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, Christopher V. Plowe

Research output: Contribution to journalArticle

Abstract

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. Plasmodiumfalciparuminfections in southern China displayedmarkedly delayed clearance following artemisinin treatment. F446I was the predominant K13 mutation and was associated with delayed parasite clearance.

Original languageEnglish (US)
Pages (from-to)1629-1635
Number of pages7
JournalJournal of Infectious Diseases
Volume212
Issue number10
DOIs
StatePublished - 2015
Externally publishedYes

Fingerprint

Plasmodium falciparum
China
Mutation
Parasites
dihydroartemisinin
Myanmar
Chromosomes, Human, Pair 13
Southeastern Asia
Parasitemia
Infection
DNA Sequence Analysis
Malaria
artemisinine
Clinical Trials
Genes
Proteins

Keywords

  • Artemisinin resistance
  • China
  • Kelch 13
  • Malaria
  • Plasmodium falciparum

ASJC Scopus subject areas

  • Immunology and Allergy
  • Medicine(all)
  • Infectious Diseases

Cite this

A Single Mutation in K13 Predominates in Southern China and Is Associated with Delayed Clearance of Plasmodium falciparum Following Artemisinin Treatment. / Huang, Fang; Takala-Harrison, Shannon; Jacob, Christopher G.; Liu, Hui; Sun, Xiaodong; Yang, Henglin; Nyunt, Myaing M.; Adams, Matthew; Zhou, Shuisen; Xia, Zhigui; Ringwald, Pascal; Bustos, Maria Dorina; Tang, Linhua; Plowe, Christopher V.

In: Journal of Infectious Diseases, Vol. 212, No. 10, 2015, p. 1629-1635.

Research output: Contribution to journalArticle

Huang, F, Takala-Harrison, S, Jacob, CG, Liu, H, Sun, X, Yang, H, Nyunt, MM, Adams, M, Zhou, S, Xia, Z, Ringwald, P, Bustos, MD, Tang, L & Plowe, CV 2015, 'A Single Mutation in K13 Predominates in Southern China and Is Associated with Delayed Clearance of Plasmodium falciparum Following Artemisinin Treatment', Journal of Infectious Diseases, vol. 212, no. 10, pp. 1629-1635. https://doi.org/10.1093/infdis/jiv249
Huang, Fang ; Takala-Harrison, Shannon ; Jacob, Christopher G. ; Liu, Hui ; Sun, Xiaodong ; Yang, Henglin ; Nyunt, Myaing M. ; Adams, Matthew ; Zhou, Shuisen ; Xia, Zhigui ; Ringwald, Pascal ; Bustos, Maria Dorina ; Tang, Linhua ; Plowe, Christopher V. / A Single Mutation in K13 Predominates in Southern China and Is Associated with Delayed Clearance of Plasmodium falciparum Following Artemisinin Treatment. In: Journal of Infectious Diseases. 2015 ; Vol. 212, No. 10. pp. 1629-1635.
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title = "A Single Mutation in K13 Predominates in Southern China and Is Associated with Delayed Clearance of Plasmodium falciparum Following Artemisinin Treatment",
abstract = "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. Plasmodiumfalciparuminfections in southern China displayedmarkedly delayed clearance following artemisinin treatment. F446I was the predominant K13 mutation and was associated with delayed parasite clearance.",
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T1 - A Single Mutation in K13 Predominates in Southern China and Is Associated with Delayed Clearance of Plasmodium falciparum Following Artemisinin Treatment

AU - Huang, Fang

AU - Takala-Harrison, Shannon

AU - Jacob, Christopher G.

AU - Liu, Hui

AU - Sun, Xiaodong

AU - Yang, Henglin

AU - Nyunt, Myaing M.

AU - Adams, Matthew

AU - Zhou, Shuisen

AU - Xia, Zhigui

AU - Ringwald, Pascal

AU - Bustos, Maria Dorina

AU - Tang, Linhua

AU - Plowe, Christopher V.

PY - 2015

Y1 - 2015

N2 - 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. Plasmodiumfalciparuminfections in southern China displayedmarkedly delayed clearance following artemisinin treatment. F446I was the predominant K13 mutation and was associated with delayed parasite clearance.

AB - 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. Plasmodiumfalciparuminfections in southern China displayedmarkedly delayed clearance following artemisinin treatment. F446I was the predominant K13 mutation and was associated with delayed parasite clearance.

KW - Artemisinin resistance

KW - China

KW - Kelch 13

KW - Malaria

KW - Plasmodium falciparum

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