Valent F, Degani G. A case-control study on the effectiveness of tick-borne encephalitis vaccination against hospitalization in an endemic area in northeastern Italy. Vaccines. 2026;14(2):164. doi:10.3390/vaccines14020164
In northeastern Italy, the Friuli Venezia Giulia region, including the former Province of Udine, is endemic for tick-borne encephalitis (TBE). This area, which is divided into nine health districts and has approximately 520,000 inhabitants, borders Austria to the north and Slovenia to the east. Although TBE vaccine effectiveness has been assessed in several European endemic countries, no such evaluation has previously been conducted in Italy. Therefore, a case-control study has been carried out in an area corresponding to the former Province of Udine.
Using linked anonymized regional databases (vaccination registry, public laboratory tests, and hospital discharges), cases were defined as residents of the former Province of Udine who, between 2017 and August 2025, were hospitalized and discharged with a diagnosis of TBE (ICD-9-CM code 063.x) and/or viral meningitis and who tested positive for TBE virus infection by detection of IgM in serum or cerebrospinal fluid during the same period and had a negative result. The study therefore used a retrospective test-negative case-control design.
From 2017 to 2025, 21 residents were hospitalized with confirmed TBE, corresponding to an average annual incidence of 0.45 TBE hospitalizations per 100,000 inhabitants. During the same period, an additional 6,044 individuals underwent laboratory testing for TBE-specific IgM antibodies and served as controls if the result was negative. Both the proportion of cases and the testing rate were substantially higher in the mountain and hill districts than in the other districts. Most TBE cases (14/21; 66.7%) were detected in the two small mountain districts of Gemona and Tarcento, which together account for approximately 13% of the population. In this retrospective review of hospitalization and laboratory records, the adjusted odds ratio for TBE hospitalization among individuals with at least three vaccine doses versus unvaccinated individuals was 0.11 (95% CI 0.02–0.88), corresponding to an estimated vaccine effectiveness of 89% after adjustment for age, sex, district of residence, and calendar year.
This was the first study attempting to estimate TBE vaccine effectiveness in an endemic area south of the Alps. The estimate of the association between vaccination and outcome was imprecise because of the small number of hospitalized TBE cases in the study area. Nevertheless, the magnitude of the effect strongly supports the effectiveness of vaccination.