Diagnostic Challenges with EBV and Dengue Infections

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, according to the Centers for Disease Control and Prevention (CDC) recommendations 1

Serological testing limitations are particularly challenging for accurate diagnosis when multiple infections may present with similar clinical features, as noted by the CDC 1
IgM antibodies for dengue can be detectable for months after infection, making timing determination difficult, especially in endemic areas, as reported by the CDC 1
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, according to the CDC 1

Use molecular testing (NAAT) when possible during acute infection, as it provides more specific results than serological testing, as recommended by the CDC 1
Consider confirmatory testing with Plaque Reduction Neutralization Tests (PRNTs) to resolve false-positive IgM antibody results caused by nonspecific reactivity, as suggested by the CDC 1
When EBV is suspected, use a comprehensive panel including VCA IgM, VCA IgG, and EBNA antibodies rather than relying solely on heterophile antibody tests, according to the Infectious Diseases Society of America 2
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, as noted by the CDC 1

Relying solely on a single serological test for definitive diagnosis of either dengue or EBV infection, as warned against by the CDC 1 and the Infectious Diseases Society of America 2