Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 29;12(6):ofaf317.
doi: 10.1093/ofid/ofaf317. eCollection 2025 Jun.

Clinical Spectrum and Dynamics of Sequelae Following Tick-Borne Encephalitis Virus Infection: A Systematic Literature Review

Kate Halsby  1 , Liesl Gildea  2 , Pingping Zhang  3 , Frederick J Angulo  4 , Andreas Pilz  5 , Jennifer Moisi  6 , Ann Colosia  7 , Johann Sellner  8   9   10
Affiliations

Clinical Spectrum and Dynamics of Sequelae Following Tick-Borne Encephalitis Virus Infection: A Systematic Literature Review

Kate Halsby et al. Open Forum Infect Dis. .

Erratum in

Abstract

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 (I 2 > 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.

Keywords: clinical manifestations; long-term outcome; nervous system damage; sequelae; tick-borne encephalitis.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. Pfizer provided funding for publication support in the form of manuscript writing, styling, and submission. L. G. and A. C. are full-time employees of RTI Health Solutions, an independent nonprofit research organization retained by Pfizer to conduct the research that is the subject of this article. Their compensation is unconnected to the studies on which they work. K. H., P. Z., F. J. A., A. P., and J. M. are employees of Pfizer and may hold shares and/or stock options in the company. J. S. has received honoraria for lectures, preparation of teaching material, and participation in scientific advisory boards from Amgen/Horizon, AstraZeneca/Alexion, Astro Pharma BMS, Biogen, BMS, GL Lannach, GSK, Immunic, Lundbeck, Novartis, Pfizer, Roche, Sandoz, and Sanofi.

Figures

Figure 1.
Figure 1.
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) diagram for systematic literature review, adapted from Page et al [28]. Abbreviation: ECDC, European Centre for Disease Prevention and Control.
Figure 2.
Figure 2.
Neurological sequelae signs and symptoms. Symptoms with 1 data point include akinesia (2.03%) and neurological deficit (3.70%) (both at <6 months).
Figure 3.
Figure 3.
Neuropsychiatric sequelae signs and symptoms. Symptoms with 1 data point include attention problems (8.04%) at 7 to ≤12 months, psychotic (0.09%) and psychoorganic (0.19%) symptoms (both at <6 months).
Figure 4.
Figure 4.
Other sequelae signs and symptoms. Symptoms with 1 data point include abdominal pain (4.05%) and muscle wasting/weakness (7.41%) (both at <6 months) and worsening of school grades (5.29%), amplified reflexes (8.04%), and electroencephalographic anomalies (1.76%) (at 7 to ≤12 months). For fatigue, note that Nygren et al [27] reported fatigue and general weakness separately; fatigue was selected for the purposes of categorization as it was reported by a higher proportion of patients.
See this image and copyright information in PMC

References

    1. European Centre for Disease Prevention and Control . Factsheet about tick-borne encephalitis (TBE). 2024. Available at: https://www.ecdc.europa.eu/en/tick-borne-encephalitis/facts/factsheet. Accessed 17 May 2024.
    1. Bojkiewicz E, Toczyłowski K, Sulik A. Tick-borne encephalitis—a review of current epidemiology, clinical symptoms, management and prevention. Przegl Epidemiol 2020; 74:316–25. - PubMed
    1. Bogovic P, Lotric-Furlan S, Strle F. What tick-borne encephalitis may look like: clinical signs and symptoms. Travel Med Infect Dis 2010; 8:246–50. - PubMed
    1. Sellner J, Bogovic P, Zajkowska J. Chapter 9: TBE in adults. In: Dobler G, Erber W, Broker M, Chitimia-Dobler L, Schmitt H-J, eds. The TBE book: a comprehensive guide to tick-borne encephalitis. 7th ed. Global Health Press, Singapore, 2024:124–139.
    1. Dai X, Shang G, Lu S, Yang J, Xu J. A new subtype of eastern tick-borne encephalitis virus discovered in Qinghai-Tibet Plateau, China. Emerg Microbes Infect 2018; 7:74. - PMC - PubMed