# Mycobacterium tuberculosis aerobiology and novel tools to assess infectiousness

> **NIH NIH UH2** · UNIVERSITY OF WASHINGTON · 2021 · $205,391

## Abstract

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.

## Key facts

- **NIH application ID:** 10151102
- **Project number:** 1UH2AI152621-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** David J. Horne
- **Activity code:** UH2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $205,391
- **Award type:** 1
- **Project period:** 2021-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151102

## Citation

> US National Institutes of Health, RePORTER application 10151102, Mycobacterium tuberculosis aerobiology and novel tools to assess infectiousness (1UH2AI152621-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10151102. Licensed CC0.

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