Polymorphisms in the K13 Gene in Plasmodium falciparum from Different Malaria Transmission Areas of Kenya

Zaydah R. de Laurent Kenya Medical Research Institute/United States Army Medical Research Directorate–Kenya, Kisumu, Kenya;
Center for Biotechnology and Bioinformatics, University of Nairobi, Nairobi, Kenya;

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Lorna J. Chebon Kenya Medical Research Institute/United States Army Medical Research Directorate–Kenya, Kisumu, Kenya;

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Luicer A. Ingasia Kenya Medical Research Institute/United States Army Medical Research Directorate–Kenya, Kisumu, Kenya;

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Hoseah M. Akala Kenya Medical Research Institute/United States Army Medical Research Directorate–Kenya, Kisumu, Kenya;

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Ben Andagalu Kenya Medical Research Institute/United States Army Medical Research Directorate–Kenya, Kisumu, Kenya;

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Lynette Isabella Ochola-Oyier Center for Biotechnology and Bioinformatics, University of Nairobi, Nairobi, Kenya;
KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya;

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Edwin Kamau Kenya Medical Research Institute/United States Army Medical Research Directorate–Kenya, Kisumu, Kenya;
Walter Reed National Military Medical Center (WRNMMC), Bethesda, Maryland

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The development of artemisinin (ART)-resistant parasites in Southeast Asia (SEA) threatens malaria control globally. Mutations in the Kelch 13 (K13)-propeller domain have been useful in identifying ART resistance in SEA. ART combination therapy (ACT) remains highly efficacious in the treatment of uncomplicated malaria in Sub-Saharan Africa (SSA). However, it is crucial that the efficacy of ACT is closely monitored. Toward this effort, this study profiled the prevalence of K13 nonsynonymous mutations in different malaria ecological zones of Kenya and in different time periods, before (pre) and after (post) the introduction of ACT as the first-line treatment of malaria. Nineteen nonsynonymous mutations were present in the pre-ACT samples (N = 64) compared with 22 in the post-ACT samples (N = 251). Eight of these mutations were present in both pre- and post-ACT parasites. Interestingly, seven of the shared single-nucleotide polymorphisms were at higher frequencies in the pre-ACT than the post-ACT parasites. The A578S mutation reported in SSA and the V568G mutation reported in SEA were found in both pre- and post-ACT parasites, with their frequencies declining post-ACT. D584Y and R539K mutations were found only in post-ACT parasites; changes in these codons have also been reported in SEA with different amino acids. The N585K mutation described for the first time in this study was present only in post-ACT parasites, and it was the most prevalent mutation at a frequency of 5.2%. This study showed the type, prevalence, and frequency of K13 mutations that varied based on the malaria ecological zones and also between the pre- and post-ACT time periods.

Author Notes

Address correspondence to Edwin Kamau, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD 20889. E-mail: edwin.kamau.mil@mail.mil

Financial support: This work was supported by the Armed Forces Health Surveillance Centre, Division of Global Emerging Infections Surveillance and Response System Operations.

Nucleotide sequence accession numbers: Nucleotide sequence data are available in the GenBank database under the accession numbers KY987161 to KY987475.

Authors’ addresses: Zaydah R. de Laurent, Kenya Medical Research Institute/United States Army Medical Research Directorate-Kenya, Kisumu, Kenya, and Centre for Biotechnology and Bioinformatics, University of Nairobi, Nairobi, Kenya, E-mail: zdelaurent@gmail.com. Lorna J. Chebon, Luicer A. Ingasia, Hoseah M. Akala, and Ben Andagalu, Kenya Medical Research Institute/United States Army Medical Research Directorate-Kenya, Kisumu, Kenya, E-mails: lorna.chebon@usamru-k.org, luiser.ingasia@usamru-k.org, hosea.akala@usamru-k.org, and ben.andagalu@usamru-k.org. Lynette Isabella Ochola-Oyier, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya, and Centre for Biotechnology and Bioinformatics, University of Nairobi, Nairobi, Kenya, E-mail: isseyochola@gmail.com. Edwin Kamau, Walter Reed National Military Medical Center (WRNMMC), Bethesda, MD, 20889, E-mail: edwin.kamau.mil@mail.mil.

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