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.

Department of Clinical Microbiology Virology Umeå University and Laboratory for Molecular Infection Sweden Umeå Univeristy Umeå Sweden

Department of Infectious Diseases and Neuroinfections Medical University of Bialystok Bialystok Poland

Department of Infectious Diseases Ceske Budejovice Hospital České Budĕjovice Czech Republic; Tropical and Infectious Disease Unit Royal Liverpool University Hospital Liverpool UK

Department of Medicine 2 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

FSBSI Chumakov FSC R and D IBP RAS Moscow 108819 Russia

FSBSI Chumakov FSC R and D IBP RAS Moscow 108819 Russia; Sechenov 1st Moscow State Medical University Moscow 119991 Russia

Institute of Chemical Biology and Fundamental Medicine Siberian Branch of Russian Academy of Science Novosibirsk Russia

Institute of Microbiology and Immunology Faculty of Medicine University of Ljubljana Zaloška 4 Ljubljana Slovenia

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

Veterinary Research Institute Hudcova 70 CZ 62100 Brno Czech Republic; KP Therapeutics Ltd 86 Deansgate Manchester M3 2ER UK

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