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Classification of TBE viruses. (Modified after [1])

Classification of TBE viruses. (Modified after [1])

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Tick-borne encephalitis (TBE) is the main tick-borne virus infection in Eurasia. It is prevalent across the entire continent from Japan to France and occurs in endemic foci. Expansion of prevalence in areas including northern Russia, Sweden, and Finland has been observed in recent years. Ticks are the most important vectors and may transmit the TBE...

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... The European TBEV subtype is common in central, northern and eastern Europe and the Baltic States. It is also found in France, South Korea, the Netherlands, and the European part of Russia [11,12]. The Far East subtype, formerly known as the Russian spring-summer encephalitis subtype, is dominant in China, Japan and the Russian Far East. ...
... In an earlier study conducted by Juceviciene et al. may be explained by the emergence of new foci or the spread of existing ones [35]. The increase in TBE incidence is likely due to several factors such as changes in climate [8,9], as well as changes in the availability of tick host species [10,11], which all impact the tick life cycle and, thus, tick distribution [1]. ...
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The Baltic states are the region in Europe where tick-borne encephalitis (TBE) is most endemic. The highest notification rate of TBE cases is reported in Lithuania, where the incidence of TBE has significantly increased since 1992. A recent study reported 0.4% prevalence of TBE virus (TBEV) in the two most common tick species distributed in Lithuania, Ixodes ricinus and Dermacentor reticulatus , with the existence of endemic foci confirmed in seven out of Lithuania’s ten counties. However, until now, no comprehensive data on molecular characterisation and phylogenetic analysis have been available for the circulating TBEV strains. The aim of this study was to analyse TBEV strains derived from I . ricinus and D . reticulatus ticks collected from Lithuania and provide a genotypic characterisation of viruses based on sequence analysis of partial E protein and NS3 genes. The 54 nucleotide sequences obtained were compared with 81 TBEV strains selected from the NCBI database. Phylogenetic analysis of the partial E and NS3 gene sequences derived from 34 Lithuanian TBEV isolates revealed that these were specific to Lithuania, and all belonged to the European subtype, with a maximum identity to the Neudoerfl reference strain (GenBank accession no. U27495) of 98.7% and 97.4%, respectively. The TBEV strains showed significant regional genetic diversity. The detected TBEV genotypes were not specific to the tick species. However, genetic differences were observed between strains from different locations, while strains from the same location showed a high similarity.
... The tick-borne encephalitis virus (TBEV) is a single-stranded, positive-sense RNA virus of the genus Flavivirus [2]. It belongs to the mammal-associated group [3] and is prevalent across the Eurasia continent, including Europe, Russia, Turkey, Kazakhstan, Kyrgyzstan, Mongolia, China, Japan, etc. [4,5]. Tick-borne encephalitis (TBE) mainly causes neurological symptoms, such as meningitis, encephalitis, and myelitis, accompanied by fever. ...
... TBEV-Eu is mainly distributed in Central Europe and has the lowest fatality rate (1-2%) among the three subtypes. TBEV-Fe, which is found in far-eastern Asia and central/eastern Siberia, has a high fatality rate of 20-40%, and TBEV-Sib, which is distributed in Siberia, has a moderately low fatality rate of 6-8% [3,8]. Recently, new TBEV subtypes, including Baikalian (TBEV-Bkl) and Himalayan (TBEV-Him), have been reported in Russia and China, respectively [9,10]. ...
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Ticks are important vectors of the tick-borne encephalitis virus (TBEV). In Kyrgyzstan, the livestock farming trade and nomadic lifestyle enable tick-borne diseases to be imported from neighboring countries, but there are few relevant studies. In this study, we collected 40 ticks from cattle in Kyrgyzstan. Molecular marker analysis identified the ticks as Ixodes persulcatus (97.5%; n = 39) and Haemaphysalis punctata (2.5%; n = 1). Real-time PCR screening revealed two ticks to be positive for TBEV, but only one tick was amplified using nested PCR targeting the TBEV envelope (E) and non-structure 5 (NS5) gene. The obtained sequences belonged to the TBEV Siberian subtype and phylogenetic tree analysis results confirmed that the virus was related to the Bosnia strain. We also performed next-generation sequencing, which confirmed the TBEV Siberian subtype. Continuous research and surveillance of TBEV in Kyrgyzstan are required to provide further information on tick-borne diseases.
... TBEV-Sib is mainly distributed in Siberia, though there are sites in Finland, while TBEV-FE is found in far eastern Asia and eastern Siberia. I. persulcatus is the main vector for both the latter types [6,7]. ...
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The tick-borne encephalitis virus (TBEV) is transmitted to humans through tick bites. In recent years, the appearance of the Siberian subtype of TBEV in Ixodes ricinus in Finland, together with deaths from the normally mild European subtype in the same country, have raised concerns about a possible spread of virulent variants of TBEV in Western Europe. Thus, there is a need to monitor the spread of strains, particularly of the European and Siberian subtypes. In this study, we develop a new real-time PCR method targeting Siberian and European subtypes of TBEV. The primers amplify a 176 bp fragment of the E gene, which is suitable for subsequent strain identification by Sanger sequencing. This study pioneers a new approach to primer design where the melting temperature (Tm) of primers annealed to representative mismatched target sequences is empirically determined and used to guide improvements in primer sequence. This allowed the range of TBEV strains detected to be extended to cover most European and Siberian strains tested, in addition to a strain of the Far-Eastern subtype. The limit of detection was 10–100 DNA copies per reaction and amplification efficiency varied between 83% and 94%, depending on the TBEV strain. Experimental determination of primer Tm proved to be a fruitful approach and will be a useful tool for future primer design and diagnostics.
... However, the highest incidence has been documented in the Baltic and Central European countries [127]. In addition, the indigenous occurrence of the infection in humans and animals, the isolation of the TBE virus from ticks, and the specific antibodies to the TBE virus detected in wild and domestic animals suggest an endemic TBE area [128]. The distribution areas of TBE range from the Bordeaux region of France in the west through Italy in the south and the Scandinavian Peninsula in the north to Siberia, China, and Japan in the east [129]. ...
... In the last two decades, an increase in TBE incidence has been observed in endemic areas but also the occurrence of sporadic cases outside endemic areas [130]. New endemic areas have been discovered in the Netherlands, England [11,131], South Korea [132], Mongolia, Denmark, high-altitude Kazakhstan, Kyrgyzstan, parts of Armenia, Azerbaijan, and Uzbekistan [128]. ...
... Second, TBE is travel-dependent and depends on the travel season and consumption of unpasteurized milk and milk products in endemic areas. Cases have been reported where the disease has been introduced to countries outside known endemic areas [128]. Approximately 1 to 2% of TBE cases are considered travel-related and pose an increased health risk to travelers [143]. ...
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Tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, can cause serious infection of the central nervous system in humans, resulting in potential neurological complications and fatal outcomes. TBEV is primarily transmitted to humans through infected tick bites, and the viral agent circulates between ticks and animals, such as deer and small mammals. The occurrence of the infection aligns with the seasonal activity of ticks. As no specific antiviral therapy exists for TBEV infection, treatment approaches primarily focus on symptomatic relief and support. Active immunization is highly effective, especially for individuals in endemic areas. The burden of TBEV infections is increasing, posing a growing health concern. Reported incidence rates rose from 0.4 to 0.9 cases per 100,000 people between 2015 and 2020. The Baltic and Central European countries have the highest incidence, but TBE is endemic across a wide geographic area. Various factors, including social and environmental aspects, improved medical awareness, and advanced diagnostics, have contributed to the observed increase. Diagnosing TBEV infection can be challenging due to the non-specific nature of the initial symptoms and potential co-infections. Accurate diagnosis is crucial for appropriate management, prevention of complications, and effective control measures. In this comprehensive review, we summarize the molecular structure of TBEV, its transmission and circulation in natural environments, the pathogenesis of TBEV infection, the epidemiology and global distribution of the virus, associated risk factors, clinical manifestations, and diagnostic approaches. By improving understanding of these aspects, we aim to enhance knowledge and promote strategies for timely and accurate diagnosis, appropriate management, and the implementation of effective control measures against TBEV infections.
... Lineages of closely related TBEV-EU genotypes were defined by selecting groups of tips whose last common ancestor was inferred to be earlier than 1960. These phylogenetic clades (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) are color-coded with the same color in the tree (a), in the boxplot (b), and on the Figure 1. (a) Dated phylogenetic tree of the analyzed TBEV-EU genotypes. ...
... Lineages of closely related TBEV-EU genotypes were defined by selecting groups of tips whose last common ancestor was inferred to be earlier than 1960. These phylogenetic clades (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) are color-coded with the same color in the tree (a), in the boxplot (b), and on the geographic map (c). Clade clusters (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) were inferred automatically. ...
... These phylogenetic clades (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) are color-coded with the same color in the tree (a), in the boxplot (b), and on the geographic map (c). Clade clusters (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) were inferred automatically. Clade 5 comprises solely an internal node and does not contain extant taxa. ...
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Tick-borne encephalitis (TBE) is an infectious disease of the central nervous system. The causative agent is the tick-borne encephalitis virus (TBEV), which is most commonly transmitted by tick bites, but which may also be transmitted through the consumption of raw dairy products or, in rare instances, via infected transfusions, transplants, or the slaughter of infected animals. The only effective preventive option is active immunization. Currently, two vaccines are available in Europe—Encepur® and FSME-IMMUN®. In Central, Eastern, and Northern Europe, isolated TBEV genotypes belong mainly to the European subtype (TBEV-EU). In this study, we investigated the ability of these two vaccines to induce neutralizing antibodies against a panel of diverse natural TBEV-EU isolates from TBE-endemic areas in southern Germany and in regions of neighboring countries. Sera of 33 donors vaccinated with either FSME-IMMUN®, Encepur®, or a mixture of both were tested against 16 TBEV-EU strains. Phylogenetic analysis of the TBEV-EU genomes revealed substantial genetic diversity and ancestry of the identified 13 genotypic clades. Although all sera were able to neutralize the TBEV-EU strains, there were significant differences among the various vaccination groups. The neutralization assays revealed that the vaccination using the two different vaccine brands significantly increased neutralization titers, decreased intra-serum variance, and reduced the inter-virus variation.
... While clusters of such cases continuously declined with the invention of milk pasteurization and overall improvements in hygiene management in cattle farming, goats and sheep flocks are still kept in traditional grazing farms where they are exposed to TBEV-infected ticks. 1,2 In other words, even in industrialized countries, consumption of raw milk products continues to be a risk factor to acquire a TBE infection. As society continues to exhibit a trend towards a preference for natural products (assuming consumers can afford these), alimentary TBEV infections may be observed more frequently in the future (see chapter 7). ...
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TBE can cause clinical symptomatic disease in dogs and horses Diagnosis of TBEV infection in animals is similar to diagnosis in humans Animals can be used as sentinels for human exposure
... Tick-borne encephalitis (TBE) is Poland's most common cause of viral encephalitis among central nervous system infections [1]. The course of the disease can make diagnosis difficult, given the non-specific symptoms that resemble other aseptic central nervous system (CNS) infections [2][3][4][5]. The first phase of the disease lasts 2-4 days and is characterised by influenza-like symptoms. ...
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Background Tick-borne encephalitis (TBE) is the most common viral central nervous system (CNS) infection in Poland. Previous research suggests that its incidence was underestimated in the pre-pandemic period. The COVID-19 pandemic caused a considerable burden on surveillance systems, which could further impact reporting.AimWe aimed to assess the completeness of reporting of TBE in the years 2008 to 2020 and explore the potential impact of the COVID-19 pandemic on reporting to the epidemiological surveillance system, compared with hospitalisations for TBEV and other viral neuro-infections.Methods We compared the Polish epidemiology of TBE and other viral infections of the CNS from national surveillance reports with data on hospitalisations from 2008 to 2020 and data from selected European countries.ResultsBetween 2008 and 2020, 3,016 TBE cases were reported to surveillance compared with 3,620 hospitalisations. There was an increasing trend in hospitalisations, while surveillance data demonstrated the opposite, with the largest discrepancy observed in the first pandemic year (354 hospitalisations vs 159 cases reported to surveillance). Serological testing for TBE was used more in the known endemic region of north-eastern Poland and less in non-endemic areas. Other European countries reported higher TBE case numbers and an increase during the COVID-19 pandemic, whereas Poland observed an opposite trend.Conclusion The sensitivity of TBE surveillance in Poland requires improvement. There are considerable regional differences. Regions that test for TBE intensively report most cases. Policymakers should be made aware of the value of quality epidemiological data for planning prophylactic measures in risk areas.
... Tick-borne encephalitis virus (TBEV), belonging to the genus Flavivirus within the family Flaviviridae, is considered to be the most relevant tick-borne pathogen in Eurasia causing tick-borne encephalitis (TBE) [1][2][3]. Since 2012, TBE has been a notifiable disease in the European Union (EU) [4], resulting in over 15,000 registered human cases with an increasing incidence in the EU and the European Economic Area (EEA) between 2016 and 2020, with the highest number of confirmed cases reported in Czechia, Lithuania, and Germany [5]. In the year 2020, over 700 human cases were seen in Germany. ...
... In addition, they serve as a virus reservoir through transstadial and transovarial transmission within tick populations [14]. The main natural mammalian hosts of TBEV are rodents, in particular, the bank vole (Clethrionomys glareolus) and the yellow-necked mouse (Apodemus flavicollis) [3,12]. In endemic areas, recent studies propose a long-lasting or persistent infection in rodents [15,16] and the possible transmission of TBEV to their offspring via maternal milk, as described in a human case study [17]. ...
... In experimentally TBEV-infected voles, the virus persisted for more than three months in multiple organs and for 50 days in the blood, analyzed with real-time polymerase chain reaction (RT-qPCR) [18]. Humans become infected with TBEV via tick bite, through the consumption of infected unpasteurized milk or such milk products, or, in rare cases, through organ transplants [3,19]. ...
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Tick-borne encephalitis (TBE) is Eurasia’s most important tick-borne viral disease. Rodents play an important role as natural hosts. Longitudinal studies on the dynamics of the seroprevalence rates in wild rodents in natural foci over the year are rare, and the dynamics of the transmission cycle still need to be understood. To better understand the infection dynamics, rodents were captured in a capture-mark-release-recapture-study in two natural foci in Bavaria, Germany, monthly from March 2019 to October 2022. Overall, 651 blood and thoracic lavage samples from 478 different wild rodents (Clethrionomys glareolus and Apodemus flavicollis) were analyzed for antibodies against tick-borne encephalitis virus (TBEV) by indirect immunofluorescence assay (IIFA) and confirmed using a serum neutralization test (SNT). Furthermore, a generalized linear mixed model (GLMM) analysis was performed to investigate ecological and individual factors for the probability of infection in rodents. Clethrionomys glareolus (19.4%) had a higher seroprevalence than A. flavicollis (10.5%). Within Cl. glareolus, more males (40.4%) than females (15.6%) were affected, and more adults (25.4%) than juveniles (9.8%). The probability of infection of rodents rather depends on factors such as species, sex, and age than on the study site of a natural focus, year, and season. The high incidence rates of rodents, particularly male adult bank voles, highlight their critical role in the transmission cycle of TBEV in a natural focus and demonstrate that serologically positive rodents can be reliably detected in a natural focus regardless of season or year. In addition, these data contribute to a better understanding of the TBEV cycle and thus could improve preventive strategies for human infections.
... Tick-borne encephalitis (TBE) is one of the most common tickborne diseases [1,2]. Approximately one third of human TBE infections are asymptomatic [3]. ...
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This study aimed to understand parental discourse about vaccination, and to provide guidance for communication that addresses the needs of parents. We analyzed parental discourse on child vaccination in general and tick-borne encephalitis (TBE) specifically in a Swiss parental online community. For this purpose, a data set containing 105k posts written by parents between 2007 and 2019 was analyzed using a combination of linguistic discourse analysis and qualitative content analysis. Results show that parents enter into a multidimensional decision-making process, characterized by elaborate practices of negotiation, consideration of vaccination recommendations as well as six distinct influencing thematic factors (vaccination safety, development and control, effectiveness, epidemiology, necessity, alternatives or additional prevention methods). The study shows a clear pattern of seasonality, with parents talking about TBE vaccination mostly triggered by events such as tick bites in spring and summer. From a public health perspective, the study emphasizes the need for sufficient, balanced, and tailored information about TBE vaccination. Online forums provide valuable information about what matters to parents and when, which can help public health authorities and practitioners provide information according to these concerns and enhance health literacy among parents.
... In line with the findings and ideas from Nosek et al. [21], to date, there is speculation over an evolving concept of various regional TBEV microfoci embedded in a larger defined natural focus. There are only scarce data or anecdotal reports [22] on the size and composition of such TBEV microfoci, notably the determinants of their size [23,24]. It can be assumed that the focus size of approximately 1ha is defined by the presence of the reservoir host, e.g., small rodents, and its biological operating range in such a habitat. ...
... In total, there were 30 different land cover types occurring at the 3575 control sampling points, while only eight different classes could be detected at the TBEV microfoci. Land-use types "vineyards" (15), "coniferous forest" (24), and "mixed forest" (25) were obviously overrepresented in the TBEV microfoci, whereas the types "discontinuous urban fabric" (02), "non-irrigated arable land" (12), "pastures" (18), and "broad-leaved forest" (23) were overrepresented at the control sampling points. The frequency of the land-use type "industrial or commercial units" (03) seemed to be more balanced. ...
... The machine-learning-based approach, called maximum entropy modeling, allowed for the calculation of a probability distribution resulting in a fine-grained prediction map (400 × 400 m). This spatial resolution approximates the biological concept of the microfoci embedded in larger natural foci very closely [21,24]. It is speculated that the microfocus size of approximately 1ha is defined by the presence of the vector, mainly Ixodes ricinus, the reservoir host, e.g., small rodents, and its biological operating range in such a habitat. ...
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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.