Dengue infection is one of the most common mosquitoborne viral diseases of public health significance.

It has been identified as a clinical entity since 1780.

More than 70% of the population at risk for dengue worldwide live in member states of the WHO South-East Asia Region and Western Pacific Region The clinical manifestations of dengue infection range from asymptomatic infection to undifferentiated fever, an influenza-like symptom known as dengue fever, and a severe, sometimes fatal disease characterized by hemorrhage and shock known as dengue hemorrhagic fever (DHF). The first and second epidemics of DHF occurred in Manila in 1954 and 1956, followed by the third in Bangkok in 1958.

In Indonesia, where more than 35% of the countrys population lives in urban areas, 150 000 cases were reported in 2007 reported from both Jakarta and West Java.

 The pathogenesis of DHF/DSS is still controversial. Two theories that have been used to explain the pathogenesis of DHF are : 1. The virulence of infecting dengue viruses 2. The antibody-dependent enhancement theory

Homologues antibodies form non-infectious complexes

Person who have experienced a dengue infection develop serum antibodies that can neutralize the dengue virus of that same (homologous) serotype
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Heterologous antibodies form infectious complexes

In a subsequent infection with a different virus serotype, the pre existing heterologous antibodies form complexes with the new virus, but these heterologous antibodies do not neutralize the new serotype
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Antibody-dependent enhancement (ADE) is the process in which certain strains of dengue virus, complexed with these nonneutralizing antibodies, can enter a greater proportion of the mononuclear cells where the virus replicates unchecked, thus increasing virus production and producing a massive infection

Heterologous complexes enter more monocytes, where virus replicates

The infected monocytes release vasoactive mediators, resulting in the increased vascular permeability and hemorrhagic manifestations that characterize dengue hemorrhagic fever or dengue shock syndrome.
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The course of dengue illness

McCall P, Lloyd L, Nathan MB. Dengue: guidelines for diagnosis, treatment, prevention and control. 2009. p59-87.

DENGUE MANIFESTATIONS

Case Definition for DHF WHO 1997

DENGUE FEVER

DENGUE HEMORRHAGIC FEVER

DENGUE SHOCK SYNDROME

Acute onset febrile illness that lasts 2-7 days With 2 or more following symptoms : - headache - ptechiea - retro-orbital pain - tourniquet test (+) - myalgia/arthralgia - maculopapular rash

WHO DENGUE FEVER

J Pediatr. 2007; 83(2): 22-35.

DENGUE MANIFESTATIONS

Case Definition for DHF WHO 1997

DENGUE FEVER

DENGUE HEMORRHAGIC FEVER

DENGUE SHOCK SYNDROME

Fever lasts 2-7 days,occasionally biphasic Hemorrhagic tendencies Thrombocytopenia (< 100,000 /mm3) Evidence of plasma leakage, manifested by : - rise in haematocrit > 20% - drop in haematocrit following volume replacement - signs of plasma leakage

WHO DENGUE HEMORRHAGIC FEVER

J Pediatr. 2007; 83(2): 22-35.
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Dengue Hemorrhagic Fever

Grading Grade I

1997

Grade II Grade III

Grade IV

Symptoms Hemoconcentration, fever, non specific constitutional symptoms, only positive tourniquet test Spontaneous bleeding in addition to the manifestation from Grade I Circulatory failure, rapid & weak pulse, narrow pulse pressure, cold clammy skin, hypotension by age, oliguria, restlessness Profound shock, hypotension or unrecordable blood pressure
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J Pediatr. 2007; 83(2): 22-35.

DENGUE MANIFESTATIONS

Case Definition for DHF WHO 1997

DENGUE FEVER

DENGUE HEMORRHAGIC FEVER

DENGUE SHOCK SYNDROME

All four criteria of DHF must be present Evidence of circulatory failure manifested by : - Rapid and weak pulse - Narrow pulse pressure (< 20 mmHg) or - Hypotension for age, and - Cold, clammy skin and restlessness

WHO DENGUE SHOCK SYNDROME

J Pediatr. 2007; 83(2): 22-35.
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WHO 2009 Dengue Case Classification and Levels of Severity

Dengue + Warning Signs
1. 2. 3.

Severe Dengue
Severe plasma leakage Severe haemorrhage Severe organ impairment

without

with warning signs

Nathan MB. Dengue: guidelines for diagnosis, treatment, prevention and control. 2009. p3-21.

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Criteria for Dengue + Warning Signs Probable Dengue Live in/travel to dengue endemic area Fever and 2 of the following criteria : - Nausea, vomiting - Rash - Aches and pain - Tourniquet test positive - Leukopenia - Any warning sign Warning Signs - Abdominal pain or tenderness - Persistent vomiting - Clinical fluid accumulation - Mucosal bleed - Lethargy, restlessness - Liver enlargement > 2 cm - Laboratory: increase in HCT concurrent with rapid decrease in platelet count

Laboratory-Confirmed Dengue Important when no sign of plasma leakage

Nathan MB. Dengue: guidelines for diagnosis, treatment, prevention and control. 2009. p3-21.
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Criteria for Severe Dengue Severe Plasma Leakage Leading to : - Shock (DSS) - Fluid accumulation with respiratory distress

Severe Bleeding As evaluated by clinician Severe Organ Involvement - Liver : AST or ALT > 1000 - CNS : Impaired consciousness - Heart and other organs
Nathan MB.Dengue: guidelines for diagnosis, treatment, prevention and control. 2009. p3-21.

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Revised and expanded edition of dengue guideline

This edition have been extensively revised and expanded by the WHO Southeast Asian Region Office, with the focus on new/additional topics of current relevance to Member States of the South-East Asia Region.

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2011 WHO-SEARO Dengue Case Classification

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WHO Classification of Dengue Infections and Grading of Severity of Dengue

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What is expanded dengue syndrome ?

Uncommon manifestation Neurological, hepatic, renal and other isolated organ involvement CNS manifestations : Convulsions, spasticity, changes in consciousness and transient paresis Limited evidences showed dengue viruses may cross the blood-brain barrier and cause encephalitis

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Febrile, critical and recovery phases in dengue

Febrile phase
Dehydration, high fever may cause neurological disturbance and febrile seizures in young children

Critical phase

Shock from plasma leakage, severe haemorrhage, organ impairment

Recovery phase

Hypervolemia (only if intravenous fluid therapy has been excessive and/or has extended into this period)
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Laboratory Diagnosis
Early illness tests
Virus isolation Nucleic acid detection Detection of antigens

Late illness tests

Serological tests

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Suspect of Dengue Infection

High fever, < 7 days Malaise, no ARI

Emergency signs (+)

Shock Seizure Encephalopathy Bleeding

Emergency signs (-)

Tourniquet test

Positive Leucocyte < 4.000/uL

Negative

Inpatient
One day observation Observe for 24 hours Symptoms & lab

Normal leucocyte

Outpatient Control until fever(-) Advice the parent

+ Thrombocyte < 100.000/uL + Rise of Ht > 10%

Fever persist > 3 days Check Hb, Ht, leucocyte & thrombocyte
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Treatment of DHF without shock

Fluid
Drink 2 litre/day to prevent dehydration Mineral water, juice, oralit

Symptomatic
Give antipiretic if high fever or history of febrile seizure occured. Suggestion is paracetamol. Asetosal & ibuprofen are contraindicated Diazepam Domperidon 1 mg/kgBB, 3 dose, 1-2 days H2 blocker (ranitidine, cimetidine) Antibiotic is not given Steroid is not effective
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Treatment of DHF without shock (DHF grade I and II)

Able to drink

Unable to drink Vomit

Infuse D5%:NaCl 0,9% = 3:1 Maintenance drips Check Hb, Ht, thrombocyte every 6-12 hours

Drink 2 L/day Paracetamol Anticonvulsive, if necessary

Evaluate the symptoms & lab Signs of shock Diuresis Bleeding Hb, Ht, thrombocyte every 6-12 hours Discharge Improve

Worsen

Change to RL D5%
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Treatment of DHF grade I and II

Improvement
Not agitated Strong pulse Stable BP Ht decrease Diuresis 1 ml/kg/hour Fluid decrease to 5 ml/kg/hour

Initial fluid 6 8 ml/kg/hour RLD5% or RAD5%

No Improvement

Monitor the vital signs Hb, Ht, thrombocyte every 6-12 hours Agitated Respiratory distress HR increase Ht increase Pulse pressure < 20mmHg Diuresis <1 ml/kg/hr
Fluid increase to 10-15 ml/kg/hour

3 ml/kg/hour

Evaluate in 12-24 hours Treatment of DSS Unable vital signs

Stop in 24-48 hours

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SHOCK

O2 2-4 L/min Isotonic fluid 20 ml/kg/hour RL/RA/NS

in 30 min Evaluate in 30 minute, has the shock resolved? Yes No Continue the RL + Kolloid + Correct acidosis Evaluate in 1 hour Ht Not resolved Increase Kolloid No improvement
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Adjust the fluid Monitor Stable

Shock has resolved

Decrease Transfusion

Stop the fluid not more than 48 hours after the shock has resolved

Inotropic

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Criteria for discharging patients

Absence of fever for at least 24 hours without the use of anti fever therapy Return of appetite Visible clinical improvement Satisfactory urine output A minimum of 2 3 days have elapsed after recovery from shock No respiratory distress from pleural effusion and no ascites Platelet count of more than 50.000/mm3. If not, patients can be recommended to avoid traumatic activities for at least 1 2 weeks for platelet count to become normal. In most uncomplicated cases, platelet rises to normal within 3 5 days

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