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

项目总结 疟疾仍然是一个主要的全球卫生问题，造成40多万人死亡 每年在撒哈拉以南非洲地区占90%以上。疟疾症状是由无性寄生虫引起的， 但疟疾是通过性别分化的配子体从人类传给蚊子的。在重复之后 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。消除疟疾的一个可能障碍是无性恋者慢性感染的蓄水池 寄生虫密度太低，无法立即治疗，但配子体足以感染蚊子。因此， 检测和治疗无症状感染可以减少传播并间接防止死亡。 布基纳法索的一项临床试验(独立试验)的初步结果表明，定期筛查， 检测和治疗(STT)干预显著降低配子体密度和传染性 蚊子。然而，STT在减少传播、预防病例和死亡方面的作用 人口水平仍然未知。我建议使用基于代理的建模来预测STT的影响，如果它 作为疟疾控制或消除努力的一部分，将被广泛实施。 首先，我将使用INDIE的数据来构建研究场地的详细空间模型，在主机内进行校准 寄生虫、配子体与感染性的关系，验证STT对配子体的影响 密度和传染性。接下来，我将预测实现通用STT对整个独立版本的影响 减少疟疾病例研究领域。由于STT是资源密集型的，我将比较 在独立研究区域实施有针对性的STT，考虑按年龄组进行定向，将STT限制在 雨季或旱季，并将STT目标对准蚊子暴露最高的家庭。使用 原型方法，在不考虑其他疟疾干预措施的情况下，我将粗略地做一个 预测普遍和有针对性的STT在所有疟疾流行的撒哈拉以南非洲地区的影响。 最后，我将根据干预历史调整现有模型，以评估影响和成本- 在高负担和接近消除的情况下，有针对性的STT战略的有效性，与 既定的干预措施。拟议的研究结果将帮助政策制定者决定是否、何时和 如何部署STT来抗击疟疾。 F31 Ruth L.Kirschstein NRSA个人博士前奖学金将允许我建立我的 量化和研究技能，提高我的科学写作和沟通能力，并在 传染病流行病学在成为一名成功的独立调查者的道路上。在……里面 在进行拟议的研究时，我将融入疟疾建模人员和 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。 项目摘要/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