Last Updated: 18/06/2024
Elucidation of African artemisinin resistance mechanism of Plasmodium falciparum
Objectives
To examine the phenotypes of the Kelch13 A675V and C469Y mutations, which were thought to be the cause of resistance, in a culture system to further clarify the nature of the new artemisinin-resistant Plasmodium falciparum found in the Republic of Uganda.
The initial goal of this study was to demonstrate resistance by introducing the same mutation into the prototype strain by genome editing. N Engl J Med. 2021) was published by another group (Stokes et al. N Engl J Med. 2021). However, the degree of resistance is weak, suggesting that another factor is required to acquire strong resistance (Mita, Fukuda, Balikagala. N Engl J Med. 2021). Therefore, the focus was set on the presence of particularly strong clinical resistance among Kelch13 mutants from Uganda. Genomic analysis revealed that coexistence of another mutation with the Kelch13 A675V mutation increased clinical resistance. This result will be examined in detail by increasing the number of cases, and will be published as an original paper. In connection with this, new overseas sampling was conducted this fiscal year. In addition, in order to prove that this new mutation enhances artemisinin resistance due to the Kelch13 A675V mutation, mutant protozoa is currently being produced by genome editing and performing phenotypic analysis in a culture system. Kelch13 A675V and C469Y mutations are major markers of African artemisinin-resistant strains, but these mutations are not single mutations that confer strong resistance, but multiple overlapping factors lead to clinically significant resistance. be done. The results of this study will clarify additional factors that determine artemisinin resistance, and are expected to elucidate the mechanism and improve the efficiency of resistance diagnosis.
Aug 2021 — Mar 2023
$26,712
