Mycobacterium tuberculosis aerobiology and novel tools to assess infectiousness

结核分枝杆菌空气生物学和评估传染性的新工具

• 批准号: 10393544
• 负责人: David J. Horne
• 金额: $ 15.94万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10393544
• 关键词: Acid Fast Bacillae Staining Method; Address; Adult; Aerosols; Bacillus; Belief; Biological Assay; Cause of Death; Characteristics; Clinical; Clinics and Hospitals; Communities; Contact Tracing; Coughing; Country; Devices; Discrimination; Disease; Enrollment; Event; Exposure to; Frequencies; Funding Mechanisms; HIV; HIV Infections; HIV Seronegativity; HIV Seropositivity; HIV/TB; Home; Household; Immunocompetence; Individual; Infection; Inhalation; Interferon Type II; Interferons; Intervention; Investigation; Kenya; Lead; Measurement; Measures; Microbiology; Minority Groups; Morbidity - disease rate; Mycobacterium tuberculosis; Newly Diagnosed; Outcome; Participant; Patients; Performance; Persons; Prevention; Preventive treatment; Public Health; Pulmonary Tuberculosis; Research; Research Personnel; Resource-limited setting; Risk; Sampling; Sputum; Study models; Symptoms; System; Testing; Thoracic Radiography; Tuberculosis; Work; aerosolized; base; clinical investigation; co-infection; community transmission; cost effective; deep learning algorithm; design; detection platform; experience; follow-up; indexing; interdisciplinary approach; mortality; novel; predictive signature; prevent; privacy preservation; programs; prospective; response; tool; transmission process; tuberculosis diagnostics; tuberculosis treatment

Tuberculosis (TB), the leading cause of death in people living with HIV, is the archetypal airborne disease, spread person-to-person through the inhalation of aerosolized bacilli. In endemic regions, most TB disease results from recently acquired infection with M. tuberculosis (Mtb), and studies support that a minority of individuals are responsible for most TB transmission events. Although focusing TB control interventions, such as TB preventive treatment (TPT), on contacts of these highly infectious individuals is cost-effective, tests that accurately determine the infectiousness of patients with TB are lacking. The overall objective of this proposal is to prevent TB-related morbidity and mortality among PLHIV by developing a novel cough-based diagnostic of TB infectiousness. We previously developed a research tool to measure Mtb cough aerosolization, the cough aerosol sampling system (CASS), that predicts TB infectiousness. Recently, we investigated cough frequency as a marker of TB infectiousness, identified unique TB-related cough signatures and developed a mobile privacy-preserving cough detection system. In the proposed study, we will enroll HIV-positive and HIV-negative Kenyan adults who are newly diagnosed with pulmonary TB to assess their level of TB infectiousness using CASS-measured aerosolized Mtb counts (the outcome). In Aim 1, we will investigate cough frequency and/or cough spectrogram (collectively “cough signature”) to estimate TB infectiousness and investigate the impact of HIV co-infection on TB infectiousness. In Aim 2, we will identify the household contacts of Aim 1 participants (index cases) to investigate for latent TB infection using interferon-gamma release assays (IGRAs) and determine whether index case cough signatures associated with high Mtb aerosol counts are associated with a greater frequency of positive IGRAs in household contacts. Additionally, at 6 months after enrollment we will re-test household contacts with IGRAs to understand if the durability of positive responses is associated with index case cough signatures. We hypothesize that individuals with high Mtb aerosol counts will have high cough frequencies and unique cough spectrograms, and that cough spectrograms will differ by HIV status despite similar Mtb aerosol counts. Furthermore, we hypothesize that household contacts to index cases with “highly infectious” cough signatures are more likely to have positive IGRAs at baseline and at 6-month follow- up. Our team has developed the tools to not only robustly determine infectiousness (CASS), but to evaluate both cough frequency and intensity (spectrogram analyses) in a high HIV/TB burden setting. By identifying cough signatures predictive of TB infectiousness, we will develop tools for clinicians and public health programs to support the targeting of TB control interventions.

结核病（TB）是艾滋病毒感染者死亡的主要原因，是典型的空气传播疾病， 通过吸入雾化的杆菌在人与人之间传播。在流行地区，大多数结核病 结果最近获得的感染M。结核病（Mtb），研究支持少数 个人对大多数结核病传播事件负有责任。虽然注重结核病控制干预措施， 作为结核病预防性治疗（TPT），对这些高传染性个体的接触者进行检测是具有成本效益的， 缺乏准确判断结核病患者传染性的方法。本建议的总体目标是 通过开发一种新的基于咳嗽的诊断方法， 结核病传染性。我们以前开发了一种研究工具来测量结核分枝杆菌咳嗽雾化， 气溶胶采样系统（卡斯），预测结核病的传染性。最近，我们调查了咳嗽频率 作为结核病传染性的标志，确定了独特的结核病相关咳嗽特征，并开发了一种移动的 隐私保护咳嗽检测系统在拟议的研究中，我们将招募艾滋病毒阳性和艾滋病毒阴性患者 新诊断为肺结核的肯尼亚成年人，使用 CASS测量的雾化Mtb计数（结果）。在目标1中，我们将研究咳嗽频率和/或 咳嗽频谱图（统称为“咳嗽特征”），以估计结核病的传染性，并调查 HIV合并感染对结核病传染性的影响。在目标2中，我们将确定目标1参与者的家庭联系人 （指示病例）使用干扰素-γ释放试验（IGRA）调查潜伏性TB感染， 确定与高Mtb气溶胶计数相关的索引病例咳嗽特征是否与 家庭接触者中IGRA阳性的频率更高。此外，在入组后6个月，我们将 重新测试与IGRA的家庭接触，以了解积极反应的持久性是否与以下因素有关： 索引病例咳嗽特征。我们假设具有高Mtb气溶胶计数的个体将具有高Mtb气溶胶计数。 咳嗽频率和独特的咳嗽谱图，咳嗽谱图将因艾滋病毒状态而异 尽管Mtb气溶胶计数相似。此外，我们假设，家庭接触，以索引案件与 “高传染性”咳嗽特征更可能在基线和6个月随访时具有阳性IGRA- 起来我们的团队已经开发出了工具，不仅可以强大地确定传染性（卡斯），而且可以评估 咳嗽频率和强度（频谱分析）在高艾滋病毒/结核病负担的设置。通过识别 预测结核病传染性的咳嗽特征，我们将为临床医生和公共卫生开发工具， 支持结核病控制干预目标的方案。

项目成果

Rethinking the syndemic of tuberculosis and dysglycaemia: a Kenyan perspective on dysglycaemia as a neglected risk factor for tuberculosis.

• DOI: 10.1186/s42269-023-01029-6
• 发表时间: 2023
• 期刊: Bulletin of the National Research Centre
• 作者: Kerama, Cheryl;Horne, David;Ong'ang'o, Jane;Anzala, Omu
• 通讯作者: Anzala, Omu

TBscreen: A passive cough classifier for tuberculosis screening with a controlled dataset.

• DOI: 10.1126/sciadv.adi0282
• 发表时间: 2024-01-05
• 期刊: SCIENCE ADVANCES
• 影响因子: 13.6
• 作者: Sharma, Manuja;Nduba, Videlis;Njagi, Lilian N.;Murithi, Wilfred;Mwongera, Zipporah;Hawn, Thomas R.;Patel, Shwetak N.;Horne, David J.
• 通讯作者: Horne, David J.