Tuberculosis

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Overview

In 1993, the World Health Organization (WHO) declared tuberculosis a global emergency. Tuberculosis (TB) is responsible for more deaths than any other infectious disease. Once called consumption, TB is a highly contagious, persistent disease characterized by the formation of hard grayish nodules, or tubercles. The disease is most often caused by the bacterium Mycobacterium tuberculosis and usually occurs in the lungs (the initial site of infection), but it also can occur in other organs.

Because its signs and symptoms are easily confused with those of many other (usually respiratory) diseases, tuberculosis can be difficult to diagnose. Common symptoms are cough that is worse in the morning and may include hemoptysis (i.e., blood in the sputum), chest pain, night sweats, and breathlessness (dyspnea). Ninety percent of those infected with M. tuberculosis mount an effective immune response and never develop the disease.

Incidence and Prevalence
Mycobacterial disease is one of the world's most difficult health problems. One-third of the population worldwide is infected with TB. Of these, 8 to 10 million develop active disease and according to the World Health Organization (WHO), 2 million die each year. It is the greatest cause of death in women of reproductive age; 900 million women are currently infected. Of these, 2.5 million will develop active disease and 1 million will die.

According to WHO, every year more than 1.5 million TB cases occur in sub-Saharan Africa; nearly 3 million cases occur in Southeast Asia; and over 250,000 occur in Eastern Europe. AIDS (autoimmune deficiency syndrome) with coexistent mycobacterial infection is bringing TB back into Western cities and seriously threatens health services in the developing world.

The rate of tuberculosis infection in the United States had been declining steadily until 1984 and then increased. Numerous factors account for the resurgence of tuberculosis in the United States and in Europe. They include the following:

• Emergence of multidrug-resistant strains of M. tuberculosis
• Erosion of systems for diagnosis and treatment of the disease
• Immigration of infected persons from countries where TB is prevalent
• Prevalence of HIV (human immunodeficiency virus) infection and AIDS
• Reactivation of disease in the elderly
• Socioeconomic decline in urban areas

The rapid response of state and federal agencies in the United States has averted a potentially drastic rise in incidence.

Pathology
M. tuberculosis is a highly contagious, airborne, rod-shaped organism (bacillus) that thrives on oxygen, grows slowly, and possesses a "waxy" cell wall. The cell wall's structure and function are not well understood but appear to allow the bacteria to survive within immune cells called macrophages (specialized cells that destroy bacteria and viruses). It also provides the organism with a resistant barrier to many common drugs.

The organism is difficult to study in the laboratory. Slow growth makes culturing a lengthy process and colony formation can take several weeks. TB bacilli form clumps, making them difficult to work with and count. Because it is a dangerous airborne pathogen, study requires special safety equipment.

The bacteria's primary host is the human. Infection spreads through direct person-to-person contact. When an infected person talks, coughs, sings, or spits, tiny aerosolized droplets containing bacteria are released into the air and inhaled by uninfected persons. Viable bacteria can remain in the air for a long time.

Once the bacteria are inhaled they are engulfed by macrophages (white blood cells) that are present in the alveoli (the air sacs of the lungs). The bacteria replicate within the macrophages for 2 to 3 weeks before spreading throughout the body. In 95% of cases the macrophages throughout the body are able to contain the bacteria and no apparent disease is noted. However, the bacteria are not completely killed and can remain dormant for years.

Granulomas prevent spread of infection by confining bacteria within a compact collection of several types of immune cells and activated macrophages, some of which fuse together. These cells work in various but specific ways to isolate, inhibit the replication of, and destroy the bacteria. At the center of this aggregate, toxic substances released by some of the immune cells create an unfavorable environment for the bacteria and most of them die. The center has a soft, dry, crumbly cheese-like appearance and the granuloma is described as caseated (ka'-see-a'-ted; from the Latin word for cheese, caseus). Granulomas then become dormant and are sealed off by scar tissue. If any bacilli survive, they may reactivate years later.

What triggers reactivation is not well understood. Five years or more after infection, the bacteria activate some immune cells to release a substance that renders host tissue cells sensitive to killing. Other immune cells are activated to release substances that liquefy the bacteria-containing center of the granuloma. When the granuloma and surrounding tissue erode, the liquefied material is discharged into an airway and a cavity (enlarged air space) forms in the lung. Oxygen and carbon dioxide then freely enter the space, and bacilli replicate in enormous numbers, thriving in this now highly favorable environment. Bacilli spread through air passages from cavities to other parts of the lung and larynx. Swallowed sputum may cause lesions in the alimentary tract.

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