Background

Following aerosol exposure to Mtb, three potential clinical outcomes are possible:

1. resistance to TB infection or early clearance of the bacteria,
2. latent Mtb infection that can persist for decades, or
3. symptomatic active TB, which includes pulmonary disease that can result in further transmission.

We need further investigative studies to understand the epidemiology of resistance to Mtb infection in different high-exposure settings in high TB burden countries and to investigate global immune pathways in macrophages, T cells, B cells and genes involved in regulating these activities.

Understanding the epidemiology of resisters in different countries and immunological mechanisms of protection could help the development of vaccines and improve TB diagnostics and treatment.

Objectives

1. To determine the differential host RNA expression profiles in resistant, latent and active TB.
2. To compare the transcriptomic and translation of relevant genes among three groups: resistant, latent and active TB, to understand the mechanisms of resistance to Mtb.

Study design

We will conduct a prospective longitudinal observational study with a 24-month follow-up of 1220 adults (≥18 years) as described below:

• Aim 1: 560 household contacts;
• Aim 2: 560 healthcare workers with long-term Mtb exposure;
• Aim 3: 100 healthy volunteers.