Prevalence of pfkelch13 Mutations and Clinical Indicators of Artemisinin Partial Resistance in Africa: A Systematic Review and Meta-Analysis of Observational Cohorts

Abstract

BackgroundArtemisinin-based combination therapies remain the mainstay of malaria control strategies; nevertheless, the advent of genetic markers linked to partial artemisinin resistance in Plasmodium falciparum has elicited substantial concern across African settings. To assess the prevalence, geographic distribution, and clinical associations of these molecular markers, we undertook a systematic review and meta-analysis of observational cohort studies. MethodsWe conducted a search of cohort studies published between January 2015 and June 2025, following PRISMA 2020 guidelines. We queried databases including PubMed/MEDLINE, Scopus, Web of Science, and CINAHL. Eligibility required prospective enrollment of patients, longitudinal monitoring (therapeutic efficacy studies), and pfkelch13 propeller domain genotyping. ResultsA meta-analytical synthesis of 888 isolates from six core prospective cohorts revealed a pooled prevalence of 6% (95% CI: 2.1%-11.8%) for validated pfkelch13 mutations. A profound geographic dichotomy was identified: while West and Central African cohorts maintained a 0% prevalence, East African hotspots showed significant expansion, with prevalence reaching 12.8% in Rwanda and up to 25.5% in Northern Uganda; high statistical heterogeneity (I 2 = 96.3 %, p < 0.001) reflects this biological divergence. ConclusionsThese findings highlight the established and expanding presence of artemisinin partial resistance in East Africa. Standardized surveillance is essential to adapt malaria control policies across the continent.