{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:27:55Z","timestamp":1793384875059,"version":"4.5.0"},"reference-count":49,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,9]]},"abstract":"<jats:p>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 (<jats:italic>N<\/jats:italic> = 64) compared with 22 in the post-ACT samples (<jats:italic>N<\/jats:italic> = 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.<\/jats:p>","DOI":"10.4269\/ajtmh.17-0505","type":"journal-article","created":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T07:00:39Z","timestamp":1522134039000},"page":"1360-1366","source":"Crossref","is-referenced-by-count":41,"title":["Polymorphisms in the K13 Gene in Plasmodium falciparum from Different Malaria Transmission Areas of Kenya"],"prefix":"10.4269","volume":"98","author":[{"given":"Zaydah R.","family":"de Laurent","sequence":"first","affiliation":[{"name":"Kenya Medical Research Institute\/United States Army Medical Research Directorate\u2013Kenya, Kisumu, Kenya;"},{"name":"Center for Biotechnology and Bioinformatics, University of Nairobi, Nairobi, Kenya;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna J.","family":"Chebon","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute\/United States Army Medical Research Directorate\u2013Kenya, Kisumu, Kenya;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luicer A.","family":"Ingasia","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute\/United States Army Medical Research Directorate\u2013Kenya, Kisumu, Kenya;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoseah M.","family":"Akala","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute\/United States Army Medical Research Directorate\u2013Kenya, Kisumu, Kenya;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Andagalu","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute\/United States Army Medical Research Directorate\u2013Kenya, Kisumu, Kenya;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynette Isabella","family":"Ochola-Oyier","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Bioinformatics, University of Nairobi, Nairobi, Kenya;"},{"name":"KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Kamau","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute\/United States Army Medical Research Directorate\u2013Kenya, Kisumu, Kenya;"},{"name":"Walter Reed National Military Medical Center (WRNMMC), Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"Nature","first-page":"50","article-title":"A molecular marker of artemisinin-resistant Plasmodium falciparum malaria","volume":"505","author":"Ariey","year":"2014"},{"key":"b2","series-title":"Science","first-page":"428","article-title":"K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates","volume":"347","author":"Straimer","year":"2014"},{"key":"b3","series-title":"N Engl J Med","first-page":"455","article-title":"Artemisinin resistance in Plasmodium falciparum malaria","volume":"361","author":"Dondorp","year":"2009"},{"key":"b4","first-page":"4935","article-title":"Plasmodium falciparum founder populations in western Cambodia have reduced artemisinin sensitivity in vitro","volume":"58","author":"Amaratunga","year":"2014"},{"key":"b5","series-title":"Lancet Infect Dis","first-page":"1043","article-title":"Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies","volume":"13","author":"Witkowski","year":"2013"},{"key":"b6","series-title":"Antimicrob Agents Chemother","first-page":"4938","article-title":"Flow cytometry-based analysis of artemisinin-resistant Plasmodium falciparum in the ring-stage survival assay","volume":"58","author":"Amaratunga","year":"2014"},{"key":"b7","series-title":"N Engl J Med","first-page":"411","article-title":"Spread of artemisinin resistance in Plasmodium falciparum Malaria","volume":"371","author":"Ashley","year":"2014"},{"key":"b8","series-title":"PLoS One","first-page":"e4551","article-title":"Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment","volume":"4","author":"Carrara","year":"2009"},{"key":"b9","series-title":"Lancet Infect Dis","first-page":"851","article-title":"Artemisinin-resistant Plasmodium falciparum in Pursat province, western Cambodia: a parasite clearance rate study","volume":"12","author":"Amaratunga","year":"2012"},{"key":"b10","series-title":"Malar J","first-page":"47","article-title":"In vivo monitoring of dihydroartemisinin-piperaquine sensitivity in Plasmodium falciparum along the China\u2013Myanmar border of Yunnan Province, China from 2007 to 2013","volume":"14","author":"Liu","year":"2015"},{"key":"b11","series-title":"Nat Genet","first-page":"648","article-title":"Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia","volume":"45","author":"Miotto","year":"2013"},{"key":"b12","series-title":"N Engl J Med","first-page":"2453","article-title":"A worldwide map of Plasmodium falciparum K13-propeller polymorphisms","volume":"374","author":"M\u00e9nard","year":"2016"},{"key":"b13","author":"WHO","year":"2016"},{"key":"b14","series-title":"Nat Genet","first-page":"226","article-title":"Genetic architecture of artemisinin-resistant Plasmodium falciparum","volume":"47","author":"Miotto","year":"2015"},{"key":"b15","series-title":"J Infect Dis","first-page":"670","article-title":"Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in Southeast Asia","volume":"211","author":"Takala-Harrison","year":"2015"},{"key":"b16","series-title":"eLife","first-page":"17","article-title":"Genomic epidemiology of artemisinin resistant malaria","volume":"5","author":"MalariaGEN Plasmodium falciparum Community Project","year":"2016"},{"key":"b17","series-title":"Am J Trop Med Hyg","first-page":"1202","article-title":"Polymorphisms in the K13-propeller gene in artemisinin-susceptible Plasmodium falciparum parasites from Bougoula-Hameau and Bandiagara, Mali","volume":"92","author":"Ouattara","year":"2015"},{"key":"b18","series-title":"J Infect Dis","first-page":"680","article-title":"Absence of putative artemisinin resistance mutations among Plasmodium falciparum in Sub-Saharan Africa: a molecular epidemiologic study","volume":"211","author":"Taylor","year":"2015"},{"key":"b19","series-title":"Emerg Infect Dis","first-page":"490","article-title":"Novel mutations in K13 propeller gene of artemisinin-resistant Plasmodium falciparum","volume":"21","author":"Isozumi","year":"2015"},{"key":"b20","series-title":"J Infect Dis","first-page":"1352","article-title":"K13-propeller polymorphisms in Plasmodium falciparum parasites from sub-Saharan Africa","volume":"211","author":"Kamau","year":"2015"},{"key":"b21","series-title":"PLoS One","first-page":"e105690","article-title":"Polymorphisms in K13 and falcipain-2 associated with artemisinin resistance are not prevalent in Plasmodium falciparum isolated from Ugandan children","volume":"9","author":"Conrad","year":"2014"},{"key":"b22","series-title":"Malar J","first-page":"36","article-title":"Lack of K13 mutations in Plasmodium falciparum persisting after artemisinin combination therapy treatment of Kenyan children","volume":"15","author":"Muwanguzi","year":"2016"},{"key":"b23","series-title":"BMC Infect Dis","first-page":"428","article-title":"Prevalence of K13-propeller gene polymorphisms among Plasmodium falciparum parasites isolated from adult symptomatic patients in northern Uganda","volume":"16","author":"Ocan","year":"2016"},{"key":"b24","series-title":"Malar J","first-page":"208","article-title":"Molecular markers of anti-malarial drug resistance in southwest Ethiopia over time: regional surveillance from 2006 to 2013","volume":"14","author":"Heuchert","year":"2015"},{"key":"b25","series-title":"N Engl J Med","first-page":"991","article-title":"Emergence of indigenous artemisinin-resistant Plasmodium falciparum in Africa","volume":"376","author":"Lu","year":"2017"},{"key":"b26"},{"key":"b27","series-title":"Malar J","first-page":"72","article-title":"The challenges of changing national malaria drug policy to artemisinin-based combinations in Kenya","volume":"6","author":"Amin","year":"2007"},{"key":"b28","series-title":"Nucleic Acids Res","first-page":"1792","article-title":"MUSCLE: multiple sequence alignment with high accuracy and high throughput","volume":"32","author":"Edgar","year":"2004"},{"key":"b29","series-title":"Malar J","first-page":"71","article-title":"Mutations in P. falciparum K13 propeller gene from Bangladesh: emerging resistance?","volume":"13","author":"Alam","year":"2014"},{"key":"b30","series-title":"Malar J","first-page":"431","article-title":"Mutations in Plasmodium falciparum K13 propeller gene from Bangladesh (2009\u20132013)","volume":"13","author":"Mohon","year":"2014"},{"key":"b31","series-title":"Antimicrob Agents Chemother","first-page":"2548","article-title":"Surveillance of artemisinin resistance in Plasmodium falciparum in India using the Kelch 13 molecular marker","volume":"59","author":"Mishra","year":"2015"},{"key":"b32","series-title":"Malar J.","first-page":"33","article-title":"Efficacy and safety of artemether-lumefantrine and dihydroartemisinin-piperaquine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children aged less than five years: results of an open-label, randomized, single-centre study","volume":"13","author":"Ogutu","year":"2014"},{"key":"b33","series-title":"Malar J","first-page":"6","article-title":"Therapeutic efficacy of artesunate-amodiaquine and artemether\u2013lumefantrine combinations in the treatment of uncomplicated malaria in two ecological zones in Ghana","volume":"15","author":"Abuaku","year":"2016"},{"key":"b34","series-title":"Malar J","first-page":"174","article-title":"Efficacy of fixed-dose combination artesunate\u2013amodiaquine versus artemether\u2013lumefantrine for uncomplicated childhood Plasmodium falciparum malaria in Democratic Republic of Congo: a randomized non-inferiority trial","volume":"11","author":"Espi\u00e9","year":"2012"},{"key":"b35","series-title":"Malar J","first-page":"53","article-title":"Artesunate-amodiaquine efficacy in Congolese children with acute uncomplicated falciparum malaria in Brazzaville","volume":"12","author":"Ndounga","year":"2013"},{"key":"b36","series-title":"Malar J","first-page":"37","article-title":"Therapeutic efficacy of artemether\u2013lumefantrine for the treatment of uncomplicated falciparum malaria in northwest Benin","volume":"15","author":"Ogouy\u00e8mi-Hounto","year":"2016"},{"key":"b37","series-title":"Malar J","first-page":"251","article-title":"Efficacy of artesunate\u2013amodiaquine and artemether\u2013lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority","volume":"12","author":"Schramm","year":"2013"},{"key":"b38","series-title":"Lancet Infect Dis","first-page":"1123","article-title":"Comparison of artesunate\u2013mefloquine and artemether\u2013lumefantrine fixed-dose combinations for treatment of uncomplicated Plasmodium falciparum malaria in children younger than 5 years in sub-Saharan Africa: a randomised, multicentre, phase 4 trial","volume":"16","author":"Sirima","year":"2016"},{"key":"b39","series-title":"N Engl J Med","first-page":"411","article-title":"Spread of artemisinin resistance in Plasmodium falciparum malaria","volume":"371","author":"Ashley","year":"2014"},{"key":"b40","series-title":"Antimicrob Agents Chemother","first-page":"5061","article-title":"Lack of artemisinin resistance in Plasmodium falciparum in Uganda based on parasitological and molecular assays","volume":"59","author":"Cooper","year":"2015"},{"key":"b41","series-title":"Parasit Vectors","first-page":"634","article-title":"Polymorphisms of the artemisinin resistant marker (K13) in Plasmodium falciparum parasite populations of Grande Comore Island 10 years after artemisinin combination therapy","volume":"8","author":"Huang","year":"2015"},{"key":"b42","series-title":"Am J Trop Med Hyg","first-page":"1202","article-title":"Polymorphisms in the K13-propeller gene in artemisinin-susceptible Plasmodium falciparum parasites from Bougoula-Hameau and Bandiagara, Mali","volume":"92","author":"Ouattara","year":"2015"},{"key":"b43","series-title":"Malar J","first-page":"472","article-title":"Limited polymorphisms in k13 gene in Plasmodium falciparum isolates from Dakar, Senegal in 2012\u20132013","volume":"13","author":"Torrentino-madamet","year":"2014"},{"key":"b44","series-title":"Nat Biotechnol","first-page":"819","article-title":"Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system","volume":"32","author":"Ghorbal","year":"2014"},{"key":"b45","series-title":"Infect Genet Evol","first-page":"372","article-title":"Genetic variability and population structure of Plasmodium falciparum parasite populations from different malaria ecological regions of Kenya","volume":"39","author":"Ingasia","year":"2016"},{"key":"b46","series-title":"Malar J","first-page":"168","article-title":"Prevalence of K13-propeller polymorphisms in Plasmodium falciparum from China\u2013Myanmar border in 2007\u20132012","volume":"14","author":"Wang","year":"2015"},{"key":"b47","series-title":"PLoS Pathog","first-page":"e1004789","article-title":"Selection and spread of artemisinin-resistant alleles in Thailand prior to the global artemisinin resistance containment campaign","volume":"11","author":"Talundzic","year":"2015"},{"key":"b48","series-title":"Science","first-page":"318","article-title":"Early origin and recent expansion of Plasmodium falciparum","volume":"300","author":"Joy","year":"2003"},{"key":"b49","series-title":"BMC Infect Dis","first-page":"180","article-title":"The risks of malaria infection in Kenya in 2009","volume":"9","author":"Noor","year":"2009"}],"container-title":["The American Journal of Tropical Medicine and 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