EBV Can Cause False Positive Dengue IgM Results
Epstein-Barr Virus (EBV) infection can cause false positive dengue IgM test results due to cross-reactivity between antibodies, which can lead to misdiagnosis in clinical settings. 1
Mechanism of Cross-Reactivity
- False positive serological results are common with IgM antibody testing for dengue and can occur due to nonspecific reactivity or cross-reactivity with other pathogens, including EBV 2
- Despite the structural differences between EBV (a double-helix DNA herpesvirus) and dengue (an RNA flavivirus), cross-reactivity has been documented in clinical cases 1
- This cross-reactivity can complicate diagnosis in areas where both infections may be prevalent or in returning travelers 1
Evidence of Cross-Reactivity
- A documented case report showed a patient with confirmed dengue infection (positive dengue IgM and IgG) who also tested positive on a heterophile antibody test (Monospot) for EBV, despite negative EBV DNA PCR and viral capsid antigen IgM 1
- This represents the first reported case demonstrating potential bidirectional cross-reactivity between dengue and EBV diagnostic tests 1
Diagnostic Implications
- Serological testing limitations are particularly challenging for accurate diagnosis when multiple infections may present with similar clinical features 2
- IgM antibodies for dengue can be detectable for months after infection, making timing determination difficult, especially in endemic areas 2
- With decreased incidence of a particular infection, a higher proportion of positive IgM antibody tests may be due to cross-reactivity with other pathogens like EBV 2
Recommendations for Accurate Diagnosis
- Use molecular testing (NAAT) when possible during acute infection, as it provides more specific results than serological testing 2
- Consider confirmatory testing with Plaque Reduction Neutralization Tests (PRNTs) to resolve false-positive IgM antibody results caused by nonspecific reactivity 2
- When EBV is suspected, use a comprehensive panel including VCA IgM, VCA IgG, and EBNA antibodies rather than relying solely on heterophile antibody tests 2
- In returning travelers with fever, consider both dengue and EBV in the differential diagnosis, especially when initial test results are inconsistent with the clinical presentation 1
Clinical Considerations
- Similar clinical presentations between dengue and EBV infections (fever, fatigue, headache, myalgia) can further complicate diagnosis 1
- Laboratory findings such as thrombocytopenia and transaminitis can occur in both conditions, requiring careful diagnostic evaluation 1
- Cross-reactivity is not limited to EBV and dengue; other flaviviruses (West Nile, yellow fever, Japanese encephalitis) also demonstrate significant cross-reactivity with dengue antibody tests 2, 3
Pitfalls to Avoid
- Relying solely on a single serological test for definitive diagnosis of either dengue or EBV infection 2
- Failing to consider alternative diagnoses when clinical presentation doesn't fully match initial serological results 1
- Not accounting for the possibility of co-infection with multiple pathogens, which can further complicate interpretation of test results 4