Chapter 3Infectious Diseases Related To Travel
Marc Fischer, Stephanie J. Yendell, Pierre E. Rollin
Tickborne encephalitis virus (TBEV) is a single-stranded RNA virus that belongs to the genus Flavivirus and is closely related to Powassan virus. TBEV has 3 subtypes: European, Siberian, and Far Eastern.
TBEV 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. Tickborne encephalitis (TBE) can also be acquired by ingesting unpasteurized dairy products (such as milk and cheese) from infected goats, sheep, or cows. TBEV transmission has infrequently been reported through laboratory exposure and slaughtering viremic animals. Direct person-to-person spread of TBEV occurs only rarely, through blood transfusion or breastfeeding.
TBE is endemic in focal areas of Europe and Asia (from eastern France to northern Japan and from northern Russia to Albania). From 1990 through 2009, an average of 8,500 cases per year (range, 5,352–12,733 cases) were reported from 19 European countries, with a peak in incidence in the late 1990s. Russia has the largest number of reported TBE cases, and western Siberia has the highest incidence of TBE in the world. Other European countries with known endemic areas include Austria, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Italy, Latvia, Lithuania, Norway, Poland, Romania, Slovakia, Slovenia, Sweden, and Switzerland. 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 TBEV 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 TBEV transmission season has been estimated at 1 case per 10,000 person-months of exposure. 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 people who remain in urban or unforested areas and who do not consume unpasteurized dairy products.
Vector tick population density and infection rates in TBEV-endemic foci are highly variable. For example, TBEV 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 TBEV, 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.
From 2000 through 2011, 5 cases of TBE among US travelers to Europe and China were reported. TBE is not a nationally notifiable disease in the United States, and additional cases may have occurred. The same ticks that transmit TBEV can also transmit other pathogens, including Borrelia burgdorferi (the agent for Lyme disease), Anaplasma phagocytophilum (anaplasmosis), and Babesia spp. (babesiosis). Therefore, simultaneous infection with multiple organisms is possible.
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 TBEV 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 may 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, tremors, cranial nerve palsies, and limb paresis.
Disease severity increases with age. Clinical course and long-term outcome also vary by TBEV subtype:
- 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 is more frequently associated with chronic or progressive disease and has a case-fatality ratio of 2%–3%.
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, TBEV or TBEV 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, CDC’s Viral Special Pathogens Branch (404-639-1115), or CDC’s 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 2, Protection against Mosquitoes, Ticks, & Other Insects & 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 (Baxter, Austria) and Encepur (Novartis, Germany). The adult formulation of FSME-IMMUN is also licensed in Canada. Two other inactivated TBE vaccines are available in Russia: TBE-Moscow (Chumakov Institute, Russia) and EnceVir (Microgen, Russia). At least one other TBE vaccine is produced in China, but information regarding this vaccine is not available in the English literature.
Immunogenicity studies suggest that the European and Russian vaccines should provide cross-protection against all 3 TBEV subtypes. For both FSME-IMMUN and Encepur, the primary vaccination series consists of 3 doses (Table 3-19). The specific recommended intervals between doses vary by country and vaccine. Although no formal efficacy trials of these vaccines have been conducted, indirect evidence suggests that their efficacy is >95%. Vaccine failures have been reported, particularly in people aged ≥50 years. Regardless of age, the first booster dose should be given 3 years after the primary series. Recommended intervals for subsequent booster doses vary by age; boosters should be given every 5 years for people aged <50 years and every 3 years for those aged ≥50 years.
Because the routine primary vaccination series requires ≥6 months for completion, most travelers to TBE-endemic areas will find avoiding tick bites to be more practical than vaccination. However, an accelerated vaccination schedule has been evaluated for both European vaccines, and results in seroconversion rates are similar to those observed with the standard vaccination schedule. 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.
CDC website: www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/TBE.htm
Table 3-19. Tickborne encephalitis (TBE) vaccines licensed in Canada, Europe, and Russia1
|TRADE NAME (MANUFACTURER, LOCATION)||AGE (Y)||DOSE||ROUTE||PRIMARY SERIES||FIRST BOOSTER (Y)||SUBSEQUENT BOOSTERS (Y)|
IMMUN (Baxter, Austria)
|≥16||0.5 mL||IM||3 doses
(0, 1–3 mo, 6–15 mo)2
IMMUN Junior (Baxter, Austria)
|1–15||0.25 mL||IM||3 doses
(0, 1–3 mo, 6–15 mo)2
|Encepur-Adults (Novartis, Germany)||≥17||0.5 mL||IM||3 doses
(0, 1–3 mo, 6–15 mo)2
|Encepur-Children (Novartis, Germany)||1–11||0.25 mL||IM||3 doses
(0, 1–3 mo, 6–15 mo)2
|EnceVir (Microgen, Russia)||≥3||0.5 mL||IM||2 doses
(0, 5–7 mo)5
|TBE-Moscow (Chumakov Institute, Russia)||≥3||0.5 mL||IM||2 doses
(0, 1–7 mo)
1 No TBE vaccines are licensed or available in the United States. FSME-IMMUN is licensed in Canada and Europe; FSME-IMMUN Junior, Encepur-Adults, and Encepur-Children are licensed in Europe; and EnceVir and TBE-Moscow are licensed in Russia.
2If a rapid immune response is required, the second dose can be administered 2 weeks after the first dose.
3Booster doses recommended every 3 years for people aged ≥50 years.
4An accelerated schedule has been used with 3 doses given on days 0, 7, and 21. After the primary series, the first booster dose is administered at 12–18 months.
5For emergency situations, there is a rapid primary series schedule of 0 and 1–2 months.
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- Stefanoff P, Polkowska A, Giambi C, Levy-Bruhl D, O’Flanagan D, Dematte L, et al. Reliable surveillance of tick-borne encephalitis in European countries is necessary to improve the quality of vaccine recommendations. Vaccine. 2011 Feb 1;29(6):1283–8.
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