Published: May 16, 2023
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Chapter 1: A short history of TBE

  • TBE virus is a flavivirus and a prominent tick-borne human pathogen occurring in parts of Asia and Europe.
  • The virus was discovered by Lev A. Zilber and co-workers in the former USSR during an expedition in the Far Eastern taiga under the most difficult conditions in 1937.
  • They and members of a second expedition under the leadership of the Academician Evgeny N. Pavlovsky 1938 elucidated the basic eco-epidemiology of the virus… >>> read more

Chapter 2a: Virology

  • TBEV is the most medically important member of the tick-borne serocomplex group within the genus Flavivirus, family Flaviviridae.
  • Three antigenic subtypes of TBEV correspond to the 3 recognized genotypes: European (TBEV-EU), also known as Western, Far Eastern (TBEV-FE), and Siberian (TBEV-SIB). Additional 2 genotypes have been identified in the Irkutsk region of Russia, currently named TBE virus Baikalian subtype (TBEV-BKL) and TBE virus Himalaya subtype (Himalayan and “178-79” group; TBEV-HIM)… >>> read more

Chapter 2b: The molecular and antigenic structure of the TBEV

  • TBEV-particles are assembled in an immature, noninfectious form in the endoplasmic reticulum by the envelopment of the viral core (containing the viral RNA) by a lipid membrane associated with two viral proteins, prM and E.
  • Immature particles are transported through the cellular exocytic pathway and conformational changes induced by acidic pH in the trans-Golgi network allow the proteolytic cleavage of prM by furin, a cellular protease, resulting in the release of mature… >>> read more

Chapter 3: Transmission/Natural cycle

  • The natural cycle of the TBE virus is dependent on vector ticks and their hosts.
  • Enzootic cycles vary between different habitats and involve sympatric tick vector and host species.
  • There are differing transmission cycles in varying environments, from cold northern coniferous forests to temperate central European forests.
  • Within a natural transmission cycle there are complex differing transmission possibilities – tick to tick…>>> read more

Chapter 4: Pathogenesis of TBE with a focus on molecular mechanisms

  • In this chapter we describe the pathogenesis of tick-borne encephalitis virus (TBEV).
  • To cause infection, TBEV needs to cross three different barriers; the physical, the innate and adaptive and the blood brain barrier.
  • The trigger of innate immune and adaptive immune responses, by TBEV is necessary to clear the infection.
  • TBEV employs strategies to evade the innate immune response.
  • Tools to study TBEV pathogenicity such as mouse… >>> read more

Chapter 5: TBE in adults

  • TBE is the most important tick-borne arbovirus disease of humans. Epidemiological data indicate a trend towards an increasing severity with higher age.
  • A number of possible genetic and non-genetic risk factors has been identified, which might have an impact on the manifestation and severity of human disease.
  • Different TBEV strains seem to cause differing clinical courses of disease. While the TBE-Eu mainly causes a biphasic course… >>> read more

Chapter 6: TBE in children

  • Most cases of TBE in childhood will present similarly as cases in adults. However, a more diffuse clinical picture is seen specially in preschool children.
  • Laboratory work-up may show elevated blood inflammatory indices, but cerebrospinal fluid analysis and anti-TBEV serology are needed for establishing the diagnosis.
  • There is no specific treatment for TBE; supportive care needs to be provided based on the individual clinical course… >>> read more

Chapter 7: TBE in special clinical situations

  • TBE often takes a severe clinical course in immuno-supressed patients.
  • In transplant patients TBE usually takes a fatal course.
  • TBE vaccination in immuno-suppressed patients can be non-effective
  • TBE in pregnancy has been rarely reported; from recent cases there is no evidence of transplacental infection of the offspring.
  • The alimentary route of infection of TBE is still common in some European countries resulting in a high clinical manifestation index.
  • TBEV can be infectious in milk and milk products… >>> read more

Chapter 8: TBE in animals

  • TBEV infection via routes other than tick bites
  • Animal hosts of the TBEV
  • Diagnosis of TBEV infection in animals
  • Implications for human TBE transmission… >>> read more

Chapter 9: Immunology of TBEV infection

  • Tick-borne encephalitis (TBE) is a viral infectious disease of the central nervous system caused by the tick-borne encephalitis virus (TBEV).
  • TBE is usually a biphasic disease and in humans the virus can only be detected during the first (unspecific) phase of the disease.
  • Pathogenesis of TBE is not well understood, but both direct viral effects and immune-mediated tissue damage of the central nervous system may contribute to the natural course of TBE.
  • The effect of TBEV on the innate immune system… >>> read more

Chapter 10: Diagnosis

Tick-borne encephalitis (TBE) manifests as a non-specific disease with symptoms of a febrile, influenza-like illness and, in some cases, an inflammatory infection of the central nervous system (CNS) that follows a few days later. Due to the lack of specific symptoms, a definitive confirmation of the diagnosis requires taking the history of the patient with regard to a possible tick bite or ingestion of unpasteurized milk in a known or suspected endemic area, plus a positive result from a classical virological test that confirms TBEV-infection…>>> read more

Chapter 11: General epidemiology of TBE

  • Tick-borne encephalitis virus (TBEV) exists in natural foci, which are areas where TBEV is circulating among its vectors (ticks of different species and genera) and reservoir hosts (usually rodents and small mammals).
  • Based on phylogenetic studies, four TBEV subtypes (Far-Eastern, Siberian, European, Baikalian) and two putative subtypes (Himalayan and “178-79” group) are known. Within each subtype, some genetic lineages are described.
  • The European subtype (TBEV-EU)… >>> read more

Chapter 12a: TBE-epidemiology by country – an overview

  • TBE is a flavivirus infection of the central nervous system (CNS), transmitted by ticks and in some rare instances by ingestion of unpasteurized milk.
  • TBE is diagnosed in the forested belts of Northern Eurasia ranging from eastern France and Norway down to northern Italy through central and Eastern Europe, Russia, Kazakhstan, and China to the northern Japanese island of Hokkaido.
  • About 10,000 cases of TBE are reported annually… >>> read more

Chapter 12b: TBE-by country – country data

While TBE is listed as a “communicable disease” in the EU since 2012, each country implements reporting nationally with own resources and methods. In most instances, reporting of TBE cases is based on passive surveillance and thus largely depend on disease awareness with physicians and on availability, cost and use of serological tests for TBE diagnosis. Systematic, regular use of TBE serology in the appropriate clinical setting is in place in few countries only, despite the fact that it would be a necessary prerequisite to gain… >>> read more

Chapter 12c: Global distribution of the TBEV

In the map below, the areas highlighted in orange indicate TBEV endemic regions as documented either by 1) TBEV detection in ticks or animals; or 2) detection of specific anti-TBE antibodies in reservoir animals or human sera; or 3) microbiologically confirmed locally acquired TBE cases in humans who contracted the disease in the respective region. This map does not reflect the incidence of the disease or the prevalence of the virus in a given area… >>> view map

Chapter 13: TBE as a matter of public health

  • The incidence of TBE ranges from ‘only single sporadic cases’ to >10/105 per year depending on the region and on the year of analysis.
  • This number may be considered as ‘low’ – not only for individual risk but also from a public health perspective.
  • If an individual does contract TBE, the disease may deeply change her/his life due to the need for acute hospital care and due to potentially severe and long-term sequelae. In 1–2% (-20%) of cases, TBE may even result in death… >>> read more

Chapter 14: TBE-Prevention: Vaccines and Immunoglobulins

  • Worldwide there are 6 different TBE vaccines – two from Western Europe, three from Russia and one from China. The two western European vaccines and one of the Russian vaccines have an adult and a pediatric formulation.
  • The products names are FSME IMMUN and FSME-IMMUN Junior; Encepur adults and Encepur children, Klesch-E-Vac, EnceVir and EnceVir Neo, Dry lyophilized TBE Moscow and Sen Tai Bao
  • All TBE vaccines except the one from China have similar…>>> read more


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