MICA: Hydroxyurea - Pragmatic Reduction In Mortality and Economic burden (H-PRIME)

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Sickle cell anaemia (SCA) is a common inherited condition that affects around 1% of all children born in much of sub-Saharan Africa. Without early diagnosis and appropriate treatment under-5 mortality in those affected is between 50 and 90%. As a result, through much of the continent SCA is responsible for between 5 and 16% of total under-5 mortality. These high levels of mortality could be reduced dramatically with simple treatments that include educating parents to recognise danger signs and seek emergency care, and by measures that protect against acute bacterial and malarial infections using vaccines and prophylactic antibiotic and anti-malarial drugs. Nevertheless, without specific treatments that modify the course of the disease, many of those affected will live lives that are characterized by frequent and recurrent bouts of severe illness that include acute and chronic pain and progressive multi-organ deterioration. Unlike diseases like HIV, malaria and tuberculosis, SCA does not enjoy a high profile in the eyes of the international community and remains widely neglected by ministries of health through much of sub-Saharan Africa. Through H-PRIME, we will address three key questions in the management of children with SCA in Africa today through a single large, efficient and pragmatic clinical trial. First, we will determine whether hydroxyurea, a common and effective treatment for SCA in resource-rich regions, could be a useful option in parts of Africa with limited access to medical care. In most countries hydroxyurea is administered and monitored in a way that will not be achievable in most of Africa and our primary question, therefore, will be whether the drug can be used safely and effectively to reduce mortality and improve the quality of life in survivors when administered pragmatically following a weight-band-based dosing strategy with minimal clinical and laboratory monitoring. Second, we will investigate whether better protection from bacterial infections in children with SCA can reduce all cause hospital admission and further reduce mortality. The current approach to the prevention of bacterial infections is through the use of oral penicillin. However, this is only effective against a narrow range of bacterial organisms and we will therefore investigate whether the addition of a second agent, co-trimoxazole, could bring further benefits in the absence of harm. Finally, the current approach to the prevention of malaria infections relies on drugs that are associated with high levels of resistance. We will therefore investigate whether malaria prevention with a more modern and highly effective drug - dihidroartemisinin-piperaquine - could be used as an alternative, and that this will not cause harm in terms of side effects and the development of further drug resistance.