A Unique Plasmodium falciparum K13 Gene Mutation in Northwest Ethiopia

Abstract

Artemisinin combination therapy (ACT) is the first line to treat uncomplicated Plasmodium falciparum malaria worldwide. Artemisinin treatment failures are on the rise in southeast Asia. Delayed parasite clearance after ACT is associated with mutations of the P. falciparum kelch 13 gene. Patients (N = 148) in five districts of northwest Ethiopia were enrolled in a 28-day ACT trial. We identified a unique kelch 13 mutation (R622I) in 3/125 (2.4%) samples. The three isolates with R622I were from Negade-Bahir and Aykel districts close to the Ethiopia-Sudan border. One of three patients with the mutant strain was parasitemic at day 3; however, all patients cleared parasites by day 28. Correlation between kelch 13 mutations and parasite clearance was not possible due to the low frequency of mutations in this study.

Figure 1.

Predicted model of the Plasmodium falciparum kelch 13 propeller protein with the R622I mutation. (A) Location of the mutation sites relative to the overall model of the protein. The beta-propeller domain of the btb-kelch protein Krp1 (PDB ID: 2WOZ) was used as the modeling template. (B) The colored bars indicate the probability that a mutation to the corresponding residue will have some effect on function of the protein (mutation sensitivity) or on the phenotype of the organism. The tall and red bars indicate that the likelihood is high. Short and blue bars indicate that the likelihood is low. The R622I substitution (vertical arrow) is predicted to impact protein function.