期刊
JOURNAL OF INFECTIOUS DISEASES
卷 212, 期 10, 页码 1629-1635出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiv249
关键词
artemisinin resistance; China; kelch 13; malaria; Plasmodium falciparum
资金
- World Health Organization (WHO) Mekong Malaria Programme [WP/08/MVP/000512, WP/10/MVP/005837]
- National ST Major Program [2012ZX10004220]
- Overseas Public Health Training Programme of the Shanghai Health Bureau [GWHW201210]
- Howard Hughes Medical Institute
- WHO Global Malaria Programme
- Bill and Melinda Gates Foundation
- National Institute of Allergy and Infectious Diseases at the National Institutes of Health [R01AI101713]
Background. Artemisinin 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. Methods. Therapeutic 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. Results. Parasite 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. Conclusions. Plasmodium 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.
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