administered safely to people with altered
immunocompetence, using the usual doses and schedules, but the effectiveness might be suboptimal. The inactivated, Vero cell–derived Japanese encephalitis vaccine, Ixiaro, is
the only Japanese encephalitis vaccine available in the United States; other types of Japanese encephalitis vaccines, including live vaccines, are available internationally but are not
included here.
16
Two doses ≥2 months apart recommended for patients with HIV infection if they are aged ≥2 years. If younger than 7 years old at previous dose, a patient should receive an additional
dose of Menactra or Menveo 3 years after the primary series. Boosters should be repeated every 5 years thereafter. If aged ≥7 years at previous dose, a patient should receive an
additional dose of Menactra or Menveo 5 years after the primary series. Boosters should be repeated every 5 years thereafter.
17
Previously unimmunized asplenic, HIV-infected, with chronic renal disease or nephrotic syndrome, or immunocompromised adults aged ≥5 years should receive 1 dose of 13-valent
pneumococcal conjugate vaccine (PCV13) followed by 1 dose of pneumococcal polysaccharide vaccine (PPSV23) ≥8 weeks later. People with these conditions previously immunized with
IMMUNOCOMPROMISED TRAVELERS
8
5
26
5. Travelers with autoimmune disease (such as significance of these increases is not known, but
systemic lupus erythematosus, inflammatory they do not preclude the use of any vaccine.
bowel disease, or rheumatoid arthritis) who
are not being treated with immunosuppres- Multiple Sclerosis (MS)
sive or immunomodulatory drugs, although Inactivated vaccines, including influenza, hepati-
definitive data are lacking. tis B, human papillomavirus, and tetanus vaccines,
are generally considered safe for people with MS,
although vaccination should be delayed during
MEDICAL CONDITIONS AND clinically significant relapses until patients have
TREATMENTS ASSOCIATED stabilized or begun to improve from the relapse,
WITH LIMITED IMMUNE typically 4–6 weeks after it began. Published stud-
DEFICITS ies are lacking on the safety and efficacy of other
Asymptomatic HIV Infection vaccines, such as those against hepatitis A, menin-
Asymptomatic HIV- infected adults with CD4 gococcal disease, pertussis, pneumococcal dis-
cell counts of 200–499/mm3 are considered to ease, polio, and typhoid. Inactivated vaccines are
have limited immune deficits and should be vac- theoretically safe for people being treated with an
cinated according to the guidelines in Table 8-1. interferon medication, glatiramer acetate, mitox-
Meningococcal (MenACWY), pneumococcal, and antrone, fingolimod, or natalizumab, although
hepatitis B vaccines are recommended for HIV- safety and efficacy data are lacking.
positive patients regardless of travel plans. Many Modern MS therapy often includes aggressive
clinicians regard patients with CD4 cell counts and early immunomodulatory therapy for many MS
≥200/mm3 who have undetectable viral loads patients, even those with stable disease. Live vac-
as immunologically normal. More specific rec- cines should not be given to people with MS during
ommendations are available for MMR (measles- therapy with immunosuppressants such as mitox-
mumps- rubella) vaccine (www.cdc.gov/mmwr/ antrone, azathioprine, methotrexate, or cyclophos-
8 preview/mmwrhtml/rr6204a1.htm). CD4 counts
while on antiretroviral drugs, rather than nadir
phamide; during chronic corticosteroid therapy; or
during therapy with immunosuppressive biologic
counts, should be used to categorize HIV-infected agents. Patients on glatiramer acetate and inter-
people. To achieve a maximal vaccine response feron therapy have more limited immune deficits.
with minimal risk, many clinicians advise a delay A few published studies suggest that mumps,
of 3 months after immune reconstitution (usu- measles, rubella, varicella, and zoster vaccines
ally 6 months after initiation of antiretroviral may be safe in people with stable MS if adminis-
therapy), if possible, before immunizations are tered 1 month before starting or at the appropri-
administered; however, the optimal time to initi- ate interval (see Duration of Iatrogenic Immunue
ate vaccination after starting antiretroviral ther- Compromise below) after discontinuing immu-
apy has been identified as a gap in knowledge by nosuppressive therapy. One study suggests yel-
the Infectious Diseases Society of America. For low fever vaccine can exacerbate symptoms in MS
MMR vaccine, the recommendation is ≥6 months patients; this risk should be considered in consul-
on antiretroviral therapy with the age-and CD4- tation with the patient’s neurologist before admin-
based criteria. Although seroconversion rates and istering the vaccine.
geometric mean titers of antibody in response
to vaccines may be less than those measured in Other Chronic Conditions
healthy controls, most vaccines can elicit pro- Chronic medical conditions that may be asso-
tective levels of antibody in many HIV-infected ciated with varying degrees of immune deficit
patients in this category. include asplenia, chronic renal disease, chronic
Transient increases in HIV viral load, which liver disease (including hepatitis C), and diabe-
return quickly to baseline, have been observed tes mellitus. These patients should be vaccinated
after administration of several different vaccines according to the guidelines in Table 8-1. Patients
to asymptomatic HIV-infected people. The clinical with complement deficiencies can receive any
live or inactivated vaccine. Factors to consider For children without asplenia aged 9 months
in assessing the general level of immune compe- through 2 years, Menactra should be admin-
tence of patients with chronic diseases include istered at 0 months and 3 months, with an
disease severity, duration, clinical stability, com- 8-week minimum interval between the doses.
plications, comorbidities, and any potentially Booster recommendations vary by age. If
immune- suppressing treatment (see the next younger than 7 years of age at the previous
section in this chapter, Travelers with Chronic dose, a patient should receive a booster dose
Illnesses). of Menactra or Menveo 3 years after the pri-
Adults aged ≥19 years with most immunocom- mary series; boosters should be repeated
promising and some chronic conditions who have every 5 years thereafter. If 7 years old or older
not previously received the 13-valent pneumococ- at the previous dose, a patient should receive
cal conjugate vaccine (PCV13) or the 23-valent an additional dose of Menactra or Menveo
pneumococcal polysaccharide vaccine (PPSV23) 5 years after the primary series; boosters
should receive a single dose of PCV13 followed should be repeated every 5 years thereafter.
by a dose of PPSV23 ≥8 weeks later; those who
have previously received ≥1 dose of PPSV23 • Menveo is recommended on a 2-dose sched-
ule for asplenic adults and children aged
should receive a dose of PCV13 ≥1 year after the
≥2 years and schedules of either 4 or 2 doses
last PPSV23 dose was received. For adults who
for children under the age of 2 depending on
require additional doses of PPSV23, the first such
age at vaccine initiation; booster vaccina-
dose should be given no sooner than 8 weeks after
tions should be repeated every 5 years if risk
PCV13 and ≥5 years after the most recent dose of
is ongoing.
PPSV23.
A blunted response to hepatitis B vaccine has • Serogroup B meningococcal (MenB) vac-
been reported in patients with immunosuppres- cine (Bexsero or Trumenba) is indicated for
sive disease, which may include chronic hepatic asplenic people ≥10 years of age. Travel itself
or renal disease; a decreased response to hepatitis
B vaccine has also been observed in patients with
is not an indication for vaccination with
the serogroup B meningococcal vaccines.
8
diabetes. Additional or higher doses of hepatitis B A booster interval has not been established.
vaccine beyond the standard primary series may
be necessary or indicated. • Asplenic people should receive a 1-time
Asplenic patients are susceptible to over- dose of H. influenzae type b (Hib) conjugate
whelming sepsis with encapsulated bacterial vaccine.
pathogens. Although response to vaccines may People with terminal complement deficiencies
be diminished compared with people who have a and those receiving eculizumab have increased
functioning spleen, immunization against menin- susceptibility to meningococcal infections and
gococcal (MenACWY and MenB), pneumococcal should be immunized against meningococcal
(see dosing above), and Haemophilus influenzae disease with both MenACWY and, if ≥10 years of
type b disease is recommended in these patients, age, MenB vaccine. The recommendations are the
regardless of travel plans. same as for patients with asplenia.
• Dosing schedules for meningococcal ACWY MEDICAL CONDITIONS AND
conjugate vaccine in asplenic people differ
for the 2 available vaccines. Menactra is indi-
TREATMENTS ASSOCIATED
cated for both pediatric and adult popula-
WITH SEVERE IMMUNE
tions aged ≥2 years, with 2 doses separated
COMPROMISE
by ≥2 months. Menactra is licensed from Severe Immune Compromise
9 months through 55 years of age. For people (Non-HIV)
with asplenia, the vaccine should be admin- Severely immunocompromised people include
istered at 2 years through 55 years of age. those who have active leukemia or lymphoma,
generalized malignancy, aplastic anemia, graft- least 3 months after potent immunosuppressive
versus-host disease, or congenital immunodefi- therapy is discontinued, patients should be revac-
ciency; others in this category include people who cinated with all indicated inactivated vaccines.
have received recent radiation therapy, those who People taking any of the following catego-
have had solid-organ transplants and who are on ries of medications are considered severely
active immunosuppression, and hematopoietic immunocompromised:
stem cell transplant recipients (within 2 years of
transplantation or still taking immunosuppressive
• High-dose corticosteroids—Most clini-
cians consider a dose of either >2 mg/kg
drugs). People who are severely immunocompro-
of body weight or ≥20 mg per day of pred-
mised should generally not be given live vaccines,
nisone or equivalent in people who weigh
and inactivated vaccines are less likely to be effec-
>10 kg, when administered for ≥2 weeks,
tive; these patients should consider postponing
as sufficiently immunosuppressive to raise
travel until their immune function improves. For
concern about the safety of vaccination with
people likely to travel in the future, usual travel-
live vaccines. Furthermore, the immune
related vaccines may be considered before start-
response to vaccines may be impaired.
ing immunosuppressive therapies, if feasible.
Clinicians should wait ≥1 month after dis-
People with chronic lymphocytic leukemia
continuation of high-dose systemic corti-
have poor humoral immunity, even early in the
costeroid therapy before administering a
disease course, and rarely respond to vaccines.
live-virus vaccine.
After hematopoietic stem cell transplant, com-
plete revaccination with standard childhood vac- • Alkylating agents (such as cyclophosphamide).
cines should begin at 12 months, with the caveat
that MMR and varicella vaccines should be
• Antimetabolites (such as azathioprine,
6-mercaptopurine, methotrexate). However,
administered 24 months after transplant and only
low-dose monotherapy (methotrexate ≤0.4
if the recipient is assumed to be immunocom-
8 petent. Inactivated influenza vaccine should be
administered beginning ≥6 months after hema-
mg/kg/week, azathioprine ≤3 mg/kg/day,
or 6-mercaptopurine ≤1.5 mg/kg/day) with
these drugs does not preclude administration
topoietic stem cell transplant and annually there-
of zoster vaccine.
after; a dose of inactivated influenza vaccine can
be given as early as 4 months after transplant if • Transplant-related immunosuppressive
there is a community outbreak. A repeat dose of drugs (such as cyclosporine, tacrolimus, siro-
zoster vaccine may be administered after hema- limus, everolimus, azathioprine, and myco-
topoietic stem cell transplant if 24 months have phenolate mofetil).
passed since the transplant, the patient does not
have graft-versus-host disease, and the patient is
• Cancer chemotherapeutic agents are clas-
sified as severely immunosuppressive, as evi-
considered immunocompetent.
denced by increased rates of opportunistic
For solid-organ transplants, the risk of infec-
infections and blunting of responses to cer-
tion is highest in the first year after transplant,
tain vaccines among patient groups.1
so travel to high-risk destinations should be post-
poned until after that time. • Tumor necrosis factor (TNF) blockers such
Doses of inactivated vaccines received while as etanercept, adalimumab, certolizumab
concurrently receiving potent immunosuppres- pegol, golimumab, and infliximab blunt
sive therapy (see below) or during the 2 weeks the immune response to certain vaccines
before starting therapy should not be counted and certain chronic infections. When used
toward completing the vaccination series or relied alone or in combination regimens with other
upon to induce adequate immune responses. At disease-modifying agents to treat rheumatoid
1
Some of these agents are less immunosuppressive than others, such as tamoxifen or trastuzumab given to breast cancer
patients, but clinical data to support safety with live vaccines are lacking.
disease, TNF blockers were associated with agents. For agents not considered highly immuno-
an impaired response to hepatitis A, influ- suppressive (see Table 8-2), consultation with the
enza, and pneumococcal vaccines. prescribing clinician (and possibly a hospital phar-
> Despite measurable impairment of the macist) is recommended to manage individual
immune response, postvaccination antibody patients and estimate degree of immunosuppres-
titers were often sufficient to provide pro- sion. No basis exists for interpreting laboratory
tection for most people; therefore, treatment studies of immune parameters to evaluate vaccine
with TNF blockers does not preclude immu- safety or efficacy. Restarting immunosuppression
nization against hepatitis A, influenza, and after live vaccination has not been studied, but
pneumococcal disease. When possible, all some experts would recommend waiting at least
doses in the hepatitis A and pneumococcal 1 month.
series should be given before travel.
> The use of live vaccines is contraindicated Severe Immune Compromise due
according to the prescribing information to Symptomatic HIV/AIDS
for most of these therapies. Knowledge of the HIV-infected traveler’s current
CD4 T lymphocyte count is necessary for optimal
• Other biologic agents that are immuno pretravel consultation. HIV-infected people with
suppressive or immunomodulatory may
CD4 cell counts <200/mm3, history of an AIDS-
result in significant immunocompro-
defining illness without immune reconstitution,
mise as outlined in Table 8-2. In particular,
or clinical manifestations of symptomatic HIV
lymphocyte-depleting agents (thymoglobulin
are considered to have severe immunosuppres-
or alemtuzumab) and B cell–depleting agents
sion (see Chapter 3, HIV Infection) and should not
(rituximab) are more significantly immuno-
receive live viral or bacterial vaccines because of
suppressive. Consideration of the clinical con-
the risk that the vaccine could cause serious sys-
text in which these were given is important,
temic disease.2 The response to inactivated vac-
especially in hematologic malignancies.
cines also will be suboptimal; thus, vaccine doses
received by HIV-infected people while CD4 cell
8
DURATION OF IATROGENIC IMMUNE counts are <200/ mm3 should be ignored, and
COMPROMISE the person should be revaccinated ≥3 months
The period of time clinicians should wait after dis- after immune reconstitution with antiretroviral
continuation of immunosuppressive therapies therapy.
before administering a live vaccine is not consistent In newly diagnosed, treatment-naïve patients
across all live vaccines. For cancer chemotherapy, with CD4 cell counts <200/mm3, travel should be
radiation therapy, and highly immunosuppressive delayed pending reconstitution of CD4 cell counts
medications (exclusive of lymphocyte- depleting with antiretroviral therapy and ideally complete
agents and organ transplant rejection prophylaxis), suppression of detectable viral replication. Such
the waiting period is 3 months. For lymphocyte- postponement helps minimize risk of infection
depleting (alemtuzumab and rituximab) agents, and avoid immune reconstitution illness during
the waiting period is ≥6 months, although many travel.
experts believe the waiting period should be
≥1 year. For steroid regimens considered immuno- Household Contacts
suppressive (see above), wait 1 month. Zoster vac- The live vaccines MMR, varicella, and rotavirus
cine is exceptional and may be given 1 month after vaccines should be administered to suscepti-
any highly immunosuppressive agent, although ble household contacts and other close contacts
many experts advocate waiting ≥1 year for anti– of immunocompromised patients when indi-
B cell antibodies and other lymphocyte-depleting cated. Zoster and yellow fever vaccine may
2
For MMR vaccine, severe immunosuppression is defined as CD4 percentages <15% at any age in addition to CD4 count <200/
mm3 for people aged >5 years. See www.cdc.gov/mmwr/preview/mmwrhtml/rr6204a1.htm.
Imatinib mesylate Gleevec, STI 571 Signal transduction inhibitor/protein-tyrosine kinase inhibitor
(continued)
Abbreviations: CTLA, cytotoxic T-lymphocyte antigen; TNF, tumor necrosis factor; CD, cluster of differentiation; IL, interleukin;
VEGF, vascular endothelial growth factor; EGFR, epidermal growth factor receptor.
1
This table is based primarily on conservative expert opinion, given the lack of clinical data. Numerous agents are often
8
given in combination with other agents (especially chemotherapy) and are immunosuppressive when given together. The
list provides examples but is not inclusive of all biologic agents that suppress or modulate the immune system. Not all
therapeutic monoclonal antibodies or other biologic agents result in immunosuppression; details of individual agents not
listed here must be reviewed before determining whether live viral vaccines can be given. Some of these agents are less
immunosuppressive than others; specifically, interferon used for hepatitis C and interferon and glatiramer acetate given to
multiple sclerosis patients are immunomodulators, but clinical data to support safety with live vaccines are lacking.
be administered when indicated. Live attenu- travel to destinations that present a true risk for
ated influenza vaccine should not be admin- yellow fever (YF). Significant immunosuppression
istered. Smallpox vaccine (mostly for military is a contraindication to YF vaccination, as there
personnel) is also transmissible to immuno- is a risk of developing a serious adverse event,
compromised household and intimate contacts. such as life- threatening yellow fever vaccine–
Immunocompromised hosts should be cautious associated viscerotropic disease.
about contact with infants who have received If travel is unavoidable to an area where YF
the live rotavirus vaccine and children who may vaccine is recommended (see Maps 3-14 and 3-15)
have received the oral polio vaccine; handwashing and the vaccine has not been given, these travel-
should be emphasized for prevention. ers should be informed of the risk of YF, care-
fully instructed in methods to avoid mosquito
bites, and be provided with a vaccination medi-
SPECIAL CONSIDERATIONS cal waiver (see Chapter 3, Yellow Fever). Travelers
FOR IMMUNOCOMPROMISED should be warned that vaccination waiver docu-
TRAVELERS ments might not be accepted by some countries
Yellow Fever Vaccine and refusal of entry or quarantine is possible.
Unvaccinated travelers with severe immune com- Patients with conditions that the Advisory
promise should be strongly discouraged from Committee on Immunization Practices considers
precautions (as opposed to contraindications) to generally provides protective antibody levels after
administration of YF vaccine, such as asympto- transplant.
matic HIV (see “Precautions” in Chapter 3, Yellow
Fever), may be offered YF vaccine if travel to YF- Response to Vaccination
endemic areas is unavoidable; recipients should Response to vaccination may be muted in
be monitored closely for possible adverse effects. severely immunocompromised hosts, and poten-
Studies show that higher CD4 cell counts and tial travelers should be informed about this. The
lower HIV viral loads seem to be the key determi- decrease in response to vaccination is not partic-
nants for development of protective neutralizing ularly predictable based on the immunosuppres-
antibodies. Patients with undetectable viral loads sive regimen. Encouragingly, recent data in solid
respond well to YF vaccination regardless of CD4 organ transplant recipients vaccinated before
count, although data are limited in those with transplant suggests that a prolonged phase of
CD4 counts <200 mm3. As vaccine response may protective antibody titers can exist after trans-
be suboptimal, such vaccinees are candidates plant. In general, serologic testing for response
for serologic testing 1 month after vaccination. to most travel-related vaccines is not clinically
For information about serologic testing, contact recommended.
your state health department or CDC’s Division
of Vector-Borne Diseases at 970-221-6400. Data Malaria Chemoprophylaxis
from clinical and epidemiologic studies are insuf- Immunocompromised travelers to malaria-
ficient at this time to evaluate the actual risk of endemic areas should be prescribed drugs for
severe adverse effects associated with YF vaccine malaria chemoprophylaxis and receive counsel-
among recipients with limited immune deficits. ing about mosquito bite avoidance—the same as
If international travel requirements, and not true for immunocompetent travelers (see Chapter 3,
exposure risk, are the only reasons to vaccinate Malaria). Special concerns for immunocom-
a traveler with asymptomatic HIV infection or a promised travelers include any of the following
8 limited immune deficit, the physician should pro-
vide a waiver letter.
possibilities:
may have significant interactions with HAART establishing the TB status of immunocompro-
drugs and sometimes with organ transplant– mised travelers going to such destinations may
related immunosuppression. Fluoroquinolones as be helpful in the evaluation of any subsequent
well as azithromycin in combination with calci- travel-associated illness. Depending on the trav-
neurin inhibitors and mTor inhibitors may cause eler’s degree of immune suppression, the baseline
a prolonged QT interval. TB status may be assessed by obtaining a tubercu-
BIBLIOGRAPHY
1. Agarwal N, Ollington K, Kaneshiro M, Frenck R, 4. Dekkiche S, de Valliere S, D’Acremont V, Genton B.
Melmed GY. Are immunosuppressive medications Travel-related health risks in moderately and severely
associated with decreased responses to routine immu- immunocompromised patients: a case-control study.
nizations? A systematic review. Vaccine. 2012 Feb J Travel Med. 2016 Mar;23(3).
14;30(8):1413–24. 5. Farez MF, Correale J. Yellow fever vaccination
2. Barte H, Horvath TH, Rutherford GW. Yellow fever vac- and increased relapse rate in travelers with
cine for patients with HIV infection. Cochrane Database multiple sclerosis. Arch Neurol. 2011 Oct;68(10):
Syst Rev. 2014 (1):Cd010929. 1267–71.
3. CDC. General recommendations on immunization— 6. Garcia Garrido HM, Wieten RW, Grobusch MP,
recommendations of the Advisory Committee on Goorhuis A. Response to hepatitis A vaccination in
Immunization Practices (ACIP). MMWR Recomm Rep. immunocompromised travelers. J Infect Dis. 2015
2011 Jan 28;60(2):1–6 4. Aug 1;212(3):378–85.
7. Kotton CN, Hibberd PL. Travel medicine and transplant vaccine CVD 103-HgR is safe and immunogenic in HIV-
tourism in solid organ transplantation. Am J Transplant. infected and HIV-noninfected adults in Mali. Bull World
2013 Mar;13 Suppl 4:337–47. Health Organ. 1998;76(1):63–71.
8. Loebermann M, Winkelmann A, Hartung HP, Hengel H, 13. Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R,
Reisinger EC, Zettl UK. Vaccination against infection Tomblyn M, et al. 2013 IDSA clinical practice guideline
in patients with multiple sclerosis. Nat Rev Neurol. for vaccination of the immunocompromised host. Clin
2011;8(3):143–51. Infect Dis. 2014 Feb;58(3):309–18.
9. Luks AM, Swenson ER. Evaluating the risks of high 14. Schwartz BS, Rosen J, Han PV, Hynes NA, Hagmann SH,
altitude travel in chronic liver disease patients. High Alt Rao SR, et al. Immunocompromised travelers: demo-
Med Biol. 2015 Jun;16(2):80–8. graphic characteristics, travel destinations, and
10. Masur H, Brooks JT, Benson CA, Holmes KK, Pau AK, pretravel health care from the U.S. Global TravEpiNet
Kaplan JE. Prevention and treatment of opportu- Consortium. Am J Trop Med Hyg. 2015 Nov;93(5):1110–6.
nistic infections in HIV-infected adults and adoles- 15. Visser LG. TNF-α antagonists and immunization. Curr
cents: updated guidelines from the Centers for Disease Infect Dis Rep. 2011 Jun;13(3):243–7.
Control and Prevention, National Institutes of Health,
16. Wieten RW, Goorhuis A, Jonker EF, de Bree GJ,
and HIV Medicine Association of the Infectious
de Visser AW, van Genderen PJ, et al. 17D yel-
Diseases Society of America. Clin Infect Dis. 2014
low fever vaccine elicits comparable long-term
May;58(9):1308–11.
immune responses in healthy individuals and
11. Pacanowski J, Lacombe K, Campa P, Dabrowska M, immune-compromised patients. J Infect. 2016
Poveda JD, Meynard JL, et al. Plasma HIV-RNA is the Jun;72(6):713–22.
key determinant of long-term antibody persistence
17. Wyplosz B, Burdet C, Francois H, Durrbach A, Duclos-
after yellow fever immunization in a cohort of 364 HIV-
Vallee JC, Mamzer-Bruneel MF, et al. Persistence
infected patients. J Acquir Immune Defic Syndr. 2012
of yellow fever vaccine-induced antibodies after
Apr 1;59(4):360–7.
solid organ transplantation. Am J Transplant. 2013
12. Perry RT, Plowe CV, Koumare B, Bougoudogo F, Kotloff Sep;13(9):2458–61.
KL, Losonsky GA, et al. A single dose of live oral cholera
TRAVELERS WITH CHRONIC 8
ILLNESSES
Deborah Nicolls Barbeau
• Advise travelers to pack medications and their medical history so it can be accessed
medical supplies (such as pouching for osto- worldwide (see Chapter 2, Obtaining Health
mies) in their original containers in carry-on Care Abroad).
luggage and to carry a copy of their prescrip- • Help travelers devise a health plan. This plan
tions. Ensure the traveler has sufficient quan- should give instructions for managing minor
tities of medications for the entire trip, plus problems or exacerbations of underlying ill-
extra in case of unexpected delays. Since med- nesses and should include information about
ications should be taken based on elapsed medical facilities available in the destination
time and not time of day, travelers may need country (see Chapter 2, Obtaining Health
guidance on scheduling when to take medica- Care Abroad).
tions during and after crossing time zones.
• Advise travelers to wear a medical alert brace-
• Advise travelers to check with the US let or carry medical information on his or
embassy or consulate to clarify medication her person (various brands of jewelry or tags,
restrictions in the destination country. Some even electronic, are available).
countries do not allow visitors to bring cer-
tain medications into the country, especially • Advise travelers to stay hydrated, wear loose-
narcotics and psychotropic medications. fitting clothing, and walk and stretch at reg-
ular intervals during long-distance travel
• Educate travelers regarding drug interactions (see Chapter 2, Deep Vein Thrombosis &
(see Chapter 2, Interactions among Travel Pulmonary Embolism).
Vaccines & Drugs). Medications (such as war-
farin) used to treat chronic medical illnesses • Consider advising the traveler to use a mobile
may interact with medications prescribed for application to track certain chronic illnesses,
self-treatment of travelers’ diarrhea or malaria such as diabetes, while traveling.
chemoprophylaxis. Discuss all medications
8 used, either daily or on an as-needed basis.
SPECIFIC CHRONIC ILLNESSES
• Provide a clinician’s letter. The letter should Issues related to specific chronic medical illnesses
be on office letterhead stationery and should are addressed in Table 8- 3. These recommen-
outline existing medical conditions, medica- dations should be used in conjunction with the
tions prescribed (including generic names), other recommendations given throughout this
and any equipment required to manage the book. Below is a noninclusive list of additional
condition. resources for information:
Cancer Severe anemia Emphasize food and water Immunosuppressive Check for medication
Cerebral edema due to intracranial tumor precautions medications may alter restrictions in the destination
≤6 weeks since cranial surgery Plan for self-management of response to immunizations country, especially if
Cardiovascular, pulmonary, or dehydration Live attenuated vaccines may controlled medications are
gastrointestinal complications referred DVT precautions be contraindicated required for pain management
to below Supplemental oxygen Revaccination may be See the Immunocompromised
Wear loose-fitting clothing necessary following cancer Travelers section later in this
to prevent worsening of treatment chapter
lymphedema
Cardiovascular Following acute coronary syndrome: Supplemental oxygen Influenza Have sublingual nitroglycerine
diseases • those at very low risk and within 3 days Plan for self-management Pneumococcal available in carry-on bag
after event of dehydration and volume Hepatitis B Mefloquine not recommended
• medium risk and within 10 days after overload; may include for people with cardiac
event adjusting medications conduction abnormalities,
• high risk or awaiting further intervention Bring copy of recent EKG particularly for those with
or treatment—should defer air travel Bring pacemaker or AICD card ventricular arrhythmias
until disease is stable DVT precautions Self-monitoring and
Unstable angina management of INR should
TRAVELERS WITH CHRONIC ILLNESSES
(continued)
573
8
45
574
7
8
ADVISING TRAVELERS WITH SPECIFIC NEEDS
Pulmonary Severe, labile asthma Supplemental oxygen Influenza Consider carrying a short course
diseases Recent hospitalization for acute respiratory Discuss with airline need for Pneumococcal of antibiotics and steroids for
illness other equipment on plane Hepatitis B exacerbations
Bullous lung disease (such as nebulizer) Consider advising an inhaler be
Active lower respiratory infection Plan for self-management of available in carry-on bag, even
Pneumothorax within 2–3 weeks exacerbations (including if not routinely used
Pleural effusion within 14 days COPD, asthma)
High supplemental oxygen requirements DVT precautions
at baseline
Major chest surgery within 10–14 days
Gastrointestinal Surgery, including laparoscopic, within Emphasize food and water Influenza May experience increased
diseases 10–14 days precautions Pneumococcal colostomy output during air travel
Gastrointestinal bleed within 24 hours Consider prescribing Hepatitis A H2 blockers and PPIs increase
Colonoscopy within 24 hours prophylactic antibiotic for TD Hepatitis B susceptibility to TD
Partial bowel obstruction Recommend avoiding Use mefloquine with caution in
Liver failure (especially cirrhosis or heavy undercooked seafood, if any chronic liver disease
alcohol use) cirrhosis or heavy alcohol For YF vaccine, see the
use (Vibrio vulnificus) Immunocompromised Travelers
section later in this chapter
Renal failure and None Emphasize food and water Influenza Know HIV, hepatitis C, and
chronic renal precautions Pneumococcal hepatitis B status
insufficiency Plan for self-management Hepatitis B Atovaquone-proguanil
of dehydration, which can contraindicated when CrCl
worsen renal function <30 mL/min
Arrange dialysis abroad, if AAKP and Global Dialysis
needed websites can help with finding
Adjust medications for CrCl dialysis centers; check for
accreditation
For YF vaccine, see the
Immunocompromised Travelers
section later in this chapter
5
7
CONDITION ABSOLUTE AND RELATIVE CONTRAINDICATIONS TO PRETRAVEL CONSIDERATIONS IMMUNIZATION CONSIDERATIONS MISCELLANEOUS
AIRLINE TRAVEL
Diabetes None Plan for self-management of Influenza Keep insulin and all glucose
mellitus dehydration, diabetic foot, Pneumococcal meter supplies in carry-on
and pressure sores Hepatitis B bag
Insulin adjustments Bring food and supplies needed
Should check FSBG at 4- to to manage hypoglycemia
6-hour intervals during air during travel
travel Check feet daily for pressure
Discuss changes in insulin sores
regimen or oral agent with For YF vaccine, see the
diabetes specialist Immunocompromised
Provide physician’s letter stating Travelers section later in this
need for all equipment, chapter
including syringes, glucose
meter, and supplies
Severe allergic None Plan for managing allergic Many airlines already have
reactions reactions while traveling policies in place for dealing
and consider bringing a with peanut allergies
short course of steroids for Make sure to carry injectable
possible allergic reactions epinephrine in case of a
Should carry injectable severe reaction while in flight
epinephrine and
antihistamines (H1 and H2
blockers)—always have on
TRAVELERS WITH CHRONIC ILLNESSES
person
Autoimmune None Should have a baseline TST Immunosuppressive Particular emphasis should
and or IGRA before starting TNF medications and TNF be placed on food and water
rheumatologic blockers blockers may alter precautions and hand hygiene
diseases response to immunizations
Live attenuated vaccines may
be contraindicated
Abbreviations: DVT, deep vein thrombosis; CHF, congestive heart failure; CABG, coronary artery bypass graft; CVA, cerebrovascular accident; EKG, electrocardiogram; AICD, automatic
implantable cardioverter defibrillators; INR, international normalized ratio; COPD, chronic obstructive pulmonary disease; TD, travelers’ diarrhea; PPIs, proton-pump inhibitors; YF, yellow
fever; CrCl, creatinine clearance; AAKP, American Association of Kidney Patients; FSBG, fingerstick blood glucose; TST, tuberculin skin test; IGRA, interferon-γ release assay; TNF, tumor
necrosis factor.
575
8
5
67
• Crohn’s and Colitis Foundation of America Travelers may also want to investigate interna-
(www.ccfa.org) tional health care accreditation agencies for cen-
ters that have been awarded recognition for high
• Global Dialysis (www.globaldialysis.com) standards and good patient safety records. If trav-
• International Narcotics Control Board elers or their health care providers have concerns
(www.incb.org) about fitness for air travel or the need to obtain
a medical certificate before travel, the medical
• International Self-╉Monitoring unit affiliated with the specific airline is a valuable
Association of Oral Anticoagulated Patients source for information. Remember to notify the
(www.ismaap.org) airline in advance if oxygen or other equipment
• National Multiple Sclerosis Society (www. is needed on the plane. The TSA Cares Helpline
nationalmssociety.org) (toll-╉free at 855-╉787-╉2227) can also provide infor-
mation on how to prepare for the airport security
• Transportation Security Administration screening process with respect to a particular dis-
(www.tsa.gov) ability or medical condition.
• Department of State (www.state.gov)
BIBLIOGRAPHY
1. Aerospace Medical Association. Medical Guidelines 5. McCarthy AE, Burchard GD. The travelers with
for Airline Travel. 2nd ed. Alexandria, VA: Aerospace pre-╉existing disease. In: Keystone JS, Freedman DO,
Medical Association; 2003 [cited 2016 Sep. 27]. Available Kozarsky PE, Connor BA, Nothdurft HD, editors. Travel
from: http://╉www.asma.org/╉asma/╉media/╉asma/╉Travel-╉ Medicine. 3rd ed. Philadelphia: Saunders Elsevier; 2013.
Publications/╉medguid.pdf. pp. 257–╉63.
2. Exemption from import/╉export requirements for per- 6. Perdue C, Noble S. Foreign travel for advanced cancer
8
sonal medical use. 21 CFR Part 1301; 2004 [cited 2016 patients: a guide for healthcare professionals. Postgrad
Sep. 27]; Available from: http://╉www.deadiversion.usdoj. Med J. 2007 Jul;83(981):437–╉44.
gov/╉fed_╉regs/╉rules/╉2004/╉fr0914.htm. 7. Pinsker JE, Becker E, Mahnke CB, Ching M, Larson NS,
3. IATA. Medical Manual. 2015 [cited 2016 Sept 27]; Roy D. Extensive clinical experience: a simple guide
7th:[Available from: www.iata.org/╉publications/╉Pages/╉ to basal insulin adjustments for long-╉distance travel.
medical-╉manual.aspx. J Diabetes Metab Disord. 2013;12(1):59.
4. Josephs LK, Coker RK, Thomas M, British Thoracic 8. Ringwald J, Strobel J, Eckstein R. Travel and oral antico-
Society Air Travel Working Group. Managing patients agulation. J Travel Med. 2009 Jul-╉Aug;16(4):276–╉83.
with stable respiratory disease planning air travel: a 9. Smith D, Toff W, Joy M, Dowdall N, Johnston R, Clark L,
primary care summary of the British Thoracic et al. Fitness to fly for passengers with cardiovascular
Society recommendations. Prim Care Respir J. 2013 disease. Heart. 2010 Aug;96 Suppl 2:ii1–╉16.
Jun;22(2):234–╉8.
PREGNANT TRAVELERS
Diane F. Morof, I. Dale Carroll
A visit with an obstetrician should be a part of the antacids, prenatal vitamins, medication for vagi-
pretravel assessment, to ensure routine prenatal nitis or yeast infection, and support hose, in addi-
care as well as identify any potential problems. The
traveler should be provided with a copy of her pre-
tion to the items recommended for all travelers
(see Chapter 2, Travel Health Kits). Pregnant trav- 8
natal records and physician’s contact information. elers should consider packing a blood pressure
Checking for immunity to various infectious dis- monitor if travel may limit access to a health cen-
eases may obviate the need for some vaccines. ter with blood pressure monitoring available.
A review of the pregnant woman’s travel itiner-
ary, including destinations, accommodations, and CONTRAINDICATIONS FOR
activities, should guide pretravel health advice. TRAVEL DURING PREGNANCY
Preparation includes educating the pregnant Although travel is rarely contraindicated during
woman regarding avoidance of travel-associated a normal pregnancy, complicated pregnancies
risks, the management of minor pregnancy dis- require extra consideration and may warrant a
comforts, and recognition of more serious compli- recommendation that travel be delayed (Box 8-3).
cations. Bleeding, severe pelvic or abdominal pain, Pregnant travelers should be advised that the risk
contractions or premature labor, premature rup- of obstetric complications is highest in the first
ture of the membranes, symptoms of preeclamp- and third trimesters.
sia (unusual swelling, severe headaches, nausea
and vomiting, vision changes), severe vomiting, PLANNING FOR
diarrhea, dehydration, and symptoms of poten- EMERGENCY CARE
tial deep vein thrombosis (unusual swelling of leg Obstetric emergencies often are sudden and life-
with pain in calf or thigh) or pulmonary embolism threatening. Travel to areas where obstetric care
(unusual shortness of breath) require urgent med- may be less than the standard at home is inadvis-
ical attention. able. For a woman in the third trimester of preg-
Pregnant travelers should pack a health kit nancy, it is advisable to identify a medical facility
that includes items such as prescription medi- at her destination that could manage complica-
cations, hemorrhoid cream, antiemetic drugs, tions of pregnancy, delivery, a caesarean section,
and neonatal problems. Some complications may 6,000–8,000 ft (1,829–2,438 m) above sea level;
be managed so the mother could travel to a facil- the lower oxygen tension should not cause fetal
ity where she could receive advanced obstetric problems in a normal pregnancy, but women
care, but some conditions are contraindications with preexisting cardiovascular problems, sickle
for any travel (Box 8-3). In such cases, it may be cell disease, or severe anemia (hemoglobin
preferable to bring help to the patient rather than <8.0 g/dL) may experience the effects of low arte-
transport the patient. rial oxygen saturation. Risks of air travel include
Many health insurance policies do not cover potential exposure to communicable diseases,
complications of pregnancy or the newborn over- immobility, and the common discomforts of fly-
seas. Supplemental travel health insurance should ing. Abdominal distention and pedal edema fre-
8 be strongly considered to cover pregnancy-related
problems and care of the neonate, as needed.
quently occur. The pregnant traveler may benefit
from an upgrade in airline seating and should seek
Evacuation insurance that includes coverage of convenient and practical accommodations (such
pregnancy- related complications is also highly as close proximity to the toilet) and aisle seating
encouraged. so she can move about frequently. Loose clothing
and comfortable shoes are recommended.
TRANSPORTATION Some experts report that the risk of deep vein
CONSIDERATIONS thrombosis in pregnancy is 5–10 times higher
Pregnant women should be advised to wear seat than for nonpregnant women. Preventive mea-
belts, when available, on all forms of transport, sures include frequent stretching, walking and
including airplanes, cars, and buses. A diagonal isometric leg exercises, and wearing graduated
shoulder strap with a lap belt provides the best pro- compression stockings.
tection. The shoulder belt should be worn between Cosmic radiation during air travel poses little
the breasts with the lap belt low across the upper threat, but may be a consideration for pregnant
thighs. When only a lap belt is available, it should travelers who are frequent fliers (such as air crew).
be worn low, between the abdomen and the pelvis. Older airport security machines are magnetome-
ters and are not harmful to the fetus. Newer secu-
Air Travel rity machines use backscatter x- ray scanners,
Most commercial airlines allow pregnant trav- which emit low levels of radiation. Most experts
elers to fly until 36 weeks’ gestation. Some limit agree that the risk of complications from radiation
international travel earlier in pregnancy, and exposure from these scanners is extremely low.
some require documentation of gestational age.
Pregnant travelers should check with the airline Cruise Ship Travel
for specific requirements or guidance. Cabins Most cruise lines restrict travel beyond 28 weeks
of most commercial jetliners are pressurized to of pregnancy, and some as early as 24 weeks.
Pregnant travelers may be required to carry a phy- falls that inject water into the birth canal. Most
sician’s note stating that they are fit to travel and experts advise against scuba diving for pregnant
including the estimated date of delivery. Pregnant women because of risk of fetal gas embolism
women should check with the cruise line for spe- during decompression. Riding bicycles, motor-
cific requirements or guidance. The pregnant trav- cycles, or animals presents risk of trauma to the
eler planning a cruise should be advised regarding abdomen.
motion sickness, gastrointestinal and respiratory
infections, and the risk of falls on a moving vessel. INFECTIOUS DISEASES
Respiratory and urinary infections and vaginitis
ENVIRONMENTAL are more likely to occur and to be more severe in
CONSIDERATIONS pregnancy. Pregnant women who develop travel-
Air pollution may cause more health problems ers’ diarrhea or other gastrointestinal infections
during pregnancy, as ciliary clearance of the bron- may be more vulnerable to dehydration than are
chial tree is slowed and mucus more abundant. nonpregnant travelers. Strict hand hygiene and
Body temperature regulation is not as efficient food and water precautions should be stressed
during pregnancy, and temperature extremes can (see Chapter 2, Food & Water Precautions). Bottled
cause more stress on the gravid woman. In addi- or boiled water is preferable to chemically treated
tion, an increase in core temperature, such as or filtered water. Iodine-containing compounds
with heat prostration or heat stroke, may harm should not be used to purify water for pregnant
the fetus. The vasodilatory effect of a hot envi- women because of potential effects on the fetal
ronment might also cause fainting. For these thyroid (see Chapter 2, Water Disinfection for
reasons, accommodation should be sought in air- Travelers). The treatment of choice for travelers’
conditioned quarters and activities restricted in diarrhea is prompt and vigorous oral hydration;
hot environments. however, azithromycin may be given to pregnant
Pregnant women should avoid activities at women if clinically indicated. Use of bismuth sub-
high altitude unless trained for and accustomed
to such activities; women unaccustomed to high
salicylate is contraindicated.
Hepatitis A and E are both spread by the
8
altitudes may experience exaggerated breathless- fecal-oral route. Hepatitis A has been reported to
ness and palpitations. The common symptoms of increase the risk of placental abruption and pre-
acute mountain sickness (insomnia, headache, mature delivery. Hepatitis E is more likely to cause
and nausea) are frequently also associated with severe disease during pregnancy and may result
pregnancy, and it may be difficult to distinguish in a case-fatality ratio of 15%–30%; when acquired
the cause of the symptoms. Most experts rec- during the third trimester, it is also associated
ommend a slower ascent with adequate time for with fetal complications and fetal death. Some
acclimatization. No studies or case reports show foodborne illnesses of particular concern during
harm to a fetus if the mother travels briefly to pregnancy include toxoplasmosis and listeriosis;
high altitudes during pregnancy. However, it may the risk during pregnancy is that the infection will
be prudent to recommend that pregnant women cross the placenta and cause spontaneous abor-
not stay at sleeping altitudes >12,000 ft (3,658 m), tion, stillbirth, or congenital or neonatal infection.
if possible. Probably the largest concern regard- The pregnant traveler should be warned, therefore,
ing high-altitude travel in pregnancy is that many to avoid unpasteurized cheeses and undercooked
such destinations are inaccessible and far from meat products. Risk of fetal infection increases
medical care (see Chapter 2, Altitude Illness). with gestational age, but severity of infection is
decreased. Parasitic diseases are less common
ACTIVITIES but may cause concern, particularly in women
Pregnant travelers should be discouraged from who are visiting friends and relatives in develop-
undertaking unaccustomed vigorous activity. ing areas. In general, intestinal helminths rarely
Swimming and snorkeling during pregnancy are cause enough illness to warrant treatment during
generally safe, but waterskiing has resulted in pregnancy. Most, in fact, can safely be addressed
with symptomatic treatment until the pregnancy Nonprescription remedies include ginger, which is
is over. On the other hand, protozoan intestinal available as a powder that can be mixed with food
infections, such as Giardia, Entamoeba histolytica, or drinks such as tea. It is also available in candy,
and Cryptosporidium, often do require treatment. such as lollipops. Similarly, pyridoxine (vitamin
These parasites may cause acute gastroenteritis, B6) is effective in reducing symptoms of morning
severe dehydration, chronic malabsorption result- sickness and is available in tablet form, as well as
ing in fetal growth restriction, and in the case of lozenges and lollipops. Antihistamines, such as
E. histolytica, invasive disease, including amebic meclizine and dimenhydrinate, are often used in
liver abscess and colitis. Pregnant women should pregnancy for morning sickness and motion sick-
avoid swimming or wading in freshwater lakes, ness and appear to have a good safety record.
streams, and rivers that may harbor schistosomes.
Pregnant women should avoid mosquito bites VACCINES
when traveling in areas where vectorborne dis- In the best possible scenario, a woman should
eases are endemic. Preventive measures include be up- to-
date on routine vaccinations before
use of bed nets, insect repellents, and protec- she becomes pregnant. The most effective way of
tive clothing (see Chapter 2, Protection against protecting the infant against many diseases is to
Mosquitoes, Ticks, & Other Arthropods). A recent immunize the mother. Tetanus, diphtheria, and
concern for pregnant women is Zika virus infec- pertussis (Tdap) vaccine should be given during
tion. Zika virus is spread primarily through the each pregnancy irrespective of the woman’s his-
bite of an infected Aedes mosquito (Ae. aegypti tory of receiving Tdap. To maximize maternal
and Ae. albopictus). The illness associated with antibody response and passive antibody transfer
Zika is usually mild, but in pregnant women, Zika to the infant, optimal timing for Tdap admin-
virus infection can cause fetal microcephaly and istration is between 27 and 36 weeks of gesta-
other congenital abnormalities. Because of the tion, although it may be given at any time during
risk of birth defects, CDC recommends pregnant pregnancy. Annual influenza vaccine (inacti-
8 women not travel to areas where Zika is present
and take precautions to avoid sexual transmission
vated) is recommended during any trimester for
all women who are or will be pregnant during
of the virus. If travel cannot be avoided, pregnant influenza season. For travelers, vaccination is rec-
women should strictly follow steps to prevent ommended ≥2 weeks before departure if vaccine
mosquito bites. Additional information, including is available. Certain vaccines, including menin-
the most current list of countries and territories gococcal and hepatitis A and B vaccines that are
where Zika virus is a risk, is available at www.cdc. considered safe during pregnancy, may be indi-
gov/travel. Guidance for pregnant women can be cated based on risk. No adverse effects of inacti-
found at the CDC Zika website (www.cdc.gov/ vated polio vaccine (IPV) have been documented
zika/pregnancy/index.html). among pregnant women or their fetuses; how-
ever, vaccination of pregnant women should be
MEDICATIONS avoided because of theoretical concerns. IPV can
Various systems are used to classify drugs in be administered in accordance with the recom-
regard to their safety in pregnancy. In most cases, mended schedules for adults if a pregnant woman
it is preferable to refer to specific data regard- is at increased risk for infection and requires
ing the effects of a given drug during pregnancy immediate protection against polio. Rabies post-
rather than simply to depend on a classification. exposure prophylaxis with rabies immune globu-
Analgesics that can be used during pregnancy lin and vaccine should be administered after any
include acetaminophen and some narcotics. moderate-or high-risk exposure to rabies; pre
Aspirin may increase the incidence of abrup- exposure vaccine may be considered for travelers
tion, and other anti-inflammatory agents could when the risk of exposure is substantial.
cause premature closure of the ductus arterio- Most live-virus vaccines, including measles-
sus. Constipation may require a mild bulk laxa- mumps-rubella vaccine, varicella vaccine, and
tive. Several simple remedies are often effective live attenuated influenza vaccine, are contra-
in relieving the symptoms of morning sickness. indicated during pregnancy; the exception is
yellow fever vaccine, for which pregnancy is con- with high risks of illness and death for both mother
sidered a precaution by the Advisory Committee and child. Malaria in pregnancy may be charac-
on Immunization Practices (ACIP). If travel terized by heavy parasitemia, severe anemia, and
is unavoidable, and the risks for yellow fever sometimes profound hypoglycemia, and may be
virus exposure are felt to outweigh the risks of complicated by cerebral malaria and acute respi-
vaccination, a pregnant woman should be vac- ratory distress syndrome. Placental sequestration
cinated. If the risks for vaccination are felt to out- of parasites may result in fetal loss due to abrup-
weigh the risks for yellow fever virus exposure, tion, premature labor, or miscarriage. An infant
pregnant women should be issued a medical born to an infected mother is apt to be of low birth
waiver to fulfill health regulations. Because preg- weight, and, although rare, congenital malaria is a
nancy might affect immunologic function, sero- concern.
logic testing to document an immune response Because no prophylactic regimen provides
to yellow fever vaccine should be considered. complete protection, pregnant women should
Postexposure prophylaxis of a nonimmune preg- avoid or delay travel to malaria-endemic areas.
nant woman exposed to measles or varicella may However, if travel is unavoidable, pregnant
be provided by administering immune globulin women should take precautions to avoid mos-
(IG) within 6 days for measles or varicella-zoster quito bites, and use of an effective prophylactic
IG within 10 days for varicella. Women plan- regimen is essential.
ning to become pregnant should be advised to Chloroquine and mefloquine are the drugs of
wait 4 weeks after receipt of a live-virus vaccine choice for pregnant women for destinations with
before conceiving. For certain travel-related vac- chloroquine-sensitive and chloroquine-resistant
cines, including Japanese encephalitis vaccine malaria, respectively. Doxycycline is contraindi-
and typhoid vaccine, data are insufficient for a cated because of teratogenic effects on the fetus
specific recommendation for use in pregnant after the fourth month of pregnancy. Primaquine
women. A summary of current ACIP guidelines is contraindicated in pregnancy because the infant
for vaccinating pregnant women is available at
www.cdc.gov/vaccines/pregnancy/hcp/guide-
cannot be tested for G6PD deficiency, putting the
infant at risk for hemolytic anemia. Atovaquone-
8
lines.html. proguanil is not recommended because of lack of
available safety data. A list of the available antima-
MALARIA CHEMOPROPHYLAXIS larial drugs and their uses and contraindications
Malaria may be much more serious in pregnant during pregnancy can be found in Table 3-10 and
than in nonpregnant women and is associated in Chapter 3, Malaria.
BIBLIOGRAPHY
1. ACOG Committee on Obstetric Practice. ACOG 7. Magann EF, Chauhan SP, Dahlke JD, McKelvey SS,
Committee Opinion No. 443: Air travel during preg- Watson EM, Morrison JC. Air travel and pregnancy out-
nancy. Obstet Gynecol. 2009 Oct;114(4):954–5. comes: a review of pregnancy regulations and outcomes
2. Carroll ID, Williams DC. Pre-travel vaccination and for passengers, flight attendants, and aviators. Obstet
medical prophylaxis in the pregnant traveler. Travel Gynecol Surv. 2010 Jun;65(6):396–4 02.
Med Infect Dis. 2008 Sep;6(5):259–75. 8. Mehta P, Smith-Bindman R. Airport full-body screen-
3. CDC. Guidelines for vaccinating pregnant women. ing: what is the risk? Arch Intern Med. 2011 Jun
Atlanta: CDC; 2014 [cited 2016 Sep 27]; Available from: 27;171(12):1112–5.
http://www.cdc.gov/vaccines/pubs/preg-guide.html. 9. Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR.
4. Dotters-Katz S, Kuller J, Heine RP. Parasitic infections in Zika virus and birth defects—reviewing the evidence for
pregnancy. Obstet Gynecol Surv. 2011 Aug;66(8):515–25. causality. N Engl J Med. 2016 May 19;374(20):1981–7.
5. Hezelgrave NL, Whitty CJ, Shennan AH, Chappell 10. Rasmussen SA, Watson AK, Kennedy ED, Broder KR,
LC. Advising on travel during pregnancy. BMJ. Jamieson DJ. Vaccines and pregnancy: past, present, and
2011;342:d2506. future. Semin Fetal Neonatal Med. 2014 Jun;19(3):161–9.
6. Irvine MH, Einarson A, Bozzo P. Prophylactic use of 11. Roggelin L, Cramer JP. Malaria prevention in the preg-
antimalarials during pregnancy. Can Fam Physician. nant traveller: a review. Travel Med Infect Dis. 2014
2011 Nov;57(11):1279–81. May-Jun;12(3):229–36.
TRAVELERS WITH DISABILITIES
Kira A. Barbre
BIBLIOGRAPHY
1. International Civil Aviation Organization. Manual on with stable respiratory disease planning air travel: a
access to air transport by persons with disabilities. primary care summary of the British Thoracic
Montréal: International Civil Aviation Organization; Society recommendations. Prim Care Respir J. 2013
economic, and attitudinal issues. Therefore, this years previously, immunity has waned and is no
review uses the more classic definition. longer protective. In recent years, a number of
VFRs have died of malaria on their return to North
DISPROPORTIONATE America; in the United States in 2012, 55% of
INFECTIOUS DISEASE RISKS those with severe malaria for whom the purpose
IN VFRS of travel was known were VFRs, mostly returned
Altered migration patterns to North America in from West Africa.
the past 30 years have resulted in many immi-
grants originating from Asia, Southeast Asia, and Other Infections
Latin America instead of Europe. Although 13% of From 2008 through 2012 in the United States,
the US population is foreign born, in 2014, 37% of 85% of typhoid and 88% of paratyphoid A cases
overseas international travelers from the United occurred in VFRs, mostly from southern Asia.
States listed VFR as a reason for travel. VFRs Most isolates were resistant or showed decreased
experience a higher incidence of travel-related susceptibility to fluoroquinolone antibiotics.
infectious diseases, such as malaria, typhoid fever, Similar rates of resistant infections were noted
tuberculosis, hepatitis A, and sexually transmitted in imported cases in Switzerland from the Indian
diseases, than do other groups of international subcontinent.
travelers, for a number of reasons: VFR children aged <15 years are at highest
risk for hepatitis A, and many are asymptomatic.
• Lack of awareness of risk A Canadian study found that 65% of hepatitis
• ≤30% have a pretravel health care encounter A cases were in VFRs aged <20 years, and in a
Swedish study of 636 cases of imported infection,
• Financial barriers to pretravel health care 52% were in VFRs, of whom 90% were <14 years
• Lack of access to clinics old. Other diseases, such as tuberculosis, hepatitis
B, cholera, and measles, occur more commonly in
• Cultural and language barriers with health
care providers
VFRs after travel.
8
• Lack of trust in the medical system PRETRAVEL HEALTH
COUNSELING FOR VFRS
• Last-minute travel plans and longer trips Table 8-4 summarizes VFR health risks and pre-
• Travel to higher-risk destinations vention recommendations. It is important to
increase awareness among VFR travelers regard-
• High-risk trip characteristics, such as staying ing their unique risks for travel-related infections
in homes and living the local lifestyle, which
and the barriers to travel health services. If possi-
often includes lack of safe food and water and
ble, clinics should incorporate culturally sensitive
not using bed nets
educational materials, provide language transla-
tors, and provide handouts in multiple languages.
Malaria However, studies in the United Kingdom aimed
In 2012, 54% of imported malaria cases in US at preventing malaria among VFRs showed that
civilians occurred among VFRs. Data from the increased awareness and availability of medica-
GeoSentinel Surveillance Network show that tions do not necessarily increase use of malaria
among ill travelers who present for medical care, chemoprophylaxis, highlighting the complex
VFRs are 8 times more likely to be diagnosed with socioecological context in which VFRs make
malaria than are tourist travelers. Reports from travel health decisions.
the United Kingdom show similar results for VFR
versus tourist travelers to West Africa. Many VFRs Vaccinations
assume they are immune; however, in most VFRs, Travel immunization recommendations and
especially those who left their countries of origin requirements for VFRs are the same as those for
US-born travelers. It is crucial, however, to first try tetanus) or has a history of specific diseases. Adult
to establish whether the immigrant traveler has travelers, in the absence of documentation of immu-
had routine immunizations (such as measles and nizations, may be considered to be susceptible.
Fish-related toxins Eating high-risk foods Avoidance counseling about specific foods (such
and infections Less pretravel advice as raw freshwater fish)
Tuberculosis Increased close contact with local Check PPD 2–3 months after return if history
(particularly population of negative tuberculin skin test and long stay
multidrug- Increased contact with HIV- (>3 months)
resistant) coinfected people Educate about tuberculosis signs, symptoms,
and avoidance
Bloodborne More likely to seek substandard Discuss high-risk behaviors, including tattoos,
and sexually local care piercings, dental work, sexual encounters
transmitted Cultural practices (tattoos, body Encourage purchase of condoms before travel
diseases modification practices) Consider providing syringes, needles, and
Longer stays and increased intravenous catheters for long-term travel
chance of blood transfusion
Higher likelihood of sexual
encounters with local population
Respiratory problems Increased close exposure to fires, Prepare for asthma exacerbations by considering
smoking, or pollution stand-by bronchodilators and steroids
(continued)
Toxin ingestion Purchase of local medications Anticipate need and purchase medications before
(medication Use of traditional therapies travel
adverse events, Use of contaminated products Counsel avoidance of known traditional medications
heavy metal (such as pottery with lead glaze) (such as Hmong bark tea with aspirin) and high-
ingestion) Eating contaminated freshwater fish risk items (such as large reef fish)
Yellow fever Unclear, partial immunity Avoid mosquitoes by taking protective measures
and Japanese from previous exposure or and receiving vaccination when appropriate
encephalitis (risk vaccination
is decreased in
adults)
8
Dengue (especially Severe dengue occurs on repeat Avoid mosquitoes by taking protective measures
risk of severe exposure to a different serotype
dengue) of dengue; VFRs more likely to
have had previous exposure
Abbreviations: VFR, visiting friends and relatives; PPD, tuberculin purified protein derivative; DEET, N,N-diethyl-m-toluamide.
1
Adapted from: Bacaner N, Stauffer W, Boulware DR, Walker PF, Keystone JS. Travel medicine considerations for North
American immigrants visiting friends and relatives. JAMA. 2004;291(23):2856–64.
2
Hypothesis unless referenced to support assertions.
3
In animal models, DEET (liposomal preparations) prevents Schistosoma cercariae from penetrating the skin.
Age-appropriate vaccinations (or serologic studies and complications from varicella disease are
to check for antibody status) should be provided, higher in adults than in children.
with 2 caveats:
Malaria Prevention
• Immunity to hepatitis A should not be VFR travelers to endemic areas should not only
assumed; many young adults and adoles-
be encouraged to take prophylactic medications
cents from developing countries are still
but also should be reminded of the benefits of
susceptible.
barrier methods of prevention, such as bed nets
• Consider varicella immunization for people and insect repellents, particularly for children
born outside the United States. Such travel- (see Chapter 2, Protection against Mosquitoes,
ers may be more susceptible because infec- Ticks, & Other Arthropods). VFRs should be
tion occurs at an older age in tropical than advised that drugs such as chloroquine and pyri-
in temperate regions. Also, rates of death methamine, as well as proguanil monotherapy,
BIBLIOGRAPHY
1. Behrens RH, Neave PE, Jones CO. Imported malaria barriers and pre-╉travel recommendations. Travel Med
among people who travel to visit friends and relatives: is Infect Dis. 2011 Jul;9(4):192–╉203.
current UK policy effective or does it need a strategic 5. LaRocque RC, Deshpande BR, Rao SR, Brunette GW,
change? Malar J. 2015;14:149. Sotir MJ, Jentes ES, et al. Pre-╉travel health care of immi-
2. Chaccour C, Kaur H, Del Pozo JL. Falsified antimalari- grants returning home to visit friends and relatives. Am
als: a minireview. Expert review of anti-╉infective therapy. J Trop Med Hyg. 2013 Feb;88(2):376–╉80.
2015 Apr;13(4):505–╉9. 6. Leder K, Tong S, Weld L, Kain KC, Wilder-╉Smith A, von
3. Date KA, Newton AE, Medalla F, Blackstock A, Sonnenburg F, et al. Illness in travelers visiting friends
Richardson L, McCullough A, et al. Changing pat- and relatives: a review of the GeoSentinel Surveillance
terns in enteric fever incidence and increasing Network. Clin Infect Dis. 2006 Nov 1;43(9):1185–╉93.
antibiotic resistance of enteric fever isolates in the 7. Monge-╉Maillo B, Norman FF, Perez-╉Molina JA, Navarro
United States, 2008–╉2012. Clin Infect Dis. 2016 Aug M, Diaz-╉Menendez M, Lopez-╉Velez R. Travelers visiting
1;63(3):322–╉9. friends and relatives (VFR) and imported infectious
4. Hendel-╉Paterson B, Swanson SJ. Pediatric travelers disease: travelers, immigrants or both? A comparative
visiting friends and relatives (VFR) abroad: illnesses, analysis. Travel Med Infect Dis. 2014 Jan-╉Feb;12(1):88–╉94.
8
HEALTH CARE WORKERS
Henry M. Wu, V. Ramana Dhara, Alan G. Czarkowski, Eric J. Nilles
These challenges should be taken into account by hepatitis C before travel is not routinely recom-
all health care workers when they consider and mended, although it should be considered if risk
prepare for international missions. of exposure will be high and reliable testing will
not be available locally in the event of an exposure.
PRETRAVEL VACCINATION
AND SCREENING PPE AND INFECTION CONTROL
In addition to vaccinations specifically indi-
Health care workers should consistently follow
cated for the country visited and routine age-
standard precautions whenever possible and
appropriate vaccines, all health care workers
apply other precautions (contact, droplet, or air-
should be up-to-date on all recommended vac-
borne) as needed. PPE, including gloves, gowns,
cinations for employment in health care set-
aprons, surgical masks, fit- tested N95 respira-
tings. These include vaccinations (or documented
tor masks, and protective eyewear, may be nec-
immunity) for the following:
essary to achieve personal protection. Workers
• Measles, mumps, and rubella untrained in infection control practices should
not participate in clinical activities, handle clini-
• Influenza cal specimens, or handle contaminated medical
• Varicella equipment. Needlestick injuries are a common
mode of percutaneous exposure to bloodborne
• Tetanus, diphtheria, and pertussis pathogens, and practices known to increase risk
• Hepatitis B of needlestick injuries, such as recapping syringes
or using needles to transfer a bodily fluid between
For hepatitis B, postvaccination serologic test-
containers, should be avoided whenever possi-
ing is recommended for health care workers; of
ble, even if they are commonly practiced locally.
those who do not respond to a primary vaccine
The traveling health care worker should be aware
series, 25%–50% respond to an additional vaccine
8
of the local practice environment in advance of
dose, and 44%–100% respond to a 3-dose revacci-
travel, since limited use of PPE or even reuse of
nation series. Inactivated polio vaccine (given as
equipment that would not be acceptable in the
an adult booster dose) or meningococcal vaccine
United States is common.
may be indicated for specific locations experienc-
For further details, guidelines, and training
ing high incidence or outbreaks of these infec-
materials on standard precautions and PPE, see
tions. Providers should consult country-specific
www.cdc.gov/HAI/prevent/ppe.html and www.cdc.
recommendations and travel alerts on the CDC
gov/hicpac/2007IP/2007isolationPrecautions.
Travelers’ Health website (www.cdc.gov/travel)
html. Specific PPE advice may be recommended
for updated vaccination recommendations.
for certain infections that pose high risk to health
Regular screening for latent TB infection with
care workers (such as MERS, avian influenza, and
tuberculin skin test or interferon-γ release assay is
Ebola virus; see disease-specific websites at www.
recommended for health care workers, and test-
cdc.gov for further advice).
ing before and after travel is particularly import-
In preparation, traveling health care workers
ant when the provider is working in a country
should:
with a high prevalence of TB infection or in a set-
ting of high TB exposure, such as in prisons (see • Ensure they are properly trained for all antic-
Chapter 3, Tuberculosis). Routine vaccination ipated procedures, considering the locally
of health care workers with bacillus Calmette- available equipment.
Guérin (BCG) is not recommended in the United
States; however, BCG vaccination may be con-
• Maintain strict safety standards, even if local
standards are less stringent.
sidered for some health care workers who will
work in settings with high TB transmission risk • Bring their own supply of PPE or safety-
and a high prevalence of strains resistant to iso- engineered medical devices if they are unsure
niazid and rifampin. Baseline testing for HIV and of local availability.
• Assess the local availability of postexposure bloodborne pathogens such as HIV, hepatitis B
prophylaxis (PEP) for HIV, and consider bring- virus (HBV), and hepatitis C virus (HCV). The risk
ing a supply for personal use if unavailable of HIV transmission is approximately 0.3% after a
(see Postexposure Prophylaxis, below). percutaneous exposure to HIV-infected blood and
approximately 0.09% after a mucous membrane
exposure. Health care workers who have received
INFECTIONS TRANSMITTED BY hepatitis B vaccine and have developed immunity
AIRBORNE OR DROPLET ROUTES to the virus are at virtually no risk for infection;
Health care workers are at risk of acquiring for an unvaccinated person the risk of HBV trans-
numerous airborne and droplet- transmitted mission from a single needlestick or a cut expo-
infections from patients. Although some of these sure to HBV-infected blood ranges from 6%–30%
pathogens are vaccine preventable (such as mea- and depends on the hepatitis B e antigen status
sles, influenza, and varicella), airborne or drop- of the source individual. Based on limited stud-
let isolation precautions for patients suspected of ies, the estimated risk for HCV transmission after
having some respiratory infections are a mainstay a needlestick or cut exposure to HCV-infected
of infection control in the United States. These blood is approximately 1.8%. Other bodily fluids
precautions include PPE such as surgical masks that may transmit HIV and viral hepatitis include
for droplet precautions and fit-tested N95 respira- cerebrospinal fluid, synovial fluid, pericardial
tor masks and negative-pressure isolation rooms fluid, pleural fluid, peritoneal fluid, amniotic fluid,
for airborne precautions. Health care workers semen, and vaginal secretions. Saliva, urine, spu-
should inquire about the availability of isolation tum, nasal secretions, tears, feces, vomitus, and
facilities when working internationally. Bringing sweat are not considered infectious for HIV and
a personal supply of PPE for use while working HCV unless they are visibly bloody. Typically,
overseas might be prudent (see above, PPE and exposures occur as a result of percutaneous expo-
Infection Control). sure to contaminated sharps, including needles,
TB is a particular concern for health care work-
ers working overseas in high- incidence areas.
lancets, scalpels, and broken glass ( from capil-
lary or test tubes). The risk of infection after per-
8
Although fit-tested N95 respirators are protective cutaneous exposures is considered increased with
for individual providers, identifying the situations exposure to larger blood volumes (visible blood on
where their use is indicated can be difficult when the injuring device, hollow-bore needles, deeper
diagnosis and isolation of patients with active injuries, or procedures that involved direct can-
tuberculosis is suboptimal. nulation of an artery or vein). Skin exposures to
Traveling health care workers should be aware potentially infectious bodily fluids are only con-
that they may encounter patients with unusual or sidered to be at risk for bloodborne pathogen
emerging respiratory pathogens, such as MERS infection if there is evidence of compromised skin
or avian influenza. Review of the disease-specific integrity ( for example, dermatitis, abrasion, or
CDC websites at www.cdc.gov and the CDC open wound). Higher circulating viral load in the
Traveler’s Health website (www.cdc.gov/travel) is source patient is also thought to increase the risk
important for the most up-to-date information of transmission, and this can be of particular con-
on the epidemiology and infection control recom- cern in resource-poor settings where treatment
mendations for emerging pathogens. for HIV and viral hepatitis is limited.
Hepatitis B vaccination, standard precautions,
INFECTIONS TRANSMITTED PPE, and safety-engineered devices are import-
THROUGH BLOOD OR ant preventative measures (see above sections,
BODILY FLUIDS Pretravel Vaccination and Screening and PPE and
Health care workers are at risk for numerous Infection Control). Numerous other infections
infections transmitted through exposure to blood have also been transmitted to health care workers
or bodily fluids via percutaneous, mucous mem- via blood or bodily fluids, including many that are
brane, or nonintact skin exposures. These include uncommon or not endemic in the United States,
such as viral infections (including Ebola virus, The decision of whether or not to initiate PEP
dengue), parasitic infections (including malaria), must weigh numerous factors. These include the
and brucellosis. Although standard infection con- timing, nature, and source of the exposure; regi-
trol precautions and avoidance of needlestick men choice as affected by drug availability; the
injuries are effective in preventing most infec- exposed person’s medical history; potential drug
tions that are spread via blood or bodily fluids, interactions; and the possibility of exposure to
enhanced levels of PPE are necessary for some a drug-resistant strain. Expert consultation is
infectious diseases (including Ebola virus disease) important when considering PEP. When expert
that pose high risk for health care workers (see advice is not immediately available, the National
above, PPE and Infection Control). Clinicians’ Postexposure Prophylaxis Hotline
Health care workers who may have been occu- (PEPline) can be reached toll-free at 888-448-4911
pationally exposed to blood or bodily fluids should (9 am to 12 am Eastern Time daily) for assistance
immediately perform the following steps: in managing occupational exposures to HIV and
hepatitis B and C (http://nccc.ucsf.edu/clinician-
• Wash the exposed area with soap and water consultation/p ep-post-exposure-prophylaxis).
thoroughly. If mucous membrane exposure
Other considerations when initiating HIV PEP
has occurred, flush the area with copious
include the following:
amounts of water or saline.
• If possible, assess the HIV and HCV status of • Initiate HIV PEP as soon as possible after
exposure.
the source patient. HBV testing of the source
patient may be indicated if the health care • PEP can be stopped if new information
worker is not a documented responder to changes the decision to treat.
hepatitis B vaccination.
• PEP recipients should be counseled regard-
• Rapid HIV testing of the source patient is pre- ing drug toxicities, drug interactions, and the
become infected with HCV after expo- exposure with follow-up testing approxi-
sure to a source coinfected with HIV mately 6 months after exposure.
and HCV.
• During the first 12 weeks after exposure,
• Baseline and follow-up testing for HCV for health care workers should take precautions
those with known or potential exposure to to avoid secondary transmission (such as
HCV. Perform a baseline test for HCV anti- abstaining from sexual contact, using con-
body and if positive perform confirmatory doms or other barriers to prevent infec-
RNA test. Follow-up testing should include tion, avoiding blood or tissue donations, and
either a test for HCV RNA at 3 or more weeks breastfeeding, if possible).
after exposure or a test for HCV antibody at 6
or more months after exposure with a confir- • Monitoring for adverse reactions from HIV
PEP (when initiated).
matory RNA test if positive.
• Baseline and follow-up testing for HBV for • Monitoring for other transmissible infec-
tions that were diagnosed or suspected in the
those with known or potential exposure to
source patient.
HBV if the health care worker is not a doc-
umented serologic responder to hepatitis B • Psychological counseling, which should be
vaccination or is incompletely vaccinated. considered essential since the emotional
Baseline testing based on hepatitis B sur- effect of occupational exposures can be sub-
face antigen and total core antibody tests stantial and exacerbated by stressors inherent
should be performed as soon as possible after to the overseas work environment.
BIBLIOGRAPHY
8
1. CDC. Healthcare-associated infections (HAIs). 8. Kuhar DT, Henderson DK, Struble KA, Heneine W,
Atlanta: CDC; 2014 [cited 2016 Sep. 27]; Available Thomas V, Cheever LW, et al. Updated US Public Health
from: http://www.cdc.gov/HAI/prevent/ppe.html. Service guidelines for the management of occupational
2. CDC. Hepatitis C and health care personnel. 2016 [cited exposures to human immunodeficiency virus and
2016 Sep. 27]; Available from: http://www.cdc.gov/ recommendations for postexposure prophylaxis. Infect
hepatitis/hcv/hcvfaq.htm#section6. Control Hosp Epidemiol. 2013 Sep;34(9):875–92.
3. CDC. Information for healthcare personnel exposed 9. Lee R. Occupational transmission of bloodborne
to hepatitis C virus (HCV). Recommended testing and diseases to healthcare workers in developing coun-
follow-up. Atlanta 2016; Available from: http://www.cdc. tries: meeting the challenges. J Hosp Infect. 2009
gov/hepatitis/hcv/management.htm. Aug;72(4):285–91.
4. Clinicians Consultation Center. Post-exposure pro- 10. Lyon RM, Wiggins CM. Expedition medicine—the risk
phylaxis (PEP): timely answers for urgent exposure of illness and injury. Wilderness Environ Med. 2010
management. San Francisco: UCSF; 2014 [cited 2016 Dec;21(4):318–24.
Sep. 27]; Available from: http://nccc.ucsf.edu/clinician- 11. Mohan S, Sarfaty S, Hamer DH. Human immunode-
consultation/post-exposure-prophylaxis-pep/. ficiency virus postexposure prophylaxis for medical
5. Connorton E, Perry MJ, Hemenway D, Miller M. trainees on international rotations. J Travel Med. 2010
Humanitarian relief workers and trauma-related mental Jul-Aug;17(4):264–8.
illness. Epidemiol Rev. 2012 Jan;34(1):145–55. 12. Schillie S, Murphy TV, Sawyer M, Ly K, Hughes E, Jiles R,
6. Grinnell M, Dixon MG, Patton M, Fitter D, Bilivogui et al. CDC guidance for evaluating health-care person-
P, Johnson C, et al. Ebola virus disease in health care nel for hepatitis B virus protection and for administer-
workers—Guinea, 2014. MMWR Morb Mortal Wkly Rep. ing postexposure management. MMWR Recomm Rep.
2015 Oct 2;64(38):1083–7. 2013 Dec 20;62(RR-10):1–19.
7. Human Rights Watch, Safeguarding Health in Conflict 13. Vaid N, Langan KM, Maude RJ. Post-exposure prophy-
Coalition. Under attack: violence against health work- laxis in resource-poor settings: review and recommen-
ers, patients, and facilities. 2014 [cited 2016 Sep. 27]; dations for pre-departure risk assessment and planning
Available from: https://www.msh.org/sites/msh.org/ for expatriate healthcare workers. Trop Med Int Health.
files/hhr0514_brochure_lowres.pdf. 2013 May;18(5):588–95.
ADVICE FOR AIR CREWS
Phyllis E. Kozarsky
• Checking at each visit to make sure that (chickenpox) vaccine, polio vaccine, and the sea-
routine immunizations are up-to-date (see sonal influenza vaccine (see the separate sections
below). on these diseases in Chapter 3).
Although there are no established guidelines
• Immunizing against seasonal influenza every or recommendations for the use of travel vacci-
year when the vaccine becomes available. nations in pilots and other air crew members, for
In addition, all medications for chronic condi- some it may be reasonable to offer meningococcal,
tions should be carried in extra quantities, as Japanese encephalitis, yellow fever, and typhoid
they may not be available at some locations, and vaccines because of their frequent, short-stay, and
even if available and less costly, may be counter- at times unpredictable travel and destinations.
feit or of poor quality (see Chapter 2, Perspectives: Hepatitis A is advisable for all travelers and may
Pharmaceutical Quality & Falsified Drugs). The be stressed for air crews, since limited data sug-
business of manufacturing counterfeit medica- gest they have low rates of protection. Hepatitis B
tions in developing countries is huge and growing; is advisable for frequent travelers because of the
it is impossible to tell from the packaging or pills if unpredictability of exposure. Air crews are gener-
they are counterfeit. Some counterfeit drugs con- ally a group who travel frequently beyond work, so
tain little or no active ingredient, and others con- they should always be asked during a consultation
tain toxic contaminants. whether they plan other travel itineraries that can
be addressed at the same time.
Vaccinations
Because of the frequency of travel to interna- Malaria Prophylaxis
tional destinations, air crews may be exposed Crew members are typically informed by their
to various diseases that are not common in the airline as to which destinations harbor malaria.
United States. For example, measles can be a life- Some European and Asian air carriers have
threatening illness for adults; it is more common longer experience flying to destinations where
in most of the world, including Europe, because
of lack of mandatory childhood immunization
malaria is endemic, and these airlines have
various policies with respect to its prevention.
8
against the disease in many countries. In addition, Although there may be malaria transmission in
flight crews may not have had chickenpox as chil- some areas of destination countries, sometimes
dren and may not have been immunized. This ill- there is none in the capitals or the larger urban
ness often occurs at a later age in the tropics; thus, areas to which the major American carriers
if there is interaction with local populations in fly (such as in China or the Philippines). This
these destinations, risk for infection will be higher. is generally not the case in sub-Saharan Africa,
International flight crews should consider a travel where there can be substantial exposure during
health visit to ensure as complete protection as a short 24-hour layover (although in Ethiopia,
possible. Some may have short notice before trav- there is no malaria risk in Addis Ababa).
eling to new destinations; thus, air crew mem- Although there may be little risk in the hotels
bers should be asked about this possibility during at the destination, risk may be increased at the
their visit, so that vaccinations for an upcoming international airports, during unpredictable
trip—that may not be imminent—may be given, delays in transit, and during outings on layovers.
or a series may be started early. Providers should Even during short single stops ( for example, in
educate travelers about health risks in the various West Africa on the way to South Africa), there
destinations; whether certain vaccinations are is some risk when the aircraft doors are open.
administered will depend on the traveler’s toler- Little published data are available on the risk of
ance for risk. malaria for flight crews with short layovers, but
All travelers should make sure they are up-to- some information suggests that it is less than
date with routine vaccinations. These vaccines that for tourists.
include measles-mumps-rubella (MMR) vaccine, Unfortunately, experience in American
diphtheria-tetanus-pertussis vaccine, varicella and European air crews to malaria- endemic
destinations has shown that air crews continue International airlines generally prefer the com-
to acquire malaria, as well as develop severe and bination drug atovaquone-proguanil; its adverse
complicated disease. Some illness may result from effect profile and its dosing make it the most suit-
lack of awareness of airline recommendations, able for air crews.
failure to take precautions against mosquito bites, Additional information on malaria prevention
lack of compliance with antimalarial prophylaxis, may be found in Chapter 3, Malaria.
or inaccurate information regarding toxicity of
medication. Transmission can be focal and inter- Other Vectorborne Diseases
mittent, so prophylaxis for every trip to a highly In the last decade, several mosquitoborne viruses
endemic region should be stressed. have emerged or reemerged, including dengue,
Flight crew members should have easy access chikungunya, and Zika (see the individual dis-
to educational materials and prophylaxis and, if ease sections in Chapter 3). Preventing mosquito
desired, should be able to have an individual risk bites in tropical and subtropical destinations is
assessment for preventive measures. For desti- critical to preventing disease. Because Zika virus
nations where the prevalence of malaria is high infection during pregnancy can cause severe birth
(countries in West Africa, for example), crew defects, airlines should develop flight destina-
members should take prophylaxis for layovers. tion policies for pilots and flight attendants who
For other destinations where crews are thought to are pregnant, plan to become pregnant, or have a
be at low risk based on local intensity of transmis- partner who is or may become pregnant.
sion, accommodations, and personal behaviors,
they may be advised to use insect repellents and Food and Water Precautions
take other precautions to avoid mosquito bites and Travelers’ Diarrhea
(see Chapter 2, Protection against Mosquitoes, Pilots and air crew members should follow the
Ticks, & Other Arthropods) but take no prophy- same safe food and water precautions and pre-
laxis. Flight crews should always: vention and management of travelers’ diarrhea as
8 • Educate themselves as much as possible other travelers (see Chapter 2, Travelers’ Diarrhea).
They should also be well versed in the recognition
about malaria.
and self-treatment of moderate to severe travel-
• Understand the importance of personal pro- ers’ diarrhea to shorten the duration of illness that
tective measures such as repellents, and use could affect their job performance.
them properly.
Bloodborne and Sexually
• Take prophylaxis if recommended. Transmitted Infections
• Know that if fever or chills occur after expo- Although these risks and preventions are
sure, it is a medical emergency. addressed in more detail in other sections, it is
worth reiterating that frequent travelers have an
• Know how they can get medical assistance at increased likelihood of engaging in casual and
their destinations or at home in the event of
unprotected sex. It is common to think that peo-
symptoms or signs of malaria.
ple from all Western countries would have the
There are several options for malaria prophy- same risk of HIV and other sexually transmitted
laxis, depending on the destination city, although infections; however, travelers have far higher rates
needed duration of prophylaxis and adverse of such infections. The risk of acquisition may be
effects profiles of some of the drugs make them higher not only for diseases such as gonorrhea
less than desirable for air crews. Country- and chlamydia but also for chronic illnesses such
specific recommendations can be accessed as hepatitis B and C. Dental procedures and activ-
either in this text (see Chapter 3, Yellow Fever & ities such as acupuncture, tattooing, and pierc-
Malaria Information, by Country) or on the CDC ing also are ill-advised during travel to developing
Travelers’ Health website (www.cdc.gov/travel). countries.
BIBLIOGRAPHY
1. Bagshaw M, Barbeau DN. The aircraft cabin 4. CDC. Notes from the field: malaria imported from West
environment. In: Keystone JS, Freedman DO, Africa by flight crews—╉Florida and Pennsylvania, 2010.
Kozarsky PE, Connor BA, Nothdurft HD, editors. MMWR Morb Mortal Wkly Rep. 2010 Nov 5;59(43):1412.
Travel Medicine. 3rd ed: Saunders Elsevier; 2013. 5. Schwartz MD, Macias-╉Moriarity LZ, Schelling J.
pp. 405–╉12. Professional aircrews’ attitudes toward infectious dis-
2. Byrne N. Urban malaria risk in sub-╉Saharan eases and aviation medical issues. Aviat Space Environ
Africa: where is the evidence? Travel Med Infect Dis. Med. 2012 Dec;83(12):1167–╉70.
2007 Mar;5(2):135–╉7. 6. Selent M, de Rochars VMB, Stanek D, Bensyl D, Martin
3. Byrne NJ, Behrens RH. Airline crews’ risk for malaria on B, Cohen NJ, et al. Malaria prevention knowledge, atti-
layovers in urban sub-╉Saharan Africa: risk assessment tudes, and practices (KAP) among international flying
and appropriate prevention policy. J Travel Med. 2004 pilots and flight attendants of a US commercial airline.
Nov-╉Dec;11(6):359–╉63. J Travel Med. 2012 Dec;19(6):366–╉72.
to violence of 16%. The same study also showed including young children. Both of these factors
that >40% found the experience more stressful engender additional travel health considerations
than expected. An earlier study of deaths among that may be different than those encountered by
Peace Corps volunteers noted that unintentional short-term humanitarian and disaster relief work-
injuries were the cause of nearly 70% of deaths, ers. For more information, see the next section in
followed by homicide at 17%. Illness was respon- this chapter, Long-Term Travelers & Expatriates.
sible for 14% of the Peace Corps fatalities. Those who will be providing medical care or
However, risks to humanitarian aid workers participating in clinical research as part of their
are not uniformly distributed across the spec- humanitarian activities should be evaluated in
trum of humanitarian aid. Ongoing surveillance terms of occupational risk and the need for pre-
of violence directed against humanitarian and ventive preexposure or postexposure inter-
disaster relief aid workers continues to demon- ventions. They should also be reminded that
strate that a small number of insecure locations providing aid during outbreak situations may
(Afghanistan, Pakistan, South Sudan, Syria, and involve contact with infected people who are
the Central African Republic) account for most of asymptomatic or have nonspecific symptoms,
these events. requiring more attention to infection control pro-
tocols. Disaster relief and humanitarian aid work-
ers destined for areas of active conflict or limited
PRETRAVEL CONSIDERATIONS police presence may benefit from specialized
Evaluation and Pretravel security briefings, either provided by the employ-
Medical Care ing agency or private sources. Medical facilities
Giving careful attention to pretravel evaluation, may be compromised by the disaster or over-
both medical and psychological, in addition to whelmed in responding to it. Therefore, volun-
educating travelers, can reduce the likelihood teers with underlying conditions likely to require
of illness and the need for emergency repatria- care and pregnant women should be counseled
8 tion. Comprehensive medical examinations can
prepare travelers by helping identify previously
against travel and encouraged to support the
response in other ways. Travelers planning to par-
unrecognized conditions and allowing for treat- ticipate in animal rescue should review informa-
ment before travel. Careful evaluation of risk tion available in Chapter 6, Taking Animals and
factors ( family history, history of alcohol or sub- Animal Products across International Borders,
stance abuse, sexually transmitted diseases, and and discuss rabies preexposure prophylaxis with
psychiatric illness) may direct additional evalua- a health care provider (see Chapter 3, Rabies).
tion and identify previously unrecognized psycho- Travelers who will be caring for people ill with
logical problems or chronic conditions. Identifying potentially life-threatening infections such as
alcohol or substance dependence, depression, or Ebola virus disease or other diseases spread by
other psychiatric illness is important, as these contact with blood or other body fluids should be
conditions may be exacerbated by the stress of the familiar with infection control measures specific
mission and are often the reason for emergency for the disease. They should also ensure that their
repatriation. People planning long-term assign- organization provides personal protective equip-
ments should have their dental condition assessed ment (PPE), such as masks, gloves, gowns, and eye
and any problems dealt with before departure. protection.
Missionaries and faith- based workers may Regardless of the area of the world in which the
have additional issues that need to be consid- aid worker will be deployed, certain basics should
ered by health care providers. Their service may be addressed in the pretravel encounter, includ-
involve extended periods of time abroad, pos- ing routine vaccinations, malaria chemoprophy-
sibly their entire professional lives, so the pro- laxis (if appropriate), food and water precautions,
vider must consider the implications of long-term self-treatment for travelers’ diarrhea, risks from
residence in areas of health risk. Additionally, insect bites, behavioral risk avoidance, and injury
they may be accompanied by family members, prevention.
1
Pack these items in checked baggage, since they are considered sharp objects and will be confiscated by airport or airline
security if packed in carry-on bags.
2
See www.tsa.gov for restrictions on traveling with lighters and matches.
BIBLIOGRAPHY
1. Aid Worker Security Database (AWSD): figures at 6. Kortepeter MG, Seaworth BJ, Tasker SA, Burgess TH,
a glance [database on the Internet]. Humanitarian Coldren RL, Aronson NE. Health care workers and
Outcomes; 2015 [cited 2016 Sep. 27]; Available researchers traveling to developing-world clinical set-
from: http://reliefweb.int/sites/reliefweb.int/files/ tings: disease transmission risk and mitigation. Clin
resources/ho_aidworkersecuritypreview2015_0.pdf. Infect Dis. 2010 Dec 1;51(11):1298–305.
2. Brooks SK, Dunn R, Sage CA, Amlot R, Greenberg N, 7. McFarlane CA. Risk associated with the psychological
Rubin GJ. Risk and resilience factors affecting the psy-
chological wellbeing of individuals deployed in human-
itarian relief roles after a disaster. J Ment Health. 2015
adjustment of humanitarian aid workers. Australas
J Disaster Trauma Stud [Internet]. 2004;[cited
Sep. 27 2016]. Available from: http://www.massey.ac.nz/
8
Dec;24(6):385–413. ~trauma/issues/2004-1/mcfarlane.htm.
3. Callahan MV, Hamer DH. On the medical edge: prepara- 8. Mitchell AM, Sakraida TJ, Kameg K. Critical incident
tion of expatriates, refugee and disaster relief workers, stress debriefing: implications for best practice. Disaster
and Peace Corps volunteers. Infect Dis Clin North Am. Manag Response. 2003 Apr-Jun;1(2):46–51.
2005 Mar;19(1):85–101. 9. Nurthen NM, Jung P. Fatalities in the Peace Corps: a
4. CDC. Coping with a traumatic event: information for retrospective study, 1984 to 2003. J Travel Med. 2008
the public. Atlanta: CDC; 2009 [cited 2016 Sep. 27]; Mar-Apr;15(2):95–101.
Available from: http://www.cdc.gov/masstrauma/ 10. Peytremann I, Baduraux M, O’Donovan S, Loutan L.
factsheets/public/coping.pdf. Medical evacuations and fatalities of United Nations
5. Connorton E, Perry MJ, Hemenway D, Miller M. High Commissioner for Refugees field employees.
Humanitarian relief workers and trauma-related mental J Travel Med. 2001 May-Jun;8(3):117–21.
illness. Epidemiol Rev. 2012 Jan;34(1):145–55.
The risk of illness or injury increases with dura- medications (antihypertensive or antihyperlipid-
tion of travel, so special consideration should be emic drugs, for example) from the United States
given to travelers who are planning long-term (see Chapter 2, Perspectives: Pharmaceutical
visits (≥6 months is a common definition) to Quality & Falsified Drugs). There are differ-
low-or middle-income countries, whether they ent options to obtain sufficient medications:
are expatriates with definite plans or adventur- (1) request an override from the insurance com-
ers with open itineraries. Points to discuss in the pany to dispense the entire quantity of medica-
pretravel consultation include accessing care at tion, (2) pay out of pocket for the full amount
the destination, vaccines, infectious diseases not of medication needed and then submit to insur-
prevented by vaccines, injury prevention, and psy- ance company for reimbursement, or (3) rely
chological and cultural issues that long-term trav- on friends or family members who visit to bring
elers may encounter. refilled medication supplies.
outdoor activities in endemic areas after dusk high relative risk of malaria for travelers in Africa,
(see Chapter 3, Japanese Encephalitis). these data on long-term travelers and expatriates
highlight worrisome risks and practices.
• Rabies preexposure prophylaxis is an import- A traveler who will be residing in an area of
ant consideration for people spending a pro-
continuous malaria transmission should con-
longed time in endemic countries, especially
tinue to use malaria prophylaxis for the entire
in areas where rabies immune globulin is not
stay. It is important to reassure the traveler that
available (which is true of many resource-
the drugs are safe and effective. Doxycycline has
limited countries). Vaccinating children who
been well-tolerated for long-term malaria pro-
will be living in high-risk areas is a priority.
phylaxis in the military, and CDC has no recom-
• Numerous unvaccinated Chinese expatriates mended limits on its duration of use for malaria
have recently fallen ill from yellow fever while prophylaxis. Mefloquine has been used fre-
working in Angola, illustrating the impor- quently during prolonged stays by Peace Corps
tance of yellow fever vaccination for travelers volunteers, with a discontinuation rate of 0.9%.
who will be staying in an endemic area or a Mefloquine may be appropriate for long-term pro-
country with a vaccine requirement. phylaxis in chloroquine-resistant areas because
of its convenient weekly dosing, but concern has
In addition to the intended destination, consider
increased regarding its neuropsychiatric side-
disease risk in surrounding areas, since long-term
effect profile, especially the recent Food and Drug
travelers may be likely to travel locally. For exam-
Administration label indicating that neurologic
ple, a short-term traveler to Seoul would not be
side effects may persist. Atovaquone-proguanil
considered at risk for Japanese encephalitis, but
has shown good long-term tolerability in post-
an expatriate living in Seoul may have opportuni-
marketing surveillance, with a discontinuation
ties to visit the Korean countryside or other areas
rate of only 1% because of diarrhea. Peace Corps
in Asia where he or she could be exposed.
Volunteers prescribed atovaquone- proguanil
INFECTIOUS DISEASES NOT adhered to prophylaxis best when compared with
those given doxycycline and mefloquine. If long-
8
PREVENTED BY VACCINES term use (>5 years) of chloroquine is planned, a
Malaria baseline ophthalmic examination with biannual
Data suggest that the incidence of malaria follow-up is recommended to screen for potential
increases and the use of preventive measures retinal toxicity.
decreases with increasing length of stay. For The possibility of pregnancy requires care-
instance, malaria incidence in British travel- ful consideration for long-term female travelers
ers returning from West Africa after a stay of 6– to malarious areas (see the Pregnant Travelers
12 months was 80 times that of the incidence in section earlier in this chapter). Malaria infection
travelers who had stayed only 1 week. Among during pregnancy can result in severe complica-
expatriate corporate employees in Ghana, adher- tions to both mother and fetus. When pregnancy
ence to malaria prophylaxis deteriorated with is anticipated, prophylaxis options may need to be
increasing duration of stay, and all those who adjusted. Ideally, this possibility should be explored
had been on the site for >1 year had abandoned before travel with all female long-term travelers of
prophylaxis. About half of the cohort used insect childbearing age. For women who are pregnant or
repellent only intermittently, and more than one- plan to become pregnant during long-term travel,
third never used repellent. Even though most mefloquine is considered safe in all trimesters.
British expatriates from the UK Foreign and Data from published studies in pregnant women
Commonwealth Office had good knowledge have shown no increase in the risk of teratogenic
about malaria and its prevention strategies, they effects or adverse pregnancy outcomes after meflo-
adhered to malaria prophylaxis <25% of the time; quine prophylaxis during pregnancy. Chloroquine
only 25% reported rigorous compliance, and 13% has also been used long-term without ill effect on
reported having contracted malaria. Given the pregnancy. If a woman traveling long-term is taking
schistosomiasis increase with long-term travel, so plans) presents unique challenges. These travel-
screening on return (and also during long-term ers benefit from broad immunization coverage
expatriate assignments for those with access to for all potential exposures to vaccine-preventable
health care) should also be discussed. Cutaneous diseases, although some prioritization may be
leishmaniasis and filariasis should be reviewed if necessary. Because their plans are unclear, these
a traveler has the potential geographic exposure travelers must understand that they may need to
risk. Compared with short-term travelers, long- diagnose and treat themselves for common ail-
term travelers experience more chronic diarrhea ments, including travelers’ diarrhea, upper respi-
and postinfectious irritable bowel syndrome (pos- ratory tract infections, urinary tract infections,
sibly because some become less adherent to food vaginitis, skin disorders, and musculoskeletal
and water precautions over time) and should be problems (see Chapter 2 for details on a variety
advised to continue food and water precautions of self-treatable conditions). For travelers such
in order to reduce the risk for these conditions. as backpackers who may go in and out of malari-
ous areas, a sensible approach is to provide a sup-
INJURY ply of atovaquone- proguanil with instructions
Since injuries are the leading cause of prevent- on how to administer it when they do visit risk
able death in travelers, long-term travelers should areas. In addition to strategies to prevent health
be educated about safety. Road and vehicle safety problems and injuries during their long sojourns,
should be stressed, and travelers should choose traveler education is imperative regarding health
the safest vehicle options available. Roads are resources, signs and symptoms that require urgent
often poorly constructed and maintained, traffic medical evaluation, and medical evacuation.
laws may not be enforced, vehicles may not have
seatbelts or be properly maintained, and drivers SCREENING LONG-TERM
may be reckless and poorly trained. See Chapter 2, TRAVELERS AND EXPATRIATES
Injury Prevention for strategies to reduce the risk AFTER RETURN
of traffic and other injuries. Long-term travelers, whether they are expatri-
ate workers, Peace Corps volunteers, or highly
8
PSYCHOLOGICAL ISSUES adventurous travelers, need a thorough medi-
The stress of long-term travel can trigger or exac- cal interview to assess potential infectious expo-
erbate psychiatric reactions. A long-term traveler sures after return to their country of origin.
should be assessed for preexisting psychiatric diag- A careful itinerary-specific history with detailed
nosis, depressed mood, recent major life stressors, questioning about potential high-risk exposures
and use of medications that may have psychiatric including food, water, animal, and human con-
effects. These conditions may suggest a need for tact is the foundation of the post-travel evalua-
further screening. All long-term travelers should tion. A physical examination focused on specific
be urged to take care of their physical and mental signs and symptoms and a selected array of tests,
health by exercising regularly and eating health- including tuberculin skin test or interferon- γ
fully. They should be able to recognize signs of release assay for tuberculosis screening, a com-
anxiety and depression and have a plan for coping plete blood count with differential, hepatic trans-
with them. Having photographs or other memen- aminases, and serologic markers depending
toes of friends and family at hand and staying in on types of exposure (but most importantly for
close contact with loved ones at home can allevi- strongyloidiasis and schistosomiasis), are help-
ate the stress of long-term travel. For more infor- ful to detect subclinical infections and deter-
mation, see Chapter 2, Mental Health. mine whether seroconversion to the more
common pathogens (where treatment would be
LONG-TERM TRAVELERS WITH advised) has occurred (see Chapter 5, Screening
OPEN ITINERARIES Asymptomatic Returned Travelers). A benefit of
Offering pretravel care to travelers with no itiner- the post-travel evaluation is preventive counsel-
ary (or those who present with only vague travel ing for potential future travel.
BIBLIOGRAPHY
1. Brown ML, Henderson SJ, Ferguson RW, 6. Hamer DH, Ruffing R, Callahan MV, Lyons SH, Abdullah
Jung P. Revisiting tuberculosis risk in Peace AS. Knowledge and use of measures to reduce health
Corps Volunteers, 2006–13. J Travel Med. 2015 Dec risks by corporate expatriate employees in western
18;23(1). Ghana. J Travel Med. 2008 Jul–Aug;15(4):237–42.
2. Chen LH, Wilson ME, Davis X, Loutan L, Schwartz 7. Landman KZ, Tan KR, Arguin PM; Centers for Disease
E, Keystone J, et al. Illness in long-term travelers Control and Prevention (CDC). Knowledge, attitudes,
visiting GeoSentinel clinics. Emerg Infect Dis. 2009 and practices regarding antimalarial chemoprophylaxis
Nov;15(11):1773–82. in U.S. Peace Corps Volunteers—Africa, 2013. MMWR
3. Chen LH, Wilson ME, Schlagenhauf P. Prevention Morb Mortal Wkly Rep. 2014 Jun 13;63(23):516–7.
of malaria in long-term travelers. JAMA. 2006 Nov 8. Lim PL, Han P, Chen LH, MacDonald S, Pandey P, Hale
8;296(18): 2234–4 4. D, et al. Expatriates ill after travel: results from the
4. Créach M-A, Velut G, de Laval F, Briolant S, Aigle L, Geosentinel Surveillance Network. BMC Infect Dis.
Marimoutou C, et al. Factors associated with malaria 2012;12:386.
chemoprophylaxis compliance among French service 9. Pierre CM, Lim PL, Hamer DH. Expatriates: special
members deployed in Central African Republic. Malaria considerations in pretravel preparation. Curr Infect Dis
J. 2016;15:174. Rep. 2013 Aug;15(4):299–306.
5. Cunningham J, Horsley J, Patel D, Tunbridge A, Lalloo 10. Visser JT, Edwards CA. Dengue fever, tuberculosis,
DG. Compliance with long-term malaria prophylaxis human immunodeficiency virus, and h epatitis C virus
in British expatriates. Travel Med Infect Dis. 2014 conversion in a group of long-term development aid
Jul–Aug;12(4):341–8. workers. J Travel Med. 2013 Nov-Dec;20(6):361–7.
…perspectives
MALARIA IN LONG-TERM
TRAVELERS & EXPATRIATES
Lin H. Chen
Long-term travelers and For this discussion, long- among Peace Corps volun-
expatriates in malarious term travelers are defined teers was associated with
areas are at risk for severe as nonimmune travelers forgetting the medication,
malaria throughout their staying in malaria-endemic fear of long-term adverse
stay, but sometimes they do countries for ≥6 months. effects, and experiencing
not recognize the contin- A review summarized adverse events attributed to
ued need for reducing risk published data on the risk the drug. Nonetheless, taking
through prophylaxis and per- of malaria in long-term a detailed assessment of the
sonal protective measures. travelers, evidence for traveler’s risk and attitude
Even those with knowledge personal protective mea- may help the clinician deter-
of the need for preventive sures, and safety and tolera- mine the traveler’s likelihood
practices may be unable to bility of malaria prophylaxis of adherence to preventive
adhere to them or may opt to during long-term use actions during long-term
discontinue them. Guidelines (Box 8-5). travel. Consider asking about
for malaria prevention might the following:
be interpreted as focusing on
preventing Plasmodium falci-
INDIVIDUALIZED
RISK • Traveler’s beliefs regard- 8
ing personal protective
parum malaria in short-term CONSIDERATIONS measures
travelers. Optimal malaria Some travelers have pre-
prevention in long-term conceived notions about • Traveler’s knowledge and
travelers poses dilemmas malaria prevention for their preferences toward con-
because of diverse traveler long-term journey or stay in tinuous prophylaxis
characteristics and itiner- an endemic region that may
• Travel characteristics,
aries (including traveling in shape their acceptance of including the quality of
and out of malarious areas), standard recommendations. accommodations, activ-
the heterogeneous quality Even when educational ities, and social support
of and access to medical efforts appear successful in and network
care, and the limited reports convincing such travelers
on long-term safety and to take prophylaxis, they • Economic considerations
efficacy of antimalarial often meet other travelers • Destination-specific
drugs. Moreover, parasite or locals who convince them infrastructure, including
resistance, seasonality, that the medication is either medical service, access
and the intensity of trans- not necessary or is in some to high-quality care,
mission evolve with envi- way detrimental to their medication supply, and
ronmental and population health. Additionally, adher- availability of repellents,
alterations. ence to malaria prophylaxis insecticides, and nets
(continued)
8
BOX 8-5. Key findings from a review of studies
relevant to long-term travelers and
expatriates1
• Long-term travelers are at during high-transmission • Poor-quality drugs (including
higher risk for malaria than periods or locations. antimalarial drugs) threaten the
short-term travelers. • All the prophylaxis health of long-term travelers
• Long-term travelers strategies have advantages who obtain their medications in
underuse personal protective and disadvantages, but developing countries.
measures and often abandon prophylaxis is recommended • Primaquine (in people with
continuous prophylaxis. for at least high-transmission adequate levels of G6PD)
• Travelers use a variety of destinations and seasons. can be used as presumptive
unproven strategies during People who elect to take antirelapse therapy after long
long stays: discontinuing prophylaxis only for high- exposures in areas with high
prophylaxis after the initial transmission destinations Plasmodium vivax prevalence.
period of stay, using different and seasons should ensure
medications for prophylaxis they have access to a reliable
1
Adapted from: Chen LH,
in succession, relying supply of a full course of an Wilson ME, Schlagenhauf
on standby emergency approved malaria treatment P. Prevention of malaria in
self-treatment, or taking regimen (Box 3-3 and long-term travelers. JAMA.
prophylaxis intermittently Table 3-8). 2006;296(18):2234–44.
the transmission season or provided that they are toler- unnecessary treatment,
when venturing into endemic ating it well. In addition, they long-term travelers and
areas. However, a traveler should be tested for malaria expatriates who are mis-
who will be staying in an area even if taking prophylaxis. diagnosed with malaria
of high continuous malaria Clearly the possibility of may stop taking their
transmission should continue other treatable causes of prophylaxis because they
to use malaria prophylaxis
for the entire stay.
fever should be explored.
Travelers who will be >24
erroneously believe that it
did not work. It is difficult 8
Another scenario that may hours from adequate med- to relay such a concept
arise and merits discussion ical care should consider during the pretravel con-
with long-term travelers is carrying a full course of sult, but the attempt should
whether they should con- malaria medication for be made.
tinue malaria prophylaxis emergency self-treatment
if they develop fever during when malaria is suspected, SUMMARY
travel. Rapid diagnostic tests regardless of whether they Recommendations for
are unreliable for self-diag- take continuous prophy- malaria prevention in all
nosis in travelers because laxis. Travelers who might travelers must be person-
most travelers are not able self-administer treatment alized. Tailoring advice by
to use and read the test cor- should be told that they assessing the traveler’s
rectly. (In the United States, still require follow-up care preferences and con-
rapid diagnostic tests are as soon as they are able to cerns and determining
only approved for laboratory access it. the traveler’s possible
use.) Because fever has Unfortunately, in many adherence, along with edu-
numerous possible causes countries malaria is a fre- cation r egarding malaria,
besides malaria, travel- quent diagnosis in people will likely result in better
ers should continue their who do not have malaria. adherence than simply
recommended prophylaxis In addition to receiving prescribing a course of
(continued)
prophylaxis. The follow-
• Reliable medical facilities • Fever is a worrisome
ing messages should be at the destination should sign, and malaria must be
conveyed to the long-term be located as soon as considered and ruled out
traveler regarding malaria feasible. (see Chapter 5, Fever in
prevention: Returned Travelers).
• Data support the safety
• Adherence to prophylaxis of long-term use of • A medical evacuation
in high-risk areas is prophylaxis. insurance policy should
essential. be purchased if the trav-
• Supplies of antimalarial
• Use of personal drugs should be brought
eler will be in an area
rotective measures,
p with inadequate medical
from home, because
such as bed nets facilities.
poor-quality drugs
and screens, is critical (substandard, falsified, • Although individual use
(as many will not or counterfeit) are preva- of rapid diagnostic tests
use repellents long lent in malaria-endemic is not advised, carrying
term). countries. standby treatment with
follow-╉up medical care perspective. J Travel Med. 2007 Corps Volunteers in the Africa
may be appropriate Sep–╉Oct;14(5):357–╉8. region, 2013. Travel Med Infect
Dis. 2015 Jan-╉Feb;13(1):61–╉8.
for some. 2. Chen LH, Wilson ME, Davis X,
Loutan L, Schwartz E, Keystone 7. Lengeler C. Insecticide-╉
• Presumptive antirelapse J, et al. Illness in long-╉term treated bed nets and cur-
therapy may be appro- travelers visiting GeoSentinel tains for preventing malaria.
priate for exposure in clinics. Emerg Infect Dis. 2009 Cochrane Database Syst Rev.
Nov;15(11):1773–╉82. 2004(2):CD000363.
areas with intense P. vivax
3. Chen LH, Wilson ME, 8. Renschler JP, Walters KM,
transmission (after a
Schlagenhauf P. Prevention Newton PN, Laxminarayan R.
normal level of G6PD is of malaria in long-╉term Estimated under-╉five deaths
documented). travelers. JAMA. 2006 Nov associated with poor-╉quality
8;296(18):2234–╉4 4. antimalarials in sub-╉Saharan
• Misconceptions regarding 4. Chen LH, Wilson ME, Africa. Am J Trop Med Hyg.
malaria are pervasive in 2015 Jun;92(6 Suppl):119–╉26.
Schlagenhauf P. Controversies
malaria-╉endemic coun- and misconceptions in 9. Tusting LS, Thwing J, Sinclair
tries among expatriates malaria prophylaxis for D, Fillinger U, Gimnig J, Bonner
and local residents, and travelers. JAMA. 2007 May KE, Bottomley C, Lindsay SW.
long-╉term travelers 23;297(20):2251–╉63. Mosquito larval source manage-
ment for controlling malaria.
should trust health advice 5. Cunningham J, Horsley
J, Patel D, Tunbridge A, Cochrane Database Syst Rev.
only from reputable and 2013 Aug 29;8:CD008923.
Lalloo DG. Compliance
respected sources.
with long-term malaria 10. Tusting LS, Ippolito MM,
�prophylaxis in British Willey BA, Kleinschmidt I,
�expatriates. Travel Dorsey G, Gosling RD,
BIBLIOGRAPHY Med Infect Dis. 2014 Lindsay SW. The evidence for
1. Berg J, Visser LG. Expatriate
chemoprophylaxis use and com-
Jul–╉Aug;12(4):341–╉8.
6. Landman KZ, Tan KR, Arguin
improving housing to reduce
malaria: a systematic review
and meta-╉analysis. Malar J.
8
pliance: past, present and future PM. Adherence to malaria
prophylaxis among Peace 2015 Jun 9;14:209.
from an occupational health
Perspectives sections are written as editorial discussions aiming to add depth and clinical perspective to the official
recommendations contained in the book. The views and opinions expressed in this section are those of the author and do
not necessarily represent the official position of CDC.
LAST-╉MINUTE TRAVELERS
Gail A. Rosselot
Ideally, travelers should seek medical advice at notice (such as some business travelers or immi-
least 4–╉6 weeks before departure, but clinicians grants returning to their home country for a fam-
are frequently asked to provide pretravel care ily emergency), or it may refer to people who have
to travelers leaving on short notice, sometimes planned a trip for some time but delayed seeking
within days or even hours. “Last-╉minute travel- pretravel care. Regardless of the reason, clinicians
ers” can refer to people who are leaving on short can offer travelers support for their upcoming trip
BIBLIOGRAPHY
1. Centers for Disease Control and Prevention. 2. Chen LH, Leder K, Wilson ME. Business travelers: vac-
Epidemiology and Prevention of Vaccine-Preventable cination considerations for this population. Expert Rev
Diseases. Hamborsky J, Kroger A, Wolfe S, eds. 13th ed. Vaccines. 2013 Apr; 12(4):453–66.
Washington D.C. Public Health Foundation; 2015 [cited 3. Cramer JP, Jelninek T, Paulke-Korinek M, Reisinger EC,
2016 Mar. 23]; Available from: http://www.cdc.gov/ Dieckmann S, Alberer M, et al. One-year immunoge-
vaccines/pubs/pinkbook/index.html. nicity kinetics and safety of a purified chick embryo
cell rabies vaccine and inactivated Vero cell-derived 5. Zuckerman JN, Van Damme P, Van Herck K, Loscher T.
Japanese encephalitis vaccine administered concomi- Vaccination options for last-minute travellers in need of
tantly according to a new, 1-week, accelerated primary travel-related prophylaxis against hepatitis A and B and
series. J Travel Med. 2016 Mar;23 (3). typhoid fever: a practical guide. Travel Med Infect Dis.
4. Sanford CA and EC Jong. Immunizations. Med Clin N 2003 Nov;1(4):219–26.
Am. 2016;100: 247–259.
SPECIAL CONSIDERATIONS
FOR US MILITARY DEPLOYMENTS
Mark Fukuda, Gregory A. Raczniak, Mark S. Riddle,
Michael Forgione, Alan J. Magill
The US military, as a matter of policy, follows most with health concerns. The specific examples will
of the recommendations in the CDC Yellow Book. be from the US military, but the concepts may be
However, certain situations apply only to the US applicable to other militaries. In 2016, approxi-
military, and some policies or recommendations mately 1.3 million US military members were on
differ from what is recommended in the Yellow active duty, and approximately 800,000 were in the
Book for civilian travel. Active-duty military phy- reserve forces.
sicians generally manage predeployment med- Several characteristics of the military force
icine, but civilian physicians may interact with
people who are on reserve status, home on leave,
differ from those of the civilian population
(Table 8-5). In general, the active duty military 8
recently discharged from active duty, or veterans. population is younger, in better health than the
Predeployment and postdeployment informa- population at large, and predominately male.
tion, policies, and guidelines for clinicians, service
members and their families, and veterans can be FORCE HEALTH PROTECTION
found on the Deployment Health Clinical Center Force health protection (FHP) is an important
website (www.pdhealth.mil). The purpose of this concept in military medicine. FHP is defined
section is to inform US military medical corps as all measures taken by commanders, supervi-
officers, who routinely consult the Yellow Book, sors, individual service members, and the mili-
about these differences. An additional purpose is tary health system to promote, protect, improve,
to provide civilian clinicians who frequently see conserve, and restore the mental and physical
military personnel with background and available well-being of service members across the range of
information sources regarding these differences military activities and operations. Delivery of vac-
and to emphasize their role in informing relevant cines and the use of malaria chemoprophylaxis
findings to military care providers. agents are 2 aspects of FHP.
In many countries, one of the largest traveling Medical interventions for FHP are the respon-
populations is their military personnel. The mil- sibility of the unit commander, with advice from
itary should be considered a special population the unit medical officer. When predeployment
with demographics, destinations, and needs that vaccines or malaria chemoprophylaxis are indi-
may differ from those of civilian travelers. This cated, the commander includes such require-
section focuses on the unique aspects of using ments in the mission plan. Service members are
pretravel vaccines and malaria chemoprophylaxis then required to receive these interventions under
in the military population and on special consid- proper medical supervision. If a particular vaccine
erations relevant to returning service members or drug is medically contraindicated, alternative
Goal Optimizing advice and interventions Ensuring mission success; optimizing advice and
for individual travelers interventions for each person is difficult
Population Not prescreened; travel health Prescreened; people with serious medical
providers see all ages and people problems are not allowed to join the military or
with preexisting medical conditions be deployed
Special populations Infants, children, pregnant women, Less frequent in military population or
elderly people, people with renal or deployments
hepatic impairment and often taking
other medications
Unusual activities Adventure activities, such as Housed in barracks or other group settings,
trekking, climbing, scuba diving, aviators, Special Forces, operating complex
spelunking weapons systems, hostile and extreme
environments, stress of combat operations, night
operations, and use of night-vision goggles
Duration of malaria Mostly short term, 2–3 weeks The US military often uses chemoprophylaxis
chemoprophylaxis for longer periods of time than do short-term
use travelers. Many deployments are for 1 year or
longer.
agents may be employed if they are available. The directives/corres/pdf/620502p.pdf. Although pol-
unit medical officer documents which military icy may be made at higher levels in Washington,
personnel have not received standard preventive DC, the final decision to use vaccines or malaria
measures, so these people may receive additional chemoprophylaxis under FHP is made by com-
monitoring or treatment if they become ill. manders in the field, guided by their medical staff.
FHP policy positions in the Department In certain circumstances, individual service mem-
of Defense (DoD) are issued as directives and bers may be exempt from vaccination. There are 2
instructions. All directives and instructions can types of exemptions from immunization: medical
be found online at www.dtic.mil/whs/directives. and administrative. Granting medical exemptions
The Policy and Program for Immunizations to is a medical function that can only be validated by
Protect the Health of Service Members and a health care professional. Granting administra-
Military Beneficiaries is found in directive 6205. tive exemptions is a nonmedical function, usually
O2E (September 19, 2006) at www.dtic.mil/whs/ controlled by the person’s unit commander.
third-line recommendation for those unable to P. vivax malaria continue to occur in returning
receive either atovaquone-proguanil or doxycy- military personnel. Use of the higher-dose pri-
cline. Before prescribing mefloquine for prophy- maquine regimen for PART is now recommended
laxis, absolute and relative contraindications as for military personnel. This recommendation is
described in the approved product label must be consistent with the spirit of DoD issuance 6200.02
considered. (February 17, 2008), in that the higher-dose rec-
In April 2013, the Assistant Secretary of Defense ommendation for primaquine when used as PART
(Health Affairs) issued new guidance on medica- is “standard medical practice in the United States.”
tions to prevent malaria. Atovaquone-proguanil Although primaquine is included as an accept-
and doxycycline are both first-line choices in areas able alternative by CDC for primary prophylaxis in
other than sub-Saharan Africa. Mefloquine should some countries where the risk of malaria is exclu-
be reserved for people with intolerance or contra- sively or mostly P. vivax malaria, primaquine is not
indications to both first-line medications. Before FDA-approved for primary prophylaxis. Because
using mefloquine for prophylaxis, care should use of primaquine for primary prophylaxis con-
be taken to identify any contraindications on an stitutes off-label use, it cannot be prescribed for
individual basis and ensure required FDA meflo- a deploying group under FHP, but it can be pre-
quine medication guide (www.accessdata.fda. scribed by a licensed medical provider on an indi-
gov/drugsatfda_docs/label/2013/076523s007lbl. vidual basis as part of medical practice.
pdf) is given to people prescribed mefloquine. The most important risk of using primaquine
As a matter of policy, the US military routinely is hemolytic anemia in those who are deficient
uses primaquine for presumptive antirelapse in G6PD. Current policy is for all US military
treatment (PART) in returning military popula- personnel to be screened for G6PD deficiency
tions to prevent the late relapse of P. vivax malaria on entry into military service. However, some
or P. ovale malaria. PART is also referred to as “ter- people, such as reservists, may have deployed
minal prophylaxis.” In PART, primaquine is given without testing, or clinicians may not be able to
8 to otherwise healthy people on their departure
from an endemic area. Primaquine is used for this
confirm results for all people in a unit requiring
PART. Clinicians should be aware that hemo-
indication much more frequently in the military lytic reactions to primaquine may occur in
than in most civilian travelers. those with unrecognized G6PD deficiency.
The FDA-approved regimen for PART is 15 A recurrent issue for military medicine is
mg (base) given daily for 14 days. This regimen the correct timing of primaquine when given as
was approved in 1952 and has not been revisited PART in conjunction with the standard chemo-
since. In the intervening decades, an overwhelm- prophylaxis drug being taken. Primaquine can
ing amount of data has accumulated to show be given at any time after personnel leave an
that the total dose of primaquine to eliminate the endemic area. For convenience and for enhanc-
dormant hypnozoite stages responsible for late ing adherence to the 14-day regimen of pri-
relapses is dependent on the infecting P. vivax maquine, it is often best for military units to
strain and the weight of the patient; therefore, the prescribe primaquine in the immediate 2 weeks
optimal human dose should be based on weight after return. During this time, the units are
and adjusted for the infecting P. vivax strain. often still at their home base completing their
In 2003, CDC recommended 30 mg (base) of in-processing before block leave. Once person-
primaquine daily for 14 days for PART based on nel depart on leave, adherence and monitoring
available evidence, but the FDA-approved regi- for side effects are more difficult.
men remains the lower dose. Adherence to the Under FHP, military personnel are required to
daily 14-day regimen is poor unless primaquine take their chemoprophylaxis agents as prescribed
is given under directly observed therapy, which to maintain mission readiness. Individual sol-
is rarely done. As a result of noncompliance and diers do not have the right to refuse an order given
subtherapeutic dosing with the 15 mg (base) for under FHP. There is great variability in practice as
14 days regimen, periodic outbreaks of relapsed to how seriously individual commanders enforce
these policies, however, and continued outbreaks Differences between civilian and US military
of malaria occur in military populations because use of chemoprophylaxis drugs are summarized
of poor compliance. in Table 8-6.
Choice of malaria Chemoprophylaxis guidelines Individualizing advice and recommendations for large
chemoprophylaxis do not recommend one drug military deployments is rarely logistically possible or
agent versus another, but rather feasible. Recognizing this reality, in April 2013, the US
emphasize the goal of tailoring military adopted a new policy on the use of malaria
the recommendation for the chemoprophylaxis in the US military. Atovaquone-
individual traveler on the basis proguanil and doxycycline are now the first-line
of past experience, itinerary, drugs of choice to prevent malaria in deployed US
possible drug interaction, military forces in all areas other than sub-Saharan
potential side effects, costs, Africa. Atovaquone-proguanil is the drug of choice for
and medical contraindications short-term travel (up to 2 or 3 weeks) and for people
such as drug allergies. who travel frequently, to minimize long postexposure
prophylaxis treatment courses. In September
2011, AFRICOM policy changed to recommending
atovaquone-proguanil for most destinations in sub-
Saharan Africa.
Atovaquone- An option for chemoprophylaxis Atovaquone-proguanil is the drug of choice for sub-
proguanil in all areas. Saharan Africa and a first-line option in all other areas.
Primaquine CDC recommends the use There is no FDA-approved indication for the use of
chemoprophylaxis of primaquine as primary primaquine to prevent malaria. Therefore, the US
chemoprophylaxis in military cannot use primaquine as a chemoprophylaxis
geographic areas with mainly agent under current FHP guidelines.
Plasmodium vivax malaria.
PART Primaquine at 30 mg (base) for There is no FDA-approved indication for the use of
14 days. primaquine at the higher dose of 30 mg (base) for
14 days. However, primaquine is an FDA-approved drug
with an indication for PART. The CDC-recommended
(higher) dose is recommended, as it is the standard of
medical practice in the United States.
Abbreviations: AFRICOM, African Command; FDA, Food and Drug Administration; FHP, Force Health Protection; PART,
presumptive antirelapse treatment.
BIBLIOGRAPHY
1. Armed Forces Health Surveillance Center. Update: 4. Food and Drug Administration. Emergency use
Malaria, U.S. Armed Forces, 2015. MSMR. 2016 authorization of medical products. Rockville,
Jan;23(1):2–6. MD: Food and Drug Administration; 2007 [cited
2. Brisson M, Brisson P. Compliance with antimalaria 2016 Sep. 27]; Available from: http://www.fda.gov/
chemoprophylaxis in a combat zone. Am J Trop Med RegulatoryInformation/Guidances/ucm125127.htm.
Hyg. 2012 Apr;86(4):587–9 0. 5. Office of the Assistant Secretary of Defense (Health
3. Carr ME, Jr., Fandre MN, Oduwa FO. Glucose- Affairs). HA-Policy 13-0 02. Guidance on medications for
6-phosphate dehydrogenase deficiency in two prophylaxis of malaria. Washington, DC 2013 Apr 15;
returning Operation Iraqi Freedom soldiers who [cited 2016 Sep. 27]; Available from: http://www.health.
developed hemolytic anemia while receiving pri- mil/~/media/MHS/Policy%20Files/Import/13-0 02.ashx.
maquine prophylaxis for malaria. Mil Med. 2005 6. Townell N, Looke D, McDougall D, McCarthy JS. Relapse
Apr;170(4):273–6. of imported Plasmodium vivax malaria is related to
Study abroad can be a life-changing and positive Whether or not a university offers pretravel
experience. However, with increasing numbers health clinic support, students should consult
8
of students choosing to study in regions where with a medical professional as a part of the plan-
health and safety concerns differ from those in the ning process. This consultation should include
United States, students and their families must information on endemic health issues in the host
plan for and understand the risks of such travel. country, travel vaccinations, availability and legal-
This planning should include researching the pol- ity of medications commonly prescribed in the
icies of the study-abroad program administrator, United States, and information on how to obtain
learning about health and safety risks at the desti- medical care abroad.
nation, making plans to mitigate those risks, and
obtaining advice from a health care professional PREDEPARTURE PLANNING
before departure. Program professionals should collaborate with
Study-abroad programs vary in structure and institutional health practitioners to provide stu-
staffing, the support provided by the program, dents with comprehensive pretravel consulta-
and obligations placed on students. Some insti- tions that include an assessment of the student’s
tutions have several employees dedicated to sup- health and immunization history, length of pro-
porting study-abroad programs while others have gram, destination country, activities, and other
no full-time staff members. Some hire specialized travel the student will undertake while abroad.
professionals to focus on health and safety issues; The consultation should also cover the following:
others have no staff dedicated to such support.
Some institutions require students to carry insur-
• Country-and region-specific health and envi-
ronmental information
ance that includes accident and illness coverage,
24-hour emergency assistance, emergency med- • A plan for continued treatment while abroad
ical evacuation, and repatriation. Other institu-
tions may recommend obtaining travel insurance
• Gender-specific health information
for study abroad but may provide limited or no • Required, recommended, and routine
information about available options. vaccinations
• Recommended prophylactic and self- and safe experiences abroad. Their travel website
treatment medications and first aid kit (see (http://travel.state.gov) provides country-specific
Chapter 2, Travel Health Kits) information, including guidance on crime and
transportation safety. Advise students to be
• Advice and resources for students with spe- aware of possible travel warnings or travel alerts
cial needs, including specific plans for stu- and to consider this information when making
dents with preexisting conditions that include travel decisions. Students also should know how
provisions for medications, ongoing care, and to get help from a US embassy or consulate in an
emergency treatment emergency. Encourage students who are not US
• Information about physiologic and psycholog- citizens to contact their country’s embassy or
ical consequences students may encounter as consulate in the United States and in the coun-
a result of culture shock or changes in routine tries where they will be traveling to find out what
support their country may provide.
• General advice on nutrition and dietary Before departure, students should register
deficiencies with the Department of State’s Smart Traveler
• Cautions about alcohol and drug use and Enrollment Program (STEP, https://step.state.
a specific plan for those with preexisting gov/step). Program professionals may be able to
dependency issues register their students as a group with STEP.
The CDC Travelers’ Health website (www.cdc.
• Rabies education (avoid feeding or petting gov/travel) contains advice for travelers on the
animals, and postexposure measures) most current health recommendations for inter-
• Bloodborne pathogens precautions (needles, national destinations. Other resources for study
blood products, tattoos, piercing, surgeries, abroad are provided in Table 8-7.
acupuncture) and safe sex (including emer-
gency contraception)
HEALTH AND SAFETY
8 • General instructions for emergency medi-
WHILE ABROAD
cal situations, including locating a physician
Food and Water Safety
Food and water contamination is one of the lead-
abroad (see Chapter 2, Obtaining Health Care
ing causes of illness for travelers. Basic precau-
Abroad)
tions can minimize the risk of diarrhea and other
• Illness and accident insurance policies and illnesses. Specific food and water recommenda-
emergency assistance coverage information, tions depend on the destination country. In most
including medical and evacuation insurance developing countries, the only safe sources of
water are factory-sealed bottles or water that has
• Pretravel medical and dental exams and treat- been purified (see Chapter 2, Water Disinfection
ment as indicated
for Travelers). Advise students to avoid ice in
Before departure, program professionals and drinks, as the ice may have been made with
health practitioners should encourage students to unsafe water.
learn about the countries they will visit to better Cooked foods should be eaten hot; raw fruits
understand the health and safety issues there, as and vegetables should be eaten only if they have
well as the cultural and political climate. The infor- been washed in clean water or peeled by the trav-
mation in the Humanitarian Aid Workers section eler. Poor refrigeration, undercooked meat, and
earlier in this chapter can be useful for students food purchased from street vendors could pose
participating in study abroad, internships, field problems related to food contamination. See
studies, community service projects, or research Chapter 2, Food and Water Precautions for more
in the developing world. information. Travelers may also wish to down-
The Department of State’s online resource load CDC’s Can I Eat This? app (wwwnc.cdc.gov/
for students (http://studentsabroad.state.gov) travel/page/apps-about) for on-the-go safe food
includes information to help students plan healthy and water guidance.
Responsible Study Abroad: Good Practices for Health & Advice for developing plans and procedures to
Safety, by the Interorganizational Task Force for Safety implement good practices for program sponsors,
and Responsibility in Study Abroad students, and parents/guardians/families, especially
www.nafsa.org/Professional_Resources/Browse_ those pertaining to health and safety issues
by_Interest/Education_Abroad/Network_Resources/
Education_Abroad/Responsible_Study_Abroad__
Good_Practices_for_Health___Safety/
Council on Standards for International Educational Standards for exchange programs for US high school
Travel (CSIET) and middle school students going abroad
http://csiet.org Health and safety good practices
Center for Global Education, SAFETI (Safety Abroad Resources to support study-abroad program
First–Educational Travel Information) Clearinghouse development and implementation, emphasizing health
http://globaled.us/safeti and safety issues and resources for US colleges and
universities offering study abroad
SAFETI Program Audit Checklist List of health and safety and study-abroad issues to
http://globaled.us/SAFETI/program_audit_checklist.asp guide institutions’ policies and procedures
http://studentsabroad.com Resource website for students that includes a country-
specific handbook
8
GlobalScholar.us and GlobalStudent.us: Online University and high school–level online courses that
Learning for Study Abroad provide students with helpful information, including
http://globalscholar.us health and safety information before, during, and after
http://globalstudent.us study abroad
Forum on Education Abroad Standards of good practice, a code of ethics, and health
www.forumea.org and safety and other resources for institutions and
organizations that sponsor and support study-abroad
programs
Federal Bureau of Investigation A brochure that introduces students to threats they may
https://www.fbi.gov/file-repository/student-travel- face and provides tips on avoiding unsafe situations
brochure-pdf.pdf/view
consider their own mental and physical well- medications while abroad unless instructed by a
being when deciding on an experience abroad health care professional.
and discuss their destination, local resources, and Students must travel with a signed prescrip-
any existing medical or mental health issues with tion for all medications. The prescription must
their families and health professionals. indicate the name of the student, the name of the
The NAFSA: Association of International Edu medication (both brand name and generic), and
cators’ publication, “Best Practices in Address the dosage and quantity prescribed. The student
ing Mental Health Issues Affecting Education should also have a letter from the US treating
Abroad Participants” (www.nafsa.org/mentalhealth) physician explaining the recommended dosage,
encourages study-abroad programs “to sensitively the student’s diagnosis, and the treatment. This
offer support that c onnects the student to profes- is especially important for controlled substances
sional help before a problem reaches a crisis state and injectable medications. Translations of these
or seriously derails the student’s academic and documents to the host country language may be
career plans.” helpful. It is a good idea to leave copies of pre-
Students should be encouraged to disclose scriptions with a family member or friend at
any chronic physical or mental health condi- home. In most countries, arriving with quanti-
tions or accommodation needs before departure. ties exceeding those prescribed for personal use is
Program professionals can encourage students’ prohibited. Students should pack all medications
disclosure by assuring confidentiality and explain- in the original, labeled containers in their carry-
ing that the information is needed to facilitate a on baggage.
safe experience while abroad— not to prevent Many countries consider marijuana to be ille-
them from going. gal. A student possessing marijuana, even with
Once a student has disclosed a chronic or a valid US prescription, may be arrested, prose-
mental health condition, health care profession- cuted, and jailed or deported.
als can assist with planning for care while abroad. If the anticipated term of study exceeds
8 Engaging students in a discussion about potential
scenarios they may encounter can help determine
90 days, students should ask if their doctor can
write prescriptions for more than 90 days of med-
their acumen for problem solving and can reveal ication and should fill all prescriptions before
areas that need further attention before depar- departure, if possible. This reduces the need to
ture. Mobility International USA (www.miusa.org) purchase medication overseas and lowers the
provides information and resources to support risk of exposure to counterfeit or poor-quality
study abroad by students with special needs and medications abroad (see Chapter 2, Perspectives:
can be contacted directly for assistance. Pharmaceutical Quality & Falsified Drugs).
US prescriptions are not accepted by phar-
Prescription Medication macies overseas. Shipping or mailing medica-
Medications commonly prescribed in the United tions may not be viable options because many
States may not be legal or available in the host countries’ laws prohibit the mailing of drugs,
country. Well before departure, students should including prescription medicines. Students who
check with the US embassy or consulate in the anticipate the need to refill a prescription while
host country or the International Narcotics abroad must plan to be assessed by a local doctor
Control Board (https://www.incb.org) regarding to obtain a local prescription. Students need to
the legality of their prescription medications— determine whether these appointments will be
particularly if they take narcotic or psychotropic covered by their insurance policy, as they may be
drugs. They also should discuss with their health considered preventive care and thus not covered
care providers whether some medications should by the policy.
be changed, and allow sufficient time to make
adjustments before departure. Students should How to Access Medical Care Abroad
avoid switching medications immediately before Adequate medical care may not be available at all
departure and should not discontinue prescribed destinations. Providing information to students
Building and Fire Safety in the host country. Many do not receive ade-
Students should think about building safety at quate alcohol-and drug- prevention education
their destination, including the potential impact explaining the consequences of risky drinking
of earthquakes, wind damage or flooding, and and drug abuse before departure. Violating drug
substandard building standards or maintenance laws abroad may result in serious consequences.
practices. Fire safety is of particular concern. In some countries, being found guilty of violating
Students should evaluate buildings for the pres- drug laws can lead to life in prison or the death
ence of functioning smoke alarms, fire extinguish- penalty. Study-abroad professionals, in collabora-
ers, emergency ladders, and fire exits. tion with institutional experts, should conduct a
proper orientation about the risks associated with
drinking and using drugs abroad.
Air Pollution
Air pollution is a problem in many cities around Bloodborne Pathogens and Safe-Sex
the world and can exacerbate symptoms for stu- Precautions
dents with chronic health conditions. Even if stu- Advise students on risk factors associated with
dents are healthy, they may experience temporary the use of needles, blood products, tattoos, pierc-
symptoms such as irritation of the eyes, nose, and ing, surgeries, and acupuncture. Most people are
throat; coughing; phlegm; chest tightness; and aware of the risk of contaminated needles, but
shortness of breath. students also need to know that the water used to
create tattoo ink is often shared and can be con-
Alcohol and Drugs taminated with bloodborne pathogens.
The misuse of alcohol and drugs can increase the Students should be encouraged to be prepared.
risk of accidents, injury, unwanted attention, and Have frank conversations about safe sex (bring
theft. Being in a foreign environment requires the adequate condoms, birth control, and emergency
ability to respond to new and changing circum- contraception) and encourage students to edu-
8 stances, which can be impaired under the influ-
ence of drugs or alcohol. Many students are not
cate themselves on social customs of their host
city and country with regard to dating, public dis-
of legal drinking age in the United States but are plays of affection, and sexual intimacy.
BIBLIOGRAPHY
1. Forum on Education Abroad. Code of ethics for 5. Interorganizational Task Force on Safety
education abroad. Carlisle, PA: Forum on Education and Responsibility in Study Abroad.
Abroad; 2008 [cited 2016 Sep. 27]; Available from: Responsible study abroad: good practices for
https://forumea.org/resources/standards-of-good- health and safety. Washington, DC: NAFSA:
practice/code-of-ethics/. Association of International Educators; 2002
2. Gore J, Green J. Issues and advising responsibilities. [cited 2016 Sep. 27]; Available from: http://www.nafsa.
NAFSA’s Guide to Education Abroad for Advisors org/Find_Resources/Supporting_Study_Abroad/
and Administrators. 3rd ed. Washington, DC: NAFSA Network_Resources/Education_Abroad/Responsible_
Association of International Educators; 2005. p. 261. Study_Abroad__Good_Practices_for_Health___
Safety/.
3. Institute of International Education. Americans study
abroad in increasing numbers. New York: Institute of 6. NAFSA: Association of International Educators. Best
International Education; 2009 [cited 2016 Sep. 27]; practices in addressing mental health issues affect-
Available from: http://www.iie.org/en/Who-We-Are/ ing education abroad participants. Washington,
News-and-Events/Press-Center/Press-Releases/2009/ DC: NAFSA: Association of International Educators;
2009-11-16-Americans-Study-Abroad-Increasing. 2006 [cited 2016 Sep. 27]; Available from: http://www.
nafsa.org/mentalhealth.
4. Institute of International Education. Host regions
of US study abroad students, 2012/13-2013/14. 7. Pedersen ER, LaBrie JW, Hummer JF. Perceived
New York: Institute of International Education; 2013 behavioral alcohol norms predict drinking for
[cited 2016 Sep. 27]; Available from: http://www.iie.org/ college students while studying abroad. J Stud
Research-and-Publications/Open-Doors/Data/US- Alcohol Drugs. 2009;70(6):924–8.
Study-Abroad/Leading-Destinations/2012-14.
Mass gathering attendees also are at risk for gatherings should be educated on the impor-
infectious disease. Previous mass gatherings have tance of regular handwashing and the use of
been associated with outbreaks of influenza, alcohol-based sanitizer when sanitation facil-
meningococcal disease, and norovirus. Mass ities are not available.
gatherings also have implications for global health
security. Travelers to mass gatherings may import
• Visit the CDC Travelers’ Health web-
site at www.cdc.gov/travel. This web-
diseases to a host site as well as spread disease
site is regularly updated with travel health
when they return home.
notices; information may also be provided
on mass gatherings such as the Hajj or
GUIDANCE FOR CLINICIANS Olympic Games.
Assessing Risk
• Ask travelers about their itineraries and GUIDANCE FOR TRAVELERS
activities. Verify a traveler’s itinerary to iden- • Consult a travel medicine provider at least
tify risks beyond those associated with the 4–6 weeks before the departure date. This
event. Patients may add side trips or extend should allow adequate time to receive most
travel beyond the mass gathering. vaccinations. Discuss your itinerary and any
• Consider your patient’s unique charac- planned activities with your provider so that
teristics. Chronic health conditions may be he or she can make more accurate recom-
exacerbated by activities at a mass gather- mendations to ensure your health and safety.
ing. Patients should ensure they have ade- If a travel medicine provider is not locally
quate supplies of medication for the duration available, a primary care provider should be
of their trip as well as documentation for any able to assist you with ensuring you have the
prescriptions. adequate vaccinations and health informa-
8 tion necessary.
• Register with the Department of State’s
Mitigating Risk
Smart Traveler Enrollment Program
• Identify requirements for mass gathering (STEP, https://step.state.gov/step).
attendees beyond those required for entry Travelers can subscribe for notifications on
to a country. For example, all participants in travel warnings, travel alerts, and other infor-
the Hajj, the Islamic pilgrimage to Mecca, are mation for their specific destination(s), as
required to have meningococcal vaccinations, well as ensure that the Department of State is
whereas other travelers to Saudi Arabia are aware of a traveler’s presence in the event of
not required to have these. serious legal, medical, or financial difficulties
while traveling. In the event of an emergency
• Identify recommendations for attend- at home, STEP can also help friends and fam-
ees, as host sites may make additional rec-
ily reach travelers abroad.
ommendations on the basis of public health
concerns. After the emergence of the Middle • Ensure any existing medical conditions
East respiratory syndrome (MERS) coronavi- are well controlled before departure.
rus, Saudi Arabia recommended that elderly Travelers should discuss their medical history
or immunocompromised people delay their with their medical provider during the pre-
pilgrimage. travel consultation.
• Educate travelers on preventive measures. • Visit the CDC Travelers’ Health website at
These may include the use of insect repel- www.cdc.gov/travel. Learn more about spe-
lent or advice on how to choose safe food cific destinations and view any travel notices
and water from vendors. All travelers to mass for your destination.
BIBLIOGRAPHY
1. Abubakar I, Gautret P, Brunette GW, Blumberg L, for mass gatherings. Johns Hopkins APL Technical
Johnson D, Poumerol G, et al. Global perspectives Digest. 2008;27(4):1–9.
for prevention of infectious diseases associated 5. McCloskey B, Endericks T. Learning from London
with mass gatherings. Lancet Infect Dis. 2012 2012: a practical guide to public health and mass gather-
Jan;12(1):66–74. ings. London: 2013 2016 Sep 28. Report No.
2. Arbon P. Mass-gathering medicine: a review of the 6. Milsten AM, Maguire BJ, Bissell RA, Seaman KG. Mass-
evidence and future directions for research. Prehosp gathering medical care: a review of the literature.
Disaster Med. 2007 Mar-Apr;22(2):131–5. Prehosp Disaster Med. 2002 Jul-Sep;17(3):151–62.
3. Emergency Management Australia. Safe and 7. Steffen R, Bouchama A, Johansson A, Dvorak J, Isla
healthy mass gatherings: a health, medical and N, Smallwood C, et al. Non-communicable health
safety planning manual for public events. Fyshwick risks during mass gatherings. Lancet Infect Dis. 2012
(Australia): Commonwealth of Australia; 1999 Feb;12(2):142–9.
[cited 2016 Sep. 28]; Available from: http://www.health.
8. World Health Organization. Communicable disease
sa.gov.au/pehs/publications/ema-mass-gatherings-
alert and response for mass gatherings: key consider-
manual.pdf.
ations. Geneva: World Health Organization; 2008 [cited
4. Lombardo JS, Sniegoski CA, Loschen WA, Westercamp 2016 Sep 28]; Available from: http://www.who.int/csr/
M, Wade M, Dearth S, et al. Public health surveillance Mass_gatherings2.pdf.
cdc.gov/i mmigrantrefugeehealth/g uidelines/ clinical practice who have not entered the United
overseas/overseas-guidelines.html. Refugees are States on an immigrant or refugee visa (some cat-
not required by federal regulations to repeat health egories of temporary visitors and undocumented
screening upon arrival in the United States; how- migrants) and, therefore, have not received this
ever, systems are in place in all states for refugees immigrant medical exam.
to receive a health assessment shortly after arrival.
These may be carried out by any qualified health
professional and are usually done in coordination
BEFORE ARRIVAL IN
with resettlement volunteer agencies and local
THE UNITED STATES
health departments. CDC’s postarrival guidelines Overseas Medical Examination
for refugee screening are available at www.cdc.gov/ and Treatment
immigrantrefugeehealth/guidelines/domestic/ CDC provides Technical Instructions to panel phy-
domestic-guidelines.html. Specific protocols may sicians and monitors the quality of the premigra-
vary by state and are usually available on the web- tion medical examination process. The purpose of
sites of the departments of health in the state or the mandated medical examination is to detect
region. inadmissible conditions, including communica-
The prearrival medical exam is only performed ble diseases of public health significance, mental
by panel physicians for those applicants who apply disorders associated with harmful behavior, and
for immigrant or refugee status prior to arrival in substance- use or substance- induced disorders
the United States. US health care providers may (www.cdc.gov/immigrantrefugeehealth/exams/
encounter a larger number of immigrants in their ti/panel/technical-instructions-panel-physicians.
html). For certain refugee populations, a visit to CDC’s Vaccine Technical Instructions are avail
the panel physician also provides an o pportunity able at www.cdc.gov/immigrantrefugeehealth/
for health interventions such as presumptive exams/ ti/ p anel/ v accination- p anel- t echnical-
therapy for parasitic diseases, including nem-
instructions.html.
atode infections and malaria (www.cdc.gov/
immigrantrefugeehealth/ g uidelines/ refugee- CHILDREN ADOPTED INTERNATIONALLY
guidelines.html). Parents adopting children internationally may
The medical examination includes a physical request to delay immunization of children
examination, mental health evaluation, syphilis <10 years of age by agreeing to begin immuniza-
serologic testing, review of vaccination records, tions within 30 days of arrival in the United States.
and chest radiography followed by acid- fast Adopting families should be aware that vaccinat-
bacillus smears and sputum cultures if the chest ing children before arrival in the United States
radiograph is consistent with tuberculosis (TB). reduces the risk of importing diseases of pub-
Chest radiographs are required for all applicants lic health concern, such as measles, which was
≥15 years of age. Applicants 2–14 years of age reported in unvaccinated children adopted from
from high-TB-burden countries (incidence rate China in 2004, 2006, and 2013.
≥20 cases per 100,000 population as estimated by
the World Health Organization) must be tested REFUGEES
for TB infection using either a tuberculin skin test Refugees are not required to meet the INA immu-
(TST) or interferon-γ release assay (IGRA); chest nization requirements before entry into the
radiographs are required for those who have a United States; however, CDC is working with
positive TST or IGRA. For people diagnosed with domestic and international migration part-
active TB, CDC’s Technical Instructions require ners to implement a vaccination program for
Mycobacterium tuberculosis culture, drug sus- US refugees. Program updates and population-
ceptibility testing, and directly observed therapy specific schedules can be found at www.cdc.gov/
through the end of treatment before immigration.
Treatment is also required before immigration
immigrantrefugeehealth/guidelines/overseas/
interventions/immunizations-schedules.html.
8
for certain other inadmissible conditions, such Refugees are required to show proof of vaccina-
as specific sexually transmitted diseases (such as tion when they apply for permanent US residence
syphilis) and Hansen disease. (adjustment of status exam performed by a US
civil surgeon), typically 1 year after arrival.
Proof of Vaccination
IMMIGRANTS Classification of Medical Conditions
Applicants who apply for a US immigrant visa Medical conditions of public health significance
outside the United States are required to receive are categorized into those that preclude an immi-
all age-appropriate immunizations before immi- grant or refugee from entering the United States
grating to the United States. Vaccines are admin- (class A) or those that indicate a departure from
istered by panel physicians according to CDC’s normal well-being and for which follow-up after
Vaccine Technical Instructions. These require- arrival is recommended (class B). An immigrant
ments are based on the Advisory Committee on or refugee who has an inadmissible class A condi-
Immunization Practices (ACIP) recommenda- tion may still be issued a visa after the illness has
tions, with some modifications for immigrant pop- been treated or after a waiver of the visa ineligibil-
ulations. For example, immigrants are not required ity has been approved by USCIS.
to complete all doses of a multidose vaccine series
as long as they have received the next dose in the Notifications and Follow-Up
series before arrival in the United States. New on Arrival
immigrant arrivals should be encouraged to com- The results of the immigrant medical exam are
plete vaccination schedules according to ACIP rec- collected at US ports of entry when immigrants
ommendations after arrival in the United States. and refugees arrive. CDC then notifies state or
local health departments of all arriving refu- new migrant should receive a complete health
gees, as well as immigrants with notifiable class assessment that includes screening for migration-
A (with waiver) and class B conditions who may associated illness plus the age- appropriate
need follow-up evaluation after arrival. State and screening and health care recommended for
local health departments are asked to report anyone residing in the United States. Clinicians
follow-up evaluation results back to CDC, as well caring for migrants who are not recent arrivals
as any serious conditions of public health con- should still ensure that migrant screening has
cern identified among recently arrived immi- been completed, especially for diseases of long
grants and refugees. Such reporting enables latency such as TB, hepatitis B, and HIV, and com-
CDC to track epidemiologic patterns of disease plete any missing tests. It would also be ideal to be
in recently arrived immigrants and refugees and able to screen each individual for diseases specific
allows for monitoring of the quality of the over- to his or her country of origin, migration route,
seas medical examinations. and individual epidemiologic risk. Described
below are guidelines available for the 2 popula-
AFTER ARRIVAL IN THE UNITED tions for which there are the most data to guide
STATES: SCREENING & HEALTH screening efforts (refugees and children adopted
ASSESSMENT internationally), followed by an approach to per-
A comprehensive postarrival health assessment is forming health assessments for other categories
an opportunity to screen for communicable and of immigrants.
noncommunicable diseases, provide preventive
services (such as immunizations and treatment HEALTH ASSESSMENT OF REFUGEES
for latent tuberculosis) and individual counseling Evidence-based guidelines for refugees have been
(such as nutritional and mental health), establish developed by CDC in collaboration with the
ongoing primary care and a medical home, and Department of Health and Human Services
orient new arrivals to the US health care system. Administration for Children and Families’ Office of
8 Challenges for health professionals in pro-
viding comprehensive health assessments for
Refugee Resettlement (ORR), clinical and subject
matter experts outside of CDC, and representatives
new arrivals include lack of familiarity with of ARHC. The full guidelines and a summary check-
CDC screening recommendations and diseases list of the postarrival exam components and rec-
endemic to a migrant’s country of origin, inabil- ommended testing are available at www.cdc.gov/
ity to find trained interpreters, and lack of knowl- immigrantrefugeehealth/guidelines/domestic/
edge of social and cultural beliefs of new migrant domestic-guidelines.html. CDC has also developed
groups. Immigrants and refugees often have other population-specific health profiles for certain popu-
priorities related to their new environment, such lations (such as Bhutanese or Congolese refugees),
as English classes, school, housing, and work, available at www.cdc.gov/immigrantrefugeehealth/
which may take precedence over accessing health profiles/index.html.
care services. Several organizations can facili- Another function of the postarrival medical
tate health screenings for refugees (such as the screening is to arrange and coordinate ongoing
Association of Refugee Health Coordinators primary care. Many refugees have not had age-
[ARHC]), and networks of clinicians who serve appropriate screening for chronic diseases such
refugees and immigrants are growing. Additional as heart disease, diabetes, cancer, or hearing,
resources are provided in the online Yellow Book vision, or dental problems; these needs should be
(see Box 8-8). addressed at early follow-up visits. Several cancers
are more prevalent in migrant populations, such
Medical Screening as cervical, liver, stomach, and nasopharyngeal
Newly arrived immigrants and refugees may have cancers. Refugees should be educated regarding
undiagnosed infectious diseases or untreated age-appropriate cancer screening tests, such as
chronic health conditions, such as hypertension, mammography, colonoscopy and Papanicolaou
diabetes, or hypercholesterolemia. Ideally, each tests during the postarrival exam.
HIV testing was removed from the require- Refugees may qualify for state Medicaid pro-
ments for US admission in January 2010, but HIV grams to cover medical screening and any ongo-
screening is highly encouraged in all newly arriv- ing medical care that may be needed. Refugees
ing refugees and routinely recommended in the determined ineligible for Medicaid are eligible
guidelines from the United States Public Health for Refugee Medical Assistance in many states,
Service (USPHS) and the American Academy of which provides for their medical care needs for
Pediatrics (AAP). Culturally sensitive counseling up to 8 months from their date of arrival. For
regarding HIV testing is critical. more information, clinicians and refugees can
Nutritional deficiencies occur commonly in contact their state health departments and can
refugee populations. For example, one study found access more information through the ORR, which
that the prevalence of vitamin B12 deficiency in administers this program (www.acf.hhs.gov/
newly arrived Bhutanese refugees from Nepal was programs/orr/programs/cma).
64% in those tested premigration and 27%–32% Other published resources available to clini-
in those tested after arrival in the United States.
Clinicians should be aware of the possibility of
cians include consensus documents on evidence-
based screening for newly arriving refugees to
8
malnutrition and micronutrient deficiencies and Canada, provided by the Canadian Collaboration
screen and treat accordingly. for Immigrant and Refugee Health. A list of
CDC recommends checking blood lead levels resources can be found in the online edition of the
of all refugee children aged 6 months to 16 years Yellow Book (see Box 8-8).
of age at the time of arrival, with follow-up blood
lead testing for children 6 months to 6 years of age HEALTH ASSESSMENT OF CHILDREN
3–6 months after settling into a permanent resi- ADOPTED INTERNATIONALLY
dence. Potential lead exposures include using lead- There are many similarities in health conditions
containing gasoline, burning fossil fuels and waste, between international adoptees and refugees.
and using lead-containing traditional remedies, One difference is that refugees generally remain in
cosmetics, foods, ceramics, or utensils. Ongoing their own cultural group for some time after arrival
lead exposure among refugee children after arrival and may have limited interactions with the wider
in the United States also has been documented. community, whereas international adoptees fre-
Mental health screening for refugees is another quently enter households and communities
component of the postarrival exam and, when that are clinically naïve to infections common in
clinically indicated, a more detailed social his- resource-poor settings. This distinction is partic-
tory including any history of trauma, torture, or ularly pertinent for conditions that may continue
rape. Risk factors that may predispose refugees to be infectious for weeks to months after arrival
to psychiatric symptoms and disorders include (such as hepatitis A or B and giardiasis). Clinicians
exposure to war, state-sponsored violence and should encourage updating immunizations prior
oppression, loss of family members, and the stress to the adoption for those who travel internation-
of adapting to a new culture. ally to meet their adopted children and travel
home with them, as well as close family mem- Basic mental health screening, including
bers and caregivers (even if they do not travel). coping strategies and support systems, can be
The AAP offers guidance in the Red Book: Report of included in the assessment so that referrals to
the Committee on Infectious Diseases for clinicians resources can be made within the medical home.
who will serve this population after their arrival in A complete blood count with differential and
the United States (the Red Book may be accessed urinalysis is appropriate for most new arrivals for
for free by AAP members at http://aapredbook. diagnosis of anemia or eosinophilia or to iden-
aappublications.org). More information is avail- tify evidence of hemoglobinopathy. A basic meta-
able in Chapter 7, International Adoption. Most bolic panel may be indicated, especially for those
families who adopt children internationally are of appropriate age or with evidence of condi-
required to have health insurance for the child tions such as renal disease or diabetes. Immigrant
effective upon arrival, so funding for the postar- health care providers should continue to follow
rival health assessment poses fewer problems the age-and risk-based guidelines provided by
than for other immigrant groups. the United States Preventive Services Task Force
(USPSTF) for the general US population when con-
HEALTH ASSESSMENT FOR OTHER tinuing to care for immigrant patients over time.
IMMIGRANTS (See the Guide to Clinical Preventative Services
All newly arrived immigrants would benefit 2014 at www.uspreventiveservicestaskforce.org,
from a comprehensive postarrival health assess- click on “Information for Health Professionals”
ment and introduction to the US health system. and then on the “Guide to Clinical Preventive
Because immigrants enter the country in so many Services, 2014”). Per CDC lead screening guide-
different ways, they access health care at multiple lines for the US population, a blood lead level
different points and with providers who have dif- should be obtained for children 12 months old
fering levels of expertise in immigrant medicine. and 24 months old if resources allow. If a child
Since there is no formal mechanism or funding has additional risks, screening should be started
8 source available for a standard comprehensive
health assessment, immigrants may never receive
at 6 months. If an immigrant has never had a
blood lead level and has lived in a highly indus-
any health assessment that targets conditions trialized city with potential for exposure to indus-
they may have acquired in their country of birth trial waste, has a developmental delay, or has a
or during their migration process unless every medical condition consistent with lead exposure,
health professional assumes the responsibil- he or she should be screened for blood lead level
ity and has the knowledge to assess these issues as well. Diagnostic testing should be considered
when caring for patients born outside the United if an immigrant presents with symptoms consis-
States. A list of screening tests that should be tent with a particular parasite if endemic in the
considered for immigrant health assessments is country of origin (malaria, intestinal parasites).
included in Table 8-9. STD screening (syphilis, gonorrhea, chlamydia,
Most experts agree that testing for TB, hepati- HIV), above that of the recommendations for the
tis B, and HIV should be performed for most new US general population, should be considered for
arrivals to the United States. Clinicians should also immigrants if their migration history places them
make a habit of ensuring that this screening has at significant risk. Known medical and family his-
been done for every new non–US-born patient they tory should be recorded, and medications and
see, regardless of time since the person’s arrival. treatments received prior to migration should be
Vaccine records, laboratory evidence of immu- discussed.
nity, and history of vaccine-preventable diseases Immigrants who travel back to their country
should be obtained and age-appropriate vaccines of origin may be at higher risk of travel-related
be given as indicated. Vaccine series do not need infectious diseases. Thus, travel vaccines can be
to be restarted if documentation of prior doses is considered in addition to age-appropriate vacci-
available. nations for these immigrants.
CBC with differential All All Screen for chronic anemias; look for absolute
and MCV eosinophilia, as it can be evidence of parasitic
infection.
Serology for All Where endemic if Consider screening with exposure history,
parasites: high risk of exposure unexplained eosinophilia. Some experts
schistosomiasis,
strongyloidiasis,
choose to treat empirically. Empiric treatment
is recommended when at-risk immigrant
8
other soil- is about to receive steroids or become
transmitted immunocompromised, if testing is unavailable
helminths or when there is insufficient time to obtain
results.
Malaria All Where malaria is Consider malaria if from highly endemic area
endemic within 3–6 months of arrival.
Blood lead level <16 years All Consider if never had a lead test and have
or if clinical additional risks: lived in a highly industrialized
indication city with potential exposure to industrial waste,
has a developmental delay, or has medical
conditions consistent with lead exposure
Urinalysis, basic All adults All Screening for renal failure and schistosomiasis
metabolic panel or if clinical (if from an endemic area)
indication
Abbreviations: IGRA, interferon-γ release assay; TST, tuberculin skin test; STD, sexually transmitted disease; CBC, complete
blood count; MCV, mean corpuscular volume
1
Consider in younger children who have signs or symptoms of disease, risk factors for transmission, or mother is missing
or deceased or has illness compatible with HIV.
BIBLIOGRAPHY
1. Barnett ED. Immunizations and infectious disease 8. Nyangoma EN, Olson CK, Benoit SR, Bos J, Debolt C,
screening for internationally adopted children. Pediatr Kay M, et al. Measles outbreak associated with adopted
Clin North Am. 2005 Oct;52(5):1287–309, vi. children from China—Missouri, Minnesota, and
2. CDC. Vitamin B12 deficiency in resettled Bhutanese Washington, July 2013. MMWR Morb Mortal Wkly Rep.
refugees—United States, 2008–2011. MMWR Morb 2014 Apr 11;63(14):301–4.
Mortal Wkly Rep. 2011 Mar 25;60(11):343–6. 9. Office of Immigration Statistics. Yearbook of
3. CDC. Technical instructions for panel physicians. Immigration Statistics: 2012. Washington, DC: US
Atlanta: CDC; 2014 [cited 2016 Sep. 28]; Available Department of Homeland Security; 2014 [cited
from: http://www.cdc.gov/immigrantrefugeehealth/ 2016 Sep. 28]; Available from: https://www.dhs.gov/
exams/ti/panel/technical-instructions-panel- yearbook-immigration-statistics.
physicians.html. 10. Posey DL, Blackburn BG, Weinberg M, Flagg EW, Ortega
4. Lowenthal P, Westenhouse J, Moore M, Posey DL, Watt L, Wilson M, et al. High prevalence and presumptive
JP, Flood J. Reduced importation of tuberculosis after treatment of schistosomiasis and strongyloidiasis
the implementation of an enhanced pre-immigration among African refugees. Clin Infect Dis. 2007 Nov
screening protocol. Int J Tuberc Lung Dis. 2011 15;45(10):1310–5.
Jun;15(6):761–6. 11. Posey DL, Naughton MP, Willacy EA, Russell M, Olson
5. Maloney SA, Fielding KL, Laserson KF, Jones W, Nguyen CK, Godwin CM, et al. Implementation of new TB
TN, Dang QA, et al. Assessing the performance of over- screening requirements for U.S.-bound immigrants and
seas tuberculosis screening programs: a study among refugees—2007–2014. MMWR Morb Mortal Wkly Rep.
US-bound immigrants in Vietnam. Arch Intern Med. 2014 Mar 21;63(11):234–6.
2006 Jan 23;166(2):234–4 0. 12. Pottie K, Greenaway C, Feightner J, Welch V, Swinkels
6. Miller LC. International adoption: infectious diseases H, Rashid M, et al. Evidence-based clinical guide-
issues. Clin Infect Dis. 2005 Jan 15;40(2):286–93. lines for immigrants and refugees. CMAJ. 2011 Sep
6;183(12):E824–925.
7. Minnesota Department of Health. Lead poisoning
in Minnesota refugee children, 2000–2002. Disease 13. Walker PF, Barnett ED, editors. Immigrant Medicine.
Control Newsletter [Internet]; 2004 [cited 2016 Sep. 28]; Philadelphia: Saunders Elsevier; 2007.
Wilderness and expedition trips are a unique and expedition travel compared with other types
aspect of travel because of challenging terrain, of travel for several reasons:
extreme weather, remote locales, and long dura-
tions. Popular destinations include trekking to
• Destinations may be remote and lack access
to care.
Everest Base Camp, climbing Mount Kilimanjaro,
hiking the Inca Trail, sailing the South Pacific, • Communication is often limited.
and exploring the poles. Adventure travel often
includes mountaineering, backpacking, cycling,
• Weather, climate, and terrain can be extreme.
diving, surfing, or river rafting. Travelers may be • Travelers exert themselves physically, increas-
working, providing humanitarian relief, or com- ing caloric, fluid, and sleep requirements.
pleting scientific research.
The risks and consequences of injury and ill-
• Trips are often long: several weeks, months,
or years.
ness are often significantly increased in wilderness
Insurers may also not authorize helicopter or air- In a travel medicine encounter, physicians may
planes for in-country transport or repatriation. only have a brief moment to educate travelers.
Insurance companies may deny claims involving Depending on the type, duration, and location of
chronic illness, drugs, alcohol, pregnancy, mental trip, a few key pearls may be worth discussing:
health, and acts of war or civil unrest.
Types of insurance include:
• Travelers should understand basic wound
care, seek help with signs of infection—
• Domestic health insurance, which may redness, swelling, pus, and warmth—and be
or may not be effective outside a home educated on self-treatment with antibiotics.
country.
• For hypothermia, cessation of shivering
• Travel insurance, which often includes medi- and mental status changes are dangerous
cal, trip cancellation, evacuation, and repatri- signs. Frostbite can be treated with throm-
ation benefits, but may exclude coverage for bolytics to aid reperfusion, but treatment
wilderness rescue and adventure sports like needs to be initiated within 72 hours in
mountaineering, skiing, and diving. An adven- a hospital (see Chapter 2, Problems with
ture sports rider is available with some travel Heat & Cold).
insurance policies, so travelers should con-
firm coverage for adventure sports.
• Heat stroke marked by a temperature of
40°C and mental status changes is a medical
• Wilderness rescue insurance (usually sepa- emergency.
rate from travel insurance), such as policies
through North American mountaineering
• Snakes, spiders, scorpions, ticks, and jellyfish
can deliver toxic venom, inoculate microbes,
clubs, outdoor and professional associations,
and cause anaphylaxis. For anaphylaxis (also
and scuba dive organizations. Short-term res-
caused by food), treatment with epinephrine
cue insurance is available in some countries,
can be life-saving if administered immedi-
8 for example, through local helicopter rescue
companies, ski resorts, and guides.
ately. Regional antivenoms exist around the
world for certain venomous snakes, spiders,
• Comprehensive expedition policies, including scorpions, and jellyfish.
travel, medical, rescue, security, and repatria-
tion services.
• Travel to high altitude may require preven-
tion and treatment with acetazolamide,
dexamethasone, and other medications.
Training Mental status changes and ataxia are omi-
If travelers have time before disembarking, they nous signs of high-altitude cerebral edema.
should consider completing a first aid and basic Breathlessness at rest is the sign of life-
life support course. Such courses can be found threatening high-altitude pulmonary edema.
through local community colleges and fire
departments.
WILDERNESS SUPPLIES
Emergency Resources Communication and Route Finding
Before they go, travelers should know emergency Travelers should carry a cell phone enabled with
escape routes, local rescue resources, embassy global positioning system (GPS), such as a smart-
contacts, and local medical facilities. phone. Importantly, not all North American cell
If travel medicine practitioners are willing to phones are compatible with international net-
accept phone calls, emails, and text messages works. Travelers should check with their cell car-
from travelers who are abroad, give out contact rier before departing.
information and approximate time of response. In many countries, a global-compatible phone
Make sure travelers understand this is not a sub- can be used with an international plan purchased
stitute for local emergency care. beforehand through the traveler’s North American
cell carrier. Global-compatible phones use the a windproof, waterproof outer layer of tightly
Global System for Mobiles system commonly woven nylon with a durable water-repellent coat-
found with AT&T and T-Mobile services. Phones ing. Gloves, hat, neck warmer, warm socks, and
that use the Code Division Multiple Access sys- goggles are vital to cover all exposed skin.
tem, such as Sprint, Verizon, and US Cellular ser- For hot weather, sun-and insect-protective
vices, often do not work internationally. clothing is important including loose- fitting,
Alternatively, an unlocked (not restricted to lightweight clothing made from nylon, polyes-
any carrier) global-compatible cell phone can be ter, or a cotton blend. Long-sleeve shirts and long
used with a local SIM card in the country of travel. pants offer the most protection. A wide brim sun
If one does not have a global-compatible phone hat and a bandana protect the head and neck.
and SIM card capability, travelers can buy an inex- Sunglasses protect eyes. Clothing should be
pensive local phone, which is best for travelers sprayed with permethrin to ward off insects and
who expect frequent use of their phone, especially arthropods. Footwear should be activity-specific
for data and local calls. Phones and SIM cards boots or shoes, equally important in a marine or
are usually available at kiosks and stores in major mountain environment.
cities and in some airports. In some countries,
registration to obtain a local SIM card requires fin- Emergency Kits
gerprinting and a passport picture. Expedition and wilderness adventures often
Where cell phone service is not available, trav- require a comprehensive, yet compact, personal
elers may consider an unlocked (no frequency emergency kit for survival, medical care, and
restrictions) VHF/UHF radio or a satellite phone. equipment repair. In addition to a basic travel
Advise travelers that restrictions exist and per- health kit (see Chapter 2, Travel Health Kits), trav-
mits are required in many countries regarding elers should consider packing additional items
use of handheld radios and satellite phones; they due to the remote nature of their travel. Items
should check local restrictions prior to departing. may include additional first aid supplies (such
Remind travelers that electronics are not fool-
proof; often they are limited by battery power,
as a pocket-size CPR mask), safety supplies, and
a more robust variety of medications (see below).
8
dense cloud cover, deep canyons, government Standard kits may also need to be augmented for
restrictions, and physical damage caused by specific activities like undersea, ocean, jungle,
impact, water, or extreme temperatures. A backup polar, and high-altitude travel.
power source, such as a solar or dynamo charger, If travelers are on guided trips, they may only
is useful. need a small personal medical kit. A list of recom-
For extreme terrain and remote locations, mended supplies and drugs, including antibiotic,
adventurers should carry and know how to analgesic, and anaphylaxis medications, should
use a GPS unit (or have GPS app installed on be available from the guide company and will
their phone), compass, altimeter, or local topo- likely need to be prescribed at the travel medicine
graphic map (the latter may need to be acquired encounter. Before they go, travelers should iden-
in-country). tify any available group emergency equipment
such as an automatic external defibrillator, a por-
Clothing table stretcher, portable hyperbaric chamber, oxy-
Remind travelers that clothing helps prevent heat gen, and comprehensive medical kit.
and cold illness as well as bites and stings from Be cautious if asked to prescribe medications
insects and arthropods. for guides to be stocked in the expedition medical
Cold weather clothing should be polyester, kit intended for use on clients. Third-party use of
nylon, Merino wool, or, in some circumstances, prescription medication is unlawful in most juris-
goose down. Layering typically consists of a base dictions and best left for the guide company med-
layer, insulating layers of heavy-pile polyester or ical director. If prescribing to a guide as a patient,
nylon-encased polyester (goose down suffices if clarify that the medication is for the guide’s
traveling to a location that is dry and cold), and personal use.
BIBLIOGRAPHY
1. Iserson KV. Medical planning for extended remote expe- 5. Mellor A, Dodds N, Joshi R, Hall J, Dhillon S, Hollis
ditions. Wilderness Environ Med. 2013 Dec;24(4):366–╉77. S, et al. Faculty of Prehospital Care, Royal College
2. Lewin M, Jensen S, Platts-╉Mills T. Wilderness of Surgeons Edinburgh guidance for medical provi-
preparation, equipment, and medical supplies. sion for wilderness medicine. Extrem Physiol Med.
WORK-╉RELATED TRAVEL
Margaret Kitt, Kristin Yeoman, Casey Chosewood, John Gibbins,
Leslie Nickels, Donna Van Bogaert, John Piacentino
Business travel is projected to grow an aver- a trend that has held steady since 2006. Building
age 6.9% through 2016. Small-╉to midsized busi- and maintaining that export business has cre-
nesses are a growing part of the global business ated an increasing need to travel business staff
market. Through 2014, nearly 98% of all US identi- overseas. Many large corporations have corpo-
fied exporters were small or midsized companies, rate medical offices or contract for services that
provide travel assistance and preparation for busi- also vary based on the expected length
ness travelers. However, small and medium enter- of stay.
prises as well as self-employed travelers may not > Determine whether site visits to factories,
possess the resources to make comprehensive industrial facilities, or other worksites will
decisions regarding travel abroad. be needed. If so, evaluate the potential haz-
ards at those sites and how those hazards
PREPARING FOR TRAVEL can be minimized.
Employers and workers traveling internationally
for job duties should take steps pretravel, during
• Travel Destination
travel, and post-travel to prevent injury or ill- > Assess the potential hazards of the travel
ness. Risks associated with the type of work or destination, including hazards related to
the travel destination, as well as ways to protect security concerns, natural disasters, infec-
and achieve optimal personal health and safety, tious diseases, and climate extremes.
should be identified during each of these three > Assess the timing of the trip. Can the trip
phases of travel. be postponed to a time when there may
Using checklists, planning tools, and various be less risk (such as after contentious elec-
information sources, employers and workers can tions, rainy seasons, or infectious disease
help maximize the likelihood that work-related outbreaks)?
travel is completed safely. This section cannot • Personal Health
give specific information on the workplace haz- > Assess whether the most appropriate
ards in every industry or travel location. Instead, personnel are selected for the trip. Think
the information in this chapter guides employers about technical and job expertise as well
and workers in recognizing and mitigating com- as current workload, responsibilities, and
mon hazards, and it generally applies to all who potential health concerns.
travel for work. > Ensure that travelers have opportunities
PRETRAVEL
to maintain optimal health during the trip
and access to care and resources they may
8
The pretravel period is the best time to iden- need while traveling.
tify risks and make plans to prevent occupa-
If travel is judged as necessary, the next step is
tional injury and illness. Planning needs vary
to give workers the information they need to
depending on the type of work; for example,
stay healthy and safe. Employers and workers
business meetings in a metropolitan office set-
together can assess risks related to the type of
ting differ from site visits at a mine or work on
work and make a plan that adequately addresses
a construction site in a remote location. The
risks. Useful steps include the following:
first step in pretravel planning is for employers
and workers to confirm the need for interna-
1. Identify points of contact.
tional travel. Make a list of assessment topics
> At the home worksite, in case problems
tailored to a given travel assignment to guide
arise.
this determination. These topics may include
> At the international worksite, to assist
the following:
with questions and problems; dis-
• Type of Work cuss the upcoming trip to ensure that
> Assess the trip’s objectives and whether workers bring adequate work clothes,
they could be met by using videoconfer- equipment, and personal protective
ences, phone meetings, or other methods. equipment (PPE).
> Assess duration of travel. Risks may
> US embassy and consulate personnel.
increase as more time is spent on a trip. 2. Assess job tasks.
Requirements (such as work visas) or rec- > Determine whether tasks will differ from
ommendations (such as immunizations) the usual work at home.
WORK-RELATED TRAVEL 641
4
62
In addition to assessing specific risks related to Each of the 3 factors to consider in work-related
the type of work, employers and workers should travel—type of work, travel destination, and per-
remember to plan for common risks associated sonal health— need to be reassessed. Issues
with the travel destination (such as risks associ- related to the travel destination and personal
ated with driving, personal safety, or infectious health may apply to either leisure or work-related
diseases) or opportunities to maintain optimal travel, but some specifics related to the job need
personal health. Workers may want to discuss to be considered that may present challenges not
their travel plans with their personal physician encountered by typical leisure travelers.
before departure. This is especially true for those
POST-TRAVEL
8 with chronic health conditions. A health care pro-
vider can evaluate workers and guide them on Travel-related safety and health concerns do not
issues such as food and water safety, vaccinations, necessarily end after returning home. The fol-
prevention of exposure to infectious diseases and lowing issues should be considered in the post-
environmental hazards, and the potential impact travel setting: transitioning back to work and life
of travel demands on personal health. Other sec- at home, reporting of incidents and exposures,
tions of the Yellow Book give extensive guidance getting necessary medical care, and capturing
on these issues. lessons learned to ensure future travel is safe for
other workers. In addition, certain elements of the
pretravel and travel periods, such as completing
DURING TRAVEL vaccination series or resuming care of a personal
Once an employee arrives in a country, reassess
health condition, may also need to be addressed
whether conditions have changed since plans
after travel.
were put into place during the pretravel phase.
Pretravel plans should be reassessed periodi-
cally throughout travel and whenever conditions
Transitioning Back to Work
change substantially. Common issues arising
and Life at Home
Depending on the length and nature of travel,
before and during travel include the following:
returning workers may need a transition period
• Type of Work before resuming pretravel work activities. It is
important that employers and workers discuss a
> Changes in working conditions that may plan for returning to regular duty that addresses
have different potential hazards
the following employee needs:
> Changes in requirements for personal
protection • Time for rest, adjusting to the new time zone,
> Changes or additions to work locations and resuming a normal sleep cycle
• Time for adjusting to work or pace of activity information related to travel history and destina-
that is different from travel tion that would normally be reported to health
providers, workers should give information about
• Refresher training (or new training) on return- specific job duties and hazards encountered in
ing work tasks and any changes in safety their work during international travel. Health
procedures or PPE providers should consider potential associations
• Time to reconnect with family or significant between new symptoms and both the work duties
others or to catch up on home responsibilities and the travel destination itself. Until proven oth-
erwise, it is safest to assume new symptoms—
• Time to wrap up unfinished business with especially fever or other signs of infection—are
employers and workers at the international related to the travel.
location Workers need to resume routine personal
Returning workers can contact their employer’s medical care upon return. This includes actively
employee assistance program, if available, or they managing ongoing chronic conditions, illness
can consult with their health care provider, espe- or injury that may have occurred during travel,
cially if the transition to home becomes difficult as well as check-ups, screenings, and medical or
or adjustment challenges are prolonged. dental visits that may have been missed while on
travel status.
Depending upon the nature of the work per-
Reporting Incidents and Exposures formed during travel, employers and returning
Returning workers need to notify their employer
workers should assess whether work- specific
of any work- related incidents that may have
medical monitoring related to hazardous expo-
occurred during travel and take appropriate
sures is necessary. This may include medical
actions. Commonly occurring incidents that
examinations, surveillance questionnaires, lab-
require reporting include the following:
oratory work, or other medical monitoring. If
• Work-related injuries or illnesses needed, specific guidance on this issue can be
obtained from a qualified occupational health
8
• Health and safety-related exposures related specialist.
to the work performed or the location visited,
including physical hazards, chemical hazards,
Lessons Learned: Revisit Travel
or infectious disease risks
Health and Safety Plan
• Incidents and close call mishaps related to It is important that workers returning from work-
the travel that could affect other workers at related travel share what they learned on travel
the site or future travelers with employers and coworkers to help assure the
health and safety of future travelers. Revisions of
• Traffic crashes pretravel safety and health plans can be guided by
• Property damage or loss considering these issues:
• Security incidents, thefts, personal violence or • Unexpected events related to the type or loca-
other crimes tion of job duties.
• Legal issues that may have occurred • Availability of all equipment and PPE.
during travel
• Unexpected weather, local condi-
tions, safety, travel arrangements, and
Medical Care accommodations.
Returning workers should immediately seek treat-
ment for any lingering, worrisome, or new med-
• Challenges related to culture, customs, and
language.
ical complaints, symptoms, or concerns that
have arisen during travel or after. In addition to • Unexpected sources of conflict or stress.
WORK-RELATED TRAVEL 643
46
BIBLIOGRAPHY
1. CDC. Qualitative risk characterization and manage- 4. International Labour Organization. International
ment of occupational hazards: control banding (CB). hazard datasheets on occupation. [cited 2016 Sep. 28];
[cited 2016 Sep. 28]; Available from: http://www.cdc. Available from: http://www.ilo.org/safework/info/
gov/niosh/docs/2009-152/pdfs/2009-152.pdf. publications/WCMS_113135/lang--en/index.htm.
2. Global Business Travel Association. U.S. business travel 5. Khan NM, Jentes ES, Brown C, Han P, Rao SR,
volume projected to rise over next two years. 2015 Kozarsky P, et al. Pre-travel medical preparation of
[cited 2016 Sep. 28]; Available from: www.gbta.org/ business and occupational travelers: an analysis of the
PressReleases/Pages/RLS_0 41515_USA.aspx. Global TravEpiNet Consortium, 2009 to 2012. J Occup
3. International Labour Organization. Environ Med. 2016 Jan;58(1):76–82.
Appendices
APPENDIX A: PROMOTING
QUALITY IN THE PRACTICE
OF TRAVEL MEDICINE
Calvin Patimeteeporn, Stephen M. Ostroff
Travel medicine remains a young area of medical medicine. This is especially relevant for travelers
practice, but even as the field continues to mature going to exotic destinations, engaging in adven-
based on a growing body of scientific and medi- ture travel, or who have special needs or medical
cal information, there remains no recognized problems.
specialty or subspecialty of travel medicine any- Providers can pursue training in travel medi-
where in the world, including the United States. cine through a number of professional organiza-
Clinicians offering travel medicine services are not tions. Providers may also look to the many open
“board certified” in travel medicine. Instead, travel and excellent courses hosted by members of the
medicine providers generally have credentials in International Society of Travel Medicine (ISTM),
other disciplines, including infectious diseases, notably those in the United States, Canada,
internal medicine, pediatrics, nursing, pharmacy, Ireland, Scotland, and Switzerland. They vary in
or family practice. Clinics in the United States that length from days to a year, depending upon the
offer travel medicine services are also not specifi- depth of the course and credential offered. Many
cally credentialed for this purpose. individuals looking for training beyond the text-
Given these circumstances, how can travel- book do so informally by spending time in a travel
ers maximize the likelihood their provider will clinic learning the basics of the pretravel consulta-
deliver quality travel-related medical care and tion. Post-travel care typically involves infectious
that the advice, preventive measures, and treat- disease and tropical medicine training.
ment services they are given fall within accepted Below is a partial list of resources for clinicians
standards? Similarly, how can providers assure who wish to enhance their knowledge of travel
patients they have sufficient knowledge of the medicine. People seeking travel-related medical
subject matter relevant to travel medicine? services may want to inquire whether their pro-
Research into the quality of travel health care vider or clinic participates in these organizations
is limited, but several studies suggest that trav- or activities.
elers who visit a clinician with training in travel
medicine are more likely to receive pretravel
TRAVEL MEDICINE–RELATED
and post-travel advice and care than if they see
PROFESSIONAL ORGANIZATIONS
other clinicians for such services. Similarly, 2006
guidelines on travel medicine published by the International Society of Travel
Infectious Diseases Society of America recom- Medicine (ISTM)
mend that pretravel and post- travel care be Founded in 1991, ISTM (www.istm.org) is the
obtained from a clinician with expertise in travel preeminent multinational organization dealing
exclusively with travel medicine. ISTM has >3,500 > Diseases related to bites and stings
members worldwide. > Diseases due to environmental hazards
ISTM activities include the following:
• Other conditions associated with travel
• Journal of Travel Medicine > Conditions occurring during or after travel
• An active listserv (TravelMed) where > Conditions due to environmental factors
embers share information and can ask
m > Threats to personal safety and security
questions > Psychocultural issues
• Special-interest groups that include travel • Post-travel management
medicine nurses and travel medicine • General travel medicine issues
pharmacists > Medical care abroad
• A biennial travel medicine meeting and > Travel clinic management
annual regional submeetings > Travel medicine information resources
• A directory of domestic and international The Certificate of Knowledge in Travel Medicine
travel clinics affiliated with ISTM members in examination has been administered since 2003,
65 countries and as of 2016 more than 3,500 exams have been
administered. The society hosts periodic 2-day
• An online learning curriculum of >60 programs intensive exam preparation courses open to all
that cover a wide range of topics and webinars qualified professionals (such as physicians, nurses,
on selected topics pharmacists, and physician assistants) who
• ISTM Travel Medicine Continuing provide travel health–related services. Those who
Professional Development Program are successful in the examination are awarded a
Certificate in Travel Health (CTH). Beginning with
• An examination leading to a Certificate of CTHs awarded in 2011, the certificate is good for
Knowledge in Travel Medicine, available to 10 years and the awardee must be recertified
physicians, nurses, pharmacists, and other either through professional development activi-
professionals offering travel advice ties or by retaking the examination. Practitioners
A The ISTM Body of Knowledge, which covers the offering travel medicine services or interested in
the subject should strongly consider member-
scope of the specialty of travel medicine, forms
the basis for Certificate of Knowledge in Travel ship in ISTM. ISTM practitioners are listed on the
Medicine examination questions. It is regularly organization’s website, and those who have the
updated by the ISTM Exam Committee. Content CTH are designated as such.
areas in the Body of Knowledge include the ISTM also offers research programs. These
following: include research grants, travel awards, and
support for such efforts as the GeoSentinel
• Epidemiology related to travel medicine Surveillance Network.
• Immunology and vaccinology (including
travel-related vaccines) American Society of Tropical
> Pretravel consultation and management Medicine and Hygiene (ASTMH)
> Patient evaluation Formed in 1951 through the merger of predeces-
> Travelers with special needs sor organizations dating back to 1903, ASTMH
> Special itineraries (www.astmh.org) has a subsection that deals
> Prevention and self-treatment exclusively with tropical and travel medicine,
> Precautions known as the American Committee on Clinical
Tropical Medicine and Travelers’ Health.
• Diseases contracted during travel ASTMH activities include the following:
> Vectorborne diseases
> Diseases transmitted from person to person • The American Journal of Tropical Medicine
> Foodborne and waterborne diseases and Hygiene
emerging infectious diseases and toxins, • The journal Aviation, Space, and
including outbreaks (www.promedmail.org) Environmental Medicine
Aerospace Medical AssociationThis organization • An annual meeting
(www.asma.org) represents professionals in the
fields of aviation, space, and environmental med- • Continuing medical education in topics
icine who deal with air and space travelers. Its related to aerospace medicine
activities include the following:
BIBLIOGRAPHY
1. Boddington NL, Simons H, Launders N, Hill DR. Quality 5. Kozarsky PE, Steffen R. Travel medicine education-what
improvement in travel medicine: a programme are the needs? J Travel Med. 2016 Jul 4;23(5).
for yellow fever vaccination centres in England,
6. LaRocque RC, Jentes ES. Health recommendations
Wales and Northern Ireland. Qual Prim Care 2011
for international travel: a review of the evidence
Jan;19(6):391–8.
base of travel medicine. Curr Opin Infect Dis. 2011
2. Chiodini JH, Anderson E, Driver C, Field VK, Flaherty Oct;24(5):403–9.
GT, Grieve AM, et al. Recommendations for the prac-
7. Ruis JR, van Rijckevorsel GG, van den Hoek A, Koeman
tice of travel medicine. Travel Med Infect Dis. 2012
SC, Sonder GJ. Does registration of professionals
May;10(3):109–28.
improve the quality of travelers’ health advice? J Travel
3. Hill DR, Ericsson CD, Pearson RD, Keystone JS, Med. 2009 Jun-Aug;16(4):263–6.
Freedman DO, Kozarsky PE, et al. The practice of
8. Schlagenhauf P, Santos-O’Connor F, Parola P. The prac-
travel medicine: guidelines by the Infectious Diseases
tice of travel medicine in Europe. Clin Microbiol Infect.
Society of America. Clin Infect Dis. 2006 Dec
2010 Mar;16(3):203–8.
15;42(12):1499–539.
9. Sistenich V. International emergency medi-
4. Kozarsky P. The Body of Knowledge for the prac-
cine: how to train for it. Emerg Med Australas. 2012
tice of travel medicine--2006. J Travel Med 2006
Aug;24(4):435–41.
Sep-Oct;13(5):251–4.
Table B-1 is a quick reference for administer- contraindications, precautions, and side effects
ing or prescribing travel-related vaccines. Before under the specific vaccines discussed in this book
administering any vaccine, please pay partic- or in the manufacturer’s prescribing information.
ular attention to the dose and whether it is For other immunizations, refer to the correspond-
to be administered intramuscularly or subcu- ing disease section in Chapter 3.
taneously. Also review detailed instructions,
A
APPENDIX B: TRAVEL VACCINE SUMMARY TABLE
Cholera CVD 103-HgR Vaxchora (PaxVax) 18–64 y 100 mL (reconstituted) Oral 1 dose Undetermined1
vaccine
Hepatitis A vaccine, Vaqta (Merck & Co., 1–18 y 0.5 mL (25 U) IM 0, 6–18 mo None
inactivated Inc.) ≥19 y 1 mL (50 U) IM 0, 6–18 mo None
Japanese encephalitis Ixiaro (Valneva) ≥17 y 0.5 mL IM 0, 28 d >1 y after primary series3
vaccine, inactivated 3–16 y 0.5 mL IM 0, 28 d Awaiting FDA assessment
2 mo–2 y 0.25 mL IM 0, 28 d Awaiting FDA assessment
651
VACCINE TRADE NAME AGE DOSE ROUTE SCHEDULE BOOSTER
(MANUFACTURER)
Polio vaccine, Ipol (Sanofi ≥18 y 0.5 mL SC or IM 1 dose if the Repeat boosters may be
inactivated Pasteur) patient has needed for long-term
APPENDIX B: TRAVEL VACCINE SUMMARY TABLE
Rabies vaccine (human Imovax (Sanofi Any 1 mL IM Preexposure None; see Chapter 3,
diploid cell) Pasteur) series: 0, 7, and Rabies for postexposure
21 or 28 d immunization
Typhoid vaccine (oral, Vivotif (PaxVax) ≥6 y 1 capsule7 Oral 0, 2, 4, 6 d Repeat primary series
live, attenuated) after 5 y
(continued)
651
A
5
652
62
A
APPENDIX B: TRAVEL VACCINE SUMMARY TABLE
Yellow fever YF-Vax (Sanofi ≥9 mo8 0.5 mL SC 1 dose Not recommended for
Pasteur) most9
Abbreviations: ELU, ELISA units of inactivated HAV; HAV, hepatitis A virus; HBsAg, hepatitis B surface antigen; IM, intramuscular; U, units HAV antigen; SC, subcutaneous.
1
In a clinical trial, vaccine efficacy was 90% at 10 days postvaccination and declined to 80% at 3 months postvaccination in prevention of severe diarrhea after oral cholera challenge.
Long-term immunogenicity is unknown. Clinicians advising travelers who are at continued or repeated risk over an extended period may consider revaccination, although the
appropriate interval and efficacy are unknown.
2
Consult the prescribing information for differences in dosing for hemodialysis and other immunocompromised patients.
3
If potential for Japanese encephalitis virus exposure continues. Data on the response to a booster dose administered ≥2 years after the primary series are not available.
4
If an infant is receiving the vaccine before travel, 2 doses may be administered as early as 8 weeks apart.
5
Revaccination with meningococcal conjugate vaccine (MenACWY-D or MenACWY-CRM) is recommended after 3 years for children who were previously vaccinated at ages 2 months
through 6 years. Revaccination with meningococcal conjugate vaccine is recommended after 5 years for people who were previously vaccinated at ages 7–55 years and every 5 years
thereafter for people who are at continued risk.
6
Revaccination with meningococcal polysaccharide vaccine is recommended for adults aged >55 years who remain at increased risk 5 years after the last dose. For adults aged
>55 years who have received meningococcal conjugate vaccine previously or for whom multiple doses are anticipated (such as people with asplenia), meningococcal conjugate
vaccine is preferred.
7
Must be kept refrigerated at 35.6°F–46.4°F (2°C–8°C); administer with cool liquid no warmer than 98.6°F (37°C).
8
Special considerations apply in deciding whether to administer yellow fever vaccine to people aged <9 months or ≥60 years. Please review Chapter 3, Yellow Fever before
administration.
9
In 2014, the World Health Assembly (of the World Health Organization) adopted the recommendation to remove the 10-year booster dose requirement from the International Health
Regulations as of July 2016. As of that time, a completed International Certificate of Vaccination or Prophylaxis is considered valid for the lifetime of the vaccinee. However, it is
uncertain when and if all countries with yellow fever vaccination entry requirements will adopt this change. In February 2015, the Advisory Committee on Immunization Practices
(ACIP) approved a new recommendation that a single primary dose of yellow fever vaccine provides long-lasting protection and is adequate for most travelers. The ACIP also
identified specific groups of travelers who should receive additional doses and others for whom additional doses may be considered. For full details see Chapter 3, Yellow Fever.
36╇
5
Index
Note: Page numbers followed by the schistosomiasis distribution in, American Society of Tropical Medicine
letter b refer to boxes; those followed 310–╉11m and Hygiene (ASTMH), 646–╉7
by the letter f refer to figures; those taeniasis in, 325 American trypanosomiasis, 332–╉3
followed by the letter m refer to maps; tuberculosis in, 337m Americas
and those followed by the letter t refer typhoid fever in, 342 dengue distribution in, 163m
to tables. yellow fever information for, 353t, malaria distribution in, 234m
364m, 397 amnesic shellfish poisoning, 80
African trypanosomiasis, 331–╉2 amoxicillin, Helicobacter pylori
A AGE. See arterial gas embolism (AGE) treatment, 182
accidents. See injuries AIDS. See human immunodeficiency Anaplasma, 297, 298t, 301. See also
acclimatization to altitude, 57, 57b virus (HIV) infection rickettsial infections
acetazolamide, 58, 59, 60t, 61, 87 air crews, 594–╉7 Andorra, 375
ACIP. See Advisory Committee on air pollution, 626 angiostrongyliasis, 140–╉1
Immunization Practices (ACIP) China travel and, 474–╉5 Angola
acquired immunodeficiency environmental hazard, 105 African trypanosomiasis in, 331
syndrome (AIDS). See human India travel and, 482 dengue distribution in, 164m
immunodeficiency virus (HIV) Mexico travel and, 462–╉3 malaria information for, 236m, 375
infection Nepal travel and, 485 Marburg hemorrhagic fever in, 171
acute mountain sickness (AMS), 57, quality in air travel, 518–╉19 yellow fever information for, 353t,
58t, 59–╉60, 60t pregnant travelers and, 579 354, 361t, 364m, 375, 603
Cusco-╉Machu Picchu travel and, Vietnam travel and, 492, 494 Anguilla (UK), 375
464, 466 air travel, 517–╉21 animal-╉associated hazards, 101–╉4
Kilimanjaro travel and, 441–╉2 after diving, 109 bats, 102, 103–╉4, 170–╉1, 287–╉9,
medication doses for, 60t breastfeeding and, 547–╉8 531, 538–╉9
pregnant travelers and, 579 international travel with infants and birds, 104, 492, 531
risk categories, 58t children, 539 bites and rabies, 481, 485, 538–╉9
activated charcoal, 117 pregnant travelers, 578 cat-╉scratch disease, 146–╉7, 510
adolescents. See infants, children, and strategies to reduce injuries, 96t India travel and, 481
adolescents travelers with disabilities, 582–╉3 marine animals, 103, 110
adoptions. See international adoptions trends in, 13–╉15 Nepal travel and, 485
Advisory Committee on Immunization Albania, 375, rodents, 102, 104, 531
Practices (ACIP), 10, 11, 32, 33b, 43. albendazole, 160–╉1, 173–╉4, 183, 275, scratch wounds, 101–╉2
See also specific vaccine listings 324, 514 stings and envenomations, 102–╉3
vaccination recommendations of, alcohol and drugs, study abroad, 626 Vietnam travel and, 492
19–╉20t, 27–╉8t, 35–╉6, 541–╉5 Algeria, 375 animals
Afghanistan, 375 allergies cats and travel, 530
leishmaniasis in, 226 considerations for travelers with, 575t dogs and travel, 530
malaria information for, 236m, 375 vaccine components, 42, 61 health certifications for, 529
rickettsial infections, 298t altered immunocompetence, 37. importation into the US, 529
yellow fever information for, 375 See also immunocompromised rescuing overseas, 529
Africa. See also East Africa: safaris; travelers safaris and, 426–╉8
South Africa; Tanzania alternative medicine. See service, for travelers with
chronic hepatitis B virus complementary & integrative disabilities, 583
prevalence, 189m health approaches taking across international
chronic hepatitis C virus altitude illness, 21t, 56–╉62. See also borders, 530–╉2
prevalence, 195m acute mountain sickness (AMS); traveling abroad with a pet, 529
chronic hepatitis E virus high-╉altitude cerebral edema Antarctica, 375
prevalence, 201m (HACE); high-╉altitude pulmonary anthrax, 141–╉4
dengue distribution in, 6, 7, 164m edema (HAPE) antibiotics, travelers’ diarrhea
HIV infection in, 203 children and, 539–╉40 treatment, 51–╉2
leishmaniasis in, 226, 228 Cusco-╉Machu Picchu travel and, antibody-╉containing blood products,
malaria information for, 233, 236m, 464, 466 34, 35t, 36
238–╉9, 242 drug interactions, 47 antidiarrheal drugs, interactions, 46–╉7
melioidosis in, 260 Kilimanjaro travel and, 441–╉2 Antigua and Barbuda, 375
meningococcal meningitis, areas of pregnant travelers and, 579 dengue distribution, 163m
frequent epidemics, 262m self-╉treatment, 117 yellow fever and malaria information
onchocerciasis in, 271 alveolar echinococcosis or hydatid for, 375
polio in, 27, 284 disease, 173 antihistamines, motion sickness
Q fever in, 286–╉7 amantadine, influenza A, 211 treatment, 65–╉6
rabies in, 288 amebiasis, 139–╉40 antimalarial chemoprophylaxis,
rickettsial infections, 298t, 299t, 300t American Samoa (US), 375 historical milestones in, 253–╉5
INDEX 653
5
46
antimalarial drugs, 235b, 238–51 malaria information for, 377 malaria information for, 234m,
availability, 11 melioidosis in, 260 377–8, 404m
breastfeeding and, 548–9 rickettsial infections, 298t, 299t yellow fever information for, 377
drug interactions, 45–6 tuberculosis in, 337m Benin
immunocompromised travelers yellow fever information for, 377 malaria information for, 236m, 378
and, 568–9 Austral Islands. See French Polynesia meningococcal meningitis, 262m
history of, 253–5 Austria, 377 yellow fever information for, 353t,
last-minute travelers and, 613 tickborne encephalitis in, 327 364m, 378
long-term travel and, 603–4, 607–8 tickborne encephalitis vaccine, Bermuda (UK), 378
military deployments, special 328, 329t Bhutan
considerations for, 617–19 autoimmune and rheumatologic dengue distribution in, 165m
pregnancy and, 581 diseases, considerations for Japanese encephalitis risk in,
recommendations for air travelers with, 575t 216m, 218t
crews, 595–6 avian influenza A (H 5N1), 206–7, malaria information for, 378
travel with infants and children, 537 208m, 213 yellow fever information for, 378
antimotility agents, travelers’ infected poultry, 104 BinaxNOW Malaria Test, 238
diarrhea, 51 Vietnam travel and, 492 birds, 104, 492, 531
aquatic injuries, 97 aviation, injury death, 95f bismuth subsalicylate (BSS), 22, 46, 50,
arenaviral diseases, 350 Azerbaijan, 377 56, 128, 534, 549
Argentina, 375, 376m azithromycin, 51, 52, 53t, 68, 147, 150, bites. See animal-associated hazards
dengue distribution in, 163m 154, 176, 277, 302, 320, 330, 343, blood donation, after travel to
malaria information for, 234m, 375 442, 467, 476, 485, 535 malarious areas, 249
medical tourism, 111 drug interactions, 45, 46 blood safety, receiving transfusion
yellow fever information for, 353t, pertussis, 273 during travel, 135
375, 376m respiratory treatment, 68 boating, water and aquatic
Armenia, 375 Azores (Portugal), 377 injuries, 97
artemether-lumefantrine, malaria boceprevir, hepatitis C treatment, 45
treatment, 115, 239, 240t boiling water, disinfection, 70, 72–4
arterial gas embolism (AGE), diving B Bolivia
disorders, 108–9 B virus, 144–6 dengue distribution in, 163m
Aruba, 377 Bacillus Calmette-Guérin (BCG) malaria information for, 234m, 253,
Asia vaccine, tuberculosis (TB), 339, 378, 380m
chronic hepatitis B virus prevalence 341, 482, 515, 551, 554, 559t, 590. reference map, 379–80m
in, 189m See also tuberculosis vaccine yellow fever information for, 353t,
chronic hepatitis C virus prevalence bacterial skin infections, 507–9 365m, 378, 379m
in, 195m Bahamas Bonaire, 378
dengue in, 6, 7, 165m dengue distribution in, 163m booster vaccinations, 34, 37, 40t, 101,
leishmaniasis in, 226, 228 yellow fever and malaria information 155, 191, 192t, 217t, 222–3, 264t
malaria in, 233, 237m, 242 for, 377 Bora-Bora. See French Polynesia
polio in, 284 Bahrain, 377 Bosnia and Herzegovina, 378
rabies in, 288 Banaba Island. See Kiribati Botswana, 142, 350, 378, 381m
rickettsial infections in, 298t, Bangladesh bovine colostrum, travelers’
299t, 300t dengue distribution in, 165m diarrhea, 50
tuberculosis in, 337m influenza in, 207 bovine tuberculosis, 334
typhoid fever in, 342 Japanese encephalitis risk in, Brazil
asthma, 21, 58, 59t 216m, 218t child sex tourists, 319
atovaquone-proguanil leishmaniasis in, 228 dengue distribution in, 163m
CDC recommendations vs. US malaria information for, 377 destination map, 445m
military policy for, 617–18, 619t yellow fever information for, 377 destination overview, 444
drug interactions, 45, 46, 619t Barbados health issues in, 444, 446–8
malaria chemoprophylaxis, 11, dengue distribution in, 163m leishmaniasis in, 228
28, 239, 240t, 241t, 243, 244t, yellow fever and malaria information malaria information for,
247–9, 250–1t for, 377 379–80, 383m
malaria treatment, 240t barotrauma medical tourism in, 112
recommendations for air air travel, 518 onchocerciasis in, 271
crews, 596 diving disorders, 107–9 schistosomiasis, 310m
Australia. See also Christmas Island Bartonella infections, 146–7 vaccinialike viruses in, 322
(Australia); Cocos (Keeling) bats, 102, 103–4 yellow fever information for, 353t,
Islands (Australia); Norfolk hazards, 103–4, 170 365m, 379, 382m
Island (Australia) importation of, 531 Zika in, 369–70
chronic hepatitis B virus prevalence bed bugs, protective measures against, breastfeeding, 546–9
in, 189m 85, 86b chemoprophylaxis for malaria
chronic hepatitis C virus prevalence bed nets, 82, 84, 85, 222, 227, 229, 240, infection, 248–9
in, 195m 333, 351, 470, 475, 491, 496b, 509, polio vaccine, 281
chronic hepatitis E virus prevalence 537, 580, 586t, 587, 596, 609–11b, 617 yellow fever vaccine and, 360, 548
in, 201m Belarus, 377 British Indian Ocean Territory, 380
dengue distribution in, 165m Belgium, 377 British Virgin Islands. See Virgin
Japanese encephalitis risk in, Belize Islands, British
216m, 218t dengue distribution in, 163m brucellosis, 148
654 INDEX
56
INDEX 655
5
6
656 INDEX
657
Emergency Operations Center (CDC), 2, tickborne encephalitis, 327 tickborne encephalitis in, 327, 328
172, 238, 351, 499, 520, 528 first aid, travel health kit, 127–9 tickborne encephalitis vaccines
England. See United Kingdom fish poisoning, 77–9 licensed in, 328, 329t
enterobiasis, 275–6 fleas, rickettsial infections, 297, 301–2 Ghana
envenomations. See stings and fluconazole, 509 malaria information for, 236m, 395
envenomations fluid and electrolyte replacement, 92 meningococcal meningitis in, 262m
environmental hazards, 105–6 fluoroquinolones, 47, 51–2, 53t, 87, 143, yellow fever information for, 353t,
Environmental Protection Agency (EPA) 147, 148, 150, 176, 225, 286, 320, 334 361t, 364m, 395
repellency graphic, 84 drug interactions, 47, 613 Giardia and giardiasis, 49, 52, 72, 179–80,
repellent products, 81 respiratory treatment, 68 580, 604
water filtration, 74 salmonellosis, 305 halogen treatment, 75
eosinophilia typhoid fever, 343 size and susceptibility to
adoptions, screening for, 554 use in children, 52, 535 filtration, 74t
returning traveler, 498 yersiniosis, 369 Gibraltar (UK), 395
Equatorial Guinea fluoxetine, 45, 46, 79 Gilbert Islands. See Kiribati
malaria information for, 236m, 391 Food and Drug Administration (FDA), ginger, 117, 580
yellow fever information for, 353t, 391 2b, 9, 41–2 ginkgo biloba, 61
Eritrea food and water precautions, 50, 69–71, global gatherings, 5, 627–8
dengue distribution in, 164m 74–6, 140, 141 Global Polio Eradication Initiative
malaria information for, 236m, 392 Force Health Protection (FHP), US (GPEI), 278–80, 283–4
meningococcal meningitis in, 262m military deployments, 615–16 Global TravEpiNet (GTEN), 7, 31
yellow fever information for, 353t, 391–2 France. See also Guadeloupe; gnathostomiasis, 509
erythromycin, 45, 46, 170, 273 Martinique (France); Mayotte goldenseal, 116
Escherichia coli, 48, 72, 74t, 174–7, 320, (France); New Caledonia granular-activated carbon (GAC), water
481, 505, 522 (France); Reunion (France); Saint treatment, 75
Estonia, 392 Pierre and Miquelon (France); grapefruit seed extract, 117
tickborne encephalitis in, 327 Wallis and Futuna Islands Great Britain. See United Kingdom
Ethiopia (France) Greece
dengue distribution in, 164m malaria and yellow fever information Lyme disease in, 232
epidemic typhus in, 301 for, 393 malaria and yellow fever information
international adoptions in, 552 rickettsial infections in, 299t for, 395
leishmaniasis in, 228 tickborne encephalitis in, 327 rickettsial infections in, 299t
malaria information for, 236m, 392, 394m French Guiana Green Book, International travel and
meningococcal meningitis in, 262m dengue distribution in, 163m health, 10
schistosomiasis in, 312 malaria information for, 234m, 394 Greenland (Denmark), 395
yellow fever information for, 353t, yellow fever information for, 353t, Grenada, 395
364m, 392, 393m 361t, 365m, 393 Guadeloupe
Europe French Polynesia, 394 malaria and yellow fever information
anthrax in, 142 frostbite, 93–4 for, 395
chronic hepatitis B virus Fukushima Daiichi plant, radiation, 106 schistosomiasis in, 310m
prevalence, 189m Guam (US),
chronic hepatitis C virus animal imports in, 530
prevalence, 195m G Japanese encephalitis in, 221t
leishmaniasis in, 226, 228 Gabon malaria and yellow fever information
Lyme disease in, 232 Ebola in, 171 for, 395
malaria-endemic countries, 236m malaria information for, 236m, 394–5 Guatemala
rickettsial infections, 298t, 299t yellow fever information for, 353t, dengue distribution in, 163m
tickborne encephalitis in, 326–9 361t, 364m, 394 malaria information for, 233m,
tickborne encephalitis vaccines Galápagos Islands (Ecuador), 163m, 396, 404m
licensed in, 328, 329t 234m, 390, 391–2m yellow fever information for, 395
tuberculosis in, 337m The Gambia Guillain-Barré syndrome (GBS), 17t, 50,
evacuation insurance. See insurance malaria information for, 236m, 395 149, 152, 213, 258, 357, 370, 511
exercise-associated hyponatremia, 90–1 meningococcal meningitis in, 262m Guinea
expedition travel. See wilderness travel yellow fever information for, 353t, 395 Ebola in, 171
gastrointestinal anthrax, 142 Lassa virus in, 350
gastrointestinal illness. See also malaria information for, 236m, 396
F travelers’ diarrhea (TD) meningococcal meningitis in, 262m
Falkland Islands (Islas Malvinas), 393 considerations for travelers with, 573t yellow fever information for, 353t,
Fanning Island. See Kiribati cruise ship travel, 522–3 364m, 396
Faroe Islands (Denmark), 393 post-travel, 504–6 Guinea-Bissau
fascioliasis, 177–8 screening internationally adopted malaria information for, 236m, 396
fevers, 497t, 499–505, 511–12 children, 552 meningococcal meningitis in, 262m
Fiji, 393 Georgia, 395 yellow fever information for, 353t,
filariasis, lymphatic, 178–9, 429, 498 GeoSentinel Surveillance Network, 361t, 364m, 396
filoviruses, 349 7, 162, 476, 495, 503, 507, 533, Guyana, 396
filtration, water disinfection, 74–5, 74t, 77t 585, 646 dengue distribution in, 163m
Finland, Germany malaria information for, 234m, 396
malaria and yellow fever information malaria and yellow fever information yellow fever information for, 353t,
for, 393 for, 395 365m, 396
INDEX 657
8
56
658 INDEX
69
5
medical conditions with severe travelers’ diarrhea in, 534–6 International Society of Travel
immune deficits, 563–5, 567 antibiotics for, 535 Medicine, 3, 7, 12, 17, 52, 134, 373,
multiple sclerosis in, 562 dietary modification for, 536 480, 486, 614, 645–6
polio vaccine, 281–2 management of, 535–6 International travel and health, Green
potential drug interactions in, oral rehydration salts (ORS) Book, 10
568, 569 for, 535–6 intravenous immune globulin (IVIG),
severely immunocompromised (HIV/ prevention of, 534 administration intervals, 35t
AIDS), 565 treatment for, 52–3, 534–5 iodine resins, water disinfection with, 76
severely immunocompromised travel stress in, 540 iodoquinol, 52, 140
(non-HIV), 563–5 vaccination recommendations IPV (inactivated polio vaccine). See
yellow fever vaccine, 559t, 560t, 567–8 for, 541–5 poliomyelitis vaccine
inactivated polio vaccine (IPV). See Infectious Diseases Society of America IR3535, 83
poliomyelitis vaccine (IDSA), 335, 562, 645, 647 Iran, 397
immunization of children, 543–4 influenza, 206–14 Iraq, 399
immunization of cruise ship travel, 523 Ireland, 80, 399. See also United
immunocompromised H1N1, 19t, 206, 432, 462 Kingdom
adults, 560t H5N1, avian influenza, 208m Islas Malvinas, 393. See also Falkland
India, 397 in-flight transmission of, 519–20 Islands
child sex tourists, 319 influenza vaccine, 32, 33b, 37, 39t, 42, Isle of Man, 419. See also United
dengue in, 165m, 481 44, 211, 212t, 213–14 Kingdom
destination map, 479m health care workers, 591 Israel, 236m, 279, 399
destination overview, 478, 480 immunization of children, 535, 542–3 Italy
health issues in, 480–2 immunization of immunocompromised Lyme disease in, 232
Japanese encephalitis risk in, adults, 559t, 565 tickborne encephalitis in, 327
216m, 219t pregnant travelers, 580 itraconazole, 45, 202
leishmaniasis in, 228 vaccinations for air crews, 595 ivermectin, 160, 272, 308, 324, 514
malaria information for, 397, injuries Ivory Coast. See Côte d’Ivoire
398m, 481 international travel with infants and
medical tourism in, 111, 482 children, 533–4
melioidosis in, 260 long-term travelers/expatriates, 605 J
NDM-1, 503 preventing, 94–8 Jamaica
reference map, 398m road traffic, 95–7, 471, 476 dengue in, 163m
rickettsial infections, 299t safety and security, 99–101 malaria and yellow fever information
tuberculosis in, 337m, 481–2 unintentional, 97 for, 399
vaccinialike viruses in, 322 violence-related, 99–101 Japan
yellow fever information for, 397 water and aquatic, 97 Japanese encephalitis risk in, 216m, 219t
Indonesia insect protection, 81–6, 119, 537–8 malaria and yellow fever information
dengue distribution in, 165m insurance, 136–8 for, 399
Japanese encephalitis risk in, evacuation, 125, 137 rickettsial infections in, 298t, 299t
216m, 219t travel health, 136–8, 540 tickborne encephalitis in, 327
malaria information for, 242, 397 interferon-γ release assay (IGRA), 34, yersiniosis in, 368
schistosomiasis distribution in, 334, 341, 515, 552, 590, 604–5, Japanese encephalitis, 2b, 214–23
309, 311m 631, 635t geographic distribution of, 216m
yellow fever information for, 397 international adoptions, 550–5 risk by country, 218–21t
infants, children, and follow-up medical examination after Japanese encephalitis (JE) vaccine, 20t,
adolescents, 533–49 arrival in United States, 551–2 28, 39t, 217t, 222–3, 650t
accidents and injuries involving, 539 immunizations in, 554–5 immunization of children, 217, 222, 544
air travel with, 539 medical screening for adoptees, 633–4 immunization of immuno-
altitude illness in, 539–40 overseas medical examination of compromised adults, 560t
animal bites involving, 538–9 adopted child, 551 last-minute travelers, 585–7, 612
breastfeeding and travel with, 546–9 screening for infectious jet lag, 62–4
dengue in, 538 diseases, 552–4 Joint Commission International (JCI),
drowning and water-related injuries screening for noninfectious 114, 134
in, 539 diseases, 554 Jordan, 399
insect repellents, 85 travel preparation for adoptive
international adoption of, 550–5 parents and families, 550–1
international travel with, 533–40 international borders, taking K
malaria in, 536–8 animals and animal products Katayama syndrome, 312, 498, 501t. See
antimalarial drugs for, 235b, across, 530–2 also schistosomiasis
241–2t, 537 International Certificate of Vaccination kava, 118
personal protection measures or Prophylaxis (ICVP), 129, 280, Kazakhstan
for, 537–8 360–3, 363f, 372, 428, 544 malaria and yellow fever information
motion sickness in, 64–6 International Health Regulations (IHR), for, 399
polio vaccine, 280 3, 10, 20t, 41, 280, 284, 356, 367, tickborne encephalitis in, 327
rabies in, 538–9 372, 544 Kenya
safety in flying with, 97, 539 International Sanitary Regulations dengue distribution in, 164m
soil contact, infections related to, 538 (ISR), 3, 367 malaria information for, 236m,
sun exposure and, 540 International Society for Infectious 399, 401m
traveler insurance coverage for, 540 Diseases (ISID), 647–8 Marburg hemorrhagic fever in, 171
INDEX 659
0
6
660 INDEX
61
Medicare beneficiaries, 138 Middle East respiratory syndrome New Zealand, 49, 80, 175, 406. See also Cook
medications (MERS), 13, 21–2t, 30, 67, 267–8, Islands (New Zealand); Niue (New
increasing nausea, 50 433, 497t, 498, 589, 628 Zealand); Tokelau (New Zealand)
interactions with vaccines, 44–7 military populations and deployments. Nicaragua
photosensitivity, 88 See US military deployments dengue distribution in, 163m
psychotropic, refills, 125 mold contamination, 105–6 malaria information for, 234m,
traveling with, 127 Moldova, 405 406–7, 406m
mefloquine, 11, 28, 45, 155, 254–5 Monaco, 405 yellow fever information for, 406
drug interactions, 45, 619t Mongolia, 405 niclosamide, 325
immunocompromised travelers Lyme disease, 232 nifedipine, 60, 61t, 79, 93, 442
and, 568–9 rickettsial infections, 299t Niger
last-minute travelers and, 613 tickborne encephalitis in, 327 malaria information for, 236m, 407
long-term travelers and, 603–4 monkeypox, 322, 531 yellow fever information for, 353t,
malaria chemoprophylaxis, 235b, 238, Montenegro, 405 361t, 364m, 407
240t, 241–2t, 245t, 246–9, 250–1t Montserrat (UK), 405 Nigeria
mental health, 125 Moorea. See French Polynesia dengue distribution in, 164m
military deployments, special Morbidity and Mortality Weekly Report Lassa virus in, 350
considerations for, 617–18, 619t (CDC), 32, 33b malaria information for, 236m, 253, 407
use in children, 537 Morocco, 405 meningococcal meningitis in, 262m
use in people with chronic rickettsial infections, 298t yellow fever information for, 353t,
disease, 573–5t mosquitoes, avoidance of, 28, 81–6, 103, 364m, 407
use in pregnancy, 581 119, 239–40, 537–8 nitazoxanide, 52, 158, 178, 180
use while breastfeeding, 548 motion sickness, 5, 64–6, 117–18, 474b Niue (New Zealand), 407
melatonin, 63–4, 118 Mozambique N,N-diethyl-3-methyl-benzamide or N,
melioidosis, 260–1 dengue distribution in, 164m N-diethyl-m-toluamide (DEET),
meningococcal disease, 261–6 malaria information for, 236m, 405 83–4, 119, 313, 332, 537–8
in-flight transmission of, 520 yellow fever information for, 405 nontyphoidal salmonellosis, 304–6
Hajj pilgrimage and, 432–3 MPSV4. See meningococcal vaccine Norfolk Island (Australia), 407
meningococcal vaccine, 19t, 37, 39t, 261, multiple sclerosis, 562 norovirus, 269–71
263, 264t, 265–6, 562–3, 580, 590, mumps, 268–9 North America
602, 612 vaccine, 19t. See also measles- chronic hepatitis B virus
Hajj pilgrimage and, 432–3 mumps-rubella (MMR) vaccine; prevalence, 188m
immunization of children, 541, 543 measles-mumps-rubella- chronic hepatitis C virus
immunization of varicella (MMRV) vaccine prevalence, 194m
immunocompromised murine typhus, 300t, 301 ehrlichiosis in, 298t
adults, 560t Myanmar. See Burma (Myanmar) malaria-endemic countries, 234m
meningoencephalitis, 152, 260, 357 myiasis, 7, 429, 508t, 509 rickettsial infections, 298t, 299t
mental health, 124–6 tuberculosis in, 336m
meropenem, melioidosis treatment, 260 Northern Mariana Islands (US), 407
MERS (Middle East respiratory N North Korea
syndrome). See Middle East Namibia, 236m, 405 Japanese encephalitis risk in, 216m, 219t
respiratory syndrome (MERS) naproxen, 87 malaria and yellow fever information
methicillin-resistant Staphylococcus natural disasters, 97, 106 for, 407
aureus (MRSA), 508 Nauru, 405 Norway, 407
metronidazole, 52, 140, 180, 182, 326, 505 Neisseria gonorrhoeae, 315 tickborne encephalitis in, 327
Mexico Neisseria meningitidis, 261, 263, 520,
bovine tuberculosis in, 334 542, 543
child sex tourists, 319 nematode eggs, size and susceptibility O
destination map, 460m to filtration, 74t occupational exposure to HIV, 23,
destination overview, 459, 461 Neorickettsia, 297, 298t, 301. See also 588, 591–3. See also human
epidemic typhus in, 301 rickettsial infections immunodeficiency virus (HIV)
health issues in, 461–3 Nepal Oceania, 230, 233
leishmaniasis, 226 altitude illness in, 56 dengue in, 165m
malaria information for, 234m, 403, dengue distribution in, 165m Ocean Island. See Kiribati
404m, 461–2 destination map, 484m oil of lemon eucalyptus (OLE), 83, 119, 537
medical tourism, 111, 461 destination overview, 483–4 Oman, 407–8
trypanosomiasis in, 332 health issues in, 484–6 onchocerciasis, 271–2, 507
tuberculosis in, 336m, 462 Japanese encephalitis risk in, 216m, 220t oral contraceptives, 47
yellow fever information for, 403 leishmaniasis in, 228 oral rehydration salts (ORS), 51, 535–6
Zika in, 461 malaria information for, 406, 485 oseltamivir, 37, 210, 211, 212t
Micronesia, Federated States of, 403 yellow fever information for, 405 oxyuriasis, 275–6
Middle East. See also Hajj pilgrimage Netherlands, 406
dengue distribution in, 164m neurologic angiostrongyliasis, 140–1
leishmaniasis in, 226, 228 neurotoxic shellfish poisoning, 80 P
malaria information for, 233, New Caledonia (France) 406 Pakistan
236m, 242 NDM-1, 30, 503 dengue distribution in, 165m
Q fever in, 286–7 newly arrived immigrants and refugees, Japanese encephalitis risk in, 216m, 220t
schistosomiasis distribution in, 629–35. See also immigrant and malaria information for, 236m, 408
309, 311m refugee health considerations yellow fever information for, 408
INDEX 661
62
662 INDEX
6
3
INDEX 663
4
6
664 INDEX
6
5
INDEX 665
6
666 INDEX
67
Photography Credits
BANNER IMAGES FOR SELECT DESTINATIONS
East Africa (Safaris): Ashley K. Barnes/Personal Collection
Saudi Arabia (Hajj/Umrah Pilgrimage): Salim Parker/Personal Collection
South Africa: Gary W. Brunette/Personal Collection
Tanzania (Kilimanjaro): Shutterstock
Brazil: David Adam Roth/Personal Collection
Cuba: Jonatan Brandt/Personal Collection
Dominican Republic: Ashley K. Barnes/Personal Collection
Haiti: Gary W. Brunette/Personal Collection
Mexico: Shutterstock
Peru: Cusco, Machu Picchu, & Other Regions: Mark J. Sotir/Personal Collection
Burma (Myanmar): Logan Scholfield/Personal Collection
China: Zlatko Unger/Personal Collection
India: Apophia Funa/Personal Collection
Nepal: Gregg Taliaferro/Personal Collection
Thailand: Logan Scholfield/Personal Collection
Vietnam: Carolina Uribe/Personal Collection