Tuberculosis

Tuberculosis 

Definition

Tuberculosis (TB) is a potentially fatal contagious disease that can affect almost any part of the body but is mainly an infection of the lungs. It is caused by a bacterial microorganism, the tubercle bacillus or Mycobacterium tuberculosis. Although TB can be treated, cured, and can be prevented if persons at risk take certain drugs, scientists have never come close to wiping it out. Few diseases have caused so much distressing illness for centuries and claimed so many lives.

Description

Overview

Tuberculosis was popularly known as consumption for a long time. Scientists know it as an infection caused by M. tuberculosis. In 1882, the microbiologist Robert Koch discovered the tubercle bacillus, at a time when one of every seven deaths in Europe was caused by TB. Because antibiotics were unknown, the only means of controlling the spread of infection was to isolate patients in private sanitoria or hospitals limited to patients with TB—a practice that continues to this day in many countries. The net effect of this pattern of treatment was to separate the study of tuberculosis from mainstream medicine. Entire organizations were set up to study not only the disease as it affected individual patients, but its impact on the society as a whole. At the turn of the twentieth century more than 80% of the population in the United States were infected before age 20, and tuberculosis was the single most common cause of death. By 1938 there were more than 700 TB hospitals in this country.

Tuberculosis spread much more widely in Europe when the industrial revolution began in the late nineteenth century. The disease became widespread somewhat later in the United States, because the movement of the population to large cities made overcrowded housing so common. When streptomycin, the first antibiotic effective against M. tuberculosis, was discovered in the early 1940s, the infection began to come under control. Although other more effective anti-tuberculosis drugs were developed in the following decades, the number of cases of TB in the United States began to rise again in the mid-1980s. This upsurge was in part again a result of overcrowding and unsanitary conditions in the poor areas of large cities, prisons, and homeless shelters. Infected visitors and immigrants to the United Stateshave also contributed to the resurgence of TB. An additional factor is the AIDS epidemic. AIDS patients are much more likely to develop tuberculosis because of their weakened immune systems. There still are an estimated 8-10 million new cases of TB each year worldwide, causing roughly 3 million deaths.

High-risk populations

THE ELDERLY. Tuberculosis is more common in elderly persons. More than one-fourth of the nearly 23,000 cases of TB reported in the United States in 1995 developed in people above age 65. Many elderly patients developed the infection some years ago when the disease was more widespread. There are additional reasons for the vulnerability of older people: those living in nursing homes and similar facilities are in close contact with others who may be infected. The aging process itself may weaken the body's immune system, which is then less able to ward off the tubercle bacillus. Finally, bacteria that have lain dormant for some time in elderly persons may be reactivated and cause illness.

RACIAL AND ETHNIC GROUPS. TB also is more common in blacks, who are more likely to live under conditions that promote infection. At the beginning of the new millennium, two-thirds of all cases of TB in the United States affect African Americans, Hispanics, Asians, and persons from the Pacific Islands. Another one-fourth of cases affect persons born outside the United States. As of 2002, the risk of TB is still increasing in all these groups.

As of late 2002, TB is a major health problem in certain specific immigrant communities, such as the Vietnamese in southern California. One team of public health experts in North Carolina maintains that treatment for tuberculosis is the most pressing health care need of recent immigrants to the United States. In some cases, the vulnerability of immigrants to tuberculosis is increased by occupational exposure, as a recent outbreak of TB among Mexican poultry farm workers in Delaware indicates. Other public health experts are recommending tuberculosis screening at the primary care level of all new immigrants and refugees.

LIFESTYLE FACTORS. The high risk of TB in AIDS patients extends to those infected by human immunodeficiency virus (HIV) who have not yet developed clinical signs of AIDS. Alcoholics and intravenous drug abusers are also at increased risk of contracting tuberculosis. Until the economic and social factors that influence the spread of tubercular infection are remedied, there is no real possibility of completely eliminating the disease.

Causes and symptoms

Transmission

Tuberculosis spreads by droplet infection. This type of transmission means that when a TB patient exhales, coughs, or sneezes, tiny droplets of fluid containing tubercle bacilli are released into the air. This mist, or aerosol as it is often called, can be taken into the nasal passages and lungs of a susceptible person nearby. Tuberculosis is not, however, highly contagious compared to some other infectious diseases. Only about one in three close contacts of a TB patient, and fewer than 15% of more remote contacts, are likely to become infected. As a rule, close, frequent, or prolonged contact is needed to spread the disease. Of course, if a severely infected patient emits huge numbers of bacilli, the chance of transmitting infection is much greater. Unlike many other infections, TB is not passed on by contact with a patient's clothing, bed linens, or dishes and cooking utensils. The most important exception is pregnancy. The fetus of an infected mother may contract TB by inhaling or swallowing the bacilli in the amniotic fluid.

Progression

Once inhaled, tubercle bacilli may reach the small breathing sacs in the lungs (the alveoli), where they are taken up by cells called macrophages. The bacilli multiply within these cells and then spread through the lymph vessels to nearby lymph nodes. Sometimes the bacilli move through blood vessels to distant organs. At this point they may either remain alive but inactive (quiescent), or they may cause active disease. Actual tissue damage is not caused directly by the tubercle bacillus, but by the reaction of the person's tissues to its presence. In a matter of weeks the host develops an immune response to the bacillus. Cells attack the bacilli, permit the initial damage to heal, and prevent future disease permanently.

Infection does not always mean disease; in fact, it usually does not. At least nine of ten patients who harbor M. tuberculosis do not develop symptoms or physical evidence of active disease, and their x-rays remain negative. They are not contagious; however, they do form a pool of infected patients who may get sick at a later date and then pass on TB to others. It is thought that more than 90% of cases of active tuberculosis come from this pool. In the United States this group numbers 10-15 million persons. Whether or not a particular infected person will become ill is impossible to predict with certainty. An estimated 5% of infected persons get sick within 12-24 months of being infected. Another 5% heal initially but, after years or decades, develop active tuberculosis either in the lungs or elsewhere in the body. This form of the disease is called reactivation TB, or post-primary disease. On rare occasions a previously infected person gets sick again after a later exposure to the tubercle bacillus.

Pulmonary tuberculosis

Pulmonary tuberculosis is TB that affects the lungs. Its initial symptoms are easily confused with those of other diseases. An infected person may at first feel vaguely unwell or develop a cough blamed on smoking or a cold. A small amount of greenish or yellow sputum may be coughed up when the person gets up in the morning. In time, more sputum is produced that is streaked with blood. Persons with pulmonary TB do not run a high fever, but they often have a low-grade one. They may wake up in the night drenched with cold sweat when the fever breaks. The patient often loses interest in food and may lose weight. Chest pain is sometimes present. If the infection allows air to escape from the lungs into the chest cavity (pneumothorax) or if fluid collects in the pleural space (pleural effusion), the patient may have difficulty breathing. If a young adult develops a pleural effusion, the chance of tubercular infection being the cause is very high. The TB bacilli may travel from the lungs to lymph nodes in the sides and back of the neck. Infection in these areas can break through the skin and discharge pus. Before the development of effective antibiotics, many patients became chronically ill with increasingly severe lung symptoms. They lost a great deal of weight and developed a wasted appearance. This outcome is uncommon today—at least where modern treatment methods are available.

Extrapulmonary tuberculosis

Although the lungs are the major site of damage caused by tuberculosis, many other organs and tissues in the body may be affected. The usual progression is for the disease to spread from the lungs to locations outside the lungs (extrapulmonary sites). In some cases, however, the first sign of disease appears outside the lungs. The many tissues or organs that tuberculosis may affect include:

Diseases similar to tuberculosis

There are many forms of mycobacteria other than M. tuberculosis, the tubercle bacillus. Some cause infections that may closely resemble tuberculosis, but they usually do so only when an infected person's immune system is defective. People who are HIV-positive are a prime example. The most common mycobacteria that infect AIDS patients are a group known as Mycobacterium avium complex (MAC). People infected by MAC are not contagious, but they may develop a serious lung infection that is highly resistant to antibiotics. MAC infections typically start with the patient coughing up mucus. The infection progresses slowly, but eventually blood is brought up and the patient has trouble breathing. In AIDS patients, MAC disease can spread throughout the body, with anemia, diarrhea, and stomach pain as common features. Often these patients die unless their immune system can be strengthened. Other mycobacteria grow in swimming pools and may cause skin infection. Some of them infect wounds and artificial body parts such as a breast implant or mechanical heart valve.

Diagnosis

The diagnosis of TB is made on the basis of laboratory test results. The standard test for tuberculosis—which is the so-called tuberculin skin test—detects the presence of infection, not of active TB. Tuberculin is an extract prepared from cultures of M. tuberculosis. It contains substances belonging to the bacillus (antigens) to which an infected person has been sensitized. When tuberculin is injected into the skin of an infected person, the area around the injection becomes hard, swollen, and red within one to three days. Today skin tests utilize a substance called purified protein derivative (PPD) that has a standard chemical composition and is therefore is a good measure of the presence of tubercular infection. The PPD test is also called the Mantoux test. The Mantoux PPD skin test is not, however, 100% accurate; it can produce false positive as well as false negative results. What these terms mean is that some people who have a skin reaction are not infected (false positive) and that some who do not react are in fact infected (false negative). The PPD test is, however, useful as a screener. Anyone who has suspicious findings on a chest x ray, or any condition that makes TB more likely should have a PPD test. In addition, those in close contact with a TB patient and persons who come from a country where TB is common also should be tested, as should all healthcare personnel and those living in crowded conditions or institutions.

Because the symptoms of TB cover a wide range of severity and affected body parts, diagnosis on the basis of external symptoms is not always possible. Often, the first indication of TB is an abnormal chest x-ray or other test result rather than physical discomfort. On a chest x ray, evidence of the disease appears as numerous white, irregular areas against a dark background, or as enlarged lymph nodes. The upper parts of the lungs are most often affected. A PPD test is always done to show whether the patient has been infected by the tubercle bacillus. To verify the test results, the physician obtains a sample of sputum or a tissue sample (biopsy) for culture. Three to five sputum samples should be taken early in the morning. If necessary, sputum for culture can be produced by spraying salt solution into the windpipe. Culturing M. tuberculosis is useful for diagnosis because the bacillus has certain distinctive characteristics. Unlike many other types of bacteria, mycobacteria can retain certain dyes even when exposed to acid. This so-called acid-fast property is characteristic of the tubercle bacillus.

Body fluids other than sputum can be used for culture. If TB has invaded the brain or spinal cord, culturing a sample of spinal fluid will make the diagnosis. If TB of the kidneys is suspected because of pus or blood in the urine, culture of the urine may reveal tubercular infection. Infection of the ovaries in women can be detected by placing a tube having a light on its end (a laparoscope) into the area. Samples also may be taken from the liver or bone marrow to detect the tubercle bacillus.

One important new advance in the diagnosis of TB is the use of molecular techniques to speed the diagnostic process as well as improve its accuracy. As of late 2005, four molecular techniques are increasingly used in laboratories around the world. They include polymerase chain reaction to detect mycobacterial DNA in patient specimens; nucleic acid probes to identify mycobacteria in culture; restriction fragment length polymorphism analysis to compare different strains of TB for epidemiological studies; and genetic-based susceptibility testing to identify drugresistant strains of mycobacteria.

Treatment

Supportive care

In the past, treatment of TB was primarily supportive. Patients were kept in isolation, encouraged to rest, and fed well. If these measures failed the lung was collapsed surgically so that it could "rest" and heal. Today surgical procedures still are used when necessary, but contemporary medicine relies on drug therapy as the mainstay of home care. Given an effective combination of drugs, patients with TB can be treated at home as well as in a sanitorium. Treatment at home does not pose the risk of infecting other household members.

Drug therapy

Most patients with TB can recover if given appropriate medication for a sufficient length of time. Three principles govern modern drug treatment of TB:

Five drugs are most commonly used today to treat tuberculosis: isoniazid (INH, Laniazid, Nydrazid); rifampin (Rifadin, Rimactane); pyrazinamide (Tebrazid); streptomycin; and ethambutol (Myambutol). The first three drugs may be given in the same capsule to minimize the number of pills in the dosage. As of 1998, many patients are given INH and rifampin together for six months, with pyrazinamide added for the first two months. Hospitalization is rarely necessary because many patients are no longer infectious after about two weeks of combination treatment. Follow-up involves monitoring of side effects and monthly sputum tests. Of the five medications, INH is the most frequently used drug for both treatment and prevention.

Surgery

Surgical treatment of TB may be used if medications are ineffective. There are three surgical treatments for pulmonary TB: pneumothorax, in which air is introduced into the chest to collapse the lung; thoracoplasty, in which one or more ribs are removed; and removal of a diseased lung, in whole or in part. It is possible for patients to survive with one healthy lung. Spinal TB may result in a severe deformity that can be corrected surgically.

Prognosis

The prognosis for recovery from TB is good for most patients, if the disease is diagnosed early and given prompt treatment with appropriate medications on a long-term regimen. According to a 2002 Johns Hopkins study, most patients in the United States who die of TB are older—average age 62—and suffer from such underlying diseases as diabetes and kidney failure.

Modern surgical methods have a good outcome in most cases in which they are needed. Miliary tuberculosis is still fatal in many cases but is rarely seen today in developed countries. Even in cases in which the bacillus proves resistant to all of the commonly used medications for TB, other seldom-used drugs may be tried because the tubercle bacilli have not yet developed resistance to them.

Prevention

General measures

General measures such as avoidance of overcrowded and unsanitary conditions are also necessary aspects of prevention. Hospital emergency rooms and similar locations can be treated with ultraviolet light, which has an antibacterial effect.

Vaccination

Vaccination is one major preventive measure against TB. A vaccine called BCG (Bacillus Calmette-Guérin, named after its French developers) is made from a weakened mycobacterium that infects cattle. Vaccination with BCG does not prevent infection by M. tuberculosis but it does strengthen the immune system of first-time TB patients. As a result, serious complications are less likely to develop. BCG is used more widely in developing countries than in the United States. The effectiveness of vaccination is still being studied; it is not clear whether the vaccine's effectiveness depends on the population in which it is used or on variations in its formulation.

Prophylactic use of isoniazid

INH can be given for the prevention as well as the treatment of TB. INH is effective when given daily over a period of six to 12 months to people in high-risk categories. INH appears to be most beneficial to persons under the age of 25. Because INH carries the risk of side-effects (liver inflammation, nerve damage, changes in mood and behavior), it is important to give it only to persons at special risk.

High-risk groups for whom isoniazid prevention may be justified include:

Resources

Books

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Infectious Diseases Caused by Mycobacteria." In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Pelletier, Kenneth R., MD. The Best Alternative Medicine, Part II, "CAM Therapies for Specific Conditions: Tuberculosis." New York: Simon & Schuster, 2002.

Periodicals

"Changing Patterns of New Tuberculosis Infections." Infectious Disease Alert August 15, 2002: 171-172.

"'Drug of Dreams' Preps for First Large-Scale Trail: Study to Begin this Year; Moxifloxacin to Debut Soon in Study 27." TB Monitor July 2002: 73.

Efferen, Linda S. "Tuberculosis: Practical Solutions to Meet the Challenge." Journal of Respiratory Diseases November 1999: 772.

Fielder, J. F., C. P. Chaulk, M. Dalvi, et al. "A High Tuberculosis Case-Fatality Rate in a Setting of Effective Tuberculosis Control: Implications for Acceptable Treatment Success Rates." International Journal of Tuberculosis and Lung Disease 6 (December 2002): 1114-1117.

"Guidelines Roll Out Two New Variations: Experts give Both a Thumbs Up." TB Monitor August 2002: 85.

Houston, H. R., N. Harada, and T. Makinodan. "Development of a Culturally Sensitive Educational Intervention Program to Reduce the High Incidence of Tuberculosis Among Foreign-Born Vietnamese." Ethnic Health 7 (November 2002): 255-265.

Kim, D. Y., R. Ridzon, B. Giles, and T. Mireles. "Pseudo-Outbreak of Tuberculosis in Poultry Plant Workers, Sussex County, Delaware." Journal of Occupational and Environmental Medicine 44 (December 2002): 1169-1172.

Moua, M., F. A. Guerra, J. D. Moore, and R. O. Valdiserri. "Immigrant Health: Legal Tools/Legal Barriers." Journal of Law and Medical Ethics 30, Supplement 3 (Fall 2002): 189-196.

"New Drugs Sought for Top Killer of Young Women Worldwide." Women's Health Weekly July 25, 2002: 20.

"Poor Patient Compliance Key to Drug Resistance in Tuberculosis." Pulse July 1, 2002: 18.

Stauffer, W. M., D. Kamat, and P. F. Walker. "Screening of International Immigrants, Refugees, and Adoptees." Primary Care 29 (December 2002): 879-905.

Su, W. J. "Recent Advances in the Molecular Diagnosis of Tuberculosis." Journal of Microbiology, Immunology, and Infection 35 (December 2002): 209-214.

Organizations

American Lung Association. 1740 Broadway, New York, NY 10019. (800) 586-4872. http://www.lungusa.org.

National Heart, Lung, and Blood Institute (NHLBI). P. O. Box 30105, Bethesda, MD 20824-0105. (301) 592-8573. www.nhlbi.nih.gov.

Other

New York State Department of Health. "Communicable Disease Fact Sheet."

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tuberculosis /tu·ber·cu·lo·sis/ (-sis) any of the infectious diseases of humans and other animals due to species of Mycobacterium and marked by formation of tubercles and caseous necrosis in tissues of any organ; in humans the lung is the major seat of infection and the usual portal through which infection reaches other organs.

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avian tuberculosis  a form affecting various birds, due to Mycobacterium avium, which may be communicated to humans and other animals.

bovine tuberculosis  an infection of cattle due to Mycobacterium bovis, transmissible to humans and other animals.

disseminated tuberculosis  an acute form of miliary t.

genital tuberculosis  tuberculosis of the genital tract, e.g., tuberculous endometritis.

tuberculosis of lungs  pulmonary t.

miliary tuberculosis  a form varying in severity, in which minute tubercles form in different organs due to dissemination of bacilli through the body by the blood stream.

open tuberculosis 

1. that in which there are lesions from which tubercle bacilli are discharged out of the body.

2. pulmonary tuberculosis with cavitation.

pulmonary tuberculosis  tuberculosis of lungs; infection of the lungs by Mycobacterium tuberculosis, with tuberculous pneumonia, formation of tuberculous granulation tissue, caseous necrosis, calcification, and cavity formation. Symptoms include weight loss, fatigue, night sweats, purulent sputum, hemoptysis, and chest pain.

renal tuberculosis  renal disease due to Mycobacterium tuberculosis.

spinal tuberculosis  osteitis or caries of vertebrae, usually as a complication of pulmonary tuberculosis.

tuberculosis verruco´sa cu´tis , warty tuberculosis a condition usually due to external inoculation of tubercle bacilli into the skin, with wartlike patches having an inflammatory, erythematous border.

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tu·ber·cu·lo·sis (t-bûrky-lss)

n. Abbr. TB

1. An infectious disease of humans and animals caused by the tubercle bacillus and characterized by the formation of tubercles on the lungs and other tissues of the body, often developing long after the initial infection.

2. Tuberculosis of the lungs, characterized by the coughing up of mucus and sputum, fever, weight loss, and chest pain.

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tuberculosis (toobur´kūlō´sis),

n an infectious disease caused by
M. tuberculosis and characterized by the formation of tubercles in the tissues.

Tuberculosis of tongue.

tuberculous lymphadenitis

n an inflammation of the lymph glands caused by the presence of
M. tuberculosis.

tuberculosis, multidrug-resistant (MDR),

n type that no longer responds to treatment due to incomplete or improper use of medication.

tuberculosis, reactivation,

n a recurrence in a patient who has been symptom free for a period of years. Reactivation tuberculosis usually responds to treatment.

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tuberculosis

applied generally to diseases caused by tuberculous group of bacteria in the genus Mycobacteria, which includes Mycobacteria tuberculosis, M. bovis and M. avium. See also fish tuberculosis, mycobacteriosis.

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atypical mycobacterial tuberculosis

see atypical mycobacteriosis.

avian tuberculosis

see Mycobacterium avium tuberculosis (below).

bovine tuberculosis

see Mycobacterium bovis tuberculosis (below).

cutaneous tuberculosis

infection with Mycobacterium tuberculosis uncommonly involves the skin; in dogs and cats it can occur as cutaneous ulcers, abscesses, plaques and nodules. More often, the term is used to describe infection with atypical mycobacteria.

fish tuberculosis

see fish tuberculosis.

Mycobacterium avium tuberculosis

causes a significant disease only in birds. In birds it is a chronic disease characterized by loss of body weight, poor egg production and eventual death. There are characteristic large gray, yellow or white tubercles in liver, spleen and intestinal wall. The disease is very persistent in a flock. In mammals it causes nonprogressive lesions, especially in lymph nodes, causing the animals to be positive to the tuberculin test.

Mycobacterium bovis tuberculosis

a chronic disease characterized by the development of tubercles or discrete nodular lesions in any organ. These may develop a necrotic center containing yellow-orange pus, often caseous. Diffuse involvement of lungs causing bronchopneumonia, and of uterus causing metritis, and of the udder also occur. The common clinical syndrome is wasting with localizing signs dependent on the organs involved. A common lesion in horses is osteomyelitis of a cervical vertebra.

Mycobacterium tuberculosis tuberculosis

infection with the human mycobacteria causes transient, usually lesionless infections in animals.

open tuberculosis

1. that in which there are lesions from which tubercle bacilli are being discharged out of the body.

2. tuberculosis of the lungs with cavitation.

skin tuberculosis

is characterized by chronic indurated lesions on the skin of the lower limbs of cattle. There are nodules on the path of corded lymphatics. Nonpathogenic acid-fast bacteria are present in the lesions and affected cattle are positive to the tuberculin test. Also occurs uncommonly in dogs and cats as single or multiple nodules, ulcers, abscesses or plaques in the skin. See also mycobacteriosis.

tuberculosis testing

tuberculin testing.