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.

Public Health Relevance

Tuberculosis is the leading cause of death by an infectious disease globally. Individuals with tuberculosis are believed to be infectious before they develop symptoms; however, it is not known how infectious they are or whether they contribute substantially to population-level transmission. This project aims to measure infectiousness of individuals according to their symptoms and test novel approaches to early diagnosis of tuberculosis in prisons with very high tuberculosis burden in Brazil. The goal is inform efficient and effective strategies for reducing tuberculosis transmission in high burden settings. !

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI149620-02
Application #
10125940
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lacourciere, Karen A
Project Start
2020-03-11
Project End
2024-02-28
Budget Start
2021-03-01
Budget End
2022-02-28
Support Year
2
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305