Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/106044
Title: Spread of artemisinin resistance in plasmodium falciparum malaria
Authors: Tripura, Rupam
Borrmann, Steffen
Bashraheil, Mahfudh
Peshu, Judy
Faiz, M. Abul
Ghose, Aniruddha
Hossain, M. Amir
Samad, Rasheda
Rahman, M. Ridwanur
Valecha, Neena
Phyo, Aung Pyae
Venkatesan, Meera
Mishra, Neelima
Yi, Poravuth
Ashley, Elizabeth A.
Dhorda, Mehul
Fairhurst, Rick M.
Amaratunga, Chanaki
Lim, Parath
Suon, Seila
Sreng, Sokunthea
Anderson, Jennifer M.
Mao, Sivanna
Sam, Baramey
Sopha, Chantha
Chuor, Char Meng
Nguon, Chea
Sovannaroth, Siv
Pukrittayakamee, Sasithon
Jittamala, Podjanee
Chotivanich, Kesinee
Chutasmit, Kitipumi
Suchatsoonthorn, Chaiyaporn
Runcharoen, Ratchadaporn
Hien, Tran Tinh
Thuy-Nhien, Nguyen Thanh
Thanh, Ngo Viet
Phu, Nguyen Hoan
Htut, Ye
Han, Kay-Thwe
Aye, Kyin Hla
Mokuolu, Olugbenga A.
Olaosebikan, Rasaq R.
Folaranmi, Olaleke O.
Mayxay, Mayfong
Khanthavong, Maniphone
Hongvanthong, Bouasy
Newton, Paul N.
Onyamboko, Marie A.
Fanello, Caterina I.
Tshefu, Antoinette K.
Nosten, Francois
Hasan, M. Mahtabuddin
Islam, Akhterul
Miotto, Olivo
Amato, Roberto
MacInnis, Bronwyn
Stalker, Jim
Kwiatkowski, Dominic P.
Bozdech, Zbynek
Jeeyapant, Atthanee
Cheah, Phaik Yeong
Sakulthaew, Tharisara
Chalk, Jeremy
Intharabut, Benjamas
Silamut, Kamolrat
Lee, Sue J.
Vihokhern, Benchawan
Kunasol, Chanon
Imwong, Mallika
Tarning, Joel
Taylor, Walter J.
Yeung, Shunmay
Woodrow, Charles J.
Flegg, Jennifer A.
Das, Debashish
Smith, Jeffery
Plowe, Christopher V.
Stepniewska, Kasia
Guerin, Philippe J.
Dondorp, Arjen M.
Day, Nicholas P.
White, Nicholas J.
Keywords: DRNTU::Science::Biological sciences::Microbiology
Issue Date: 2014
Source: Ashley, E. A., Dhorda, M., Fairhurst, R. M., Amaratunga, C., Lim, P., Suon, S., et al. (2014). Spread of artemisinin resistance in plasmodium falciparum malaria. New England journal of medicine, 371(5), 411-423.
Series/Report no.: New England journal of medicine
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.
URI: https://hdl.handle.net/10356/106044
http://hdl.handle.net/10220/26243
DOI: 10.1056/NEJMoa1314981
Rights: © 2014 Massachusetts Medical Society. This paper was published in The New England Journal of Medicine and is made available as an electronic reprint (preprint) with permission of Massachusetts Medical Society. The published version is available at: [http://dx.doi.org/10.1056/NEJMoa1314981]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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