Underrecognized Tick-Borne Encephalitis in Serbia: Evidence from Patients with Suspected West Nile Virus Neuroinvasive Disease
Dragana Mijatović, Ana Marija Radevska, Dejan Jakimovski, Lidija Popović-Dragonjić, Biljana Popovska Jovičić, Jagoda Gavrilović, Siniša Sević, Dajana Lendak, Irina Stojanac, Alejandro Cabezas-Cruz, Andreas Pilz, Tomás Cervantes Rincón, Jasmine Oberti-Cantergiani, Davide F. Robbiani and Pavle Banović
A new multicenter study from Serbia suggests that tick-borne encephalitis may be going undetected among patients initially suspected of having West Nile virus-related neurological disease.
Researchers analyzed serum samples from 79 patients hospitalized between 2018 and 2023 at clinical centers in Niš, Novi Sad, and Kragujevac. The patients had been treated for suspected West Nile virus neuroinvasive disease or viral encephalitis of unknown cause. Using a microneutralization assay, the team found tick-borne encephalitis virus-neutralizing antibodies in four patients, representing 5.1% of the cohort.
All four reactive cases had originally been classified as suspected West Nile virus-associated meningoencephalitis, but tick-borne encephalitis had not been considered in the differential diagnosis at hospital admission. The findings highlight a diagnostic challenge in Serbia, where West Nile virus is endemic and routine serological testing may be complicated by cross-reactivity among related orthoflaviviruses.
The study found that the TBEV-reactive patients were older on average, with a mean age of 72.5 years, and cases were identified across several regions of Serbia, including Novi Sad, Aranđelovac, Topola, and Kragujevac. One patient had a high TBEV neutralization titer of 1:640, while the remaining positive samples showed lower titers.
The authors caution that the results do not prove that TBEV caused the acute neurological illness in every reactive patient, because the study relied on single serum samples and did not include paired sera, cerebrospinal fluid analysis, TBEV-specific IgM testing, or molecular confirmation. Still, the findings provide evidence that TBEV exposure occurs in this patient population and may be missed in routine clinical practice.
The study calls for greater clinical awareness of tick-borne encephalitis in Serbia, especially during seasons when patients present with central nervous system infections and West Nile virus is suspected. The authors also recommend broader use of confirmatory neutralization testing and stronger national surveillance to better define the burden of TBE and inform prevention strategies, including future vaccine policy.
More information here.