BackgroundEvidence from one trial in Africa suggests that pre-referral Rectal Artesunate (RAS) can be a life-saving intervention for severe malaria in remote settings, where parenteral treatment is not available. Recognition of danger signs indicative of severe malaria is critical for prompt and appropriate case management.MethodsAn observational study was conducted in the Democratic Republic of the Congo (DRC) in the frame of the multi-country CARAMAL project, to assess the effectiveness of RAS under real-world conditions. Severely ill feverish children <5 years seeking care from a community-based healthcare provider were recruited in three rural health zones into a patient surveillance system. They were subsequently followed within the healthcare system and at home after 28 days to determine care seeking, antimalarial treatment provision and health outcomes.ResultsOverall, 66.4% of patients had iCCM general danger signs, as well as more specific danger signs. Children aged 2-5 years (aOR=1.58, 95% CI 1.20–2.08) and those presenting iCCM general danger signs were more likely to receive RAS (aOR = 2.77, 95% CI 2.04–3.77). Injectable treatment was less likely with RAS pre-referral treatment (aOR=0.21, 95% 0.13– 0.33). In the post-RAS phase, the case fatality ratio was 7.1%. Children not receiving RAS had a higher risk of dying, but this was not statistically significant (aOR = 1.50, 95% CI 0.86– 2.60). The odds of dying were reduced in patients without iCCM general danger signs, but just not statistically so (aOR = 0.64, 95% CI 0.38–1.06). Full oral therapy at a RHF was highly protective (aOR = 0.13, 95% CI 0.07-0.26), while a full treatment of severe malaria (injectable + oral) was shown to also decrease massively the odds of dying (aOR = 0.26, 95% CI 0.09– 0.79) compared to injectable treatment alone.ConclusionsBetter understanding the determinants of successful case management, and targeted improvements of the health system (especially the provision of a full course of an oral antimalarial) are crucial for improving health oucomes of children with suspected severe malaria.