title: Selection of drug resistance-mediating Plasmodium falciparum genetic polymorphisms by seasonal malaria chemoprevention in Burkina Faso.
abstract: Seasonal malaria chemoprevention (SMC), with regular use of amodiaquine plus sulfadoxine-pyrimethamine (AQ/SP) during the transmission season, is now a standard malaria control measure in the Sahel subregion of Africa. Another strategy under study is SMC with dihydroartemisinin plus piperaquine (DP). Plasmodium falciparum single nucleotide polymorphisms (SNPs) in P. falciparum crt (pfcrt), pfmdr1, pfdhfr, and pfdhps are associated with decreased response to aminoquinoline and antifolate antimalarials and are selected by use of these drugs. To characterize selection by SMC of key polymorphisms, we assessed 13 SNPs in P. falciparum isolated from children aged 3 to 59 months living in southwestern Burkina Faso and randomized to receive monthly DP or AQ/SP for 3 months in 2009. We compared SNP prevalence before the onset of SMC and 1 month after the third treatment in P. falciparum PCR-positive samples from 120 randomly selected children from each treatment arm and an additional 120 randomly selected children from a control group that did not receive SMC. The prevalence of relevant mutations was increased after SMC with AQ/SP. Significant selection was seen for pfcrt 76T (68.5% to 83.0%, P = 0.04), pfdhfr 59R (54.8% to 83.3%, P = 0.0002), and pfdhfr 108N (55.0% to 87.2%, P = 0.0001), with trends toward selection of pfmdr1 86Y, pfdhfr 51I, and pfdhps 437G. After SMC with DP, only borderline selection of wild-type pfmdr1 D1246 (mutant; 7.7% to 0%, P = 0.05) was seen. In contrast to AQ/SP, SMC with DP did not clearly select for known resistance-mediating polymorphisms. SMC with AQ/SP, but not DP, may hasten the development of resistance to components of this regimen. (This study has been registered at ClinicalTrials.gov under registration no. NCT00941785.).
authors.affiliation: Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
authors.forename: Anyirékun Fabrice
authors.initials: AF
authors.lastname: Somé
authors.affiliation: Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
authors.forename: Issaka
authors.initials: I
authors.lastname: Zongo
authors.affiliation: Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
authors.forename: Yves-Daniel
authors.initials: YD
authors.lastname: Compaoré
authors.affiliation: Centre Muraz, Bobo-Dioulasso, Burkina Faso.
authors.forename: Souleymane
authors.initials: S
authors.lastname: Sakandé
authors.affiliation: Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sod, Thailand Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: François
authors.initials: F
authors.lastname: Nosten
authors.affiliation: Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso Centre Muraz, Bobo-Dioulasso, Burkina Faso.
authors.forename: Jean-Bosco
authors.initials: JB
authors.lastname: Ouédraogo
authors.affiliation: Department of Medicine, University of California, San Francisco, California, USA prosenthal@medsfgh.ucsf.edu.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
mesh_terms: D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002050:Burkina Faso; D002648:Child; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000469:parasitology / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012424:Rural Population; D012621:Seasons
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan
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