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

镰状细胞贫血（SCA）是一种常见的遗传性疾病，影响了撒哈拉以南非洲大部分地区出生的所有儿童的约1%。如果没有早期诊断和适当治疗，5岁以下儿童的死亡率在50%至90%之间。因此，在非洲大陆的大部分地区，SCA占5岁以下儿童死亡总数的5%至16%。通过简单的治疗方法，包括教育父母识别危险信号并寻求紧急护理，以及通过使用疫苗和预防性抗生素和抗疟疾药物预防急性细菌和疟疾感染的措施，可以大大降低这些高死亡率。然而，如果没有改变病程的具体治疗，许多受影响的人将过上以频繁和反复发作严重疾病为特征的生活，包括急性和慢性疼痛以及进行性多器官退化。与艾滋病毒、疟疾和结核病等疾病不同，SCA在国际社会眼中并不引人注目，在撒哈拉以南非洲的大部分地区，它仍然被卫生部广泛忽视。通过H-PRIME，我们将通过一项大型、高效和务实的临床试验，解决当今非洲SCA儿童管理中的三个关键问题。首先，我们将确定在资源丰富的地区普遍有效的SCA治疗方法--在大多数国家，羟基脲的给药和监测方式在非洲大部分地区是无法实现的，因此，我们的主要问题是，当按照基于体重带的给药策略务实地给药时，该药物是否可以安全有效地用于降低死亡率和改善幸存者的生活质量，并进行最少的临床和实验室监测。其次，我们将研究更好地保护SCA儿童免受细菌感染是否可以减少全因住院并进一步降低死亡率。目前预防细菌感染的方法是使用口服青霉素。然而，这只对一小部分细菌有效，因此我们将研究添加第二种药物复方新诺明是否会在没有危害的情况下带来更多益处。最后，目前预防疟疾感染的方法依赖于与高耐药性有关的药物。因此，我们将研究是否可以使用一种更现代和更有效的药物-双氢青蒿素-哌喹-来预防疟疾，并确保这不会造成副作用和进一步产生抗药性方面的伤害。

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.