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The emergence of tick-borne encephalitis (TBE) in Europe marked several significant milestones. The discovery of TBE in Czechoslovakia in 1948, with Gallia and Krejčí simultaneously isolating the TBE virus (TBEV) from human samples for the first time in Europe outside the Soviet Union, was pivotal. Subsequent TBEV isolation from ticks suggested the viral transmission via this vector. In 1951, the outbreak in Rožňava in Slovakia (Czechoslovakia) revealed an unexpected mode of transmission, unpasteurized milk from a local dairy, challenging existing understanding. Investigations exposed illicit practices of mixing cow's milk with goat's milk for economic gains. Laboratory research confirmed the outbreak was caused by TBEV, which was substantiated by serological analyses. This was the first and largest documented alimentary TBE outbreak in history. In this review, we delve into both published sources and unpublished archival data, offering a comprehensive understanding of these historic accomplishments and shedding light on these pivotal moments., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Tick-borne encephalitis (TBE) is a potentially fatal disease common in much of Europe and Asia. There is no specific therapy for the treatment of TBE patients. However, several efforts are being made to develop small molecules that specifically interfere with the life cycle of TBE virus. In particular, recently various nucleoside analogues that can inhibit the viral replicase, such as the RNA-dependent RNA polymerase or viral methyltransferases, have been explored. In addition, human or chimeric (i.e., structural chimeras that combine mouse variable domains with human constant domains) monoclonal antibodies with promising potential for post-exposure prophylaxis or early therapy have been developed. This review summarizes the latest directions and experimental approaches that may be used to combat TBE in humans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)