A new model for testing gametocytocidal effects of some antimalarial drugs on Plasmodium falciparum in vitro.

A technique is described for obtaining pure gametocyte cultures of Plasmodium falciparum, using pyrimethamine at the minimum concentration for inhibition of asexual parasites. Routine cultures producing sexual stages were exposed to pyrimethamine on days 5 and 6. These cultures grew synchronously and contained gametocytes of stages II, III and V on day 7, 9 and 15 of the cultures respectively. The pyrimethamine-treated gametocytes were more infective to mosquitoes than were untreated controls. This model for the culture of pure gametocytes was used to observe the activity of chloroquine, halofantrine, pyrimethamine and quinine on the gametocyte stage III of Plasmodium falciparum strain NF54 in vitro. NF54 was shown to be sensitive to chloroquine, quinine and pyrimethamine, but the results showed that halofantrine was the most effective drug in reducing the number of gametocytes. A concentration of 3 x 10(-9) M halofantrine was lethal to both asexual parasites and gametocytes. The gametocytocidal EC90 of chloroquine (1 x 10(-6) M) and that of quinine (9 x 10(-7) M) were equal to the minimum inhibitory concentration of asexual stages of isolates of P. falciparum considered as highly resistant to these drugs. A high concentration of pyrimethamine (1 x 10(-4) M) had, in contrast, little effect on gametocytes.