Training Protocol on the Natural History of Tuberculosis

Overview

Background: \- Tuberculosis (TB) is an infectious disease that affects numerous people worldwide. Researchers are interested in actively recruiting individuals with TB for research and treatment studies. Objectives: \- To collect blood and other samples to study the natural history of tuberculosis. Eligibility: \- Individuals 2 years of age and older who have either active or latent tuberculosis. Design: * Latent TB patients: Participants will have a single study visit with a physical examination and medical history, and will provide blood samples for testing. * Active TB patients: Participants will have an initial visit with a physical examination and medical history, and will provide blood samples for testing. Participants will also provide sputum samples if required, and may have an optional skin punch biopsy to collect a sample of skin tissue for study. * Treatment for active TB will be provided as part of this protocol. * Active TB participants may be asked to return for study visits every 1-2 months while receiving treatment....

Mycobacterium tuberculosis (MTB) is a slow-growing bacterium that establishes latent infection in millions of persons worldwide, but only leads to disease in 10% or less of these individuals. It typically causes pneumonia, however dissemination to almost any other organ is possible. Drug resistance of the organism, co-infection with HIV, and paradoxical reactions upon treatment are all factors that may complicate treatment. Host defense against mycobacterial infections is important. Specific defects within the innate immune system lead to Mendelian susceptibility to mycobacterial infections. HIV infected individuals and persons treated with anti-tumor necrosis factor antibodies are highly susceptible to tuberculosis (TB) infection. Genetic influence on susceptibility to TB disease is complex and does not seem to be confined to a single gene or pathway. Advancement in molecular techniques has expanded our understanding of the pathogenesis and epidemiology of MTB. Identification of gene mutations that confer antibiotic resistance are being exploited as alternatives to conventional drug susceptibility testing. The natural history of all forms of TB disease (including co-infection with HIV and other infections) will be followed, and MTB isolates and blood from 100 infected patients will be obtained in order to study organism virulence and host immune function and genetic/epigenetic factors. While it is recognized that the number of TB cases that occur in the Washington, DC area and nationally is low, it is imperative that a mechanism is in place to evaluate and treat these patients at the NIH Clinical Center. This protocol will also allow NIH infectious diseases trainees to manage challenging cases of TB.