Application of an in vitro semi-microtest to the study of drug sensitivity of 66 Plasmodium falciparum isolates from 15 countries.
The activity of four antimalarial drugs against 66 Plasmodium falciparum isolates from 15 countries was assessed by an in vitro semi-microtest. Median inhibitory concentrations (IC50) for chloroquine were less than 120 nM in 22 isolates from patients successfully treated with chloroquine, and more than 250 nM in six isolates from patients with chloroquine-resistant malaria. 10 of 15 isolates from Brazil (Amazonia), 7 of 12 isolates from Madagascar, two from Kenya and two from Thailand had IC50 for chloroquine of more than 250 nM. None of the 35 isolates from West and Central Africa had IC50 of more than 120 nM. Very different levels of sensitivity were observed in Brazil and Madagascar. 27 of 28 isolates (including two that were chloroquine-resistant in vivo) had IC50 of less than 50 nM for dichlorquinazine, a 4-aminoquinoline. The IC50 for mefloquine was less than 160 nM in 55 isolates including ten from patients who were successfully treated with mefloquine. IC50 for quinine were between 140 and 660 nM for 30 isolates. This test has proved useful in epidemiological studies, therapeutic monitoring of clinical cases and in the evaluation of new drugs.
D000818:Animals; D002738:Chloroquine / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D015767:Mefloquine; D008826:Microbial Sensitivity Tests / Q000379:methods; D010879:Piperazines / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011803:Quinine / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology
D010879:Piperazines; D011804:Quinolines; C043112:dichlorquinazine; D002738:Chloroquine; D011803:Quinine; D015767:Mefloquine