CASE REPORT

“Dengue Fever”

Preceptor :

dr. Hj. Ihsanil Husna, Sp.PD

By :

Digit Galuh Gantina

MEDICAL PROFESSION PROGRAMME DEPARTMENT OF

INTERNAL MEDICINE
JAKARTA ISLAMIC HOSPITAL CEMPAKA PUTIH
FACULTY OF MEDICINE UNIVERSITY OF
MUHAMMADIYAH JAKARTA
2019
 PATIENT’S IDENTITY

1.1 PATIENT’S IDENTITY

• Name : Mr. Z
• Age : 21 years old
• Marital Status : Single
• Religion : Moslem
• Date of Admission : 7 March 2019

1.2 ANAMNESIS (AUTOANAMNESIS)

a. Chief Complaint
Fever 4 days ago

b. Another Complaint
Headache (+), Nausea (+), Myalgia (+), Epigastric pain (+).

c. History of Present Illness

The patient complaining about the fever he had 4 days before came to the
Jakarta Islamic Hospital Cempaka Putih. The fever starts with sudden high
temperature and continuously high all day. It followed with headache and
muscle pains. Spontaneous bleeding from nose and gums are denied. The
patient is also complained nausea, lose of appetite since 2 days ago and
also epigastric pain. Urinary and defecation remains normal. No history of
traveling to endemic areas.

d. History of Past Illness

- No history same problem

- No history of traveling to endemic areas

- Dyspepsia syndrome

e. History of Family

None of his family has the same problem

 f. History of Allergy

Patient has no allergy to food and drugs

g. History of Treatment

The patient had treated his complaint with Paracetamol.

h. Habits

- The patient let his clothes hanging untidy

- Only clean his bathtub once a month

1.3 PHYSICAL EXAMINATION

• Generalis Status : Mild ill
• Consciusness : Composmentis, GCS E4M6V5
• Vital Sign
• Temperature 37,9oC
• RR 20x/minutes
• HR 82x/minutes
• BP 120/80 mmHg

Anthropometric Status
Body weight : 60 kg
Body high : 169 cm

BMI : 21,1 (Normoweight)

GENERAL PHYSICAL EXAMINATION

• Head : Normocephal, Deformity (-)
• Eyes : Anemic Conjungtiva (-/-), Icteric Sclera (-/-)
• Nose : Epistaksis (-/-), Secret (-/-), Deviated Septum (-/-)
• Mouth, Lips, Tongue : Oral Mucosa Moist, Cyanosis (-), Coated Tongue (-
)

• Neck : Palpable Mass (-), Lymphadenopathy (-)

• Ear : Secret (-/-)
Thorax
• Inspection : The movement of the chest symmetrical
• Palpation : Same vocal fremitus in dextra and sinistra
• Percussion : Sonor
• Auscultacion : Vesicular breath sounds + / +, Ronkhi -/-, Wheezing - / -

Cor
• Inspection : Ictus cordis not seen in ICS V LMCS
• Palpation : Ictus cordis not palpable ICS V LMCS
• Percussion : Right heart margin: Sternalis line sinistra ICS-V Left
heart margin: Midclavicula line sinistra ICS-V.
• Auscultation : Regular 1st & 2nd heart sounds, Murmur (-), Gallop (-)

Abdomen
 Inspection : Flat, scar (-), darm contour (-) darm steifung (-)

 Auscultation : Bowel Sound (+) 12x/minutes

 Palpation : Epigastric Pain (+), Hepatomegaly (-), Spleenomegaly (-)

 Percussion : Tympanic in all abdominal fields

Extremities
• Superior : Edema (- / -), Warm acral (+ / +), RCT ≤2 seconds (+ /

+), Cyanosis (-/-), Petechia (-/-)

• Inferior : Edema (-/ -), Warm acral (+ / +), RCT ≤2 seconds (+ / +),
Cyanosis (-/-), Petechia (-/-)
1.4 LABORATORY EXAMINATION
7 March 2019 – 12.14 WIB
EXAMINATION VALUE UNITS NORMAL
Hemoglobin 16,7 g/dL 13,2 – 17,3

Hematocrit 49 % 40 - 52
Leukocyte 6,79 103/uL 3.8 – 10,6
Thrombocyte 146 ↓ 103/µl 150 - 440
Erythrocytes 5.82 106/µl 4,4 – 5,9
MCV 84 Fl 80-100
MCH 29 pg 26-34
MCHC 34 g/dl 32-36

8 March 201

EXAMINATION VALUE UNITS NORMAL

Hemoglobin 16,4 g/dL 13,2 – 17,3
Hematocrit 47 % 40 - 52
Leukocyte 5,32 103/uL 3.8 – 10,6
Thrombocyte 139 ↓ 103/µl 150 - 440
Erythrocytes 5.75 106/µl 4,4 – 5,9
MCV 82 Fl 80-100
MCH 28 Pg 26-34
MCHC 34 g/dl 32-36
1.5 RESUME

Mr Z, 21 years old complaining about the febris he had 4 days before

came to the Jakarta Islamic Hospital Cempaka Putih. The febris starts with
sudden high temperature and continuously high all day. It followed with
headache and myalgia. The patient is also complained nausea, lose of appetite
and epigastric pain since 2 days ago.

On Physical Examination

Tourniquet Test (+)

Vital Sign

o Temperature: 37,9 ° C Febris

Laboratory Findings
7/5/2019
- Thrombocytopenia

8/5/2019

- Thrombocytopenia

1.6 PROBLEM LIST

- Fever + Headache + Myalgia e.c Dengue Haemorrhagic Fever dd/ Typhoid

Fever
- Nausea + Epigastric pain e.c Enteric infection dd/ Functional Dyspepsia
1.7 ASSESMENT

1. Fever, Headache, and Myalgia e.c Dengue Hemorrhage Fever Grade I dd/
Typhoid Fever

S Complained of fever 4 days ago, starts with sudden high temperature and
continuously high all day. It followed with headache and muscle pains.

O Vital sign
Temperature: 37,9 ° C  Sub Febris
Physical Examination : tourniquet (+)
Laboratory Findings
7/5/2019

- Thrombocytopenia

8/5/2019
- Thrombocytopenia

A Fever e.c Susp Dengue Fever dd/ Typhoid Fever

P Planning Diagnostic:

- Routine Haemotology/24hour
- IgG & IgM Anti-dengue
- Widal Test
Planning Non Therapeutics

- Bed Rest
- Monitoring vital signs
Planning Therapeutics

- IVFD RL 2300 cc/24 jam

- Paracetamol 3x500mg
1. Nausea and Epigastric Pain e.c Enteric infection dd/ Functional Dyspepsia

S The patient is also complained nausea, lose of appetite since 2

days ago, and also epigastric pain.

O Vital sign
Temperature: 37,9 ° C  Sub Febris
Physical Examination
Palpation : Epigastric pain (+)

A Nausea and Epigastric Pain e.c Enteric infection dd/

Functional Dyspepsia

P
Planning Non Therapeutics
- Bed Rest
- Diet Modification

Planning Therapeutics
- Ranitidine inj 2 x 1 amp
 1.8 FOLLOW UP

Date Subjective Objective Assesment Planning

8/5/20 Fever (+), Vital Signs : Dengue Planning Diagnostic:

19 Fever dd/
Headache BP, HR, and RR Typhoid - Routine
(+), within Fever haemotology/
Myalgia nor 24 hour
(+), mal limits
- IgG &
Nausea
IgM Anti-
(+), Temperature:
dengue
37,7
°C - Widal Test
Epigastric
Physical Planning Non
pain (+) Examination Therapeutics
:
- Bed Rest
Tourniquet
- Monitoring
Test (+) vital signs

Laborat Planning
ory Therapeutics
Findings

8/5/2019 - IVFD RL

Thrombocytope 2300cc/24

nia hours

- Paraceta
mol
 3x500mg

- Ranitidine inj
2 x 1 amp
 CHAPTER II
LITERATURE REVIEW
DENGUE FEVER

2.1 Definition

Dengue fever caused by several arthropod-borne viruses, family

Flaviviridae, genus Flavivirus, and is transmitted to humans by
Aedes mosquitoes, mainly Aedes aegypti1. It characterized by biphasic fever,
myalgia or arthralgia, rash, leukopenia, and lymphadenopathy. Dengue
hemorrhagic fever is a severe, often fatal, febrile disease characterized by capillary
permeability, abnormalities of hemostasis, and, in severe cases, a protein-losing
shock syndrome (dengue shock syndrome)2.

2.2 Classification

In 1997 World Health Organization (WHO) classifies DHF in four grades

(I to IV). DHF grades I and II represent relatively mild cases without shock, whereas
grade III and IV cases are more severe and accompanied by shock. DHF is
characterized by all the symptoms of DF rapid onset of fever in combination with
severe headache, retro-orbital pain, myalgia, arthralgia, gastrointestinal discomfort,
and usually rash and in combination with hemorrhagic manifestations (positive
tourniquet test or spontaneous bleeding), thrombocytopenia, and evidence of
increased vascular permeability (increased hemoconcentration or fluid effusion in
chest or abdominal cavities)4.
 Figure 1. The 1998 WHO Classification of Dengue Virus

The life-threatening DSS stage occurs at the time of or shortly after

defervescence, which is characterized by a rapid, weak pulse (≤20 mm Hg) or
hypotension with cold, clammy skin in the early stage of shock (grade III). If
patients do not receive prompt and appropriate treatment, a stage of profound shock
may set in, in which pulse and blood pressure become undetectable (grade IV),
resulting in death within 12 to 36h after onset of shock2.
The 2009 WHO criteria classify dengue according to levels of severity:
dengue without warning signs; dengue with warning signs (abdominal pain,
persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver
enlargement, increasing haematocrit with decreasing platelets); and severe dengue
(dengue with severe plasma leakage, severe bleeding, or organ failure). Patients
who recover following defervescence are considered to have non-severe dengue,
but those who deteriorate tend to manifest warning signs. These individuals are
likely to recover with intravenous rehydration3.
DHF is classified into four grades of severity, where grades III and IV are
considered to be DSS. The presence of thrombocytopenia with concurrent
haemoconcentration differentiates grades I and II DHF from DF.5
• Grade I : fever accompanied by non-speesific constitutional symptoms; the
only haemorrhagic manifestation is a positive tourniquet test and/or easy bruising
• Grade II : spontaneous bleeding in addition to the manifestations of grade I
patients, usually in the forms of skin or other haemorrhages
• Grade III : circulatory failure manifested by a rapid, weak pulse and
narrowing of pulse pressure or hypotension, with the presence of cold clammy
skin and restlessness.
• Grade IV : profound shock with undetectable blood pressure or pulse.
Grading the severity of the disease at the time of discharge has been found
clinically and epidemiologically useful in DHF epidemics in children in the WHO
regions of the Americas, south-east asia and the western pacific, and experience in
cuba, Puerto rico and Venezuela suggest that grading is alsouseful for adult cases.5

2.3 Etiology
There are at least 4 distinct antigenic types of dengue virus (dengue 1, 2, 3, and 4),
members of the family Flaviviridae. In addition, 3 other arthropod-borne viruses
(arboviruses) cause similar or identical febrile diseases with rash4
2.4 Course of Dengue Illness

The Febrile Phase: Early in the course of illness, patients with DHF can
present much like DF, but they may also have hepatomegaly without jaundice (later
in the Febrile Phase). The hemorrhagic manifestations that occur in the early course
of DHF most frequently consist of mild hemorrhagic manifestations as in DF. Less
commonly, epistaxis, bleeding of the gums, or frank gastrointestinal bleeding occur
while the patient is still febrile (gastrointestinal bleeding may commence at this
point, but commonly does not become apparent until a melenic stool is passed much
later in the course). Dengue viremia is typically highest in the first three to four
days after onset of fever but then falls quickly to undetectable levels over the next
few days. The level of viremia and fever usually follow each other closely, and anti-
dengue IgM anti-bodies increase as fever abates.4

The Critical (Plasma Leak) Phase: About the time when the fever abates,
the patient enters a period of highest risk for developing the severe manifestations
of plasma leak and hemorrhage. At this time, it is vital to watch for evidence of
hemorrhage and plasma leak into the pleural and abdominal cavities and to
implement appropriate therapies replacing intravascular losses and stabilizing
effective volume. If left untreated, this can lead to intravascular volume depletion
and cardiovascular compromise. Evidence of plasma leak includes sudden increase
in hematocrit (≥20% increase from baseline), presence of ascites, a new pleural
effusion on lateral decubitus chest x-ray, or low serum albumin or protein for age
and sex. Patients with plasma leak should be monitored for early changes in
hemodynamic parameters consistent with compensated shock such as increased
heart rate (tachycardia) for age especially in the absence of fever, weak and thready
pulse, cool extremities, narrowing pulse pressure (systolic blood pressure minus
diastolic blood pressure <20 mmHg), delayed capillary refill (>2 seconds), and
decrease in urination (i.e., oliguria). Patients exhibiting signs of increasing
intravascular depletion, impending or frank shock, or severe hemorrhage should be
admitted to an appropriate level intensive care unit for monitoring and intravascular
volume replacement. Once a patient experiences frank shock he or she will be
categorized as having DSS. Prolonged shock is the main factor associated with
complications that can lead to death including massive gastrointestinal hemorrhage.
Interestingly, many patients with DHF/DSS remain alert and lucid throughout the
course of the illness, even at the tipping point of profound shock. 4

Anticipatory management and monitoring indicators are essential in

effectively administering therapies as the patient enters the Critical Phase. New-
onset leucopenia (WBC <5,000 cells/mm3) with a lymphocytosis and an increase
in atypical lymphocytes indicate that the fever will likely dissipate within the next
24 hours and that the patient is entering into the Critical Phase. Indicators that
suggest the patient has already entered the Critical Phase include sudden change
from high (>38.0°C) to normal or subnormal temperatures, thrombocytopenia
(≤100,000 cells/mm3) with a rising or elevated hematocrit (≥20% increase from
baseline), new hypoalbuminemia or hypocholesterolemia, new pleural effusion or
ascites, and signs and symptoms of impending or frank shock. 4

Again, the key to successfully managing patients with DHF and lowering
the probability of complications or death is early recognition and anticipatory
treatment. Supportive care and timely but measured intravascular volume
replacement during the Critical Period are the mainstays of treatment for DHF and
DSS. 4
 Fortunately, the Critical Period lasts no more than 24 to 48 hours. Most of
the complications that arise during this period—such as hemorrhage and metabolic
abnormalities (e.g., hypocalcemia, hypoglycemia, hyperglycemia, lactic acidosis,
and hyponatremia) are frequently related to prolonged shock. Hence, the principal
objective during this period is to prevent prolonged shock and support vital systems
until plasma leak subsides. Careful attention must be paid to the type of intravenous
fluid (or blood product if transfusion is needed) administered, the rate, and the
volume received over time. Frequent monitoring of intravascular volume, vital
organ function, and the patient’s response are essential for successful management
during the Critical Phase. Monitoring for overt and occult hemorrhage (which may
be another source of intravascular depletion) is also important. Transfusion of
volume-replacing blood products should be considered if substantial hemorrhage is
suspected during this phase. 4

The Convalescent (Reabsorption) Phase: The third phase begins when the
Critical Phase ends and is characterized when plasma leak stops and reabsorption
begins. During this phase, fluids that leaked from the intravascular space (i.e.,
plasma and administered intravenous fluids) during the Critical Phase are
reabsorbed. Indicators suggesting that the patient is entering the Convalescent
Phase include sense of improved well being reported by the patient, return of
appetite, stabilizing vital signs (widen pulse pressure, strong palpable pulse),
bradycardia, hematocrit levels returning to normal, increased urine output, and
appearance of the characteristic Convalescence Rash of Dengue (i.e., a confluent
sometimes pruritic, petechial rash with multiple small round islands of unaffected
skin). At this point, care must be taken to recognize signs indicating that the
intravascular volume has stabilized (i.e., that plasma leak has halted) and that
reabsorption has begun. Modifying the rate and volume of intravenous fluids (and
often times discontinuing intravenous fluids altogether) to avoid fluid overload as
the extravasated fluids return to the intravascular compartment is important.
Complications that arise during Convalescent (Reabsorption) Phase are frequently
related to the intravenous fluid management. Fluid overload may result from use of
hypotonic intravenous fluids or over use or continued use of isotonic intravenous
fluids during the Convalescence Phase. 4

2.5 Clinical Finding

• Symptoms and Signs
 A history of travel to a dengue-endemic area within 14 days of symptom
onset is helpful in establishing a diagnosis of dengue. Dengue infection may range
from asymptomatic to severe hemorrhagic fever to fatal shock (dengue shock
syndrome). Dengue fever is usually a nonspecific, self-limited biphasic febrile
illness. More than half of infected children are asymptomatic. The illness is more
severe and begins more suddenly in adults. After an incubation period of 4–5 days,
there is a sudden onset of high fever, chills, and “break bone” aching of the head,
back, and extremities accompanied by sore throat, prostration, and malaise. There
may be conjunctival redness. Initially, the skin appears flushed or blotched, but 3–
4 days after the lysis of the fever, a maculopapular rash, which sparespalms and
soles, appears in over 50% of cases. As the rash fades, localized clusters of petechiae
on the extensor surface of the limbs become apparent. Up to 25% may manifest
signs of cardiac involvement. Hepatitis frequentlycomplicates dengue fever with
acute fulminant hepatitis in up to 5%.
Dengue hemorrhagic fever usually affects children living in endemic areas
and is most likely to occur in secondary infections and in infections with serotype
2. A few days into the illness, signs of hemorrhage such as ecchymoses,
gastrointestinal bleeding, and epistaxis appear. Symptoms found more often among
the dengue hemorrhagic fever subset of patients include restlessness, epistaxis, and
abdominal pain. Gastroenterologic complications, including hemorrhage,
tenderness, and ascites, are more common with dengue hemorrhagic fever and often
require intensive care observation.
A subset of patients (more often girls than boys) often with secondary
infection, may progress to dengue shock syndrome in which acute fever,
hemorrhagic manifestations, and marked capillary leak are prominent; the latter
manifests as pleural effusions and ascites, and there is a tendency for shock to
develop. In infants, even primary infection can lead to dengue shock syndrome.
While the infection is difficult to distinguish from malaria, yellow fever, or
influenza, the rash makes dengue far more likely. Continuous abdominal pain with
vomiting, bleeding, a decrease in the level of consciousness, rash, conjunctival
congestion, and hypothermia should raise concern about dengue shock syndrome.
Acute kidney injury in dengue largely occurs with dengue shock syndrome and
shows a high mortality. While acute severe hepatitis can occur with dengue,
concomitant other hepatotropic agents are usually responsible.
Distinguishing between dengue and other causes of febrile illness in
endemic areas is difficult. Fevers due to dengue are more often associated with
 neutropenia and thrombocytopenia and with myalgias, arthralgias/arthritis, and
lethargy among adults.
- Laboratory Finding
Leukopenia is characteristic, and elevated transaminases are found frequently
in dengue fever. Thrombocytopenia, increased fibrinolysis, and hemoconcentration
occur more often in the hemorrhagic form of the disease. Liver biochemical test
abnormalities are nearly universal. Thrombocytopenia, plasma leakage, and acute
hepatitis are identified as predictors of severe manifestations of dengue and higher
mortality. The nonspecific nature of the illness mandates laboratory verification for
diagnosis, usually with IgM and IgG ELISAs after the febrile phase. Virus may be
recovered from the blood during the acute phase. PCR or detection of the specific
viral protein NS1 by ELISA may be diagnostic during the first few days of infection
and may be appropriate for febrile travelers. Immunohistochemistry for antigen
detection in tissue samples can also be used. Because the erythrocyte sedimentation
rate is normal in most cases, elevation may help with the differential. Chest
radiographs in dengue hemorrhagic fever show infiltrates and effusions, which
follow the course of laboratory abnormalities.
2.6 Treatment

Treatment of uncomplicated dengue fever is supportive. Bed rest is advised

during the febrile period. Antipyretics should be used to keep body temperature
<40°C (104°F)8. Fluid and electrolyte replacement is required for deficits caused
by sweating, fasting, thirsting, vomiting, and diarrhea. Patients with ≥ 3 days of
illness should be reviewed daily for disease progression (indicated by decreasing
white blood cell and platelet counts and increasing haematocrit, defervescence and
warning signs) until they are out of the critical period.6

The Indonesian Society of Internal Medicine arranged protocols for

dengue hemorrhagic fever management in adult patients. The protocols divided into
five category. 7
a. Protocol 1 : management of probable dengue hemorrhagic fever without
shock

 Hemoglobin, haematocrit, or thrombocyte within normal limits or

thrombocyte between 100.000 – 150.000, the can be sent home but
should be advised to return to the nearest hospital immediately if
they develop any of the warning signs.
 Hemoglobin, haematocrit,within normal limits, but the thrombocyte
< 100.000 should be admitted for in-hospital.
 Increasing hemoglobin, haematocrit and thrombocyte remains
normal or decrease should be admitted for in-hospital.
b. Protocol 2 : fluid and electrolyte replacement

 Intravenous fluid therapy begins. Give only isotonic solutions such as

crystalloid, according to the formula (1500 + {20xBB dalam kg-20)}. After
giving fluid resuscitation, then check (hemoglobin, haematocrit) per 24
hours.
 If hemoglobin, haematocrit increase 10-20% and thrombocyte < 100.000,
monitoring hemoglobin, haematocrit, and thrombocyte per 12 hours.
 If hemoglobin, haematocrit increase >20% and thrombocyte < 100.000, so
fluid replacement in accordance with the protocol of management dengue
hemorrhagic fever with increasing haematocrit > 20%.

c. Protocol 3 : increase of >20% in haematocrit

Increasing of haematocrit > 20% shows that the body lose 5% of the fluid.
At this moment, give crystalloid solution start with 6−7 ml/kg/hour, then
for 3−4 hours, then reduce to 5 ml/kg/hour for 2−hours, and then reduce to
3 ml/kg/hour or less according to the clinical response. 7
d. Protocol 4 : management of spontaneous bleeding

e. Protocol 5 : management of dengue shock syndrome

 These are patients with severe dengue who require emergency treatment
and urgent referral because they are in the critical phase of the disease and have,
severe plasma leakage leading to dengue shock and/or fluid accumulation with
respiratory distress, severe haemorrhages; and severe organ impairment
(hepatic damage, renal impairment, cardiomyopathy, encephalopathy or
encephalitis). 7

All patients with severe dengue should be admitted to a hospital with

access to blood transfusion facilities. Intravenous fluid resuscitation is the
essential and usually sole intervention required. The crystalloid solution should
be isotonic and the volume just sufficient to maintain an effective circulation
during the period of plasma leakage. Plasma losses should be replaced
immediately and rapidly with isotonic crystalloid solution: in the case of
hypotensive shock, colloid solution is preferred. If possible, obtain haematocrit
levels before and after fluid resuscitation. 7

Continue replacement of further plasma losses to maintain effective

circulation for 24−48 hours. For overweight or obese patients, the ideal body
weight should be used for calculating fluid infusion rates. All shock patients
should have their blood group taken and a cross-match carried out. Blood
transfusion should be given only in cases with established severe bleeding, or
suspected severe bleeding in combination with otherwise unexplained
hypotension.7

Fluid resuscitation must be clearly separated from simple fluid

administration. This is a strategy in which larger volumes of fluids (e.g. 10−20
ml/kg boluses) are administered for a limited period of time under close
supervision, to evaluate the patient’s response and to avoid the development of
pulmonary oedema.7

2.7 Prognosis
Fatalities are rare but do occur (and more often among girls and the very
young), especially during epidemic outbreaks, with occasional patients dying of
fulminant hepatitis. Renal failure in dengue shock syndrome portends an especially
poor prognosis. Convalescence for most patients is slow.
 CHAPTER III
LITERATURE REVIEW
TYPHOID FEVER
3.1 Definition

Typhoid fever is a systemic disease characterized by fever and

abdominal pain and caused by dissemination of S. Typhi or S. Paratyphi.6 The
disease was initially called typhoid fever because of its clinical similarity to
typhus.

3.2 Epidemiology

In contrast to other Salmonella serotypes, the etiologic agents of enteric

fever—S. Typhi and S. Paratyphi serotypes A, B, and C—have no known hosts
other than humans10. Most commonly, food-borne or waterborne transmission
results from fecal contamination by ill or asymptomatic chronic carriers8.
Sexual transmission between male partners has been described. Health care
workers occasionally acquire enteric fever after exposure to infected patients or
during processing of clinical specimens and cultures.6

Typhoid fever occurs worldwide, primarily in developing nations whose

sanitary conditions are poor. Typhoid fever is endemic in Asia, Africa, Latin
America, the Caribbean, and Oceania, but 80% of cases come from Bangladesh,
China, India, Indonesia, Laos, Nepal, Pakistan, or Vietnam. Within those
countries, typhoid fever is most common in underdeveloped areas. Typhoid
fever infects roughly 21.6 million people (incidence of 3.6 per 1,000 population)
and kills an estimated 200,000 people every year.6

In endemic regions, enteric fever is more common in urban than rural

areas and among young children and adolescents than among other age groups8.
Risk factors include contaminated water or ice, flooding, food and drinks
purchased from street vendors, raw fruits and vegetables grown in fields
fertilized with sewage, ill household contacts, lack of hand washing and
 toilet access, and evidence of prior Helicobacter pylori infection (an association
probably related to chronically reduced gastric acidity).7

3.3 Clinical Manifestations

The incubation period for S. Typhi 1175 averages 10–14 days but ranges
from 5 to 21 days, depending on the inoculumsize and the host’s health and
immune status. The most prominent symptom is prolonged fever (38.8°–
40.5°C; 101.8°– 104.9°F), which can continue for up to 4 weeks if untreated. 6

The clinical presentation varies from a mild illness with low-grade fever,
malaise, and slight, dry cough to a severe clinical picture with abdominal
discomfort and multiple complications11. Many factors influence the severity
and overall clinical outcome of the infection. They include the duration of
illness before the initiation of appropriate therapy, choice of antimicrobial
treatment, age, previous exposure or vaccination history, virulence of the
bacterial strain, quantity of inoculum ingested, and several host factors affecting
immune status11. However, some of the other features and complications of
typhoid fever seen in adults, such as relative bradycardia, neurologic
manifestations, and gastrointestinal bleeding, are rare in children.

Typhoid fever usually manifests as high-grade fever with a wide variety

of associated features, such as generalized myalgia, abdominal pain,
hepatosplenomegaly, abdominal pain, and anorexia. The early stage of the
disease may be difficult to differentiate from other endemic diseases such as
malaria and dengue fever. The fever may rise gradually, but the classic
stepladder rise of fever is relatively rare.

In approximately 25% of cases, a macular or maculopapular rash (rose

spots) make up a faint, salmon-colored, blanching, maculopapular rash located
primarily on the trunk and chest may be visible around the 7th-10th day of the
illness, and lesions may appear in crops of 10-15 on the lower chest and
abdomen and last 2-3 days.6
3.4 Diagnosis

Because the clinical presentation of enteric fever is relatively non-

specific, the diagnosis needs to be considered in any febrile traveler returning
from a developing region, especially the Indian subcontinent, the Philippines,
or Latin America. Other diagnoses that should be considered in these travelers
include malaria, hepatitis, bacterial enteritis, dengue fever, rickettsial
infections, leptospirosis, amebic liver abscesses, and acute HIV infection.

The mainstay of the diagnosis of typhoid fever is a positive result of

culture from from blood, bone marrow, other sterile sites, rose spots, stool, or
intestinal secretions11. Results of blood cultures are positive in 40-60% of the
patients seen early in the course of the disease, and stool and urine culture
results become positive after the 1st wk. The stool culture result is also
occasionally positive during the incubation period. However, the sensitivity
of blood cultures in diagnosing typhoid fever in many parts of the developing
world is limited because widespread liberal antibiotic use may render
bacteriologic confirmation difficult.

Bone marrow culture is >80% sensitive, and, unlike that of blood

culture, its yield is not reduced by up to 5 days of prior antibiotic therapy8.
Culture of intestinal secretions (best obtained by a noninvasive duodenal
string test) can be positive despite a negative bone marrow culture. If blood,
bone marrow, and intestinal secretions are all cultured, the yield is >90%.
Stool cultures, although negative in 60–70% of cases during the first week,
can become positive during the third week of infection in untreated patients.6

Other than a positive culture, no specific laboratory test is diagnostic

for enteric fever. In 15–25% of cases, leukopenia and neutropenia are
detectable. Leukocytosis is more common among children, during the first 10
days of illness, and in cases complicated by intestinal perforation or
secondary infection. Other nonspecific laboratory findings include
 moderately elevated values in liver function tests and muscle enzyme levels.6

The classic Widal test measures antibodies against O and H antigens of

S. Typhi but lacks sensitivity and specificity in endemic areas. Because many
false-positive and false-negative results occur, diagnosis of typhoid fever by
Widal test alone is prone to error.

O antibodies increase on days 6-8 and H antibodies to 10-12 days from

the beginning of the disease. Interpretation of Widal examination must be
done carefully because several factors influence the outcome, including the
stage of disease, administration of antibiotics, laboratory techniques,
endemicity of typhoid disease, immunological features of the local
community, and a history of immunization for typhoid fever8. Low sensitivity
and specificity depending on the quality of the antigen used can even give a
negative result in 30% of positive culture samples of typhoid fever.
Widal examination had a sensitivity of 40%, specificity 91.4%, and a
positive predictive value of 80%12. False positive Widal examination results
can occur due to cross reactions with non-typhoidal Salmonella,
enterobacteriaceae, examinations carried out in endemic areas of dengue and
malaria infection, history of typhoid immunization, and varied commercial
antigen preparations and poor standardization8.

Widal examination should be done 1-2 weeks later until the results
increase 4 times, especially agglutinin O has an important diagnostic value
for typhoid fever. Positive agglutinin O titers can differ from> 1/80 to> 1/320
between laboratories depending on the endemicity of typhoid fever in the
local community with the last 8 months not getting vaccinated or recovering
from typhoid fever.8

3.5 Treatment

An early diagnosis of typhoid fever and institution of appropriate

treatment are essential. The vast majority with typhoid fever can be
 managed at home with oral antibiotics and close medical follow-up for
complications or failure of response to therapy. Patients with persistent
vomiting, severe diarrhea, and abdominal distention may require
hospitalization and parenteral antibiotic therapy. There are general principles
of typhoid fever management. Adequate rest, hydration, and attention are
important to correct fluid and electrolyte imbalance.6

For treatment of drug-susceptible typhoid fever, fluoroquinolones are

the most effective class of agents, with cure rates of ~98% and relapse and
fecal carriage rates of <2%. Experience is most extensive with ciprofloxacin.
Short-course ofloxacin therapy is similarly successful against infection
caused by quinolone-susceptible strains.6

Ceftriaxone, cefotaxime, and (oral) cefixime are effective for

treatment of MDR enteric fever, including that caused by DSC and
fluoroquinolone-resistant strains. These agents clear fever in ~1 week, with
failure rates of ~5–10%, fecal carriage rates of <3%, and relapse rates of 3–
6%. Oral azithromycin results in defervescence in 4–6 days, with rates of
relapse and convalescent stool carriage of <3%.6

In addition to antibiotics, the importance of supportive treatment and

maintenance of appropriate fluid and electrolyte balance must be
underscored12. Although additional treatment with dexamethasone (3 mg/kg
for the initial dose, followed by 1 mg/kg every 6 hr for 48 hr) is recommended
for severely ill patients with shock, obtundation, stupor, or coma;
corticosteroids should be administered only under strict controlled conditions
and supervision, because their use may mask signs of abdominal
complications.

3.6 Prognosis

The prognosis for a patient with enteric fever depends on the rapidity
of diagnosis and institution of appropriate antibiotic therapy. Other factors are
the patient’s, age, general state of health, and nutrition, the causative
Salmonella serotype, and the appearance of complications. Individuals who
excrete S. Typhi for 3 mo or longer after infection are regarded as chronic
carriers. The risk for becoming a carrier is low in children (<2% for all
infected children) and increases with age.6
 Reference

1. https://www.cdc.gov/dengue/resources/30jan2012/aegyptifactsheet.pdf.
(Dengue and the Aedes aegypti mosquito)
2. Handbook For Clinical Management Of Dengue. World Health
Organization.
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381438/. (The Revised
WHO dengue case classification : does the system need to be modified)
4. https://www.cdc.gov/dengue/clinicallab/clinical.html. (Dengue Virus)
5. https://www.who.int/csr/resources/publications/dengue/012-23.pdf

6. Harrison’s Principles of Internal Medicine 20th edition. 2018.

7. Buku Ajar Ilmu Penyakit Dalam. Perhimpunan Dokter Spesialis Penyakit Dalam
Indonesia Ed. Kelima
8. https://www.nhs.uk/conditions/typhoid-fever/diagnosis/
(Diagnosis Typhoid Fever)