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

1

Issued Date

2010-11-13

Resource Type

Article

ISSN

01406736

DOI

10.1016/S0140-6736(10)61924-1

Other identifier(s)

2-s2.0-78449267241

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Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

The Lancet. Vol.376, No.9753 (2010), 1647-1657

Suggested Citation

Arjen M. Dondorp, Caterina I. Fanello, Ilse Ce Hendriksen, Ermelinda Gomes, Amir Seni, Kajal D. Chhaganlal, Kalifa Bojang, Rasaq Olaosebikan, Nkechinyere Anunobi, Kathryn Maitland, Esther Kivaya, Tsiri Agbenyega, Samuel Blay Nguah, Jennifer Evans, Samwel Gesase, Catherine Kahabuka, George Mtove, Behzad Nadjm, Jacqueline Deen, Juliet Mwanga-Amumpaire, Margaret Nansumba, Corine Karema, Noella Umulisa, Aline Uwimana, Olugbenga A. Mokuolu, Olanrewaju T. Adedoyin, Wahab Br Johnson, Antoinette K. Tshefu, Marie A. Onyamboko, Tharisara Sakulthaew, Wirichada Pan Ngum, Kamolrat Silamut, Kasia Stepniewska, Charles J. Woodrow, Delia Bethell, Bridget Wills, Martina Oneko, Tim E. Peto, Lorenz Von Seidlein, Nicholas Pj Day, Nicholas J. White Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): An open-label, randomised trial. The Lancet. Vol.376, No.9753 (2010), 1647-1657. doi:10.1016/S0140-6736(10)61924-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/29443

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Title

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

Author(s)

Arjen M. Dondorp
 Caterina I. Fanello
 Ilse Ce Hendriksen
 Ermelinda Gomes
 Amir Seni
 Kajal D. Chhaganlal
 Kalifa Bojang
 Rasaq Olaosebikan
 Nkechinyere Anunobi
 Kathryn Maitland
 Esther Kivaya
 Tsiri Agbenyega
 Samuel Blay Nguah
 Jennifer Evans
 Samwel Gesase
 Catherine Kahabuka
 George Mtove
 Behzad Nadjm
 Jacqueline Deen
 Juliet Mwanga-Amumpaire
 Margaret Nansumba
 Corine Karema
 Noella Umulisa
 Aline Uwimana
 Olugbenga A. Mokuolu
 Olanrewaju T. Adedoyin
 Wahab Br Johnson
 Antoinette K. Tshefu
 Marie A. Onyamboko
 Tharisara Sakulthaew
 Wirichada Pan Ngum
 Kamolrat Silamut
 Kasia Stepniewska
 Charles J. Woodrow
 Delia Bethell
 Bridget Wills
 Martina Oneko
 Tim E. Peto
 Lorenz Von Seidlein
 Nicholas Pj Day
 Nicholas J. White

Other Contributor(s)

Hospital Central da Beira
 Medical Research Council Laboratories Gambia
 I/C Komfo Anokye Hosp.
 Kilifi District Hospital
 Magunga District Hospital
 Teule Designated District Hospital
 NIMR-Amani Centre
 Ministry of Health
 University of Ilorin
 Mbarara University of Science and Technology
 Kinshasa School of Public Health-Kingasani Research Centre
 Mahidol University
 Nuffield Department of Clinical Medicine
 Menzies School of Health Research
 Oxford University Clinical Research Unit
 KEMRI-CDC Kisumu

Abstract

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. 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. 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. 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. The Wellcome Trust. © 2010 Elsevier Ltd.

Keyword(s)

Medicine

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https://repository.li.mahidol.ac.th/handle/123456789/29443

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