Modifications in the rhythm of schizogony in Plasmodium chabaudi chabaudi associated with the selection of chloroquine resistance

A high level of drug resistance was obtained with a line of Plasmodiumchabaudi maintained under intense chloroquine selection pressure according to the protocols established for P. berghei. The main objective of this work was to verify if the characteristic asynchronous schizogonic rhythm of naturally resistant rodent malaria parasites was also found when the drug resistance was induced experimentally. The degree of resistance was evaluated through the use of the “2% delay test” (DT) and the schizogonic rhythm, by reference to the synchronicity index (SI). The strain had originally a DT of 4.26 and an SI of 0.52. Following the application of 80 mg/kg chloroquine at each passage, as early as at the 8th passage the parasites rapidly became resistant and asynchronous. At the 17th passage the DT was 3.32 and the SI, 0.20. In the drug-resistant line the original indices, both the DT and the SI, were restored after deep-freezing, sporogony, or passage through a Percoll gradient, or simply by repeated intravenous subinoculations of blood. The clear correlation between asynchronicity and drug resistance is easily explained by the action of chloroquine, which favours the schizogonic cycles initiated by latent merozoites.