Past infection with hepatitis A virus among Vancouver

street youth, injection drug users and men who have

sex with men: implications
Research
for vaccination programs
Recherche
From the *Vaccine Evaluation Center, British Columbia’s Children’s Hospital and the Jan J. Ochnio,* David
Patrick,† Margaret Ho,* Douglas N. Talling,*
University of British
Simon R. Dobson*
Columbia, and the †University of British
Abstract
Columbia Centre for Disease Control, Vancouver, BC.
Background: In Canada, inactivated hepatitis A vaccines are targeted selectively at those at increased
risk for infection or its complications. In order to evaluate the
This article has been peer reviewed.
need for routine hepatitis A vaccination programs in Vancouver for street youth,
CMAJ 2001;165(3):293-7
injection drug users (IDUs) and men who have sex with men (MSM), we deter- mined the prevalence of
antibodies against hepatitis A virus (HAV) and risk fac- tors for HAV in these groups. Methods: The
frequency of past HAV infection was measured in a sample of Van- couver street youth, IDUs and MSM
attending outreach and STD clinics and needle exchange facilities by testing their saliva for anti-HAV
immunoglobulin G. A self-administered, structured questionnaire was used to gather sociodemo- graphic
data. Stepwise logistic regression was used to evaluate the association between presumed risk factors
and groups and past HAV infection. Results: Of 494 study participants, 235 self-reported injection drug
use, 51 were self-identified as MSM and 111 met street youth criteria. Positive test results for anti-HAV
were found in 6.3% of street youth (95% confidence interval [CI] 2.6%–12.6%), 42.6% (95% CI
36.2%–48.9%) of IDUs and 14.7% (95% CI 10.4%–19.1%) of individuals who denied injection drug use.
Among men who denied injection drug use, the prevalence was 26.3% (10/38) for MSM and 12%
(21/175) for heterosexuals. Logistic regression showed that past HAV infection was associated with
increased age and birth in a country with high rates of hepatitis infection. Injection drug use among young
adults (25–34 years old) was a significant risk factor for a positive anti-HAV test (p = 0.009). MSM were
also at higher risk for past HAV infection, although this association was nomi- nally significant (p = 0.07).
Interpretation: Low rates of past HAV infection among Vancouver street youth indi- cate a low rate of virus
circulation in this population, which is vulnerable to hepatitis A outbreaks. An increased risk for HAV
infection in IDUs and MSM sup- ports the need to develop routine vaccination programs for these groups
also. H
epatitis tion but even rates A within virus have CMAJ • AUG. 7, 2001; 165 (3) 293
© 2001 Canadian Medical Association or its licensors (HAV) is the most frequent improved through better low-risk
countries such as cause of viral hepatitis. Infec- hygiene and public sanitation, Canada and the United States the
incidence of infection remains heterogeneous across geographic and socioeco- nomic strata.1–3 The availability of
effective inactivated vaccines provides a powerful new tool to enhance HAV control. Universal vaccination
programs for children and youth are being designed and implemented in the United States in areas of in- creased
hepatitis A incidence.4 In Canada, the vaccine is still targeted selectively at those at increased risk for infection or its
complications.
Recurrent hepatitis A outbreaks among men who have sex with men (MSM) and
Ochnio et al
injection drug users (IDUs) have contributed significantly to Vancouver’s high hepatitis A incidence rates of 24–27
cases per 100 000 population.3,5 These exceed the provincial average by up to 3 times.
Within the past decade, the health risks of street youth have been studied extensively, yet the prevalence of HAV
infection in this population in developed countries has not been investigated. Youth living on the streets may be at
in- creased risk for HAV infection as they are frequently in- volved in behaviours associated with higher risk, such
as in- jection drug use6,7 or involvement in the sex trade, resulting in multiple sexual partners.8,9 Street youth often
have re- stricted access to adequate sanitary facilities.
This study explored the risk of HAV infection among Vancouver’s street youth, IDUs and MSM through testing
for the presence of HAV-specific immunoglobulin G in their saliva. In order to assess the need for routine vaccina-
tion programs in these communities, we evaluated whether being in each category (MSM, IDUs, street youth)
consti- tutes an independent risk factor for HAV infection. The beginning of study enrolment coincided with the
launch of a public health effort in the Greater Vancouver area to pro- vide one dose of hepatitis A vaccine to
Vancouver’s MSM and IDUs as an outbreak control measure.

Methods
Study recruitment was conducted over a 6-month period from March to August 1998 through 4 locations in Greater
Vancouver: 2 “street outreach clinics” operating in the Vancouver downtown area, one of which mainly serves a street youth
population, whereas the other clinic, which is located near to the Vancouver needle exchange facility, was frequented
predominantly by injec- tion drug users; a needle exchange facility serving injection drug users in Surrey; and an STD clinic
located in Vancouver.
All those who attended the outreach clinics and the needle ex- change facility were invited to participate in this study, whereas
at the STD clinic the invitation was extended only to males. This re- striction was dictated by the feasibility of securing a
sufficient sample of MSM and heterosexual men who did not use drugs and were of similar social status. Excluded from the
study were those individuals who said that they had already been immunized against hepatitis A. At each location, recruitment
was conducted until about 120 individuals were enrolled. The rate of refusal to participate in the study was not recorded.
Saliva collection was facilitated by the use of Salivette (Sarstedt, Rommelsdorf, Germany) with a neutral cotton insert. Study
par- ticipants were asked to place the insert into the mouth, chewing occasionally until the insert was wet. Within 24 hours of
collec- tion, the saliva was recovered by centrifugation, divided into aliquots and frozen at –70° C until assayed. The presence of
HAV- specific IgG was evaluated using an ultrasensitive capture enzyme immunoassay–based method, which demonstrates 99%
sensitivity and specificity when compared with serum-based tests.10
Information about demographics, sexual orientation and prac- tices, previous injection drug use and hours per day spent on the
streets was collected using a 1-page, self-administered, structured questionnaire. The questionnaire was based on a similar instru-
ment used successfully to survey Vancouver MSM at the onset of
294 JAMC • 7 AOÛT 2001; 165 (3)
a hepatitis A outbreak. The study design, including the question- naire, was reviewed and approved by the Clinical Research
Ethics Board at the University of British Columbia
Individuals who reported having injected drugs in the past were identified as injection drug users (IDUs), whereas males who
reported a homosexual or bisexual orientation were identified as men who have sex with men (MSM). To qualify as street youth,
respondents had to be less than 25 years of age and had to have reported spending at least 8 hours daily on the streets.
The association between potential risk factors and groups and past infection with HAV was evaluated using stepdown logistic
re- gression. Goodness-of-fit statistics were examined to determine the appropriateness of the final model.
Besides the 3 groups (MSM, IDUs and street youth) who were originally thought to be at increased risk for HAV infec- tion,
the initial model also included sex, age group and birth in a country where there was an increased risk of HAV infection, the last
2 being well-recognized factors associated with past HAV infection. The 2-way interactions between age and hypothesized risk
groups were examined, as were the 2- and 3-way interac- tions among the risk groups themselves. The site of recruitment was not
considered to be a separate risk factor, because it was self-evident that there was a substantial overlap of the risk groups under
investigation due to the specialized nature of these clinics.

Results
A total of 494 individuals were recruited into the study (Table 1). The majority (77.5%) of the 111 study partici-
pants who met street youth criteria were enrolled through a street youth–oriented, downtown outreach clinic,
whereas most of the 235 subjects who reported past injection drug use were recruited through the needle exchange
facility (41.7%) and through the second downtown outreach clinic (42.1%). An MSM orientation was reported by 51
males,
Table 1: Prevalence of anti-HAV antibodies among Vancouver street youth, injection drug users and men
who have sex with men
Study subjects
Risk group
Total no.
% positive for anti-HAV
Mean age , yr (and SD)
IDUs (all) 235 42.6 34.6 (10.5) MSM (all) 51 25.5 33.7 (12.2) IDUs who are MSM 13 23.1 34.5 (13.0) Street youth
(all) 111 6.3 19.6 (2.7) Street youth who are IDUs 42 9.5 20.4 (2.6) Street youth who are not MSM or IDU 64 3.1 19.0
(2.5) Born in countries where HAV is prevalent (all) 32 40.6 34.6 (11.8)
Total 494 27.9 31.9 (11.2)
Note: HAV = hepatitis A virus, SD = standard deviation, IDU = injection drug user, MSM = men who have sex with
men.
most of whom were recruited at the STD clinic (54.9%) and at the youth-oriented outreach clinic (25.5%). Most
(71%) of the 157 participants who did not fall into any of the 3 risk groups were re- cruited at the STD clinic.
The presence of HAV-specific IgG was de- tected in saliva specimens from 138 individuals, resulting in an
overall prevalence rate of 27.9% (Table 1). Evidence of past HAV infection was detected in 7 of 111 participants
who met the street youth criteria, indicating a prevalence of 6.3% (95% confidence interval [CI] 2.6–12.6). Street
youth who were IDUs had higher rates of past infection with hepatitis A (4/42, 9.5%, 95% CI 2.7%–22.6%)
compared with street youth who denied a history of injection drug use (3/69, 4.3%, 95% CI 0.9%–12.2%), although
these dif- ferences were not statistically significant. The presence of anti-HAV was almost 3 times more common
among all IDUs (100/235, 42.6%, 95% CI 36.2%–48.9%) than among subjects who de- nied injection drug use
(38/258, 14.7%, 95% CI 10.4%–19.1%). The differences in rates of previ- ous HAV infection among IDUs and
non-IDUs were most pronounced in those aged 25–34 and 35–44 years and not present among those aged 45 years
and above, as illustrated in Fig. 1. Anti- HAV prevalence among MSM (13/51, 25.5%) was almost identical to that
of heterosexual men (83/315, 26.3%). After the exclusion of IDUs, however, it was more than twice as high among
MSM (10/38, 26.3%) than among heterosexuals (21/175, 12%).
Logistic regression identified 2 factors to be significantly associated with increased anti-HAV prevalence (Table
2): most obviously with greater age but also with birth in a country where there was increased risk for HAV
infection. IDUs and MSM were also at higher risk for past HAV in- fection, although these associations were nomi-
nally significant.
The regression analysis also identified 2 inter- actions that were significantly associated with in- creased
anti-HAV prevalence. First, an interac- tion between IDUs and age (p = 0.05) indicates that injection drug use
especially among young adults (25–34 years old) is a significant risk factor for a positive anti-HAV test (p = 0.009).
Second, a significant interaction between IDUs and MSM (p = 0.03) indicates that among MSM injection drug use
is not associated with the increased presence of anti-HAV. Among those who are not MSM, however, the anti-HAV
rate was 3.9 times higher in IDUs than in those who denied injec- tion drug use (95/218, 43.6%) versus (24/213,
11.3%).
Past infection with hepatitis A virus
60
50
40
30
20
10
0
< 25 25–34 35–44 > 44 Age, yr
Injection drug users Participants who denied injection drug use
Fig. 1: Prevalence of antibodies against hepatitis A virus (HAV) according to age and self-reported injection
drug use.
Table 2: Factors and groups associated with anti-HAV antibodies
Variable
CMAJ • AUG. 7, 2001; 165 (3) 295
Unadjusted OR* (95% CI)
Adjusted OR*
(95% CI) p value
Sex Male 0.72 (0.46–1.13) 0.75 (0.43–1.30) 0.30 Female† 1.00 – 1.00 – – Age group, yr < 0.001 < 25 0.09
(0.04–0.20) 0.10 (0.06–0.31) < 0.001 25–34 0.40 (0.22–0.73) 0.14 (0.05–0.36) < 0.001 35–44 1.17 (0.65–2.11) 0.84
(0.29–2.42) 0.75 > 44† 1.00 – 1.00 – – Risk group‡ IDUs 4.70 (3.01–7.34) 2.48 (0.88–6.99) 0.09 MSM 0.90
(0.46–1.74) 2.39 (0.93–6.14) 0.07 Street youth 0.13 (0.06–0.29) 0.69 (0.18–2.60) 0.59 Born in countries where HAV
is prevalent 1.85 (0.86–3.94) 2.93 (1.13–7.58) 0.03 Interaction IDUs x MSM – 0.15 (0.03–0.80) 0.03 Age group, yr ×
IDUs – 0.05 < 25 × IDUs – 1.26 (0.26–6.18) 0.78 25–34 × IDUs – 6.45 (1.58–26.26) 0.009 35–44 × IDUs – 1.59
(0.43–5.84) 0.48
Note: OR = odds ratio, CI = confidence interval. *Ten individuals were not included in the crude and adjusted models
because of gaps in the completeness of their questionnaire. Two individuals identified as transsexuals were also
excluded. †Reference category. ‡Study subjects who did not belong to a given risk group constituted the reference
category.
Ochnio et al

Interpretation
Our findings stress once again that injection drug use is not only associated with an unfavourable course of HAV
infection due to the likelihood of underlying chronic liver diseases,11,12 but also with an increased risk for HAV
infection itself, particularly among young adults. The stable, as opposed to increasing, prevalence of anti-HAV in
the older IDUs could reflect a past pat- tern of risk reduction behaviour and the cyclic nature of HAV transmission.
The development and implementa- tion of a routine vaccination program for IDUs appears to be the only rational
approach to breaking the cycle of hepatitis A outbreaks and, in the long run, saving costs and health care resources.
Similarly, in the case of MSM, our limited data tend to support calls for a routine 2-dose vaccination program to
provide long-term protection, as opposed to sporadic 1-dose vaccine interventions as an outbreak control measure
requiring sudden bursts of public health activity.
The high, age-independent HAV infection rate ob- served among IDUs in Vancouver is in accordance with
previous reports associating injection drug use with in- creased risk for this infection.13–15 The difference in anti-
HAV rates between young adult IDUs and those who de- nied prior injection drug use should be interpreted with
some caution. The majority of participants who denied in- jection drug use were enrolled into the study through clin-
ics other than the needle exchange program, which also in- cluded an STD clinic located in a more affluent
Vancouver neighbourhood. It is possible that the observed low rate in this group reflects not only lack of
involvement in injection drug use but also different social background. Socioeco- nomic status is a significant factor
associated with the prevalence of HAV infection,16 and it could not be con- trolled for in our study.
Discrepancies in social background, however, are un- likely to play any significant role in the difference in anti-
HAV prevalence observed between MSM and heterosexual men, because the proportion of individuals enrolled
through the STD clinic into each group was almost identi- cal. The similar rates of anti-HAV prevalence among
MSM and heterosexual men are probably the result of there being a higher proportion of IDUs among the
heterosexual men (44%) than among MSM (25%) and the lack of any addi- tional effect of injection drug use on
anti-HAV rates in MSM. The absence of additional risk may be because the harm reduction message that has been
delivered to MSM has spilled over into their injection drug–using habits. Al- though the difference in anti-HAV rate
between MSM and heterosexual men was more than 2-fold when individuals who denied injection drug use were
considered, being MSM on its own did not emerge as a significant risk factor in logistic regression. This result may
have been a conse- quence of the relatively small number of MSM studied (51); they constituted only about 10% of
study participants,
296 JAMC • 7 AOÛT 2001; 165 (3)
Competing interests: None declared.
Contributors: Drs. Ochnio, Patrick and Dobson contributed to the design and exe- cution of this study. Ms. Ho was responsible
for the accuracy of laboratory results and for data analysis. Mr. Talling designed the logistic regression model used for evaluation
of risk factors. All the authors took part in the drafting and revising of the article.
Acknowledgements: We are indebted to the nursing staff of Vancouver Outreach and STD clinics and the Surrey Needle
Exchange for their work in study enrol- ment, supervision of specimen collection and data gathering. We also thank Dr. Robert
Strang, Dr. Danuta Skowronski and Mr. Jim Bennett for their continued support throughout the study in allowing access to
clinics.
This work was supported by a British Columbia Health Research Foundation grant.
and of these only 33 denied injection drug use and were not street youth.
Evidence of past HAV infection was present in only 6.3% of Vancouver street youth. This closely resembles the
anti-HAV prevalence of 7.1% (95% CI 4.1%–11.3%) detected 2 years earlier among grade six students in Van-
couver.17 More than 25% of the sixth graders, however, were born outside Canada, and this subgroup contained the
majority of anti-HAV-positive children, whereas the sample of street youth included only 5 individuals born
elsewhere. Although the anti-HAV positivity rate among Canadian-born street youth (6.6%) was twice as high as the
rate observed among Canadian-born grade six students (3%), it still should be considered to be relatively low. Such
a low rate means that almost all of Vancouver street youth are likely to be susceptible to HAV. When this vul-
nerability is considered in addition to the substandard liv- ing conditions of a high proportion of this population and
their exposure to other risk factors associated with HAV infection, such as injection drug use (often resulting in
needle sharing6) and involvement in the sex trade (“survival sex,” multiple sexual partners), it would seem that an
out- break of hepatitis A is just waiting to happen. The design and implementation of a routine hepatitis A
vaccination program for street youth is challenging, because it is diffi- cult to reach all of this elusive and dynamic
population, but street youth do tend to concentrate in relatively small areas in certain parts of the city. However, they
represent a heterogeneous group whose time spent on the streets may vary considerably.
Reports from countries such as Brazil where there is an increased risk of contracting HAV infection indicate a
very high prevalence of 80%–92% in street youth.18 The preva- lence of HAV infection in street youth in other
Canadian ur- ban populations or in other low-risk countries might be very different from Vancouver’s, reflecting
local outbreak histo- ries. Such outbreaks involving street youth, however, might be difficult to recognize and
attribute to this population, be- cause it is elusive, it overlaps considerably with IDUs and it is often characterized by
limited access to health care ser- vices. The availability of a vaccine, which is easy to use and, thus, a very effective
preventive tool, calls for investigation of HAV prevalence in street youth populations particularly in low-risk
countries that have not adopted universal hepatitis A vaccination programs for children and youth.
References
1. Bell BP, Shapiro CN, Alter MJ, Moyer LA, Judson FN, Mottram K, et al. The diverse patterns of hepatitis A epidemiology in
the United States — im- plications for vaccination strategies. J Infect Dis 1998;178:1579-84. 2. Notifiable disease annual
summary 1997. Can Commun Dis Rep 1999;25(S6):
119-21. 3. BC reportable communicable diseases, annual summary 1998. Vancouver: UBC
Centre for Disease Control; 1999. p. 23-5. 4. Advisory Committee on Immunization Practices. Prevention of hepatitis A
through active or passive immunization. MMWR Morb Mortal Wkly Rep 1999;48(RR12):1-37. 5. BC reportable communicable
diseases, annual summary 1997. Vancouver: UBC
Centre for Disease Control; 1998. p. 21-3. 6. Roy E, Lemire N, Haley N, Boivin JF, Frappier JV, Classens C. Injection
drug use among street youth. Can J Public Health 1998;89(4):239-40. 7. Roy E, Haley N, Lemire N, Boivin JF, Leclerc P,
Vincelette J. Hepatitis B virus infection among street youths in Montreal. CMAJ 1999;161(6):689-93. Available:
www.cma.ca/cmaj/vol-161/issue-6/0689.htm 8. Greene JM, Ennett ST, Ringwald CL. Prevalence and correlates of survival sex
among runaway and homeless youth. Am J Public Health 1999;89(9):1406-9. 9. MacDonald NE, Fisher WA, Wells GA, Doherty
JA, Bowie WR. Canadian street youth: correlates of sexual risk-taking activity. Pediatr Infect Disease J 1994;13(8):690-7. 10.
Ochnio JJ, Scheifele DW, Ho M, Mitchell LA. New, ultrasensitive enzyme immunoassay for detection of vaccine- and
disease-induced hepatitis A virus-
specific immunoglobulin G in saliva. J Clin Microbiol 1997;35(1):98-101. 11. Vento S, Garofano T, Renzini C, Cainelli F,
Casali F, Ferraro T, et al. Ful- minant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis
C. N Engl J Med 1998;338(5):26-90. 12. Akriviadis EA, Redeker AG. Fulminant hepatitis A in intravenous drug users
with chronic liver disease. Ann Intern Med 1989;110(10):838-9. 13. Widell A, Hansson BG, Moestrup T, Nordenfelt E.
Increased occurrence of hepatitis A with cyclic outbreaks among drug addicts in a Swedish commu- nity. Infection
1983;11:198-200. 14. Hepatitis A among drug abusers. MMWR Morb Mortal Wkly Rep 1988;37(19):
297-300,305. 15. Harkess J, Gildon B, Istre GR. Outbreaks of hepatitis A among illicit drug
users, Oklahoma, 1984-87. Am J Public Health 1989;79(4):463-6. 16. Szmuness W, Dienstag JL, Purcell RH, Harley EJ,
Steavens SE, Wong DC. Distribution of antibody to hepatitis A antigen in urban adult populations. N Engl J Med
1976;295(14):755-9. 17. Ochnio JJ, Scheifele DW, Ho M. Hepatitis A virus infections in urban chil- dren — are preventive
opportunities being missed? J Infect Dis 1997;176: 1610-3. 18. Queiroz DA, Cardoso DD, Martelli CM, Martins RM, Porto SO,
Azevedo MS, et al. Seroepidemiology of hepatitis A virus infection in street children of Goiania-Goias. Rev Soc Bras Med Trop
1995;28(3):199-203.
Correspondence to: Dr. Jan J. Ochnio, Vaccine Evaluation Center, Rm 317A, 950 W 28th Ave., Vancouver BC V5Z
4H4; fax 604 875-2496; [email protected]

available for your handheld (PDA)

Enjoy quick access to eCMAJ on the run with downloadable content for your personal digital assistant. Content is
available in three popular formats — AvantGo, iSilo and handheld-friendly HTML — for any type of handheld —
Palm OS, Pocket PC (Windows CE) or Psion.
When each issue appears, you receive:
• table of contents
• abstracts
• news
• Public Health
• Clinical Update
• Preventive Health Care
And you can sign up for our bioethics series, or the clinical practice guidelines on breast cancer (available in both
languages). More content is coming soon!

Visit www.cma.ca/cmaj and click on “eCMAJ on your PDA (handheld)”

Past infection with hepatitis A virus
What they’re saying . . .
“I was pleased to be point- ed to the eCMAJ site re- cently . . . and I have added the [AvantGo] channel.” — Dr. Robert Pless,
National Immunization Program, US Centers for Disease Control and Prevention, Atlanta
“Bravo!” — Dr. Andrew Morris, infectious diseases and general internal medicine, Hamilton Health Sciences, Hamilton
“I find this format much more user-friendly than the paper version. It is much more portable. I have used the journal regularly
since this feature was introduced.” — Dr. John Haggie, general and vascular surgery, Gander, Nfld.
CMAJ • AUG. 7, 2001; 165 (3) 297