Concomitant resistance to pyrimethamine and cycloguanil of chloroquine-resistant falciparum malaria from East Africa: an in vitro study of 12 isolates

Abstract
The susceptibility of 12 isolates of Plasmodium falciparum to chloroquine, pyrimethamine and cycloguanil was studied in vitro after adaptation of the isolates to continuous culture by a 48-hour single-step multiplication inhibition assay. All of seven isolates imported from Tanzania since 1981 proved chloroquine resistant and six of these had an IC50 above 0.64 X 10(-6)M suggesting RII-RIII resistance. All chloroquine-resistant isolates were concomitantly resistant to pyrimethamine (IC50 above 10(-6)M). All chloroquine and pyrimethamine-resistant strains had IC50 values for cycloguanil of at least 0.6 X 10(-6)M which is higher than the Malayan (Camp.) strain studied in vitro and known to be proguanil/cycloguanil-resistant in vivo. Cycloguanil is the active metabolite of proguanil, and this result makes it doubtful whether proguanil would be a more effective prophylactic than chloroquine in East Africa, and whether any advantage over chloroquine alone would be derived from a combination of the two.