Pulmonary tuberculosis

The development of TB requires infection by Mycobacterium tuberculosis and inadequate containment by the immune system. Patients infected with M tuberculosis who have no clinical, bacteriological, or radiographic evidence of active TB are said to have latent TB infection. Active TB may occur from re-activation of previously latent infection or from progression of primary infection.

Transmission of TB occurs from individuals infected with pulmonary (and rarely laryngeal) disease. Infection results from the inhalation of aerosolised particles (droplet nuclei) containing the bacterium. The likelihood of transmission depends on the infectivity of the source patient (e.g., smear status and extent of cavitation on chest x-ray), the degree of exposure to the patient (e.g., proximity, ventilation, and the length of exposure), and susceptibility of the person in contact with an infected patient.[8]Lienhardt C. From exposure to disease: the role of environmental factors in susceptibility to an development of tuberculosis. Epidemiol Rev. 2001 Jul;23(2):288-301. http://www.ncbi.nlm.nih.gov/pubmed/12192738?tool=bestpractice.com HIV-infected individuals are at greater risk of reactivation as well as progression to primary TB. Other groups at increased risk for the development of active TB include persons with recent tuberculin skin test conversion, the homeless, injection drug users, cigarette smokers, and immunocompromised individuals (e.g., people with diabetes, prolonged corticosteroid therapy, end-stage renal disease, malnutrition, or haematological malignancies).[9]Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis. 2016 Oct 1;63(7):e147-95. https://academic.oup.com/cid/article/63/7/e147/2196792 http://www.ncbi.nlm.nih.gov/pubmed/27516382?tool=bestpractice.com [10]Lin HH, Ezzati M, Murray M. Tobacco smoke, indoor air pollution and tuberculosis: a systematic review and meta-analysis. PLoS Med. 2007 Jan;4(1):e20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769410/?tool=pubmed http://www.ncbi.nlm.nih.gov/pubmed/17227135?tool=bestpractice.com

Infection with TB requires inhalation of aerosolised particles called droplet nuclei. Following deposition in the alveoli, Mycobacterium tuberculosis is engulfed by alveolar macrophages, but survives and multiplies within the macrophages. Proliferating bacilli kill macrophages and are released; this event produces a response from the immune system. Exposure may lead to clearance of M tuberculosis, persistent latent infection, or progression to primary disease.

Successful containment of TB is dependent on the cellular immune system, mediated primarily through T-helper cells (TH1 response). T cells and macrophages form a granuloma with a centre that contains necrotic material (caseous centre), M tuberculosis, and peripheral granulation tissue consisting primarily of macrophages and lymphocytes; the granuloma serves to prevent further growth and spread of M tuberculosis. These individuals are non-infectious and have latent TB infection; the majority of these patients will have a normal chest x-ray and be tuberculin skin test-positive.

Active TB typically occurs through a process of re-activation. Approximately 10% of individuals with latent infection will progress to active disease over their lifetime. The risk is greatest within the 2 years following initial acquisition of M tuberculosis. A number of conditions can alter this risk, particularly untreated HIV infection, in which the annual risk of developing active TB is 8% to 10%. Immunocompromised conditions and treatment with immunosuppressing medicines, including systemic corticosteroids and tumour necrosis factor-alpha antagonists, also contribute to re-activation.