Research Activities in Support of Malaria Prevention and Control in Uganda (PMI)

疟疾仍然是最重要的全球卫生挑战之一，估计有30亿人面临感染风险，每年导致约2.5亿例病例和100万人死亡，大部分疾病负担集中在撒哈拉以南非洲。自2005年在乌干达设立以来，美国总统疟疾倡议在扩大已被证明有效的疟疾控制干预措施的覆盖范围方面取得了巨大成功。尽管有这些改善，乌干达的疟疾负担仍然很高，没有明确的证据表明发病率和死亡率有所下降。仍然非常需要系统地评价目前疟疾控制干预措施的有效性，并调查新的干预措施。拟议中的项目旨在扩大美国疾病控制和预防中心的合作机构网络，向非洲目标国家提供研究和技术援助，特别侧重于推进疟疾控制工作的研究。乌干达疟疾监测项目（UMSP）成立于2001年，目的是建立一个多地点监测系统，以监测抗疟药物的有效性和安全性、与疟疾有关的发病率和死亡率，并建设以设施为基础的疟疾管理能力，以期在疟疾控制方面取得可持续进展。针对这一宣布，UMSP提出了以下四项独立的研究，以帮助指导乌干达的疟疾政策决策：1)我们将采用中断时间序列研究设计进行干预研究，以验证以下假设：与目前治疗复杂疟疾住院儿童的做法相比，包括实验室治疗决策、静脉注射青蒿琥酯和标准化给药在内的一揽子干预措施将改善患者的预后。2)我们将开展一项临床试验，测量磺胺多辛-乙胺嘧啶（SP）对孕妇无症状寄生虫病清除的体内疗效，作为评估SP在妊娠期间歇预防治疗有效性的手段。3)我们将在乌干达多个地点进行随机临床试验，比较蒿甲醚-氨苯曲明和双氢青蒿素-哌喹治疗无并发症恶性疟疾的疗效和安全性。4)我们将前瞻性地评估主要疟疾控制干预措施（包括驱虫蚊帐、室内杀虫剂残留喷洒和基于青蒿素的联合疗法）的覆盖率，并在乌干达多个地点测量疟疾传播、感染和疾病的指标。统计技术将用于估计控制干预措施的覆盖水平变化对我们的结果测量的影响。

DESCRIPTION (provided by applicant): Abstract Malaria remains one of the most important global health challenges, with an estimated 3 billion people at risk of infection, leading to approximately 250 million cases and 1 million deaths each year, with a majority of the disease burden concentrated in sub-Saharan Africa. Since its establishment in Uganda in 2005, the U.S. President's Malaria Initiative has been highly successful in expanding the coverage of proven effective malaria control interventions. Despite these improvements, the burden of malaria remains very high in Uganda with no clear evidence of reductions in morbidity and mortality. There remains a great need to systematically evaluative the effectiveness of current malaria control interventions and investigate new interventions. The proposed program is intended to expand the Centers for Disease Control and Prevention network of collaborating institutes for both research and technical assistance to targeted African countries, with a particular focus on research to advance malaria control efforts. The Uganda Malaria Surveillance Project (UMSP) was established in 2001 with the purpose of creating a multi-site surveillance system for monitoring antimalarial drug efficacy and safety, malaria related morbidity and mortality, and building capacity for facility- based management of malaria with the goal of providing sustainable progress in malaria control. In response to this announcement, UMSP is proposing the following four separate research studies to help guide malaria policy decision making in Uganda: 1) We will perform an intervention study using an interrupted time series study design to test the hypothesis that a package of interventions including laboratory-based treatment decision making, IV artesunate, and standardized dosing and administration will improve patient outcomes compared to current practices for children hospitalized with complicated malaria. 2) We will perform a clinical trial to measure the in vivo efficacy of sulfadoxine-pyrimethamine (SP) for the clearance of asymptomatic parasitemia in pregnant women as a means of evaluating the effectiveness of intermittent preventive therapy with SP in pregnancy. 3) We will perform randomized clinical trials at multiple sites in Uganda to compare the efficacy and safety of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria. 4) We will prospectively assess the coverage of key malaria control interventions (including insecticide treated bed nets, indoor residual spraying of insecticide, and artemisinin- based combination therapy) and measure metrics of malaria transmission, infection, and disease at multiple sites in Uganda. Statistical techniques will be used to estimate the impact of changing coverage levels of control interventions on our outcome measures.