Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): An open-label, randomised trial
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 parentera...
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Medicine 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 |
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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. |
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Hospital Central da Beira |
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Hospital Central da Beira 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 |
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Article |
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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 |
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Arjen M. Dondorp |
title |
Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): An open-label, randomised trial |
title_short |
Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): An open-label, randomised trial |
title_full |
Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): An open-label, randomised trial |
title_fullStr |
Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): An open-label, randomised trial |
title_full_unstemmed |
Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): An open-label, randomised trial |
title_sort |
artesunate versus quinine in the treatment of severe falciparum malaria in african children (aquamat): an open-label, randomised trial |
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2018 |
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https://repository.li.mahidol.ac.th/handle/123456789/29443 |
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th-mahidol.294432018-09-24T16:17:31Z Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): An open-label, randomised trial 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 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 Medicine 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. 2018-09-24T09:17:31Z 2018-09-24T09:17:31Z 2010-11-13 Article The Lancet. Vol.376, No.9753 (2010), 1647-1657 10.1016/S0140-6736(10)61924-1 01406736 2-s2.0-78449267241 https://repository.li.mahidol.ac.th/handle/123456789/29443 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=78449267241&origin=inward |