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Background: The Powassan virus is a rare neurotropic, tick-borne arbovirus associated with meningoencephalitis. Despite the virus's known predilection for the basal ganglia, there are no reports detailing the spectrum of movement disorders in children with Powassan meningoencephalitis., Cases: We present 3 cases of pediatric Powassan encephalitis, highlighting the diverse and evolving movement disorders associated with this disease. We observed subcortical myoclonus and progressive generalized dystonia (patient 1), transient dyskinesias and refractory focal dystonia (patient 2), and generalized dystonia evolving into chorea and lingual dyskinesias (patient 3). One patient exhibited multifocal vasculitis on magnetic resonance imaging angiography, a novel finding., Conclusions: Movement disorders were a primary source of the morbidity experienced by pediatric Powassan encephalitis patients throughout their disease course, underscoring the importance of regular monitoring and adaptable treatment strategies in this condition. Larger, prospective studies are necessary to fully delineate the spectrum of associated movement disorders in this rare and severe disease., (© 2024 International Parkinson and Movement Disorder Society.)

Aim: The aim of the study was to assess the usefulness of cytokines and other soluble mediators in differentiation between severe and mild course of tick-borne encephalitis (TBE) as well as the predictor of sequalae development., Material and Methods: 122 patients (mean age 47.66 ± 14.77 years, 43 females, 79 males) with TBE were included in the study. Concentrations of 82 cytokines, growth factors, selectins, matrix metalloproteinases and other soluble mediators were measured in serum and CSF samples according to the manufacturer's instruction on a Bio-Plex 200 System using the custom made Luminex assays. Enzyme-linked immunosorbent assays for the quantitative detection of human IL-26, IL-29 IL-22, CXCL12 were performed., Results: No significant differences between serum concentrations of examined factors between group with sequelae and group with complete recovery were observed. In the CSF the concentrations of GM-CSF, Il-1α, Il-2, Il-4, Il-6, Il-12p70, Il-17A, CXCL1, CXCL6, Il-8, CCL4, CCL20, TRAIL, CD40L, MMP8 were significantly higher in patients who developed sequelae than in patients with complete recovery. For TRAIL concentration over 26.65 pg/ml in CSF the probability of sequalae development was 10.5 higher. In case of CCL20 - the concentration over 21.38 pg/ml in CSF the odds ratio was 6.429 times. For MMP-8 over 4210.54 pg/ml, the odds ratio was 11.222 times., Conclusions: TRAIL, CCL-20 and MMP-8 are promising biomarkers of prediction of the sequalae development of TBE. Pro-inflammatory cytokines IL-8, IL-1, IL-2, IL-12, IL-17A also associate well with the risk of sequelae and could be further evaluated as prognostic markers in TBE, individually or as elements of a larger model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In a retrospective metatranscriptomics study, we identified tick-borne encephalitis virus (TBEV) to be the causative agent for a fatal non-suppurative meningoencephalitis in a three-week-old Dalmatian puppy in Switzerland. Further investigations showed that the two other littermates with similar signs and pathological lesions were also positive for TBEV. By using an unbiased approach of combining high-throughput sequencing (HTS) and bioinformatics we were able to solve the etiology and discover an unusual case of TBEV in three young puppies. Based on our findings, we suggest that a vector-independent transmission of TBEV occurred and that most likely an intrauterine infection led to the severe and fulminant disease of the entire litter. We were able to demonstrate the presence of TBEV RNA by in situ hybridization (ISH) in the brain of all three puppies. Furthermore, we were able to detect TBEV by RT-qPCR in total RNA extracted from formalin-fixed and paraffin embedded (FFPE) blocks containing multiple peripheral organs. Overall, our findings shed light on alternative vector-independent transmission routes of TBEV infections in dogs and encourage veterinary practitioners to consider TBEV as an important differential diagnosis in neurological cases in dogs.

Bourbon virus is a tickborne virus that can cause human disease. Cases have been reported in Kansas, Oklahoma, and Missouri, USA. We identified Bourbon virus-specific neutralizing antibodies in patients from North Carolina. Bourbon virus infections are likely more common than previously thought, highlighting the need for improved diagnostics and surveillance.

Powassan virus (POWV) is an emerging tick-borne virus that causes severe meningoencephalitis in the United States, Canada, and Russia. Serology is generally the preferred diagnostic modality, but PCR on cerebrospinal fluid, blood, or urine has an important role, particularly in immunocompromised patients who are unable to mount a serologic response. Although the perceived poor sensitivity of PCR in the general population may be due to the biology of infection and health-seeking behavior (with short viremic periods that end before hospital presentation), limitations in assay design may also contribute. Genome sequences from clinical POWV cases are extremely scarce; PCR assay design has been informed by those available, but the numbers are limited. Larger numbers of genome sequences from tick-derived POWV are available, but it is not known if POWV genomes from human infections broadly mirror genomes from tick hosts, or if human infections are caused by a subset of more virulent strains. We obtained viral genomic data from 10 previously unpublished POWV human infections and showed that they broadly mirror the diversity of genome sequences seen in ticks, including all three major clades (lineage I, lineage II Northeast, and lineage II Midwest). These newly published clinical POWV genome sequences include the first confirmed lineage I infection in the United States, highlighting the relevance of all clades in human disease. An in silico analysis of published POWV PCR assays shows that many assays were optimized against a single clade and have mismatches that may affect their sensitivity when applied across clades. This analysis serves as a launching point for improved PCR design for clinical diagnostics and environmental surveillance.

The aim of this study was to evaluate the clinical usefulness of VirClia IgM/IgG single-assay chemiluminescence tests for the diagnosis of tick-borne encephalitis (TBE) in an endemic part of Norway. Patients hospitalized at Vestfold or Telemark Hospitals with suspected infection in the central nervous system (CNS) in the period between May 2021 and December 2023 were included, with 85 TBE cases identified. The VirClia IgM assay was positive in the initial serum sample in 75/85 cases, giving a sensitivity of 88.2% (95% CI, 79.4-94.2). The ReaScan TBE IgM rapid test was positive in 80/85 cases, with an estimated sensitivity of 94.1% (95% CI, 86.8-98.1). Vaccine breakthrough infections were the predominant cause of non-reactive IgM cases. The calculated specificity for the VirClia IgM was 95.8% (95% CI, 92.5-98.0). In conclusion, the sensitivity of the VirClia IgM was non-inferior to the ReaScan TBE IgM rapid test. However, isolated IgM reactive results must be interpreted with caution, since false-reactive results occur.

A case of Powassan encephalitis occurred in Manitoba, Canada, after the bite of a black-legged tick. Awareness of this emerging tickborne illness is needed because the number of vector tick species is growing. No specific treatment options exist, and cases with illness and death are high. Prevention is crucial.

Competing Interests: Competing interests:: Anne Rowan-Legg is a member of the Canadian Paediatric Society Board of Directors. No other competing interests were declared.

Powassan virus is a tick-borne flavivirus that can cause severe neuroinvasive disease, with areas of endemicity in the Northeast and Midwest United States, Canada, and Russia. Diagnosis is challenging and relies on a high index of suspicion and choosing the right test based on duration of infection and the patient's immune status. This review covers laboratory testing for Powassan virus, including historical considerations, modern options, and methods being developed in the research space., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Tick-borne encephalitis (TBE) virus is the most prevalent tick-transmitted orthoflavivirus in Europe. Due to the nonspecific nature of its symptoms, TBE is primarily diagnosed by ELISA-based detection of specific antibodies in the patient serum. However, cross-reactivity between orthoflaviviruses complicates the diagnosis. Specificity issues may be mitigated by serum neutralization assays (SNT), although the handling of clinically relevant orthoflaviviruses requires biosafety level (BSL) 3 conditions and they have highly divergent viral kinetics and cell tropisms. In the present study, we established a reporter virus particle (RVP)-based SNT in which the infectivity is measured by luminescence and that can be performed under BSL-2 conditions. The RVP-based SNT for TBEV exhibited a highly significant correlation with the traditional virus-based SNT (R 2  = 0.8637, p < 0.0001). The RVP-based assay demonstrated a sensitivity of 92.3% (95% CI: 79.7%-97.4%) and specificity of 100% (95% CI: 81.6%-100%). We also tested the cross-reactivity of serum samples in RVP-based assays against other orthoflaviviruses (yellow fever virus, dengue virus type 2, Zika virus, West Nile virus and Japanese encephalitis virus). Interestingly, all serum samples which had tested TBEV-positive by ELISA but negative by RVP-based SNT were reactive for antibodies against other orthoflaviviruses. Thus, the RVP-based seroneutralization assay provides an added value in clinical diagnostics as well as in epidemiological studies., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Tick-borne encephalitis virus (TBEV), a zoonotic pathogen, can cause severe neurological complications and fatal outcomes in humans. Early diagnosis of TBEV infection is crucial for clinical practice. Although serological assays are frequently employed for detection, the lack of antibodies in the early stages of infection and the cross-reactivity of antibodies limit their efficacy. Conventional molecular diagnostic methods such as RT-qPCR can achieve early and accurate identification but require specialized instrumentation and professionals, hindering their application in resource-limited areas. Our study developed a rapid and visual TBEV molecular detection method by combining RT-recombinase-aided amplification, the CRISPR/Cas13a system, and lateral flow dipsticks. The diagnostic sensitivity of this method is 50 CFU/ml, with no cross-reactivity with a variety of viruses. The detection can be carried out within 1 h at a temperature between 37 and 42 °C, and the results can be visually determined without the need for complex instruments and professionals. Subsequently, this assay was used to analyze clinical samples from 15 patients suspected of TBEV infection and 10 healthy volunteers, and its sensitivity and specificity reached 100 %, which was consistent with the results of RT-qPCR. These results indicate that this new method can be a promising point-of-care test for the diagnosis of tick-borne encephalitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Tick-borne encephalitis (TBE) is one of the main diseases transmitted by ticks, the incidence of which is increasing. Moreover, its diagnosis and therapy are often long and difficult according to nonspecific symptoms and complex etiology. This study aimed to observe changes in the proteome of cerebrospinal fluid from TBE patients. Cerebrospinal fluid (CSF) of TBE patients (n = 20) and healthy individuals (n = 10) was analyzed using a proteomic approach (QExactiveHF-Orbitrap mass spectrometer) and zymography. Obtained results show that in CSF of TBE patients, the top-upregulated proteins are involved in pro-inflammatory reaction (interleukins), as well as antioxidant/protective response (peroxiredoxins, heat shock proteins). Moreover, changes in the proteome of CSF are not only the result of this disease development, but they can also be an indicator of its course. This mainly applies to proteins involved in proteolysis including serpins and metalloproteinases, whose activity is proportional to the length of patients' convalescence. The obtained proteomic data strongly direct attention to the changes caused by the development of TBE to antioxidant, pro-inflammatory, and proteolytic proteins, knowledge about which can significantly contribute to faster and more accurate diagnosis of various clinical forms of TBE., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Purpose: To describe the clinical characteristics and factors associated with disease severity in a Norwegian cohort of hospitalized patients with tick-borne encephalitis (TBE)., Methods: This observational multicenter study included hospitalized patients with TBE in the endemic area in the southeastern region of Norway from 2018 to 2022. Clinical signs and findings from laboratory tests, EEG, CT and MRI scans were recorded. Patient characteristics were compared among those with mild, moderate, and severe TBE, and factors associated with disease severity were identified., Results: Nearly all eligible patients were included in the final cohort (153/189 participants, 81%). The median age was 56 years, 63% were men, and 7% were vaccinated against TBE; no participants were fully vaccinated. TBE presented as mild (meningeal) disease in 31% of patients and as moderate or severe (encephalitic) disease in 54% and 14% of patients, respectively. We found that 46% of the patients had a monophasic course, 64% had hyponatremia, and 7% presented with central nervous system (CNS) symptoms without pleocytosis in cerebrospinal fluid (CSF). Dysesthesia, a symptom previously not described, was reported in 10% of the patients. Most objective findings were related to the CNS. Preexisting comorbidities, CRP and CSF protein levels were predictors of more severe disease., Conclusion: This novel presentation of a large Norwegian cohort supports TBE as a serious disease in the southeastern region of Norway. The majority of hospitalized patients presented with encephalitis, and fewer presented with meningitis. Comorbidities, CRP and CSF protein levels were associated with more severe disease., Trial Registration: Prosjekt #2,296,959 - The Norwegian Tick-borne Encephalitis Study - NOTES. Acute phase characteristics and long-term outcomes. - Cristin., (© 2024. The Author(s).)

Tick-borne encephalitis (TBE) is usually diagnosed based on the presence of TBE virus (TBEV)-specific IgM and IgG antibodies in serum. However, antibodies induced by vaccination or cross-reactivity to previous flavivirus infections may result in false positive TBEV serology. Detection of TBEV RNA may be an alternative diagnostic approach to detect viral presence and circumvent the diagnostic difficulties present when using serology. Viral RNA in blood is commonly detectable only in the first viremic phase usually lasting up to two weeks, and not in the second neurologic phase, when the patients contact the health care system and undergo diagnostic work-up. TBEV RNA has previously been detected in urine in a few retrospective TBE cases in the neurologic phase, and furthermore RNA of other flaviviruses has been detected in patient saliva. In this study, blood, saliva and urine were collected from 31 hospitalised immunocompetent patients with pleocytosis and symptoms of aseptic meningitis and/or encephalitis, suspected to have TBE. We wanted to pursue if molecular testing of TBEV RNA in these patient materials may be useful in the diagnostics. Eleven of the 31 study patients were diagnosed with TBE based on ELISA detection of TBEV specific IgG and IgM antibodies. None of the study patients had TBEV RNA detectable in any of the collected patient material., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Quarsten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tick-borne encephalitis virus (TBEV) is a common virus in Europe and Asia, causing around 10,000 to 10,500 infections annually. It affects the central nervous system and poses threats to public health. However, the exact molecular mechanisms of TBE pathogenesis are not yet fully understood due to the complex interactions between the virus and its host. In this study, a comprehensive analysis was conducted to characterize the serum metabolome and proteome of adult patients infected with TBEV, in comparison to a control group of healthy individuals. Liquid chromatography tandem mass spectrometry (LC-MS) was employed to monitor metabolic and proteomic alternations throughout the progression of the disease, significant physiological changes associated with different stages of the disease were identified. A total of 44 proteins and 115 metabolites exhibited significantly alternations in the sera of patients diagnosed with TBE. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of these metabolites and proteins revealed differential enrichment of genes associated with the extracellular matrix, complement binding, hemostasis, lipid metabolism, and amino acid metabolism between TBE patients and healthy controls. We gained valuable understanding of the specific metabolites implicated in the host's responses to TBE, establishing a basis for further research on TBE disease. SIGNIFICANCE: The current investigation revealed a comprehensive and systematic differences on TBE using LC-MS platform from human serum samples of TBE patients and healthy individuals providing the immune response to the invasion of TBE., Competing Interests: Declaration of competing interest The authors declare that there are no financial or other potential conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: A patient with X-linked agammaglobulinemia (XLA) and severe tick-borne encephalitis (TBE) was treated with TBE virus (TBEV) IgG positive plasma. The patient's clinical response, humoral and cellular immune responses were characterized pre- and post-infection., Methods: ELISA and neutralisation assays were performed on sera and TBEV PCR assay on sera and cerebrospinal fluid. T cell assays were conducted on peripheral blood the patient and five healthy vaccinated controls., Results: The patient was admitted to the hospital with headache and fever. He was not vaccinated against TBE but receiving subcutaneous IgG-replacement therapy (IGRT). TBEV IgG antibodies were low-level positive (due to scIGRT), but the TBEV IgM and TBEV neutralisation tests were negative. During hospitalisation his clinical condition deteriorated (Glasgow coma scale 3/15) and he was treated in the ICU with corticosteroids and external ventricular drainage. He was then treated with plasma containing TBEV IgG without apparent side effects. His symptoms improved within a few days and the TBEV neutralisation test converted to positive. Robust CD8 + T cell responses were observed at three and 18-months post-infection, in the absence of B cells. This was confirmed by tetramers specific for TBEV., Conclusion: TBEV IgG-positive plasma given to an XLA patient with TBE without evident adverse reactions may have contributed to a positive clinical outcome. Similar approaches could offer a promising foundation for researching therapeutic options for patients with humoral immunodeficiencies. Importantly, a robust CD8 + T cell response was observed after infection despite the lack of B cells and indicates that these patients can clear acute viral infections and could benefit from future vaccination programs., (© 2024. The Author(s).)

Wild rodents are considered to be one of the most important TBEV-amplifying reservoir hosts; therefore, they may be suitable for foci detection studies. To investigate the effectiveness of viral RNA detection in wild rodents for suspected TBEV foci confirmation, we trapped small rodents ( n = 139) in various locations in Lithuania where TBEV was previously detected in questing ticks. Murine neuroblastoma Neuro-2a cells were inoculated with each rodent sample to maximize the chances of detecting viral RNA in rodent samples. TBEV RNA was detected in 74.8% (CI 95% 66.7-81.1) of the brain and/or internal organ mix suspensions, and the prevalence rate increased significantly following sample cultivation in Neuro-2a cells. Moreover, a strong correlation (r = 0.88; p < 0.05) was found between the average monthly air temperature of rodent trapping and the TBEV RNA prevalence rate in cell culture isolates of rodent suspensions, which were PCR-negative before cultivation in cell culture. This study shows that wild rodents are suitable sentinel animals to confirm TBEV foci. In addition, the study results demonstrate that sample cultivation in cell culture is a highly efficient method for increasing TBEV viral load to detectable quantities.

Tick-borne encephalitis (TBE) and Lyme neuroborreliosis (LNB), the most common tick-borne diseases of the central nervous system in Central Europe, are frequently associated with pareses. The aim of this study was to characterise paretic complications in patients with TBE and LNB, including their severity, persistence and impact on the patients' quality of life. Our retrospective observational study included patients with aseptic CNS infection due to TBE virus or Borrelia burgdorferi sensu lato. Paretic complications were evaluated in the acute phase and the patients were followed up until complete regression or long-term stabilisation of any neurological deficit. The severity of the neurological deficit was graded according to the modified Rankin Scale (mRS). A total of 823 patients (582 with TBE, 241 with LNB) was included. Paretic complications were diagnosed in 63 TBE patients (10.8 %) and in 147 LNB patients (61.0 %). In TBE, the most common neurological deficit was brachial plexus paresis in 21 patients (33 %) and bulbar symptoms in 18 patients (29 %). In LNB patients, facial nerve palsy was the most frequent neurological deficit (117patients; 79.6 %), followed by lower limb paresis in 23 patients (15.6 %). Forty-nine TBE patients and 134 LNB paretic patients completed follow-up. Paresis resolved within 3 weeks in 16 TBE patients (33 %) and 53 LNB patients (39.5 %), but the proportion of patients with paresis persisting for more than 12 months was significantly higher in TBE (34.7 vs. 3.7 %, p < 0.001). The mean mRS was significantly higher in TBE paretic patients compared to LNB (p < 0.001). Paretic complications are significantly more common in LNB than in TBE but pareses associated with TBE last longer than in LNB and considerably reduce the quality of life of patients. Prevention remains the only way to influence the long-term motor deficits of TBE., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Forest encephalitis is a natural focal disease transmitted through the bite of hard ticks, and its pathogen is the tick-borne encephalitis virus from the Flaviviridae family. The mortality rate of forest encephalitis is relatively high, making laboratory testing significant in diagnosing this disease. This article elaborates on the etiological diagnostic methods and recent research progress in forest encephalitis. Laboratory tests for forest encephalitis mainly include routine examinations, serological tests, virus isolation, and molecular biological testing. The detection of serum-specific IgM antibodies against the forest encephalitis virus is of great importance for early diagnosis, and specific IgG antibodies serve as a "gold standard" for differentiation from other diseases. Techniques such as enzyme-linked immunosorbent assay (ELISA) or indirect immunofluorescence assay for detecting specific IgM antibodies in serum and/or cerebrospinal fluid, the serum hemagglutination inhibition test or serum complement fixation test, and the double serum hemagglutination inhibition test or complement fixation test all contribute to the early diagnosis. The development of molecular testing methods is rapid, and techniques such as metabolomics, digital PCR, and matrix metalloproteinases are also applied in the early diagnosis of forest encephalitis.

Objectives: Tick-borne encephalitis virus and louping ill virus are neurotropic flaviviruses transmitted by ticks. Epidemiologically, tick-borne encephalitis is endemic in Europe whereas louping ill's predominant geographical distribution is the UK. Rarely, these flaviviruses affect dogs causing neurological signs. This case series aimed to describe the clinical, clinicopathological, and imaging findings, as well as the outcomes in six dogs with meningoencephalitis and/or meningomyelitis caused by a flavivirus in the UK in 2021., Materials and Methods: Observational retrospective case-series study. Clinical data were retrieved from medical records of dogs with positive serological or immunohistochemical results from three different institutions from spring to winter 2021., Results: Six dogs were included in the study. All dogs presented an initial phase of pyrexia and/or lethargy followed by progressive signs of spinal cord and/or intracranial disease. Magnetic resonance imaging showed bilateral and symmetrical lesions affecting the grey matter of the thalamus, pons, medulla oblongata, and thoracic or lumbar intumescences with none or mild parenchymal and meningeal contrast enhancement. Serology for tick-borne encephalitis virus was positive in five dogs with the presence of seroconversion in two dogs. The viral distinction between flaviviruses was not achieved. One dog with negative serology presented positive immunohistochemistry at post-mortem examination. Three dogs survived but presented neurological sequelae. Three dogs were euthanased due to the rapid progression of the clinical signs or static neurological signs., Clinical Significance: These cases raise awareness of the presence of tick-borne encephalitis as an emergent disease or the increased prevalence of louping ill virus affecting dogs in the UK., (© 2023 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

Background: Powassan virus (POWV) is an emerging arthropod-borne flavivirus, transmitted by Ixodes spp. ticks, which has been associated with neuroinvasive disease and poor outcomes., Methods: A retrospective study was conducted at Mayo Clinic from 2013 to 2022. We included clinical and epidemiologic data of probable and confirmed neuroinvasive POWV cases., Results: Sixteen patients with neuroinvasive POWV were identified; their median age was 63.2 years, and 62.5% were male. Six patients presented with rhombencephalitis, 4 with isolated meningitis, 3 with meningoencephalitis, 2 with meningoencephalomyelitis, and 1 with opsoclonus myoclonus syndrome. A median time of 18 days was observed between symptom onset and diagnosis. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with elevated protein and normal glucose in the majority of patients. Death occurred within 90 days in 3 patients (18.8%), and residual neurologic deficits were seen in 8 survivors (72.7%)., Conclusions: To our knowledge, this is the largest case series of patients with neuroinvasive POWV infection. We highlight the importance of a high clinical suspicion among patients who live in or travel to high-risk areas during the spring to fall months. Our data show high morbidity and mortality rates among patients with neuroinvasive disease., Competing Interests: Potential conflicts of interest. E. S. T. reports consulting fees from Roche Diagnostics and Euroimmune US and travel support from American Society for Microbiology, the Pan American Society for Clinical Virology, and the American Association for Clinical Chemistry. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Lymphocytic choriomeningitis virus (LCMV) is one of the arenaviruses infecting humans. LCMV infections have been reported worldwide in humans with varying levels of severity. To detect arenavirus RNA and LCMV-reactive antibodies in different geographical regions of Finland, we screened human serum and cerebrospinal fluid (CSF) samples, taken from suspected tick-borne encephalitis (TBE) cases, using reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence assay (IFA). No arenavirus nucleic acids were detected, and the overall LCMV seroprevalence was 4.5%. No seroconversions were detected in paired serum samples. The highest seroprevalence (5.2%) was detected among individuals of age group III (40-59 years), followed by age group I (under-20-year-olds, 4.9%), while the lowest seroprevalence (3.8%) was found in age group IV (60 years or older). A lower LCMV seroprevalence in older age groups may suggest waning of immunity over time. The observation of a higher seroprevalence in the younger age group and the decreasing population size of the main reservoir host, the house mouse, may suggest exposure to another LCMV-like virus in Finland.

Tick-borne encephalitis (TBE) is an infection of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is endemic in parts of Europe and Asia. TBEV is transmitted to humans primarily by Ixodes ticks. There have been 5 TBE cases identified in Japan, all on the northern island of Hokkaido. Rodents with TBEV antibodies and Ixodes ticks have been identified throughout Japan, indicating that TBEV infection might be undiagnosed in Japan. Residual serum and cerebrospinal fluid (CSF) collected in 2010-2021 from 520 patients ≥1 year-of-age previously hospitalized with encephalitis or meningitis of unknown etiology at 15 hospitals (including 13 hospitals outside of Hokkaido) were screened by ELISA for TBEV IgG and IgM antibodies; TBEV infection was confirmed by the gold standard neutralization test. Residual serum was available from 331 (63.6%) patients and CSF from 430 (82.6%) patients; both serum and CSF were available from 189 (36.3%). Two patients were TBE cases: a female aged 61 years hospitalized for 104 days in Oita (2000 km south of Hokkaido) and a male aged 24 years hospitalized for 11 days in Tokyo (1200 km south of Hokkaido). Retrospective testing also identified a previous TBEV infection in a female aged 45 years hospitalized for 12 days in Okayama (1700 km south of Hokkaido). TBEV infection should be considered as a potential cause of encephalitis or meningitis in Japan. TBE cases are likely undiagnosed in Japan, including outside of Hokkaido, due to limited clinical awareness and lack of availability of TBE diagnostic tests.

Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted neurotropic flavivirus in Europe and Asia. Our analysis aimed to investigate the contribution of TBEV-specific antibody detection by serological assays and TBEV RNA detection by real-time PCR to the diagnosis of tick-borne encephalitis (TBE). We analyzed data from 3713 patients from 16 years of laboratory TBEV diagnostics in an endemic area in Southern Germany. During this period, 126 cases of TBE were diagnosed. TBEV-specific IgM ELISA tests showed a high clinical sensitivity (96.8%) and a very high clinical specificity (99.7%). In immunocompetent patients, TBE was reliably diagnosed by detection of TBEV IgM antibodies in serum. Intrathecal TBEV IgG antibody synthesis was detected in 46 of 84 (55%) cases by analysis of paired serum and cerebrospinal fluid (CSF) samples. None of the 87 immunocompetent TBE patients tested had detectable TBEV RNA in serum or CSF. In contrast, in two TBE patients without TBEV-specific antibodies, diagnosis could only be made by the detection of TBEV RNA in CSF. Both patients had previously been treated with the B cell-depleting antibody rituximab. Therefore, in patients with CNS infection and humoral immunodeficiency, it is necessary to include TBEV PCR in the diagnostic approach.

Tick-borne encephalitis virus (TBEV) causes tick-borne encephalitis (TBE), affecting human health in Europe and Asia. Reports on canine clinical cases of TBE are rare, although dogs are used as sentinels for assessing human health risks. The first canine clinical TBE case in Greece is reported in this case report. The dog had a history of tick infestation and displayed neurological symptoms, particularly tetraparesis, neck hyperalgesia, and a sudden behavior change. Serum samples were obtained and examined in a commercial ELISA to detect anti-TBEV specific IgG and IgM antibodies. The dog tested seropositive for both IgG and IgM, and based on its history and compatible clinical signs, the diagnosis of TBE infection was reached. The prognosis was initially poor, and treatment included the administration of fluids, corticosteroids, and antibiotics, followed by physical therapy. After a 10-day hospitalization, the dog had a much better prognosis. This case highlights that TBEV does emerge in new locations, increasing human and animal infection risk. Veterinarians should include TBE in their differential diagnosis of canine patients with a history of tick infestations, progressive neurological symptoms, and abnormal behavior., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2023. Published by Elsevier GmbH.)

Tick-borne encephalitis (TBE) is a viral tick-borne infection occurring in many parts of Europe and Asia as described in this review. Increasing TBE case numbers have been reported over recent decades. In Denmark the infection is rare (1-14 annual cases). The rise in TBE in Denmark is mainly driven by microfoci outside of Bornholm, primarily North Zealand. Clinical illness has a bi-phasic presentation: "summer-flu" which may be followed by a neuroinfection. No specific treatment exists, and mortality is less-than 1%. A considerable percentage of patients may experience neurological sequelae. TBE is preventable through vaccination., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Tick-borne encephalitis is a rare infection in Denmark. The infection has been endemic to the island of Bornholm for many years. During the past 10 years, transmission has occurred in other parts of Denmark, particularly North Zealand. This case report describes a typical tick-borne encephalitis case diagnosed in the first viraemic phase of the disease course. Clinical presentation and diagnostic criteria are described., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Introduction: Viral infections are a frequent cause of disseminated non-suppurative encephalitis in dogs. However, using routine diagnostic methods, the specific virus may remain unknown due to extensive or complete viral clearance or because the virus is unexpected or new. A metatranscriptomics-based approach of combining high-throughput sequencing (HTS) and bioinformatics analysis was used to investigate the viral etiology in archival cases of dogs with non-suppurative encephalitis. In formalin-fixed paraffin embedded (FFPE) brain material from the years 1976 to 2021 a high incidence of tick-borne encephalitis virus (TBEV) was detected. Moreover, canine distemper virus (CDV) was identified without typical demyelinating lesions and canine vesivirus (CaVV) was detected as an unexpected virus associated with non-suppurative encephalitis. We demonstrated the viral presence in brain tissues at the sites of inflammation by immunohistochemistry (IHC) and in situ hybridization (ISH). These results highlight the value of emerging sequencing technologies in veterinary diagnostics and expand our knowledge on the etiologies of encephalitis in dogs.

Introduction: We report a 23-year-old patient who presented to the general practitioner due to persisting headache, fever, and vomiting. In the further course, a tetraparesis dominated on the right side, dysphagia and dysarthria occurred, and a general tonic-clonic seizure. Further examinations confirmed tick-borne encephalomyelitis as well as polyradiculitis. After two months of rehabilitation, neuropsychological as well as focal-neurological deficits persisted in the unvaccinated patient., Competing Interests: Es bestehen keine Interessenskonflikte., (© 2023 Aerzteverlag medinfo AG.)

Purpose: Despite being vaccine-preventable, tick-borne encephalitis (TBE) continues to cause considerable morbidity in Germany. Limited insight into potentially debilitating consequences of TBE may partially underly low (~ 20%) TBE vaccine uptake. We aimed to systematically assess TBE sequelae and other consequences., Methods: Routinely notified TBE patients from 2018 to 2020 from Southern Germany were invited to telephone interviews acutely and again after 18 months. Duration of acute symptoms was prospectively assessed. Recovery was defined as score 0 on the modified RANKIN scale. Determinants of time to recovery were analysed with cox regression, adjusted for covariates identified using directed acyclic graphs, yielding hazard ratios (HR) and 95% confidence intervals (CI)., Results: Of 558 cases, 523 (93.7%) completed follow-up. Full recovery was reported by 67.3% (children: 94.9%, adults: 63.8%). Sequelae included fatigue (17.0%), weakness (13.4%), concentration deficit (13.0%), and impaired balance (12.0%). Compared with 18-39-year-olds, recovery rates were 44% lower in ≥ 50-year-olds (HR: 0.56, 95%CI 0.42-0.75) and 79% higher in children (HR: 1.79, 95%CI 1.25-2.56). The recovery rate was 64% lower after severe TBE (compared to mild; HR: 0.36, 95%CI 0.25-0.52) and 22% lower with comorbidities (HR: 0.78, 95%CI 0.62-0.99). Substantial health-care use was reported (90.1% hospitalisation, 39.8% rehabilitation). Of employed cases, 88.4% required sick leave; 10.3% planned/reported premature retirement due to sequelae., Conclusion: Half the adult and 5% of paediatric patients reported persisting sequelae after 18 months. Improved prevention could alleviate both individual (morbidity) and societal TBE burden (health-care costs, productivity losses). Insights into sequelae can help guide at-risk populations towards tick-avoidant strategies and encourage TBE vaccination., (© 2023. The Author(s).)

As evidenced by sero-epidemiological studies, infections of horses with the tick-borne encephalitis virus (TBEV) occur frequently in TBEV-endemic areas. However, there are only very few reports of clinical cases. A possible underreporting may be due to a variety of diagnostic challenges. In this study, ELISA and neutralization tests were applied to serum samples. Brain tissue samples were investigated for the presence of nucleic acids of TBEV, Equid alphaherpesvirus 1 , Borna disease virus 1, West Nile and Usutu viruses, rustrela virus, as well as Eastern, Western, and Venezuelan equine encephalitis viruses with RT-qPCR, RT-PCR, and qPCR, respectively. TBEV-specific amplification products were subjected to Sanger sequencing. In addition, a direct fluorescent antibody test for rabies was performed. Clinical and patho-histological findings are reported. Using specific RT-qPCR and RT-PCR assays, TBEV nucleic acids were demonstrated in brain tissue samples. Sequencing revealed the Western (formerly Central) European subtype of TBEV as the etiological agent. A high titer of TBEV-specific neutralizing antibodies was found in the serum. RNAscope in situ hybridization revealed TBEV RNA confined to neuronal cell bodies and processes. No other pathogens or nucleic acids thereof could be detected. Diagnostic procedures need to be carried out early after the onset of neurological signs to allow for a final etiological diagnosis of acute TBEV infections in horses.

The incidence of tick-borne encephalitis in Norway is increasing. The risk of infection shows considerable geographical variations, with clusters of cases in certain municipalities in the counties of Agder, and Vestfold and Telemark. There is also a major variation in clinical presentation. Only a small number of cases of tick-borne encephalitis in children have been reported in Norway, and the condition may be underdiagnosed. We present a clinical review, including two case studies, that focuses on the clinical presentation and diagnosis of tick-borne encephalitis in children.

Tick-borne encephalitis (TBE) is a severe disease caused by the tick-borne encephalitis virus (TBEV). TBEV is endemic throughout Eurasia and can cause persistent neurologic deficits and death. Special Operations Forces (SOF) participating in field exercises or operations in TBE-endemic countries are at significantly increased risk of infection. Unlike Lyme disease and other tick-borne illnesses, transmission of TBEV can be immediate, and early tick removal does not reduce the risk of infection. While there are no virus-specific treatments available, the US Food and Drug Administration (FDA) recently approved a TBE vaccine that has yet to be incorporated into formal Department of Defense (DoD) recommendations. SOF medical providers should be aware of this disease entity and consider the TBE vaccine when planning exercises and operations in areas of responsibility (AORs) with TBE-endemic countries. This review serves as a refresher and update on the epidemiology, transmission, and management of TBE for the SOF provider., (2023.)

BackgroundTick-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.MethodsWe 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.ConclusionThe 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.

Background: Tick-borne encephalitis virus (TBEV) can cause severe neurological disease in humans. Its geographical distribution is expanding in Western Europe with unresolved causes and spatial patterns, necessitating enhanced surveillance. Monitoring the virus in the environment is complicated, as it usually relies on destructive sampling of small rodents to test organs for TBEV, which in addition to ethical considerations also raises issues for long-term monitoring or longitudinal studies. Moreover, even when the virus is not detected in the blood or organs of the rodent, TBEV can still be transmitted from an infected tick to uninfected ticks feeding nearby. This is due to the ability of TBEV to replicate and migrate locally within the epidermis of small mammals, including those that do not appear to have systemic infection. This suggests that the virus may be detectable in skin biopsies, which has been confirmed in experimentally infected laboratory rodents, but it remains unknown if this sample type may be a viable alternative to destructively obtained samples in the monitoring of natural TBEV infection. Here we test ear tissue and dried blood spot (DBS) samples from rodents to determine whether TBEV-RNA can be detected in biological samples obtained non-destructively., Methods: Rodents were live-trapped and sampled at three woodland areas in The Netherlands where presence of TBEV has previously been recorded. Ear tissue (n = 79) and DBSs (n = 112) were collected from a total of 117 individuals and were tested for TBEV-RNA by real-time RT-PCR., Results: TBEV-RNA was detected in five rodents (4.3% of tested individuals), all of which had a TBEV-positive ear sample, while only two out of four of these individuals (for which a DBS was available) had a positive DBS. This equated to 6.3% of ear samples and 1.8% of DBSs testing positive for TBEV-RNA., Conclusions: We provide the first evidence to our knowledge that TBEV-RNA can be detected in samples obtained non-destructively from naturally infected wild rodents, providing a viable sampling alternative suitable for longitudinal surveillance of the virus., (© 2023. The Author(s).)

Background: Tick-borne encephalitis (TBE), a viral infectious disease affecting the central nervous system, potentially resulting in prolonged neurological symptoms and other long-term sequelae. Case identification can be challenging as TBE can be associated with non-specific symptoms, and even in cases consistent with typical TBE symptoms, the rate of laboratory testing to confirm cases is unknown. This study assessed real-world TBE laboratory testing rates across Germany., Methods: In this retrospective cross-sectional study, physicians provided data on TBE decision-making, laboratory testing (serological), and diagnostics behavior via in-depth qualitative interviews (N = 12) or a web-based quantitative survey of their patient medical records (N = 166). Hospital-based physicians who specialized in infectious disease, intensive care unit, emergency room, neurology, or pediatrics with experience managing and ordering testing for patients with meningitis, encephalitis, or non-specific central nervous system symptoms in the past 12 months were included. Data were summarized via descriptive statistics. TBE testing and positivity rates were assessed for the aggregate sample of 1400 patient charts and reported by presenting symptoms, region, and tick bite exposure., Results: TBE testing rates ranged from 54.0% (non-specific neurological symptoms only) to 65.6% (encephalitis symptoms only); the percentage of TBE positive results ranged from 5.3% (non-specific neurological symptoms only) to 36.9% (meningitis symptoms only). TBE testing rates were higher among those with a tick bite history and/or who presented with headache, high fever, or flu-like symptoms., Conclusions: The findings of this study suggest that patients with typical TBE symptoms are likely under-tested, thus likely leading to under-diagnosis in Germany. To ensure appropriate case identification, TBE testing should be consistently integrated into routine practice for all patients who present with relevant symptoms or exposure to common risk factors., (© 2023. The Author(s).)

Tick-borne encephalitis (TBE) is a vector-borne disease caused by a flavivirus, the tick-borne encephalitis virus (TBEV), and transmitted by the bite of infected Ixodes ricinus ticks. The European subtype (TBEV-Eu) is endemic in 27 European countries. During the last decade, increased TBE incidence was observed in many countries, including some of those believed to be of low endemicity/devoid of TBEV circulation. However, data dealing with TBE in children are far less profuse than with adults. Historically, children are known to have mild TBEV infection with favorable outcomes. That said, recent case reports and observational studies on pediatric cohorts have challenged this point of view. Like adults, children may present severe forms and fail to completely recover following TBE infection, at times leading to long-term cognitive impairment. In this review, we comprehensively describe the incidence, exposure factors, and transmission routes of TBEV in children, as well as the clinical and biological manifestations of TBE and imaging findings in this population. We also harness new data on long-term outcomes and sequelae in pediatric cohorts. Finally, we provide an overview of vaccination recommendations for children in European countries., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

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

Viral infections caused by viruses from the family Flaviviridae such as Zika (ZIKV), Dengue (DENV), yellow fever (YFV), tick-borne encephalitis (TBEV), West Nile (WNV), and Usutu (USUV) are some of the most challenging diseases for recognition in clinical diagnostics and epidemiological tracking thanks to their short viremia, non-specific symptoms, and high cross-reactivity observed in laboratory techniques. In Central Europe, the most relevant endemic flaviviruses are mosquito-borne WNV and USUV, and tick-borne TBEV. All three viruses have been recognised to be responsible for human neuroinvasive diseases. Moreover, they are interrupting the blood and transplantation safety processes, when the great efforts made to save a patient's life could be defeated by acquired infection from donors. Due to the trend of changing distribution and abundance of flaviviruses and their vectors influenced by global change, the co-circulation of WNV, USUV, and TBEV can be observed in the same area. In this perspective, we discuss the problems of flavivirus diagnostics and epidemiology monitoring in Slovakia as a model area of Central Europe, where co-circulation of WNV, USUV, and TBEV in the same zone has been recently detected. This new situation presents multiple challenges not only for diagnostics or surveillance but particularly also for blood and organ safety. We conclude that the current routinely used laboratory diagnostics and donor screening applied by the European Union (EU) regulations are out of date and the novel methods which have become available in recent years, e.g., next-gene sequencing or urine screening should be implemented immediately.

Matrix metalloproteinases (MMPs) play an important role in central nervous system infections. We analysed the levels of 8 different MMPs in the cerebrospinal fluid (CSF) of 89 adult patients infected with tick-borne encephalitis (TBE) virus and compared them with the levels in a control group. MMP-9 was the only MMP that showed significantly increased CSF levels in TBE patients. Serum MMP-9 levels were subsequently measured in 101 adult TBE patients at various time points during the neurological phase of TBE and at follow-up. In addition, serum MMP-9 was analysed in 37 paediatric TBE patients. Compared with control levels, both paediatric and adult TBE patients had significantly elevated serum MMP-9 levels. In most adult patients, serum MMP-9 levels peaked at hospital admission, with higher serum MMP-9 levels observed in patients with encephalitis than in patients with meningitis. Elevated serum MMP-9 levels were observed throughout hospitalisation but decreased to normal levels at follow-up. Serum MMP-9 levels correlated with clinical course, especially in patients heterozygous for the single-nucleotide polymorphism rs17576 (A/G; Gln279Arg) in the MMP9 gene. The results highlight the importance of MMP-9 in the pathogenesis of TBE and suggest that serum MMP-9 may serve as a promising bioindicator of TBE in both paediatric and adult TBE patients., Competing Interests: Declaration of Competing Interest We declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

More than 40 human cases of severe encephalitis caused by Borna disease virus 1 (BoDV-1) have been reported to German health authorities. In an endemic region in southern Germany, we conducted the seroepidemiological BoSOT study ("BoDV-1 after solid-organ transplantation") to assess whether there are undetected oligo- or asymptomatic courses of infection. A total of 216 healthy blood donors and 280 outpatients after solid organ transplantation were screened by a recombinant BoDV-1 ELISA followed by an indirect immunofluorescence assay (iIFA) as confirmatory test. For comparison, 288 serum and 258 cerebrospinal fluid (CSF) samples with a request for tick-borne encephalitis (TBE) diagnostics were analyzed for BoDV-1 infections. ELISA screening reactivity rates ranged from 3.5% to 18.6% depending on the cohort and the used ELISA antigen, but only one sample of a patient from the cohort with requested TBE diagnostics was confirmed to be positive for anti-BoDV-1-IgG by iIFA. In addition, the corresponding CSF sample of this patient with a three-week history of severe neurological disease tested positive for BoDV-1 RNA. Due to the iIFA results, all other results were interpreted as false-reactive in the ELISA screening. By linear serological epitope mapping, cross-reactions with human and bacterial proteins were identified as possible underlying mechanism for the false-reactive ELISA screening results. In conclusion, no oligo- or asymptomatic infections were detected in the studied cohorts. Serological tests based on a single recombinant BoDV-1 antigen should be interpreted with caution, and an iIFA should always be performed in addition.

A case report describing the case of a young and healthy pregnant patient who manifested tick-borne encephalitis in her peripartal period. This neuroinfection is rare in pregnant women. A more severe encephalomyelitic form of the disease, resulting in lasting consequences, occurred in the patient even though she had recently undergone a proper vaccination. In the course of 11-month observation, her newborn showed no symptoms of the disease nor psychomotor developmental disorders.

Infections transmitted by ixodic ticks in childhood account for about 20%, and tick-borne encephalitis accounts for up to 25% of cases. A feature of the course of tick-borne encephalitis is unpredictability and the possibility of chronization in 1-3% of cases with late diagnosis and inadequate therapy. The article presents a clinical observation of the disease in a child whose chronically progressive course of amyotrophic form was diagnosed 1 year and 8 months after the onset of the disease. The presence of anamnestic data, features of clinical manifestations in the dynamics and typical neurovirualization picture of the disease, even with negative results of serological and molecular genetic studies of blood and cerebrospinal fluid, allowed to make a diagnosis, prescribe etio-pathogenetic therapy and thereby stabilize the patient's condition. The use of complex drugs in the treatment, such as Cytoflavin, allows to optimize the course of the disease.

Tick-Borne Encephalitis (TBE) - Clinical and Therapeutical Aspects Abstract. Tick-borne encephalitis (TBE) is an acute inflammatory disease of the central nervous system transmitted by ticks and caused by the TBE virus, which is found in more and more parts of Europe and Asia. Only 2-30% of infections are symptomatic, and a biphasic course of fever is typical in the prodromal stage. Clinically-neurologically, 50% of cases develop meningitis, 40% meningoencephalitis, and 10% meningoencephalomyelitis. The latter is often associated with feared brainstem involvement. Encephalitis is characterized by impaired consciousness, fatigue, emotional lability, and neurocognitive deficits; myelitis is characterized by flaccid paralysis of the arms or legs. Simultaneous detection of TBEV-specific IgM and IgG antibodies in serum and a matching inflammatory CSF syndrome is required to confirm the diagnosis. Meningitis heals without sequelae; 80% of cases of encephalitis and only 20% of cases of myelitis recover completely. The overall lethality rate is 1%. Immunocompromised, elderly, and myelitic patients are at higher risk for severe disease progression and mortality. Because no specific antiviral therapy is available, active TBE vaccination remains the most important preventive measure for all persons 6 years of age and older residing in high-risk areas.

Tick-Borne Encephalitis (TBE) - Fundamentals Abstract. There is widespread endemicity of tick-borne encephalitis (TBE) in all German-speaking countries. In most regions there is a gradual increase in incidence and further territorial spread. As a proportion of the cases is not diagnosed and since the clinical course is getting worse with growing age, substantial underreporting occurs particularly in the pediatric and adolescent patient population. Infected ticks are transmitting the TBE virus, a flavivirus, within a few minutes after the bite. After an incubation period of 4 to 28 days uncharacteristic flu-like symptoms usually occur during a first viremic phase. This is followed by a brief asymptomatic interval before a minority of patients suffer of a variety of symptoms associated with damage of different parts of the central nervous system. This often results in permanent neurological injury and in about 1% the clinical course is fatal. To establish a diagnosis, it is essential to suspect the infection and to obtain a history of exposure. Depending on the phase of illness IgM and/or IgG antibodies can be detected in the serum and/or in the cerebrospinal fluid. In the early phase of the infection the TBE virus may be detected by PCR.

Background: Lithuania has the highest tick-borne encephalitis (TBE) rates in Europe. Although TBE incidence in children is lower, it may still cause long-term consequences. So far pediatric epidemiological and clinical characteristics of TBE in Lithuania were not described., Methods: We performed a retrospective analysis of 87 cases of children who were hospitalized for TBE in Kaunas Hospital of the Lithuanian University of Health Sciences from 2012 to 2019. Each case was identified with neurological symptoms and positive serological tests., Results: Around half of the children (50.6%) reported having a tick bite, whereas 6.9% stated having exposure to unpasteurized milk. Biphasic course of the disease occurred in 70.1% of the cases. The most common clinical symptoms were headache (100%), fever (100%), nausea (85.1%), vomiting (78.2%), drowsiness (67.8%) and general weakness (66.7%). Meningeal symptoms were present in 93.1% of the cases, and 93.1% of the children had at least one focal neurological sign (tremor 82.3%, impaired balance 73.6%). Isolated meningitis was diagnosed in 57.5%, meningoencephalitis in 41.4% and meningoencephalomyelitis in 1.1% of the cases. Majority of younger children (1-8 years old) had meningitis (77.3%), whereas 49.2% of older children (9-17 years old) had more severe forms of TBE. Cerebrospinal fluid pleocytosis was found in 94.3% of cases (average white blood cell count: 111.7 per μL, protein: 0.5 g/L). Higher levels of cerebrospinal fluid protein were associated with more severe forms of TBE and older age. Duration of the symptomatic disease lasted ≈11 days. Early residual signs were observed in 75.9% of all cases., Conclusions: The epidemiological and clinical characteristics of TBE in children in Lithuania are similar to those described in other countries. Only half of the subjects reported having a tick bite. Younger children tend to suffer from meningoencephalitis and meningoencephalomyelitis less frequently than elder ones. Focal neurological signs were commonly observed. Majority of children had lasting symptoms of TBE upon discharge from the hospital., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Powassan virus is an increasingly recognized cause of severe encephalitis that is transmitted by Ixodes ticks. Given the nonspecific clinical, laboratory, and imaging features of Powassan virus disease, providers should consider it in patients with compatible exposures and request appropriate testing., Competing Interests: Disclosure The authors have no financial or commercial conflicts of interest to report. A. Piantadosi is funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number K08AI139348. A. Piantadosi and I.H. Solomon are funded by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award number R21NS119660., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Flavivirus diagnostics are complicated by substantial cross-reactivity of antibodies between different flavivirus species. This is of particular importance in regions with multiple endemic flaviviruses in co-circulation. Tick-borne encephalitis virus (TBEV) is the causative agent of tick-borne encephalitis, the most common infection of the central nervous system in endemic regions of Europe and Asia. Since 2018, the related West Nile virus (WNV) has spread to Germany where its geographic distribution overlaps with TBEV endemic regions. Besides humans, various animal species are susceptible to TBEV and WNV infection. To compare antibody responses against these flaviviruses and test for cross-reactivity, we developed a multi-species luciferase immunoprecipitation system antibody detection assay for several different antigens. We performed a serosurvey of 682 dogs from five different European countries to detect antibodies against TBEV and WNV. Twelve specimens were positive for TBEV NS1 only and seven for WNV NS1 only. Two specimens were reactive to both NS1 antigens and another two were equivocal for WNV NS1. Interestingly, 89.5% of positive specimens had TBEV/WNV or WNV/TBEV signal ratios of 10 to >300 between individual NS1 antigens, allowing for a clear distinction between the two viruses. The remaining 10.5% of reactive specimens showed a five- to 10-fold difference between the two viruses and included possible dual exposures to both viruses. In contrast, equivocal samples showed low signal ratios between the NS1 antigens, suggesting unspecific reactivity. Based on these data, we found the NS1 protein to be a suitable antigen to distinguish between TBEV- and WNV-specific antibodies in dogs with sensitivity and specificity similar to virus neutralization tests., (© 2022 The Authors. Transboundary and Emerging Diseases published by Wiley-VCH GmbH.)