Toscana virus - an emerging Mediterranean arbovirus transmitted by sand flies

Toscana virus (TOSV) is an emerging arthropod-borne virus (arbovirus) of medical importance that is increasing its range across much of the Mediterranean Basin, Europe and the Middle East. Transmitted by Phlebotomus spp. sand flies, it is the most clinically relevant sand fly-borne phlebovirus. Initially isolated in the Tuscany region of Central Italy, it has now been detected in multiple countries that surround this geographical area. Infection of the vertebrate host can cause fever and neurological disease, following the dissemination of the virus to the brain. The prevalence is high in some regions, with a notable percentage of individuals showing seroconversion. TOSV can be a leading cause of acute meningitis and encephalitis (AME) during the summer months. In this comprehensive review, we will focus on several key topics. We discuss how TOSV has spread to establish outbreaks of infection in both humans and animals around the Mediterranean and the wider region. Clinical aspects of TOSV infection in humans are described, along with the best standards in diagnosis. Finally, we focus our discussion on the role of the sand fly vector, describing their biology, vector competency, implications for putative vertebrate reservoirs, the effect of the climate emergency on sand fly distribution and the putative role that sand fly-derived salivary factors may have on modulating host susceptibility to TOSV infection.