title: Prolonged selection of pfmdr1 polymorphisms after treatment of falciparum malaria with artemether-lumefantrine in Uganda.
abstract: We compared the prevalence of key pfmdr1 alleles between pretreatment Plasmodium falciparum parasite isolates and parasites that emerged after treatment of uncomplicated malaria in a longitudinal cohort of Ugandan children. The pfmdr1 86N, 184F, and 1246D alleles were selected after treatment with artemether-lumefantrine, but not after artesunate-amodiaquine or amodiaquine-sulfadoxine-pyrimethamine. Remarkably, selection persisted in infections presenting up to about 60 days after treatment with artemether-lumefantrine. Thus, parasites selected for decreased drug sensitivity can appear long after predicted exposure to antimalarial drugs. Continued surveillance of the clinical efficacy and in vitro activity of new combination therapies is warranted.
authors: Department of Medicine, University of California, San Francisco, CA 94143-0811, USA.
authors: Frederick N
authors: FN
authors: Baliraine
authors: Philip J
authors: PJ
authors: Rosenthal
mesh_terms: D000483:Alleles; D000655:Amodiaquine / Q000008:administration & dosage / Q000494:pharmacology; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology*; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D011110:Polymorphism, Genetic; D011739:Pyrimethamine / Q000008:administration & dosage / Q000494:pharmacology; D013413:Sulfadoxine / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D014454:Uganda
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine; D013413:Sulfadoxine; D011739:Pyrimethamine