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

MICA：羟基脲 - 务实降低死亡率和经济负担 (H-PRIME)

• 批准号: MR/S004904/1
• 负责人: Thomas Williams
• 金额: $ 570.73万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS004904%2F1
• 关键词: MICA; Hydroxyurea; Pragmatic; Reduction; Mortality

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.

镰状细胞贫血（SCA）是一种常见的遗传病，影响撒哈拉以南非洲大部分儿童中约1％。没有早期诊断和在受影响者中的5岁以下死亡率的适当治疗介于50％至90％之间。结果，通过大陆，SCA的大部分地区负责5至5岁以下死亡率的5％至16％。可以通过简单的治疗方法大幅度降低这些高水平的死亡率，包括教育父母识别危险体征并寻求急诊护理，并采取措施使用疫苗和预防性抗生素和抗癌药物来防止急性细菌和疟疾感染。然而，如果没有改变疾病病程的特定治疗，许多受影响的生活将以频繁而经常发生的严重疾病发作为特征，包括急性和慢性疼痛以及进行性多器官的衰减。与诸如艾滋病毒，疟疾和结核病等疾病不同，SCA在国际社会的眼中并不享有很高的知名度，并且通过大部分撒哈拉以南非洲的卫生部门仍然被卫生部广泛忽视。通过H-Prime，我们将通过一项大型，高效且务实的临床试验来解决非洲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对SCA的常见且有效的治疗方法，在非洲部分地区是否可以选择医疗服务，这是一种有用的选择。在大多数国家 /地区，在非洲大部分地区都无法实现和监测羟基脲，因此我们的主要问题将是该药物是否可以安全有效地用于降低死亡率并改善与最小临床和实验室监控的基于体重的剂量剂量策略后，在实用下进行了疏远的剂量，并改善了幸存者的生活质量。其次，我们将调查SCA儿童中更好地保​​护细菌感染是否会减少所有医院入院并进一步降低死亡率。当前预防细菌感染的方法是使用口服青霉素。但是，这仅在狭窄的细菌生物范围内有效，因此我们将研究第二种药物辅助三氧唑是否在没有损害的情况下会带来进一步的好处。最后，当前预防疟疾感染的方法取决于与高耐药性相关的药物。因此，我们将研究使用更现代和高效的药物预防疟疾 - 二氢甲性胺 - 二喹 - 可以用作替代方案，这不会在副作用和进一步耐药性的发展方面造成伤害。

项目成果

Characterising demographics, knowledge, practices and clinical care among patients attending sickle cell disease clinics in Eastern Uganda.

描述乌干达东部镰状细胞病诊所患者的人口统计、知识、实践和临床护理特征。

• DOI: 10.12688/wellcomeopenres.15847.2
• 发表时间: 2020
• 期刊: Wellcome open research
• 作者: Olupot-Olupot P

Red Blood Cell Deformability Demonstrated with the Oxygenscan: Exploring the Association with Hydroxyurea Treatment, Co-Inherited a-Thalassemia, and Frequency of Pain in Children with Sickle Cell Anemia

使用 Oxygenscan 证明红细胞变形能力：探索与羟基脲治疗、共同遗传性 α-地中海贫血以及镰状细胞性贫血儿童疼痛频率的关系

• DOI: 10.1182/blood-2019-129836
• 发表时间: 2019
• 期刊: Blood
• 影响因子: 20.3
• 作者: Nardo-Marino A

Filling the data gaps on sickle cell anaemia in sub-Saharan Africa.

• DOI: 10.1016/s2352-3026(22)00042-4
• 发表时间: 2022-03
• 期刊: The Lancet. Haematology
• 作者: Williams TN