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Impfstoffe gegen Durchfallserkrankungen – am Beispiel der Impfstoffe gegen Reisediarrhoe und gegen Rotavirus

Examples for vaccines against diarrheal diseases – rotavirus and traveller's diarrhea

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Summary

Diarrheal diseases constitute one of the most important health problems worldwide. Children less than 5 years, living in developing countries, are particularly in danger with respect to the incidence and severity of the gastrointestinal disorders. Travelers to developing countries are also at risk to develop diarrheal disorders; around 30–50% of them acquire so called "travelers's diarrhea" caused by bacteria, viruses or protozoa. It has been estimated that approximately 30–70% of diarrhea are due to bacteria, of which the most frequently detected enteric pathogens are non-invasive, enterotoxigenic Escherichia coli (ETEC). Their exotoxins, the heat stabile (ST) and the heat labile (LT) toxins are in large part responsible for the pathogenicity of the bacteria. About 20% of cases of traveler's diarrhea are caused by LT producing ETEC. This heat labile toxin exhibits a 80% sequence homology with cholera toxin. The presently available vaccine against cholera (Dukoral®) contains inactivated Vibrio cholerae bacteria and the recombinant non-toxic B subunit of cholera toxin. Consequently, this vaccine displays also some efficacy against traveler's diarrhoea with up to 25 % of travelers being protected against this disease. Rotaviruses are the leading recognized cause of diarrhoea-related illness and deaths among infants worldwide in developing and industrialized countries. Based on the high incidence of this disease two oral vaccines have been developed and are available in Europe in 2007. Due to the impact of rotavirus diseases also in Austria vaccination against this disease has been already suggested in the Austrian vaccination schedules for infants from 6–24 weeks of age. One of the two vaccines, Rotarix®, is an attenuated monovalent vaccine with a broad cross-reactivity against the most frequent serotypes. The second one, RotaTeq®, is a pentavalent attenuated vaccine containing 5 human-bovine reassortants. Both vaccines display 85–98% efficacy against severe rotavirus disease and an excellent tolerability with no difference in side reactions to the placebo controls, particularly with respect to intussusceptions.

Zusammenfassung

Durchfallserkrankungen stellen ein weltweit großes Gesundheitsproblem dar. Besonders betroffen, sowohl in der Häufigkeit wie auch in der Schwere der Erkrankung, sind Kinder bis zu 5 Jahren in Entwicklungsländern. Bei Reisenden in diese Gebiete spielen Durchfallserkrankungen ebenfalls eine große Rolle; etwa 20–50 % der Reisenden entwickeln Reisediarrhoe, vorwiegend hervorgerufen durch Bakterien, Viren oder Protozoen. Bei den bakteriellen Durchfallserkrankungen werden in Abhängigkeit des betreffenden Landes (Mexiko, Lateinamerika, Afrika, Philippinen) 30–70 % der Fälle durch enterotoxigene E.coli (ETEC) hervorgerufen. Die Pathogenität dieser nicht invasiven Bakterien wird primär durch hitze-stabile (ST) und hitze-labile (LT) Toxine bedingt, wobei etwa 20 % aller Reisedurchfallserkrankungen durch LT-sezernierende ETEC hervorgerufen werden. Dieses hitzelabile Toxin hat eine strukturelle Identität und 80 % Sequenzhomologie mit Choleratoxin. Der derzeit am Markt befindliche orale Choleraimpfstoff (Dukoral®) enthält nebst abgetöteter Choleravibrionen auch die nicht toxische, aber immunogene B-subunit des Cholera Toxins in rekombinanter Form. Daher ist dieser orale Impfstoff auch für ETEC-Reisediarrhoe von Nutzen. Effizienzberechnungen der Impfung ergaben, dass bis zu 25 % der Reisenden dadurch gegen Diarrhoe geschützt werden können. Rotaviren (RV) gehören besonders bei Kindern zu den wichtigsten Durchfallserregern in Industrie- und Entwicklungsländern. Aufgrund der weltweit hohen Inzidenz dieser Durchfallserkrankung wurden 2 orale Lebendimpf-stoffe gegen Rotaviren entwickelt, die seit 2006 in Europa registriert sind. Aufgrund der Bedeutung dieser Erkrankung auch in Österreich wurde im österreichischen Impfplan eine allgemeine Impfempfehlung von Säuglingen zwischen 6 und 24 Wochen ausgegeben. Es handelt sich bei den oralen Impfstoffen einerseits um einen attenuierten, humanen, monovalenten RV-Lebendimpfstoff, der eine breite Kreuzimmunität gegen die gängigsten Serotypen aufweist (Rotarix®), und andererseits um einen attenuierten pentavalenten Lebendimpfstoff, der 5 human-bovine Reassortanten enthält (RotaTeq®). Verträglichkeit und Wirksamkeit der beiden Impfstoffe sind in etwa vergleichbar: die Wirksamkeit gegen schwere RV-Gastroenteritiden liegt zwischen 85–98 %, bezüglich Verträglichkeit bestand kein Unterscheid zur Placebokontrolle und keine Assoziationen mit Invaginationen konnten festgestellt werden.

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  1. Institut für Spezifische Prophylaxe und Tropenmedizin, Zentrum für Physiologie und Pathophysiologie, Medizinische Universität Wien, Wien, Austria

    Herwig Kollaritsch & Ursula Wiedermann

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  1. Herwig Kollaritsch
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  2. Ursula Wiedermann
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Correspondence to Herwig Kollaritsch.

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Kollaritsch, H., Wiedermann, U. Impfstoffe gegen Durchfallserkrankungen – am Beispiel der Impfstoffe gegen Reisediarrhoe und gegen Rotavirus. Wien Med Wochenschr 157, 102–106 (2007). https://doi.org/10.1007/s10354-007-0390-1

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  • DOI: https://doi.org/10.1007/s10354-007-0390-1

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