title: 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.
mesh_terms: D000351:Africa, Eastern; D002738:Chloroquine / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D006801:Humans; D008288:Malaria / Q000517:prevention & control; D008826:Microbial Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D002727:Proguanil; D011739:Pyrimethamine / Q000494:pharmacology*; D014227:Triazines / Q000494:pharmacology*
chemical_list: D014227:Triazines; C026009:cycloguanil; D002738:Chloroquine; D002727:Proguanil; D011739:Pyrimethamine