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: 10214456
• 负责人: Thomas R Hawn
• 金额: $ 69.36万
• 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/10214456
• 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; 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.

虽然预防结核分枝杆菌（Mtb）感染对于控制结核病至关重要， 结核病（TB）流行，在地方性环境中的传播知之甚少。在各社区， 在负担环境中，结核病流行率以空间集群或“环境热点”的形式存在变异性。 结核病患者的传染性也存在异质性，导致“个体”概念的产生。 超级传播者，”谁负责大多数结核病传播事件。本报告的总体目标 该项目的目的是开发新的干预措施，通过发现结核病传播的主要驱动因素， 通过对热点和超级传播者的评估，在个人和社区层面上进行评估。我们之前 开发了一种新的结核分枝杆菌咳嗽气溶胶采样系统（卡斯）和数字咳嗽特征评估 平台和发现的免疫遗传因素与耐药性和易感性结核分枝杆菌感染 和结核病。2015年，肯尼亚国家结核病计划在全国范围内开展了一项基于人口的结核病调查， 调查发现，结核病负担很高，在接受调查的社区之间存在很大差异。我们现建议 调查10个以前调查过的内罗毕社区（结核病负担不同）的结核病患病率， 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学分析， 调查最近在家庭接触者（HHC）中传播的生物标志物。我们假设 感染性个体具有独特的数字咳嗽和免疫特征，并且他们的HHC具有 持续阳性干扰素-γ释放试验（IGRA）频率较高，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 流行率与人口统计学上向年轻男性倾斜、高移民率、 卫生保健设施和通风不良的社区空间。通过使用创新的方法，我们将获得洞察力 了解小地区结核病流行率的时间趋势，确定与高流行率相关的因素， 开发工具，以确定对结核病传播不成比例负有责任的个人。知识 这项研究的结果将使资源有针对性地用于改善结核病控制。