Selection of drug resistance-mediating Plasmodium falciparum genetic polymorphisms by seasonal malaria chemoprevention in Burkina Faso

TitleSelection of drug resistance-mediating Plasmodium falciparum genetic polymorphisms by seasonal malaria chemoprevention in Burkina Faso
Publication TypeJournal Article
Year of Publication2014
AuthorsSome, AF, Zongo, I, Compaore, YD, Sakande, S, Nosten, F, Ouedraogo, JB, Rosenthal, PJ
JournalAntimicrob Agents Chemother
Date PublishedApr 14
ISBN Number1098-6596 (Electronic)0066-4804 (Linking)
Abstract

Seasonal malaria chemoprevention (SMC), with regular use of amodiaquine/sulfadoxine-pyrimethamine (AQ/SP) during the transmission season, is now a standard malaria control measure in the Sahel sub-region of Africa. Another strategy under study is SMC with dihydroartemisinin/piperaquine (DP). Plasmodium falciparum single nucleotide polymorphisms (SNPs) in 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 3-59 months living in south-western 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 one 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.

URLhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068591/pdf/zac3660.pdf
Short TitleAntimicrobial agents and chemotherapy