Tick-borne encephalitis virus (TBEV) is an emerging pathogen that initially causes flu-like symptoms and can progress to central nervous system (CNS) infections. Tick-borne encephalitis (TBE) is an endemic disease in southern coastal counties with regular human cases, while the causative agent, TBEV, is prevalent in ticks in most of the coastal regions of Norway. This study was aimed to understand TBEV infection status across Norway including both TBE endemic and non-endemic areas. For this, we analyzed a total of 1940 residual serum samples from 19 counties of Norway (as of 2016). The samples were initially screened by ELISA, followed by virus neutralization tests for TBEV confirmation. We found a similar TBEV seroprevalence of 1.7% in TBE endemic and 1.6% in non-endemic areas. Since TBE cases are only reported from endemic regions, our findings suggest a potential subclinical or asymptomatic infection and underdiagnosis in non-endemic areas. Notably, only 43% of the ELISA-positive samples were confirmed by virus neutralization tests indicating that not all ELISA positives are true TBEV infections. Additionally, 137 samples of patients presenting with symptoms of CNS infections from a non-endemic area were included. Of these samples, 11 ELISA-positive samples were analyzed for cross-reactivity among flaviviruses. Cross-reactivity was detected with Dengue virus, West Nile Virus, and non-specific reactions. This underscores the importance of using multiple diagnostic tests to confirm TBEV infections. None of the patients with CNS infection was found to be TBE positive, and in the whole cohort, we found a low TBEV seroprevalence of 0.7%.

• Keywords
• Norway, TBEV prevalence, central nervous system infections, seroprevalence study, tick-borne encephalitis virus,
• MeSH
• Child MeSH
• Adult MeSH
• Enzyme-Linked Immunosorbent Assay MeSH
• Encephalitis, Tick-Borne * blood   diagnosis   epidemiology   MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Neutralization Tests MeSH
• Child, Preschool MeSH
• Antibodies, Viral * blood   MeSH
• Retrospective Studies MeSH
• Sensitivity and Specificity MeSH
• Seroepidemiologic Studies MeSH
• Encephalitis Viruses, Tick-Borne MeSH
• Cross Reactions MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Norway epidemiology   MeSH
• Names of Substances
• Antibodies, Viral * MeSH

Tick-borne encephalitis (TBE) is a viral disease endemic in Eurasia. The virus is mainly transmitted to humans via ticks and occasionally via the consumption of unpasteurized milk products. The European Centre for Disease Prevention and Control reported an increase in TBE incidence over the past years in Europe as well as the emergence of the disease in new areas. To better understand this phenomenon, we investigated the drivers of TBE emergence and increase in incidence in humans through an expert knowledge elicitation. We listed 59 possible drivers grouped in eight domains and elicited forty European experts to: (i) allocate a score per driver, (ii) weight this score within each domain, and (iii) weight the different domains and attribute an uncertainty level per domain. An overall weighted score per driver was calculated, and drivers with comparable scores were grouped into three terminal nodes using a regression tree analysis. The drivers with the highest scores were: (i) changes in human behavior/activities; (ii) changes in eating habits or consumer demand; (iii) changes in the landscape; (iv) influence of humidity on the survival and transmission of the pathogen; (v) difficulty to control reservoir(s) and/or vector(s); (vi) influence of temperature on virus survival and transmission; (vii) number of wildlife compartments/groups acting as reservoirs or amplifying hosts; (viii) increase of autochthonous wild mammals; and (ix) number of tick species vectors and their distribution. Our results support researchers in prioritizing studies targeting the most relevant drivers of emergence and increasing TBE incidence.

• Keywords
• Dermacentor reticulatus, TBEV, clustering analysis, drivers, expert elicitation, flavivirus, genus Ixodes, multi-criteria decision analysis (MCDA), sensitivity analysis, tick-borne encephalitis (TBE), ticks, uncertainty,
• MeSH
• Dermacentor * MeSH
• Animals, Wild MeSH
• Ixodes * MeSH
• Encephalitis, Tick-Borne * MeSH
• Humans MeSH
• Mammals MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe epidemiology   MeSH