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Am J Trop Med Hyg ; 68(1): 107-10, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12557835

ABSTRACT

We assessed whether mutations in the Plasmodium falciparum multidrug-resistance gene 1 (pfmdr1) (C1034S, D1042N, and Y1246D) would predict treatment outcome during a 28-day in vivo treatment trial in the Peruvian Amazon. Mefloquine (MQ) was compared with mefloquine-artesunate (MQ-AS) in a randomized, multi-clinic protocol for the first time in the Americas. Of 115 patients enrolled in the in vivo arm, 97 patients were eligible for molecular analysis. All 97 patients remained parasite-free during 28 days of follow-up (MQ, n = 46; MQ-AS, n = 51), indicating 100% clinical efficacy of the MQ and MQ-AS treatment regimens. The reported MQ-sensitive alleles (C1034, D1042, and Y1246) were present in 48.5% (n = 47) of the cases, whereas 49 isolates (50.5%) contained the D1246 mutation reported to confer MQ resistance in vitro. However, neither this mutation nor a double mutation (S1034, D1246; n = 16) was predictive of MQ treatment outcome.


Subject(s)
ATP-Binding Cassette Transporters , Antimalarials/therapeutic use , Artemisinins/therapeutic use , Malaria, Falciparum/drug therapy , Mefloquine/therapeutic use , Plasmodium falciparum/genetics , Protozoan Proteins/genetics , Sesquiterpenes/therapeutic use , Adult , Animals , Antimalarials/pharmacology , Artemisinins/pharmacology , Artesunate , Base Sequence , Cohort Studies , DNA, Protozoan/chemistry , Drug Resistance/genetics , Female , Humans , Malaria, Falciparum/parasitology , Male , Mefloquine/pharmacology , Molecular Sequence Data , Mutation , Peru , Plasmodium falciparum/drug effects , Predictive Value of Tests , Sequence Alignment , Sesquiterpenes/pharmacology
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