Tick-borne encephalitis in Latvia: an epidemiological and clinical comparison of European and Siberian subtype infections

To date, it has been almost impossible to ascertain tick-borne encephalitis virus (TBEV) subtype-specific information in a clinical setting from patients with tick-borne encephalitis (TBE) infection. As different subtype infections have been reported to exhibit varying clinical courses and outcomes, especially in European areas where more than one TBEV subtype prevails, this information is therefore hugely important. We conducted a cross-sectional descriptive study based on a nationwide, active search for all TBEV infections in Latvia between 2020 and 2021. Blood samples collected during acute disease and stored frozen at -80 °C were retrospectively analysed in November 2024. We utilised anti-TBE Virus IgG ELISA, Version 2 (Euroimmun, Germany) for the screening and detection of TBEV (whole virus) IgG antibodies and the newly established, research-use anti-TBEV NS1 IgG ELISA for the detection of subtype-specific TBEV NS1 IgG antibodies against three virus subtypes (European, TBEV-EU; Siberian, TBEV-Sib and Far Eastern, TBEV-FE). Of the 123 acute cases of TBE analysed, the TBEV subtype (EU, Sib, FE) was differentiated in 103 (83.7%). Specifically, European subtype was detected in 98 cases (95.1%), Siberian subtype in 5 cases (4.9%) and Far Eastern subtype in 0 cases. The most common clinical forms of TBE among TBEV-EU cases were meningitis (84 cases, 91.3%) and encephalitis (8 cases, 8.7%). For the TBEV-Sib cases, meningitis was also the most common clinical form (4 cases, 80.0%), while encephalitis was reported in one case (20.0%). This analysis of acute TBE patient data from nationwide clinical settings provides the first clinical assessment of subtype-specific differences in the presentation and progression of TBE in Latvia. Despite previous reports of disease severity and outcome differences, we did not observe any significant clinical differences in our cohort between patients infected with either the European or Siberian subtype. However, given the limited size of the patient population here, further studies with larger cohorts are needed to clarify any tangible clinical differences amongst the various TBEV subtype infections.