OBJECTIVE: 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.
CONCLUSIONS: 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.
BACKGROUND: Prosjekt #2,296,959 - The Norwegian Tick-borne Encephalitis Study - NOTES. Acute phase characteristics and long-term outcomes. - Cristin.

BACKGROUND: Ticks are vectors of various pathogens, including tick-borne encephalitis virus causing TBE and bacteria such as Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum causing e.g. viral-bacterial co-infections (TBE + LB/HGA), which pose diagnostic and therapeutic problems. Since these infections are usually accompanied by inflammation and oxidative stress causing metabolic modifications, including phospholipids, the aim of the study was to assess the level of polyunsaturated fatty acids and their metabolism (ROS- and enzyme-dependent) products in the blood plasma of patients with TBE and TBE + LB/HGA before and after pharmacotherapy.
METHODS: The total antioxidant status was determined using 2,20-azino-bis-3-ethylbenzothiazolin-6-sulfonic acid. The phospholipid and free fatty acids were analysed by gas chromatography. Lipid peroxidation was estimated by measuring small molecular weight reactive aldehyde, malondialdehyde and neuroprostanes. The reactive aldehyde was determined using gas chromatography coupled with mass spectrometry. The activity of enzymes was examined spectrophotometrically. An analysis of endocannabinoids and eicosanoids was performed using a Shimadzu UPLC system coupled with an electrospray ionization source to a Shimadzu 8060 Triple Quadrupole system. Receptor expression was measured using an enzyme-linked immunosorbent assay (ELISA).
RESULTS: The reduced antioxidant status as a result of infection was accompanied by a decrease in the level of phospholipid arachidonic acid (AA) and docosahexaenoic acid (DHA) in TBE, an increase in DHA in co-infection and in free DHA in TBE with an increase in the level of lipid peroxidation products. The enhanced activity of enzymes metabolizing phospholipids and free PUFAs increased the level of endocannabinoids and eicosanoids, while decreased 15-PGJ2 and PGE2 was accompanied by activation of granulocyte receptors before pharmacotherapy and only tending to normalize after treatment.
CONCLUSIONS: Since classical pharmacotherapy does not prevent disorders of phospholipid metabolism, the need to support treatment with antioxidants may be suggested.

Tick-borne encephalitis was limited to northeast portions of Italy. We report in Lombardy, a populous region in the northwest, a chamois displaying clinical signs of tickborne encephalitis virus that had multiple virus-positive ticks attached, as well as a symptomatic man. Further, we show serologic evidence of viral circulation in the area.

During the pandemic outdoor activities were encouraged to mitigate transmission risk while providing safe spaces for social interactions. Human behaviour, which may favour or disfavour, contact rates between questing ticks and humans, is a key factor impacting tick-borne encephalitis (TBE) incidence. We analyzed annual and weekly TBE cases in Finland, Norway and Sweden from 2010 to 2021 to assess trend, seasonality, and discuss changes in human tick exposure imposed by COVID-19. We compared the pre-pandemic incidence (2010-2019) with the pandemic incidence (2020-2021) by fitting a generalized linear model (GLM) to incidence data. Pre-pandemic incidence was 1.0, 0.29 and 2.8 for Finland, Norway and Sweden, respectively, compared to incidence of 2.2, 1.0 and 3.9 during the pandemic years. However, there was an increasing trend for all countries across the whole study period. Therefore, we predicted the number of cases in 2020/2021 based on a model fitted to the annual cases in 2010-2019. The incidences during the pandemic were 1.3 times higher for Finland, 1.7 times higher for Norway and no difference for Sweden. When social restrictions were enforced to curb the spread of SARS-CoV-2 there were profound changes in outdoor recreational behavior. Future consideration of public health interventions that promote outdoor activities may increase exposure to vector-borne diseases.

Tick-borne encephalitis (TBE) is a viral arthropod infection, endemic to large parts of Europe and Asia, and is characterised by neurological involvement, which can range from mild to severe, and in 33-60% of cases, it leads to a post-encephalitis syndrome and long-term morbidity. While TBE virus, now identified as Orthoflavivirus encephalitidis, was originally isolated in 1937, the pathogenesis of TBE is not fully appreciated with the mode of transmission (blood, tick, alimentary), viral strain, host immune response, and age, likely helping to shape the disease phenotype that we explore in this review. Importantly, the incidence of TBE is increasing, and due to global warming, its epidemiology is evolving, with new foci of transmission reported across Europe and in the UK. As such, a better understanding of the symptomatology, diagnostics, treatment, and prevention of TBE is required to inform healthcare professionals going forward, which this review addresses in detail. To this end, the need for robust national surveillance data and randomised control trial data regarding the use of various antivirals (e.g., Galidesivir and 7-deaza-2\'-CMA), monoclonal antibodies, and glucocorticoids is required to improve the management and outcomes of TBE.

BACKGROUND: Despite the availability of vaccination, TBE (tick-borne encephalitis) remains a global public health problem. Therefore, the aim of our study was to assess the long-term efficacy of vaccinations against tick-borne encephalitis using vaccines available on the European market.
METHODS: The analysis was conducted on the results of a systematic review conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. The search was performed in three databases, namely Medline (via PubMed), EMBASE (via Ovid), and the Cochrane Library database. The authors followed the PRISMA method and the selection of the articles was performed with two independent researchers.
RESULTS: From a total of 199 citations, 9 studies were included in this review. According to the primary studies identified in the search, the efficacy of available anti-TBE vaccines ranges from 90.1% to 98.9%; however, in individuals above the age of 60, the protection wanes as early as one year after vaccination. Administration of a booster dose 3 years after completion of the basic vaccination schedule significantly extended the period of protection against TBE.
CONCLUSIONS: Anti-TBE vaccines available in Europe have a high level of efficacy. However, the level of protection against TBE is decreasing after vaccination. Therefore, in addition to the conventional schedule, booster vaccines should be administered every 5 years in individuals before the age of 60 and more frequently, e.g. every 3 years, in individuals aged 60 and beyond.

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.

In 2020, a record number of tick-borne encephalitis (TBE) cases was reported in major endemic areas in Germany, i.e., the southern federal states of Baden-Wuerttemberg and Bavaria. Most cases were unvaccinated. Other tick-borne diseases (TBDs), including Lyme borreliosis and tularemia, are rising, too. Thus, strategies are needed to increase TBE vaccination uptake in risk areas and promote education on TBD prevention. Primary care physicians are key providers of both vaccinations and TBD education. The TBD-Prevention (TBD-Prev) study aimed to investigate the knowledge, attitudes and behaviors of primary care physicians in Baden-Wuerttemberg and Bavaria with regard to TBE vaccination and prevention of TBDs and to derive strategies for increasing vaccination rates and improving knowledge about TBE and other TBDs in the population and among primary care physicians. We invited all primary care physicians (N = 14,046) in both states to participate by mail. Using standardized, self-administered questionnaires, available both on paper and online, we asked physicians anonymously about their knowledge, attitudes and behaviors with respect to TBE vaccination and TBD prevention and their need for further information/educational materials. A total of 2321 physicians participated between May and September 2022 (response rate 17%), of whom 1222 (53%) worked in Baden-Wuerttemberg and 1067 (46%) in Bavaria. Among the participating physicians, 56% were male, 71% were >50 years and 51% worked in an individual practice. Furthermore, 91% were aware of the German national vaccination guidelines, and 98% perceived their knowledge of the risks and benefits of vaccination as adequate. A total of 97% offer TBE vaccinations, 67% provide vaccination counselling during initial consultations with new patients and 64% actively remind patients about due vaccinations. In addition, 24% expressed a need for further information materials, mainly traditional, analogue media such as flyers (82%) and posters (50%), and named timeliness, quality assurance, easy comprehensibility and independence from the pharmaceutical industry as the most important characteristics of such materials. Almost all participating physicians reported offering TBE vaccinations and feeling well-informed about TBE vaccination and TBDs. However, active offering of vaccinations and education could be further improved, and additional, low-threshold information materials are needed. Based on these results, we will develop and provide various materials on TBE vaccination and TBDs, in particular flyers and posters, for use by physicians during consultations.

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

Tick-borne encephalitis (TBE) is 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.