A specific disease caused by infection with Mycobacterium tuberculosis, the tubercle bacillus, which can affect almost any tissue or organ of the body, the most common site of the disease being the lungs. Primary TB is typically a mild or asymptomatic local pulmonary infection. Regional lymph nodes may become involved, but in otherwise healthy people generalized disease does not immediately develop. A cell-mediated immune response arrests the spread of organisms and walls off the zone of infection. Infected tissues and lymph nodes may eventually calcify. The tuberculin skin test result becomes positive within a few weeks and remains positive throughout life. Organisms in a primary lesion remain viable and can become reactivated months or years later to initiate secondary TB. Progression to the secondary stage eventually occurs in 10-15% of people who have had primary TB; in one half of these, progression occurs within 2 years. The risk of reactivation is increased by diabetes mellitus, malnutrition, HIV infection, silicosis, and various systemic or malignant conditions, as well as in patients with alcoholism, IV drug abusers, nursing home residents, and those receiving adrenocortical steroid or immunosuppressive therapy. Secondary or reactivation TB usually results in a chronic, spreading lung infection, most often involving the upper lobes. Minute granulomas (tubercles), just visible to the naked eye, develop in involved lung tissue, each consisting of a zone of caseation necrosis surrounded by chronic inflammatory cells (epithelioid histiocytes and giant cells). These lesions, which give the disease its name, are also found in other tissues (lymph nodes, bowel, kidney, skin) to which the disease may spread. Rarely, reactivation results in widespread dissemination of tubercles throughout the body (miliary TB). The symptoms of active pulmonary TB are fatigue, anorexia, weight loss, low-grade fever, night sweats, chronic cough, and hemoptysis. Local symptoms depend on the parts affected. Active pulmonary TB is relentlessly chronic and, if untreated, leads to progressive destruction of lung tissue. Cavities form in the lungs, and erosion into pulmonary blood vessels can result in life-threatening hemorrhage. Gradual deterioration of nutritional status and general health culminates in death due to wasting, infection, or multiple organ failure. Variant syndromes (tuberculous lymphadenitis in children, severe systemic disease in persons with AIDS) are caused by organisms of the Mycobacterium avium-intracellulare complex (MAIC). The diagnosis of TB is based on tuberculin skin testing (negative in 20% of people with active TB), imaging studies (computed tomography is more sensitive than standard chest radiography in detecting pleural effusion, miliary disease, and cavitation), and the finding of the causative organism in sputum or tissue specimens by acid-fast or fluorochrome staining, nucleic acid amplificatin, or culture. [tuberculo- + G. -osis, condition]In 1993 the World Health Organization (WHO) declared TB a global emergency. Fully one third of the world's population is infected with TB. On a global scale, TB ranks first among infectious diseases as a cause of death. Two thirds of all the world's cases are in Asia, but the disease is also endemic in parts of Africa (where the highest incidence rates per capita are found) and eastern Europe. War and social upheaval have played a role in the spread of tuberculosis beyond endemic zones. Prevalence of infection is higher among refugees and immigrants. One third of all people with tuberculosis in the U.S. were born outside this country, and more than 50% of newly diagnosed cases occur in people of foreign birth. From the 1950s, when antibiotics began to be used for the treatment of TB, until the 1980s, the incidence and mortality of the disease declined steadily in the U.S. During the 1980s the incidence began to rise because of many new cases in people with AIDS and because of increasing prevalence of multidrug-resistant strains of M. tuberculosis. Since 1993 the figures have again declined, chiefly because of improvements in TB prevention and control programs in state and local health departments as a result of increased federal funding provided to states. At least one third of people with AIDS contract TB, and TB is the cause of death in one third of people who die of AIDS. Because antibiotic resistance in M. tuberculosis has been a growing problem for years, multidrug regimens, usually including isoniazid, rifampin, and pyrazinamide, are standard. Other drugs, such as ethambutol, streptomycin, kanamycin, and capreomycin, may be added or substituted. The success of treatment is limited not only by the resistance of organisms to several agents but also by the risk of severe toxic effects with all standard agents. Unlike most infections treated with antibiotics, TB requires not merely days or weeks of treatment but rather months and years. Long-term compliance with treatment regimens tends to be poor among mobile, indigent, and uneducated people. According to WHO, the principal reason for the spread of multidrug-resistant strains of M. tuberculosis is ineffectual management of TB control programs, particularly in developing countries. An inappropriate or unfinished course of chemotherapy not only leaves the patient still sick and still contagious, but favors the selection of resistant bacteria. It is estimated that 50 million of the world's cases of TB involve multiply resistant tubercle bacilli. The prevalence of infection due to drug-resistant strains is particularly high in some former Soviet states. Currently WHO urges that TB programs worldwide adopt the practice of directly observed therapy (DOT), in which a health care worker observes each patient swallowing each dose of medicine. In a study performed at several U.S. centers, DOT for TB was found to be cost effective when the cost of relapses and treatment failures was added to the cost of self-administered therapy, even though the raw cost of DOT was higher. U.S. public health authorities have established as a national goal the elimination of TB (defined as an incidence of less than 1 case per 1 million population) by 2010.