Profiling Antimalarial Drug-resistant Haplotypes in , 1, and Genes in Causing Malaria in the Central Region of Ghana: a Multicentre Cross-sectional Study
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Background: The proliferation of parasites resistant to antimalarial drugs poses a serious threat to human life and remains an obstacle to managing and eradicating . The surveillance of molecular markers has become necessary to monitor the spread of resistant haplotypes and discover emerging mutations.
Objective: This molecular epidemiological study aimed to evaluate the prevalence of known mutations in the drug resistance genes , 1, and in the Central Region of Ghana.
Design: A multi-centre cross-sectional study.
Methods: This prospective study utilised dried blood spots from individuals with from five districts in the Central Region of Ghana. Selective Whole Genome Amplification (sWGA) and Single Nucleotide Polymorphisms (SNPs) in chloroquine transporter genes (), multidrug resistance 1 (1), dihydropteroate synthase () and dihydrofolate reductase () were analysed.
Results: Whole genome sequencing was carried out on 522 samples. Of these, 409 (78%) samples were successfully sequenced. Six (6) of the sequenced samples were of co-infection of other parasite species with and excluded from the analysis. Analysis of the gene revealed 0.5% were CVIET (C72, V73, M74I, N75E, K76T) while the CVMNK (C72, V73, M74, N75, K76) wild-type haplotypes were 97% with (2.5%) (CV[M/I][N/E][K/T]) being mixed haplotypes. In the 1 gene, monoclonal haplotypes; NFD (N86, Y184F, D1246) and YFN (N86Y, Y184F, D1246N) occurred at 44% and 9.8%, respectively, whereas mixed- haplotypes (N[Y/F]D and [N/Y][Y/F]D) were 23.5% and 0.3%, respectively. Combined / genes yielded about 88% IRNI (N51I, C59R, S108N, I164) + A437G haplotypes (conferring partial resistance to Sulphadoxine-Pyrimethamine (SP)) while 9% of the parasites had IRNI + A437G + K540E haplotypes (conferring full resistance to SP). The wild-type haplotype, (N51, C59, S108, I164) and (S436, A437, K540, A581, A613) was not observed.
Conclusion: The findings show a low prevalence of CVIET and relatively higher rates for 1 NFD and parasites with IRNI (N51I, C59R, S108N, I164) + A437G haplotypes. These observations advocate for enhanced surveillance which is inimical to malaria management in an endemic area.