Dengue infection is caused by the dengue virus that belongs to the family Flaviviridae.
There are 4 serotypes (DEN-1, DEN-2, DEN-3, DEN-4). Each serotype provides specific lifetime protective immunity against reinfection of the same serotype, but only temporary (within 2-3 months of the primary infection) and partial protection against other serotypes.
It is transmitted to humans through the bites of infected Aedes mosquitoes. It is primarily transmitted by female Aedes aegypti, a tropical and subtropical species. Humans are the main host of the virus.
After 4-10 days of incubation period, illness begins immediately.


New Classification of Dengue Infection

  • Based on the 2009 case classification by the World Health Organization (WHO)
  • Patients are categorized depending on patient’s severity level as severe dengue or non-severe dengue (with or without warning signs)
  • Studies found the new classification more practical with respect to triage, surveillance reporting, dengue vaccine & drug trial end-point measurements

Old Classification of Dengue Infection

Undifferentiated fever

  • May be the most common manifestation of dengue infection

Dengue fever (DF)

  • An acute febrile illness with ≥2 of the following features:
    • Headache
    • Retro-orbital pain
    • Myalgia, arthralgia
    • Rash (usually maculopapular)
    • Hemorrhagic manifestations (rarely)
    • Leukopenia

Dengue hemorrhagic fever (DHF)

  • Patient should present with the following:
    • 2-7 days duration of fever or recent history of fever, which may be biphasic
    • ≥1 of the following hemorrhagic manifestations
      • Positive tourniquet test
      • Petechiae, ecchymosis, purpura
      • Bleeding from mucosa (eg epistaxis, gum bleeding), injection sites or other sites
      • Gastrointestinal bleeding, hematuria, menorrhagia
    • Platelets ≤100,000/mm3
    • Manifests with plasma leakage as shown by either of the following:
      • ≥20% rise in hematocrit for age & gender
      • ≥20% drop in hematocrit following fluid therapy as compared to baseline
      • Presence of pleural effusion, ascites, or hypoproteinemia

Dengue shock syndrome (DSS)

  • Occurs when DHF is accompanied by signs of circulatory failure:
    • Hypotension for age [systolic blood pressure (SBP) decrease of >40 mmHg or <2 SD below normal for age; for children ≤10 years old: 5th centile for SBP = 70 + (age in years x 2) mmHg]
    • Cold clammy skin, restlessness, rapid weak pulse
    • Narrow pulse pressure (≤20 mmHg)
    • Profound shock


Criteria for Home Management

  • Tolerates adequate oral fluids
  • With urine output every 6 hours
  • Absence of warning signs (eg abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleed, lethargy, restlessness, >2 cm increase in liver size, increasing hematocrit concomitant with decreasing platelet count), especially during defervescence

Criteria for Hospital Admission

  • Presence of warning signs
  • Co-existing conditions that may make dengue & its management more complicated (eg infants, patients with diabetes mellitus, obesity, renal failure, chronic hemolytic diseases)
  • Patients with certain social circumstances (eg living far from a healthy facility without reliable means of transport)

Criteria for Emergency/Intensive Care Management

  • Severe plasma leakage that may lead to shock &/or fluid accumulation with respiratory distress
  • Severe bleeding
  • Severe organ impairment (eg hepatic damage, renal impairment, cardiomyopathy, encephalopathy, encephalitis)


Grading of the severity of dengue hemorrhagic fever (DHF)

  • DHF is classified into 4 grades of severity, where grades III & IV are considered as dengue shock syndrome (DSS)
  • The presence of thrombocytopenia, hemoconcentration & evidence of plasma leakage differentiate DHF from dengue fever (DF)
    Grade Manifestations Lab Features
    DHF Grade I Features of DF plus positive tourniquet test &/or easy bruising Thrombocytopenia ≤100,000/mm3 Hematocrit rise or hemoconcentration ≥20%
    DHF Grade II Features of DHF grade I plus spontaneous bleeding
    DHF Grade III (DSS) Features of DHF grade II plus signs of circulatory failure
    DHF Grade IV (DSS) Profound shock with undetectable blood pressure (BP) or pulse

Laboratory Tests

  • Should be done to confirm the diagnosis
    • Not required for the acute management of patients except for those with unusual presentations

Complete blood count (CBC)

  • Should be done at the 1st visit
  • Guides physician to the onset of critical phase & plasma leakage in patients who progress to critical phase without defervescence
  • Progressive decrease in total white cell count is the earliest abnormality which should alert the physician to a high probability of dengue
  • Hematocrit test in the early phase establishes the patient’s own baseline hematocrit
    • Age-specific population hematocrit levels can be used if the baseline was not obtained
  • Fast decrease in platelet count concurrent with increasing hematocrit as compared to the baseline is indicative of progression to plasma leakage or critical phase

Detection of the virus, viral nucleic acid, antigens or antibodies

  • Dengue virus can be identified for 4-5 days after the onset of illness in the serum, plasma, circulating blood cells or other tissues
  • Dengue virus & antigens are usually gone from the blood simultaneous with the appearance of specific antibodies after day 5 of illness
  • Isolation of the virus in cell culture & detection of viral RNA by nucleic acid amplification tests, or by detection of antigen by enzyme-linked immunosorbent assay (ELISA) or rapid tests can help detect dengue infection during the early stages of the disease (before day 5 of illness or during the febrile period)
    • More specific than serology, however, practical considerations limit its use
    • Viral isolation & serotype identification method should be done using whole blood, serum, or tissues after 1-5 days of symptom onset & confirms acute infection within 1-2 weeks
    • Nucleic acid detection test should be done using whole blood, serum, plasma, or tissues after 1-5 days of symptom onset & confirms acute infection within 1-2 days
    • Antigen detection method using tissue for immunochemistry can confirm acute infection within >1 day
      • Nonstructural protein 1 (NS 1) antigen may be detected in some patients for a few days after defervescence
  • Serology is the diagnostic method of choice during the end of the acute phase of infection
    • Response of antibodies to infection may vary depending on patient’s immune status
    • Immunoglobulin M (IgM) antibodies are the 1st immunoglobulin to appear & usually detected 3-5 days after the onset of illness in 50% of patients & 99% by day 10
      • Level of IgM antibody is highest 2 weeks after the onset of symptoms & becomes undetected after 2-3 months
      • IgM detection ELISA or rapid tests are ideally done using serum, plasma, or whole blood after 5 days of symptom onset & may probably diagnose acute infection within 30 minutes-2 days
    • Low levels of anti-dengue serum immunoglobulin G (IgG) may initially be detected at the end of the 1st week of illness & may remain detectable for life
      • IgG identification by ELISA, hemagglutination-inhibition (HI) or neutralization tests are ideally done using serum, plasma, or whole blood after 1-5 days of symptom onset & confirms acute infection within ≥7 days
      • IgG is the main immunoglobulin identified during an acute phase of a secondary dengue infection & persists for 10 months to life
    • More available in dengue-endemic countries than the virological tests
  • IgM/IgG antibody ratios are now more commonly used to determine if the infection is primary or secondary
  • Dengue infection is confirmed if polymerase chain reaction (PCR) or virus culture is positive, presence of IgM or IgG seroconversion in paired sera or 4-fold increase of IgG titer in paired sera
    • Infection is highly suggestive if IgM is positive in a single serum sample or IgG is positive in a single serum sample with HI titre >1280

Other tests

  • May include liver function test, glucose, serum electrolytes, urea & creatinine, bicarbonate or lactate, cardiac enzymes, electrocardiogram (ECG), urine specific gravity


Hemorrhagic Complications

  • Patient with bleeding that remains stable with intravenous fluid (IVF) replacement is considered to have minor bleeding
    • Patients with severe bleeding are those with unstable hemodynamic status with severe overt bleeding or low hematocrit level even after fluid resuscitation, refractory shock that did not improve with consecutive fluid replacement of 40-60 mL/kg, hypotensive shock with low or normal baseline hematocrit level, or those with worsening metabolic acidosis particularly those with severe abdominal tenderness & distension
  • Major bleeding usually comes from gastrointestinal tract (GIT)
  • Patients who have prolonged shock, hypotensive shock & renal or liver failure &/or severe metabolic acidosis, pre-existing peptic ulcer disease, trauma, are given nonsteroidal anti-inflammatory drugs (NSAIDs) or on anticoagulant therapy are at high risk for major bleeding
    • Those with hemolytic disorder are at risk of acute hemolysis with hemoglobinuria and needs blood transfusion

Fluid Overload

  • Common cause of acute respiratory distress and failure in severe dengue
  • Usually secondary to excessive or rapid IVF, wrong use of crystalloid solutions, incorrect use of large volumes of IVF in patients with unrecognized severe bleeding, inappropriate transfusion of fresh-frozen plasma or platelet concentrates and cryoprecipitates, continuation of IVF even after plasma leakage has resolved, or presence of comorbid conditions like congenital or ischemic heart disease, chronic lung & renal disease
  • Patient usually present with fast or difficulty in breathing, chest wall in-drawing, wheezing, large pleural effusions, tense ascites, increased jugular venous pressure, pulmonary edema or irreversible shock
  • Chest x-ray, electrocardiogram (ECG), arterial blood gases, echocardiogram & cardiac enzymes may be done
  • Patient should be given oxygen & IVF either discontinued or decreased depending on the phase of the disease and patient’s hemodynamic status

Other Complications

  • Hyper- or hypoglycemia
  • Electrolyte & acid-base imbalances
  • Co-infections & nosocomial infections
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