Background and objective:
Among viruses of the _Phlebovirus genus _in the Mediterranean area, sand flies transmitted Toscana virus (TOSV) can cause human neuro-invasive disease. Due to a lack of international surveillance, its impact on human health is poorly known, and considering high phlebotomine vectors density detected in some disease foci. We aim to describe the epidemiology all cases of neuro-invasive TOSV notified in Italy from 2016 to 2021.

Methods:
We analysed data from the Italian national TOSV surveillance system on all notified cases of neuro-invasive disease laboratory-confirmed with at least one of the following: TOSV isolation, TOSV-IgM in cerebrospinal fluid (CSF); TOSV RT–PCR on CSF/blood/urine/other; TOSV IgM and IgG in serum; seroconversion/four-fold increase in TOSV antibody titre.

Results:
Between July 2016 and October 2021, 6 transmission seasons, 331 confirmed cases of neuro-invasive TOSV were reported in Italy (median 56 cases/year, range 35 in 2016 - 85 in 2018). Most cases were confirmed by PCR (271, 82%) and/or TOSV IgM and IgG detection (235, 71%). Cases were reported in 9/21 Italian Regions, mainly in the north-east. Average age was 46 (range 0 –89 years), most cases were male (233, 70%). Disease onset occurred mainly between July and August (205, 62%). The mean annual incidence was 0.09 cases/ 100.000 ranging between 0.06 cases/100.000 in 2016 and 0.15 cases/100.000 in 2018. The annual mean 6-year incidence was similar across age groups (0.07 cases/100.000 ≥80 years, 0.09 cases/100.000 in the 0-59 and 60-79 age groups).

Conclusions:
TOSV infection is endemic in Italy, causing on average 50 cases of neuro-invasive disease each year. This likely under-estimates infections, as neuro-invasive cases are rare events, most TOSV infections are mild, and in our analysis we only considered laboratory-confirmed cases. Increased disease detection and international surveillance could improve our understanding of the public health impact of TOSV.