Chapter 4 Travel-Related Infectious Diseases
Marc Fischer, Carolyn V. Gould, Pierre E. Rollin
Tickborne encephalitis (TBE) virus is a single-stranded RNA virus that belongs to the genus Flavivirus. TBE virus has 3 subtypes: European, Siberian, and Far Eastern.
TBE virus is transmitted to humans through the bite of an infected tick of the Ixodes species, primarily I. ricinus (European subtype) or I. persulcatus (Siberian and Far Eastern subtypes). The virus is maintained in discrete areas of deciduous forests. Ticks act as both vector and virus reservoir, and small rodents are the primary amplifying host. TBE can also be acquired by ingesting unpasteurized dairy products (such as milk and cheese) from infected goats, sheep, or cows. TBE virus transmission has infrequently been reported through laboratory exposure and slaughtering viremic animals. Direct person-to-person spread of TBE virus occurs only rarely, through blood transfusion, solid organ transplantation, or breastfeeding.
TBE is endemic to focal areas of Europe and Asia, extending from eastern France to northern Japan and from northern Russia to Albania. Approximately 5,000–13,000 TBE cases are reported each year, with large annual fluctuations. Russia has the largest number of reported cases. The highest disease incidence has been reported from western Siberia, Slovenia, and the Baltic States (Estonia, Latvia, Lithuania). Other European countries with reported cases or known endemic areas include Albania, Austria, Belarus, Bosnia, Croatia, Czech Republic, Denmark, Finland, France, Germany, Hungary, Italy, Netherlands, Norway, Poland, Romania, Serbia, Slovakia, Sweden, Switzerland, and Ukraine. Asian countries with reported TBE cases or virus activity include China, Japan, Kazakhstan, Kyrgyzstan, Mongolia, and South Korea.
Most cases occur from April through November, with peaks in early and late summer when ticks are active. The incidence and severity of disease are highest in people aged ≥50 years. Most cases occur in areas <2,500 ft (750 m). In the last 30 years, the geographic range of TBE virus appears to have expanded to new areas, and the virus has been found at altitudes up to and above 5,000 ft (1,500 m). These trends are likely due to a complex combination of changes in diagnosis and surveillance, human activities and socioeconomic factors, and ecology and climate.
The overall risk of acquiring TBE for an unvaccinated visitor to a highly endemic area during the TBE virus transmission season has been estimated at 1 case per 10,000 person-months of exposure. Most TBE virus 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 people who remain in urban or unforested areas and who do not consume unpasteurized dairy products.
Vector tick population density and infection rates in TBE virus-endemic foci are highly variable. For example, TBE virus infection rates in I. ricinus in central Europe vary from <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. The number of TBE cases reported from a country depends on the ecology and geographic distribution of TBE virus, the intensity of diagnosis and surveillance, and the vaccine coverage in the population. Therefore, the number of human TBE cases reported from an area may not be a reliable predictor of a traveler’s risk for infection. The same ticks that transmit TBE virus can also transmit other pathogens, including Borrelia burgdorferi (the agent for Lyme disease), Anaplasma phagocytophilum (anaplasmosis), and Babesia spp. (babesiosis); simultaneous infection with multiple organisms has been described.
From 2000 through 2017, 8 cases of TBE among US travelers to Europe and China were reported. TBE is not a nationally notifiable disease in the United States.
Approximately two-thirds of infections are asymptomatic. The median incubation period for TBE is 8 days (range, 4–28 days). The incubation period for milkborne exposure is usually shorter (3–4 days). Acute neuroinvasive disease is the most commonly recognized clinical manifestation of TBE virus infection. However, TBE disease often presents with milder forms of the disease or a biphasic course.
- First phase: nonspecific febrile illness with headache, myalgia, and fatigue. Usually lasts for several days and may be followed by an afebrile and relatively asymptomatic period. Up to two-thirds of patients recover without any further illness.
- Second phase: central nervous system involvement resulting in aseptic meningitis, encephalitis, or myelitis. Findings include meningeal signs, altered mental status, cognitive dysfunction, ataxia, rigidity, seizures, tremors, cranial nerve palsies, and limb paresis.
Disease severity increases with age. Although TBE tends to be less severe in children, residual symptoms and neurologic deficits have been described. Clinical course and long-term outcome also vary by TBE virus subtype, although some of the reported differences may be due to patient selection, access to medical care, or age-specific exposure. The European subtype is associated with milder disease, a case-fatality ratio of <2%, and neurologic sequelae in up to 30% of patients. The Far Eastern subtype is often associated with a more severe disease course, including a case-fatality ratio of 20%–40% and higher rates of severe neurologic sequelae. The Siberian subtype has a case-fatality ratio of 6%–8%, with rare reports of cases with slow or chronic progression over months.
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. A history of tick bite may be a clue to this diagnosis; however, approximately 30% of TBE patients do not recall a tick bite.
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. Vaccination history, date of onset of symptoms, and information regarding other flaviviruses known to circulate in the geographic area that may cross-react in serologic assays need to be considered when interpreting results. During the first phase of the illness, TBE virus or viral RNA can sometimes be detected in serum samples by virus isolation or RT-PCR. However, by the time neurologic symptoms are recognized, the virus or viral RNA is usually undetectable. Therefore, virus isolation and RT-PCR should not be used to rule out a diagnosis of TBE. Clinicians should contact their state or local health department, the CDC Viral Special Pathogens Branch (404-639-1115), or CDC Division of Vector-Borne Diseases (970-221-6400) for assistance with diagnostic testing.
There is no specific antiviral treatment for TBE; therapy consists of supportive care and management of complications.
Personal Protection Measures
Travelers should avoid consuming unpasteurized dairy products and use all measures to avoid tick bites (see Chapter 3, Mosquitoes, Ticks & Other Arthropods).
No TBE vaccines are licensed or available in the United States. Two inactivated cell culture-derived TBE vaccines are available in Europe, in adult and pediatric formulations: FSME-IMMUN (also marketed as TicoVac) (Pfizer, France) and Encepur (GSK, Germany). Two inactivated TBE vaccines are available in Russia: TBE-Moscow (Chumakov Institute) and EnceVir (Microgen). SenTaiBao (Changchun Institute of Biological Products in China) also manufactures an inactivated TBE vaccine. Immunogenicity studies suggest that the European and Russian vaccines provide cross-protection against all 3 TBE virus subtypes.
Although no formal efficacy trials of these vaccines have been conducted, immunogenicity data and postlicensure effectiveness studies suggest that their efficacy is >95%. Rare vaccine failures have been reported, particularly in people aged ≥50 years.
Because the routine primary vaccination series requires ≥6 months for completion, most travelers going to TBE-endemic areas will find avoiding tick bites to be more practical than vaccination. However, a rapid vaccination schedule has been evaluated for both European vaccines, and seroconversion rates are similar to those observed with the standard vaccination schedules. Travelers anticipating high-risk exposures, such as working or camping in forested areas or farmland, adventure travel, or living in TBE-endemic countries for extended periods, may wish to be vaccinated in Europe.
CDC website: www.cdc.gov/vhf/tbe
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