CASE REPORT

“Dengue Hemorrhage Fever”

Preceptor :

dr. Hj. Ihsanil Husna, Sp.PD

By :

Nadya Mujahidah Chairunnisa Ramly

(2014730071)

MEDICAL PROFESSION PROGRAMME DEPARTMENT OF

INTERNAL MEDICINE
JAKARTA ISLAMIC HOSPITAL CEMPAKA PUTIH
FACULTY OF MEDICINE UNIVERSITY OF
MUHAMMADIYAH JAKARTA
2019
 PREFACE

AssalamualaikumWr. Wb.

Alhamdulillah, All praise to Allah SWT the almighty and the most merciful.
Shalawat and salaam to Rasulullah Muhammad Peace be Upon Him which bring us
from the darkest of time into the lights.

The writer also wish to express his deep and sincere gratitude for those who
have guided in completing this case report paper with the title “Dengue Hemorrhage
Fever” to fulfill the criteria for completing Medical Profession Programme in Internal
Medicine Department of Jakarta Islamic Hospital Cempaka Putih, Faculty of
Medicine University of Muhammadiyah Jakarta.

The writer wish this paper to be useful and add another dimension of
knowledge for the writer himself, medical profession student, and anyone else who
never stop in learning.

The writer acknowledge in the process of making this paper, there are a lot of
mistake and far from perfect, cause perfection are only belong to Allah SWT. All the
critics and advice are needed for the writer for the better of ourselves in this journey
to be the long life learner.

WassalamualaikumWr. Wb

Jakarta, Februari 2019

Nadya M. Chaiarunnisa Ramly

 CHAPTER I

PATIENT’S IDENTITY

1.1 PATIENT’S IDENTITY

• Name : Mr. E

• Age : 25 years old

• Marital Status : Single

• Occupation : Entrepreneur

• Religion : Moslem

• Date of Admission : February 26th 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. The fever has not
been confirm with thermometer, only by hand. 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. The patient already see a Doctor and prescribed
Paracetamol, and suggested him to be treated at the hospital.

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, which is
given by Doctor in the clinic before entering the hospital.
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 38,0oC

• RR 20x/minutes

• HR 82x/minutes

• BP 120/80 mmHg

Anthropometric Status

Body weight : 59 kg

Body high : 169 cm

 BMI : 20.7 (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

February 26th 2019 - 08.51

EXAMINATION VALUE UNITS NORMAL

Hemoglobin 16.1 g/dL 13,2 – 17,3

Hematocrit 45 % 40 - 52

Leukocyte 3.45 ↓ 103/uL 3.8 – 10,6

Thrombocyte 85 ↓ 103/µl 150 - 440

Erythrocytes 5.52 106/µl 4,4 – 5,9

MCV 82 Fl 80-100

MCH 29 pg 26-34

MCHC 36 g/dl 32-36

February 26th 2019 - 18.36

EXAMINATION VALUE UNITS NORMAL

Hemoglobin 15.1 g/dL 13,2 – 17,3

Hematocrit 42 % 40 - 52

Leukocyte 4.12 103/uL 3.8 – 10,6

Thrombocyte 74 ↓ 103/µl 150 - 440

Erythrocytes 5.26 106/µl 4,4 – 5,9

MCV 81 Fl 80-100

MCH 29 pg 26-34

MCHC 36 g/dl 32-36

February 27th 2019 – 09.31

EXAMINATION VALUE UNITS NORMAL

Hemoglobin 14.5 g/dL 13,2 – 17,3

Hematocrit 41 % 40 - 52
 Leukocyte 3.06 ↓ 103/uL 3.8 – 10,6

Thrombocyte 59 ↓ 103/µl 150 - 440

Erythrocytes 5.02 106/µl 4,4 – 5,9

MCV 82 Fl 80-100

MCH 29 pg 26-34

MCHC 35 g/dl 32-36

February 27th 2019 – 19.49

EXAMINATION VALUE UNITS NORMAL

Hemoglobin 15.5 g/dL 13,2 – 17,3

Hematocrit 43 % 40 - 52

Leukocyte 2.68 ↓ 103/uL 3.8 – 10,6

Thrombocyte 52 ↓ 103/µl 150 - 440

Erythrocytes 5.36 106/µl 4,4 – 5,9

MCV 81 Fl 80-100
MCH 29 pg 26-34

MCHC 36 g/dl 32-36

1.5 RESUME

Mr E, 25 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: 38,0 ° C  Sub Febris
Laboratory Findings
26/02/2019 08.51
- Leukopenia
- Thrombocytopenia

26/02/2019 18.36
- Thrombocytopenia

27/02/2019 09.31
- Leukopenia
- Thrombocytopenia

27/02/2019 19.49

- Leukopenia
- Thrombocytopenia
1.6 PROBLEM LIST

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

Fevere

- 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: 38,0 ° C  Sub Febris
Physical Examination : petechie on the extremities (+)
Laboratory Findings
26/02/2019 08.51
- Leukopenia
- Thrombocytopenia

26/02/2019 18.36
- Thrombocytopenia

27/02/2019 09.31
- Leukopenia
- Thrombocytopenia

27/02/2019 19.49
- Leukopenia
- Thrombocytopenia

A Fever e.c Susp Dengue Hemorrhage Fever Grade I 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 Asering 2280cc/24 hours

- Paracetamol 3x500mg

2. 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: 38,0 ° C  Sub Febris
Physical Examination

Palpation : Epigastric pain (+)

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

Functional Dyspepsia

P Planning Diagnostic:

- Routine Haemotology/24hour
Planning Non Therapeutics
- Bed Rest
 - Diet Modification

Planning Therapeutics
- Ranitidine inj 2 x 1 amp
- Ondansetron 4 mg inj 3 x 1
 1.8 FOLLOW UP

Date Subjective Objective Assesment Planning

26/02/19 Fever (+), Vital Signs : Dengue Planning Diagnostic:

Headache BP, HR, and RR Hemorrhage
- Routine
(+), Myalgia within normal Fever Grade
haemotology/24
limits
(+), Nausea I dd/ hour
Temperature: 38,0
(+), - IgG & IgM
° C  Sub Febris Typhoid
Anti-dengue
Epigastric Fever
Physical
pain (+) - Widal Test
Examination :
Tourniquet Test Planning Non
(+)
Therapeutics
Laboratory
Findings - Bed Rest
26/02/2019 08.51 - Monitoring vital
signs
Leukopenia
Planning Therapeutics
Thrombocytopenia

26/02/2019 18.36 - IVFD Asering

2280cc/24 hours
Thrombocytopenia
- Paracetamol
3x500mg
- Ranitidine inj 2
x 1 amp
- Ondansetron 4
mg inj 3 x 1
27/02/19 Fever ↓ , Vital Signs : Dengue Planning Diagnostic:
Headache ↓, BP, HR, RR and T Hemorrhage
- Routine
Myalgia (+), within normal Fever Grade
haemotology/24hour
limits
Nausea I dd/
Planning Non
Physical
(+),Epigastric Typhoid
Examination : Therapeutics
pain (+) Tourniquet Test Fever
(+) - Bed Rest
Laboratory - Monitoring vital
Findings signs
27/02/2019 09.31 Planning Therapeutics
Leukopenia
- IVFD Asering
Thrombocytopenia 2280cc/24 hours

- Paracetamol
3x500mg
- Ranitidine inj 2 x 1
amp
- Ondansetron 4 mg
inj 3 x 1

28/02/19 Fever ↓ , Vital Signs : Dengue Planning Diagnostic:

Headache ↓, BP, HR, RR and T Hemorrhage
- Routine
Myalgia (-), within normal Fever Grade
haemotology/24hour
limits
Nausea (- I dd/
Planning Non
Physical
),Epigastric Typhoid
Examination : Therapeutics
pain (-) Tourniquet Test Fever
(+) - Bed Rest
Laboratory - Monitoring vital
Findings signs
27/02/2019 19.49 Planning Therapeutics
Leukopenia
- IVFD Asering
Thrombocytopenia 2280cc/24 hours

- Paracetamol
 3x500mg
- Ranitidine inj 2 x 1
amp
- Ondansetron 4 mg
inj 3 x 1
 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.

Figure 2. The 2009 revised dengue case classification

However, further deterioration is classified as severe dengue, though

recovery is possible if appropriate and timely treatment is given. The 2009
classification into severity levels is considered to be more sensitive in capturing
severe disease than the 1997 guidelines, with observed sensitivities of up to 92%
and 39%, respectively.
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 Epidemiology

Dengue viruses are transmitted by mosquitoes of the Stegomyia family.

Aedes aegypti, a daytime biting mosquito, is the principal vector, and all 4 virus
types have been recovered from it4. In most tropical areas, A. aegypti is highly
urbanized, breeding in water stored for drinking or bathing and in rainwater
collected in any container1.

About 2.5 billion people, or 40% of the world’s population, live in areas
where there is a risk of dengue transmission. Dengue is endemic in at least 100
countries in Asia, the Pacific, the Americas, Africa, and the Caribbean. The World
Health Organization (WHO) estimates that 50 to 100 million infections occur
yearly, including 500,000 DHF cases and 22,000 deaths5.
2.5 Transmission of Dengue Virus

The Aedes aegypti mosquito can transmit the viruses that cause dengue
fever. The female mosquito bites people and animals. These mosquitoes use
natural locations or habitats and artificial containers with water to lay their egss.
Most frequently found in tropical and subtropical areas of the world. Aedes
aegypti bites primarily during the day. This species is most active for
approximately two hours after sunrise and several hours before sunser, but it can
bite at night in well lit areas1.

Dengue is transmitted to people by the bite of an Aedes mosquito that is

infected with a dengue virus. The mosquito becomes infected with dengue virus
when it bites a person who has dengue or DHF, virus replicates in mosquito
midgut and other organs, and replicates in salivary glands6. There must be a
person-to-mosquito-to another person pathway, dengue cannot be spread directly
from person to person because virus is not contagious.

Aedes aegypti bites infected person, it takes a week for dengue virus to
incubate7. Infected mosquito bites another person, virus transmitted to human in
mosquito saliva. After that, virus replicates in target organs, infects white blood
cells and lymphatic tissues, also released and circulate in blood6.

2.6 Course of Dengue Illness

Dengue viruses cause symptomatic infections or asymptomatic.

Symptomatic dengue infection is a systemic and dynamic disease. It has a wide
clinical spectrum that includes both severe and non-severe clinical manifestations.
After the incubation period, the illness begins abruptly and, in patients with
moderate to severe disease, is followed by three phases − febrile, critical and
recovery4. Due to its dynamic nature, the severity of the disease will usually only
be apparent around defervescence i.e. during the transition of the febrile to the
afebrile phase, which often coincides with the onset of the critical phase.

Figure 3. Clinical Course of Dengue Illness

 Febrile phase

Its typically develop a high-grade fever suddenly. This acute

febrile phase usually lasts 2−7 days and is often accompanied by facial
flushing, skin erythema, generalized body ache, myalgia, arthralgia, retro-
orbital eye pain, rubeliform exanthema and headache. Some patients may
 have a sore throat, and conjunctival injection. Anorexia, nausea and
vomiting are common. It can be difficult to distinguish dengue clinically
from non-dengue febrile diseases in the early febrile phase2.

A positive tourniquet test in this phase indicates an increased

probability of dengue. However, these clinical features do not predict the
severity of disease. Therefore it is crucial to monitor for warning signs and
other clinical parameters in order to recognize progression to the critical
phase. Mild haemorrhagic manifestations such as petechiae and mucosal
membrane bleeding (e.g. of the nose and gums) may be seen. The earliest
abnormality in the full blood count is a progressive decrease in total white
cell count, which should alert the physician to a high probability of
dengue4. In addition to these somatic symptoms, with the onset of fever
patients may suffer an acute and progressive loss in their ability to perform
their daily functions.

 Critical phase
During the transition from the febrile to afebrile phase, patients
without an increase in capillary permeability will improve without going
through the critical phase. Instead of improving with the subsidence of
high fever; patients with increased capillary permeability may manifest
with the warning signs, mostly as a result of plasma leakage. The warning
signs mark the beginning of the critical phase2. These patients become
worse around the time of defervescence, when the temperature drops to
37.5−38°C or less and remains below this level, usually on days 3–8 of
illness.

Progressive leukopenia followed by a rapid decrease in platelet count

usually precedes plasma leakage. An increasing haematocrit above the
baseline may be one of the earliest additional signs. The period of
clinically significant plasma leakage usually lasts 24−48 hours. The degree
of plasma leakage varies. A rising haematocrit precedes changes in blood
pressure (BP) and pulse volume2. The degree of haemoconcentration
 above the baseline haematocrit reflects the severity of plasma leakage;
however, this may be reduced by early intravenous fluid therapy.

If shock occurs when a critical volume of plasma is lost through

leakage, it is often preceded by warning signs. The body temperature may
be subnormal when shock occurs. With profound and/or prolonged shock,
hypoperfusion results in metabolic acidosis, progressive organ
impairment, and disseminated intravascular coagulation2.

In addition, severe organ involvement may develop such as severe

hepatitis, encephalitis, myocarditis, and/or severe bleeding, without
obvious plasma leakage or shock. Cases of dengue with warning signs will
usually recover with intravenous rehydration.

 Recovery phase

As the patient survives the 24−48 hour critical phase, a gradual

reabsorption of extravascular compartment fluid takes place in the
following 48−72 hours2. General well-being improves, appetite returns,
gastrointestinal symptoms become less, haemodynamic status stabilizes,
and diuresis good.

The haematocrit stabilizes or may be lower due to the dilutional

effect of reabsorbed fluid. The white blood cell count usually starts to
increase soon after defervescence but the recovery of the platelet count is
typically later than that of the white blood cell count4.

2.7 Clinical Manifestations

The incubation period is 1-7 days. The clinical manifestations are variable
and are influenced by the age of the patient. A majority of infected older children
and adults experience sudden onset of fever, with temperature rapidly increasing
to 39.4-41.1°C (103- 106°F), usually accompanied by frontal or retroorbital pain,
particularly when pressure is applied to the eyes2. A transient, macular,
generalized rash that blanches under pressure may be seen during the 1st 24-48 hr
of fever. The pulse rate may be slow relative to the degree of fever.
 Myalgia and arthralgia occur soon after the onset of fevers and increase in
severity over time8. Joint symptoms may be particularly severe in patients with
chikungunya or o’nyong-nyong infection. From the 2nd-6th day of fever, nausea
and vomiting are occur, and generalized lymphadenopathy, and pronounced
anorexia may develop2.

Approximately 1-2 days after defervescence, a generalized, morbilliform,

maculopapular rash appears that spares the palms and soles. It disappears in 1-5
days; desquamation may occur4. About the time this second rash appears, the
body temperature, which has previously decreased to normal, may become
slightly elevated and demonstrate the characteristic biphasic temperature pattern.

Differentiation between dengue fever and dengue hemorrhagic fever is

difficult early in the course of illness. A relatively mild 1st phase with abrupt
onset of fever, malaise, vomiting, headache, anorexia, and cough may be followed
after 2-5 days by rapid clinical deterioration and collapse. In this 2nd phase, the
patient usually has cold, clammy extremities, a warm trunk, flushed face,
diaphoresis, restlessness, irritability, midepigastric pain, and decreased urinary
output2. Frequently, there are scattered petechiae on the forehead and extremities;
spontaneous ecchymoses may appear, and easy bruising and bleeding at sites of
venipuncture are common.

The liver may enlarge to 4-6 cm below the costal margin and is usually firm
and somewhat tender. Approximately 20-30% of cases of dengue hemorrhagic
fever are complicated by shock (dengue shock syndrome)3. Dengue shock can be
subtle, arising in patients who are fully alert, and is accompanied by increased
peripheral vascular resistance and raised diastolic blood pressure. Shock is not
from congestive heart failure but from venous pooling. With increasing
cardiovascular compromise, diastolic pressure rises toward the systolic level and
the pulse pressure narrows.

2.8 Diagnosis

Laboratory diagnosis methods for confirming dengue virus infection may

involve detection of the virus, viral nucleic acid, antigens or antibodies, or a
combination of these techniques. After the onset of illness, the virus can be
detected in serum, plasma, circulating blood cells and other tissues for 4–5 days2.
During the early stages of the disease, virus isolation, nucleic acid or antigen
detection can be used to diagnose the infection. At the end of the acute phase of
infection, serology is the method of choice for diagnosis2.

In dengue fever, pancytopenia may develop after the 3-4 days of illness.
Neutropenia may persist or reappear during the latter stage of the disease and may
continue into convalescence, with white blood cell counts <2,000/μL. Platelet
counts rarely fall below 100,000/μL13. Venous clotting, bleeding and prothrombin
times, and plasma fibrinogen values are within normal ranges. The tourniquet test
result may be positive. The most common hematologic abnormalities during
dengue hemorrhagic fever and dengue shock syndrome are hemoconcentration
with an increase of >20% in haematocrit4.

Figure 4. Virological and Serological Markers According To Time Of

Illness

NS1 Ag is a marker of acute dengue infection from day one. Both enzyme-
linked immunosorbent assay (ELISA) and rapid commercial tests are available for
NS1 Ag detection9. The sensitivity and specificity of commercial kits in different
serotype infections and days of illness are being evaluated. NS1 cannot
distinguish between dengue fever or dengue hemorrhagic fever, so the
interpretation must be done carefully.9
 Specific IgM is the best marker of a recent dengue infection, IgM will
appear in the blood on the 3rd day of fever and reaches its peak on day 5th and
then decreases and disaapears after 60-90 days2. After that, IgG appears later and
continues to be in the blood. In secondary infections, IgM in the acute period is
detected in 70% of cases, whereas IgG can be detected earlier in most (90%)
patients, on the 2nd day13.

If IgM and IgG results negative are found but symptoms continue to show
suspicion of DHF, it is recommended to take a second sample with a distance of
3-5 days for primary infection and 2-3 days for secondary infection. So, primary
infections are characterized by high levels of IgM and low levels of IgG, while
low levels of IgM with high levels of IgG characterize secondary infections13.

2.9 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.8

The Indonesian Society of Internal Medicine arranged protocols for

dengue hemorrhagic fever management in adult patients. The protocols divided
into five category10.
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.

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)2.

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.

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
hypotension10.

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 oedema10.

2.10 Prognosis

Hypervolemia during the fluid reabsorptive phase may be lifethreatening

and is heralded by a decrease in hematocrit with wide pulse pressure. Diuretics
and digitalization may be necessary. Primary infections with dengue fever and
dengue-like diseases are usually self-limited and benign2.

The prognosis of dengue fever is good. Care should be taken to avoid use
of drugs that suppress platelet activity. The prognosis of dengue hemorrhagic
fever is adversely affected by late diagnosis and delayed or improper treatment.
Death has occurred in 40-50% of patients with shock, but with adequate intensive
care, deaths should occur in <1% of cases. Infrequently, there is residual brain
damage as a consequence of prolonged shock or occasionally of intracranial
hemorrhage. Many fatalities are caused by overhydration8.
 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. Paratyphi8. 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 cultures8.

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 year8.

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)10.

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 untreated8.

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 rare11.

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 days8.
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
patients8.

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
levels8.

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 error11.

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
fever11.
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 standardization12.

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 fever12.

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 imbalance8.

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 strains8.

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%8.

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 age8.
 Reference

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(Dengue and the Aedes aegypti mosquito)
2. Handbook For Clinical Management Of Dengue. World Health
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3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381438/. (The Revised
WHO dengue case classification : does the system need to be modified)
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10. Buku Ajar Ilmu Penyakit Dalam. Perhimpunan Dokter Spesialis Penyakit
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(Typhoid Fever)
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(Diagnosis Typhoid Fever)
13. Update Management of Infection Diseases and Gastrointestinal Disorders.
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