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Background  Malawi experienced prolonged use of sulfadoxine/pyrimethamine (SP) as the front-line anti-malarial drug, with early replacement of chloroquine and delayed introduction of artemisinin-based combination therapy. Extended use of SP, and its continued application in pregnancy is impacting the genomic variation of the  Plasmodium falciparum  population.    Methods  Whole genome sequence data of  P. falciparum  isolates covering 2 years of transmission within Malawi, alongside global datasets, were used. More than 745,000 SNPs were identified, and differences in allele frequencies between countries assessed, as well as genetic regions under positive selection determined.    Results  Positive selection signals were identified within  dhps ,  dhfr  and  gch1 , all components of the parasite folate pathway associated with SP resistance. Sitting predominantly on a  dhfr  triple mutation background, a novel copy number increase of ~twofold was identified in the  gch1  promoter. This copy number was almost fixed (96.8% frequency) in Malawi samples, but found at less than 45% frequency in other African populations, and distinct from a whole gene duplication previously reported in Southeast Asian parasites.    Conclusions  SP resistance selection pressures have been retained in the Malawian population, with known resistance  dhfr  mutations at fixation, complemented by a novel  gch1  promoter duplication. The effects of the duplication on the fitness costs of SP variants and resistance need to be elucidated.    Electronic supplementary material  The online version of this article (doi:10.1186/s12936-016-1634-6) contains supplementary material, which is available to authorized users.

Characterizing the impact of sustained sulfadoxine/pyrimethamine use upon the Plasmodium falciparum population in Malawi