VIABILITY OF PLASMODIUM-FALCIPARUM EX-VIVO - COMPARISON OF THE EFFECTS OF ARTEMETHER AND SULFADOXINE-PYRIMETHAMINE

Objective: Severe malaria is increasingly treated with artemether and sulfadoxine-pyrimethamine, but their effects on the viability of Plasm odium falciparum ex vivo following therapeutic doses, and the relation ship between conventional indices of therapeutic response and parasite viability, have not been evaluated. We assessed these parameters in c hildren with severe non-cerebral falciparum malaria. Methods: Between May and August 1995, 17 children with severe non-cerebral malaria were randomized to receive therapeutic doses of artemether or sulfadoxine- pyrimethamine. Parasitemia quantification and withdrawal of blood cult ure of P. falciparum in vitro were done before and at specific interva ls after drug administration. Therapeutic indices of response were det ermined by the conventional method. The corresponding viability estima tes ex vivo were derived for each drug and compared with conventional therapeutic indices. Results: Artemether produced a significantly more rapid reduction of parasitemia and fever than sulfadoxine-pyrimethami ne. Resistance to sulfadoxine-pyrimethamine was present in three out o f seven patients (RI, RII and RIII) and was readily detectable by the functional viability estimate ex vivo. Ex vivo, functional reduction o f parasite viability was significant 8 or 12 h after administration of artemether, with no functionally viable parasites 30 h after administ ration. In contrast, functional viability in isolates sensitive to sul fadoxine-pyrimethamine became significant by 16-20 h after drug admini stration and viable parasites were still evident after 36 h in some is olates. Indices of therapeutic response estimated by the conventional methods, i.e., time to 50% or 90% reduction of parasitemia and parasit e clearance time, were significantly higher than those derived from th e corresponding functional viability estimates ex vivo for each drug. There was correlation between some of the two sets of parameters. Conc lusions: These data suggest the rapid and relatively broad stage effec ts of artemether when compared with sulfadoxine-pyrimethamine on P. fa lciparum asexual forms. Estimation of parasite viability indices ex vi vo permits comparison of the relative speed of antimalarial drug actio n.