How is dengue fever diagnosed?

Diagnosis of Dengue Fever

Dengue fever is definitively diagnosed through laboratory testing, with the optimal method depending on the timing of presentation, using either viral detection methods within the first week of symptoms or serological testing thereafter.

Clinical Presentation and Initial Evaluation

• Dengue fever typically presents as an acute febrile illness characterized by frontal headache, retro-orbital pain, muscle and joint pain, and rash 1, 2
• The incubation period ranges from 3-14 days, with most cases developing symptoms 4-8 days after infection 1, 2
• Classic dengue fever should be suspected in patients with fever and travel history to endemic regions (tropical or subtropical areas where Aedes mosquitoes are present) 2

Laboratory Diagnostic Methods

Early Phase Testing (≤7 days after symptom onset)

• Nucleic Acid Amplification Tests (NAATs) are the preferred diagnostic method during the first week of illness 1

  • PCR testing on serum is most effective in the first few days of infection when patients are viremic 1, 3
  • Viremia typically lasts approximately 3 days during the febrile phase 4

• NS1 Antigen Detection is an excellent alternative to NAAT in the acute phase 1, 5

  • NS1 antigen is secreted from infected host cells as early as 1 day after symptom onset and remains detectable up to 10 days thereafter 1
  • Available as both laboratory-based enzyme immunoassays and rapid point-of-care tests 5

Late Phase Testing (>7 days after symptom onset)

• Serological Testing becomes more appropriate after the first week of illness 1, 3

  • IgM antibody capture ELISA (MAC-ELISA) is the primary serological test 1
  • IgM antibodies typically develop during the first week of illness and may remain detectable for 2-3 months 1, 2
  • A positive IgM antibody test on a single acute (late) or convalescent-phase serum specimen supports a probable case diagnosis 1

• Paired Serum Samples provide the most definitive serological diagnosis 1

  • Demonstration of a fourfold or greater rise or fall in reciprocal IgG or IgM antibody titers to dengue virus antigens in paired serum samples confirms infection 1
  • Seroconversion to either anti-dengue IgM and/or IgG seropositivity strongly suggests recent infection 1

Case Classification

• Confirmed Case: A clinically compatible case that is laboratory confirmed through one of the following 1:

  • Isolation of dengue virus from serum and/or autopsy tissue samples
  • Demonstration of a fourfold or greater change in antibody titers in paired samples
  • Detection of dengue virus antigen or viral nucleic acid

• Probable Case: A clinically compatible case with supportive serologic findings (IgG antibody titer ≥1280 or positive IgM antibody test on a single specimen) 1

Diagnostic Challenges and Considerations

• Cross-reactivity with other flaviviruses (e.g., Zika virus, West Nile virus) can complicate serological diagnosis 1, 6

  • Plaque reduction neutralization tests (PRNTs) provide improved specificity but are only available at select public health laboratories 1

• Combination testing using both viral detection (PCR or NS1) and serological methods provides the most comprehensive diagnostic approach 5, 3

  • Point-of-care combination tests that detect both NS1 antigen and IgM antibodies have simplified diagnosis 7, 5

• Hematological monitoring is important for assessing disease severity 4

  • An increase in hematocrit (≥20% from baseline) indicates significant plasma leakage and is a criterion for identifying dengue hemorrhagic fever 4
  • Thrombocytopenia (≤100,000/mm³) is a key laboratory finding in severe dengue 1

Special Considerations for Pregnant Women

• Pregnant women should receive comprehensive testing due to potential complications 1
  • Testing should include both NAAT and serology for dengue virus 1
  • Dengue infection during pregnancy may increase risk for maternal death or obstetric complications 1