• J. Infect. Dis. · Nov 2015

    A Single Mutation in K13 Predominates in Southern China and Is Associated With Delayed Clearance of Plasmodium falciparum Following Artemisinin Treatment.

    • Fang Huang, Shannon Takala-Harrison, Christopher G Jacob, Hui Liu, Xiaodong Sun, Henglin Yang, Myaing M Nyunt, Matthew Adams, Shuisen Zhou, Zhigui Xia, Pascal Ringwald, Maria Dorina Bustos, Linhua Tang, and Christopher V Plowe.
    • National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, World Health Organization Collaborating Centre for Malaria, Schistosomiasis and Filariasis, Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, PR China Center for Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore.
    • J. Infect. Dis. 2015 Nov 15; 212 (10): 1629-35.

    BackgroundArtemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and poses a threat to malaria control and elimination. Mutations in a P. falciparum gene encoding a kelch protein on chromosome 13 have been associated with delayed parasite clearance following artemisinin treatment elsewhere in the region, but not yet in China.MethodsTherapeutic efficacy studies of artesunate and dihydroartemisinin-piperaquine were conducted from 2009 to 2012 in the Yunnan Province of China near the border with Myanmar. K13 mutations were genotyped by capillary sequencing of DNA extracted from dried blood spots collected in these clinical trials and in routine surveillance. Associations between K13 mutations and delayed parasite clearance were tested using regression models.ResultsParasite clearance half-lives were prolonged after artemisinin treatment, with 44% of infections having half-lives >5 hours (n = 109). Fourteen mutations in K13 were observed, with an overall prevalence of 47.7% (n = 329). A single mutation, F446I, predominated, with a prevalence of 36.5%. Infections with F446I were significantly associated with parasitemia on day 3 following artemisinin treatment and with longer clearance half-lives.ConclusionsPlasmodium falciparum infections in southern China displayed markedly delayed clearance following artemisinin treatment. F446I was the predominant K13 mutation and was associated with delayed parasite clearance.© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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