West Nile Virus: Epidemiology, Surveillance, and Prophylaxis with a Comparative Insight from Italy and Iran

Background: West Nile Virus (WNV) is a mosquito-borne flavivirus responsible for seasonal outbreaks in temperate and tropical regions, including Europe, the Mediterranean, and the Middle East. Its transmission via mosquitoes, particularly Culex species, poses persistent challenges to public health. Despite ongoing efforts, comprehensive prevention and treatment strategies remain limited. Methods: A comprehensive search of peer-reviewed literature, clinical trials, and government surveillance data was conducted using PubMed, Scopus, Web of Science, and supplementary web-based resources. Inclusion criteria focused on molecular studies of WNV, vaccine and antiviral drug development, and regional outbreak reports. Results: WNV transmission is influenced by climatic conditions, vector distribution, and ecological patterns. While human vaccines are currently under development, only veterinary vaccines resulted promising but still partial insights. Remarkably, therapeutic measures are currently limited to supportive care, whereas investigational antiviral drugs are in early-stage trials. Interestingly, Italy demonstrates robust surveillance with regular reporting of outbreaks, whereas data from Iran indicate that despite a widespread serological footprint, especially in southern and southwestern provinces, but the reported clinical impact on humans and animals appears comparatively less severe. Conclusions: Bridging gaps in vaccine availability, therapeutic innovation, and disease monitoring is essential for effective WNV management to prepare for potential severe future outbreaks in Europe and the Middle East. Regional differences between Italy and Iran reveal the need for tailored public health interventions, enhanced surveillance, and sustained investment in research. In our view, collaborative frameworks across Mediterranean and Middle Eastern countries in a “One Health” approach may improve preparedness and response to future WNV outbreaks.