Spatio-temporal trends of the prevalence of Plasmodium falciparum antimalarial drug resistance markers across sub-Saharan Africa from 2010 to 2024: a systematic review and meta-analysis.

BACKGROUND: The emergence and subsequent spread of antimalarial drug resistance represent a significant threat to the efficacy of artemisinin-based combination therapies (ACTs) in sub-Saharan Africa. Multiple molecular markers have been implicated in resistance to artemisinin and its partner drugs. We conducted a systematic review and meta-analysis of studies published between 2010 and 2024 in sub-Saharan Africa. METHODS: The protocol was registered in PROSPERO (CRD42023432718). Studies were identified through PubMed/MEDLINE, Web of Science, Scopus, Embase, and African Journal Online. Study selection, data extraction, and risk-of-bias assessment were performed independently by two reviewers in accordance with the PRISMA 2020 guidelines. Prevalence data for mutations in PfKelch13, Pfcrt, Pfmdr1, and Pfdhfr/Pfdhps were extracted and analysed using random-effects models, with pooled prevalence estimates generated using a generalized linear mixed model (GLMM) with logit transformation. Between-study heterogeneity was assessed using Cochran's Q and I2 statistics. RESULTS: A total of 172 studies on PfKelch13, 182 on Pfcrt, 196 on Pfmdr1, and 176 on Pfdhfr/Pfdhps were included. From 2014 to 2023, validated PfKelch13 mutations exhibited marked spatial and temporal heterogeneity, with R622I, R561H, and A675V expanding primarily in East Africa, reaching prevalences of 10-25% in Rwanda, Uganda, and Tanzania. In Central Africa, emergence was observed in 2021 at low levels (below 5%), while West Africa reported only sporadic low-prevalence (below 1%) detections. In contrast, resistance to some partner drugs declined substantially across Africa, with Pfcrt K76T decreasing from 76% (95% CI: 49% - 91%; I2 = 97.9%) in 2010 to 9% (95% CI: 8.7% - 9.5%; I2 = 96.8%) in 2023 and Pfmdr1 N86Y falling from 34% (95% CI: 26% - 43%; I2 = 93.5%) to zero (95% CI: 0% - 11%; I2 = 97.1%), with persistent regional heterogeneity. Certain markers of sulfadoxine-pyrimethamine (SP) resistance (Pfdhfr N51I, C59R, S108N and Pfdhps A437G) remained near fixation, whereas Pfdhfr I164L, Pfdhps K540E, and Pfdhps A581G showed pronounced spatial clustering, with the highest prevalence reported in East and parts of Central Africa. CONCLUSION: Overall, the temporal and regional patterns of antimalarial drug resistance molecular markers across sub-Saharan Africa underscore the need for sustained molecular surveillance tailored to local epidemiological trends of resistance markers. REGISTRATION: Protocol registered in the International Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42023432718).