Funding Opportunity Number: RFA-AI-24-049
Deadline: December 4, 2024
Background
Tuberculosis (TB) is one of the leading infectious disease causes of mortality in the world. It is estimated that a quarter of the world’s population is infected with Mycobacterium tuberculosis (Mtb) and are at risk of developing active TB disease. In 2023, the World Health Organization (WHO) estimated that TB claimed the lives of 1.3 million people in the previous year, including 167,000 people co-infected with HIV. Efforts to control this global epidemic have been hampered by inadequate understanding of the underlying epidemiology and biologic mechanisms of transmission and lack of effective interventions to prevent TB transmission. The key drivers of transmission are not completely understood. Recent evidence suggests that individuals with subclinical and asymptomatic TB may be a significant source of transmission. More evidence is needed to determine their contribution to transmission as this could inform treatment options.
TB disease incidence appears to be driven more by recent transmission rather than by reactivation events, so identification of biomarkers of recent infection would allow identification of people more likely to develop active disease. The TB transmission cycle is extremely complex with multiple contributing host/pathogen/micro-environmental factors. Improved knowledge of these interactions and factors driving transmission would allow efficacious approaches for preventing transmission to be developed or improved and adapted for a broad scale-up. This is particularly timely, as advances in understanding aerobiology and transmission for COVID-19 may be leveraged to understand and prevent transmission of TB.
Research Objectives
Areas of interest include but are not limited to:
- Understanding the impact of the spectrum of TB disease, including the role of asymptomatic, pre-symptomatic and differentially culturable TB, in transmission;
- Aerobiology;
- Environmental impacts on transmission;
- Understanding non-traditional spread (e.g., without cough or other symptoms, community spread with limited contact);
- Development or assessment of new methods or tools to measure transmission;
- Identifying host factors or host/pathogen interactions that encourage transmission;
- Defining characteristics or sub-populations of Mtb strains that impact transmission, including the role of Mtb strain heterogeneity;
- Studies of transmission in high-risk groups (e.g., healthcare workers, congregate settings);
- Studies to understand the impact of HIV coinfection and antiretroviral therapy on transmission of TB;
- Studies to understand the impact of co-morbidities on TB transmission (e.g., diabetes, malnutrition, etc.);
- Studies to understand how to most effectively utilize resources to reduce transmission (e.g., preventive therapy, active screening strategies, targeted diagnosis, improved ventilation or airflow patterns).
Currently, tracking the spread of TB relies on analogue tools in many settings, which does not allow tracking of transmission in real time. Projects are encouraged to consider incorporating the use of improved data systems for tracking TB transmission and explore how digitized health can improve our understanding of control of TB transmission.
Low risk, non-IND clinical trials are allowed, however, any clinical trial should include outcomes that improve the understanding of drivers of TB transmission.
Applications proposing research in the areas listed below will be considered non-responsive and will NOT be reviewed:
- Applications that propose to study zoonotic TB transmission (e.g., TB transmission from animals to humans or animals to animals). Animal studies are allowed if they are a readout of human-to-human TB transmission.
- Studies proposing a clinical trial that requires an Investigational New Drug Application (IND).
- Projects for development of systemic chemoprophylaxis, development of host-directed therapeutic agents or development of vaccines as potential interventions.
For more information, please see the opportunity webpage.