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

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.

Sociodemographic and Clinical Determinants of Time to Care-Seeking Among Febrile Children Under-Five in North-Central Nigeria.

OBJECTIVES: Our study sought to determine the time parents of febrile children under the age of five took to seek competent medical care. We also looked at the possible sociodemographic/ clinical factors that influenced this presentation. METHODS: Four hundred and nine under-fives presenting at the emergency unit with a history of fever in the last 48 hours along with their mothers were recruited over four months. Relevant sociodemographic information as well as symptoms and duration of illness were obtained. Multinomial regression analysis was performed to determine the predictors of early and late presentation. RESULTS: Over half (57%) of patients presented within 24 hours of onset of fever. The mean age of the children and mothers were 22±15 months and 30±5 years, respectively. High social class (odds ratio (OR) 6.5, 95% CI 1.6-26.4), Hausa ethnic group (OR 19.3, 95% CI 5.7-65.6), convulsions (OR 3.2, 95% CI 1.6-6.5) and appearance of other symptoms (OR 6.0, 95% CI 3.0-12.0) were significant predictors of early presentation. Secondary school education, belonging to another ethnic group, and non-resolution of fever were significant predictors of late presentation. CONCLUSION: The majority of febrile under-fives came to the hospital to seek competent medical care within the first 24 hours of illness. However, there is a need for more parental education on early hospital presentation for parents of low socioeconomic status and educational background.