Emergence and Rising Prevalence of Artemisinin Partial Resistance Marker Kelch13 P441L in a Low Malaria Transmission Setting in Southern Zambia

Anne C Martin; Jacob M Sadler; Alfred Simkin; Michael Musonda; Ben Katowa; Japhet Matoba; Jessica Schue; Edgar Simulundu; Jeffrey A Bailey; William J Moss; Jonathan J Juliano; Abebe A Fola

doi:10.1093/infdis/jiaf188

Emergence and Rising Prevalence of Artemisinin Partial Resistance Marker Kelch13 P441L in a Low Malaria Transmission Setting in Southern Zambia

J Infect Dis. 2025 Apr 17:jiaf188. doi: 10.1093/infdis/jiaf188. Online ahead of print.

Authors

Anne C Martin¹, Jacob M Sadler², Alfred Simkin³, Michael Musonda⁴, Ben Katowa⁴, Japhet Matoba⁴, Jessica Schue⁵, Edgar Simulundu⁴, Jeffrey A Bailey³, William J Moss^{1

5

6}, Jonathan J Juliano², Abebe A Fola³

Affiliations

¹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore USA.
² Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
³ Department of Pathology and Laboratory Medicine, Brown University, Providence USA.
⁴ Macha Research Trust, Choma, Zambia.
⁵ Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore USA.
⁶ Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore USA.

PMID: 40241390
DOI: 10.1093/infdis/jiaf188

Abstract

Increasing artemisinin partial resistance (ART-R) due to mutations in the gene encoding Kelch13 (Pfk13) protein in eastern Africa is of urgent concern, and mutations, such as Pfk13 P441L, continue to emerge. We used an amplicon deep-sequencing panel to estimate the prevalence of validated and candidate ART-R Pfk13 mutations in samples collected between 2018 and 2023 in southern Zambia. Pfk13 P441L was present in 30 of 501 samples (6%), and prevalence increased over time (0% to 7.2%). Further studies of the P441L mutation are needed to document its geographical origin, distribution and impact on treatment outcomes.

Keywords: P441L; Zambia; amplicon; artemisinin; deep-sequencing; drug resistance; malaria.

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