Clinical endpoints during rabies vaccine control tests.

All warm-blooded animals, including humans, are susceptible to rabies. The infection with the virus leads inevitably to the death of the recipient. Va ccines and anti-serums are at present the only possibility to prevent rabie s infections in the human and veterinary medicine. In order to be able to g uarantee the production of a reliably safe and effective vaccine, each batc h has to be tested. These tests contain animal experiments. Alone for effic acy 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 d eaths rates of immunised animals are compared with non vaccinated control a nimals. At present several replacement methods for this test are in develop ment. However, so far none of them has been validated in an international m ulticenter study. The modifications necessary for example in the WHO (World Health Organization) or O.I.E. (Office International d'Epizooties) guideli nes will need several more years. Therefore, this test method will be inter nationally used in the forseeable future. In order to avoid unnecessary suf fering of the animals, we looked for signs, which can be used to replace le thality as criterion. For this purpose score-sheets were developed, on whic h the observed clinical signs were recorded. The decrease of body-temperatu re, 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, ar e the first neurological symptoms of rabies. The combination of these param eters can serve as a reliable indicator for humane endpoints. This saves th e 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 s ense of the 3R. A video which shows the clinical signs is available.