In vitro susceptibility of African Plasmodium falciparum isolates to dihydroartemisinin and the risk factors for resistance to qinghaosu.
In vitro susceptibility to dihydroartemisinin (DHART) and to artemether of 476 Plasmodium falciparum fresh clinical isolates obtained from non immune travellers returning from Africa to France in 1993-1996 were analysed to search for natural resistance and cross resistance of these compounds with available antimalarials. The mean median inhibitory concentration (IC50) values for artemether and DHART were 2.69 nM and 1.17 nM, respectively. Nineteen isolates presented with a decreased IC50 to artemether or DHART. Chloroquine-resistant isolates were more susceptible to artemether (2.15 versus 3.26 nM) and DHART (0.876 versus 1.51 nM) than chloroquine-susceptible ones. Artemether and DHART responses were correlated (r2 = 0.599). The isolates identified as resistant to DHART or artemether in this study had IC50's close to the cut-off and limited cross-resistant profiles.
Le Bras
J
J
Centre National de Référence pour la Chimiosensibilité du Paludisme, Laboratoire de Parasitologie, Université Paris V, Hôpital Bichat-Claude Bernard, Paris. jacques.lebras@bch.ap-hop-paris.fr
D000349:Africa; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins; D002738:Chloroquine / Q000494:pharmacology; D003429:Cross Reactions; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D005602:France; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D015767:Mefloquine / Q000494:pharmacology; D010616:Phenanthrenes / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification; D012717:Sesquiterpenes / Q000494:pharmacology*; D014195:Travel
D000962:Antimalarials; D037621:Artemisinins; D010616:Phenanthrenes; D012717:Sesquiterpenes; C039060:artenimol; D002738:Chloroquine; C031327:artemisinin; C023768:halofantrine; D015767:Mefloquine