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Antiviral Res. 2019 Apr;164:23-51. doi: 10.1016/j.antiviral.2019.01.014. Epub 2019 Jan 31.

Tick-borne encephalitis in Europe and Russia: Review of pathogenesis, clinical features, therapy, and vaccines.

Author information

1
Veterinary Research Institute, Hudcova 70, CZ-62100, Brno, Czech Republic; Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, CZ-37005, Ceske Budejovice, Czech Republic. Electronic address: ruzekd@paru.cas.cz.
2
Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Zaloška 4, Ljubljana, Slovenia.
3
Department of Medicine II, Division of Infectious Diseases, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106, Freiburg, Germany; Gesundheitszentrum Oberkirch, Am Marktplatz 8, 77704, Oberkirch, Germany.
4
Department of Infectious Diseases, Ceske Budejovice Hospital, České Budĕjovice, Czech Republic; Tropical and Infectious Disease Unit, Royal Liverpool University Hospital, Liverpool, UK.
5
Veterinary Research Institute, Hudcova 70, CZ-62100, Brno, Czech Republic; Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, CZ-37005, Ceske Budejovice, Czech Republic.
6
FSBSI "Chumakov FSC R&D IBP RAS", Moscow, 108819, Russia; Sechenov First Moscow State Medical University, Moscow, 119991, Russia.
7
FSBSI "Chumakov FSC R&D IBP RAS", Moscow, 108819, Russia.
8
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Science, Novosibirsk, Russia.
9
Veterinary Research Institute, Hudcova 70, CZ-62100, Brno, Czech Republic; KP Therapeutics Ltd, 86 Deansgate, Manchester, M3 2ER, UK.
10
Department of Clinical Microbiology, Virology, Umeå University and Laboratory for Molecular Infection Sweden (MIMS), Umeå Univeristy, Umeå, Sweden.
11
Department of Infectious Diseases and Neuroinfections, Medical University of Bialystok, Bialystok, Poland.

Abstract

Tick-borne encephalitis (TBE) is an illness caused by tick-borne encephalitis virus (TBEV) infection which is often limited to a febrile illness, but may lead to very aggressive downstream neurological manifestations. The disease is prevalent in forested areas of Europe and northeastern Asia, and is typically caused by infection involving one of three TBEV subtypes, namely the European (TBEV-Eu), the Siberian (TBEV-Sib), or the Far Eastern (TBEV-FE) subtypes. In addition to the three main TBEV subtypes, two other subtypes; i.e., the Baikalian (TBEV-Bkl) and the Himalayan subtype (TBEV-Him), have been described recently. In Europe, TBEV-Eu infection usually results in only mild TBE associated with a mortality rate of <2%. TBEV-Sib infection also results in a generally mild TBE associated with a non-paralytic febrile form of encephalitis, although there is a tendency towards persistent TBE caused by chronic viral infection. TBE-FE infection is considered to induce the most severe forms of TBE. Importantly though, viral subtype is not the sole determinant of TBE severity; both mild and severe cases of TBE are in fact associated with infection by any of the subtypes. In keeping with this observation, the overall TBE mortality rate in Russia is ∼2%, in spite of the fact that TBEV-Sib and TBEV-FE subtypes appear to be inducers of more severe TBE than TBEV-Eu. On the other hand, TBEV-Sib and TBEV-FE subtype infections in Russia are associated with essentially unique forms of TBE rarely seen elsewhere if at all, such as the hemorrhagic and chronic (progressive) forms of the disease. For post-exposure prophylaxis and TBE treatment in Russia and Kazakhstan, a specific anti-TBEV immunoglobulin is currently used with well-documented efficacy, but the use of specific TBEV immunoglobulins has been discontinued in Europe due to concerns regarding antibody-enhanced disease in naïve individuals. Therefore, new treatments are essential. This review summarizes available data on the pathogenesis and clinical features of TBE, plus different vaccine preparations available in Europe and Russia. In addition, new treatment possibilities, including small molecule drugs and experimental immunotherapies are reviewed. The authors caution that their descriptions of approved or experimental therapies should not be considered to be recommendations for patient care.

KEYWORDS:

Antiviral therapy; Clinical course; Pathogenesis; Tick-borne encephalitis; Tick-borne encephalitis virus; Vaccines

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