Evidence of Artemisinin-Resistant Malaria in Africa

Background In the six Southeast Asian countries that make up the Greater Mekong Subregion, Plasmodium falciparum has developed resistance to derivatives of artemisinin, the main component of first-line treatments for malaria. Clinical resistance to artemisinin monotherapy in other global regions, including Africa, would be problematic. Methods In this longitudinal study conducted in Northern Uganda, we treated patients who had P. falciparum infection with intravenous artesunate (a water-soluble artemisinin derivative) and estimated the parasite clearance half-life. We evaluated ex vivo susceptibility of the parasite using a ring-stage survival assay and genotyped resistance-related genes. Results From 2017 through 2019, a total of 14 of 240 patients who received intravenous artesunate had evidence of in vivo artemisinin resistance (parasite clearance half-life, >5 hours). Of these 14 patients, 13 were infected with P. falciparum parasites with mutations in the A675V or C469Y allele in the kelch13 gene. Such mutations were associated with prolonged parasite clearance half-lives (geometric mean, 3.95 hours for A675V and 3.30 hours for C469Y, vs. 1.78 hours for wild-type allele; P<0.001 and P=0.05, respectively). The ring-stage survival assay showed a higher frequency of parasite survival among organisms with the A675V allele than among those with the wild-type allele. The prevalence of parasites with kelch13 mutations increased significantly, from 3.9% in 2015 to 19.8% in 2019, due primarily to the increased frequency of the A675V and C469Y alleles (P<0.001 and P=0.004, respectively). Single-nucleotide polymorphisms flanking the A675V mutation in Uganda were substantially different from those in Southeast Asia. Conclusions The independent emergence and local spread of clinically artemisinin-resistant P. falciparum has been identified in Africa. The two kelch13 mutations may be markers for detection of these resistant parasites. (Funded by the Japan Society for the Promotion of Science and others.) Artemisinin-Resistant Malaria in Africa Artemisinin compounds are the backbone of global malaria treatment strategies, but resistant strains are emerging in Southeast Asia. In this report, the investigators report the emergence of artemisinin-resistant Plasmodium falciparum strains in Northern Uganda, with the predominant mutations observed in the kelch13 gene.

Automated summary

Research conducted in Northern Uganda revealed the emergence of artemisinin-resistant Plasmodium falciparum strains, with predominant mutations found in the kelch13 gene. Thirteen patients were infected with P. falciparum parasites carrying mutations in the A675V or C469Y allele, which were associated with prolonged parasite clearance half-lives.