Lancet. 2010 Nov 13;376(9753):1647-57. doi: 10.1016/S0140-6736(10)61924-1. Epub 2010 Nov 7.

Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial.

Collaborators (201)

Gomes E, Seni A, Chhaganlal KD, Hendriksen IC, Pedro AJ, Jarach CD, Wingi O, Fernando EI, Zambruni M, Raimundo Z, de Oliveira CJ, Dondorp A, Songane F, Barreto A, Lucas M, Bojang K, Olaosebikan R, Anunobi N, Corrah T, Conway D, Rowland-Jones S, Akor F, Okebe J, Jallow M, Chimah O, Ismaela A, Sanneh M, Mamodou S, Jammeh F, Fullah J, Bah A, Saine H, Agbenyega T, Nguah SB, Evans J, Ansong D, Sylverken J, Akoto AO, Owusu LD, Sambian D, Ntim M, Maitland K, Kivaya E, Abubakar M, Mpoya A, Newton C, Gwer S, Akech S, Kazungu M, Kihara M, Timbwa M, Boga M, Gesase S, Kahabuka C, Lemnge M, von Seidlein L, Barongo A, Malabeja A, Abdul O, Savael Z, Tilaus G, Chuwa L, Kabela S, Nadjm B, Deen J, Reyburn H, Whitty C, Hendriksen IC, Shao A, Mtunguja S, Mwikwabe M, Msuya W, Kiemi C, Mtili E, von Seidlein L, Swai E, Amos B, Malahiyo R, Malugu R, Mnongea M, Emmanuel S, Msengi NJ, Mtimbo FM, Kimera J, Mtove G, Karema C, Umulisa N, Uwimana A, Mulumba JN, Uwase A, Rugandura D, Kawite C, Ruhangaza D, Ndagijimana JC, Mukeshiyaremye J, Kayitesi A, Mukamugenzi V, Ndizeye N, Munyaneza T, Mokuolu OA, Adedoyin OT, Johnson WB, Ojuawo A, Ernest SK, Adesiyun OO, Abdulkarim AA, Adegboye AO, Timi-Oladipo AO, Kelani BR, Ogunkanbi O, Yusuf A, Adegboye O, Oyewale OT, Oladele O, Jacob A, Faniyi O, Mwanga-Amumpaire J, Nansumba M, Piola P, Debeaudrap P, Boum Y 2nd, Dhorda M, Turyakira E, Kumbakumba E, Nyesigire E, Kalubi P, Data S, Natukunda N, Ssegane A, Dan N, Tumwebaze B, Twinomujuni B, Kinyatta J, Asaasira SE, Tumuhairwe J, Scovia S, Kyohairwe P, Mbabazi S, Adrama H, Turuho T, Muwanga S, Ariyo JB, Magezi P, Twebaze A, Tshefu AK, Onyamboko MA, Zandibeni JK, Katokale EK, Kabedi CN, Nkuadiolandu AB, Mpoyi RN, Sakina MM, Fela CK, Omari JA, Muniaka OK, Omba BD, Boyanga AI, Biyela EK, Badjanga BB, Kambashi YB, Dondorp AM, Sakulthaew T, Fanello CI, Pan Ngum W, Stepniewska K, Silamut K, Hendriksen IC, Panachuenwongsakul N, Rijaibun M, Lindegardh N, Hanpithakpong W, Nuchsongsin F, Intarabut B, Srinamon K, Saiwaew S, Chotivanich K, White NJ, Day NP, Fanello CI, Dondorp AM, Hendriksen IC, Day NP, von Seidlein L, White NJ, Bojang K, Maitland K, Dondorp AM, Day NP, White NJ, Greenwood B, Oneko M, Wills B, White N, Woodrow CJ, Bethell D, Peto TE, Lalloo D, Walker S, Koram K, Molyneux M, Malenga G.

Source

Mahidol Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Erratum in

Lancet. 2011 Jan 8;377(9760):126.

Abstract

BACKGROUND:

Severe malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa. Quinine is still the established treatment of choice, although evidence from Asia suggests that artesunate is associated with a lower mortality. We compared parenteral treatment with either artesunate or quinine in African children with severe malaria.

METHODS:

This open-label, randomised trial was undertaken in 11 centres in nine African countries. Children (<15 years) with severe falciparum malaria were randomly assigned to parenteral artesunate or parenteral quinine. Randomisation was in blocks of 20, with study numbers corresponding to treatment allocations kept inside opaque sealed paper envelopes. The trial was open label at each site, and none of the investigators or trialists, apart from for the trial statistician, had access to the summaries of treatment allocations. The primary outcome measure was in-hospital mortality, analysed by intention to treat. This trial is registered, number ISRCTN50258054.

FINDINGS:

5425 children were enrolled; 2712 were assigned to artesunate and 2713 to quinine. All patients were analysed for the primary outcome. 230 (8·5%) patients assigned to artesunate treatment died compared with 297 (10·9%) assigned to quinine treatment (odds ratio [OR] stratified for study site 0·75, 95% CI 0·63-0·90; relative reduction 22·5%, 95% CI 8·1-36·9; p=0·0022). Incidence of neurological sequelae did not differ significantly between groups, but the development of coma (65/1832 [3·5%] with artesunate vs 91/1768 [5·1%] with quinine; OR 0·69 95% CI 0·49-0·95; p=0·0231), convulsions (224/2712 [8·3%] vs 273/2713 [10·1%]; OR 0·80, 0·66-0·97; p=0·0199), and deterioration of the coma score (166/2712 [6·1%] vs 208/2713 [7·7%]; OR 0·78, 0·64-0·97; p=0·0245) were all significantly less frequent in artesunate recipients than in quinine recipients. Post-treatment hypoglycaemia was also less frequent in patients assigned to artesunate than in those assigned to quinine (48/2712 [1·8%] vs 75/2713 [2·8%]; OR 0·63, 0·43-0·91; p=0·0134). Artesunate was well tolerated, with no serious drug-related adverse effects.

INTERPRETATION:

Artesunate substantially reduces mortality in African children with severe malaria. These data, together with a meta-analysis of all trials comparing artesunate and quinine, strongly suggest that parenteral artesunate should replace quinine as the treatment of choice for severe falciparum malaria worldwide.

FUNDING:

The Wellcome Trust.

Comment in

Artesunate for severe malaria in African children. [Lancet. 2011]
Artesunate for severe malaria in African children.Obaro SK. Lancet. 2011 Apr 2; 377(9772):1153-4; author reply 1154.
For severe malaria, artesunate is the answer. [Lancet. 2010]
For severe malaria, artesunate is the answer.Shanks GD. Lancet. 2010 Nov 13; 376(9753):1621-2. Epub 2010 Nov 7.