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

描述（由申请人提供）：疟疾和艾滋病毒是世界上两种最重要的传染病，在撒哈拉以南非洲重叠和协同作用。尽管加强了第一线的预防工作，但疟疾在孕妇和儿童中的负担仍然令人震惊;营养不良和发育迟缓是儿童健康的主要威胁。“托罗罗预防疟疾和艾滋病毒”方案项目的目的是通过基于假设的干预研究，评估有希望的干预措施，以减少疟疾和艾滋病毒的负担，改善母婴健康。 PROMOTE II将检验以下假设：a）加强艾滋病毒感染和未感染孕妇的疟疾化学预防将减少胎盘疟疾; B）在怀孕和儿童时期提供的加强的化学预防将减少2岁以下儿童的疟疾，以及在怀孕期间限制子宫内接触疟疾抗原并增强疟疾化学预防将减少胎儿对疟疾的免疫耐受性的发展抗原拟议的临床研究将评估双氢青蒿素-哌喹（DP）的化学预防作用，这是一种新型青蒿素联合疗法（ACT），被认为对孕妇和儿童的疟疾治疗高度安全有效。 PROMOTE II包括3个项目和3个核心。在未感染HIV的孕妇（项目1）和感染HIV的孕妇（项目2）及其所生子女中开展了2项相互关联的双盲、随机对照试验，具有平行结构，可比较不同HIV状态和暴露人群之间的疟疾、免疫应答和DP药代动力学。项目3是以实验室为基础的，重点是使用来自2项临床试验的充分表征的标本来检验疟疾免疫力的中心假设。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.