Flaviviruses
The flavivirus genus comprises over 70 distinct viral species, with the most clinically significant human pathogens including dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), yellow fever virus (YFV), Japanese encephalitis virus (JEV), St. Louis encephalitis virus, and tick-borne encephalitis virus (TBEV). 1
Major Mosquito-Borne Flaviviruses
Primary Human Pathogens
- Dengue virus (DENV): Four serotypes (DENV-1, DENV-2, DENV-3, DENV-4) causing approximately 400 million infections annually worldwide 2, 3, 4
- Zika virus (ZIKV): Known for causing congenital microcephaly and neurological complications during pregnancy 1, 4
- West Nile virus (WNV): Two main strains (WNV-1 and WNV-2), with WNV-1 causing severe neurological disease 1, 4
- Yellow fever virus (YFV): Causes hemorrhagic fever with mortality rates up to 60% in severe cases 1, 5
- Japanese encephalitis virus (JEV): Five genotypes identified, causing 35,000-50,000 cases annually with 20-30% mortality 1
Emerging Mosquito-Borne Flaviviruses
- Usutu virus (USUV): Demonstrates pathogenicity in animal models and human infection capability 4
- Wesselsbron virus (WSLV): Causes significant pathology in animals with documented human infections 4
- Spondweni virus (SPOV): Closely related to Zika virus with human infection potential 4
- Ilheus virus (ILHV): Circulates in tropical regions with documented human cases 4
- Rocio virus (ROCV): Associated with neurological disease 4
- Murray Valley encephalitis virus (MVEV): Causes encephalitis in endemic regions 4
- Alfuy virus (ALFV): Related to Murray Valley encephalitis virus 4
Tick-Borne Flaviviruses
- Tick-borne encephalitis virus (TBEV): Major pathogen in Europe and Asia with effective vaccines available 5, 6
Other Clinically Relevant Flaviviruses
- St. Louis encephalitis virus: Causes cross-reactive antibody responses with other flaviviruses, complicating serological diagnosis 1
Key Clinical Considerations
Cross-Reactivity Issues
All flaviviruses demonstrate significant serological cross-reactivity due to shared antigenic structures, which creates substantial diagnostic challenges 1, 7. IgM antibody testing can produce false-positive results due to cross-reactivity between dengue, Zika, West Nile, St. Louis encephalitis, Japanese encephalitis, and yellow fever viruses 1, 7.
Geographic Distribution
Historically, most flaviviruses originated in Africa and predominantly affected tropical and subtropical regions 4. However, climate change and vector migration have contributed to geographical expansion, with West Nile virus now endemic in North America and Aedes albopictus mosquitoes spreading throughout Europe 1.
Common Pitfall
Do not rely solely on serological testing for flavivirus diagnosis, as IgM antibodies can persist for months to years after infection and cross-react extensively between different flaviviruses 1, 7. Molecular testing (NAAT) during acute infection provides more specific results and should be prioritized when clinically feasible 8, 7.