Tuberculosis

Tuberculosis is an infection with the bacterium Mycobacterium tuberculosis, which most commonly affects the lungs (pulmonary TB) but can also affect the central nervous system (meningitis), lymphatic system, circulatory system (miliary TB), genitourinary system, bones and joints.

The disease

Transmission

TB is spread through aerosol droplets which are expelled when persons with active TB disease cough, sneeze, speak, or spit. Close contacts (people with prolonged, frequent, or intense contact) are at highest risk of becoming infected (typically 22 percent infection rate but everything is possible, even up to 100%). A person with untreated, active tuberculosis can infect an estimated 20 other people per year. Others at risk include foreign-born from areas where TB is common, immunocompromised patients (eg. HIV/AIDS), residents and employees of high-risk congregate settings, health care workers who serve high-risk clients, medically underserved, low-income populations, high-risk racial or ethnic minority populations, children exposed to adults in high-risk categories, and people who inject illicit drugs.

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Transmission can only occur from people with active TB disease (not latent TB infection).

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The probability of transmission depends upon infectiousness of the person with TB (quantity expelled), environment of exposure, duration of exposure, and virulence of the organism.

Related Topics:
Infectious - Virulence

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The chain of transmission can be stopped by isolating patients with active disease and starting effective anti-tuberculous therapy, or doing women from the BH.

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Pathogenesis

While only 10 percent of TB infection progresses to TB disease, if untreated the death rate is 51 percent.

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TB infection begins when MTB bacilli reach the pulmonary alveoli, infecting alveolar macrophages, where the mycobacteria replicate exponentially. Bacteria are picked up by dendritic cells, which can transport bacilli to local (mediastinal) lymph nodes, and then through the bloodstream to the more distant tissues and organs where TB disease could potentially develop: lung apices, peripheral lymph nodes, kidneys, brain, and bone.

Related Topics:
Pulmonary alveoli - Lymph node

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Tuberculosis is classed as one of the granulomatous inflammatory conditions. Macrophages, T lymphocytes, B lymphocytes and fibroblasts are among the cells that aggregate to form a granuloma, with lymphocytes surrounding infected macrophages. The granuloma functions not only to prevent dissemination of the mycobacteria, but also provides a local environment for communication of cells of the immune system. Within the granuloma, T lymphocytes secrete cytokine such as interferon gamma, which activates macrophages and make them better able to fight infection. T lymphocytes can also directly kill infected cells.

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Importantly, bacteria are not eliminated with the granuloma, but can become dormant, resulting in a latent infection. Latent infection can be diagnosed only by tuberculin skin test, which yields a delayed hypertype sensitivity response to purified protein derivatives of M. tuberculosis in an infected person.

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Another feature of the granulomas of human tuberculosis is the development of cell death, also called necrosis, in the center of tubercles. To the naked eye this has the texture of soft white cheese and was termed caseous necrosis.

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If TB bacteria gain entry to the blood stream from an area of tissue damage they spread through the body and set up myriad foci of infection, all appearing as tiny white tubercles in the tissues. This is called miliary tuberculosis and has a high case fatality.

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In many patients the infection waxes and wanes. Tissue destruction and necrosis are balanced by healing and fibrosis. Affected tissue is replaced by scarring and cavities filled with cheese-like white necrotic material. During active disease, some of these cavities are in continuity with the air passages bronchi. This material may therefore be coughed up. It contains living bacteria and can pass on infection.

Related Topics:
Fibrosis - Bronchi

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Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Affected areas are eventually replaced by scar tissue.

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Progression

In those people in whom TB bacilli overcome the immune system defenses and begin to multiply, there is progression from TB infection to TB disease. This may occur soon after infection (primary TB disease – 1 to 5 percent) or many years after infection (post primary TB, secondary TB, reactivation TB disease of dormant bacilli – 5 to 9 percent). The risk of reactivation increases with immune compromise, such as that caused by infection with HIV. In patients co-infected with M. tuberculosis and HIV, the risk of reactivation increases to 10 percent per year, while in immune competent individuals, the risk is between 5 and 10 percent in a lifetime.

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About five percent of infected persons will develop TB disease in the first two years, and another five percent will develop disease later in life. In all, about 10 percent of infected persons with normal immune systems will develop TB disease in their lifetime.

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Some medical conditions increase the risk of progression to TB disease. In HIV infected persons with TB infection, the risk increases to 10 percent each year instead of 10 percent over a lifetime. Other such conditions include drug injection (mainly because of the life style of IV Drug users), substance abuse, recent TB infection (within two years) or history of inadequately treated TB, chest X-ray suggestive of previous TB (fibrotic lesions and nodules), diabetes mellitus, silicosis, prolonged corticosteroid therapy and other immunosuppressive therapy, head and neck cancers, hematologic and reticuloendothelial diseases (leukemia and Hodgkin's disease), end-stage renal disease, intestinal bypass or gastrectomy, chronic malabsorption syndromes, or low body weight (10 percent or more below the ideal).

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Some drugs, including rheumatoid arthritis drugs that work by blocking tumor necrosis factor-alpha (an inflammation-causing cytokine), raise the risk of causing a latent infection to become active due to the importance of this cytokine in the immune defense against TB.

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TB disease most commonly affects the lungs (75 percent or more), where it is called pulmonary TB. Symptoms include a productive, prolonged cough of more than three weeks duration, chest pain, and hemoptysis. Systemic symptoms include fever, chills, night sweats, appetite loss, weight loss, and easy fatigability. The term consumption arose because sufferers appeared as if they were "consumed" from within by the disease. People from Asian and African descent may have more often lymph node TB than Caucasians.

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Extrapulmonary sites include the pleura, central nervous system (meningitis), lymphatic system (scrofula of the neck), genitourinary system, and bones and joints (Pott's disease of the spine). An especially serious form is "disseminated", or "miliary" TB, so named because the lung lesions so-formed resemble millet seeds on x-ray. These are more common in immunosuppressed persons and in young children. Pulmonary TB may co-exist with extrapulmonary TB.

Related Topics:
Meningitis - Scrofula - Pott's disease

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Drug resistance

Drug-resistant TB is transmitted in the same way as drug-susceptible TB. Primary resistance develops in persons initially infected with resistant organisms. Secondary resistance (acquired resistance) may develop during TB therapy due to inadequate treatment regimen, not taking the prescribed regimen appropriately or using low quality medication.

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