Stage sensitivity of Plasmodium vinckei petteri to quinine, mefloquine, and pyrimethamine

The stage-dependent sensitivity of Plasmodium vinckei petteri to the antimalarial drugs quinine, mefloquine, and pyrimethamine was investigated using single subcurative doses and 2 different tests: a prepatency test evidencing the extension of the prepatent period according to the stage at which the drug was administered, and a patency test showing the morphological alterations of the parasites and the modifications of the parasitic pattern following drug treatment. Quinine activity was maximal when it hit the midterm trophozoite. No pigment clumping was seen and parasites developed normally until they reached the schizogonic stage when they became morphologically altered and unproductive. Mefloquine also acted on the midterm trophozoites. Parasites at this stage were killed immediately by the drug as evidenced by their degenerative appearance, and dead parasites lingered in the blood smears for at least 6 hr. However, although mefloquine was active during at least 48 hr (2 cycles), some trophozoites escaped destruction. The schizont stage was found to be the most sensitive to pyrimethamine, as previously reported for other parasite species. These results add to our previous reports showing that each drug acts preferentially on a specific stage of parasite development.