What does a dengue NS1 (Non-Structural 1) negative, dengue IgM (Immunoglobulin M) and IgG (Immunoglobulin G) positive result indicate?

Interpretation of Dengue NS1 Negative, IgM and IgG Positive Results

This serologic pattern indicates a past dengue infection (not acute infection) or a late-stage dengue infection collected beyond the optimal window for NS1 detection, and requires confirmatory plaque reduction neutralization testing (PRNT) to definitively distinguish dengue from other flavivirus infections. 1

Understanding the Test Results

NS1 Antigen Negative

• NS1 antigen is only detectable during acute infection, typically from day 1 through day 5-10 of symptom onset, with highest sensitivity in the first week of illness 2, 3
• A negative NS1 does not rule out dengue infection, particularly if the specimen was collected after the first week of illness or in secondary dengue infections where antibody responses may suppress NS1 detection 4
• The presence of measurable IgG and IgM antibodies is associated with significantly lower rates of NS1 detection, as the immune response clears the NS1 antigen from circulation 4

IgM and IgG Both Positive

• IgM antibodies typically appear 3-5 days after symptom onset, while IgG antibodies develop around day 5-7 in primary infections and earlier in secondary infections 2
• The presence of both IgM and IgG indicates either:
  • A secondary dengue infection (reinfection with a different dengue serotype) 5
  • A late primary infection where IgG has begun to develop 2
  • A past dengue infection where IgM is still detectable (IgM can persist for months after infection) 1

Clinical Interpretation Algorithm

Most Likely Scenario

This pattern most commonly represents a secondary dengue infection or late-stage primary infection where:

• The specimen was collected >7 days after symptom onset when NS1 is no longer detectable 1, 2
• Both antibody classes have developed, indicating an established immune response 2
• In secondary infections, 62% of patients show this IgG+/IgM+/- pattern 5

Critical Limitation

Without confirmatory PRNT testing, you cannot definitively distinguish between:

• Recent dengue infection
• Recent infection with another flavivirus (Zika, Japanese encephalitis, yellow fever)
• False-positive results due to cross-reactivity 1

Required Next Steps

For Definitive Diagnosis

Perform confirmatory PRNT testing against dengue and other endemic flaviviruses 1:

• PRNT titer ≥10 for dengue with <10 for other flaviviruses = confirmed recent dengue infection 1
• PRNT titer ≥10 for both dengue and another flavivirus = recent flavivirus infection but cannot determine specific virus 1
• PRNT titer <10 for all flaviviruses = false-positive antibody results, no evidence of dengue or Zika infection 1

If PRNT Not Available

Report as "presumptive recent dengue virus infection" if both IgM and IgG are positive for dengue specifically, but acknowledge the timing of infection cannot be determined 1

Common Pitfalls to Avoid

Timing Misinterpretation

• Do not assume acute infection based on positive antibodies alone - IgM can persist for months after the initial infection 1, 2
• The specific timing of infection cannot be determined from serology alone 1

Geographic Considerations

• In areas with multiple circulating flaviviruses, the positive predictive value of antibody tests decreases due to cross-reactivity 2
• Previous flavivirus infections or vaccinations can cause false-positive results 2

Clinical Context Required

• Integrate epidemiologic data about viruses circulating at the location of exposure when interpreting results 1
• Consider clinical findings and warning signs for severe dengue regardless of NS1 status 6

Clinical Management Implications

Hospital admission decisions should be based on clinical warning signs (persistent vomiting, severe abdominal pain, bleeding, lethargy, fluid accumulation) rather than NS1 positivity or antibody status 6

The NS1 negative result with positive antibodies does not predict disease severity and cannot be used as an early predictor of severe dengue infection 6