Burden of Tick-borne Encephalitis and Cost-effectiveness of Vaccination in the Czech Republic

Clinical and Public-Health Impact of Tick-Borne Encephalitis: A Prospective Multicenter Observational Study With 12-Month Follow-up and Cost-Effectiveness Analysis

This observational study follows children and adults who were hospitalized with tick-borne encephalitis (TBE) in the Czech Republic. The aim is to better understand how individuals recover from TBE, which symptoms may persist after the infection, and which patients may require additional support during their recovery. Participants are examined several times after hospital discharge (at 2-4 weeks, 3 months, 6 months, and 12 months) to observe changes in symptoms, functional status, and daily activities. Follow-up assessments include evaluation of common post-infection problems such as tiredness, headaches, memory or concentration difficulties, sleep issues, or limb weakness. Symptoms lasting for several months are categorized as post-encephalitic syndrome (PES).

The study also assesses how TBE affects daily functioning, school and work performance, and overall quality of life using questionnaires and short functional assessments. In addition, the study includes a public-health component that estimates the broader impact of TBE in the population and evaluates the potential benefits of vaccination in preventing long-term health complications.

The findings aim to support improved patient care, follow-up planning, and evidence-based public-health decision-making in the Czech Republic.

Tick-borne encephalitis (TBE) is a serious viral infection of the central nervous system and represents a longstanding public-health challenge in the Czech Republic, a country with one of the highest TBE incidences in Europe. Although an effective vaccine has been available for decades, population-level vaccination coverage remains low, resulting in persistently high incidence across all age groups and numerous severe cases requiring hospitalization. Despite extensive clinical experience with TBE, the long-term course of the disease, the full spectrum of postencephalitic syndrome (PES), and the associated functional and neurocognitive burden remain incompletely quantified in contemporary, real-world populations. Updated evidence is also needed to inform public-health planning and to evaluate the potential health and economic benefits of broader TBE vaccination in this high-endemicity setting.

The study is a prospective multicenter observational investigation enrolling children and adults hospitalized with laboratory-confirmed TBE across four major infectious disease centers in the Czech Republic. Standardized clinical and functional assessments are applied to capture both the acute clinical course and the long-term recovery trajectory. Acute disease severity is classified using predefined clinical criteria, including the presence of motor deficit (paresis) during hospitalization, intensive-care unit admission, prolonged hospitalization (length of stay >10 days), or death. Follow-up assessments occur at 2-4 weeks, 3 months, 6 months, and 12 months after discharge.

Long-term outcomes are evaluated using validated tools, including the modified Rankin Scale (mRankin) to assess global functional disability and the Minimum European Health Module (MEHM) to capture self-perceived health, activity limitation, and chronic morbidity. A central focus of the study is the characterization of postencephalitic syndrome (PES), the most common long-term complication of TBE. PES is defined as the persistence of one or more neurological, cognitive, or functional symptoms lasting for at least 6 months after acute infection. These symptoms may include chronic fatigue, impaired concentration or memory, cognitive slowing, sleep disturbances, headaches, irritability, anxiety, or reduced exercise tolerance. Persistent motor deficits, such as paresis or impaired coordination, are evaluated as integral components of PES, reflecting a more severe neurological phenotype. Detailed symptom-level data and functional assessments are collected to comprehensively describe the prevalence, severity, and heterogeneity of PES and its impact on long-term quality of life.

The study examines demographic and clinical predictors of adverse outcomes, including the role of age, comorbidities, markers of central nervous system involvement during the acute phase, and initial disease severity. These analyses are intended to support improved prognostic counseling and inform follow-up and rehabilitation strategies.

A public-health and economic component quantifies the overall burden of TBE in disability-adjusted life years (DALYs), integrating observed functional outcomes, sequelae duration, disability weights, and TBE-related mortality. DALY estimates are combined with national epidemiological surveillance data to ensure representativeness across age groups and regions. These outcomes will form the basis for a decision-analytic model evaluating the cost-effectiveness of increasing TBE vaccination coverage. The model compares current vaccination uptake with expanded coverage scenarios across different age groups and generates estimates of incremental cost-effectiveness ratios (ICERs), projected health gains, reductions in long-term disability, and potential healthcare cost savings. The economic modeling relies solely on aggregated clinical and epidemiological data and does not include any patient-level interventions.

By integrating prospective clinical follow-up, standardized functional assessments, detailed characterization of PES, and health-economic modeling, the study provides a comprehensive evaluation of the clinical and economic burden of TBE in the Czech Republic. The findings may inform clinical practice, long-term patient management, and national vaccination policy, contributing to improved prevention and mitigation of TBE-related morbidity.

Inclusion Criteria:

• Hospitalization due to suspected central nervous system (CNS) infection.
• Laboratory-confirmed TBE, defined as:

the presence of CNS symptoms and cerebrospinal fluid pleocytosis (>5 × 10⁶/L) and TBEV IgM and IgG seropositivity in serum, or detection of TBEV IgM in CSF in previously vaccinated individuals.

• All age groups (children and adults).
• Ability to participate in scheduled follow-up (in person or via telephone).
• Informed consent provided by the patient or legal guardian (for minors).

Exclusion Criteria:

• Alternative diagnosis explaining the CNS symptoms
• Missing essential clinical or laboratory data required to confirm TBE or assess outcomes.
• Refusal or inability to provide informed consent.
• Inability to complete follow-up assessments, including situations where reliable contact cannot be maintained.
• Coexisting severe neurological disorder unrelated to TBE that prevents meaningful evaluation of sequelae (e.g., advanced neurodegenerative disease, severe preexisting motor disability).