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

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.

Study Overview

• Status: Recruiting
• Conditions: Tick Borne Encephalitis (TBE)
• Intervention / Treatment: Other: No intervention

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 209

Contacts and Locations

• Study Contact: Name: Martin Slížek, MD; Phone Number: 00420602269494; Email: martin.slizek89@gmail.com

Study Locations

• Czechia
  • Jihočeský kraj
    • České Budějovice, Jihočeský kraj, Czechia, 37001
      • Recruiting
      • Ceske Budejovice Hospital
      • Contact: Vojtěch Pražák, MD; Phone Number: 00420387874601; Email: infekcni@nemcb.cz
      • Principal Investigator: Vojtěch Pražák, MD
  • Moravskoslezský kraj
    • Ostrava, Moravskoslezský kraj, Czechia, 70800
      • Recruiting
      • Ostrava University Hospital
      • Contact: Kateřina Pohludková, MD; Phone Number: 00420 597 373 480; Email: katerina.pohludkova@fno.cz
      • Principal Investigator: Kateřina Pohludková, MD
  • Pardubický kraj
    • Pardubice, Pardubický kraj, Czechia, 53001
      • Recruiting
      • Pardubická nemocnice
      • Contact: Lukáš Chovanec, MD; Phone Number: +420 466 014 613; Email: lukas.chovanec@nempk.cz
      • Principal Investigator: Lukáš Chovanec, MD
  • Prague
    • Prague, Prague, Czechia, 18081
      • Recruiting
      • Bulovka University Hospital
      • Contact: Martin Slížek, MD; Phone Number: 00420602269494; Email: martin.slizek89@gmail.com
      • Principal Investigator: Martin Slížek, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Hospitalized children and adults with confirmed tick-borne encephalitis (TBE) treated at four infectious disease centers in the Czech Republic. All participants had clinical symptoms of central nervous system involvement, cerebrospinal fluid pleocytosis, and laboratory confirmation of TBEV infection. Patients were enrolled during their acute hospitalization and followed prospectively for up to 12 months as part of a standardized clinical and functional outcome assessment program.

Description

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).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
TBE cohort; Children and adults hospitalized with confirmed tick-borne encephalitis, followed prospectively for 12 months.	Other: No intervention; Observational study only. Participants receive standard clinical care; no experimental or study-specific interventions are administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence and Severity of Post-Encephalitic Syndrome (PES)	PES is defined as the presence of ≥1 neurological, cognitive, or functional symptom persisting ≥6 months after acute TBE. PES severity is graded as: Mild: mRankin = 1, no limitation of usual activities Moderate: mRankin = 2 and/or limited but preserved independence, or poor self-perceived health (MEHM) Severe: mRankin ≥3, severe limitation of daily activities, very poor self-perceived health, or death.	6 months post-discharge and 12 months post-discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistent Motor Deficit	Presence of persistent paresis or other objective motor impairment at follow-up attributed to TBE.	6 months post-discharge and 12 months post-discharge
Acute Disease Severity Classification	Acute course categorized as severe if any of the following criteria are present: motor deficit (paresis) during hospitalization, ICU admission, hospitalization >10 days, death. All others classified as mild.	During index hospitalization
Functional Status by Modified Rankin Scale (mRankin)	Global functional disability assessed by mRankin (0-6).	2-4 weeks post-discharge; 3 months; 6 months; 12 months
Self-perceived Health and Activity Limitation (MEHM Score)	Minimum European Health Module (MEHM), including perceived health, activity limitation, and chronic morbidity.	2-4 weeks post-discharge; 3 months; 6 months; 12 months
Persistence or Resolution of Individual PES Symptoms (Structured Symptom Checklist)	This outcome is assessed using a structured PES Symptom Checklist developed for standardized evaluation of post-encephalitic symptoms. The checklist captures the presence or absence of individual symptoms associated with post-encephalitic syndrome (PES), including fatigue, exertion intolerance, headache, cognitive slowing, memory problems, concentration difficulties, sleep disturbances, sensory deficits, and emotional instability. Each symptom is recorded as present or absent at each follow-up assessment. The outcome will be reported as: number of symptoms present (range 0-X), and presence/absence of each individual symptom (binary assessment). Unit of Measure: Number of symptoms (count) and binary presence/absence for each symptom	2-4 weeks post-discharge; 3 months; 6 months; 12 months
Hospital Length of Stay (LOS)	Total duration of the index hospital stay in days, from hospital admission for acute TBE to hospital discharge.	From hospital admission to hospital discharge, assessed over an expected hospitalization period of up to 90 days.
ICU Admission	Whether the patient was admitted to intensive care during acute TBE and the length of ICU stay.	From hospital admission to hospital discharge, including any ICU stay, assessed over an expected hospitalization period of up to 90 days.
All-Cause Mortality (binary outcome)	All-cause mortality recorded as a binary outcome (alive/deceased) at predefined time points. Mortality during the index hospitalization and mortality during follow-up (6 and 12 months post-discharge) are recorded separately. Unit of Measure: Proportion of participants deceased (%)	During index hospitalization; 6 months post-discharge; 12 months post-discharge
Cost-Effectiveness of TBE Vaccination	Cost-effectiveness of increasing TBE vaccination coverage in the Czech Republic based on disability-adjusted life years (DALYs) derived from observed functional outcomes (mRankin, MEHM), PES prevalence, symptom duration, and TBE-associated mortality. A decision-analytic model will estimate incremental cost-effectiveness ratios (ICERs) across different age groups and vaccination coverage scenarios using real-world clinical data combined with national surveillance data.	Final analysis at 12 months after completion of follow-up.
Change in Functional Status (modified Rankin Scale, mRankin)	Change in global functional disability assessed using the modified Rankin Scale (0-6). Scores are recorded at each follow-up visit to evaluate recovery trajectory and functional outcomes after acute TBE.	Baseline (hospitalization), 2-4 weeks post-discharge, 3 months, 6 months, 12 months.
Change in Self-Perceived Health (Minimum European Health Module, MEHM)	Change in self-perceived health, activity limitation, and chronic morbidity assessed using the Minimum European Health Module (MEHM). Unit of Measure: MEHM score (categorical responses)	Baseline (hospitalization), 2-4 weeks post-discharge, 3 months, 6 months, 12 months.

Collaborators and Investigators

• Sponsor: Charles University, Czech Republic
• Collaborators: University Hospital Ostrava; Bulovka Hospital; České Budějovice Hospital; Hospital Pardubice

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: December 9, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: age; cost-effectiveness; sequelae; encephalitis; TBEV; tick-borne encephalitis; post-encephalitic syndrome
• Additional Relevant MeSH Terms: Infectious Encephalitis; Vector Borne Diseases; Neuroinflammatory Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; RNA Virus Infections; Virus Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Tick-Borne Diseases; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Encephalitis, Arbovirus; Encephalitis; Encephalitis, Tick-Borne
• Other Study ID Numbers: TBE-CZ-OBS-2023-01; 06_SM_FNB_002 (Other Grant/Funding Number: Bulovka University Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared. Only aggregated, anonymized results will be made available in publications.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No