The World Health Organization (WHO) recommends surveillance of molecular markers of resistance to anti-malarial drugs. This is particularly important in the case of mass drug administration (MDA), which is endorsed by the WHO in some settings to combat malaria. Dihydroartemisinin-piperaquine (DHA-PPQ) is an artemisinin-based combination therapy which has been used in MDA. This review analyses the impact of MDA with DHA-PPQ on the evolution of molecular markers of drug resistance. The review is split into two parts. Section I reviews the current evidence for different molecular markers of resistance to DHA-PPQ. This includes an overview of the prevalence of these molecular markers in Plasmodium falciparum Whole Genome Sequence data from the MalariaGEN Pf3k project. Section II is a systematic literature review of the impact that MDA with DHA-PPQ has had on the evolution of molecular markers of resistance. This systematic review followed PRISMA guidelines. This review found that despite being a recognised surveillance tool by the WHO, the surveillance of molecular markers of resistance following MDA with DHA-PPQ was not commonly performed. Of the total 96 papers screened for eligibility in this review, only 20 analysed molecular markers of drug resistance. The molecular markers published were also not standardized. Overall, this warrants greater reporting of molecular marker prevalence following MDA implementation. This should include putative pfcrt mutations which have been found to convey resistance to DHA-PPQ in vitro.
Following integrated malaria control interventions, malaria burden on the Bijagós Archipelago has significantly decreased. Understanding the genomic diversity of circulating Plasmodium falciparum malaria parasites can assist infection control, through identifying drug resistance mutations and characterising the complexity of population structure. This study presents the first whole genome sequence data for P. falciparum isolates from the Bijagós Archipelago. Amplified DNA from P. falciparum isolates sourced from dried blood spot samples of 15 asymptomatic malaria cases were sequenced. Using 1.3 million SNPs characterised across 795 African P. falciparum isolates, population structure analyses revealed that isolates from the archipelago cluster with samples from mainland West Africa and appear closely related to mainland populations; without forming a separate phylogenetic cluster. This study characterises SNPs associated with antimalarial drug resistance on the archipelago. We observed fixation of the PfDHFR mutations N51I and S108N, associated with resistance to sulphadoxine-pyrimethamine, and the continued presence of PfCRT K76T, associated with chloroquine resistance. These data have relevance for infection control and drug resistance surveillance; particularly considering expected increases in antimalarial drug use following updated WHO recommendations, and the recent implementation of seasonal malaria chemoprevention and mass drug administration in the region.
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