Mapping the prevalence of molecular markers of Plasmodium falciparum artemisinin partial resistance in Africa: a spatial-temporal modelling study.

Background: Plasmodium falciparum kelch13 (k13) mutations in Africa signal emerging artemisinin partial resistance (ART-R), endangering malaria control by undermining artemisinin-based combination therapies (ACTs). Sparse surveillance obscures whether rising k13 ART-R prevalence reflects local emergence or geographic expansion. We aimed to model and infer high-resolution spatial-temporal prevalence of k13 ART-R and ACT partner-drug markers to inform public health policy. Methods: We conducted a systematic literature review (PROSPERO-ID CRD42024593923) spanning the years 2014-2025, complementing existing data from WWARN, MalariaGEN Pf7, and the WHO Malaria Threats Map. This integrated dataset, comprising 3,806 distinct molecular epidemiology surveys and 182,071 genotyped samples, was harmonized using a standardized data schema. We applied a spatial-temporal Gaussian process model to estimate the continuous prevalence of WHO k13 ART-R mutations, mdr1 86Y, and crt 76T. Findings: ART-R increases were driven by distinct emergences of k13 561H in Rwanda, k13 675V in Uganda, and k13 622I in Ethiopia and Eritrea. From 2012 to 2024, predicted k13 prevalence rose steadily in Northern Province, Uganda (1.81% per year) and Northern Province, Rwanda (3.49% per year), reaching 26.36% in Uganda and 39.44% in Rwanda by 2024. Modelling indicated a rapid transition from localized k13 ART-R mutation emergence to entrenched regional hotspots centred on Uganda-Rwanda and the Ethiopia-Eritrea border. Partner drug amodiaquine marker mdr1 86Y is fading, but crt 76T remains prevalent in the Horn of Africa. Interpretation: The rapid and multicentric expansion of k13 ART-R mutations in East Africa threatens ACT efficacy, especially where ART-R k13 and partner drug markers co-occur, mirroring early patterns observed before ACT failure in Southeast Asia. This study provides an updated k13 ART-R mutation database and high-resolution resistance maps with uncertainty quantification, demonstrating a crucial need to prioritize targeted molecular surveillance across greater East Africa to safeguard ACT efficacy.