Dengue infection is caused by the dengue virus that belongs to the family Flaviviridae. It is generally self-limiting and rarely fatal.
There are 4 serotypes (DEN-1, DEN-2, DEN-3, DEN-4). Infection w/ dengue serotype confers lifetime protective immunity to that specific serotype; cross-protection for other serotypes is only short-term.
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 & monkeys are the amplifying hosts after the mosquito bite.
After 4-10 days of incubation period, illness begins immediately.
The acute phase of illness lasts for 3-7 days, but the convalescent phase may be prolonged for a week and may be associated with weakness and depression especially in adults.


WHO Case Definition of Dengue Fever (DF)

Probable dengue fever (DF) refers to an acute febrile illness with ≥2 of the following:

  • Headache, retro-orbital pain
  • Myalgia, arthralgia
  • Rash
  • Hemorrhagic manifestations
  • Leukopenia, thrombocytopenia, hematocrit rise of 5-10%
  • Supportive serology
    • Hemagglutination-inhibition (HI) Ab titer of ≥1:1280
    • Comparable immunoglobulin G (IgG) titer w/ enzyme-linked immunosorbent assay (ELISA)
    • Positive immunoglobulin M antibody (IgM Ab) test on a late acute or convalescent-phase serum specimen
  • Occurrence at the same location & time as other confirmed cases of DF

Confirmed dengue fever (DF) is a probable case confirmed by at least 1 of the following laboratory criteria:

  • Isolation of the dengue virus from serum, cerebrospinal fluid (CSF), or autopsy samples
  • Demonstration of a ≥4-fold rise in serum IgG or IgM antibody titers particular to dengue virus
  • Demonstration of dengue virus Ag in autopsy tissue, serum or CSF samples by immunohistochemistry, immunofluorescence or ELISA
  • Detection of dengue virus genomic sequences through reverse transcriptase-polymerase chain reaction (RT-PCR)

Any probable or confirmed case of dengue should be reported

WHO Case Definition of Dengue Hemorrhagic Fever (DHF)

All of the following must be present:

  • Fever, or history of acute fever, lasting 2-7 days, occasionally biphasic
  • Hemorrhagic tendencies, evidenced by at least 1 of the following:
    • Positive tourniquet test
    • Petechiae, ecchymoses or purpura
    • Bleeding from the mucosa, gastrointestinal (GI) tract, injection sites or other locations
    • Hematemesis or melena
  • Thrombocytopenia (≤100,000/mm3)
  • Evidence of plasma leakage due to increased vascular permeability, manifested by at least 1 of the following:
    • A rise in the hematocrit (Hct) ≥20% above average for the corresponding age, sex & population
    • A drop in the hematocrit following volume-replacement treatment ≥20%
    • Signs of plasma leakage eg pleural effusion, ascites & hypoproteinemia

WHO Case Definition of Dengue Shock Syndrome (DSS)

All of the 4 criteria for dengue hemorrhagic fever (DHF) must be present, plus evidence of circulatory failure manifested by:

  • Rapid & weak pulse, tachycardia
  • Narrow pulse pressure (<20 mmHg) with increased diastolic blood pressure (DBP)
  • Hypotension for age
  • Cold clammy skin, restlessness, lethargy


Grading Severity of Dengue Hemorrhagic Fever (DHF) [Based on World Health Organization (WHO)]

  • DHF is classified into 4 grades of severity, where grades III & IV are considered to be dengue shock syndrome (DSS). The presence of thrombocytopenia with concurrent hemoconcentration differentiates grades I & II from dengue fever (DF)
  • Grade I: Fever accompanied by nonspecific constitutional symptoms; hemorrhagic manifestation is a positive tourniquet test, evidence of plasma leakage
  • Grade II: Spontaneous bleeding in addition to the manifestations of Grade I patients, usually in the form of skin or other hemorrhages
  • Grade III: Circulatory failure manifested by a rapid weak pulse & narrowing of pulse pressure or hypotension,with the presence of cold clammy skin & restlessness
  • Grade IV: Profound shock with undetectable blood pressure (BP) &/or pulse


Criteria for Hospitalization

General Condition

  • Continuous fever ≥3 days
  • Lethargy, restlessness, irritability, excessive tiredness, drowsiness
  • Generalized flushing
  • Shortness of breath
  • No improvement or worsening of condition


  • Unable to tolerate oral fluid intake
  • Vomiting, diarrhea

Abdominal Discomfort

  • Epigastric pain, tender hepatomegaly

Hemorrhagic Manifestations

  • Positive tourniquet test
  • Petechiae, ecchymoses or purpura
  • Spontaneous mucosal bleeding, epistaxis
  • GI bleeding, excessive menstrual bleeding, hematuria
  • Thrombocytopenia (platelet count: ≤100,000/mm3)
  • Patients with active bleeding regardless of platelet count
  • Patients without bleeding tendency but platelet count on a rapid downward trend

Plasma Leakage

  • Rapidly rising hematocrit
  • Hematocrit ≥20% of baseline
  • Serositis eg pleural effusion, ascites
  • Suspected plasma leakage in:
    • Males with hematocrit >47%
    • Females with hematocrit >40%

Circulatory Failure/Shock

  • Rapid & weak pulse
  • Narrowing of the pulse pressure to <20 mmHg
  • Hypotension
  • Cool, mottled or pale skin; cold extremities with circumoral cyanosis
  • Changes in mental status, restlessness, lethargy
  • Oliguria
  • Tachypnea due to metabolic acidosis

Clinical Predictors for Bleeding

  • Hypotension
  • Narrowing of pulse pressure to <20 mmHg
  • Hepatosplenomegaly or hepatomegaly
  • Severe thrombocytopenia (platelet count <50,000/mm3
  • Leukopenia
  • Elevated serum ALT (>3x compared to normal value)
  • Presence of vomiting, abdominal pain, restlessness, serosal effusion, or rashes

Criteria for Discharging Hospitalized Patients

  • Absence of fever for at least 24 hours without the use of antipyretics
  • Rising platelet count of >50,000/mm3
  • Stable hematocrit
  • Visible clinical improvement
  • Return of appetite
  • Good urine output
  • No respiratory distress
  • At least 2-3 days have passed after recovering from shock

Physical Examination

Dengue Fever (DF)

  • Blood pressure (BP)
  • Hydration status, capillary refill time
  • Tourniquet test which is performed as follows:
    • Inflate a BP cuff on the upper arm to a point midway between the systolic & diastolic pressures for 5 minutes
    • Test is positive when ≥20 petechiae/square inch are observed

Dengue Hemorrhagic Fever (DHF)

  • Positive tourniquet test
    • Discrete fine petechiae scattered in the extremities, axillae, face & soft palate seen during the early febrile phase
    • Increase in capillary fragility reflected by positive tourniquet test & easy bruising
  • BP is decreased as an effect of plasma leakage into the extravascular compartment following an acute increase in vascular permeability

Dengue Shock Syndrome (DSS)

  • Rapid weak pulse with narrowing of the pulse pressure (<20 mmHg)
  • Pleural effusion & ascites detected by physical examination or radiography

Laboratory Tests

Other Lab Tests for Dengue

Complete blood count (CBC)

  • Normal total white blood cell (WBC) but leukopenia may develop throughout the febrile period
  • Mild increase in hematocrit may be due to dehydration
  • Platelet counts & factors of blood clotting mechanism can be normal
    • Thrombocytopenia may occur


  • Usually low

Liver function tests (LFTs)

  • Elevation of alanine aminotransferase (ALT) & aspartate aminotransferase (AST) levels


  • Check for hematuria


Dengue Hemorrhagic Fever (DHF)


  • Evidence of pleural effusion & ascites due to acute increase in vascular permeability


Dengue Fever (DF)

Detection of antigens

  • Developments in enzyme-linked immunosorbent assay (ELISA) & dot blot assays directed to the envelope/membrane (E/M) antigen & the non-structural protein (NS1) showed that high concentrations of these antigens (immune complexes) could be detected in patients during the early period of the disease & in patients with primary & secondary dengue infections up to 6 days after the start of illness
  • Non-structural protein 1 (NS1) ELISA
    • Has been shown to be a useful diagnostic tool in acute dengue infections
    • Produced by all flaviviruses & is secreted from mammalian cells
    • Dengue NS1 antigen has been detected in the serum of dengue virus-infected patients as early as 1 day post-symptom onset (PSO) & up to 18 days post onset (DPO)
    • May also be useful for differential diagnosis between flaviviruses because of its specificity
    • NS1 antigen detection kits are commercially available & can be used by laboratories with limited equipment & yield results within a few hours


  • Hemagglutination inhibition (HI) test
    • Simple, sensitive & reproducible
    • Requires paired sera: Soon following hospital admission (acute) & 10-14 days after discharge (convalescent)
    • Titer of ≥1:1280 in an acute or convalescent phase serum sample is considered presumptive evidence of current dengue
    • Negative in early acute blood specimen & a repeat specimen should be tested before confirming or excluding dengue infection
    • Limited by inability to discriminate between infections by closely related flaviviruses
  • Immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay (MAC-ELISA)
    • Serological test of choice because ELISA IgM detected is specific for flavivirus
    • Rapid, simple, requires little sophisticated equipment
    • A single, properly timed blood sample may be adequate
    • High increase in molar fraction of IgM indicates a primary acute flavivirus infection & low increase in molar fraction of IgM indicates a secondary acute flavivirus infection
    • High IgM antibody (Ab) response indicates recent primary flavivirus infection & low IgM Ab response indicates recent secondary flavivirus infection
    • Positive dengue IgM result indicates acute or recent past infections (up to 90 days); a single positive dengue IgM may not be indicative of a present dengue infection
    • May also be used to detect cerebrospinal fluid (CSF) IgM
    • However, MAC-ELISA cannot be used to identify infecting virus serotype
    • Positive results do not necessarily denote a current dengue infection
      • Caution must be exercised when making decisions about patient management
    • Comparable to the HI test & can be used to differentiate primary & secondary infections
  • Neutralization test (NT)
    • Most specific & sensitive serologic test for dengue virus
    • Not commonly used because it is expensive, requires a long time for performance & is technically difficult
    • Serum dilution plaque reduction NT is the most common protocol
  • Complement fixation (CF) test
    • Least sensitive serological assay
    • CF appears later than IgM or HI Ab & is usually less specific
    • Has greater specificity for primary infections but is not specific in secondary infections

Other diagnostic tests

  • Virus isolation
  • Molecular techniques including reverse transcriptase-polymerase chain reaction (RT-PCR)
    • Specificity & sensitivity are better than virus isolation with a faster turnaround time

Dengue Hemorrhagic Fever (DHF)

Hematology Tests

  • Evidence of disseminated intravascular coagulation
    • Thrombocytopenia on complete blood count (CBC)
    • Prolonged prothrombin time & partial thromboplastin time (PTT)
    • Decreased fibrinogen level & increased level of fibrinogen degradation products
  • Leukopenia, hemoconcentration (rising hematocrit)

Dengue Shock Syndrome (DSS)

  • The finding of a continuing drop in the platelet count concurrent with a rise in the hematocrit is an important indication of DSS


Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Infectious Diseases - Malaysia digital copy today!
Sign In To Download
Editor's Recommendations
Most Read Articles
Roshini Claire Anthony, 4 days ago

Individuals with moderate-to-severe plaque psoriasis may reap better long-term improvements in the severity of their condition when treated with guselkumab over secukinumab, according to findings of the phase III ECLIPSE* trial presented at the recent Inflammatory Skin Disease Summit (ISDS 2018) held in Vienna, Austria.

Jairia Dela Cruz, 11 Jan 2019
Use of standard-dose aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) appears to confer protection against the risk of endometrial cancer in overweight and obese women, according to a meta-analysis.
Elvira Manzano, 5 days ago
Treatment with two investigational, oral JAK inhibitors may be beneficial in individuals with moderate‐to‐severe alopecia areata (spot baldness), an autoimmune disease that can cause a lot of anxiety, according to an ongoing phase II study.
3 days ago
Discontinuing the use of tyrosine kinase inhibitors (TKIs) in the treatment of patients with chronic myeloid leukaemia appears to be feasible in real-life clinical practice in the context of close molecular monitoring, a study reports.