Identifying TB transmitters in high TB/HIV burdened communities

识别结核病/艾滋病毒高发社区的结核病传播者

• 批准号: 10249091
• 负责人: Robin Wood
• 金额: $ 77.72万
• 依托单位: DESMOND TUTU HIV FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-05 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249091
• 关键词: Address; Aerosols; Animals; Bacillus; Biological; Biological Assay; Breathing; Cause of Death; Cavia; Cell Separation; Clinical; Collection; Communicable Diseases; Coughing; Data; Detection; Development; Devices; Disease; Drug resistance; Ensure; Epidemiology; Etiology; Exhalation; Filtration; Fluorescence; Frequencies; HIV; HIV Seropositivity; HIV/TB; Hospitals; Human; Individual; Infection; Interruption; Intervention; Link; Lipids; Liquid substance; Mass Spectrum Analysis; Measures; Metabolic; Methods; Microbiology; Minority; Modeling; Molecular; Mycobacteriophages; Mycobacterium tuberculosis; Newly Diagnosed; Non-Invasive Cancer Detection; Particulate; Patients; Peru; Population; Prevalence; Production; Rapid diagnostics; Reporting; Research; Resources; Risk; Sampling; Site; Source; South Africa; Stains; Surrogate Markers; Symptoms; System; Technology; Time; Tuberculosis; Validation; Walking; Work; accurate diagnostics; air sampling; automated image analysis; base; case finding; cohort; community burden; community clinic; comparative; design; effective therapy; human pathogen; insight; interest; mycobacterial; novel; particle; pathogen; respiratory; sample collection; screening; tool; transmission process; tuberculosis chemotherapy; ward

ABSTRACT Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb), an obligate human pathogen whose persistence within the human population depends on the ability to drive successive cycles of transmission, infection, and disease. Consistent with its importance in maintaining elevated TB prevalence rates, there is renewed interest in the potential for novel interventions to interrupt Mtb transmission in endemic regions. While attractive, this approach requires rapid, reliable, and scalable technologies to detect live bacilli released by Mtb- infected individuals independent of TB symptoms. This is a challenging undertaking given the practical and biosafety difficulties posed by working with often paucibacillary samples of an infectious pathogen increasingly associated with drug resistance. For this reason, most studies to date have focused on smear-positive TB disease, thereby ignoring the potential contribution of sub-clinically infected individuals (i.e., those who are minimally symptomatic or even asymptomatic) to Mtb transmission. In attempting to address this limitation, we recently described the development and preliminary validation of the Respiratory Aerosol Sampling Chamber (RASC), a personal clean-room equipped with advanced, high-efficiency filtration, sampling, and particulate detection technologies that allows biosafe, non-invasive capture and isolation of live Mtb bacilli from confirmed TB patients during normal respiratory activity; that is, without the requirement for induced cough. Building on the postulate that the number of viable Mtb bacilli produced per unit of exhaled bioaerosol provides a reliable measure of TB transmission potential, we propose here to optimize the RASC platform for rapid, semi- quantitative detection of viable Mtb bioaerosols in large numbers of individuals. Existing, well-defined cohorts of subjects will be screened to identify the proportion and infectiousness of Mtb transmitters and, importantly, will be extended beyond smear-positive TB cases – a first for direct studies of Mtb transmission. Results will be stratified by HIV status and used to model the contribution of sub-clinical Mtb transmission to TB prevalence rates, in turn informing the design of implementable interventions to reduce the TB burden in endemic TB/HIV settings. Finally, this approach also suggests the potential to use the RASC to understand the impact of TB chemotherapy on Mtb bioaerosol release.

抽象的 结核病 (TB) 是由结核分枝杆菌 (Mtb) 引起的，它是一种人类专性病原体，其 在人群中的持久性取决于驱动连续传播周期的能力， 感染和疾病。与其在维持结核病高患病率方面的重要性相一致， 人们对新的干预措施在流行地区阻断结核分枝杆菌传播的潜力重新产生了兴趣。尽管 有吸引力的是，这种方法需要快速、可靠和可扩展的技术来检测结核分枝杆菌释放的活杆菌 感染者与结核病症状无关。鉴于实际情况和实际情况，这是一项具有挑战性的任务 越来越多地处理感染性病原体的细菌样本所带来的生物安全困难 与耐药性有关。因此，迄今为止大多数研究都集中在涂片阳性结核病上 疾病，从而忽略了亚临床感染者（即那些患有 轻微症状甚至无症状）到结核分枝杆菌传播。为了解决这个限制，我们 最近描述了呼吸气溶胶采样室的开发和初步验证 (RASC)，一个配备先进、高效过滤、采样和颗粒物的个人洁净室 检测技术可实现生物安全、非侵入性地从确诊病例中捕获和分离活结核杆菌 正常呼吸活动期间的结核病患者；也就是说，不需要诱导咳嗽。建立在 假设每单位呼出的生物气溶胶产生的活结核杆菌数量提供了可靠的 为了衡量结核病传播潜力，我们在此建议优化 RASC 平台，以实现快速、半 对大量个体中活的结核分枝杆菌生物气溶胶进行定量检测。现有的、明确的群体 将对受试者进行筛查，以确定结核分枝杆菌传播者的比例和传染性，重要的是，将 扩展到涂片阳性结核病病例之外——这是首次对结核分枝杆菌传播进行直接研究。结果将是 按 HIV 状况分层，用于模拟亚临床 Mtb 传播对结核病患病率的贡献 率，进而为设计可实施的干预措施提供信息，以减少地方性结核病/艾滋病毒的结核病负担 设置。最后，这种方法还表明有可能使用 RASC 来了解结核病的影响 化疗对 Mtb 生物气溶胶释放的影响。