title: K13 Propeller Mutations in Plasmodium falciparum Populations in Regions of Malaria Endemicity in Vietnam from 2009 to 2016.
abstract: The spread of artemisinin-resistantPlasmodium falciparumcompromises the therapeutic efficacy of artemisinin combination therapies (ACTs) and is considered the greatest threat to current global initiatives to control and eliminate malaria. This is particularly relevant in Vietnam, where dihydroartemisinin-piperaquine (DP) is the recommended ACT forP. falciparuminfection. The propeller domain gene of K13, a molecular marker of artemisinin resistance, was successfully sequenced in 1,060P. falciparumisolates collected at 3 malaria hot spots in Vietnam between 2009 and 2016. Eight K13 propeller mutations (Thr474Ile, Tyr493His, Arg539Thr, Ile543Thr, Pro553Leu, Val568Gly, Pro574Leu, and Cys580Tyr), including several that have been validated to be artemisinin resistance markers, were found. The prevalences of K13 mutations were 29% (222/767), 6% (11/188), and 43% (45/105) in the Binh Phuoc, Ninh Thuan, and Gia Lai Provinces of Vietnam, respectively. Cys580Tyr became the dominant genotype in recent years, with 79.1% (34/43) of isolates in Binh Phuoc Province and 63% (17/27) of isolates in Gia Lai Province carrying this mutation. K13 mutations were associated with reduced ring-stage susceptibility to dihydroartemisinin (DHA)in vitroand prolonged parasite clearancein vivoAn analysis of haplotypes flanking K13 suggested the presence of multiple strains with the Cys580Tyr mutation rather than a single strain expanding across the three sites.
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam nhienntt@oucru.org.
authors.forename: Nguyen
authors.initials: N
authors.lastname: Thuy-Nhien
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Kim
authors.initials: NK
authors.lastname: Tuyen
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Thanh
authors.initials: NT
authors.lastname: Tong
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Tuong
authors.initials: NT
authors.lastname: Vy
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
authors.forename: Ngo Viet
authors.initials: NV
authors.lastname: Thanh
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
authors.forename: Huynh Thuy
authors.initials: HT
authors.lastname: Van
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
authors.forename: Pham
authors.initials: P
authors.lastname: Huong-Thu
authors.affiliation: Institute of Malariology, Parasitology, and Entomology, Quy Nhon, Vietnam.
authors.forename: Huynh Hong
authors.initials: HH
authors.lastname: Quang
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.|Center for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Maciej F
authors.initials: MF
authors.lastname: Boni
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.|Center for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.|Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
authors.forename: Christiane
authors.initials: C
authors.lastname: Dolecek
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.|Center for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Guy E
authors.initials: GE
authors.lastname: Thwaites
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.|Centre for Genomics and Global Health, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.|Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Olivo
authors.initials: O
authors.lastname: Miotto
authors.affiliation: Center for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.|Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.|Center for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Tran Tinh
authors.initials: TT
authors.lastname: Hien
mesh_terms: D000483:Alleles; D000962:Antimalarials / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology; D002986:Clinical Trials as Topic; D004338:Drug Combinations; D019353:Endemic Diseases; D062665:Epidemiological Monitoring; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D015870:Gene Expression; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology* / Q000469:parasitology; D009154:Mutation; D018512:Parasitemia / Q000188:drug therapy / Q000453:epidemiology* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D014744:Vietnam / Q000453:epidemiology; D010879:Piperazines
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D015800:Protozoan Proteins; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines
keywords: K13 mutation; Plasmodium falciparum; RSA; Vietnam; artemisinin resistance; frequency; parasite clearance