Mijatovic et al.
Underrecognized tick-borne encephalitis in Serbia: Evidence from patients with suspected West Nile virus neuroinvasive disease. Pathogens. 2026;15(6):587. doi:10.3390/pathogens15060587
In Serbia, tick-borne encephalitis (TBE) is a notifiable disease; however, awareness among medical professionals remains low, which may contribute to under-recognition and underreporting. In this context, a retrospective study was conducted in which sera from patients presenting to hospitals in three Serbian cities with either suspected West Nile virus (WNV) infection involving the central nervous system (CNS) or viral encephalitis of unknown etiology were analyzed in detail.
Among 79 sera from patients who had been diagnosed as WNV-positive based on IgG ELISA results, four samples exhibited higher reactivity to TBE virus than to WNV when tested by ELISAs using glycoprotein E domain III of either TBE virus or WNV as antigens. When all 79 sera were subsequently examined in a TBE virus neutralization assay, only these four samples demonstrated neutralizing activity. The geographic distribution of patients with TBE-neutralizing antibodies encompassed multiple regions of Serbia.
The detection of TBE-neutralizing antibodies in geographically dispersed patients suggests that TBE virus circulation in Serbia may be more widespread than currently recognized. This study further demonstrates that WNV IgG positivity alone is insufficient to establish acute WNV infection. Cross-reactivity among flaviviruses can complicate the interpretation of ELISA-based results, reinforcing the need for confirmatory neutralization testing in regions where multiple flaviviruses co-circulate.
Strengthening clinical awareness and surveillance will be essential for defining the true burden of TBE and informing prevention strategies, not only in Serbia but also in other regions where flaviviruses co-circulate.