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

表征亚临床结核病的传染性并确定预防传播的新型早期诊断策略

• 批准号: 10579176
• 负责人: Jason Randolph Andrews
• 金额: $ 15.48万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-11 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10579176
• 关键词: Address; Aerosols; Algorithms; Biological Assay; Blood; Brazil; Calibration; Caring; Cause of Death; Characteristics; Clinical; Collaborations; Communicable Diseases; Communities; Coughing; Country; Data; Development; Diagnosis; Diagnostic; Disease; Disparity; Early Diagnosis; Early treatment; Effectiveness of Interventions; Environment; Epidemic; Exhalation; Gene Expression; Gene Expression Profile; Gene Expression Profiling; General Population; Goals; HIV Seronegativity; Health; Imprisonment; Incidence; Individual; Infection; Intervention; Joints; Knowledge; Masks; Mass Screening; Measures; Medical; Methods; Modality; Modeling; Mycobacterium tuberculosis; Population; Prevalence; Prisoner; Prisons; Recommendation; Reference Standards; Research; Research Infrastructure; Roentgen Rays; Role; Sampling; Sputum; Sustainable Development; Symptoms; System; Testing; Time; Tuberculosis; Tuberculosis diagnosis; Whole Blood; case finding; cost effective; cost effectiveness; design; diagnostic screening; diagnostic strategy; effective therapy; epidemiologic data; genetic signature; genomic data; mathematical model; molecular diagnostics; novel; novel diagnostics; novel strategies; point of care; prevent; screening; symptom treatment; tool; transmission process

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.

项目摘要 结核病仍然是全球传染病的主要原因， 尽管有效治疗的可用性宽度。两个主要科学知识 差距限制了我们有效反应这种流行的能力：1）理解 在人群中传播感染的个体的特征；和2） 在疾病过程中，确定这些人的有效诊断手段 防止正在进行的传输。我们的初步研究和其他研究 证明，在人口中的任何给定时间中，很大一部分 有微生物学确认的结核病的个体几乎没有经典 症状。该状态被描述为“亚临床结核病”。什么部分 案件是亚临床的，这些人的感染力，以及 对人群传播的亚临床结核病对传播的了解很少。这 提案利用我们在西方中部监狱中的独特研究基础设施 巴西评估新颖的工具，包括一次性面具，以捕捉疲惫 生物素，用于早期检测非对称个体的结核病。我们将测试 以下假设：1）缺乏符号的结核病的人 平均至少50％的感染与具有符号的感染，并同等地贡献 总体传输； 2）蒙版气溶胶采样将比痰液更有效 在症状很少或没有症状的个体中测试结核病诊断； 3）双年一次 针对亚临床结核病的诊断症的大规模筛查将是成本 - 对监狱有效。总体而言，该项目将解决有关的基本问题 结核病的传播，同时测试控制结核病的实用方法 高伯恩设置。