Genetic Architecture and Dynamics of PfKelch13’s Propeller Domain in Plasmodium Falciparum Clinical Isolates Collected in Senegal.

Abstract Plasmodium resistance to Artemisinin Combination-based Therapies (ACT) in Southeast Asia is a major public health concern that is sporadically appearing in Africa. Senegal has shifted from malaria control to elimination plans. Given notable progresses obtained through robust strategic plans, it is still crucial to assess genetic variability of the Plasmodium falciparum artemisinin resistance gene marker Kelch13 (PfKelch13) in circulating field isolates. We here report an analysis of PfKelch13-propeller polymorphism in clinical isolates collected nine years after ACT introduction in five Senegalese regions with different malaria transmission settings. Sequencing of PfKelch13-propeller domain from 280 clinical isolates reveals that 16% (45/280) of the parasite population harbored variants. Dynamics of PfKelch13 variants reveals emerging, persistent but also disappearing mutations over time. In addition to the malaria epidemiology, our survey also shows the dynamics of PfKelch13 variants in different malaria transmission settings in Senegal. Despite the absence of PfKelch13 associated artemisinin resistance mutations, a shift from 86% to 68% of PfKelch13WT was observed when comparing parasites collected prior vs. post ACT intensive usage in Dakar a low malaria transmission area. All together, our data confirms the need to closely monitor PfKelch13 polymorphism to anticipate and or prevent emergence of P. falciparum resistance in Senegal.