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LACK OF PREDICTION OF MEFLOQUINE AND MEFLOQUINE-ARTESUNATE TREATMENT OUTCOME BY MUTATIONS IN THE PLASMODIUM FALCIPARUM MULTIDRUG RESISTANCE 1 (PFMDR1) GENE FOR PLASMODIUM FALCIPARUM MALARIA IN PERU

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  • 1 Tropical Disease Unit, Toronto General Hospital and University of Toronto, Toronto, Ontario, Canada; Instituto Nacional de Salud, Lima, Peru; U.S. Naval Medical Research Center Detachment, Lima, Peru; Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
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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.

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