Public Health

Evidence brief: Plasmodium falciparum non-synonymous Kelch13 mutations mediating artemisinin resistance in East Africa: A systematic review and meta-analysis: 2014–2024

A sourced PLOS One study, published 2026-07-28. Read the researchers’ findings, methods and context, with links to connected African health evidence.

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Published in PLOS One on 2026-07-28, this study is presented as an attributed evidence briefing. The excerpts below are the original researchers’ words, reproduced under their Creative Commons Attribution licence. Health Signal has selected the abstract and, where needed, opening background paragraphs; the complete methods, results, limitations and references remain in the linked paper.

Original authors: Anthony Kapesa, Vito Baraka, Richard Mwaiswelo, Maria Zinga, Karol J Marwa, Eliningaya J Kweka, Erasmus Kamugisha

Source: PLOS One • DOI 10.1371/journal.pone.0354429

Read the complete primary study ↗ · Creative Commons Attribution licence

From the researchers

Abstract

Resistance to antimalarial drugs has posed a significant challenge to global efforts to control and eliminate malaria. Partial artemisinin resistance has been observed in East Africa, a region that has been a historical hotspot for antimalarial drug resistance across the continent. Consequently, this review assesses the extent of non-synonymous mutations mediating artemisinin resistance, the varieties of these mutations, and their effects on treatment outcomes in East Africa.

Studies reporting artemisinin resistance (samples collected between 2014 and 2024), particularly the Pf-Kelch13 mutation among malaria patients in East Africa, were searched through the Medline, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, and EMBASE online databases. The protocol for the review was registered at PROSPERO (Reference number: CRD42024602752). Two independent reviewers extracted data. Potential publication bias was assessed using a funnel plot. Pooled proportion estimates were calculated using a random-effects model, and heterogeneity was assessed using I2 statistics.

Twenty-four (24) studies were deemed eligible for data extraction. The heterogeneity among the studies included in the meta-analysis was high (I2 > 95% and p < 0.01). The overall estimated pooled proportions of non-synonymous Pf-Kelch13 mutations, using the random effects model, were 5.0% (95% CI 3.0%–7.0%), with the pooled proportion estimates being higher in Rwanda and Uganda (10.0%, 95% CI 4.0%–16.0%) and (10.0%, 95% CI 6.0%–14.0%), respectively. Subgroup analysis (per mutation type) revealed that R561H and A675V were the most prevalent non-synonymous mutations (9.0%, 95% CI 5.0%–15.0% and 7.0%, 95% CI 4.0%–10.0%, respectively). Patients harbouring parasites with Pf-Kelch13 non-synonymous mutations were significantly more likely to experience treatment failure than those harbouring wild P. falciparum parasites (Log OR: −2.06, 95% CI, −2.71–1.41).

The prevalence of Pf-Kelch13 non-synonymous mutations known to be associated with artemisinin resistance was significant. The most common mutations identified were R561H and A675V. Continued molecular surveillance and coordinated efforts are essential to contain the partial artemisinin resistance in the East African region and prevent its spread across the continent.

Background

Despite the substantial progress made in sub-Saharan Africa (sSA), particularly in East Africa, the reduction of malaria transmission has recently stagnated [1]. In general, the current malaria control and elimination efforts confront challenges due to insufficient funding, emerging vector resistance, and the looming threat of artemisinin resistance [2]. The recent emergence and spread of partial artemisinin resistance in the East African region is concerning [3], as it could further compromise the progress made in reducing the disease burden in the region and Africa at large.

Previous evidence showed that resistance to the primary antimalarials, chloroquine (CQ) and later sulfadoxine-pyrimethamine (SP), spread from SEA to the East African region and throughout Africa; thus, EA is a historical hotspot for antimalarial resistance in Africa [4,5]. However, recent evidence on artemisinin records a change in trend whereby the Pf-Kelch13 mutations identified in the East African region have been confirmed to be indigenous (do not relate to those reported in SEA [3,6]. Partial artemisinin resistance was first recorded in Rwanda, followed by other neighbouring countries (Uganda and Tanzania). The emergence of partial artemisinin resistance in the region is crucial because of its potential to spread to different parts of Africa, considering the Horn of Africa, which borders EA, has also recorded partial artemisinin resistance [7].

Reading this evidence

Use the full paper to check the study design, participant selection, comparator and outcome definitions before drawing a practical conclusion. An association does not by itself show cause and effect. A reported performance measure needs its denominator and uncertainty. A finding from a particular facility, sample or time period should retain that scope when it is discussed elsewhere.

This briefing makes the source accessible within the wider public health desk. It does not assess an individual patient or certify a product. When considering relevance to another health system, examine the original authors’ account of context and limitations, then seek local implementation evidence. The related reporting below provides other studies to read alongside this one; it is a topic connection, rather than a claim that their results are directly comparable.

© 2026 Anthony Kapesa, Vito Baraka, Richard Mwaiswelo, Maria Zinga, Karol J Marwa, Eliningaya J Kweka, Erasmus Kamugisha. Excerpts reproduced under CC BY. Selection, formatting and contextual notes by Health Signal. The researchers are the authors of the source study, not members of Health Signal’s staff.

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Health Signal’s publication desk curates source-based health analysis and attributed research briefings. Study authors and originating institutions are credited within each article. Preparation used AI assistance; source and licence checks do not constitute independent replication or clinical endorsement.

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