The quiet erosion of artemisinin's effectiveness — the backbone of malaria treatment worldwide — is now measurable at a population level in East Africa, a region that historically incubated resistance to chloroquine and sulfadoxine-pyrimethamine before those failures spread globally. Understanding how far Kelch13 mutations have penetrated East African parasite populations matters not just for regional health systems, but for the entire global malaria control architecture.
This systematic review and meta-analysis synthesized data from 24 eligible studies covering a decade of surveillance (2014–2024) across East Africa, specifically tracking non-synonymous mutations in the Plasmodium falciparum Kelch13 (Pf-Kelch13) propeller domain — the primary molecular marker of partial artemisinin resistance. Using a random-effects model to account for substantial between-study heterogeneity (I² exceeding 95%), the pooled prevalence of these resistance-conferring mutations was estimated at 5.0% (95% CI: 3.0%–7.0%). Critically, Rwanda and Uganda showed disproportionately higher pooled proportions compared to other East African nations, suggesting uneven geographic spread rather than uniform regional saturation.
This finding carries layered significance when placed against the broader global resistance timeline. The validated Kelch13 mutations — particularly C580Y, which dominates in Southeast Asia — have been spreading in East Africa with a distinct regional mutation profile, including the locally prevalent A675V and C469Y variants. A 5% regional average may understate focal hotspots while masking relatively lower-burden zones, and the extreme heterogeneity (I² >95%) underscores that country-level and even district-level granularity is essential for clinical and policy decisions. The observational and cross-sectional nature of most constituent studies limits causal inference about treatment failure rates, and publication bias — assessed via funnel plots — remains a methodological concern. Still, as a decade-spanning meta-analysis with PROSPERO registration, this work provides the most comprehensive quantitative baseline yet for East African Kelch13 surveillance, making it a pivotal reference for artemisinin combination therapy stewardship going forward.