African Journal of Parasitology Research

African Journal of Parasitology Research | Vol. 14, No. 8, August 2026 | pp. 565–572

DOI: 10.46882/AJPR/170544

Article Type: Full Length Research Paper

Title: Emergence of kelch13 gene mutations associated with partial artemisinin resistance in Plasmodium falciparum isolates from northern Uganda

Names of Authors: Joseph O. Okello¹, Harriet A. Akello¹, Moses D. Wandera²

Authors’ Affiliations: ¹Department of Medical Microbiology, College of Health Sciences, Makerere University, Kampala, Uganda. ²Gulu Regional Referral Hospital, Clinical Research Unit, Gulu, Uganda.

Abstract: The evolution of antimalarial drug resistance poses a critical threat to global malaria control efforts. This clinical surveillance program monitored molecular markers of artemisinin resistance across three districts in northern Uganda following reports of delayed parasite clearance times. Blood samples were collected from 480 patients presenting with uncomplicated Plasmodium falciparum malaria who were treated with standard artemether-lumefantrine. DNA extraction and targeted sequencing of the Pfkelch13 propeller domain were conducted alongside in vitro ring-stage survival assays. Genetic profiling identified Pfkelch13 mutations in 14.2 percent (n = 68) of the isolates, with the A675V and C469Y substitutions being the most prevalent alleles. Patients harboring these mutant parasites exhibited a significantly higher risk of persistent parasitaemia on day 3 post-treatment (relative risk = 3.84, 95 percent confidence interval [2.11 to 6.98]). The in vitro ring-stage survival assays confirmed phenotypic partial artemisinin resistance, demonstrating a mean survival rate of 8.6 percent in mutant isolates compared to 1.1 percent in wild-type strains (P < 0.001). No significant changes were detected in the copy number of the Pfmdr1 gene, suggesting sustained baseline efficacy of the partner drug lumefantrine. These molecular findings confirm the established focus of indigenous artemisinin resistance mutations in northern Uganda, demanding an urgent transition to triple artemisinin-based combination therapies to contain further spread.

Keywords: Plasmodium falciparum, Antimalarial resistance, Pfkelch13, Ring-stage survival assay, Genomics, Uganda

Manuscript Timeline: Received: 04 June 2026; Revised: 01 July 2026; Accepted: 22 July 2026; Published: 15 August 2026

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