title: Roles of specific Plasmodium falciparum mutations in resistance to amodiaquine and sulfadoxine-pyrimethamine in Burkina Faso.
abstract: We evaluated associations between key polymorphisms in target genes and responses to treatment with sulfadoxine-pyrimethamine (SP) or amodiaquine (AQ) for uncomplicated Plasmodium falciparum malaria in Bobo-Dioulasso, Burkina Faso. Presence of the dihydrofolate reductase (dhfr) 108N or 59R mutations (but not dhfr 51I or dihydropteroate synthetase [dhps] 437G) and P. falciparum chloroquine resistance transporter (pfcrt) 76T or P. falciparum multidrug resistance 1 (pfmdr1) 86Y or 1246Y mutations (but not pfmdr1 184F) predicted recrudescence after treatment with SP and AQ, respectively. Treatment led to significant increases in the prevalence of the same mutations (except 1246Y) in new infections that presented after therapy. The dhfr 164L and dhps 540E mutations were not seen in any isolates. These results clarify the key roles of a small number of mutations in P. falciparum resistance to SP and AQ in west Africa.
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California 94143, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Dokomajilar
authors.forename: Zambende Moise
authors.initials: ZM
authors.lastname: Lankoande
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
authors.forename: Issaka
authors.initials: I
authors.lastname: Zongo
authors.forename: Jean-Bosco
authors.initials: JB
authors.lastname: Ouedraogo
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
mesh_terms: D000655:Amodiaquine / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002050:Burkina Faso; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D019450:Genes, MDR / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009154:Mutation / Q000235:genetics; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000502:physiology; D015800:Protozoan Proteins; D011739:Pyrimethamine / Q000494:pharmacology*; D012008:Recurrence; D013413:Sulfadoxine / Q000494:pharmacology*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine