UH2AI152621

Mycobacterium tuberculosis aerobiology and novel tools to assess infectiousness - 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.

University Of Washington

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Washington United States

State-Wide

NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed) (PA-19-053)

Amendment Since initial award the End Date has been extended from 03/31/23 to 03/31/25 and the total obligations have increased 69% from $205,391 to $347,753.