title: Distinctive origin of artemisinin-resistant Plasmodium falciparum on the China-Myanmar border.
abstract: The artemisinin (ART), discovered in China, has been widely used against malaria in China over the last 30 years. Understanding the emergence and origin of ART resistance in China is therefore of great interest. We analyzed 111 culture-adapted isolates of P. falciparum from China-Myanmar (CM) border for their susceptibility to dihydroartemisinin using the ring stage survival assay (RSA0-3h) and genotyped their K13 genes. Of the isolates, 59 had a wild type of the K13 marker and a median ring survival rate of 0.26% (P95 = 1.005%). Among the remaining isolates harboring single mutations in the K13 marker, 26 survived at >P95(median survival rate = 2.95%). Further, we genotyped the K13 gene of 693 isolates collected from different regions in China and China-Myanmar/Thai-Cambodia/Thai-Myanmar (CM/TC/TM) borders, 308 (44.4%) had K13 mutations and marked differences in the patterns of K13 mutations were observed between the CM and the TC/TM borders. A network diagram showed that majority of the K13 mutant alleles from the CM border clustered together including those harboring the high resistant-associated R539T mutations. The resistant parasites carrying distinct halplotypes suggested the multiple indigenous origins of the resistant alleles, which highlight the importance of surveillance of resistance in all malaria endemic areas where ART has been introduced.
authors.affiliation: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China.
authors.forename: Run
authors.initials: R
authors.lastname: Ye
authors.affiliation: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yufu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Yunnan Institute of Parasitic Diseases, Puer 665000, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Yunnan Institute of Parasitic Diseases, Puer 665000, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xuedi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Yunnan Institute of Parasitic Diseases, Puer 665000, China.
authors.forename: Hongning
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Parasitology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand.
authors.forename: Mathirut
authors.initials: M
authors.lastname: Mungthin
authors.affiliation: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Pan
mesh_terms: D000483:Alleles; D037621:Artemisinins; D002681:China; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D007783:Lactones; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D009154:Mutation; D002052:Myanmar; D010963:Plasmodium falciparum / Q000235:genetics*
chemical_list: D037621:Artemisinins; D007783:Lactones; C075875:artemisin
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