Tick-borne Encephalitis Endemic Areas Research Articles

The Prevalence of Asymptomatic Infections with Tick-Borne Encephalitis Virus and Attitude towards Tick-Borne Encephalitis Vaccine in the Endemic Area of Northeastern Poland.

In Poland, tick-borne encephalitis (TBE) vaccination rate is low despite high incidence of severe infections with TBE virus (TBEV). However, infection with TBEV can be asymptomatic or mild, which makes the total number of cases difficult to assess. We aimed at assessing asymptomatic TBEV infections and describing attitudes towards the TBE vaccine. We studied 298 healthy adult blood donors and 180 children from the TBE endemic area of northeastern Poland for the presence of anti-TBEV IgG antibodies. We also surveyed a separate cohort of 444 adults. Thirty-eight blood donors (13%) and 38 survey respondents (9%) reported a history of a prior anti-TBEV vaccination. Forty respondents (9%) reported vaccinating their child in the past. Fourteen unvaccinated blood donors (5%) and four children (2%) were seropositive for specific anti-TBEV antibodies, suggesting a history of an undiagnosed TBEV infection. In the surveyed cohort, 130 (32%) expressed their intention to be vaccinated and 144 (36%) expressed their intention to vaccinate their child. This intention was significantly higher in respondents with a recent tick-bite, a diagnosis of tick-borne disease in a close relative, and in males. Our study shows that asymptomatic TBEV infections are common. The acceptance of TBE vaccine is low, but might be increased by communicating risks associated with tick bites.

Food-Borne Transmission of Tick-Borne Encephalitis Virus-Spread, Consequences, and Prophylaxis.

Tick-borne encephalitis (TBE) is the most common viral neurological disease in Eurasia. It is usually transmitted via tick bites but can also occur through ingestion of TBEV-infected milk and dairy products. The present paper summarises the knowledge of the food-borne TBEV transmission and presents methods for the prevention of its spread. The incidence of milk-borne TBE outbreaks is recorded in central, eastern, and north-eastern Europe, where Ixodes ricinus, Ixodes persulcatus, and/or Dermacentor reticulatus ticks, i.e., the main vectors of TBEV, occur abundantly. The growing occurrence range and population size of these ticks increases the risk of infection of dairy animals, i.e., goats, sheep, and cows, with viruses transmitted by these ticks. Consumers of unpasteurised milk and dairy products purchased from local farms located in TBE endemic areas are the most vulnerable to alimentary TBEV infections. Familial infections with these viruses are frequently recorded, mainly in children. Food-transmitted TBE can be monophasic or biphasic, and some of its neurological and psychiatric symptoms may persist in patients for a long time. Alimentary TBEV infections can be effectively prevented by consumption of pasteurised milk and the use of TBEV vaccines. It is recommended that milk and dairy products should be checked for the presence of TBE viruses prior to distribution. Protection of dairy animals against tick attacks and education of humans regarding the epidemiology and prophylaxis of TBE are equally important.

IS THERE AN OUTBREAK OF TICK-BORNE ENCEPHALITIS IN PERNIK DISTRICT, BULGARIA? FOUR CASES REGISTERED FOR A PERIOD OF FOUR YEARS – CLINICAL MANIFESTATIONS AND EPIDEMIOLOGICAL RELATIONS

In Europe, the number of tick-borne encephalitis (TBE) cases has been increasing in the last decade, and the number of endemic areas has also been increasing. Bulgaria, located in southeastern Europe, is not in the TBE endemic area. However, sporadic TBE cases have been occasionally detected. The disease has a natural-focal nature, pronounced seasonality, with a vector- Ixodes ticks that transmit the infection from animals to humans. TBE is severe infection with specific lesions of the central nervous system (CNS), with residual phenomena and high lethality. The first cases of TBE in Pernik district were registered in 2015. The aim of the study is to consider clinical cases of TBE in Pernik district during period 2017-2020, to look for an epidemiological link between them and to monitor severity of the infection. We briefly present the most characteristic clinical and laboratory features of four laboratory confirmed cases of tick-borne encephalitis in the last 4 years. The mean age of all of the patients was 56. All four cases were observed in May, June, and July. They proceeded relatively smoothly with a favorable outcome, without paresis or paralysis of the limbs, without seizures or loss of consciousness. In the first case of computed tomography, no pathological changes in the brain were observed, while in the other three cases multiinfarction encephalopathy, evidence of initial cerebral edema and two porencephalic foci were found. Two of the patients had meningoradicular irritation with positive symptoms of Kerning, Brudzinski and Babinski, while in the other two patients these symptoms were absent. In all four cases there was a classic change in the hemogram: moderate leukocytosis with granulocytosis, and in the study of cerebrospinal fluid - a slight increase in total protein, moderate pleiocytosis and normal values of sugar and chloride. Only one of the patients was reported to be bitten by a tick, and the other three were most likely infected through food (raw goat's milk). Confirmed cases of TBE in Pernik district, although isolated, show that the virus is circulating in this region. This is facilitated by a number of factors: climate change, activity of the epizootic process in the tick population, different species of vertebrates in natural foci; presence of a large number of goats infected with viruses. Although cases of TBE have been reported only sporadically due to a lack of sufficient testing, TBE virus is circulating in Pernik district. Comprehensive measures are needed: through good awareness of clinicians, search for infection in patients with viral meningitis, increased screening of raw milk by the Bulgarian Food Safety Agency, future studies on ticks and farm animals for presence of TBE in this region. This study is a prerequisite for future research in this direction.

Low prevalence of tick-borne encephalitis virus antibodies in Norwegian blood donors

Background Tick-borne encephalitis (TBE) constitutes a public health concern in Europe. Certain coastal municipalities in southern Norway are considered TBE risk areas and in the last two years, there have been increasing numbers of TBE cases. Since the majority of infections are claimed to be asymptomatic, the aim of the current study was to assess the seroprevalence of antibodies to tick-borne encephalitis virus (TBEV) among unvaccinated adults living in a TBE endemic area in Norway. Methods One thousand one hundred and twenty-three blood donors living in Vestfold and Telemark county were included and associated sera were analysed for TBEV IgG antibodies. Information regarding tick bites, previous flavivirus exposure and knowledge regarding TBE and TBE prevention were obtained through a questionnaire. Results Fifty-eight samples were reactive by ELISA, of which 21 (36.2%) were confirmed by a TBEV-specific serum neutralization test. Of the 21 blood donors with neutralizing TBEV antibodies detected, 17 reported previous TBE vaccination. Thus, only four blood donors (0.4%) had TBEV neutralizing antibodies consistent with previously undergone TBEV infection. Regarding TBE awareness, half of the blood donors were familiar with TBE, but only 35% were aware of a preventive TBE vaccine. Conclusions Our study indicates low prevalence of subclinical TBEV infections among blood donors living in Vestfold and Telemark county and there is a lack of awareness among general public.

First Isolation and Phylogenetic Analyses of Tick-Borne Encephalitis Virus in Lower Saxony, Germany.

Tick-borne encephalitis (TBE) is the most important tick-borne arboviral disease in Europe. Presently, the main endemic regions in Germany are located in the southern half of the country. Although recently, sporadic human TBE cases were reported outside of these known endemic regions. The detection and characterization of invading TBE virus (TBEV) strains will considerably facilitate the surveillance and assessment of this important disease. In 2018, ticks were collected by flagging in several locations of the German federal state of Lower Saxony where TBEV-infections in humans (diagnosed clinical TBE disease or detection of TBEV antibodies) were reported previously. Ticks were pooled according to their developmental stage and tested for TBEV-RNA by RT-qPCR. Five of 730 (0.68%) pools from Ixodes spp. ticks collected in the areas of “Rauher Busch” and “Barsinghausen/Mooshuette” were found positive for TBEV-RNA. Phylogenetic analysis of the whole genomes and E gene sequences revealed a close relationship between the two TBEV isolates, which cluster with a TBEV strain from Poland isolated in 1971. This study provides first data on the phylogeny of TBEV in the German federal state of Lower Saxony, outside of the known TBE endemic areas of Germany. Our results support the hypothesis of an east-west invasion of TBEV strains in Western Europe.

Assessing natural herd immunity to tick-borne encephalitis in Republic Sakha (Yakutia)

Tick-borne encephalitis (TBE) is a natural focal viral neuroinfection vastly spread in the mid-latitude climate zone of theEurasia. Lethal cases and disability related to TBE determine its high epidemiological significance as well as underlie undiminished attention to prevent it in endemic territories. At the same time, TBE epidemiologic features significantly differ in various geographic areas. Importantly, Republic Sakha (Yakutia) is not among TBE endemic areas in theRussian Federation. However, in the last decade an increased incidence of ixodic tick bites was registered in the Republic Sakha. A pattern of pathogen-specific population immunity is one of the most valuable criteria for assessing magnitude of epidemic process in TBE foci. Hence, our study was aimed at assessing natural herd immunity TBEV in Republic Sakha associated with elevated incidence of tick bite visits. Here, we analyzed the data regarding the rate of tick attacks in the period of 2001–2007 in Republic Sakha. Residents and individuals unvaccinated against TBEV in the city ofYakutskas well as various administrative regions were examined to record the peak incidence of tick attacks. It was found that a range of the administrative regions recording with registered of ixodic tick attacks and elevated incidence of tick bites was expanded. Moreover, the top incidence of tick bites was annually recorded in the south regions of the republic Aldanian, Neryungri, Olyekminsk, Leninsk, Khangalassky districts, city ofYakutskand its suburbs. Furthermore, TBEV-specific immunoglobulins were detected in 5.7±0.68% of the residents examined suggesting about contacts with the pathogen. In addition, the peak count of seropositive people (8.9±1.85%) was identified in Namsky district located in the central part of the republic. Overall, detection rate of TBEV-specific antibodies among general adult population (6.9±0.95%) was significantly higher compared to those observed in children (3.9±0.89%, р 0.05). no significant differences in urban (5.8±1.12%) vs. rural population (5.63±0.84%) was found.

Continued expansion of tick-borne pathogens: Tick-borne encephalitis virus complex and Anaplasma phagocytophilum in Denmark

Tick-borne encephalitis virus (TBEV) is a tick-transmitted flavivirus within the tick-borne encephalitis (TBE) complex. The TBE complex is represented by both TBEV and louping ill virus (LIV) in Denmark. Anaplasma phagocytophilum is also transmitted by ticks and is believed to play an essential role in facilitating and aggravating LIV infection in sheep.This study aimed to describe the distribution of TBE complex viruses in Denmark, to establish the possible emergence of new foci and their association with the distribution of A. phagocytophilum. We performed a nationwide seroprevalence study of TBE complex viruses using roe deer (Capreolus capreolus) as sentinels and determined the prevalence of A. phagocytophilum in roe deer. Danish hunters obtained blood samples from roe deer during the hunting season of 2013-14. The samples were examined for TBEV-specific antibodies by virus neutralization tests (NT). A. phagocytophilum infection was assessed by specific real-time-PCR.The overall seroprevalence of the TBE complex viruses in roe deer was 6.9% (51/736). The positive samples were primarily obtained from a known TBE endemic foci and risk areas identified in previous sentinel studies. However, new TBE complex risk areas were also identified. The overall prevalence of A. phagocytophilum was 94.0% (173 PCR-positive of 184 roe deer), which is twice the rate observed ten years ago.These results point to an expansion of these tick-borne diseases geographically and within reservoir populations and, therefore, rationalize the use of sentinel models to monitor changes in transmission of tick-borne diseases and development of new risk areas. We found no association between TBE complex-positive roe deer and the prevalence of A. phagocytophilum, as almost all roe deer were infected. Based on our findings we encourage health care providers to be attentive to tick-borne illnesses such as TBE when treating patients with compatible symptoms.

Prevalence of antibodies against Tick-Borne Encephalitis virus in dogs from Saxony, Germany

Tick-borne encephalitis (TBE) is the most important tick-transmitted viral disease in Europe and is caused by the TBE virus (TBEV), a member of the Flaviviridae family. In Germany, the vast majority of human TBE cases occurs in the south in so-called risk areas. However, in areas with only sporadic TBE cases, the respective risk assessment is hard to achieve. We therefore intend to use the prevalence of antibodies against TBEV in dogs as an indicator to trace such TBE endemic areas. Between August 2012 and March 2014, a total of 331 blood sera were collected from dogs all over Saxony, which hadn't left the state for the past five years. For the detection of antibodies against TBE-virus a commercial ELISA was used. Ten sera with positive or borderline ELISA results were retested by serum neutralization test. All seven ELISA-positive serum samples could be verified to contain TBE-virus-specific antibodieswith SNT titres between 1:15 and more than 1:40. We therefore found 2.1% seroprevalence in our samples. We conclude, that dogs can very well be used as sentinels, especially in areas with only sporadic TBE cases, although larger sample sizes are desired.

Isolation and characterization of tick-borne encephalitis virus from Ixodes persulcatus in Mongolia in 2012

Tick-borne encephalitis virus (TBEV) is a zoonotic virus belonging to the genus Flavivirus, in the family Flaviviridae. The virus, which is endemic in Europe and northern parts of Asia, causes severe encephalitis. Tick-borne encephalitis (TBE) has been reported in Mongolia since the 1980s, but details about the biological characteristics of the endemic virus are lacking. In this study, 680 ticks (Ixodes persulcatus) were collected in Selenge aimag, northern Mongolia, in 2012. Nine Mongolian TBEV strains were isolated from tick homogenates. A sequence analysis of the envelope protein gene revealed that all isolates belonged to the Siberian subtype of TBEV. Two strains showed similar growth properties in cultured cells, but their virulence in mice differed. Whole genome sequencing revealed only thirteen amino acid differences between these Mongolian TBEV strains. Our results suggest that these naturally occurring amino acid mutations affected the pathogenicity of Mongolian TBEV. Our results may be an important platform for monitoring TBEV to evaluate the epidemiological risk in TBE endemic areas of Mongolia.

Review: Sentinels of tick-borne encephalitis risk

Tick-borne encephalitis (TBE) is a viral zoonotic disease endemic in many regions of Eurasia. The definition of TBE risk areas is complicated by the focal nature of the TBE virus transmission. Furthermore, vaccination may reduce case numbers and thus mask infection risk to unvaccinated persons. Therefore, additional risk indicators are sought to complement the current risk assessment solely based on human incidence. We reviewed studies published over the past ten years investigating potential new sentinels of TBE risk to understand the advantages and disadvantages of the various sentinel animal surveys and surrogate indicator methods. Virus prevalence in questing ticks is an unsuitable indicator of TBE infection risk as viral RNA is rarely detected even in large sample sizes collected at known TBE endemic areas. Seroprevalence in domestic animals, on the other hand, showed good spatial correlation with TBE incidence in humans and might also uncover presently unknown TBEV foci.

Predictors for diagnosis of tick-borne encephalitis infection in Poland, 2009–2010

Background: Tick-borne encephalitis (TBE) is a viral infection with no available treatment. Due to its non-specific symptoms, TBE tends to be under-diagnosed and under-reported. We aimed to identify factors predicting TBE diagnosis to develop a diagnostic algorithm for use by physicians. Methods: We conducted a case-control study using data routinely collected in Poland during 2009–2010. We included patients admitted to hospitals, who were assigned an International Classification of Disease (ICD) code indicating aseptic meningo-encephalitis. Cases were confirmed by detection of specific IgG and IgM antibodies. Patients that tested negative for TBE were included as controls. We used logistic regression to determine associations and recursive partitioning to build a diagnostic algorithm based on 70% of the dataset, and validated the algorithm using the remaining 30%. Results: Of 774 patients, 273 (35%) were TBE-positive. Cerebrospinal fluid protein levels and presence of a tick bite were key decision points in the algorithm, while living in a TBE endemic area was not important. Application of the algorithm to the validation dataset yielded a sensitivity of 89% and specificity of 37%. Conclusions: TBE should be included in routine diagnostic protocols for all cases admitted to hospitals with meningitis or encephalitis. However, in resource-limited settings and in regions with unknown TBE endemicity status, our algorithm could indicate which cases should be tested for TBE.

Emergence of tick-borne encephalitis in new endemic areas in Austria: 42 years of surveillance.

Human infections with tick-borne encephalitis (TBE)virus are a public health concern in certain regions of Europe, central and eastern Asia. Expansions of endemic areas and increased incidences have been associated with different factors including ecological changes supporting tick reproduction, socioeconomic changes increasing human outdoor activities and climatic changes favouring virus circulation in natural foci. Austria is among the most strongly affected countries in Central Europe, but the annual number of cases has strongly declined due to vaccination. Here,we have analysed changes of the incidence of TBE in the unvaccinated population of all federal states of Austria over a period of 42 years. The overall incidence in Austria has remained constant, but new strongly affected endemic regions have emerged in alpine valleys in the west of Austria. In parallel, the incidence in low-land regions in the north-east of the country is decreasing. There is no evidence for a shift to higher altitudes of infection sites in the traditional TBE zones,but the average altitudes of some newly established endemic areas in the west are significantly higher. Our analyses underscore the focal nature of TBE endemic areas and the potential of TBE virus to emerge in previously unaffected regions.

Tick-borne encephalitis 2010: Epidemiology, risk areas, and virus strains in Europe and Asia—An overview

Over the past decades, tick-borne encephalitis (TBE) has become a growing public health concern in Europe and Asia and is the most important viral tick-borne disease in Europe. It is also important in the Far East and in other parts of Asia. Vaccination can effectively prevent TBE. It is indicated for persons inhabiting or visiting a TBE endemic area who are likely to be exposed to tick bites. For this purpose, it is necessary to know where TBE virus (TBEV) occurs, where vectors are a potential hazard, and where as a consequence autochthonous TBE cases have been registered. Natural changes in the known TBE foci and the detection of new foci necessitate a summarizing data update to optimize the protection of inhabitants and visitors to TBE endemic areas. The present review includes an overview of the epidemiological data on TBE in Europe and Asia gathered between 1990 and 2009 and describes old and especially new TBE risk areas in Europe and Asia.

Reliable surveillance of tick-borne encephalitis in European countries is necessary to improve the quality of vaccine recommendations

In July–November 2009, 26 European Union (EU) Member States (MSs), Norway and Iceland, participated in a survey seeking information on national tick-borne encephalitis (TBE) vaccination recommendations. Information on TBE surveillance, methods used to ascertain endemic areas, vaccination recommendations, vaccine coverage and methods of monitoring of vaccine coverage were obtained. Sixteen countries (57%) reported presence of TBE endemic areas on their territory. Vaccination against TBE was recommended for the general population in 8 (28%) countries, for occupational risk groups – in 13 (46%) countries, and for tourists going abroad – in 22 (78%) countries. Although vaccination recommendations for country residents, and for tourists always referred to endemic areas, there was no uniform, standardized method used to define endemic areas. For this reason, clear recommendations for tourists need to be developed, and standardized surveillance directed to efficient assessment of TBE risk need to be implemented in European countries.

Seroprevalence of tick-borne encephalitis (TBE) in naturally exposed monkeys ( Macaca sylvanus) and sheep and prevalence of TBE virus in ticks in a TBE endemic area in Germany

In a recently published study, a clinical case of severe tick-borne encephalitis (TBE) in a monkey ( Macaca sylvanus) was described after natural exposure (tick bite) in a TBE endemic area in Germany, and from the tissue of this monkey the strain ‘Salem’, closely related to the strain ‘Neudoerfl’, was isolated and characterized. In this study, it was our aim to test all the available data for characterizing a TBE endemic area like TBE cases in humans and animals, TBE virus (TBEV) in ticks, and TBE-positive sera from animals. Sera from 283 monkeys and 100 sheep as well as 294 unfed ticks were collected at the monkey mountain Salem and its surroundings. A seroprevalence of 2.6% in monkeys and 9% in sheep were found. Furthermore, a new real-time RT-PCR method was established and used, in combination with an already published RT-qPCR, for TBEV genome detection in field-collected ticks, but no TBEV could be detected in the ticks tested.

Genetic characterisation of a tick-borne encephalitis virus isolated from the brain of a naturally exposed monkey ( Macaca sylvanus)

In a recently published case study, we have described a clinical case of severe tick-borne encephalitis (TBE) in a monkey ( Macaca sylvanus) after natural exposure (tick bite) in a TBE endemic area in Germany. Using histological, immunohistochemical, serological methods, and RT-PCR, the TBE virus infection was confirmed. Here, we describe the isolation of a TBE virus from the brain tissue in Vero-B4 cell cultures and the sequencing of the complete genome of that isolate. The isolated TBE virus strain (named ‘Salem’) is closely related to the Kumlinge strain or strain Neudoerfl, the prototype of the Central European TBE virus subtype. However, a total of 268 nt changes were found in comparison with TBE virus strain Neudoerfl resulting in 28 amino acid changes, none of which affecting any of the known or supposed functional regions of the viral genome. Further investigation of the distribution of viral antigen in brain tissue and characterisation of the host's inflammatory reactions by immunohistology revealed similarities between the course of the TBE virus infection in the macaque and acute to peracute cases of TBE in humans.

Tick infestation on roe deer in relation to geographic and remotely sensed climatic variables in a tick-borne encephalitis endemic area

Roe deer Capreolus capreolus are among the most important feeding hosts for the sheep tick Ixodes ricinus, thus contributing to the occurrence of tick-borne diseases in Europe. Tick-borne encephalitis (TBE), which is transmitted by co-feeding of larvae and nymphs on rodents, requires precise climatic conditions to occur. We used roe deer as sentinels for potential circulation of TBE virus in Northern Italy, by examining the association between tick infestation, occurrence of TBE human cases, geographical and climatic parameters. Tick infestation on roe deer, and particularly frequency of co-feeding, was clearly associated with the geographic location and the autumnal cooling rate. Consistently, TBE occurrence in humans was geographically related to co-feeding tick abundance. The surveillance of tick infestation on roe deer, combined with remotely sensed climatic data, could therefore be used as an inexpensive early risk assessment tool of favourable conditions for TBE emergence and persistence in humans.

Tickborne Meningoencephalitis, First Case after 19 Years in Northeastern Germany

Tickborne Meningoencephalitis, First Case after 19 Years in Northeastern Germany

A controlled trial of tick-borne encephalitis vaccination in patients with multiple sclerosis

The aim of this study was to investigate a possible link between a single vaccination against tick-borne encephalitis (TBE) and the appearance of one or more new cerebral lesions in magnetic resonance imaging (MRI) and/or a clinical relapse of MS. Fifteen MS patients with documented history of MS relapses living in a TBE endemic area were matched with 15 patients selected from a patient database containing 500 cases of MS. Three patients in each group were unvaccinated while all others had basic immunisation and regular booster vaccinations. Patients of the vaccination group received a single dose (3.3 μg) of a TBE vaccine. TBE antibodies were detected by ELISA and confirmed by neutralisation test. MRI was used as marker for disease activity and progression in addition to the clinical neurological examination. No association was seen between TBE vaccination and MRI detected disease activity, clinical relapse or disease progression of MS.

Prevalence of antibodies to Borrelia burgdorferi flagellin in Styrian blood donors

Lyme borreliosis and tick-borne encephalitis (TBE) are the most common diseases in Austria caused by tick bites. TBE endemic areas are well defined. It seemed to be of interest to compare prevalence data of antibodies against Borrelia burgdorferi (B.b.) to TBE endemic and non endemic areas. Blood samples (n = 1162) were obtained from healthy blood donors in combination with a standardized questionnaire during 21 excursions to 7 selected regions of Styria, Austria. Serum samples were screened for IgG antibodies against B.b. by a commercial flagellum ELISA. None of the tested persons showed symptoms of active Lyme borreliosis. A higher prevalence of antibodies against B.b. could be found in TBE endemic areas (7.7%) compared to TBE nonendemic areas (3.8%). There was a significant increase in positive antibodies against B.b. with age, exposure and number of tick bites remembered by test persons. The antibody prevalence to B.b. flagellin antigen is significantly higher in TBE endemic areas than in non-endemic comparative regions.