Distribution of Plasmodium falciparum K13 gene polymorphisms across transmission settings in Ghana

Abstract

Malaria is a signifcant global health concern, with a majority of cases in Sub-Saharan African nations. Numerous anti malarial drugs have been developed to counter the rampant prevalence of Plasmodium falciparum malaria. Arte misinin-based Combination Therapy (ACT) has served as the primary treatment of uncomplicated malaria in Ghana since 2005. However, a growing concern has emerged due to the escalating reports of ACT resistance, particularly in Southeast Asia, and its encroachment into Africa. Specifcally, mutations in the Kelch propeller domain on chromo some 13 (Pfk13) have been linked to ACT resistance. Yet, our understanding of mutation prevalence in Africa remains largely uncharted. In this study, we compared Pfk13 sequences obtained from 172 P. falciparum samples across three ecological and transmission zones in Ghana. We identifed 27 non-synonymous mutations among these sequences, of which two of the mutations, C580Y (found in two samples from the central region) and Y493H (found in one sam ple from the north), had previously been validated for their association with artemisinin resistance, a phenomenon widespread in Southeast Asia. The Pfk13 gene diversity was most pronounced in the northern savannah than the cen tral forest and south coastal regions, where transmission rates are lower. The observed mutations were not signif cantly associated with geographical regions, suggesting a frequent spread of mutations across the country. The ongo ing global surveillance of artemisinin resistance remains pivotal, and our fndings provides insights into the potential spread of resistant parasites in West Africa. Furthermore, the identifcation of novel codon mutations in this study raises their potential association to ACT resistance, warranting further investigation through in vitro assays to ascertain their functional signifcance.

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Research Article

Keywords

Artemisinin resistance, Plasmodium falciparum, Kelch13 propeller domain

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