Aerobiology, immunology, and Mycobacterium tuberculosis transmission

空气生物学、免疫学和结核分枝杆菌传播

• 批准号: 10427333
• 负责人: Thomas R Hawn
• 金额: $ 73.39万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-10 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10427333
• 关键词: Address; Aerosols; Area; Biological; Biological Assay; Biological Markers; Characteristics; Communities; Community Surveys; Coughing; Country; Data; Development; Disease; Disease Progression; Enrollment; Epidemic; Epidemiology; Evaluation; Event; Exposure to; Frequencies; Gene Expression Profile; Genetic Transcription; Geographic Locations; HIV; Healthcare; Heterogeneity; High Prevalence; Household; Immunogenetics; Immunologics; Immunology; Individual; Infection; Infection prevention; Interferon Type II; Interruption; Intervention; Investigation; Kenya; Knowledge; Lead; Link; Measurement; Methods; Minority; Mycobacterium tuberculosis; Neighborhoods; Newly Diagnosed; Pathogenesis; Patients; Phenotype; Predisposition; Prevalence; Public Health; Publishing; Pulmonary Tuberculosis; Research; Research Design; Resistance; Resources; Risk; Risk Factors; Sampling; Sputum; Surveys; System; Time trend; Tuberculosis; Variant; aerosolized; base; case finding; community transmission; community-level factor; demographics; design; digital; follow-up; health care availability; high risk; improved; indexing; innovation; insight; interdisciplinary approach; male; migration; novel; peripheral blood; population based; programs; response; tool; transcriptome sequencing; transmission process; urban area; young man

Although preventing infection by Mycobacterium tuberculosis (Mtb) is paramount for controlling the tuberculosis (TB) epidemic, transmission in endemic settings is poorly understood. Across communities in high burden settings, there is variability in TB prevalence in the form of spatial clusters or “environmental hotspots”. Heterogeneity is also present in the infectiousness of patients with TB, leading to the concept of “individual superspreaders,” who are responsible for the majority of Mtb transmission events. The overall objective of this project is to develop novel interventions to interrupt Mtb transmission by discovering the primary drivers at the individual and community levels through evaluations of hotspots and superspreaders. We previously developed a novel Mtb cough aerosol sampling system (CASS) and a digital cough signature assessment platform and discovered immunogenetic factors associated with resistance and susceptibility to Mtb infection and TB disease. In 2015, the Kenya National TB Program, conducted a nationwide population-based TB survey, that found a high burden of TB with wide variation between surveyed communities. We now propose to investigate TB prevalence within 10 previously surveyed Nairobi neighborhoods (with varying TB burdens), develop novel tools for identifying superspreaders including aerobiology and immunogenetic profiling, and investigate biomarkers of recent transmission among household contacts (HHCs). We hypothesize that highly infectious individuals have unique digital cough and immunologic signatures, and that their HHCs have a higher frequency of persistently positive interferon-gamma release assays (IGRAs), specific transcriptional profiles, and higher rate of progression to TB disease. We hypothesize that neighborhoods with stably high TB prevalence rates are associated with demographics skewed to young men, high in-migration, decreased healthcare access, and poorly ventilated community spaces. By using innovative methods, we will gain insights into temporal trends of TB prevalence in small areas, identify factors associated with high prevalence, and develop tools to identify individuals responsible for a disproportionate amount of TB transmission. Knowledge from this study will enable targeting of resources to improve TB control.

尽管预防结核分枝杆菌(Mtb)感染对控制结核病至关重要 结核病流行，对流行环境中的传播知之甚少。在高中的各个社区 在负担情况下，结核病流行率以空间集群或“环境热点”的形式存在差异。 结核病患者的传染性中也存在异质性，这导致了“个体”的概念 超级传播者“，他们对大多数结核分枝杆菌传播事件负责。这样做的总体目标是 该项目是开发新的干预措施，通过在 通过对热点和超级传播者的评估，个人和社区层面。我们之前 开发了一种新的Mtb咳嗽气溶胶采样系统(CASS)和数字咳嗽信号评估 平台和已发现的与结核分枝杆菌感染抗性和易感性相关的免疫遗传因素 和结核病。2015年，肯尼亚国家结核病方案在全国范围内开展了以人口为基础的结核病 调查发现，结核病的负担很高，在接受调查的社区之间差异很大。我们现在提议 调查以前调查过的内罗毕10个社区内的结核病流行情况(结核病负担各不相同)， 开发识别超级传播者的新工具，包括空气生物学和免疫遗传图谱，以及 调查家庭接触者(HHC)最近传播的生物标志物。我们高度假设 感染者有独特的数字咳嗽和免疫学特征，他们的HHC有 持续阳性的干扰素-伽马释放试验(IGRAs)频率更高，特异性转录 和更高的结核病进展率。我们假设结核病稳定高发的社区 流行率与人口结构向年轻男性倾斜、迁入人口高、人口减少有关 医疗保健通道，以及通风不良的社区空间。通过使用创新的方法，我们将获得洞察 了解小地区结核病流行的时间趋势，找出与高发病率相关的因素，以及 开发工具，找出造成不成比例的结核病传播的个人。知识 这项研究将使我们能够有针对性地利用资源来改善结核病控制。