title: In vitro sensitivity of Plasmodium falciparum to amodiaquine compared with other major antimalarials in Madagascar.
abstract: Chloroquine has been used in Madagascar since 1945 and remains the first-line treatment for uncomplicated cases of malaria. Low-grades of resistance type R1 and R2 have been reported. Thus, in vitro tests were performed in order to monitor the drug sensitivity of Plasmodium falciparum from different study sites, with the aim of identifying alternatives to chloroquine. Chloroquine IC50 values ranged from 0.2 nM to 283.4 nM (n = 190, mean IC50 = 52.6 nM; 95% CI = 46.1-59.1 nM). Fifteen isolates (7.9%) were chloroquine-resistant. One mefloquine-resistant isolate was detected (1/139). The test isolates were sensitive to amodiaquine (n = 118), quinine (n = 212), pyrimethamine (n = 86) and cycloguanil (n = 79). The median IC50 for amodiaquine was 12.3 nM (mean IC50 = 15.3 nM, 95% CI = 13.3-17.3 nM). Amodiaquine was 3.4 times as active as chloroquine in vitro and 7 times as active as quinine against P. falciparum. These results indicate that amodiaquine may be a potent alternative to chloroquine in Madagascar. There was positive correlation between tested quinoline-containing drugs activities, which suggests in vitro cross-susceptibility.
authors.affiliation: Groupe de Recherche sur le Paludisme, Institut Pasteur de Madagascar, BP 1274, Antananarivo 101, République de Madagascar. milijaon@pasteur.mg
authors.forename: M
authors.initials: M
authors.lastname: Randrianarivelojosia
authors.forename: J L Sahondra
authors.initials: JL
authors.lastname: Harisoa
authors.forename: L P
authors.initials: LP
authors.lastname: Rabarijaona
authors.forename: L A
authors.initials: LA
authors.lastname: Raharimalala
authors.forename: L
authors.initials: L
authors.lastname: Ranaivo
authors.forename: V
authors.initials: V
authors.lastname: Pietra
authors.forename: J B
authors.initials: JB
authors.lastname: Duchemin
authors.forename: F
authors.initials: F
authors.lastname: Rakotomanana
authors.forename: V
authors.initials: V
authors.lastname: Robert
authors.forename: P
authors.initials: P
authors.lastname: Mauclere
authors.forename: F
authors.initials: F
authors.lastname: Ariey
mesh_terms: D000655:Amodiaquine / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D018432:Drug Resistance, Multiple; D006801:Humans; D020128:Inhibitory Concentration 50; D008270:Madagascar; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D015767:Mefloquine / Q000494:pharmacology; D018512:Parasitemia / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification; D002727:Proguanil; D011739:Pyrimethamine / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D014227:Triazines; D000655:Amodiaquine; C026009:cycloguanil; D002738:Chloroquine; D011803:Quinine; D002727:Proguanil; D015767:Mefloquine; D011739:Pyrimethamine