High Prevalence of Plasmodium falciparum K13 Mutations in Rwanda Is Associated With Slow Parasite Clearance After Treatment With Artemether-Lumefantrine

Abstract

In Southeast Asia, mutations in the Plasmodium falciparum K13 gene have led to delayed parasite clearance and treatment failures in patients with malaria receiving artemisinin combination therapies. Until recently, relevant K13 mutations had been mostly absent from Africa. Between 2018 and 2019, a phase 2 clinical study with 186 patients was conducted in Mali, Gabon, Ghana, Uganda, and Rwanda. Patients with malaria were randomized and treated with artemether-lumefantrine or cipargamin. Here we report an allele frequency of 22% for R561H in Rwanda and associated delayed parasite clearance. Notwithstanding, efficacy of artemether-lumefantrine remained high in Rwanda, with a 94.4% polymerase chain reaction-corrected cure rate.

Keywords: P. falciparum malaria; K13 mutations; R561H; Rwanda; artemether-lumefantrine; artemisinin-resistance; clinical study; parasite clearance half-lives.

Figure 1.

K13 mutations are associated with longer parasite clearance half-life (PCT_½) after treatment with artemether-lumefantrine. K13 alleles are plotted against the observed PCT_½ in patients. The figure shows patients treated with artemether-lumefantrine (upper panel) or cipargamin (lower panel). Mutant alleles were exclusively found in Rwanda and were associated with slower parasite clearance in patients treated with artemether-lumefantrine but not in those treated with cipargamin. Cipargamin was given in single doses of 10–150 mg or multiple doses (3 days) of 10–50 mg, which accounts for the observed range of PCT_½. Abbreviation: WT, wild type.