Prevalence and selection of antimalarial drug resistance markers after implementation of seasonal malaria chemoprevention (SMC) in children from Mali

Across the Sahel sub-region, most childhood malaria infections occur during the rainy season. To prevent both uncomplicated and severe malaria in children, The World Health Organization recommends seasonal malaria chemoprevention for children aged 0-5 years. SMC is an intermittent distribution of the antimalarial drugs, sulfadoxine-pyrimethamine (SP), and amodiaquine (AQ) when the malarial transmission is high. Albeit effective, large-scale use of SMC treatments in children can lead to antimalarial drug resistance in the main malaria parasite, Plasmodium falciparum, and render this crucial strategy ineffective. Resistance to the drug SP is already prominent in areas of Africa. Consequently, treatment with another drug combination, dihydroartemisinin-piperaquine (DHA-PQ), has been suggested as an alternative. Antimalarial drug resistance can be monitored by detecting molecular markers of drugs resistance, particularly Single Nucleotide Polymorphisms (SNPs), and copy number variations (CNV) of specific genes of P. falciparum associated with antimalarial drug resistance. Assessing these SNPs and CNV before and after SMC could give an insight into the impact of the prophylactic strategy on the prevalence and selection of antimalarial drug resistance in P. falciparum. This project will determine and compare the prevalence of SNPs and CNV in specific P. falciparum genes in infections of children of different age groups from Mali who have received either SP-AQ or DHAPQ. After DNA extraction of the P. falciparum positive blood samples from Mali, the samples will be examined by PCR followed by targeted amplicon sequencing using an in-house developed nextgeneration sequencing platform (Illumina MiSeq platform) for the prevalence of SNPs in an array of genes that have been associated with SP, AQ, DHA, and PQ resistance. Additionally, a qPCR methodology will be applied to determine gene copy numbers of spec