Novel Strategies to Prevent Malaria and Improve Maternal-Child Health in Africa

描述(申请人提供)：疟疾和艾滋病毒是世界上两种最重要的传染病，在撒哈拉以南非洲是重叠和协同的。尽管加强了前线预防工作，但疟疾在孕妇和儿童中的负担仍然令人震惊；营养不良和生长迟缓是对儿童健康的主要威胁。“在托罗罗预防疟疾和艾滋病”(PROCESS)计划项目(POI)的目的是评估有希望的干预措施，以减轻疟疾和艾滋病毒的负担，并通过基于假设的干预研究改善母婴健康。PROCESS II将测试以下假设：a)在感染艾滋病毒和未感染的孕妇中加强疟疾化学预防将减少胎盘疟疾；b)在孕期和儿童期提供的加强化学预防将减少生命头两年儿童的疟疾；以及c)通过在怀孕期间加强疟疾化学预防来限制宫内接触疟疾抗原，将减少胎儿对疟疾抗原的免疫耐受性。拟议的临床研究将评估双氢青蒿素-哌喹(DP)的化学预防，这是一种新的青蒿素联合疗法(ACT)，被证实对孕妇和儿童的疟疾治疗非常安全和有效。Promote II由3个项目和3个核心组成。在未感染艾滋病毒的孕妇(项目1)和感染艾滋病毒的孕妇(项目2)及其所生子女中有2个相互关联的双盲随机对照试验，其平行结构允许在不同艾滋病毒状况和暴露的人群之间比较疟疾、免疫反应和DP的药代动力学。项目3以实验室为基础，重点是使用来自2个临床试验的具有良好特征的标本来检验疟疾免疫的中心假说。行政、实验室和数据核心为项目提供基础设施支持，包括利用组织病理学处理和评估胎盘疟疾的能力。

DESCRIPTION (provided by applicant): Malaria and HIV are two of the most important Infectious diseases worldwide that are overlapping and synergistic in sub-Saharan Africa. Despite the scale up of front line prevention efforts, the burden of malaria remains staggering among pregnant women and children; and malnutrition and growth retardation are major threats to child health. The purpose of the "Prevention of Malaria and HIV Disease in Tororo" (PROMOTE) program project (POI) is to evaluate promising interventions to reduce the burden of malaria and HIV and Improve maternal-child health through hypothesis based intervention studies. PROMOTE II will test the hypotheses that a) enhanced malaria chemoprevention in HIV infected and uninfected pregnant women will reduce placenta malaria; b) enhanced chemoprevention provided during both pregnancy and childhood will reduce malaria in children in the first 2 years of life and c) limiting in utero exposure to malaria antigens with enhanced malaria chemoprevention during pregnancy will reduce development of fetal immune tolerance to malaria antigens. The proposed clinical studies will evaluate chemoprevention with dihydroartemisinin-piperaquine (DP), a new artemisinin combination therapy (ACT), established as highly safe and effective for malaria treatment in pregnant women and children. PROMOTE II consists of 3 projects and 3 cores. There are 2 interlinked double blinded, randomized controlled trials in HIV-uninfected pregnant women (Project 1), and HIV-infected pregnant women (Project 2) and the children born to them with parallel structure that permits comparisons in malaria, immune responses and pharmacokinetics of DP between populations with differing HIV status and exposure. Project 3 is laboratory based, and is focused on testing central hypothesis of malaria immunity using well characterized specimens from the 2 clinical trials. Administrative, laboratory, and data cores provide infrastructure support to the projects, including the capacity to process and evaluate placental malaria using histopathology.