General FeaturesMycobacterium tuberculosis is the organism that is the causative agent for tuberculosis (TB). There are other "atypical" mycobacteria such as M. kansasii that may produced a similar clincal and pathologic appearance of disease. M. avium-intracellulare (MAI) seen in immunocompromised hosts (particularly in persons with AIDS) is not primarily a pulmonary infection in terms of its organ distribution (mostly in organs of the mononuclear phagocyte system). Tuberculosis is becoming a world-wide problem. War, famine, homelessness, and a lack of medical care all contribute to the increasing incidence of tuberculosis among disadvantaged persons. Since TB is easily transmissible between persons, then the increase in TB in any segment of the population represents a threat to all segments of the population. This means that it is important to institute and maintain appropriate public health measures, including screening, vaccination (where deemed of value), and treatment. A laxity of public health measures will contribute to an increase in cases. Failure of adequate treatment promotes the development of resistant strains of tuberculosis. Patterns of InfectionThere are two major patterns of disease with TB:
When resistance to infection is particularly poor, a "miliary" pattern of spread can occur in which there are a myriad of small millet seed (1-3 mm) sized granulomas, either in lung or in other organs. Dissemination of tuberculosis outside of lungs can lead to the appearance of a number of uncommon findings with characteristic patterns:
The following images illustrate gross pathologic findings with tuberculosis:
Microscopic FindingsMicroscopically, the inflammation produced with TB infection is granulomatous, with epithelioid macrophages and Langhans giant cells along with lymphocytes, plasma cells, maybe a few PMN's, fibroblasts with collagen, and characteristic caseous necrosis in the center. The inflammatory response is mediated by a type IV hypersensitivity reaction. This can be utilized as a basis for diagnosis by a TB skin test. An acid fast stain (Ziehl-Neelsen or Kinyoun's acid fast stains) will show the organisms as slender red rods. An auramine stain of the organisms as viewed under fluorescence microscopy will be easier to screen and more organisms will be apparent. The most common specimen screened is sputum, but the histologic stains can also be performed on tissues or other body fluids. Culture of sputum or tissues or other body fluids can be done to determine drug sensitivities.
Tuberculin Skin TestingSkin testing for tuberculosis is useful in countries where the incidence of tuberculosis is low, and the health care system works well to detect and treat new cases. In countries where BCG vaccination has been widely used, the TB skin test is not useful, because persons vaccinated with BCG will have a positive skin test. The TB skin test is based upon the type 4 hypersensitivity reaction. If a previous TB infection has occurred, then there are sensitized lymphocytes that can react to another encounter with antigens from TB organisms. For the TB skin test, a measured amount (the intermediate strength of 5 tuberculin units, used in North America) of tuberculin purified protein derivative (PPD) is injected intracutaneously to form a small wheal, typically on the forearm. In 48 to 72 hours, a positive reaction is marked by an area of red induration that can be measured by gentle palpation (redness from itching and scratching doesn't count). Reactions over 10 mm in size are considered positive in non-immunocompromised persons. Repeated testing may increase the size of the reaction (induration), but repeated TB skin testing will not lead to a positive test in a person not infected by TB. Anergy, or absence of PPD reactivity in persons infected with TB, can occur in immunocompromised persons, or it may even occur in persons newly infected with TB, or in persons with miliary TB. |