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.
Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Zaloška 4, Ljubljana, Slovenia.
Antiviral Res. 2019 Apr;164:23-51. doi: 10.1016/j.antiviral.2019.01.014. Epub 2019 Jan 31.
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.
蜱传脑炎（TBE）是由蜱传脑炎病毒（TBEV）感染引起的疾病，通常局限于发热性疾病，但可能导致非常侵袭性的下游神经表现。该疾病在欧洲和东北亚的森林地区流行，通常由三种 TBEV 亚型之一的感染引起，即欧洲（TBEV-Eu）、西伯利亚（TBEV-Sib）或远东（TBEV-FE）亚型。除了这三种主要的 TBEV 亚型外，最近还描述了另外两种亚型，即贝加尔湖（TBEV-Bkl）和喜马拉雅山（TBEV-Him）亚型。在欧洲，TBEV-Eu 感染通常只会导致与死亡率<2%相关的轻度 TBE。TBEV-Sib 感染也会导致通常较轻的 TBE，伴有非瘫痪性发热性脑炎，但存在由慢性病毒感染引起的持续性 TBE 的趋势。TBE-FE 感染被认为会引起最严重的 TBE 形式。然而，重要的是，病毒亚型并不是 TBE 严重程度的唯一决定因素；实际上，任何亚型的感染都与轻度和重度 TBE 有关。与这一观察结果一致的是，尽管 TBEV-Sib 和 TBEV-FE 亚型似乎比 TBEV-Eu 更能引起严重的 TBE，但俄罗斯的总体 TBE 死亡率约为 2%。另一方面，俄罗斯的 TBEV-Sib 和 TBEV-FE 亚型感染与其他地方很少见甚至不存在的独特形式的 TBE 有关，例如出血性和慢性（进行性）疾病。对于俄罗斯和哈萨克斯坦的暴露后预防和 TBE 治疗，目前使用一种特定的抗 TBEV 免疫球蛋白，其疗效有充分的记录，但由于担心在天真个体中抗体增强疾病，欧洲已停止使用特定的 TBEV 免疫球蛋白。因此，新的治疗方法至关重要。本综述总结了 TBE 的发病机制和临床特征以及欧洲和俄罗斯可用的不同疫苗制剂的现有数据。此外，还回顾了新的治疗可能性，包括小分子药物和实验性免疫疗法。作者警告说，他们对批准或实验性治疗的描述不应被视为对患者护理的建议。
