STUDIES ON ANTIMALARIALS DRUG——Ⅱ. The causal prophylactic activity of antimalarial in animal model. Part Ⅰ. Plasmodium yoelii-Anopheles stephensi system

For the purpose of screening new causal prophylactic antimalarials, Plasmodium yoelii-Anopheles stephensi system was established. It was demonstrated from the exper-imental results obtained in 9. years that the infection rate of the Anopheles and the mice was 33±4.05% and 94±0.0011%, respectively. Mice were fairly susceptible to par-asite infection as shown by the more or less constant and high infection rate in the control groups of different batches of experiments. Based on the results of a number of experiments, a routine procedure is suggested for primary screening of drugs as follows. Mice are intraperitoneally injected with the sporozoites of P. yoelii at a rate of one infective mosquito per mouse. Immediately after infection the drug to be tested is ad-ministered in 3 consecutive days. Blood examinations are made for parasites on the 7th and 14th days after drug administration. In case of negative finding, blood pooled from about one half of the negative mice is subinoculated into normal mice, and the other half is splenectomized. Blood examinations are made again 1 and 2 weeks later to det-ermine the activity of the drug. A number of current antimalarial drugs were tested in the model with the result that drugs like pyrimethamine and primaquine exhibited causal prophylactic activity, whereas others like chloroquine not. More than 500 comp-ounds were screened by means of this system, the results indicated that it is a depend-able method for primary screening. As regards differentiation of causal prophylactic action of drug from its residual effect on the blood forms of parasites, it is not very difficult to distinguish both prophylactic and therapeutic actions of drug from each other. However, for some compounds like long-acting piperaquine, atebrine and so on, it is necessary to make a further study in the simian malaria model recommended by Schmidt.