High Prevalence of Plasmodium Falciparum Drug Resistance Markers in Ghana, An Artemisinin-Based Combination Therapy (Act) Setting

Abstract

Resistance to the artemisinins has been reported in less than a decade after their global deployment. The molecular markers for artemisinin resistance, however, have not been clearly characterized. The aim of this study is to determine and describe the genetic polymorphisms of the Pfcrt, Pfmdrl, and PfATPase6 genes as associated to artemisinin resistance. A total of 1,318 subjects were recruited for the study. A 12.75% prevalence of malaria was recorded. Malaria transmission was not found to be seasonal. PCR-RFLP was employed to analyze mutations at codon positions 76 of the Pfcrt gene as well as positions 86 and 184 of the Pfmdrl gene which have been associated with artemisinin resistance. These mutations were found in very high prevalence among 246 cases of 1,318 subjects recruited for the study. Mutations in the PfATPase6 gene were analyzed by PCR-RFLP and Sequencing. The SNPs of PfATPase6 gene that are said to confer resistance to artemisinins were not found in this study, like in many others, suggesting a growing irrelevance of the PfATPase6 gene as a marker for artemisinin resistance. Two novel SNPs in the PfATPase6 gene were, however, discovered confirming the highly diverse nature of this gene. With the current artemisinin drug pressure and the observed high prevalence of SNPs associated with artemisinin resistance, it is only a matter of time for a stable drug resistance to be recorded in Ghana. A national programme to monitor the development of resistance to artemisinin is, thus, crucially needed.