Tick-borne encephalitis (TBE) is an infectious disease caused by the tick-borne encephalitis virus (TBEV) in patients with symptoms of central nervous system (CNS) inflammation. More than 25 European countries have one or more TBE-endemic areas. Although two TBE vaccines, FSME-IMMUN® and Encepur®, are commonly used in Europe, there are no published reviews of the real-world effectiveness of TBE vaccines in Europe or elsewhere. We searched PubMed for TBE vaccine effectiveness (VE) articles and extracted information on country, study design, study period, study population, number of TBEV-infected cases, number of participants, and VE against TBEV infection and outcomes. We identified 13 studies, conducted in Austria, the Czech Republic, Latvia, Germany, and Switzerland, published in 2003-2023. One study was a cohort investigation of a milk-borne outbreak. In the other studies, 11 (91.7%) used the screening method and two (16.7%) used a case-control design (one study used both). TBE vaccines were highly effective (VE estimates >92%) against TBEV infection in all age groups. Vaccines were also highly protective against mild infections (i.e., infections in patients without symptoms of CNS inflammation), and against infections resulting in TBE and hospitalization. Vaccines were also highly protective against the most serious outcomes such as hospitalization greater than 12 days. Product-specific VE estimates were also high, though limited data were available. Studies in Austria, the Czech Republic, Latvia, and Switzerland estimated that TBE vaccines prevented >1,000 TBE cases a year, avoiding many hospitalizations and deaths, in these countries combined. Published VE studies demonstrate a high real-world effectiveness of the commercially available TBE vaccines in Europe. Although cases averted have been estimated in only four countries, TBE vaccination prevents thousands of cases in Europe each year. To prevent life-threatening TBE, TBE vaccine uptake and compliance with the vaccination schedule should be increased in residents of, and travelers to, TBE-endemic countries in Europe.

Tick-borne encephalitis (TBE) is caused by a viral infection and can lead to acute and persistent damage to the central and peripheral nervous systems. Recently, the incidence of TBE in Europe has risen, and epidemiological patterns of disease have changed, emphasising the need for improved understanding of this vaccine-preventable disease. Although TBE is endemic in many countries, the disease spectrum of TBE is not well described. We sought to characterise the clinical manifestations and outcomes of TBE by estimating the proportions of TBE patients with each type of manifestation and the risk of adverse outcomes for children and adults separately. A systematic literature review was conducted on 2 August 2022 for articles published in any language since 1 January 2007. Additional relevant studies were found in reference lists of identified articles. The review was limited to countries where only the European subtype of TBEV circulates. Of the 1,632 unique titles and abstracts identified and reviewed, 21 were retained for data analysis. The 21 studies were split into a main analysis (15 studies reporting patients hospitalised with laboratory-confirmed TBE) and a secondary analysis (6 studies reporting hospitalised and non-hospitalised patients who sought medical treatment for laboratory-confirmed TBE). The main analysis included 5,012 adults and 640 children. The predominant clinical manifestation in adults was encephalitis (61 %), followed by meningitis (33 %), radiculitis (14 %), and myelitis (6 %) (the manifestations were evaluated independently, so they will not sum to 100 %). With outliers removed, similar proportions of adults had encephalitis (48 %) and meningitis (44 %). Among cases in children, meningitis (77 %) was the most common manifestation, whereas encephalitis (23 %) and myelitis (1.3 %) were less frequent. Among hospitalised patients with TBE, the proportion of intensive care unit (ICU) admissions and deaths were similar for adults (15.5 % and 0.9 %, respectively) and children (16.4 % and 0 %, respectively.) The percentage of patients with sequelae when examined >12 months from acute TBE was 39.5 % for adults and 16.2 % for children. The evidence was challenging to aggregate due to study heterogeneity, variability in categorising clinical manifestations of central nervous system disease, variability of denominator populations, and differences in healthcare systems and diagnostic practices across countries. Our study disclosed distinct patterns of clinical manifestation among hospitalised adult and child patients with TBE and a high proportion of ICU admissions and long-term neurological sequelae across both age groups. These findings reinforce the continued need for preventive measures in the populations at risk. Moreover, variability of study admission criteria, including difficulty with clinical manifestation categorisation, calls for a more standardised approach to summarising TBE manifestations and outcomes across Europe.

Tick-borne encephalitis (TBE) is a viral infection affecting the central nervous system (CNS) with potential long-term consequences including neurological sequelae. Vaccination is critical to reduce TBE morbidity and mortality, as no antiviral treatment is available. The World Health Organization (WHO) defines areas with an incidence of ≥5 cases/100,000 PPY as highly endemic and recommends that vaccination is offered to all individuals in these areas. However, access to TBE vaccination depends on recommendations and funding by national or subnational decision-makers. We assessed if TBE vaccination could offer good value for money at incidences below this threshold. Methods: A closed-cohort Markov model was developed to estimate the cost-effectiveness of TBE vaccination. We compared primary vaccination applied to the whole population (aged above 1 year) and to a subpopulation aged between 60 and 85 years to a scenario without vaccination. Since TBE incidence is often underestimated, we included under-ascertained TBE cases and non-CNS TBE infections. Germany was used as a case study due to the availability of detailed incidence data. Results: Our incidence threshold analysis showed that TBE vaccination offers good value for money well below the WHO threshold in most of the analyzed scenarios. Conclusions: Our results support a recommendation for TBE vaccination even in settings with low numbers of reported cases, especially for older patients. Furthermore, this analysis identified major research gaps regarding the costs, utilities, and clinical progression of TBE.

Despite the availability of tick-borne encephalitis (TBE) vaccines, the incidence of TBE is increasing. To understand the historical patterns of infection, we conducted a global meta-analysis of studies before December 2023 reporting human antibody prevalence against TBEV (TBE virus) among general or high-risk population groups stratified by country, collection year, serological method, and vaccination status. Pooled data were compared within groups over time by random-effects modeling. In total, 2403 articles were retrieved; 130 articles published since 1959 were included. Data were extracted from 96 general populations (117,620 participants) and 71 high-risk populations (53,986 participants) across 33 countries. Germany had the most population groups (21), and Poland had the most participants (44,688). Seven serological methods were used; conventional IgG/IgM ELISAs were the most common (44%). Four studies (1.7%) used NS1-ELISA serology. Between 1956–1991 and 1992–2022, anti-TBEV seroprevalence remained at ~2.75% across all population groups from “high-risk” areas (p = 0.458) but decreased within general populations (1.7% to 1%; p = 0.001) and high-risk populations (5.1% to 1.3%; p < 0.001), possibly due to differences in the study methodologies between periods. This global summary explores how serological methods can be used to assess TBE vaccination coverage and potential exposure to TBEV or measure TBE burden and highlights the need for standardized methodology when conducting TBE seroprevalence studies to compare across populations.

Background: Infection with the tick-borne encephalitis virus (TBEV) can affect the nervous system and lead to significant morbidity. To summarize current knowledge of long-term outcomes following TBEV infection, we systematically reviewed the prevalence of TBEV infection sequelae after hospital discharge across different age groups and follow-up time points. Methods: Studies of adults, children, and “all-age” populations with laboratory-confirmed TBEV infection were identified via electronic database searches. Study categorization was based on follow-up time after hospital discharge: ≤6, 7 to ≤12, or >12 months. Sequelae signs/symptoms were divided into 3 categories: neurological, neuropsychiatric, and other. Data were normalized using weighted means. Heterogeneity was estimated using a meta-analytic random-effects model. Results: Fifteen studies were eligible for analysis (13 included only hospitalized patients). Seventy-nine unique sequelae symptoms were identified. Adults had a higher frequency of persistent symptoms than children (20.6%–100% vs 1.7%–69%). There were high levels of data heterogeneity (I2 > 90%) among all studies. Although the proportion of patients with each sequela fluctuated across time, headache was reported by ≥20% of patients at all time points. Some sequelae also varied by age group; for example, irritability was more frequent in children, while insomnia/sleep disorders were more frequent in adults. Predominant neurological symptoms included balance disorders and headache. Predominant neuropsychiatric symptoms included concentration and memory disorders. Conclusions: Patients experience a variety of neurological, neuropsychiatric, or other sequelae symptoms following TBEV infection that vary over time and across age groups. This study highlights the need for standardized symptom categorization and follow-up time for TBE sequelae studies.

Categorization systems for tick-borne encephalitis virus (TBEV) infection lack consistency in classifying disease severity. To evaluate the need for a standard, consensus-based categorisation system for TBEV infection across subtypes, we gathered an expert panel of clinicians and scientists with diverse expertise in TBEV infection. Consensus was sought using the Delphi technique, which consisted of 2 web-based survey questionnaires and a final, virtual, consensus-building exercise. Ten panellists representing 8 European countries participated in the Delphi exercise, with specialities in neurology, infectious disease, paediatrics, immunology, virology, and epidemiology. Panellists reached unanimous consensus on the need for a standardised, international categorisation system to capture both clinical presentation and severity of TBEV infection. Ideally, such a system should be feasible for use at bedside, be clear and easy to understand, and capture both the acute and follow-up phases of TBEV infection. Areas requiring further discussion were (1) the timepoints at which assessments should be made and (2) whether there should be a separate system for children. This Delphi panel study found that a critical gap persists in the absence of a feasible and practical classification system for TBEV infection. Specifically, the findings of our Delphi exercise highlight the need for the development of a user-friendly classification system that captures the acute and follow-up (i.e., outcome) phases of TBEV infection and optimally reflects both clinical presentation and severity. Development of a clinical categorisation system will enhance patient care and foster comparability among studies, thereby supporting treatment development, refining vaccine strategies, and fortifying public health surveillance.