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Tick-borne encephalitis (TBE) and neuroborreliosis (NB) are well-known central nervous system (CNS) infections in children. Childhood tick-borne CNS infections are generally described as mild conditions. However, this view has recently been challenged, and the natural course, including potential sequelae, has been debated. If the diseases present with nonspecific symptoms and signs, some children may elude diagnosis. This study estimates the incidence of symptomatic tick-borne CNS infections in children under medical care and describes the spectrum of manifestations. One hundred twenty-four children with neurologic symptoms attending the Pediatric Emergency Department were included prospectively. Anti-TBE virus and anti- Borrelia serology results were analyzed together with inflammatory parameters in the blood and cerebrospinal fluid. Nearly one fourth of the children with neurologic symptoms were diagnosed with a tick-borne CNS infection (TBE, n = 10 [8%] and NB, n = 21 [16.8%]). In general, these children displayed an indistinct medical history and presented with nonspecific signs such as malaise/fatigue and headache. Diagnosis was based on analysis of acute and convalescent sera. Blood inflammatory parameters were nonspecific and did not contribute to the diagnostics. Conclusion: Pediatric tick-borne CNS infections are unexpectedly common and should be considered in children with unspecific and unexplained acute CNS-related symptoms. [ABSTRACT FROM AUTHOR]

Abstract: Information is scarce regarding the antibody response when TBE-vaccine booster doses are delayed, which is a common situation in daily life. We have investigated the immune response after a delayed booster dose compared to a normal booster interval in an every-day setting. Overall, 250/260 (96%) of the study participants had neutralizing antibodies post-booster, with no significant difference between normal and delayed booster intervals. Based on our findings we propose that healthy individuals who have failed adherence to the recommended schedule of TBE-vaccination can be given a delayed dose without concern of immunogenicity. [Copyright &y& Elsevier]

Abstract: Tick-borne encephalitis (TBE) is a potentially life-threatening disease in humans and is caused by a flavivirus spread by infected ticks (Ixodes ricinus and Ixodes persulcatus). TBE is endemic across much of Central and Eastern Europe and the incidence is increasing, with numbers estimated to be as many as 8755 cases per year. The reasons for this increase are multi-faceted and may involve improvements in diagnosis and reporting of TBE cases, increases in recreational activities in areas inhabited by infected ticks and changes in climatic conditions affecting tick habitats. Vaccination is the most effective method of preventing TBE; following a successful nationwide vaccination campaign in Austria, the annual number of TBE cases fell to about 10% of those reported in the pre-vaccination era. This report describes the findings of a group of leading experts from six Central and Eastern European countries who convened to discuss TBE in their region during the 28th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID) Nice, France, 4–8 May 2010. [Copyright &y& Elsevier]

Tick-borne encephalitis (TBE) is an emerging disease in Europe as in Poland, especially in north-eastern part of the country. The aim of the study was to characterize the epidemiology and clinical features of TBE in this region. Clinical and epidemiological data of 687 patients hospitalized between 1993 and 2008 at the Department of Infectious Diseases and Neuroinfections with the diagnosis of TBE were analysed. In the case of 59 patients (9.5%), the disease was job related (forestry workers, farmers). In the examined group, TBE presented with meningitis in 282 cases (41%), with meningoencephalitis in 353 cases (51.3%) and with meningoencephalomyelitis in 52 cases (7.6%). The most common neurological abnormalities were ataxia in 88 cases (14.17%) and pareses in 53 cases (8.53%). Four patients (0.6%) died, 144 patients (23.2%) were discharged with neurological sequelae of TBE. Two hundred and seventy-two patients (43.8%) required further psychiatric treatment. At least 38 patients (6.1%) developed long-term sequelae and required further hospitalizations. Dexamethasone in the dosage of 6-32 mg was administered in 407 patients for 1-64 days. The diagnosis of TBE sometimes is difficult as the disease symptoms may be non-characteristic. Therefore, a detailed anamnesis is very important in the process of TBE diagnosis and may alone justify lumbar puncture conduction. Despite usually mild course of the disease, patients may develop neurological and psychiatrical sequelae. Click for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Background: Over the past quarter century, the incidence of tick-borne encephalitis (TBE) has increased in most European nations. However, the number of humans stricken by the disease varies from year to year. A method for predicting major increases and decreases is needed. Methods: We assembled a 25-y database (1984--2008) of the number of human TBE victims and wildlife and climate data for the Stockholm region of Sweden, and used it to create easy-to-use mathematical models that predict increases and decreases in the number of humans stricken by TBE. Results: Our best model, which uses December precipitation and mink (Neovison vison, formerly Mustela vison) bagging figures, successfully predicted every major increase or decrease in TBE during the past quarter century, with a minimum of false alarms. However, this model was not efficient in predicting small increases and decreases. Conclusions: Predictions from our models can be used to determine when preventive and adaptive programmes should be implemented. For example, in years when the frequency of TBE in humans is predicted to be high, vector control could be intensified where infested ticks have a higher probability of encountering humans, such as at playgrounds, bathing lakes, barbecue areas and camping facilities. Because our models use only wildlife and climate data, they can be used even when the human population is vaccinated. Another advantage is that because our models employ data from previously-established databases, no additional funding for surveillance is required. [ABSTRACT FROM AUTHOR]

Abstract: Omsk hemorrhagic fever virus (OHFV) and Russian spring–summer encephalitis virus (RSSEV) are tick-borne flaviviruses that have close homology but different pathology and disease outcomes. Previously, we reported that C57BL/6 and BALB/c mice were excellent models to study the pathology and clinical signs of human RSSEV and OHFV infection. In the study described here, we found that RSSEV infection induced robust release of proinflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α) and chemokines (MCP-1, MIP-1β, RANTES and KC) in the brain at 9 and 11dpi, together with moderate to low Th1 and Th2 cytokines. In contrast, OHFV infection stimulated an early and prominent induction of IL-1α, TNF-α, IL-12p70, MCP-1, MIP-1α and MIP-1β in the spleen of infected mice. Collectively our data suggest that a differential host response to infection may lead to the alternate disease outcomes seen following OHFV or RSSEV infection. [ABSTRACT FROM AUTHOR]

Abstract: The electrical characteristics of tunnel barrier engineered charge trap flash (TBE-CTF) memory of MAHONOS (Metal/Al2O3/HfO2/SiO2/Si3N4/SiO2/Si) structure were investigated. The stack of SiO2/Si3N4/SiO2 films were used as engineered tunnel barrier, HfO2 and Al2O3 films were used as charge trap layer and blocking oxide layer, respectively. For comparison, the electrical characteristics of MONOS (Metal/SiO2/Si3N4/SiO2/Si), MONONOS (Metal/SiO2/Si3N4/SiO2/Si3N4/SiO2/Si), and MAHOS (Metal/Al2O3/HfO2/SiO2/Si) were also evaluated. The energy band diagram was designed by using the quantum-mechanical tunnel model (QM) and then the CTF memory devices were fabricated. As a result, the optimized thickness combination of MAHONOS structure was confirmed. The tunnel barrier engineered MAHONOS CTF memory showed a considerable enhancement of program/erase (P/E) speeds, retention time and endurance characteristics. [ABSTRACT FROM AUTHOR]

Abstract: Powassan virus (POWV, Flaviviridae: Flavivirus) is the sole North American member of the tick-borne encephalitis complex and consists of two distinct lineages that are maintained in ecologically discrete enzootic transmission cycles. The underlying genetic mechanisms that lead to niche partitioning in arboviruses are poorly understood. Therefore, intra- and interhost genetic diversity was analyzed to determine if POWV exists as a quasispecies in nature and quantify selective pressures within and between hosts. In contrast to previous reports for West Nile virus (WNV), significant intrahost genetic diversity was not observed. However, pN (0.238) and d N /d S ratios (0.092) for interhost diversity were similar to those of WNV. Combined, these data suggest that purifying selection and/or population bottlenecks constrain quasispecies diversity within ticks. These same selective and stochastic mechanisms appear to drive minor sequence changes between ticks. Moreover, Powassan virus populations seem not to be structured as quasispecies in naturally infected adult deer ticks. [Copyright &y& Elsevier]

Abstract: Two dose-finding studies and one open label safety study with a paediatric FSME-IMMUN® formulation were conducted in children and adolescents aged 1–15 years (N =3697). The 1.2μg antigen dose was identified as the optimal dose, inducing high seroconversion rates following the primary vaccination series. Adolescents (aged 12–15 years) vaccinated with the optimal paediatric dose (1.2μg) attained similarly high seroprotective rates to adults (aged 16–35 years) vaccinated with the 2.4μg formulation of FSME-IMMUN®. We concluded that the FSME-IMMUN® paediatric vaccine formulation is safe and highly immunogenic, not only for children <12 years, but also for adolescents <16 years. [Copyright &y& Elsevier]

Abstract: Tick-borne encephalitis (TBE) is the most important viral infection transmitted by ticks in Central Europe. In Germany, where TBE was classified as a notifiable disease in 2001, a highly variable number of clinically apparent human cases was reported in the last few years, ranging from the lowest number of 238 in 2007 to a maximum of 546 in 2006. The dynamics of the virus and its vector tick remain poorly understood. We investigated a highly active TBE focus in south-eastern Germany where from 2003 to 2008 a total of 9 clinical human cases was diagnosed. Three out of these 9 cases were fatal indicating an unusually high mortality rate possibly due to a highly virulent TBEV strain. From 2005 till 2008, 2150 Ixodes ricinus ticks were collected and tested for the presence of TBE virus. Five TBEV-positive ticks were detected by real-time RT-PCR. A viable virus strain was isolated from one of the positive ticks sampled in 2005. This is the first TBE virus isolate from a tick in Germany for 30 years. Sequencing of the full-length genome of this virus strain (AS33) revealed 2 unique amino acid substitutions in the envelope protein known to play a role in the pathogenicity of TBE virus. Amplification of the envelope gene using 2 TBEV-PCR-positive ticks from 2006 also showed these particular mutations indicating that this TBE virus strain was present in at least 2 consecutive years. The entire sampling area was divided into smaller sectors for the exact location of TBEV-positive ticks. Virus-positive ticks were found to be randomly distributed throughout the investigated focus, which is used as recreational area by the local people. [Copyright &y& Elsevier]

Abstract: Five and 6 years post-booster, immunity to tick-borne encephalitis (TBE) virus was assessed in 225 and 195 vaccinees, respectively, out of 430 healthy volunteers with at least three TBE-immunizations prior to study inclusion and booster intervals exceeding recommended limits. Neutralizing antibody titers of ≥1:10 (reliable level of protection) were present in 86–96% depending on age group, with lower percentages in participants >60 years. TBE antibody levels remained stable for many years in most vaccinees. However, in a few persons a shorter period of protection against TBE was indicated. Therefore, recommendations on booster intervals in TBE endemic areas should be adapted by weighting the risk of infection against the risk of short-lived immunity. [Copyright &y& Elsevier]

Tick-borne encephalitis (TBE) is endemic in several European countries, and its incidence has recently increased. Various factors may explain this phenomenon: social factors (changes in human behavior, duration and type of leisure activities and increased tourism in European high-risk areas), ecological factors (e.g., effects of climate change on the tick population and reservoir animals), and technological factors (improved diagnostics, increased medical awareness). Furthermore, the real burden of TBE is not completely known, as the performance of surveillance systems is suboptimal and cases of disease are under-reported in several areas. Given the potentially severe clinical course of the disease, the absence of any antiviral therapy, and the impossibility of interrupting the transmission of the virus in nature, vaccination is the mainstay of prevention and control. TBE vaccines are effective (protective effect of approximately 95% after completion of the basic vaccination—three doses) and well tolerated. However, their uptake in endemic areas is suboptimal. In the main endemic countries where vaccination is included in the national/regional immunization program (with reimbursed vaccination programs), this decision was driven by a cost-effectiveness assessment (CEA), which is a helpful tool in the decision-making process. All CEA studies conducted have demonstrated the cost-effectiveness of TBE vaccination. Unfortunately, CEA is still lacking in many endemic countries, including Italy. In the future, it will be necessary to fill this gap in order to introduce an effective vaccination strategy in endemic areas. Finally, raising awareness of TBE, its consequences and the benefit of vaccination is critical in order to increase vaccination coverage and reduce the burden of the disease. [ABSTRACT FROM AUTHOR]

Abstract: All cases of tick-borne encephalitis (TBE), which were recorded in the Tyrol (Austria) between 2000 and 2006, were investigated, in order to detect changes in incidence and endemicity, to identify particular risk groups, and to evaluate the indication for vaccination. Patients, who presented with an acute febrile illness, positive anti-TBE IgM and/or seroconversion, an at least two-fold increase of anti-TBE IgG or confirmation of TBE by the reference centre were questioned about previous vaccination, circumstances and possible places of infection, outdoor activities, and changes in their personal risk of infection. Sixty-one cases of TBE (among them 2 imported cases) were identified between January 2000 and December 2006, yielding an average annual incidence of 5.8 cases for 2000–2004 and 16 cases for 2005–2006. This increase was largely due to patients >60 years of age who had never been vaccinated against TBE. In 2005–2006, there was an increase in case fatality rates, admission to intensive care units, and duration of intensive care. During 2005 and 2006, new endemic areas were identified upstream the valleys of Inn and Isel, and there is evidence of a rise of new foci within the known endemic areas. Possible reasons for this development include climatic factors like a lower saturation deficit in August than in comparative years. Vaccination strategies should be focused on patients >60 years of age without previous vaccination who are convinced that sticking to the habits of a lifetime offers sufficient protection against TBE. [Copyright &y& Elsevier]

Background: Tick-borne encephalitis in children appears to be more benign than in adults and shows also a more favourable outcome. Only some authors report of sequelae like paralysis, paresis or seizures and behavioural abnormalities. The aim was to describe the clinical features of tick-borne encephalitis in children with special attention to sequelae and to review the literature. Methods: Retrospective review of all charts of children with serologically confirmed tick-borne encephalitis hospitalised in Styria between 1981 and 2005. Results: One hundred sixteen children were diagnosed with tick-borne encephalitis. Ninety-two children (79.3%) developed meningitis and 24 (20.7%) meningoencephalitis. Eleven patients with meningoencephalitis showed somnolence, 5 confusion, 5 tremors, 2 facial palsy, 1 ataxia, 1 epileptic seizure and 1 hemi paresis. Seven patients had to be admitted to the intensive care unit. Two children (1.7%) developed long time neurological sequelae: one epileptic seizure with requirement of antiepileptic therapy and one left-sided hemi paresis. One hundred twelve children had been not and 3 incompletely vaccinated against tick-borne encephalitis. Only one child had been fully vaccinated according to the Austrian vaccination schedule. Conclusion: Our study provides further evidence that tick-borne encephalitis in children has a substantial morbidity and in single cases severe long-time neurological sequelae are observed. [ABSTRACT FROM AUTHOR]

Summary: If a person suffers a tick bite in tick-borne encephalitis (TBE) endemic areas, there is uncertainty on post-exposure treatment of naϊve (non-immune) persons in order to protect the patient against TBE. Particularly, there are no distinct positions on the use of TBE active immunization as post-exposure treatment. Of special concern is the possibility of antibody-dependent enhancement of infection and exacerbation of disease in case of post-exposure vaccination. Such phenomena have been reported for other flavivirus infections. In the past, immune globulin treatment was recommended, but these preparations are no longer available. Active immunization by using the current immunization schedules after a tick bite will not result in appropriate neutralizing antibody concentrations within due time. Based on the assumptions that vaccination is not quick acting enough after a tick bite and that the theoretical risk of antibody-dependent enhancement cannot be excluded, no vaccination or other specific measure is currently recommended after a tick bite in non-vaccinated patients, leaving the patient in a completely dissatisfactory position. A risk/benefit analysis has been re-assessed for persons with a history with at least one vaccine injection, certain patient groups and in relation to the vaccination schedule which has been used and to the geographic area where the tick bite has occurred. In order to evaluate the value of the vaccine for post-exposure immunization, new immunization schedules have to be evaluated with respect to their capacity to induce antibodies more quickly. [Copyright &y& Elsevier]

Summary: This is a case report on a 50-year-old patient, working as a forest guard in a high-endemic region. The subject was immunized with two doses of FSME Immun 0.5 Baxter vaccine (with a time interval of 18 days between the two doses). Approx. two months after the second vaccination the subject developed symptoms of Tick-borne encephalitis. Clinical course and laboratory findings confirmed diagnosis of meningo-encephalo-myelitis with moderate sequelae 1 year after infection. Based on this clinical case we recommend in subjects with an accumulation of risk factors, as age older than 50 years who are living and working in high-endemic areas, a vaccination with conventional schedule (at least two doses applied at 0 to 1–3 months) ahead of TBE season or a rapid schedule with three doses (0, 7 and 21 days) of vaccine. [Copyright &y& Elsevier]

Abstract: Tick-borne encephalitis (TBE) is caused by an arthropod-borne virus, belonging to the family of Flaviviridae. In case of disease, which can lead to neurological sequelae or even fatal outcomes, only symptomatic treatment is available. TBE can be prevented by vaccination. Various primary immunization schedules have been developed. To identify the most suitable schedule, the present randomised, controlled study was designed to provide data on the immune response elicited by four different immunization schedules obtained by ELISA and by neutralization test (NT). A total of 398 healthy subjects aged ≥12 years were randomised to vaccination according to either the rapid schedule (Group R, vaccination on days 0, 7 and 21), the conventional schedule (Group C, vaccination on days 0, 28 and 300), the modified conventional schedule (Group M, vaccination on days 0, 21 and 300) or the accelerated conventional schedule (Group A, vaccination on days 0, 14 and 300). Within 3 weeks (i.e. by day 21) antibody levels were higher in Group R and Group A than in Group M and Group C. Group R and Group C both had higher titres on days 42, 180 and 300, than Group A and Group M. The rapid schedule thus combines the advantages of fast protection and of high titres over the observation period of 300 days. [Copyright &y& Elsevier]

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Deer support high tick intensities, perpetuating tick populations, but they do not support tick-borne pathogen transmission, so are dilution hosts. We test the hypothesis that absence of deer (loss of a dilution host) will result in either an increase or a reduction in tick density, and that the outcome is scale dependent. We use a complementary methodological approach starting with meta-analysis, followed up by a field experiment. Meta-analysis indicated that larger deer exclosures reduce questing (host-seeking) tick density, but as the exclosure becomes smaller (<2.5 ha) the questing tick density is increased (amplified). To determine the consequences for tick-borne pathogen transmission we carried out a field experiment, comparing the intensity of ticks that fed on hosts competent for tick-borne pathogen transmission (rodents) in two small (<1 ha) deer exclosures and their replicated controls. Intensity of larval ticks on rodents was not significantly different between treatments, but nymph intensity, the tick stage responsible for tick-borne encephalitis (TBE) transmission, was higher in deer exclosures. TBE seropositive rodents were found in a deer exclosure but not in the controls. We propose that localized absence of deer (loss of a dilution host) increases tick feeding on rodents, leading to the potential for tick-borne disease hotspots. [ABSTRACT FROM AUTHOR]

Abstract: Tick-borne encephalitis can be prevented by active immunization, for which different schedules and booster recommendations exist. However, recommended booster intervals are often exceeded. In the present study, 178 adults aged 18–81 years received the first booster dose 2–11 years after primary immunization (instead of 12–18 months as recommended) according to the rapid schedule (vaccination on days 0, 7, and 21). The booster dose was well tolerated. All subjects showed a typical anamnestic response with an 11-fold increase in the geometric mean titre as measured both by neutralization test and ELISA. [Copyright &y& Elsevier]

Abstract: In Western Siberia, tick-borne encephalitis (TBE) morbidity among residents of all ages and social groups has remained high over many years. The frequency of tick bites is high, and 2.6–5.7% of bitten persons are hospitalized each year because of suspected TBE infection. According to official statistical data, children <14 years account for 20–30% of TBE cases. Adult, working-age people (20–49 years) are at highest risk of infection. TBE may progress in a febrile, meningeal, or focal (paralytic) form, becoming chronic in 1–1.7% of cases. Severe progression and fatal outcomes of the disease have been recorded in all age groups. Over the past 20 years, mortality varied from 1.8% to 3%, increasing in periods of high TBE morbidity. This data stresses the necessity for more effective measures aimed at preventing TBE infection in the region. The results of our analyses of TBE peculiarities in Western Siberia lead to the conclusion that people in that region have been at high risk of infection and developing the most complicated forms of TBE. [Copyright &y& Elsevier]

Abstract: As early as in the 1960s, Professor M.P. Chumakov suggested that primary tick-borne encephalitis (TBE) diagnoses made by practicing physicians should be verified by serological or virological methods. Verification showed that a large proportion of TBE cases (included in the official statistics of TBE morbidity) was accounted for by the so-called seronegative forms of the disease. Ixodid tick-borne borrelioses (ITBBs), or infections of the Lyme borreliosis group, which proved to be sympatric to TBE in Russia accounted for an even higher morbidity in past years. Some other tick-borne diseases were still unknown at that time. We analyzed 1062 case histories of patients with febrile diseases acquired through tick bites in the Udmurt Republic, Russia (one of the most hazardous regions with respect to TBE morbidity), recorded from 1965 to 1968, and 1509 similar cases recorded from 1983 to 1988. In the first period, 97 out of 684 cases (14.2%) included in the official statistics of TBE morbidity could be classified as ITBB according to modern case criteria. In the second period, 464 out of 1509 cases recorded as TBE (30.7%) were retrospectively diagnosed as ITBB. No specific diagnosis could be made in 7–17% of the total number of cases interpreted as ‘tick-borne’ diseases. A similar situation existed in other regions of Russia before 1996 and, as a consequence, the official parameters of annual TBE morbidity in different periods were overestimated by a factor of 1.2–1.6. Here, the long-term dynamics of TBE morbidity in Russia are presented as they appear according to official data and after correction with regard to estimations. [Copyright &y& Elsevier]

Abstract: Five hundred and forty-five serum samples from donors from various parts of Mongolia were investigated for antibodies against the tick-borne encephalitis (TBE) virus, Borrelia burgdorferi, and Anaplasma phagocytophilum. Seroprevalence against TBE was 5.1% in the province of Selenge and 0.9% in Bulgan province, seroprevalence against B. burgdorferi was 1.9% in Selenge province and Bulgan province, 13.9% in Dornogov province, and 3.0% in Tov province and Ulaanbaatar. Seroprevalence against A. phagocytophilum was 2.3% in Selenge province, 5.6% in Bulgan province, 2.8% in Dornogov province, and 3.0% in Tov province and Ulaanbaatar. We conclude that all three pathogens are endemic in Mongolia. [Copyright &y& Elsevier]

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Tick borne encephalitis virus (TBEV), is a human flavivirus causing tick borne encephalitis (TBE), a viral infection of the central nervous system endemic in Europe and Asia. Objectives: To develop a reverse transcription polymerase chain reaction (RT-PCR) assay based on quantitative real-time RT-PCR technology (TaqMan) for detection and quantification of TBEV RNA. The test includes an internal control (IC) to avoid false negative results. Study design: The system was established and validated using wild-type (WT) non-infectious synthetic RNA representing a fragment of the 3′ non-coding region of the TBEV genome. In addition, synthetic RNA differing from the WT synthetic RNA by a unique probe binding region was used as IC to monitor the overall efficiency of the RT-PCR. Results: The analytical sensitivity of the assay was at least ten copies of the TBEV synthetic transcript in presence of 50 copies of the IC. Successful amplification was obtained for different strains within the TBEV complex (Hypr, Hochosterwitz, Laibach, Elsass=Alsace, ZZ9, Wladiwostok). Among 14 serum and 21 cerebrospinal fluid (CSF) samples obtained from 28 patients with clinical suspicion of TBEV 1 CSF sample tested positive for TBEV RNA. In addition, no TBEV RNA could be detected in blood samples obtained from three vaccinated people 1 and 3 days post-vaccination. Thus indicating that a positive result is unlikely to be caused by recent vaccination. Conclusions: A quantitative, highly sensitive and specific real-time RT-PCR assay has been developed for the detection of TBEV RNA. Inclusion of an IC is important to monitor the possible occurrence of false-negative results caused by the presence of inhibitory factors. This assay should be an important asset for the routine laboratory detection of TBEV RNA. [Copyright &y& Elsevier]

As microfluidic technologies mature, increasingly complex solutions are employed, and accurate methods for the measurement of electroosmotic flow rates are becoming increasingly important. The methodologies of both a direct method and an indirect method of flow rate measurement are presented here. The direct method involves flow visualization using trace amounts of a caged fluorescent dye. The indirect method is based on the change in current that occurs when one solution in the microchannel is replaced by another. The results of concurrent and independent measurements of electroosmotic velocities of Tris–acetate with EDTA (TAE) and Tris–borate with EDTA (TBE) at 1× concentration in fused silica capillaries are presented. Although these buffers are commonly used in biological chemistry, these mobilities have not previously been reported. Strong agreement among data collected with both methods establishes confidence in the electroosmotic mobility values obtained and indicates that the current-based method, which requires less infrastructure than the direct method, can provide accurate flow rate measurements under these conditions. Constant electroosmotic mobilities of 4.90×10−8 m2 V−1 s−1 for TAE and 3.10×10−8 m2 V−1 s−1 for TBE were determined by tests in a range of electrical field strengths from 5 to 20 kV/m. A linear flow rate increase with applied field strength indicated that constant mobility and negligible Joule heating effects were present. Applicability and limitations of both the measurement methods and these buffers are discussed in the context of microfluidic applications. [Copyright &y& Elsevier]

Abstract: Tick-borne encephalitis virus (TBEV) has been endemic in many countries in central, northern and eastern Europe. More than 3000 human cases are reported annually, the Baltic states included. TBEV causes CNS infections presented as meningitis or meningoencephalitis with or without myelitis. The case fatality rate in Europe is approximately 0.5%, and up to 40% of the patients are left with long-lasting sequelae. The endemicity of TBE in Sweden has been stable over the years but during the last decade several new foci have been discovered. In Norway the first verified cases of TBE have now been found. The reason for this changing epidemiology of TBE is discussed. [Copyright &y& Elsevier]

Abstract: To give information about the situation in Switzerland and especially in the canton Thurgau. Tick-borne encephalitis (TBE) in Switzerland has to be reported to official bodies, such as the Cantonal Office of Health and the Swiss Federal Office of Public Health. The registered cases are published weekly in the Bulletin of the Swiss Federal Office of Public Health. A map with geographical sites of infection has been published by the Swiss Federal Office of Public Health from time to time. In addition we collect epidemiological data in our diagnostic setting servicing part of eastern Switzerland. The situation of every patient diagnosed in our laboratory is followed up by a questionnaire. Some data derive from an epidemiological study conducted by and from another study conducted in the principality of Liechtenstein (). The data of a more recent publication are also included (Schwanda et al., 2000). More historical data are taken from . Recently, the global positioning system (GPS) connected to a laptop computer containing a geographical map on CD-ROM was used for better determination of possible TBE microfoci. TBE is endemic in areas of northern Switzerland and the principality of Liechtenstein. The number of reported new infections in Switzerland per year ranges between 60 and 120 cases, most of them with neurological manifestations. This represents an incidence of 0.5–1.5 per 100,000 inhabitants per year. In the last 10 years a prominent increase of the number of reported cases occurred in Switzerland, namely from 30–70 cases per year to 60–120 cases per year. This increase was mainly caused by the emergence of TBE in the cantons of Thurgau, Aargau and St. Gallen, all localised in the north-eastern part of Switzerland. The canton Thurgau became the most dangerous region in Switzerland for TBE during the last ten years. Besides the known endemic areas of the regions of Schaffhausen, Thun and Biel-Ins, a number of additional foci have been detected during the last 20 years. These are situated, for instance, around the lake of Zurich or in the region of Chur. In the canton Thurgau, new cases could be located east of the formerly known foci. Besides the larger epidemic areas known there are several TBE virus microfoci in Switzerland and more microfoci are still recognized. Despite active vaccination of persons at risk the incidence of reported TBE cases has increased during the last 20 years, now being between 60 and 120 cases per year, some of them with a severe and prolonged course. No TBE foci have been recognized in western und southern Switzerland so far. From our observations we have got the impression that real new TBE foci are emerging in some regions of eastern Switzerland. [Copyright &y& Elsevier]

Objective: To estimate effectiveness of tickborne encephalitis (TBE) vaccination by time interval (<5, 5-10 and 10+years) postvaccination., Design: A retrospective, matched case-control study PARTICIPANTS: Cases-all adult (age 18-79) TBE cases in Switzerland reported via the national mandatory disease reporting surveillance system from 2006 to 2020 (final n=1868). Controls-community controls from a database of randomly selected adults (age 18-79) participating in a 2018 cross-sectional study of TBE vaccination in Switzerland (final n=4625)., Primary Outcome Measures: For cases and controls, the number of TBE vaccine doses received and the time since last vaccination were determined. Individuals were classified as being 'unvaccinated' (0 doses), 'incomplete' (1-2 doses) or 'complete' (3+ doses). Individuals with 'complete' vaccination were further classified by time since the last dose was received (<5 years, 5-10 years or 10+ years). A conditional logistic regression model was used to calculate vaccine effectiveness (VE: 100 × [1-OR]) for each vaccination status category., Results: VE for incomplete vaccination was 76.8% (95% CI 69.0% to 82.6%). For complete vaccination, overall VE was 95.0% (95% CI 93.5% to 96.1%). When the most recent dose was received <5 years prior VE was 91.6% (95% CI 88.4% to 94.0%), 95.2% (95% CI 92.4% to 97.0%) when the most recent dose was received 5-10 years prior, and 98.5% (95% CI 96.8% to 99.2%) when the most recent dose was received 10+ years prior., Conclusions: That VE does not decrease among completely vaccinated individuals over 10+ years since last vaccination supports the longevity of the protective response following complete TBE vaccination. Our findings support the effectiveness of 10-year TBE booster intervals currently used in Switzerland., Competing Interests: Competing interests: The authors declare no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Tick-borne encephalitis (TBE) is a vaccine-preventable disease which may cause long-term sequelae and even death. The data on the long-term effectiveness of TBE vaccines are limited. Additionally, the vaccination schedule is complex which in part contributes towards sub-optimal uptake in TBE-endemic areas. The current ecological study measures vaccine effectiveness (VE) in two European countries., Methods: TBE VE was measured from 2007 to 2018 in Latvia and Southern German states by age group, vaccination history, and schedule compliance. TBE cases and vaccination history were obtained from the public health agencies for Latvia and the southern German federal states of Bavaria and Baden-Wuerttemberg. Cases were "within schedule" if a TBE infection was diagnosed within the time interval preceding the next scheduled dose and "outside schedule" if the diagnosis occurred after the next scheduled dose. Vaccine uptake was estimated via representative nationwide surveys., Results: VE after 2, 3, and ≥4 doses was high in both countries at 97.2%, 95.0%, and 95.4% for southern Germany, and 98.1%, 99.4%, and 98.8% for Latvia while within- schedule, and only showed marginal differences outside schedule at 90.6%, 89.9%, and 95.6% for southern Germany, and 97.4%, 98.4%, and 99.0% for Latvia regardless of age groups., Conclusions: In both countries, VE after two and three primary doses within-schedule was very high in all age groups. Once receiving booster doses, high VE continued to be observed even in persons with extended intervals since the last dose received, suggesting that longer and more flexible booster intervals may be considered for sustainable long-term protection., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: WE, FK, LJ, and HJS are full time employees of Pfizer Vaccines and may hold stock or stock options., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tick-borne encephalitis (TBE) is one of the most important infectious diseases of the central nervous system in dogs from endemic areas. While in humans survival rate and long-term outcomes are well described, these data are lacking in veterinary literature. The aim of the present paper is to characterize the clinical aspects of TBE and to investigate fatality rate, long-term outcome and the long-term neurological sequelae in a population of dogs infected with TBE. We performed a retrospective analysis of 54 dogs diagnosed with TBE at the veterinary hospital of the University of Zurich between 1999 and 2016. Medical data such as signalment, clinical presentation, results of diagnostic procedures, treatment and outcome were collected and analyzed. Statistical analysis including a cox proportional hazard model using a backward stepwise regression approach was performed. In 62% of the TBE cases unspecific signs were described before the onset of neurological signs, resembling a biphasic appearance that is well known in human TBE. Case fatality rate was 33% and all dogs died within the first 4 months after diagnosis. Long-term neurological sequalae were detected in 17% of the TBE cases. For each day of clinical signs before hospital entry the odds of sequalae increased by a factor of 1.88 (CI 1.04-3.15). Older dogs and dogs presented with seizure activity had an increased hazard risk of death (Hazard ration = 1.2, p = 0.03; and 9.38, p = 0.001, respectively). In conclusion, despite TBE being a life-threatening disease with severe clinical signs, the survival rate in our study was 67%. However, long-term sequalae can be of concern especially in dogs with longer clinical course., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kleeb, Golini, Beckmann, Torgerson and Steffen.)

• Travelers in TBE endemic areas should be proactive when found to be tick exposed. • Medical doctors should consider travel history and tick exposure of their patients. • Detached ticks and traveler's blood should be tested for the presence of TBEV. Although travel-related tick-borne encephalitis (TBE) cases have been increasingly registered worldwide, very few published case studies are available to date. The present report describes a travel-related TBE case and provides genotypic characterization of two viral isolates. Laboratory diagnostics were based on complement fixation test and virus isolation. This report is unique because the TBE case was first confirmed by virus isolation from the engorged tick and only later from the patient's blood. Moreover, this case demonstrated a successful prophylaxis performed on day 8 post tick exposure although it is generally recommended that anti-TBEV immunoglobulins should be administered not later than on day 4 after tick bite. Sequences of E protein gene fragments were used to phylogenetically characterize the two isolates. The results demonstrated that both viral isolates belonged to clusteron 3A (Zausaev group) of the Asian lineage of the TBEV Siberian subtype. The synonymous nucleotide substitution, C351 T, was identified in E protein gene fragments of TBEV 88 and TBEV 89, which could have been induced by virus transmission. A few important take-home messages can be gleaned from the reported case. First, travelers should be aware of TBE endemic areas that they plan to visit and be proactive when exposed to Ixodes ticks. Second, medical practitioners should always consider travel history and potential tick exposure of patients. Lastly, engorged Ixodes spp. ticks removed from the patients, who have arrived from endemic areas, should be tested for TBEV even in the absence of TBE clinical signs. [ABSTRACT FROM AUTHOR]

During spring and autumn 2001, we screened 13,260 migrating birds at Ottenby Bird Observatory, Sweden, and found 3.4% were infested with ticks. Four birds, each a different passerine species, carried tickborne encephalitis virus (TBEV)–infected ticks (Ixodes ricinus). Migrating birds may play a role in the geographic dispersal of TBEV-infected ticks.

Various animal species have been evaluated in depth for their potential as Tick-borne encephalitis virus (TBEV) sentinel species, although evidence for equine capacity is incomplete. Therefore, a comprehensive cross-sectional stratified serosurvey and PCR analysis of selected horses (n = 301) were performed in TBEV endemic localities in Lithuania. Attached and moving ticks (n = 241) have been collected from aforementioned hosts to evaluate natural infectivity of TBEV vectors (Ixodes spp.) in the recreational environments surrounding equestrian centers. All samples were screened for TBEV IgG and positive samples were confirmed by virus neutralization test (VNT). 113 (37.5%) horses from all counties of Lithuania tested positive for TBEV IgG, revealing age and sex indifferent results of equine seroprevalence that were significantly dependent on pedigree: horses of mixed breed were more susceptible to infection possibly due to their management practices. TBEV prevalence in equine species corresponded to TBEV-confirmed human cases in the precedent year. As much as 3.9% of horses were viraemic with TBEV-RNA with subsequent confirmation of TBEV European subtype. 4/38 of tested tick pools were positive for TBEV-RNA (Minimal infectious rate 1.2%). Several unknown microfoci were revealed during the study indicating areas of extreme risk close to popular human entertainment sites. The study provides important evidence in favor of horses' usage as sentinel species, as equines could provide more detailed epidemiological mapping of TBEV, as well as more efficient collection of ticks for surveillance studies. [ABSTRACT FROM AUTHOR]

Abstract: The 15th Meeting of the International Scientific Working Group on Tick-Borne Encephalitis (ISW-TBE) – a group of neurologists, general practicioners, clinicians, travel physicans, virologists, pediatricians, and epidemiologists – was held under the title “Tick-Borne Encephalitis – a notifiable disease”. With the inclusion of TBE in the list of notifiable diseases, an important measure was established to continue improving the level of evidence on TBE in Europe to better help guide policies and methods to lower the burden of this disease. Due to differences in diagnosis, case definition, and reporting in European countries, the overall epidemiology and burden of TBE remains unclear. During the meeting, important issues regarding epidemiology, risk areas, vaccination rates, and latest news on vaccination were presented and extensively discussed. A poster session provided an overview of the epidemiological situation 2012 in 13 European countries. [Copyright &y& Elsevier]

The article focuses on the significance of tick-borne encephalitis (TBE) in young children. A study was conducted in 19 children which showed that after TBE the children performed worse in neuropsychological testing, and electroencephalograms (EEGs) were more often abnormal. All children were considered to be fully recovered by their parents. In highly endemic areas, like Austria, before a broad TBE vaccination level was reached, the age-related incidence was different with a high incidence also in children, especially in the age group between 7 and 14 years of age. Same pattern was also reported from highly endemic areas in Russia.

Tick-borne encephalitis (TBE) is one of the most important viral zoonosis caused by a neurotropic arbovirus (TBEV). In Germany, TBE is classified as a notifiable disease with an average of 350 autochthonous human cases annually. The incidence-based risk assessment in Germany came under criticism because every year, a number of autochthonous human TBE cases have been detected outside of the official risk areas. Therefore, it is necessary to find additional parameters to strengthen TBEV surveillance. The aim of this study was to examine red foxes as sentinels for TBE. Thus far, there are no published data about the sensitivity and specificity for serological methods testing fox samples. Hence, we aimed to define a system for the screening of TBEV-specific antibodies in red foxes. A total of 1233 fox sera were collected and examined by ELISA and IIFA and confirmed by micro-NT. The overall seroprevalence of antibodies against TBEV in red foxes from Germany confirmed by micro-NT was 21.1%. The seroprevalence differed significantly between risk (30.5%) and non-risk areas (13.1%), with good correlations to local TBE incidence in humans. In conclusion, serological monitoring of red foxes represents a promising surrogate marker system and may even determine unexpected TBEV foci in regions currently regarded as non-risk areas. [ABSTRACT FROM AUTHOR]

Tick-borne encephalitis (TBE) is increasing in Europe. We aimed to evaluate the immunogenicity and safety of TBE-vaccination. This systematic review was registered at PROSPERO (#CRD42020155737) and conducted in accordance with PRISMA guidelines. We searched CINAHL, Cochrane, Embase, PubMed, and Scopus using specific terms. Original articles, case reports and research abstracts in English, French, German and Italian were included for screening and extracting (JER; PS). Of a total of 2464 records, 49 original research publications were evaluated for immunogenicity and safety. TBE-vaccines showed adequate immunogenicity, good safety and interchangeability in adults and children with some differences in long-term protection (Seropositivity in 90.6–100% after primary vaccination; 84.9%–99.4% at 5 year follow up). Primary conventional vaccination schedule (days 0, 28, and 300) demonstrated the best immunogenic results (99–100% of seropositivity). Mixed brand primary vaccination presented adequate safety and immunogenicity with some exceptions. After booster follow-ups, accelerated conventional and rapid vaccination schedules were shown to be comparable in terms of immunogenicity and safety. First booster vaccinations five years after primary vaccination were protective in adults aged <50 years, leading to protective antibody levels from at least 5 years up to 10 years after booster vaccination. In older vaccinees, > 50 years, lower protective antibody titers were found. Allergic individuals showed an adequate response and immunosuppressed individuals a diminished response to TBE-vaccination. The TBE-vaccination is generally safe with rare serious adverse events. Schedules should, if possible, use the same vaccine brand (non-mixed). TBE-vaccines are immunogenic in terms of antibody response but less so when vaccination is started after the age of 50 years. Age at priming is a key factor in the duration of protection. [ABSTRACT FROM AUTHOR]

There are few data available regarding the clinical course of tick-borne encephalitis virus (TBEV) vaccination breakthrough infections. The published studies suggest that vaccination breakthrough infections may have a more severe course than native TBEV infection in unvaccinated individuals—potentially due to antibody-dependent enhancement. Here we report a large analysis of vaccination breakthrough infections. This retrospective analysis was based on a national surveillance dataset spanning the years 2001–2018. Variables reflecting disease severity, such as 'CNS symptoms', 'myelitis', 'fatal outcome' and 'hospitalization' were analysed as well as general epidemiological variables. Cases were categorized as 'unvaccinated' or 'ever vaccinated', the latter category including cases with at least one dose of a TBEV vaccine. A total of 6073 notified TBEV infection cases were included in our analysis. Sufficient data on vaccination status were available for 95.1% of patients (5777/6073); of these, 5298 presented with a native infection. A total of (334/5777) cases developed an infection despite having been vaccinated at least once. Comparing unvaccinated patients with those with at least one vaccination, we find an odds ratio (OR) 2.73, (95% confidence interval (CI) 0.79–9.50) regarding the variable fatal outcome that did not reach statistical significance. Analysing the clinical variables 'CNS symptoms' and 'myelitis', there is no difference between these groups (OR 0.86, 95% CI 0.68–1.08; and OR 1.30, 95% CI 0.74–2.27 respectively). Patients who were vaccinated and had an assumed protection at symptom onset (n = 100) had a higher risk for the development of myelitic symptoms (OR 2.21, 95% CI 1.01–4.86]) than unvaccinated patients. Our findings could neither verify that vaccination breakthrough infections might cause a more severe disease than native infections nor prove a clear antibody-dependent enhancement phenomenon. It remains unclear whether the increased myelitis risk in a subgroup of vaccinated patients is a true effect or confounded. [ABSTRACT FROM AUTHOR]