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Title: Spread of artemisinin resistance in Plasmodium falciparum malaria
Authors: 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
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
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
Keywords: Medicine
Issue Date: 1-Jan-2014
Citation: New England Journal of Medicine. Vol.371, No.5 (2014), 411-423
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.
ISSN: 15334406
Appears in Collections:Scopus 2011-2015

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