Research report: 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

A systematic review and meta-analysis of studies published from 2010 through 2024 found that molecular markers of antimalarial drug resistance in Plasmodium falciparum followed contrasting geographic and temporal patterns across sub-Saharan Africa. Validated mutations in the kelch13 gene, associated with artemisinin resistance, became more prevalent in East Africa between 2014 and 2023, while pooled prevalence declined substantially for several markers associated with resistance to partner drugs used in artemisinin-based combination therapies. Markers linked to sulfadoxine–pyrimethamine resistance showed mixed results, with some remaining near fixation and others displaying pronounced regional clustering.

The review synthesized 172 studies concerning PfKelch13 mutations, 182 on Pfcrt , 196 on Pfmdr1 , and 176 on mutations in Pfdhfr and Pfdhps . Investigators searched PubMed/MEDLINE, Web of Science, Scopus, Embase, and African Journals Online. Two reviewers independently performed study selection, data extraction and risk-of-bias assessment in accordance with PRISMA 2020 guidelines.

The protocol was registered in PROSPERO under number CRD42023432718. Prevalence estimates were analyzed with random-effects models. Pooled prevalence was generated using a generalized linear mixed model with a logit transformation, while Cochran’s Q and I² statistics assessed heterogeneity between studies.

This statistical approach is relevant because the estimates combine prevalence measurements reported across different locations and periods. High heterogeneity, however, means that a single pooled percentage may conceal substantial variation among the underlying studies. From 2014 to 2023, the validated PfKelch13 mutations R622I, R561H and A675V expanded primarily in East Africa.

Their estimated prevalences reached 10–25% in Rwanda, Uganda and Tanzania. Central Africa recorded low-level emergence in 2021, with prevalence below 5%, whereas West Africa had only sporadic detections below 1%. These observations describe distinct regional patterns rather than a uniform continent-wide increase, and the review found marked spatial and temporal heterogeneity among studies of these mutations.

The pooled results for markers associated with resistance to some partner drugs pointed in the opposite direction. Prevalence of the Pfcrt K76T mutation fell from 76% in 2010, with a 95% confidence interval of 49–91% and I² of 97.9%, to 9% in 2023, with a 95% confidence interval of 8.7–9.5% and I² of 96.8%. The exceptionally high I² values indicate that prevalence estimates differed widely across the studies contributing to both pooled estimates.

The Pfmdr1 N86Y mutation also showed a substantial decline in the pooled analysis, falling from 34% in 2010, with a 95% confidence interval of 26–43% and I² of 93.5%, to an estimated zero in 2023, with a 95% confidence interval of 0–11% and I² of 97.1%. Regional heterogeneity remained high. The pooled estimate of zero therefore describes the combined analysis for 2023 rather than demonstrating that N86Y was absent in every locality or population represented by the included studies.

Markers associated with sulfadoxine–pyrimethamine resistance displayed another set of patterns. The Pfdhfr N51I, C59R and S108N mutations, together with the Pfdhps A437G mutation, remained near fixation in the pooled analysis. In contrast, Pfdhfr I164L, Pfdhps K540E and Pfdhps A581G showed pronounced spatial clustering, with the highest prevalence reported in East Africa and parts of Central Africa.

The contrast shows that mutations grouped by the same antimalarial drug did not necessarily share one regional or temporal trajectory. Taken together, the analysis identifies distinct trajectories for different resistance markers: expansion of several validated PfKelch13 mutations in East Africa, large pooled declines in Pfcrt K76T and Pfmdr1 N86Y, persistence of some sulfadoxine–pyrimethamine markers near fixation, and geographic concentration of others. The study measured the prevalence of molecular markers, not clinical treatment outcomes, and its results do not establish that changes in marker prevalence directly caused changes in parasite clearance or treatment failure.

The review’s broad geographic and temporal scope also places limits on interpretation. The authors concluded that the contrasting regional patterns underscore the need for sustained molecular surveillance tailored to local epidemiological trends. Continued surveillance is therefore presented as a response to the observed variation in resistance markers, rather than as evidence that any particular clinical intervention has already been shown to improve outcomes.

Subject of Research: Spatiotemporal prevalence of Plasmodium falciparum antimalarial drug-resistance markers in sub-Saharan Africa

Article Title: 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

Article References: Towanou Bohissou, F. E., Wilfried Nassa, G. J., Inoue, J., Sondo, P., Rouamba, T., Yessinou, J., Held, J., & Tinto, H. (2026). 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. BMC Infectious Diseases, 26(1), Article 1605. https://doi.org/10.1186/s12879-026-14233-2

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14233-2

Keywords: malaria, drug resistance, Plasmodium falciparum, artemisinin, PfKelch13, sub-Saharan Africa, systematic review, meta-analysis, molecular surveillance, sulfadoxine–pyrimethamine, Spatio-temporal, trends