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）是艾滋病毒患者死亡的主要原因，是原型空气疾病， 通过吸入雾化的杆菌来传播人与人。在地方性地区，大多数结核病疾病 最近获得结核分枝杆菌（MTB）感染的结果，研究支持少数 个人负责大多数结核病传输事件。尽管集中了结核病控制干预措施，但 作为结核病预防治疗（TPT），这些高度感染性个体的接触是具有成本效益的，测试了 准确地确定缺乏结核病患者的传染性。该提议的总体目标是 通过开发基于Coug的新型诊断，以防止PLHIV中与TB相关的发病率和死亡率 结核病感染力。我们以前开发了一种研究工具，用于测量MTB咳嗽，咳嗽 气溶胶采样系统（CASS），可预测结核病感染性。最近，我们研究了美洲狮频率 作为结核病感染性的标志，确定了独特的与结核病相关的咳嗽签名并开发了手机 保护隐私的牛检测系统。在拟议的研究中，我们将注册HIV阳性和HIV阴性 肯尼亚成年人被新诊断为肺结核，以评估其使用TB传染性的水平 卡斯测量的雾化MTB计数（结果）。在AIM 1中，我们将研究咳嗽频率和/或 咳嗽光谱图（统称为“咳嗽签名”）以估计结核病感染性并研究 HIV对结核病感染性的感染。在AIM 2中，我们将确定目标1参与者的家庭联系 （索引病例）使用干扰素释放测定法（IGRAS）和 确定索引病例咳嗽是否与高MTB气溶胶计数有关 家庭接触中阳性的阳性频率更高。此外，入学后6个月我们将 重新测试与IGRAS的家庭接触，以了解积极响应的持久性是否与 索引病例咳嗽签名。我们假设高MTB气溶胶计数的人将具有较高的 咳嗽频率和独特的咳嗽光谱图，咳嗽光谱图会因HIV状态而异 尽管MTB气溶胶计数类似。此外，我们假设与 “高度感染力”的美洲狮签名更有可能在基线时具有正面的IGRA，并且在6个月的后续行动中 - 向上。我们的团队开发了不仅坚定确定感染性（CASS）的工具，还可以评估 在高HIV/TB Burnen设置中，咳嗽频率和强度（光谱图分析）。通过识别 咳嗽签名可以预测结核病感染性，我们将为临床医生和公共卫生开发工具 支持针对结核病控制干预措施的程序。

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.