Spatial surveillance of Plasmodium falciparum Kelch 13 mutations reveals High-Frequency A675V and the First Molecular Evidence of Suspected Partial Artemisinin Resistance in Baringo in Kenya

Abstract

Abstract Background This surveillance study evaluated the polymorphisms of Pfk13 gene in samples from symptomatic individuals from eight geographically distinct locations in Kenya to determine the prevalence of mutations associated with partial artemisinin resistance. Methods Between 2018 and 2024, blood samples from individuals with symptoms of uncomplicated malaria at eight hospitals in four of the five distinct malaria transmission zones of Kenya were sequenced for single-nucleotide polymorphisms (SNPs) in Pfk13 and Pfmdr1 . Subsequent positive samples were tested to monitor treatment outcomes. Results A total of 44/679 (6.5%) samples harbored 49 Pfk13 mutations. These include 14 nonsynonymous mutations at Pfk13: A675V ( n = 20, 2.9%), A578S ( n = 4, 0.6%), C469Y ( n = 3, 0.44%), V386A ( n = 1, 0.15%), P553L ( n = 1, 0.15%), R561H/P ( n = 1, 0.15%), S522C (n = 1, 0.15%), K455E ( n = 1, 0.15%), S600F ( n = 1, 0.15%), E612D ( n = 1, 0.15%), N489K (n = 1, 0.15%), F491L ( n = 1, 0.15%) plus A504V ( n = 1, 0.15%). Four WHO-validated markers of partial artemisinin resistance were detected in 25/679 (3.7%) samples. Most Pfk13 A675V mutations (n = 12, 1.8%) were detected in Baringo County, where the mutation frequency reached 16.9%, exceeding the WHO 5% threshold for classification of areas with suspected partial artemisinin resistance. This represents the first molecular evidence consistent with suspected artemisinin resistance in Baringo County. Conclusion The detection of four WHO-validated Pfk13 markers of partial artemisinin resistance across multiple malaria transmission zones indicates emerging artemisinin resistance in Kenya. The high frequency of A675V in Baringo provides the first molecular evidence consistent with suspected partial artemisinin resistance in Kenya and highlights the need for enhanced therapeutic efficacy, deployment of Multiple first-line therapies, and molecular surveillance.