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

Saturday 13 November 2010

Dondorp AM Fanello CI Hendriksen IC Gomes E Seni A Chhaganlal KD Bojang K Olaosebikan R Anunobi N Maitland K Kivaya E Agbenyega T Nguah SB Evans J Gesase S Kahabuka C Mtove G Nadjm B Deen J Mwanga-Amumpaire J Nansumba M Karema C Umulisa N Uwimana A Mokuolu OA Adedoyin OT Johnson WB Tshefu AK Onyamboko MA Sakulthaew T Ngum WP Silamut K Stepniewska K Woodrow CJ Bethell D Wills B Oneko M Peto TE von Seidlein L Day NP White NJ

Lancet (London, England) 2010 Nov 13; 376(9753); 1647-57. doi: 10.1016/S0140-6736(10)61924-1. Epub 2010 11 07

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 (

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.

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