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

<b>Background</b>: 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 <i>Culex</i> species, poses persistent challenges to public health. Despite ongoing efforts, comprehensive prevention and treatment strategies remain limited. <b>Methods</b>: A comprehensive search of peer-reviewed literature, clinical trials, and government surveillance data from Italy and Iran 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. <b>Results</b>: WNV transmission is influenced by climatic conditions, as well as vector distribution and ecological patterns. While human vaccines are currently under development, only veterinary vaccines yielded promising but still limited evidence of effectiveness. Notably, 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, the reported clinical impact on humans and animals appears comparatively less severe. <b>Conclusions</b>: 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. On the other hand, regional differences between Italy and Iran reveal the need not only for tailored public health interventions and enhanced surveillance, but also for 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.