Description

Tickborne encephalitis (TBE), also known as Central European encephalitis or Russian spring-summer encephalitis, is a flavivirus infection of the central nervous system. The two most important genotypes of tickborne encephalitis virus (TBEV) are European and Far Eastern, transmitted by the hard ticks Ixodes ricinus and I. persulcatus, respectively. Human TBEV infections are acquired through bites of infected ticks or, rarely, by ingesting unpasteurized dairy products primarily from infected goats, sheep, or cows (1-4).

Occurrence

TBEV is endemic in temperate regions of Europe and Asia, from approximately 6 to 143 degrees of longitude (eastern France to northern Japan), from 40 to 65 degrees of latitude (northern Russia to Albania), and up to about 1,400 m in altitude. It exists in highly discontinuous, woodland foci that harbor the tick vectors and small mammalian hosts (especially rodents). Countries considered to have the highest incidences include Austria, Belarus, Croatia, Czech Republic, Estonia, Finland, Germany, Hungary, Latvia, Lithuania, Poland, Russia, Slovakia, Slovenia, Sweden, Switzerland, and Ukraine. Countries considered to have lower incidences include Albania, Bosnia, China, Denmark (Bornholm Island only), France, Greece, Italy, Japan, Kazakhstan, Moldavia, Mongolia, Norway, Romania, and Serbia. Countries from which no TBE cases have ever been reported include Belgium, Ireland, Luxembourg, the Netherlands, Portugal, Spain, and the United Kingdom (5-8). A crude map of TBE risk areas in Europe and a table of reported TBE cases in European countries in 2005 is available from The International Scientific Working Group on Tick-Borne Encephalitis (ISW-TBE) at http://www.isw-tbe.info (select “News”).

Most TBE cases occur during April-November. Infections with the Eastern TBEV genotype usually occur in the spring, while infections with the European genotype usually occur in early autumn. Infected ticks can be found in deciduous forests with ample ground cover or in transition zones between forests and grasslands. Questing, or blood-seeking, ticks are found on low-lying vegetation, especially near trails used by small mammals (2,5).

Risk for Travelers

Most TBEV infections result from tick bites acquired in forested areas through activities such as camping, hiking, fishing, bicycling; collecting mushrooms, berries, or flowers; and outdoor occupations such as forestry or military training. The risk is negligible for persons who remain in urban or unforested areas and who do not consume unpasteurized dairy products (9). Vector tick density and infection rates in TBEV- endemic foci are highly variable. For example, TBEV infection rates in I. ricinus in central Europe vary from less than 0.1% to approximately 5%, depending on geographic location and time of year, while rates of up to 40% have been reported in I. persulcatus in Siberia (2-5).

Surveillance for TBEV activity and TBE cases can vary markedly among countries and among regions within a given country (8). The number of TBE cases reported by a country depends on the ecology and geographic distribution of TBEV in that country, the intensity of diagnosis and surveillance, and the vaccine coverage of the population. Therefore, the number of TBE cases reported in an area is an unreliable predictor of a traveler’s risk of infection. In Austria, for example, the reported annual incidence of TBE has declined approximately 10-fold since 1981, when a national vaccination program was implemented (10). However, the risk of TBEV infection to unvaccinated tourists to Austria is likely to be constant, because while vaccination prevents TBEV infection in humans, it has no effect on tick infection rates. During the TBEV transmission season in a highly endemic Austrian province, the risk of TBE in unvaccinated tourists has been estimated at 1 case per 10,000 person-months of exposure (9). In members of a U.S. military unit that trained in a highly endemic area of Bosnia, the estimated rate of TBEV infections (including asymptomatic infections) was 9 per 10,000 per-son-months of exposure (11).

Clinical Presentation

The incubation period of TBEV infection ranges from 2 to 28 days, with a median of 7-8 days (3,12). Approximately two-thirds of human TBEV infections are asymptomatic (1). In clinical cases, TBE often has a biphasic course. The first phase consists of a few days of fever, fatigue, headache, and muscle pain. This phase is followed by a week-long asymptomatic interval that precedes the second phase, when signs of central nervous system involvement (meningitis, encephalitis, and myelitis) develop (12). The European genotype is associated with milder disease, with 20%-30% of patients experiencing the second phase, mortality rates of 0.5%-2%, and severe neurologic sequelae in up to 10% of patients. The Far Eastern genotype is associated with monophasic illness, with no asymptomatic interval preceding the onset of neurologic disease, mortality rates of around 20%, and higher rates of severe neurologic sequelae (1,4,13).

TBE should be suspected in travelers who develop a nonspecific febrile illness that progresses to neuroinvasive disease within 4 weeks of arriving from an endemic area. Approximately 30% of TBE patients do not recall a tick bite (12). Serology is typically used for laboratory diagnosis. IgM-capture ELISA performed on serum or cerebrospinal fluid is virtually always positive during the neuroinvasive phase of the illness. Because serologic tests for TBEV cross-react with anti-bodies to other flaviviruses (e.g., West Nile and dengue) and flavivirus vaccines (e.g., yellow fever and Japanese encephalitis), a thorough travel and vaccination history, the use of an experienced arboviral diagnostic laboratory, and consultation with a clinician specialist are important factors in the accurate diagnosis and management of TBE (1-3,14). Recovery from TBE or subclinical TBEV infection is associated with long-term immunity to reinfection with TBEV, but not necessarily to infection with other flaviviruses(14).

Prevention

Travelers can reduce their risk of TBEV infection by avoiding exposure to woodland habitats in endemic countries during the spring and summer when ticks are active, and by avoiding unpasteurized dairy products (9). They can also protect themselves from tick bites by wearing clothing with long sleeves and taping trouser legs or tucking them into socks or shoes. Clothing and camping gear can be treated with products containing permethrin, which repels and kills ticks. Permethrin can be used in concert with products containing N,N-diethylmetatoluamide (DEET), which can be applied to clothing and exposed skin (see Chapter 2). Travelers to tick-infested areas should also inspect their bodies and clothing daily for ticks and promptly remove them with tweezers or forceps (15).

VACCINE

No TBE vaccines are licensed or available in the United States. Two equivalent, safe, and effective inactivated TBE vaccines are available in Europe, in adult and pediatric formulations: FSME-IMMUN (Baxter Vaccine AG, Vienna, Austria) and Encepur (Chiron Vaccines, Marburg, Germany) (1). The adult formulation of FSME-IMMUN is also licensed in Canada (4). Other TBE vaccines are also produced in the former Soviet Union, but little is known about their safety and efficacy. For both FSME-IMMUN and Encepur, the recommended primary vaccination series consists of three doses (the second given 1-3 months after the first, and the third given 9-12 months after the second). Although no formal efficacy trials of these vaccines have been conducted, indirect evidence suggests that their efficacy is above 95% (1,3). Booster doses are recommended every 3 years, although protective immunity in many recipients lasts substantially longer (1,9). Because the primary vaccination series requires at least 9 months for completion, most travelers to TBE-endemic areas will find tick-bite prevention to be more practical than vaccination. An accelerated vaccination schedule (doses on days 0, 7, and 21 followed by a booster dose 12-18 months later) produces seroconversion rates that are virtually identical to those observed with the standard vaccination schedule (1). Travelers anticipating high-risk exposures, such as working or camping in forested areas or farmland, adventure travel, or living in TBE-endemic countries for an extended period of time may wish to be vaccinated in Canada or Europe. Because the primary tick vectors of TBEV in Europe and Asia are also the primary vectors of Lyme borreliosis and ehrlichiosis in those areas, persons vaccinated against TBEV should continue to take tick-bite precautions when in tick habitat.

Treatment

Because no TBEV-specific drugs are available, treatment of TBE is supportive (16).

References

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3. Dumpis U, Crook D, Oksi J. Tick-borne encephalitis. Clin Infect Dis. 1999;28:882-90.  
4. Public Health Agency of Canada. Statement on tick-borne encephalitis. An Advisory Committee Statement (ACS). Can Commun Dis Rep. 2006;32:1-18.
5. Suss J. Epidemiology and ecology of TBE relevant to the production of effective vaccines. Vaccine. 2003;21 Suppl 1:S19-35.  
6. Baxter Vaccines. TBE Vaccine. Available at: http://www.baxtervaccines.com/?node_id=1452. (Accessed July 2006)  
7. The International Scientific Working Group on Tick-Borne Encephalitis (TBE/FSME). TBE. Available at: http://www.isw-tbe.info. (Accessed July 2006)
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12. Kaiser R. The clinical and epidemiological profile of tick-borne encephalitis in southern Germany 1994-98: a prospective study of 656 patients. Brain. 1999;122(Pt 11):2067-78.
13. Haglund M, Gunther G. Tick-borne encephalitis—pathogenesis, clinical course and long-term follow-up. Vaccine. 2003;21 Suppl 1:S11-8.
14. Holzmann H. Diagnosis of tick-borne encephalitis. Vaccine. 2003;21 Suppl 1:S36-40.
15. Needham GR. Evaluation of five popular methods for tick removal. Pediatrics. 1985;75:997-1002.
16. Waldvogel K, Bossart W, Huisman T, Boltshauser E, Nadal D. Severe tick-borne encephalitis following passive immunization. Eur J Pediatr. 1996;155:775-9.