[Clinical endpoints during rabies vaccine control tests] [Article in German]

Abstract

All warm-blooded animals, including humans, are susceptible to rabies. The infection with the virus leads inevitably to the death of the recipient. Vaccines and anti-serums are at present the only possibility to prevent rabies infections in the human and veterinary medicine. In order to be able to guarantee the production of a reliably safe and effective vaccine, each batch has to be tested. These tests contain animal experiments. Alone for efficacy tests of rabies vaccines done for each batch far over one hundred mice are used. In a defined time period in challenge experiments the number of death rates of immunised animals are compared with non vaccinated control animals. At present several replacement methods for this test are in development. However, so far none of them has been validated in an international multicenter study. The modifications necessary for example in the WHO (World Health Organization) or O.I.E. (Office International d'Epizooties) guidelines will need several more years. Therefore, this test method will be internationally used in the foreseeable future. In order to avoid unnecessary suffering of the animals, we looked for signs which can be used to replace lethality as criterion. For this purpose score-sheets were developed, on which the observed clinical signs were recorded. The decrease of body-temperature, which was measured with transplanted transponders, occurred too late to be usable. A clear reduction of the body weight is the earliest sign of an illness. Slow and circular movements followed by cramps and paralyses are the first neurological symptoms of rabies. The combination of these parameters can serve as a reliable indicator for humane endpoints. This saves the mice on average between four and five days of the most stressful phase of the experiment and is a clear "refinement" of the test conditions in the sense of the 3R. A video which shows the clinical signs is available.