Incidence of kelch13 and Pfmdr1 gene mutations associated with antimalarial drug resistance in Plasmodium falciparum isolates from Ethiopia: a systematic review and meta-analysis

Abstract

The increasing prevalence of drug-resistant Plasmodium parasites, driven by factors including genetic mutations, intensifies the challenge of malaria eradication. This meta-analysis focused on the genetic component of resistance, specifically evaluating mutations in the kelch13 (R622I, P441L and A675V) and Pfmdr1 (Y184F and D1246Y) genes within Ethiopian Plasmodium falciparum strains. A systematic literature search was conducted across the PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library, and Google Scholar databases. Eligible studies included primary data on the prevalence of kelch13 and Pfmdr1 gene mutations in Plasmodium falciparum isolates from Ethiopia. Two reviewers independently conducted study selection, data extraction, and quality assessment. Heterogeneity was evaluated using the I² statistic, and a random-effects model was utilized to pool prevalence estimates with 95% confidence intervals (CI). Subgroup and sensitivity analyses were performed to explore sources of heterogeneity. Publication bias was assessed using funnel plots and Eggers test. All analyses were carried out using STATA software version 16. A total of fifteen studies were reviewed and analyzed, comprising 11,269 samples and 5,521 positive cases of Plasmodium falciparum. Pooled prevalence of kelch13 gene mutations at R622I, A675V, and P441L was 11%, 1% and 0% respectively. Pooled prevalence of Pfmdr1 gene mutations at D1246Y and Y184F was 6% and 77%, respectively. Subgroup analysis revealed this resistance marker has significantly increased over time, rising from 66% (2007–2014) to a concerning 91% (2015–2025). While most resistance markers remain rare or absent, the significant rise in the Pfmdr1 Y184F mutation highlights a growing concern regarding antimalarial drug resistance in Ethiopia.