In 2017, the first autochthonous cases of tick-borne encephalitis (TBE) were reported in the region of Saint-Étienne, a forested and mountainous area in Auvergne-Rhône-Alpes (AURA), France. We aimed to describe the frequency of TBE among patients in this area with acute and subacute neurological symptoms and to characterize the confirmed TBE cases.

We included patients over two years of age with neurological symptoms evolving for up to three months and having undergone cerebrospinal fluid (CSF) analysis between January 1, 2021 and December 31, 2023 at Saint-Étienne University Hospital. We retrospectively analyzed available CSF and/or serum for antibodies against TBE virus (TBEV) by means of enzyme-linked immunosorbent assay and chemiluminescent immunoassay, respectively. Seroneutralization testing confirmed positive specimens.

Among the 544 included patients, 84 had a nervous system infection, including seven cases of TBE. TBEV represented the second cause of infectious encephalitis/meningoencephalitis (six cases), along with varicella-zoster virus (six cases) and after herpes simplex virus (seven cases). TBEV was also responsible for one case of meningitis. Overall, TBEV ranked among the first five causes of central nervous system infection. We retrospectively diagnosed one patient through systematic screening. In the remaining six cases, the median time to diagnosis was 23 days (range 6–157). All patients lived in rural autochthonous areas, including four in the Pilat Massif, where the estimated annual incidence rate was 13 cases per 100,000 inhabitants. None died.

In Western AURA, TBE needs to be systematically screened in patients presenting with evocative symptoms, and prevention should be prioritized.