Impact of Spatial Location and Movement Patterns on Tuberculosis Transmission in Urban Uganda

项目总结 结核病(TB)是世界范围内单一病原体导致死亡的主要原因。尽管有进展， 在结核病诊断和治疗方面，结核病发病率每年下降2%，远低于实现 世界卫生组织的最终结核病目标。更好地了解面临感染和感染风险的人群 要使干预措施发挥最大作用，传播结核病至关重要。位置和移动模式可以 在结核病传播中起关键作用；人们居住的地方以及他们的旅行习惯影响他们的模式 与他人接触。到目前为止，研究还没有整合先进的空间方法和测量 发展对地理流动性空间关系的全面理解 以及流动模式和结核病传播。这项建议嵌套在一项现有的研究中，题为 乌干达城市社区结核病传播综合快照“(STOMP-TB； R01HL138728，PI：Dowdy)正在乌干达坎帕拉进行。STOMP-TB研究招募成年人 (15岁，≥)在4个卫生机构被诊断为结核病，并分两波进行活跃病例发现，在这两波中 研究区域内的成年人有资格接受结核病检测。所有培养呈阳性的参与者的样本 结核分枝杆菌被提交进行全基因组测序，提供有关传播网络的数据。 该提案包括两个具体目标，每个目标都有三个子目标，每个目标都有相关的培训 瞄准。在目标1(结核病风险的空间分析)中，我将量化居住地点与结核病的关系 传输作为欧几里德距离的函数，估计行政区域之间的关联 居住地和结核病传播，并评估结核病接触者调查的潜在影响 从索引案例定义的半径。我的相关培训目标1是学习和应用先进的方法 空间分析和包括参加关于空间分析的短期课程培训，参与空间 分析工作组，和我的一位导师一起实践R代码在空间分析中的应用。在AIM 2 (地理流动性和结核病风险评估)，我将进行系统的回顾，总结现有的 衡量行动能力的方法，评估行动能力和结核病传播之间的联系，并评估 生物性别作为流动性对结核病影响的修饰者的作用。我的相关培训目标2是 学会将健康的社会决定因素应用于结核病的风险因素，包括流动性，通过 关于社会流行病学和因果推断的课程，以及关于这个主题的特定读物的讨论 其中一位导师。我的训练目标3是提高我的科学技能；主要活动是参加 资助发展研讨会，并在此奖学金结束前开发K01或同等应用程序。 这些目标的成功实现将有助于我成为一名独立的 在空间流行病学和地理流动性应用方面具有独特专业知识的研究人员 提高我们对高负担环境中结核病传播的了解的措施。

PROJECT SUMMARY Tuberculosis (TB) is the leading cause of mortality by a single pathogen worldwide. Despite developments in TB diagnostics and treatment, TB incidence declines 2% annually, well below the rate needed to achieve the World Health Organization's End TB Goals. A better understanding of populations at risk for acquiring and transmitting TB is critical to targeting interventions for greatest impact. Location and movement patterns may play a key role in TB transmission; where people live as well as their travel habits influence their patterns of contact with others. Research to date has not integrated advanced spatial methods and measurement of geographic mobility to develop a comprehensive understanding of the relationship between spatial and mobility patterns and TB transmission. This proposal is nested within an existing study entitled, “A Comprehensive Snapshot of Tuberculosis Transmission in an Urban Ugandan Community” (STOMP-TB; R01HL138728, PI: Dowdy) being conducted in Kampala, Uganda. The STOMP-TB study enrolls adults (age≥15) diagnosed with TB at 4 health facilities and conducts active case finding in two waves in which all adults within the study area are eligible for TB testing. Specimens from all participants with positive cultures for M. tuberculosis are submitted for whole genome sequencing (WGS), providing data on transmission networks. This proposal consists of two Specific Aims, each with three sub-aims, and each with an associated Training Aim. In Aim 1 (spatial analysis of TB risk), I will quantify the association of residential location with TB transmission as a function of Euclidean distance, estimate the association between administrative zone of residence and TB transmission, and evaluate the potential impact of TB contact investigation based on a defined radius from an index case. My associated Training Aim 1 is to learn and apply advanced methods for spatial analysis and includes participation in short-course training on spatial analysis, participation in a spatial analysis workgroup, and practice in application of R code for spatial analysis with one of my mentors. In Aim 2 (assessment of geographic mobility and TB risk), I will conduct a systematic review to summarize existing methods of measuring mobility, estimate the association between mobility and TB transmission, and assess the role of biological sex as a modifier of the effect of mobility on TB disease. My associated Training Aim 2 is to learn to apply a social determinants of health framework to risk factors for TB, including mobility, through coursework on social epidemiology and causal inference and discussion of specified readings on this topic with one of mentors. My Training Aim 3 is to improve my scientific skills; the main activity is participating in grant development seminars and developing a K01 or equivalent application by the end of this fellowship. The successful completion of these aims will facilitate my progress toward becoming an independent researcher with unique expertise in the application of spatial epidemiology and geographic mobility measurement to improve our understanding of TB transmission in high-burden settings.