Characterizing infectiousness of subclinical TB and identifying novel early diagnostic strategies for preventing transmission

项目摘要 结核病仍然是世界范围内一种传染病导致的主要死亡原因， 尽管普遍存在有效的治疗方法。两大科学知识 差距限制了我们有效应对这一流行病的能力：1)理解 在人群中传播感染的个人特征；以及2) 找出在病程早期诊断这些患者的有效方法 以防止持续的传播。我们和其他人的初步研究已经 证明了，在人口中的任何给定时间，相当大比例的 经微生物学确诊的结核病患者很少或没有典型的 症状。这种状态被描述为“亚临床肺结核”。有多少部分 病例是亚临床的，这些人的传染性有多大，以及 对亚临床结核病在人群中的传播知之甚少。这 提案利用我们在中西区监狱中独特的研究基础设施 巴西将评估新工具，包括捕捉呼气的一次性口罩 生物气雾剂，用于无症状个体的结核病早期检测。我们将测试 以下假设：1)没有症状的结核病患者 平均至少有50%的传染性与有症状的人一样，并对 总体传播；2)口罩气雾剂采样将比痰更有效 对症状较少或没有症状的个人进行结核病诊断检测；3)半年一次 针对亚临床结核病的大规模筛查和诊断将是昂贵的- 在监狱里有效。总体而言，该项目将解决以下基本问题 结核病传播，同时测试控制结核病的实用方法 高负荷设置。

Project Summary Tuberculosis remains the leading cause of death by an infectious disease worldwide, despite the widespread availability of effective therapy. Two major scientific knowledge gaps constrain our ability to effectively respond this epidemic: 1) understanding characteristics of individuals who are transmitting infection within the population; and 2) identifying efficient means of diagnosing these individuals early in their course of disease to prevent ongoing transmission. Our preliminary research and that of others has demonstrated that, for any given time in a population, a substantial proportion of individuals with microbiologically confirmed tuberculosis have few or no classical symptoms. This state has been described as “subclinical tuberculosis”. What fraction of cases are subclinical, how infectious these individuals are, and the total contribution of subclinical tuberculosis towards transmission in the population is poorly understood. This proposal leverages our unique research infrastructure in prisons in Central-Western Brazil to evaluate novel tools, including a disposable mask to capture exhaled bioaerosols, for early detection of tuberculosis in asymptomatic individuals. We will test the following hypotheses: 1) individuals with tuberculosis who lack symptoms are on average at least 50% as infectious as those with symptoms, and contribute equally to overall transmission; 2) mask aerosol sampling will be more effective than sputum testing for tuberculosis diagnosis in individuals with few or no symptoms; 3) biannual mass screening with diagnostics targeted at subclinical tuberculosis would be cost- effective in prisons. Overall, this project will address fundamental questions about tuberculosis transmission, while testing practical approaches to control tuberculosis in high burden settings.