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

项目摘要 结核病仍然是全世界传染病导致死亡的主要原因， 尽管有效的治疗方法广泛存在。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）了解 在人群中传播感染的个人的特征;以及2） 确定在这些个体的疾病过程的早期诊断这些个体的有效方法 以防止持续传播。我们和其他人的初步研究 这表明，在任何给定的时间，在人口中，相当大的比例， 微生物学确诊的结核病患者很少或没有典型的 症状这种状态被称为“亚临床结核病”。多大比例的 病例是亚临床的，这些个体的传染性如何，以及 对亚临床结核病在人群中的传播了解甚少。这 该提案利用了我们在中西部监狱的独特研究基础设施 巴西将评估新工具，包括一次性口罩，以捕捉呼出的气体 生物气溶胶，用于早期发现无症状个体的结核病。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%的感染性为那些有症状，并作出同样的贡献， 总体传播; 2）面罩气溶胶采样将比痰液更有效 在很少或没有症状的个体中进行结核病诊断测试; 3）每年两次 针对亚临床结核病的诊断的大规模筛查将是成本- 在监狱里有效。总的来说，这个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.