Efficacy of artemisinin derivatives and kelch13 mutations in Plasmodium falciparum: a systematic review and meta-analysis.

Artemisinin-based combination therapies (ACTs) remain the cornerstone of treatment for uncomplicated Plasmodium falciparum malaria; however, the spread of artemisinin resistance linked to kelch13 (pfk13) mutations poses a major global concern. This study aimed to systematically evaluate ACT efficacy in parallel with the global distribution of pfk13 mutations and to explore the relationship between molecular markers and clinical outcomes. A systematic review and meta-analysis were conducted using PubMed, Web of Science, and Scopus. Studies reporting 28-day adequate clinical and parasitological response (ACPR) following ACTs and assessing pfk13 mutations were included. Thirty studies from Asia, Africa, and the Americas were analyzed. ACTs maintained high efficacy, with pooled ACPR rates exceeding 95% and no significant regional differences (P = .99). By contrast, pfk13 mutation prevalence was significantly higher in Asia (P = .001). Notably, high treatment success rates were maintained despite the increasing prevalence of pfk13 mutations, indicating that the relationship between molecular resistance markers and clinical outcomes remains complex and may be modulated by partner-drug efficacy, host immunity, and local transmission dynamics. While ACTs remain highly effective, the marked geographical variation and persistence of resistance-associated mutations underscore the need for integrated molecular surveillance and therapeutic efficacy monitoring.