In vitro activity of dihydroartemisinin against clinical isolates of Plasmodium falciparum in Yaounde, Cameroon.
The in vitro activities of dihydroartemisinin (the biologically active metabolite of artemisinin derivatives), chloroquine, monodesethylamodiaquine (the biologically active metabolite of amodiaquine), quinine, mefloquine, halofantrine, and pyrimethamine were assessed in 65 African isolates of Plasmodium falciparum from Yaounde, Cameroon using an isotopic microtest. The 50% inhibitory concentration (IC50) values for dihydroartemisinin were within a narrow range from 0.25 to 4.56 nM, with a geometric mean of 1.11 nM (95% confidence interval = 0.96-1.28 nM). Dihydroartemisinin was equally active (P > 0.05) against the chloroquine-sensitive isolates (geometric mean IC50 = 1.25 nM, 95% confidence interval = 0.99-1.57 nM) and the chloroquine-resistant isolates (geometric mean IC50 = 0.979 nM, 95% confidence interval = 0.816-1.18 nM). A significant positive correlation was observed between the responses to dihydroartemisinin and mefloquine (r = 0.662) or halofantrine (r = 0.284), suggesting in vitro cross-resistance. There was no correlation between the responses to dihydroartemisinin and other antimalarial drugs.
Ringwald
P
P
Institut de Recherche pour le Développement (1RD, formerly ORSTO) and Laboratoire de Recherches sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon.
Bickii
J
J
Basco
L K
LK
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins; D002163:Cameroon; D006801:Humans; D020128:Inhibitory Concentration 50; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification; D012717:Sesquiterpenes / Q000494:pharmacology*
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C039060:artenimol