Tuberculosis

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is estimated to have infected one quarter of the world’s population and is a leading cause of infectious disease death worldwide. M. tuberculosis is spread by aerosol transmission. Most often, infected individuals develop latent TB infection, but approximately 10% of individuals will develop active disease, either due to progressive primary infection or reactivation of latent infection. Interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and CD4 T cells are critical in host immune control of infection. In individuals in whom these responses are impaired, such as inborn errors in the IL-12-IFN-γ signaling axis, treatment with anti-TNF-α agents, and HIV coinfection, the risk of developing active infection and disseminated disease is markedly increased. Active TB is most often pulmonary, but a wide variety of extrapulmonary disease manifestations also occur. The challenges associated with diagnosing and treating TB are compounded by HIV coinfection and drug resistance. As a result, TB remains an enormous global health threat.