Can the dengue (Dengue virus) vaccine cause false positive results in dengue combo (combination) tests?

Dengue Vaccine and False Positive Combo Tests

Yes, dengue vaccination causes false positive results on dengue combo tests, particularly IgM and IgG serological assays, with the highest rate of false positivity occurring within 2 months post-vaccination. 1, 2

Mechanism of False Positivity

The dengue vaccine (CYD-TDV/Dengvaxia) induces an immune response that generates anti-dengue antibodies, which are then detected by standard serological tests designed to diagnose natural dengue infection. 1, 2

• IgM and IgG antibody tests have low specificity (77-85%) in vaccinated populations, leading to significant false positive rates when used for diagnosis. 1, 2
• The false positivity is most pronounced in the first 2 months following vaccination, when vaccine-induced antibody responses are at their peak. 1
• Individuals who were dengue-seronegative before vaccination show higher rates of false positives compared to those who were seropositive pre-vaccination. 2

Impact on Specific Test Components

IgM and IgG Antibody Tests (Most Affected)

• Serological diagnosis using IgM/IgG has only 85.1% specificity in vaccinated populations, compared to virological confirmation. 1
• The positive predictive value drops dramatically to 22.9% in vaccinated cohorts, meaning most positive serological results in vaccinated individuals are false positives. 2
• Cross-reactivity with vaccine-induced antibodies makes it impossible to distinguish vaccine response from natural infection using standard IgM/IgG assays alone. 3, 1

NS1 Antigen Tests (Less Affected)

• NS1 antigen detection is NOT significantly affected by prior vaccination, as NS1 is a viral protein only present during active viral replication, not produced by the vaccine. 4, 5
• NS1 testing remains reliable for diagnosing acute dengue infection in vaccinated individuals during the first 7-10 days of illness. 4, 6

Molecular Testing/PCR (Not Affected)

• Nucleic acid amplification tests (NAATs) are not impacted by vaccination status and remain the gold standard for acute diagnosis in vaccinated populations. 7, 5
• PCR detects viral RNA only during active infection and cannot be falsely positive due to vaccine-induced immunity. 5

Diagnostic Algorithm for Vaccinated Individuals

For acute illness (≤7 days after symptom onset):

• Prioritize NS1 antigen testing or PCR/NAAT as first-line diagnostics, as these are not affected by vaccination. 7, 6, 5
• Avoid relying on IgM/IgG serology alone during this window in vaccinated patients. 1, 2

For later presentation (>7 days after symptom onset):

• If IgM/IgG testing is positive, confirmatory plaque reduction neutralization testing (PRNT) is essential to distinguish vaccine response from natural infection. 7, 3
• A PRNT titer ≥10 for dengue with negative titers for other flaviviruses confirms recent natural dengue infection. 7
• Without PRNT confirmation, positive serology should be interpreted as "presumptive recent flavivirus infection" with acknowledgment that vaccination may be the cause. 7

Critical Pitfalls to Avoid

• Never rely solely on IgM/IgG serology for dengue diagnosis in vaccinated individuals, as this leads to unacceptably high false positive rates. 1, 2, 5
• Do not assume positive serology indicates acute infection in recently vaccinated persons (especially within 2 months of vaccination). 1
• Japanese encephalitis vaccination also causes cross-reactivity with dengue serological tests, compounding the problem in populations receiving multiple flavivirus vaccines. 8
• The CDC warns that relying on serological assessments in vaccinated populations will lead to significant numbers of false positives during routine clinical practice and surveillance. 1, 2

Practical Recommendations

• In dengue-endemic areas with vaccination programs, establish diagnostic protocols that prioritize NS1 and molecular testing over serology. 5, 9
• Document vaccination status for all patients undergoing dengue testing, as this fundamentally changes test interpretation. 5, 9
• Consider epidemiologic context: in areas with ongoing dengue outbreaks where only one virus is circulating, clinical diagnosis combined with NS1/PCR may be sufficient without serology. 7
• For surveillance purposes in vaccinated populations, new dengue-specific diagnostic algorithms are urgently needed that account for vaccine-induced immunity. 2, 9