Elsevier

Vaccine

Volume 25, Issue 43, 23 October 2007, Pages 7559-7567
Vaccine

Field effectiveness of vaccination against tick-borne encephalitis

https://doi.org/10.1016/j.vaccine.2007.08.024Get rights and content

Abstract

Tick-borne encephalitis (TBE) is a vaccine-preventable disease caused by a flavivirus (TBE virus) that is endemic in many European countries and large parts of Central and Eastern Asia. In Europe, highly purified formalin-inactivated whole virus vaccines are in widespread use, but the vaccination coverage differs significantly between countries with TBE endemicity. Austria presents an exceptional situation because 88% of the total population have a history of TBE vaccination, with 58% being regularly vaccinated within the recommended schedule. In this study, we investigated the field effectiveness of TBE vaccination in Austria for the years 2000–2006 in different age groups on the basis of the documented numbers of hospitalized cases in unvaccinated and vaccinated people and the sizes of these population groups as revealed by representative inquiries. We show that the overall effectiveness in regularly vaccinated persons is about 99% with no statistically significant difference between age groups. It is at least as high after the first two vaccinations, i.e. before the completion of the basic vaccination scheme by a third vaccination, but is significantly lower (about 95%) in those with a record of irregular vaccination. Our data confirm the excellent performance of TBE vaccine under field conditions and provide evidence that, in Austria, about 2800 cases were prevented by vaccination in the years 2000–2006.

Introduction

Tick-borne encephalitis (TBE) virus is one of the major human pathogenic flaviviruses, a group of about 70 viruses that also includes the mosquito-borne yellow fever, dengue, Japanese encephalitis and West Nile viruses [1], [2]. TBE virus circulates in endemic regions of many countries of Central, Southern, Northern, and Eastern Europe as well as Central and Eastern Asia including Northern Japan and Northern China [1], [3], [4]. Based on sequence comparisons, three subtypes can be differentiated – designated European, Siberian, and Far Eastern subtypes – that are antigenically closely related [5], [6] and transmitted by the ticks Ixodes ricinus (European subtype) and Ixodes persulcatus (Asian subtypes) [4], [7]. Consistent with the overlap of distribution areas for I. ricinus and I. persulcatus in North-Eastern Europe, European and Asian subtype viruses have both been isolated in the Baltics and Finland [8], [9], [10].

About 3000 hospitalized cases of TBE are recorded annually in Europe [11] and between about 5500 and 10,000 in Russia [12], [13]. After the acute phase of the disease, a significant proportion of the patients (up to 46%) suffers from neurological sequelae for a certain period of time or even life-long [14]. In Europe, the lethality as a consequence of TBE lies between 1 and 2% [14] but has been reported to reach 20–40% in the Far East [7]. It has to be considered, however, that these comparisons were not made under standardized conditions and may be biased by differences in the rates of laboratory diagnosis and hospitalization of less severe cases. They thus cannot be ascribed solely to the higher pathogenicity of Far-Eastern strains without further scrutiny and data analysis.

Starting with the development of a formalin-inactivated TBE vaccine in 1973 and its further purification [15], [16], [17], [18], [19], highly purified inactivated vaccines are now available in Europe from two manufacturers: Baxter (formerly Immuno), designated ‘FSME Immun™’ [15], [16], [18], using an Austrian isolate (strain Neudoerfl), and Novartis (formerly Chiron, formerly Behring), designated ‘Encepur™’, using a German isolate (strain Karlsruhe) [20], [21]. Both of the manufacturing strains belong to the European subtype [5]. In Austria, FSME Immun™ has been in use since 1976, and Encepur™ was introduced in 1999; in this country, these vaccines are currently used at a ratio of ca. 90 to 10, respectively (Institute for Medical Statistics Austria; www.imshealth.at).

Human vaccines are usually licensed and controlled on the basis of seroconversion data, using different assays for measuring the formation of specific antibodies. In the case of TBE virus and other flaviviruses, there is abundant evidence from animal studies that the presence of virus-neutralizing antibodies in serum provides an excellent correlate for protection against virus challenge [22], [23], [24], [25], [26], [27], [28], [29]. Nevertheless, the final proof for the success of vaccines depends on the evaluation of their effectiveness in the field. In terms of this field effectiveness, a wide range has been observed for different inactivated vaccines, from 50 to 80% for influenza vaccines [30] to more than 90% for hepatitis B vaccines [31], [32] and hepatitis A vaccines [33], [34]. The vaccine most closely related to the TBE vaccine investigated here is the inactivated Japanese encephalitis vaccine, which proved to have an effectiveness of 91% under field conditions [35].

With respect to TBE, Austria is an exceptional example because vaccination coverage has been steadily increasing since the 1970s, when the first vaccine (a precursor of the current vaccines [15], [16], [18]) became available. Today, 88% of the total population in Austria have been vaccinated at least once, with 58% being regularly vaccinated within the officially recommended vaccination schedule. This is in sharp contrast to neighbouring countries with comparable TBE virus endemicity such as Germany and the Czech Republic, where vaccination coverage has reached only 13 and 11%, respectively.

In this work, we have analyzed the field effectiveness of TBE vaccination (i.e. prevention of laboratory-diagnosed cases of TBE virus infections with neurological symptoms causing hospitalization) in Austria for the years 2000–2006 in different age groups and groups with different vaccination histories. The study is based on (1) the annual numbers of hospitalized TBE cases confirmed by laboratory diagnosis, (2) the vaccination history of these cases, (3) the annual population figures in Austria, and (4) the TBE vaccination coverage data in the different groups collected by representative inquiries involving 8500 to 10,000 individuals annually (see Section 2). Our analysis reveals an extraordinarily high degree of protection by TBE vaccination in Austria in the range of 99% which does not exhibit significant differences between age groups. Protection is equally high in the months following the first two vaccinations—i.e. before the third shot of the basic vaccination schedule, but is somewhat lower in persons with an irregular history of vaccination that lies outside the recommended regular scheme. The data presented confirm the excellent protection record of TBE vaccination under field conditions which – when compared to that of other vaccines – is among the best achievable by active immunization against viral diseases [15], [30], [31], [32], [33], [34], [35].

Section snippets

TBE vaccination

Like in other European countries, two TBE vaccines are commercially available in Austria, FSME-Immun™ manufactured by Baxter [15] and Encepur™ manufactured by Novartis [21]. Both vaccines are highly purified formalin-inactivated whole virus vaccines adjuvanted with aluminium hydroxide and can be used interchangeably. According to the Institute of Medical Statistics Austria (www.imshealth.at), the market coverage in Austria for the Baxter and Novartis vaccines in 2000 was about 95 and 5%,

Vaccination status of the Austrian population

The percentages of people in Austria in the categories: (1) unvaccinated, (2) regularly vaccinated, (3) vaccinated with two doses only of the basic immunization schedule, and (4) irregularly vaccinated were determined by means of representative inquiries conducted annually (see Section 2). The results generated through these inquiries are displayed in Fig. 1 for the years 2000–2006 with respect to the total Austrian population. For the purposes of this study, these data were further dissected

Discussion

It was the objective of this study to evaluate the field effectiveness of TBE vaccination in Austria for the years 2000–2006 by making use of the documentation systems for clinical cases of TBE, their vaccination histories and the vaccination status of the Austrian population as determined by representative inquiries. When all age groups are included, our analysis reveals an overall effectiveness of about 99% in persons that had followed the recommended vaccination schedule, with a possible

Acknowledgements

The authors are grateful for the excellent technical assistance of Silvia Röhnke and Jutta Hutecek, to Karin Stiasny for figure design, and to Karin Stiasny and Christian Kunz for critically reading the manuscript (all at the Institute of Virology, Medical University of Vienna, Austria). We also thank Egon Marth and Elisabeth Daghofer (Institute of Hygiene, Medical University of Graz) as well as Manfred Dierich and Gernot Walder (Institute of Hygiene, Medical University of Innsbruck) for their

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