Quantifying the potential contribution of asymptomatic screening and treatment to malaria control and elimination

项目摘要 疟疾仍然是一个主要的全球健康问题，造成40多万人死亡。 每年在撒哈拉以南非洲地区超过90%。疟疾的症状是由无性寄生虫引起的， 但疟疾是通过性分化的配子母细胞从人类传播给蚊子的。经反复 暴露，获得性免疫限制了无性寄生虫的密度和发展的可能性， 症状消灭疟疾的一个可能障碍是无性生殖的慢性感染的储存者 寄生虫密度太低，无法进行治疗，但配子母细胞足以感染蚊子。因此，我们认为， 发现和治疗无症状感染者可以减少传播并间接防止死亡。 布基纳法索临床试验（INDIE试验）的初步结果表明，定期筛查， 测试和治疗（STT）干预显著降低配子体密度和感染性， 蚊子然而，短期艾滋病治疗在减少传播和预防病例和死亡方面的作用， 人口数量仍然未知。我建议使用基于代理的建模来预测短期培训的影响，如果它 作为控制或消灭疟疾工作的一部分，将得到广泛实施。 首先，我将使用来自INDIE的数据来建立研究地点的详细空间模型， 寄生虫、配子体和感染性之间的关系，验证STT对配子体的影响 密度和传染性。接下来，我将预测在整个印度实施普遍短期租约的影响 减少疟疾病例的研究领域。由于短期租约需要大量资源，我会比较 在印度独立教育研究地区实施有针对性的短期培训，考虑按年龄组确定目标， 在潮湿或干燥季节，并针对蚊子暴露最高的家庭进行短期T。使用 在不考虑其他疟疾干预措施的情况下， 预测在撒哈拉以南非洲所有疟疾流行地区普及和有针对性的STT的影响。 最后，我将根据干预历史调整现有模型，以评估影响和成本- 有针对性的短期培训战略在高负担和接近消除环境中的有效性， 建立干预措施。拟议研究的结果将有助于决策者决定是否、何时以及 如何利用短期疗法防治疟疾。 F31 Ruth L. Kirschstein NRSA个人博士前奖学金奖将使我能够建立我的 定量和研究技能，提高我的科学写作和沟通，并获得专业知识， 传染病流行病学的道路上成为一个成功的独立调查员。在 在进行拟议的研究时，我将融入一个全球疟疾建模者网络， 流行病学家，熟悉基于代理的建模，并为 评估STT作为控制和消除疟疾的工具。 项目总结/摘要

PROJECT SUMMARY Malaria continues to be a major global health concern and is responsible for more than 400,000 deaths annually with more than 90% in Sub-Saharan Africa. Symptoms of malaria are caused by asexual parasites, but malaria is passed from humans to mosquitoes by sexually-differentiated gametocytes. After repeat exposures, acquired immunity limits the density of asexual parasites and the likelihood of developing symptoms. One possible barrier to malaria elimination is the reservoir of chronic infections with asexual parasite densities too low to prompt treatment, but sufficient gametocytes to infect mosquitoes. Therefore, detecting and treating asymptomatic infections could reduce transmission and indirectly prevent deaths. Preliminary results from a clinical trial in Burkina Faso (the INDIE trial) suggest that regular screening, testing, and treatment (STT) interventions significantly reduce gametocyte density and infectivity to mosquitoes. However, the effect of STT on reducing transmission and preventing cases and deaths at the population level remains unknown. I propose to use agent-based modeling to predict the impact of STT if it were to be widely implemented as part of malaria control or elimination efforts. First, I will use data from INDIE to build a detailed spatial model of the study site, calibrate within-host relationships between parasites, gametocytes, and infectivity, and validate the effect of STT on gametocyte density and infectivity. Next, I will predict the impact of implementing universal STT for the entire INDIE study area on reducing malaria cases. Since STT is resource-intensive, I will compare the effectiveness of implementing targeted STT in the INDIE study area, considering targeting by age group, limiting STT to the wet or dry season, and targeting STT to households with the highest mosquito exposure. Using an archetypes approach and without considering other malaria interventions, I will make a back-of-the-envelope prediction of the impact of universal and targeted STT across all malaria-endemic Sub-Saharan Africa. Finally, I will adapt existing models contextualized by intervention history to assess the impact and cost- effectiveness of targeted STT strategies in high-burden and near-elimination settings, compared to established interventions. The results of the proposed research will help policymakers decide if, when, and how to deploy STT to combat malaria. The F31 Ruth L. Kirschstein NRSA Individual Predoctoral Fellowship award will allow me to build my quantitative and research skills, improve my scientific writing and communication, and gain expertise in infectious disease epidemiology on the path toward becoming a successful independent investigator. In conducting the proposed research, I will integrate into a global network of malaria modelers and epidemiologists, gain familiarity with agent-based modeling, and make scientific contributions to the assessment of STT as a tool for malaria control and elimination. Project Summary/Abstract