INTRODUCTION:Brucellosis is a globally significant zoonotic disease, caused by Brucella spp., with wildlife reservoirs such as wild boars posing a potential threat to brucellosis-free livestock populations and public health. Despite eradication of brucellosis in domestic animals in Germany, the disease persists in wildlife. Reliable and specific diagnostic tools are essential for effective surveillance. MATERIAL AND METHODS:In this study, 149 serum samples from wild boars hunted during the 2023/2024 season in Bavaria (Germany) were analyzed using four serological tests: 1.the rose bengal test (RBT), 2. a conventional sLPS-based ELISA (BMS),3. a novel biwell ELISA (BSI) using both sLPS and rLPS antigens and 4. the complement fixation test (CFT) as gold standard. Sensitivity, specificity, and accuracy of all assays were calculated in comparison to the CFT. RESULTS:Of the 149 samples analyzed, 9 tested positive by CFT, resulting in a seroprevalence of 6.0 % [3.1 %, 11.2 %]in the sampled wild boar population. The BMS-ELISA demonstrated the highest sensitivity (100 %) but moderate specificity (85.0 %), whereas the BSI ELISA showed improved specificity (94.3 %) and accuracy (92.6 %) through combined detection of antibodies against sLPS and rLPS, albeit with lower sensitivity (66.7 %). The RBT performed least favorably with a sensitivity of 55.6 % and specificity of 92.7 %. DISCUSSION:The findings confirm that brucellosis remains endemic among wild boars in Bavaria. While the BSI ELISA shows promise due to its high specificity, its lower sensitivity limits its utility as a stand-alone diagnostic. Cross-reactions in sLPS-based assays highlight the importance of combining antigens for improved test reliability. The varying seroprevalence compared to previous studies underscores the dynamic nature of infection in wildlife populations. CONCLUSION:A dual-step diagnostic approach - utilizing a sensitive ELISA for screening followed by CFT for confirmation - remains the most effective strategy for wildlife surveillance. The BSI ELISA may serve as a viable alternative in clinical or resource-limited settings. Continued monitoring is crucial to mitigate the zoonotic risk posed by wildlife reservoirs.

BACKGROUND:Notified tularemia cases have been increasing in both the European Union and Austria, yet no contemporary seroprevalence data are available. This study aimed to estimate the current tularemia seroprevalence in Western Austria and to inform prevention programs by comparing seroprevalence-derived incidence rates with notified case numbers. METHODS:Between December 2023 and February 2024, serum samples from 3008 healthy blood donors aged 18-70 years in Western Austria were collected and analyzed for anti-Francisella-tularensis-IgG-antibodies using a commercially available ELISA. In the absence of confirmatory serological assays, the manufacturer's cutoff values were increased to enhance specificity, as recommended by a previous serological evaluation. RESULTS:Overall seroprevalence was 2.0% (95% confidence intervals, 95% CI 1.6-2.6), with comparable results in Vorarlberg and Tyrol. The 10-year mean notified incidence rate in Western Austria was 0.30/100,000/year, compared to 29/100,000/year based on seroprevalence data, indicating a substantial proportion of unreported infections (mean manifestation index of 1.05%). Seroprevalence varied markedly across districts, identifying potential tularemia hotspots. CONCLUSION:Estimated annual tularemia incidence rates were substantially higher than notified case numbers, underscoring the need for public education, increased clinical awareness, and targeted prevention programs. The observed district-level variation in seroprevalence should be used to inform the geographic prioritization of such interventions.

ABSTRACT Tick‐borne encephalitis virus (TBEV) is an emerging flavivirus in Europe and Asia, causing severe neurological disease in humans. Recent advances in serological diagnostics, in particular the detection of antibodies against the nonstructural protein 1 (NS1), enable epidemiological research by differentiation of vaccine‐ and infection‐induced antibodies. This assay facilitates precise studies on TBEV seroprevalence. Our study investigates the TBEV seroprevalence in the district of Passau and the surrounding high‐risk areas in Lower Bavaria, Germany. A total of 1339 serum samples from voluntary blood donors were examined using a combination of IgG ELISA, NS1‐antibody ELISA, and micro‐neutralization test (NT). The results showed a TBEV‐specific IgG antibody prevalence of 84.8% (1135/1339). Of these, 3.6% (41/1135) were NS1‐antibody positive samples, which indicates infection‐related antibodies. The vaccination coverage rate was estimated at 81.2% (1094/1339), which is in line with the results from neighboring Austria but exceeds previous vaccination estimates for Bavaria. The study showed a discrepancy between the officially reported incidences (3.7 new cases/100 000 inhabitants annually) and the actual infection rate based on NS1‐antibody seroprevalence (180.6 infections/100 000 inhabitants annually). The manifestation index was calculated at 2.1%, confirming that the majority of TBE infections are subclinical or asymptomatic. The results emphasize the usefulness of NS1‐antibody‐based diagnostics in the accurate assessment of TBEV prevalence and highlight the need for improved surveillance in endemic areas.

Reported tick-borne-encephalitis (TBE) cases have been increasing in Western Austria, but no data are available on vaccination- and infection-specific seroprevalence. This study aimed to estimate current TBEV-seroprevalence in the region and inform prevention programs by comparing anti-NS1-based-incidence rates with reported case numbers and vaccination coverage. Between December 2023 and February 2024, serum samples from 4619 blood donors in Western Austria were collected and analyzed using TBEV- and WNV-IgG-ELISA assays. Seropositive samples were tested with a TBEV-anti-NS1-IgG-ELISA to distinguish infections from vaccinations. Borderline samples were retested with serum neutralization and triple-NS1-assays. The overall anti-TBEV-IgG-seroprevalence was 80.1% (95%CI 78.9-81.3); 2.7% (95%CI 2.3-3.2) of donors tested positive for anti-TBEV-NS1 IgG antibodies, indicating previous infection. The notified incidence rate in Western Austria was 2.7/100 000/year, compared to 136.2/100 000/year based on anti-TBEV-NS1-seropositive donors, denoting a substantial number of unreported cases (mean manifestation index 1.9%). The number of donors with TBEV-infections varied considerably by district, highlighting potential hotspots for TBEV-infections. The high anti-NS1-based, estimated annual TBE incidence rates show significant differences between districts, highlighting the need for targeted prevention programs. The high rate of undiagnosed TBE cases further suggests that estimated anti-NS1-based incidence rates should be considered when defining high-risk areas.

The West Nile Virus (WNV), a member of the family Flaviviridae, is an emerging mosquito-borne flavivirus causing potentially severe infections in humans and animals involving the central nervous system (CNS). Due to its emerging tendency, WNV now occurs in many areas where other flaviviruses are co-occurring. Cross-reactive antibodies with flavivirus infections or vaccination (e.g., tick-borne encephalitis virus (TBEV), Usutu virus (USUV), yellow fever virus (YFV), dengue virus (DENV), Japanese encephalitis virus (JEV)) therefore remain a major challenge in diagnosing flavivirus infections. Virus neutralization tests are considered as reference tests for the detection of specific flavivirus antibodies, but are elaborate, time-consuming and need biosafety level 3 facilities. A simple and straightforward assay for the differentiation and detection of specific WNV IgG antibodies for the routine laboratory is urgently needed. In this study, we compared two commercially available enzyme-linked immunosorbent assays (anti-IgG WNV ELISA and anti-NS1-IgG WNV), a commercially available indirect immunofluorescence assay, and a newly developed in-house ELISA for the detection of WNV-NS1-IgG antibodies. All four tests were compared to an in-house NT to determine both the sensitivity and specificity of the four test systems. None of the assays could match the specificity of the NT, although the two NS1-IgG based ELISAs were very close to the specificity of the NT at 97.3% and 94.6%. The in-house WNV-NS1-IgG ELISA had the best performance regarding sensitivity and specificity. The specificities of the ELISA assays and the indirect immunofluorescence assays could not meet the necessary specificity and/or sensitivity.

Background: Tick-borne encephalitis (TBE) is the most significant tick-borne disease in Europe and Asia, with more than 10,000 cases per year worldwide. A surge of reported TBE cases can be observed despite the availability of highly efficient vaccines. There is little known about the serological immune protection rate of the population in Germany. The seroprotection rate is defined as the presence of neutralizing antibodies. In contrast, the vaccination rate, as defined by public health agencies, may differ from the true protection rate in a population. Materials and Methods: 2220 blood samples from inhabitants of the county Ortenaukreis in the Federal State of Baden-Württemberg in Germany were included in the study. These were tested for anti-TBEV IgG antibodies by an anti-TBEV-IgG-ELISA. Subsequently, all TBEV-IgG positive samples were confirmed for neutralizing antibodies in the micro serum neutralization assay. Results: From the overall 2220 samples, 2104 were included in the comparison because of the selection of specific age groups (ages 20–69). In our sample size, we found an average serological protection rate (presence of neutralizing antibodies) of 57% (518/908) for the female blood donors and of 52% (632/1196) for the male blood donors. Discussion: In this study, we present new findings on a highly endemic region in southern Germany. Additionally, we present current data regarding the serological TBEV protection rates in the Ortenaukreis in southern Germany and compare these with a dataset published by the RKI, which is based on vaccination reports of the primary care providers and health care insurers, and with a self-reporting study conducted by a vaccine manufacturer. Our results significantly exceed the official numbers of average active vaccination status by 23.2% for females and by 21% for males. This might indicate an even longer persistence of TBE-vaccination-induced antibody titers than previously assumed.

BackgroundThe exact epidemiology of tick-borne encephalitis virus (TBEV) infections is unknown because many TBEV infections have an influenza-like or asymptomatic course. Surveillance data are based on patients with any (predominantly neurological) symptoms that prompted diagnostic testing. Infection- and vaccine-induced antibodies against TBEV can be distinguished using an NS1 IgG ELISA.AimIn a seroprevalence study we aimed to investigate TBEV antibody prevalence, incidences, manifestation indices and potential protection rates in a highly endemic district in south-western Germany.MethodsWe analysed 2,220 samples from healthy blood donors collected between May and September 2021. The reported number of TBEV infections was provided on a sub-district level by the local public health authorities. Blood samples were first screened using a TBEV IgG ELISA. In a second step, all positive samples were further analysed with a recently established NS1 IgG ELISA. The presence of specific antibodies against TBEV (excluding cross-reacting antibodies against other flaviviruses) was confirmed by testing screening-positive samples with a microneutralisation assay.ResultsOf 2,220 included samples, 1,257 (57%) tested positive by TBEV IgG ELISA and 125 tested positive for infection-induced TBEV NS1 antibodies, resulting in a TBEV NS1 IgG seroprevalence at 5.6% in our population. The yearly incidence based on the NS1 ELISA findings resulted in 283 cases per 100,000 inhabitants.ConclusionUsing the TBEV NS1 IgG assay, we confirmed a manifestation index of ca 2% and a high incidence of predominantly silent TBEV infections (> 250/100,000/year), which exceeds the incidence of notified cases (4.7/100,000/year) considerably.

Tick-borne encephalitis (TBE) is the most important viral tick-borne infection in Europe and Asia. It is emerging in new areas. The mechanisms of emergence are fairly unknown or speculative. In the Ravensburg district in southern Germany, TBE emerged, mainly over the last five years. Here, we analyzed the underlying epidemiology in humans. The resulting identified natural foci of the causal TBE virus (TBEV) were genetically characterized. We sampled 13 potential infection sites at these foci and detected TBEV in ticks (Ixodes ricinus) at eight sites. Phylogenetic analysis spurred the introduction of at least four distinct TBEV lineages of the European subtype into the Ravensburg district over the last few years. In two instances, a continuous spread of these virus strains over up to 10 km was observed.

TBE is the most important tick-borne arbovirus disease of humans. Epidemiological data indicate a trend towards an increasing severity with higher age.A number of possible genetic and non-genetic risk factors have been identified, which might have an impact on the manifestation and severity of human disease.Different TBEV strains seem to cause differing clinical courses of disease. While the TBE-EU mainly causes a biphasic course, the clinical course of TBEV-FE and TBEV-SIB are mainly monophasic.The diagnosis of TBE is based on serological tests.So far there is no effective treatment of TBEV infections.

Background: Tickborne-encephalitis (TBE) is a potentially life-threating neurological disease that is mainly transmitted by ticks. The goal of the present study is to analyze the potential uniform environmental patterns of the identified TBEV microfoci in Germany. The results are used to calculate probabilities for the present distribution of TBEV microfoci in Germany based on a geostatistical model. Methods: We aim to consider the specification of environmental characteristics of locations of TBEV microfoci detected in Germany using open access epidemiological, geographical and climatological data sources. We use a two-step geostatistical approach, where in a first step, the characteristics of a broad set of environmental variables between the 56 TBEV microfoci and a control or comparator set of 3575 sampling points covering Germany are compared using Fisher's Exact Test. In the second step, we select the most important variables, which are then used in a MaxEnt distribution model to calculate a high resolution (400 × 400 m) probability map for the presence of TBEV covering the entire area of Germany. Results: The findings from the MaxEnt prediction model indicate that multi annual actual evapotranspiration (27.0%) and multi annual hot days (22.5%) have the highest contribution to our model. These two variables are followed by four additional variables with a lower, but still important, explanatory influence: Land cover classes (19.6%), multi annual minimum air temperature (14.9%), multi annual sunshine duration (9.0%), and distance to coniferous and mixed forest border (7.0%). Conclusions: Our findings are based on defined TBEV microfoci with known histories of infection and the repeated confirmation of the virus in the last years, resulting in an in-depth high-resolution model/map of TBEV microfoci in Germany. Multi annual actual evapotranspiration (27%) and multi annual hot days (22.5%) have the most explanatory power in our model. The results may be used to tailor specific regional preventive measures and investigations.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is associated with a potentially severe clinical manifestation, coronavirus disease 2019 (COVID-19), and currently poses a worldwide challenge. Health care workers (HCWs) are at the forefront of any health care system and thus especially at risk for SARS-CoV-2 infection due to their potentially frequent and close contact with patients suffering from COVID-19. Serum samples from 198 HCWs with direct patient contact of a regional medical center and several outpatient facilities were collected during the early phase of the pandemic (April 2020) and tested for SARS-CoV-2-specific antibodies. Commercially available IgA- and IgG-specific ELISAs were used as screening technique, followed by an in-house neutralization assay for confirmation. Neutralizing SARS-CoV-2-specific antibodies were detected in seven of 198 (3.5%) tested HCWs. There was no significant difference in seroprevalence between the regional medical center (3.4%) and the outpatient institution (5%). The overall seroprevalence of neutralizing SARS-CoV-2-specific antibodies in HCWs in both a large regional medical center and a small outpatient institution was low (3.5%) at the beginning of April 2020. The findings may indicate that the timely implemented preventive measures (strict hygiene protocols, personal protective equipment) were effective to protect from transmission of an airborne virus when only limited information on the pathogen was available.

Background Tick-borne encephalitis (TBE) is the most important tick-borne viral disease in Eurasia and causes disease in humans and in a number of animals, among them dogs and horses. There is still no good correlation between tick numbers, weather conditions and human cases. There is the hypothesis that co-feeding due to simultaneous occurrence of larvae and nymphs may be a factor for the increased transmission of the virus in nature and for human disease. Based on long-term data from a natural TBEV focus, phylogenetic results and meteorological data we sought to challenge this hypothesis. Methods Ticks from an identified TBE natural focus were sampled monthly from 04/2009 to 12/2018. Ticks were identified and pooled. Pools were tested by RT-qPCR. Positive pools were confirmed by virus isolation and/or sequencing of additional genes (E gene, NS2 gene). Temperature data such as the decadal (10-day) mean daily maximum air temperature (DMDMAT) were obtained from a nearby weather station and statistical correlations between tick occurrence and minimal infection rates (MIR) were calculated. Results In the study period from 04/2009 to 12/2018 a total of 15,530 ticks (2,226 females, 2,268 males, 11,036 nymphs) were collected. The overall MIR in nymphs over the whole period was 77/15,530 (0.49%), ranging from 0.09% (2009) to 1.36% (2015). The overall MIR of female ticks was 0.76% (17/2,226 ticks), range 0.14% (2013) to 3.59% (2016). The overall MIR of males was 0.57% (13/2,268 ticks), range from 0.26% (2009) to 0.97% (2015). The number of nymphs was statistically associated with a later start of spring/vegetation period, indicated by the onset of forsythia flowering. Conclusion There was no particular correlation between DMDMAT dynamics in spring and/or autumn and the MIR of nymphs or adult ticks detected. However, there was a positive correlation between the number of nymphs and the number of reported human TBE cases in the following months, but not in the following year. The hypothesis of the importance of co-feeding of larvae and nymphs for the maintenance of transmission cycle of TBEV in nature is not supported by our findings.

Tick-borne encephalitis virus (TBEV) is an important central nervous system (CNS) infection in Europe and Asia. It is a flavivirus in the tick-borne group. Effective vaccines against TBE are available in the affected countries. However, diagnosing TBE is challenging due to cross-reactive antibodies between different viruses of the genus Flavivirus, family Flaviviridae. Differentiation between infection-induced and vaccine-induced antibodies can be difficult and in many cases impossible, due to the increasing vaccination rate against TBEV. We present a new approach to detect antibodies against the TBEV nonstructural protein 1 (NS1) as a diagnostic marker, which is exclusively indicative for virus replication in natural infection, on the basis of an enzyme-linked immunosorbent assay (ELISA). A total of 188 anonymous serum samples from the National Consultant Laboratory for TBEV were included in our study. The assay was validated according to the European Laboratory Norm DIN EN ISO 15189 for diagnostic use. The ELISA for the detection of TBEV NS1 specific IgG class antibodies has demonstrated a sensitivity of >94% and a specificity of >93% in broadly cross-reacting sera from patients with vaccinations against flaviviral diseases and single or multiple flavivirus infections, respectively. The detection of anti-NS1 antibodies is feasible and facilitates reliable differentiation between different flavivirus infections, TBEV infection, and TBE vaccination.

Background Little is known regarding the changing seasonality of infections with the tick-borne encephalitis virus (TBEV) and the incidence of the resulting disease over the last two decades. Seasonal patterns have to our knowledge not previously been systematically investigated and are poorly understood. We investigate emerging seasonal changes in clinical aspects like potentially increasing hospitalization during the year, variations in clinical symptoms and disease severity during the season and seasonal dynamics of fatal outcomes. Material and methods TBEV infection became a notifiable disease in Germany in 2001. We used the national reporting dataset spanning from 2001-2018, provided by the Robert Koch-Institute (RKI). There were general epidemiological variables available, including "symptom onset", "age" and "sex". Furthermore, several variables documented disease severity. These included "CNS symptoms", "myelitis", "fatal outcome" and "hospitalization". Potential factors influencing the occurrence of CNS symptoms, myelitis, hospitalizations and fatal outcome were analyzed using logistic regression models. Linear trends, including the "time point in year" at which TBEV infection related symptoms were detected, were tested using calendar year as a continuous covariate. In addition, seasonal trends and age and sex specific differences were exploratively tested for non-linear effects using restricted cubic splines with knot locations based on Harrell's recommended percentiles. Finally, the dynamic relationship between in-seasonal trends year of detection, sex and age was tested using interaction terms. Results 6,073 TBEV infection cases from 2001-2018 were included in our analysis. We find that from 2001-2018 TBEV infections are reported 0.69 days earlier each year (p<0.001). There was no detectable seasonal variation regarding the occurrence of fatal outcome, CNS and myelitis. However, there was a significant changing trend regarding hospitalizations over the course of the year: The risk for hospitalization increases until August, decreases again from October on. Conclusion We present epidemiological evidence that the TBE season in Germany has shifted to start earlier over the last years, beginning approximately 12 days earlier in 2018 than it did in 2001. There are seasonal patterns regarding a higher risk of hospitalization during August.

In July 2018, brucellosis was diagnosed in a German patient without a travel history to regions endemic for Brucella. Microbiological analysis, including whole-genome sequencing, revealed Brucella suis biovar 1 as the etiologic agent. Core-genome-based multilocus sequence-typing analysis placed the isolate in close proximity to strains originating from Argentina. Notably, despite a strong IgM response, the patient did not develop Brucella-specific IgG antibodies during infection. Here, we describe the clinical course of infection, the extensive epidemiological investigations, and discuss possible routes of transmission.

OBJECTIVES:The capability to measure and monitor the quality of antibiotic prescribing is an important component of antibiotic stewardship (ABS) programmes. Several catalogues of consensus-based structure and process-of-care quality indicators (QIs) have been proposed, but only a few studies have tested and validated ABS QIs in practice tests. This multicentre study determined the clinimetric properties and suitability of a set of 33 process QIs for ABS that had earlier been developed and in part recommended in a German-Austrian hospital ABS practice guideline.METHODS:Two point prevalence surveys were conducted in a convenience sample of 24 acute care hospitals throughout Germany, and data of all screened adult inpatients with prescription of a systemic antibiotic at a given day (n=4310) were included in the study. For each QI, the following clinimetric properties were assessed: applicability, feasibility, performance, case mix stability and interobserver reliability.RESULTS:Eighteen QIs were considered sufficiently feasible, applicable and reliable, and had adequate room for improvement. The finally selected QIs primarily cover antibiotic therapy of common infections (bloodstream infection, pneumonia and urinary tract infection), while two of the QIs each address surgical prophylaxis and general aspects of antibiotic administration.CONCLUSIONS:Practice tests may be important to test the suitability of consensus process-of-care QIs in the field of hospital ABS. The 18 selected QIs considered suitable enough for hospital ABS in this study should be regarded as priority QIs useful for internal quality control and assurance. More research and additional practice tests may be needed to confirm their suitability for external quality assessment schemes.

Tick-borne encephalitis (TBE) is an occupational hazard for forestry workers. We measured knowledge levels, misbeliefs, and vaccination rates in forestry trainees in order to tailor specific measures aimed at reducing occupational TBE incidence. A paper-based survey was performed at a central training site for forestry workers in the state of Baden-Wuerttemberg. The questionnaire contained items regarding vaccination status against tickborne encephalitis virus (TBEV), self-reported tick-borne diseases, knowledge of and attitudes towards tickborne disease, and practices in the context of ticks and tick bites. All trainees in the period June-December 2018 were surveyed. Statistical analyses were conducted using Mann-Whitney-Rank sum test and one-way ANOVA tests. Two-hundred-twenty-five trainees participated in the survey. Almost all (> 99%) were aware of living in a TBE high-risk area. Eighty-three percent of respondents were vaccinated in line with current recommendations. Seventeen percent had no effective vaccination status. Twenty-seven percent believed that ticks can transmit only TBEV and Borrelia spp. Sixty-two percent knew that TBEV infections can be fatal. Only 8% of respondents use tick repellents and only 17% wear long sleeves and pants. Trainees who graduated from a six and (eight or) nine secondary school (Realschule and Abitur respectively) had more knowledge on ticks and tick-borne disease compared to graduates from a five year school (Hauptschule) (p= 0.002 and p= 0,037 respectively). Overall, the TBE vaccination rate is not high enough in this high-risk occupational group. We identified gaps in knowledge and practices that could have an impact on TBE incidence in this group if addressed. Further epidemiological research is needed on knowledge, attitudes, and practices in different high-risk populations.

Tick-borne encephalitis (TBE) is an illness caused by tick-borne encephalitis virus (TBEV) infection which is often limited to a febrile illness, but may lead to very aggressive downstream neurological manifestations. The disease is prevalent in forested areas of Europe and northeastern Asia, and is typically caused by infection involving one of three TBEV subtypes, namely the European (TBEV-Eu), the Siberian (TBEV-Sib), or the Far Eastern (TBEV-FE) subtypes. In addition to the three main TBEV subtypes, two other subtypes; i.e., the Baikalian (TBEV-Bkl) and the Himalayan subtype (TBEV-Him), have been described recently. In Europe, TBEV-Eu infection usually results in only mild TBE associated with a mortality rate of <2%. TBEV-Sib infection also results in a generally mild TBE associated with a non-paralytic febrile form of encephalitis, although there is a tendency towards persistent TBE caused by chronic viral infection. TBE-FE infection is considered to induce the most severe forms of TBE. Importantly though, viral subtype is not the sole determinant of TBE severity; both mild and severe cases of TBE are in fact associated with infection by any of the subtypes. In keeping with this observation, the overall TBE mortality rate in Russia is ∼2%, in spite of the fact that TBEV-Sib and TBEV-FE subtypes appear to be inducers of more severe TBE than TBEV-Eu. On the other hand, TBEV-Sib and TBEV-FE subtype infections in Russia are associated with essentially unique forms of TBE rarely seen elsewhere if at all, such as the hemorrhagic and chronic (progressive) forms of the disease. For post-exposure prophylaxis and TBE treatment in Russia and Kazakhstan, a specific anti-TBEV immunoglobulin is currently used with well-documented efficacy, but the use of specific TBEV immunoglobulins has been discontinued in Europe due to concerns regarding antibody-enhanced disease in naïve individuals. Therefore, new treatments are essential. This review summarizes available data on the pathogenesis and clinical features of TBE, plus different vaccine preparations available in Europe and Russia. In addition, new treatment possibilities, including small molecule drugs and experimental immunotherapies are reviewed. The authors caution that their descriptions of approved or experimental therapies should not be considered to be recommendations for patient care.

Objective Tick-borne encephalitis (TBE) caused by the tick-borne encephalitis virus (TBEV) is the most important tick-borne arboviral disease in Europe and Asia. The Upper Rhine Valley is thought to be the very western border of TBEV distribution in Europe. The aim of our study was to identify natural foci and isolate TBEV from ticks, to determine the prevalence of TBEV in local tick populations and to study the phylogenetic relatedness of circulating TBEV strains in this region. Material and methods Ticks were collected between 2016, 2017 and 2018 by flagging. TBEV was isolated from collected ticks and phylogenetic analyses were performed. Minimal infection rates (MIR) of the collected ticks were calculated. Results At 12 sampling sites, a total of 4,064 Ixodes ticks were collected in 2016 and 2017 -(and one single collection 2018). 953 male, 856 female adult ticks and 2,255 nymphs were identified. The MIR rates were 0,17% (1/595) for Schiltach (Germany) and 0,11% (1/944) for Foret de la Robertsau (France), respectively. Overall, the three newly described TBEV strains, isolated in the years 2016 and 2017 from the Upper Rhine Valley have no close phylogenetic relation and show a genetic relationship with strains from eastern Europe. The 2018 TBEV strain from Aubachstrasse (Germany), however, is closely related to the TBEV found in Schiltach (Germany). Conclusion In conclusion, we demonstrate, to our knowledge for the first time, the phylogenetic relations of the newly isolated TBEV strains on both sides of the upper Rhine river.