SummaryBackgroundSevere 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.MethodsThis 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.Findings5425 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.InterpretationArtesunate 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.FundingThe Wellcome Trust.
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.
Mean (SD) rectal temperature was 38.8 (0.7)°C, and mean (SD) tympanic and axillary temperatures were 38.7 (0.7)°C and 38.1 (0.7)°C, respectively. There was no significant difference between rectal and tympanic temperatures (P = 0.14), and a strong correlation was identified between values from these two sites (r = 0.91). At 91.5%, the sensitivity of tympanic thermometry in determining fever was higher than that of axillary measurements (54.0%). A mathematical relationship was demonstrated between rectal/tympanic temperatures and between rectal/axillary temperatures as follows: Rectal temperature (°C) = 6.03+0.85 * Mean tympanic temperature (°C) Rectal temperature (°C) = 11.7+0.71 * Axillary temperature (°C) Conclusion: In febrile children, tympanic temperature better reflects rectal temperature than does axillary temperature; tympanic temperature should therefore be measured when there are no contra-indications for its use.
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