Elsevier

The Lancet

Volume 371, Issue 9627, 31 May–6 June 2008, Pages 1861-1871
The Lancet

Seminar
Tick-borne encephalitis

https://doi.org/10.1016/S0140-6736(08)60800-4Get rights and content

Summary

We review the epidemiological and clinical characteristics of tick-borne encephalitis, and summarise biological and virological aspects that are important for understanding the life-cycle and transmission of the virus. Tick-borne encephalitis virus is a flavivirus that is transmitted by Ixodes spp ticks in a vast area from western Europe to the eastern coast of Japan. Tick-borne encephalitis causes acute meningoencephalitis with or without myelitis. Morbidity is age dependent, and is highest in adults of whom half develop encephalitis. A third of patients have longlasting sequelae, frequently with cognitive dysfunction and substantial impairment in quality of life. The disease arises in patchy endemic foci in Europe, with climatic and ecological conditions suitable for circulation of the virus. Climate change and leisure habits expose more people to tick-bites and have contributed to the increase in number of cases despite availability of effective vaccines. The serological diagnosis is usually straightforward. No specific treatment for the disease exists, and immunisation is the main preventive measure.

Introduction

The first description of a tick-borne encephalitis-like disease dates back to Scandinavian church records from the 18th century. The disease was described as a clinical entity in Austria in 19311 and its causative agent was isolated in the eastern region of Russia in 1937. More than 10 000 cases of the disease arise every year,2 and in terms of morbidity, this frequency is second only to Japanese encephalitis among neurotropic flaviviruses. In Europe (Russia excluded), 3000 cases are treated in hospital and reported each year,3 with increasing numbers during the past decade.

We review here clinical and epidemiological aspects, with emphasis on the European virus subtype, and summarise the virological and biological properties of the virus that are important for the understanding of transmission and prevention.4, 5, 6, 7

Section snippets

Virology and cellular physiology

Tick-borne encephalitis virus (TBEV) is a member of the genus flavivirus, family Flaviviridae. Flaviviruses are icosahedral enveloped 50 nm viruses with an RNA genome of about 11 kb. The TBEV genome per se acts as an infectious messenger RNA, and codes in one open reading frame for a polyprotein of 3414 aminoacids, which is co-translationally and post-translationally cleaved by viral and cellular proteases to three structural (C, prM, and E) and seven non-structural proteins (NS1, NS2A, NS2B,

Evolution and epidemiology

Other medically important flaviviruses include the mosquito-borne yellow fever, dengue (DENV 1,2,3,4), Japanese encephalitis, and West Nile viruses. The substantial homology between these viruses has practical implications in diagnostics because of cross-reactions. Phylogenetic analyses have shown that tick-borne flaviviruses are distinct from mosquito-borne viruses and seem to evolve more slowly16 because of the tick's long lifespan of usually about 2 years. Unlike mosquito-borne viruses, no

Clinical presentation and pathogenesis

Tick-borne encephalitis follows an incubation period of a median of 8 days (range 4–28) after tick bite,36 which is unnoticed in about a third of patients.36, 38, 64 Typically, the disease is biphasic in 72–87% of patients.36, 38, 64 The median duration of the first stage of illness is 5 days (range 2–10) with a 7 day (range 1–21) symptom-free interval to the second phase. In the first viraemic stage, the dominant symptoms are fever (99%), fatigue (63%), general malaise (62%), and headache and

Laboratory diagnosis

The diagnostics of TBEV are straightforward: as a rule, TBEV-immunoglobulin M (IgM) and usually TBEV-IgG antibodies are present in the first serum samples taken when CNS symptoms manifest in the second phase of the disease. In the first phase of illness, the virus can be isolated or detected by RT-PCR from blood, but only rarely is TBEV detected at the beginning of the second phase in CSF109 and occasionally in cases of progressive disease.106 Intrathecal IgM and IgG antibody response can be

Treatment and prophylaxis

No specific treatment for tick-borne encephalitis exists. In a large German study,36 12% of patients needed intensive care and 5% assisted ventilation. The use of corticosteroids is not supported by any controlled study or uncontrolled studies.38 No established treatment exists for chronic progressive forms. However, one progressive case from Lithuania38 responded to corticosteroid treatment and plasma exchange. This finding suggests the existence of two categories of progressive disease: (1)

Search strategy and selection criteria

A search was done in PubMed on “encephalitis”, “tick-borne” (MeSH), from 1970 and onwards. 1318 titles were screened in English or German for this Seminar. Additionally, references from the reference list of these publications were included if relevant.

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