Prevalence of Plasmodium falciparum Antimalarial Drugs Resistance Genetic Markers in Selected Lake Victoria Islands, Western Kenya

Abstract

Plasmodium falciparum multidrug resistance has been linked to Single Nucleotide Polymorphisms (SNPs) on chloroquine resistance transporter (Pfcrt), multidrug resistant-1 (Pfmdr1), dihydrofolate reductase (Pfdhfr), and dihydropteroate synthase (Pfdhps) genes. Delayed parasite clearance against Artemisinin-based Combination Therapies (ACTs) has been linked to the Kelch-13 (Pf-k13) gene SNPs. The global health burden due to this resistance translates to approximately 229 million cases and over 400,000 deaths annually, with significant morbidity, economic impact This cross-sectional study analyzed isolates from Lake Victoria islands, Kenya, a malaria-endemic region, providing baseline information on the prevalence of SNPs in the five genes associated with drug-resistant parasites. Fifty-nine whole blood samples were collected from symptomatic malaria patients visiting dispensaries in five selected islands on Lake Victoria, Kenya between 2014 and 2016. DNA was extracted and quality checks performed.Whole-genome sequencing of the isolates was then performed on the Illumina platform. Reads were analyzed for antimalarial resistance-associated SNPs via a pipeline based on the Genome Analysis Tool kit (GATK) practices and data compared with isolates from West Africa and East Africa parasite populations derived from MalariaGEN repository. Out of twenty-seven isolates that passed quality checks, it was observed that all isolates harbored the Pf-k13 wildtypes for all resistance validated markers. K76T mutation of Pfcrt was observed at 18.51%, n=5, Pfmdr1 Y184F (48.15%,n=13), D1246Y (7.40%, n=2), Pfdhps K540E (88.89%,n=24), Pfdhfr N51I (96.30%,n=26), C59R (77.78%,n=21) and S108N (96.30%, n=26). Pfcrt haplotype CVMNK was observed in 81.48%(n=22) of isolates, Pfdhfr haplotype IRN (70.37%, n=19), and Pfdhps SAEAA (74.01%, n=20). This study provides baseline data for subsequent surveillance studies on the prevalence of antimalarial resistance markers. This study revealed a low circulation of chloroquine (CQ) and artemisinin-resistant associated alleles, and a high prevalence of polymorphisms linked to SP resistance. Similar trends of prevalence were also observed in West Africa and East Africa parasite populations. Surveillance studies are recommended to monitor resistance in the region as well as temporal trends of these polymorphisms.