What laboratory tests are recommended for diagnosing dengue fever in children?

Laboratory Testing for Dengue Fever in Children

Diagnostic Testing Algorithm

For children with suspected dengue fever, the timing of specimen collection determines the optimal laboratory test: perform nucleic acid amplification testing (NAAT) or NS1 antigen detection on serum collected ≤7 days after symptom onset, and IgM antibody testing for specimens collected >7 days after onset or when NAAT is unavailable. 1, 2

Acute Phase Testing (Days 1-7 of Illness)

• NAAT/PCR on serum is the preferred initial diagnostic test during the first week of symptoms, as viral RNA is detectable for 4-6 days after symptom onset 1, 2, 3
• NS1 antigen detection serves as an acceptable alternative to NAAT, as NS1 is secreted from infected cells as early as 1 day after symptom onset and remains detectable up to 10 days 1, 4
• Specimens should be collected as soon as possible and transported at room temperature within 2 hours 1
• Both serum (clot or SST tube) and plasma (EDTA or PPT tube) are acceptable specimens for NAAT 1

Post-Acute Phase Testing (After Day 7)

• IgM capture ELISA (MAC-ELISA) becomes the primary diagnostic test after 7 days of symptoms 1, 2, 3
• IgM antibodies appear 3-5 days after symptom onset and remain detectable for 2-3 months 1, 4
• In primary dengue infections, IgG antibodies appear 10-12 days after onset 1
• Critical caveat: In secondary dengue infections, IgM response may be diminished or absent, making interpretation more challenging 1, 2

Confirmatory Testing

• Plaque reduction neutralization test (PRNT) is the reference standard when cross-reactivity with other flaviviruses (Zika, yellow fever, Japanese encephalitis) is suspected 1, 5
• PRNT titer ≥10 defines a positive result and provides improved specificity over commercial serologic assays 1, 5
• PRNT should be performed when definitive diagnosis affects clinical management, particularly in pregnant patients or when distinguishing dengue from Zika virus 1, 5

Essential Monitoring Laboratory Tests

Complete Blood Count (Daily Monitoring Required)

• Daily CBC monitoring is essential to track platelet counts and hematocrit levels in hospitalized children 2, 6
• Thrombocytopenia (platelets <100,000/mm³) is independently associated with severe dengue in children, though its absence does not exclude dengue 6, 7, 8
• Hemoconcentration (rising hematocrit >20% from baseline) indicates plasma leakage and progression to severe disease 2, 7
• Important pitfall: In pediatric referral hospitals, absence of hemoconcentration does not exclude plasma leakage, particularly in children who received prior fluid replacement 7

Liver Function Tests

• Serum albumin should be obtained urgently in suspected dengue cases, as hypoalbuminemia is one of the best laboratory markers of serious dengue disease in hospitalized children 4, 7
• Elevated transaminases (SGOT/AST) are found in 47% of pediatric dengue cases and correlate significantly with hepatomegaly 8
• Monitor transaminases weekly until normalized if elevated 2-5× normal at discharge, or every 3 days if >5× normal 2

Additional Laboratory Parameters

• Renal function tests should be obtained urgently in patients with suspected dengue 4
• Blood glucose monitoring is essential, particularly in children who are at risk for hypoglycemia 4, 2
• White blood cell count combined with platelet count (the "DF-2 scale") provides a simple but clinically useful screening tool for dengue in children 9

Interpretation of Serologic Patterns

Primary vs. Secondary Infection

• IgM positive, IgG negative, NS1 negative: Indicates recent primary dengue infection with specimen collected >7 days after symptom onset, after NS1 has cleared 4, 5
• Both IgM and IgG positive: Suggests recent or current dengue infection, but requires confirmatory PRNT testing if definitive diagnosis is needed 5
• IgG positive alone: Indicates past infection (months to years prior) and does not confirm acute disease 2, 5

Cross-Reactivity Considerations

• False-positive IgM results commonly occur due to cross-reactivity with other flaviviruses 2, 5
• Document complete vaccination history (yellow fever, Japanese encephalitis, tick-borne encephalitis) to interpret results accurately 2, 5
• In secondary flavivirus infections, neutralizing antibodies against multiple flaviviruses rise rapidly, potentially precluding conclusive determination of the infecting virus 2

Special Considerations for Children

• Hepatomegaly, lethargy, abdominal pain, and bleeding are clinical parameters independently associated with severe dengue in children and should prompt more intensive laboratory monitoring 6, 7
• Pleural effusion and abdominal distension have higher sensitivity (82.6%) for serious dengue disease in hospitalized children 7
• The combination of fever, pain, rashes, and vomiting associated with hepatomegaly and elevated SGOT in the context of low platelet count strongly suggests dengue fever in children, especially in epidemic settings 8
• Children with secondary heterologous dengue infections are at highest risk for severe disease and require closer laboratory monitoring 3