Emergence and Spread of Plasmodium falciparum Kelch 13 Mutations in Selected Counties of Kenya: Implications for Responding to Artemisinin Partial Resistance.

Background This study evaluated the polymorphisms of Pfk13 gene alongside other malaria drug resistance markers in clinical samples 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 hospitals in eight hospitals in four of the five distinct malaria transmission zones of Kenya were sequenced for single nucleotide polymorphisms (SNPs) in Pfk13, and Pfmdr1, then a subset tested for in vitro susceptibility to selected antimalarials. Each individual was followed up on day 7 to monitor treatment outcomes Findings A total of 44/679 (6.5%) samples harbored 49 Pfk13 mutations. The mutations include 14 nonsynonymous at Pfk13 A675V 2.9% (n=20), A578S 0.6% (n=4), C469Y (n=3), V386A (n=1) at 0.44%, and P553L(n=1), R561H/P (n=1), S522C(n=1), K455E(n=1), S600F(n=1), E612D(n=1), N489K(n=1), F491L(n=1) plus A504V at 0.15% (n=1) alongside eleven synonymous mutations. Prevalence of the five validated markers of partial artemisinin resistance was 27/679 (4.0%). Most of Pfk13 675V mutations n=12 (1.8%) were detected in Baringo County of Kenya. 178/823 (21.6%) of the individuals tested positive by PCR on day 7 follow-up after treatment with artemether-lumefantrine. The median 50% inhibition concentration for lumefantrine against field samples was significantly higher than that of reference clones. Interpretation The detection of nonsynonymous mutations in 14 loci including five validated makers of partial artemisinin resistance in more samples than previously detected in Kenya and in diverse transmission zones suggests intense selective pressure consistent with emerging burden of partial artemisinin resistance. Funding Armed Forces Health Surveillance Branch and its Global Emerging Infections Surveillance Section.