title: In-vitro susceptibility of Plasmodium falciparum to monodesethylamodiaquine, dihydroartemisinin and quinine in an area of high chloroquine resistance in Rwanda.
abstract: Plasmodium falciparum in-vitro susceptibility to chloroquine (CQ), monodesethylamodiaquine, quinine and dihydroartemisinin was investigated in Rwandan patients with a parasitaemia of at least >or=4000/microl. The study was carried out in November-December 2003. Dihydroartemisinin was the most potent (GM IC(50)=2.6nmol/l, 95% CI 2.2-3.2) among the drugs tested. Resistance to chloroquine was 45% (33/74) and that to monodesethylamodiaquine 7% (5/74). All the tested isolates were susceptible to quinine. The mean IC(50) of monodesethylamodiaquine, quinine and dihydroartemisinin was significantly higher for chloroquine-resistant than for chloroquine-sensitive strains (P<0.05). The IC(50) of each drug was significantly and positively correlated to that of the other three drugs (P<0.005), and this correlation was higher between CQ and monodesethylamodiaquine (r=0.8). In-vitro CQ resistance is linked to that of the other drugs tested. Most worrying is the positive correlation between the IC(50) of dihydroartemisinin and the other drugs, more particularly with CQ, suggesting an increased tolerance of the parasites to all drugs.
authors.affiliation: Institut de Recherche en Sciences de la Santé/Centre Muraz, Bobo Dioulasso, Burkina Faso. tintohalidou@yahoo.fr
authors.forename: Halidou
authors.initials: H
authors.lastname: Tinto
authors.forename: Claude
authors.initials: C
authors.lastname: Rwagacondo
authors.forename: Corinne
authors.initials: C
authors.lastname: Karema
authors.forename: Denise
authors.initials: D
authors.lastname: Mupfasoni
authors.forename: Waltruda
authors.initials: W
authors.lastname: Vandoren
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Rusanganwa
authors.forename: Annette
authors.initials: A
authors.lastname: Erhart
authors.forename: Chantal
authors.initials: C
authors.lastname: Van Overmeir
authors.forename: Eric
authors.initials: E
authors.lastname: Van Marck
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
mesh_terms: D000293:Adolescent; D000328:Adult; D000655:Amodiaquine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D037621:Artemisinins / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D007223:Infant; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000187:drug effects*; D011803:Quinine / Q000494:pharmacology; D012432:Rwanda; D012717:Sesquiterpenes / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000655:Amodiaquine; C039060:artenimol; C047386:desethylamodiaquine; D002738:Chloroquine; D011803:Quinine