Identifying TB transmitters in high TB/HIV burdened communities

摘要 结核病(TB)是由结核分枝杆菌(Mtb)引起的，它是一种人类特有的病原体，其 在人类群体中的持久性取决于驱动连续传播周期的能力， 感染和疾病。与其在维持较高的结核病患病率方面的重要性一致，有 对新的干预措施在流行地区阻断结核分枝杆菌传播的可能性重新产生了兴趣。而当 这种方法很有吸引力，需要快速、可靠和可扩展的技术来检测结核分枝杆菌- 不受结核病症状影响的感染者。这是一项具有挑战性的任务，因为 越来越多的传染性病原体样本经常是稀少细菌的，这给生物安全带来了困难 与抗药性有关。出于这个原因，到目前为止，大多数研究都集中在涂阳结核病上 疾病，从而忽视了亚临床感染者(即那些 最小症状或甚至无症状)到结核分枝杆菌的传播。为了解决这一限制，我们 最近介绍了呼吸性气溶胶采样箱的研制和初步验证 (RASC)，一个配备了先进的高效过滤、采样和微粒的个人洁净室 检测技术，允许生物安全、非侵入性地捕获和分离活的结核分枝杆菌 肺结核患者在正常呼吸活动期间；即无需诱发咳嗽。建立在 假设每单位呼出的生物气溶胶产生的活的结核分枝杆菌的数量提供了可靠的 衡量结核病的传播潜力，我们建议在这里优化RASC平台，以实现快速、半 大量个体中活的结核分枝杆菌生物气溶胶的定量检测。现有的、定义明确的 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，更重要的是，将 扩大到涂阳肺结核病例之外--首次对结核分枝杆菌传播进行直接研究。结果将是 根据艾滋病毒状况分层，并用于模拟亚临床结核分枝杆菌传播对结核病流行的贡献 发病率，进而为设计可实施的干预措施提供信息，以减轻地方性结核病/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 化疗对结核分枝杆菌生物气雾剂释放的影响。

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.