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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Spread of artemisinin resistance in Plasmodium falciparum malaria
New England Journal of Medicine, Volume 371, No. 5, Year 2014
Notification
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Description
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.
Authors & Co-Authors
Ashley, Elizabeth A.
Unknown Affiliation
Dhorda, M. J.
Unknown Affiliation
Fairhurst, Rick M.
Unknown Affiliation
Amaratunga, Chanaki
Unknown Affiliation
Lim, Pharath
Unknown Affiliation
Suon, Seila
Unknown Affiliation
Sreng, Sokunthea
Unknown Affiliation
Anderson, Jennifer M.
Unknown Affiliation
Mao, Sivanna
Unknown Affiliation
Sam, B.
Unknown Affiliation
Sopha, C.
Unknown Affiliation
Chuor, Char Meng
Unknown Affiliation
Nguon, Chea
Unknown Affiliation
Sovannaroth, Siv
Unknown Affiliation
Pukrittayakamee, Sasithon
Unknown Affiliation
Jittamala, Podjanee
Unknown Affiliation
Chotivanich, Kesinee T.
Unknown Affiliation
Chutasmit, Kitipumi
Unknown Affiliation
Suchatsoonthorn, C.
Unknown Affiliation
Runcharoen, R.
Unknown Affiliation
Hien, Tran Tinh
Unknown Affiliation
Thuy-Nhien, Nguyen Thanh
Unknown Affiliation
Thanh, Ngo Viet
Unknown Affiliation
Phu, Nguyen Hoan
Unknown Affiliation
Htut, Ye
Unknown Affiliation
Han, Kay Thwe
Unknown Affiliation
Aye, Kay Hla
Unknown Affiliation
Mokuolu, Olugbenga Ayodeji
Unknown Affiliation
Olaosebikan, Rasaq R.
Unknown Affiliation
Folaranmi, Olaleke Oluwasegun
Unknown Affiliation
Mayxay, Mayfong
Unknown Affiliation
Khanthavong, Maniphone
Unknown Affiliation
Hongvanthong, Bouasy
Unknown Affiliation
Newton, Paul N.
Unknown Affiliation
Onyamboko, Marie A.
Unknown Affiliation
Fanello, Caterina I.
Unknown Affiliation
Tshefu, Antoinette Kitoto
Unknown Affiliation
Mishra, Neelima N.
Unknown Affiliation
Valecha, Neena
Unknown Affiliation
Pyae Phyo, Aung Pyae P.
Unknown Affiliation
Nosten, François Henry
Unknown Affiliation
Yi, Poravuth
Unknown Affiliation
Tripura, Rupam
Unknown Affiliation
Borrmann, Steffen
Unknown Affiliation
Bashraheil, Mahfudh
Unknown Affiliation
Peshu, Judy
Unknown Affiliation
Faiz, Mohammad Abul
Unknown Affiliation
Ghose, Aniruddha
Unknown Affiliation
Hossain, Md Amir
Unknown Affiliation
Samad, R.
Unknown Affiliation
Rahman, Muhibur
Unknown Affiliation
Hasan, Mahtab Uddin
Unknown Affiliation
Islam, Akhter Ul
Unknown Affiliation
Miotto, Olivo
Unknown Affiliation
Amato, Roberto
Unknown Affiliation
MacInnis, Bronwyn L.
Unknown Affiliation
Stalker, Jim W.
Unknown Affiliation
Kwiatkowski, Dominic P.
Unknown Affiliation
Bozdech, Zbynek
Unknown Affiliation
Jeeyapant, Atthanee
Unknown Affiliation
Cheah, Phaikyeong
Unknown Affiliation
Sakulthaew, Tharisara
Unknown Affiliation
Chalk, Jeremy
Unknown Affiliation
Intharabut, B.
Unknown Affiliation
Silamut, Kamolrat
Unknown Affiliation
Lee, Sue J.
Unknown Affiliation
Vihokhern, Benchawan
Unknown Affiliation
Kunasol, Chanon
Unknown Affiliation
Imwong, Mallika
Unknown Affiliation
Tarning, Joel
Unknown Affiliation
Taylor, W. J.
Unknown Affiliation
Yeung, Shunmay M.
Unknown Affiliation
Woodrow, Charles Jonathan
Unknown Affiliation
Flegg, Jennifer A.
Unknown Affiliation
Das, Debashish
Unknown Affiliation
Smith, Jeffery J.
Unknown Affiliation
Venkatesan, Meera
Unknown Affiliation
Plowe, Christopher Vv
Unknown Affiliation
Stepniewska, K. A.
Unknown Affiliation
Guérin, Philippe Jean Jean
Unknown Affiliation
Dondorp, A. M.
Unknown Affiliation
Day, Nichloas P.J.
Unknown Affiliation
White, Nicholas J.
Unknown Affiliation
Statistics
Citations: 1,807
Authors: 83
Affiliations: 30
Identifiers
Doi:
10.1056/NEJMoa1314981
ISSN:
00284793
e-ISSN:
15334406
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Design
Cohort Study
Study Locations
Congo