Functional assessment of prevalent kelch13 mutations reveals high-level artemisinin resistance potential in Bangladeshi Plasmodium falciparum - PubMed
6 hours ago
- #malaria
- #drug resistance
- #CRISPR
- Artemisinin partial resistance (ART-R) in Plasmodium falciparum is driven by mutations in the kelch13 (k13) gene, primarily observed in the Greater Mekong Subregion (GMS).
- The Chittagong Hill Tracts (CHTs) of Bangladesh, accounting for 90% of national malaria cases, show no reported K13-mediated ART-R but are at risk due to proximity to mutation-endemic areas.
- A meta-analysis identified C580Y, F446I, and R561H as the most prevalent K13 mutations globally, especially in the GMS.
- CRISPR-Cas9 was used to introduce these mutations into Bangladeshi P. falciparum isolates, revealing C580Y and R561H significantly increased ART-R, while F446I had a modest effect.
- R561H, expanding in Rwanda and dominant at the Thai-Myanmar border, conferred extreme resistance in CHT-R isolates, alongside asexual growth advantages.
- The study highlights that Bangladeshi parasites are genetically primed to sustain high-level ART-R, necessitating enhanced surveillance during malaria elimination efforts.
- This research underscores the risk of ART-R spreading beyond Southeast Asia and the importance of monitoring resistance in low-transmission regions.