Malaria chemoprevention in children with sickle cell anemia in Western Kenya

在撒哈拉以南非洲，患有镰状细胞性贫血（SCA）的儿童患疟疾的风险很高。 非洲的其他高危人群--包括孕妇和婴儿--也被管理 使用抗疟药物进行间歇性预防性治疗，以减轻疟疾负担，但 所以在SCA中，孩子们是缺乏的。目前，很少有战略已经过测试，没有一个大的 样本大小对疟疾和SCA的临床重要结果起作用。本课题 提出一个三臂，随机，积极安慰剂临床试验的疟疾化学预防方案 在肯尼亚西部患有SCA的儿童中。利用杜克临床试验中心的临床试验专业知识 研究所，杜克全球健康研究所的全球实地研究足迹，以及现有的 与莫伊大学和肯尼亚西部的合作伙伴合作，我们将招收SCA儿童， 肯尼亚的荷马湾，那里是恶性疟疾的流行地。儿童将被随机分配至 每日一次氯胍（现行标准治疗），每月一次磺胺嘧啶/乙胺嘧啶-阿莫地喹，或 每月服用双氢青蒿素-哌喹，并随访12个月。主要结果将是 分配组之间恶性疟疾发病率和其他预先规定的结果比较 将是SCA发病率的指标，包括疼痛事件、指炎和输血需求， 衡量疟疾的严重程度、住院人数和死亡人数。在研究结束时，我们 希望为使用两种替代战略保护儿童提供证据基础， 该项目的目的是从疟疾中减少SCA，并有可能降低非洲疟疾流行地区SCA的发病率。 这些数据将直接使非洲的临床医生能够改善SCA儿童的护理。

Children with sickle cell anemia (SCA) in sub-Saharan Africa are at high risk to suffer from malaria. Other high-risk groups in Africa – including pregnant women and infants – are administered intermittent preventive therapy with antimalarials to reduce the burden of malaria, but strategies to do so in SCA children are lacking. Currently, few strategies have been tested, and none with large sample sizes powered on clinically-important outcomes for malaria and SCA. In this project, we propose a three-arm, randomized, active-placebo clinical trial of malaria chemoprophylaxis regimens in children with SCA in Western Kenya. Capitalizing on the clinical trial expertise of the Duke Clinical Research Institute, the global field research footprint of the Duke Global Health Institute, and existing collaborations with Moi University and partners in Western Kenya, we will enroll children with SCA in Homa Bay, Kenya, which is endemic for falciparum malaria. Children will be randomized to either daily Proguanil (current standard of care), monthly sulfadoxine/pyrimethamine-amodiaquine, or monthly dihydroartemisinin-piperaquine, and followed for 12 months. The primary outcome will be the incidence of falciparum malaria, and other prespecified outcomes compared between allocation arms will be measures of SCA morbidity including painful events, dactylitis, and need for transfusion, measures of malaria severity, and hospitalizations and deaths. At the conclusion of the study, we expect to provide an evidence base for the use of two alternative strategies to protect children with SCA from malaria, and to potentially reduce the morbidity of SCA in malaria-endemic areas in Africa. These data will directly enable clinicians in Africa to improve the care of children with SCA.