Report of the Meningitis Program of the International Scientific Working Group on TBE. Serological screening of patients with viral CNS-infection of unknown etiology in search of undiagnosed TBE cases.

The endemicity of tick-borne encephalitis (TBE) in Europe is changing. Potential undetected or emerging TBEV foci and the risk of underdiagnosis due to a low awareness among the medical community form the background of this retrospective multicenter follow-up study. We investigated the possibility of undiagnosed TBE cases among patients with presumed viral central nervous system (CNS)-infection of unknown etiology. Eight centers in four European countries provided sera and/or cerebrospinal fluid (CSF) samples from 233 individuals. The samples were screened with a commercial TBEV ELISA test system (IgM and IgG). Positive or borderline samples were re-evaluated at the Institute of Virology in Vienna by an in-house ELISA test and a neutralization test (NT). Two previously undiagnosed Swedish TBE patients were verified. Three additional individuals from Swedish centers were IgG ELISA and NT positive. No NT positive individuals were found from France, Belgium or The Netherlands. Nineteen individuals were found IgG TBE ELISA positive, but negative in NT, indicating unspecific reactivity. At least four of those patients were vaccinated against yellow fever. The probable reason for the reactivity seen in these individuals is the well-known cross-reactivity existing among flaviviruses.