Vaccination and Tick-borne Encephalitis, Central Europe

Franz X. Heinz

, Karin Stiasny, Heidemarie Holzmann, Marta Grgic-Vitek, Bohumir Kriz, Astrid Essl, and Michael Kundi

Author affiliations: Author affiliations: Medical University of Vienna, Vienna, Austria (F.X. Heinz, K. Stiasny, H. Holzmann, M. Kundi); National Institute of Public Health, Ljubljana, Slovenia (M. Grgic-Vitek); National Institute of Public Health, Prague, Czech Republic (B. Kriz); and GfK Austria Healthcare, Vienna (A. Essl)

Abstract

Tick-borne encephalitis (TBE) is a substantial public health problem in many parts of Europe and Asia. To assess the effect of increasing TBE vaccination coverage in Austria, we compared incidence rates over 40 years for highly TBE-endemic countries of central Europe (Czech Republic, Slovenia, and Austria). For all 3 countries we found extensive annual and longer range fluctuations and shifts in distribution of patient ages, suggesting major variations in the complex interplay of factors influencing risk for exposure to TBE virus. The most distinctive effect was found for Austria, where mass vaccination decreased incidence to ≈16% of that of the prevaccination era. Incidence rates remained high for the nonvaccinated population. The vaccine was effective for persons in all age groups. During 2000–2011 in Austria, ≈4,000 cases of TBE were prevented by vaccination.

Tick-borne encephalitis (TBE) is the most common arthropod-transmitted viral infection of humans in Europe and central and eastern Asia (1); each year, >10,000 TBE patients are hospitalized. The role of TBE as a travel-associated disease is probably underestimated (2,3). TBE virus is a member of the family Flaviviridae, genus Flavivirus, and a close relative of the mosquito-transmitted viruses that cause yellow fever, dengue fever, Japanese encephalitis, and West Nile fever (4). Three antigenically closely related subtypes are carried primarily by Ixodes ricinus (European subtype) and I. persulcatus ticks (Siberian and Far-Eastern subtypes) (5). In TBE-endemic areas, the virus circulates between ticks and vertebrate hosts (primarily rodents) (5,6); humans are dead-end hosts only and do not play any role in the maintenance of TBE virus in nature. In most instances, transmission to humans occurs by the bites of infected ticks; however, in some TBE-endemic areas, alimentary infections—obtained through consumption of raw milk or milk products from infected goats, sheep, or cattle—are common (6,7). Because virus circulation depends on an intricate balance of virus and host factors that are controlled by environmental conditions, TBE-endemic areas do not follow all areas of tick infestation but are restricted to certain regions that are conducive to maintenance of natural virus cycles (8–11). In Europe, the most strongly affected countries are southern Germany, Switzerland, Austria, the Czech Republic, Slovakia, Hungary, Slovenia, the Baltic countries, Poland, parts of Scandinavia, and European Russia.
Similar to other flavivirus infections, only a subset of TBE virus infections leads to neurologic diseases such as meningitis, encephalitis, encephalomyelitis, and radiculitis (12). On average, the severity of disease increases with patient age (13), and case-fatality rates of <1 1="1" and="and" class="text-underline" span="span"><
35% have been reported in Europe, Siberia, and the Far East, respectively (12). Effective inactivated whole virus vaccines are produced in Europe (European subtype strain) and Russia (Far-Eastern subtype strain) (1), but their usage differs widely among TBE-endemic countries (14,15). Experiments with postvaccination serum and direct mouse challenge experiments have shown that vaccines manufactured with 1 subtype will also protect against strains of the other TBE virus subtypes (16,17), consistent with their antigenic similarity. A strong upsurge of TBE in Europe in recent years (6) has been associated with climatic, ecologic, and human behavioral changes that might increase the risk for virus exposure (8,18–20). To determine the effectiveness of vaccination, we examined incidence of TBE in Austria over 40 years, including 10 years without vaccination followed by 30 years with increasing vaccination coverage. We compared these data with those for the Czech Republic and Slovenia, 2 neighboring central European countries with high TBE incidence rates but comparatively low vaccination rates. We demonstrate that the strong decline of TBE observed only in Austria resulted from protection by vaccination and that the incidence rate for the nonvaccinated population remained as high as it was during the prevaccination era. The data from all 3 countries reveal a strong degree of annual and longer range variations, which are coincident in some but not all instances.