Arjen M Dondorp MD l, Caterina I Fanello PhD l, Ilse CE Hendriksen MD l, Ermelinda Gomes MD a, Amir Seni MD a, Kajal D Chhaganlal MD a, Kalifa Bojang FRCP b, Rasaq Olaosebikan FWACP b, Nkechinyere Anunobi FMCpaed b, Prof Kathryn Maitland PhD d, Esther Kivaya MSc d, Prof Tsiri Agbenyega PhD c, Samuel Blay Nguah FWACPCH c, Jennifer Evans MRCPCH c, Samwel Gesase MD e, Catherine Kahabuka MD e, George Mtove MD g, Behzad Nadjm MD f, Jacqueline Deen MD f, Juliet Mwanga-Amumpaire MD j, Margaret Nansumba MD j, Corine Karema MD h, Noella Umulisa MD h, Aline Uwimana MD h, Olugbenga A Mokuolu FWACP i, Olanrewaju T Adedoyin FWACP i, Prof Wahab BR Johnson FWACP i, Prof Antoinette K Tshefu MD k, Marie A Onyamboko MB k, Tharisara Sakulthaew BNS l, Wirichada Pan Ngum PhD l, Kamolrat Silamut PhD l, Kasia Stepniewska PhD l, Charles J Woodrow MRCP l, Delia Bethell MRCPCH m, Bridget Wills FRCPCH o, Martina Oneko MD p, Prof Tim E Peto FRCP m, Lorenz von Seidlein PhD n, Prof Nicholas PJ Day FRCP l, Prof Nicholas J White FRS l , for the AQUAMAT group‡. The Lancet, Early Online Publication, 8 November 2010doi:10.1016/S0140-6736(10)61924-1Cite or Link Using DOIBackground
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