Publication:
Spread of artemisinin resistance in Plasmodium falciparum malaria

Issued Date

2014-01-01

Resource Type

Article

ISSN

15334406
00284793

DOI

10.1056/NEJMoa1314981

Other identifier(s)

2-s2.0-84904892931

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

New England Journal of Medicine. Vol.371, No.5 (2014), 411-423

Suggested Citation

E. A. Ashley, M. Dhorda, R. M. Fairhurst, C. Amaratunga, P. Lim, S. Suon, S. Sreng, J. M. Anderson, S. Mao, B. Sam, C. Sopha, C. M. Chuor, C. Nguon, S. Sovannaroth, S. Pukrittayakamee, P. Jittamala, K. Chotivanich, K. Chutasmit, C. Suchatsoonthorn, R. Runcharoen, T. T. Hien, N. T. Thuy-Nhien, N. V. Thanh, N. H. Phu, Y. Htut, K. T. Han, K. H. Aye, O. A. Mokuolu, R. R. Olaosebikan, O. O. Folaranmi, M. Mayxay, M. Khanthavong, B. Hongvanthong, P. N. Newton, M. A. Onyamboko, C. I. Fanello, A. K. Tshefu, N. Mishra, N. Valecha, A. P. Phyo, F. Nosten, P. Yi, R. Tripura, S. Borrmann, M. Bashraheil, J. Peshu, M. A. Faiz, A. Ghose, M. A. Hossain, R. Samad, M. R. Rahman, M. M. Hasan, A. Islam, O. Miotto, R. Amato, B. MacInnis, J. Stalker, D. P. Kwiatkowski, Z. Bozdech, A. Jeeyapant, P. Y. Cheah, T. Sakulthaew, J. Chalk, B. Intharabut, K. Silamut, S. J. Lee, B. Vihokhern, C. Kunasol, M. Imwong, J. Tarning Spread of artemisinin resistance in Plasmodium falciparum malaria. New England Journal of Medicine. Vol.371, No.5 (2014), 411-423. doi:10.1056/NEJMoa1314981 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/34882

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Thesis

Title

Spread of artemisinin resistance in Plasmodium falciparum malaria

Author(s)

E. A. Ashley
 M. Dhorda
 R. M. Fairhurst
 C. Amaratunga
 P. Lim
 S. Suon
 S. Sreng
 J. M. Anderson
 S. Mao
 B. Sam
 C. Sopha
 C. M. Chuor
 C. Nguon
 S. Sovannaroth
 S. Pukrittayakamee
 P. Jittamala
 K. Chotivanich
 K. Chutasmit
 C. Suchatsoonthorn
 R. Runcharoen
 T. T. Hien
 N. T. Thuy-Nhien
 N. V. Thanh
 N. H. Phu
 Y. Htut
 K. T. Han
 K. H. Aye
 O. A. Mokuolu
 R. R. Olaosebikan
 O. O. Folaranmi
 M. Mayxay
 M. Khanthavong
 B. Hongvanthong
 P. N. Newton
 M. A. Onyamboko
 C. I. Fanello
 A. K. Tshefu
 N. Mishra
 N. Valecha
 A. P. Phyo
 F. Nosten
 P. Yi
 R. Tripura
 S. Borrmann
 M. Bashraheil
 J. Peshu
 M. A. Faiz
 A. Ghose
 M. A. Hossain
 R. Samad
 M. R. Rahman
 M. M. Hasan
 A. Islam
 O. Miotto
 R. Amato
 B. MacInnis
 J. Stalker
 D. P. Kwiatkowski
 Z. Bozdech
 A. Jeeyapant
 P. Y. Cheah
 T. Sakulthaew
 J. Chalk
 B. Intharabut
 K. Silamut
 S. J. Lee
 B. Vihokhern
 C. Kunasol
 M. Imwong
 J. Tarning

Other Contributor(s)

Mahidol University
 Phusing Hospital
 Khunhan Hospital
 Kraburi Hospital
 University of Oxford
 Nuffield Department of Clinical Medicine
 Wellcome Trust Centre for Human Genetics
 Wellcome Trust Sanger Institute
 London School of Hygiene & Tropical Medicine
 University of Maryland, Baltimore
 National Institute of Allergy and Infectious Diseases
 National Center for Parasitology, Entomology and Malaria Control
 Sampov Meas Referral Hospital
 Ratanakiri Referral Hospital
 Makara 16 Referral Hospital
 UCL
 Department of Medical Research
 University of Ilorin
 Mahosot Hospital
 University of Health Sciences
 Centre of Malariology
 Kinshasa School of Public Health
 National Institute of Malaria Research India
 Wellcome Trust Research Laboratories Nairobi
 Universitat Tubingen
 Malaria Research Group and Dev Care Foundation
 Shaheed Suhrawardy Medical College
 Chittagong Medical College
 Ramu Upazila Health Complex
 Nanyang Technological University

Abstract

BACKGROUND: Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies. METHODS: Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined. RESULTS: The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand-Cambodia border. Slowly clearing infections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the "propeller" region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days. CONCLUSIONS: Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. Copyright © 2014 Massachusetts Medical Society.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/34882

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