Tuberculosis

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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 and cured, and can be prevented if persons at risk take certain drugs, medical science has never succeeded in eradicating the disease. Few diseases have caused so much distressing illness for centuries and claimed so many lives.

Description

Overview

Tuberculosis was popularly known as consumption for many years. Scientists now know that it is an infection caused by M. tuberculosis. In 1882, one of every seven deaths in Europe was caused by TB. In that year, the microbiologist Robert Koch discovered the tubercle bacillus. Because antibiotics were unknown, the only means of controlling the spread of infection was to isolate patients in private sanitariums or hospitals limited to treating persons with TB. In many countries, this practice continues to this day. The net effect of this approach to 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 persons, but also its impact on society as a whole. At the turn of the twentieth century, more than 80% of the population in the United States was infected with TB before age 20, and tuberculosis was the single most common cause of death. By 1938, there were more than 700 TB hospitals in the United States.

When the industrial revolution began in the late nineteenth century, tuberculosis spread much more widely in Europe. Later, the disease began to spread throughout the United States, primarily due to the population migration to large cities that 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. In part, this upsurge was again a result of overcrowding and unsanitary conditions in poor areas of large cities, prisons, and homeless shelters. Infected visitors and immigrants to the United States also contributed to the resurgence of TB. An additional factor was the emergence of acquired immunodeficiency syndrome (AIDS ). Persons with AIDS are much more likely to develop tuberculosis because of their weakened immune systems than are others in the general population. As of 2001, experts estimate that between 8 and 11 million new cases of TB are reported each year throughout the world. These are estimated to cause approximately 3 million deaths. This situation is worsening. The World Health Organization estimates that by 2020, there will be 1 billion TB cases worldwide and 35 million deaths each year.

High-risk populations

THE ELDERLY Tuberculosis is more common in elderly persons. More than one-fourth of the 19,855 cases of TB (7.4 cases per 100,000 population) reported in the United States in 1997 developed in people above the age of 65. Many elderly individuals 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 successfully eliminate the tubercle bacillus. Finally, bacteria that have been dormant for some time in elderly persons may be reactivated and cause illness.

RACIAL AND ETHNIC GROUPS. TB also is more common among members of minority groups who may be likely to live under conditions that promote infection. As of 2001, approximately 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. The risk of TB has not diminished among members of these groups.

PERSONS WITH RELEVANT 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 addressed and eliminated, there is no real possibility of completely eliminating the disease.

Causes and symptoms

Transmission

Tuberculosis is spread 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, often referred to as aerosol, can be taken into the nasal passages and lungs of a nearby susceptible person. Compared to some other infectious diseases, TB is not highly contagious. Only about one in three close contacts of a person with TB is likely to become infected. 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 bacilli that may be present in amniotic fluid.

Progression

Once inhaled, tubercle bacilli may reach the small breathing sacs in the lungs (alveoli), where they are taken up by cells called macrophages. The bacilli multiply within these cells and then spread through 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 a 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 permanently prevent future disease.

Exposure and infection does not always mean that active TB disease will develop. In fact, most people who are infected do not develop TB. At least nine out of ten people 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 people who may get sick at a later date and then pass their TB on to others. It is thought that more than 90% of active tuberculosis cases come from this pool. In the United States, this group numbers 10 to 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 develop active cases of TB 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 light green 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. A person 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), an affected person may have difficulty breathing. If a young adult develops a pleural effusion, the probability of tubercular infection being the cause is very high. 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, lost a great deal of weight, and developed a wasted appearance. This outcome is uncommon today—at least where modern methods of treatment are available.

Extrapulmonary tuberculosis

Although the lungs are the major site for 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:

Bones. TB is particularly likely to attack the spine and the ends of the long bones. Children are especially prone to spinal tuberculosis. If not treated, the spinal bones (vertebrae) may collapse and cause paralysis in one or both legs.
Kidneys. Along with bones, the kidneys are probably the most common site of extrapulmonary TB. There may, however, be few symptoms even though part of a kidney is destroyed. TB may spread to the bladder. In men, it may spread to the prostate gland and nearby structures.
Female reproductive organs. The ovaries in women may become infected as TB can spread from them to the peritoneum, which is the membrane lining the abdominal cavity.
Abdominal cavity. Tuberculous peritonitis may cause pain ranging from the vague discomfort of stomach cramps to intense pain that may mimic the symptoms of appendicitis.
Joints. Tubercular infection of joints causes a form of arthritis that most often affects the hips and knees. The wrist, hand, and elbow joints also may become painful and inflamed.
Meninges. The meninges are tissues that cover the brain and the spinal cord. Infection of the meninges by TB bacillus causes tuberculous meningitis, a condition that is most common in young children but is especially dangerous in the elderly. Affected people develop headaches, become drowsy, and may eventually fall into a coma. Permanent brain damage is the rule unless prompt treatment is given. Some people with tuberculous meningitis develop a tumor-like brain mass called a tuberculoma that can cause symptoms that resemble those of a stroke.
Skin, intestines, adrenal glands, and blood vessels. All these parts of the body can be infected by M. tuberculosis. Infection of the wall of the body's main artery (the aorta) can cause it to rupture with catastrophic results. Tuberculous pericarditis occurs when the membrane surrounding the heart (the pericardium) is infected and fills up with fluid that interferes with the heart's ability to pump blood. Miliary tuberculosis.
Miliary TB is a life-threatening condition that occurs when large numbers of tubercle bacilli spread throughout the body. Huge numbers of tiny tubercular lesions develop, causing marked weakness and weight loss, severe anemia, and gradual wasting of the body.

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 usually do so only when an infected person's immune system is defective. People who are HIV-positive are a good 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 may develop a serious lung infection that is highly resistant to antibiotics. MAC infections typically start with an affected person coughing up mucus. The infection progresses slowly, but eventually blood is brought up and the person has trouble breathing. Among people with AIDS, MAC disease can spread throughout the body, with anemia, diarrhea, and stomach pain as common features. Often, these people die unless their immune systems can be strengthened. Other mycobacteria grow in swimming pools and may cause skin infections. Some of them infect wounds and artificial body parts such as a breast implant or mechanical heart valve. The organism that causes leprosy, M. leprae, is also related to TB.

Diagnosis

The diagnosis of TB is made on the basis of laboratory test results. The standard test for tuberculosis, 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. These terms have specific meanings. People who have a skin reaction and are not infected are referred to having a false positive result. Those who do not react but are in fact infected are classified as having a false negative result. The PPD test is, however, useful as a screening device. 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 someone who has active TB or persons who come from a country where TB is common should be tested, as should all healthcare personnel and those living in crowded conditions or institutions.

Because the symptoms of TB encompass a wide range of severity and affect many parts of the body, 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 performed to show whether an individual has been infected by the tubercle bacillus. To verify test results, a 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.

Treatment

Supportive care

In the past, treatment of TB was primarily supportive. People being treated for TB were kept in isolation, encouraged to rest, and fed well. If these measures failed, their affected lungs were collapsed surgically so that they 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, individuals 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 people with TB can recover if given appropriate medication for a sufficient length of time. Three principles govern modern drug treatment of TB:

Lowering the number of bacilli as quickly as possible. This measure minimizes the risk of transmitting the disease. When sputum cultures become negative, this has been achieved. Conversely, if the sputum cultures remain positive after five to six months, treatment has failed.
Preventing the development of drug resistance. For this reason, at least two different drugs and sometimes three are always given at first. If drug resistance is suspected, at least two different drugs should be tried.
Long-term, continuous treatment to prevent relapse.

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 2001, many persons are given isoniazid and rifampin together for six months, with pyrazinamide added for the first two months. Hospitalization is rarely necessary because most persons are no longer infectious after about two weeks of combination treatment. Follow-up involves monitoring for the presence of side effects and having monthly sputum tests. Of the five medications, isoniazid is the most frequently used drug for both treatment and prevention of TB.

Surgery

Surgical treatment of TB may be used if oral 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 individuals to survive with one healthy lung. Spinal TB may result in a severe deformity that can be surgically corrected.

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. Modern surgical methods have good outcomes 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 seldomused drugs may be tried because the tubercle bacilli have not yet developed resistance to them.

Health care team roles

Screening for tuberculosis may be conducted by nurses, physicians, physician assistants, or other trained health workers. The test is read or evaluated by a nurse, physician, or physician assistant. Treatment for TB must be prescribed and supervised by a physician. A surgeon may provide surgical intervention, often assisted by a physician assistant trained in surgery. Administration of TB medications is often supervised by nurses, although other non-medical personnel may observe TB drug ingestion. Epidemiologists collect data from many individual caregivers, and are key members of the health care team even though they do not directly provide clinical services. Pharmaceutical scientists are constantly searching for new drugs for useintreating TB.

Prevention

General measures

General measures such as avoiding overcrowded and unsanitary conditions are important aspects of prevention. Hospital emergency rooms and similar locations that are used to treat or house TB patients can be treated with ultraviolet light, which has an antibacterial effect.

KEY TERMS

Alveoli— Several small, sac-shaped cavities. In the lungs, alveoli (plural of alveolus) are found at the ends of airways, the sites where oxygen and carbon dioxide are exchanged in the blood.

Bacillus Calmette-Guérin (BCG)— A vaccine made from a damaged bacillus that is related to the tubercle bacillus, which may help prevent serious pulmonary TB and its complications. Macrophage—A large, phagocytic cell that is found in the blood system and loose connective tissue.

Mantoux test— Another name for the PPD test.

Miliary tuberculosis— The form of TB in which the bacillus spreads through all body tissues and organs, producing many thousands of tiny tubercular lesions. Miliary TB is often fatal unless promptly treated.

Mycobacteria— A group of bacteria that includes Mycobacterium tuberculosis, the bacterium that causes tuberculosis, and other forms that cause related illnesses.

Peritonitis— An infection in the peritoneum (abdominal cavity).

Pleural effusion— Fluid that collects in the space normally occupied by a lung.

Pneumothorax— Air inside the chest cavity, which may cause a lung to collapse. Pneumothorax is both a complication of pulmonary tuberculosis and a means of treatment designed to allow an infected lung to rest and heal.

Pulmonary— Refers to the lungs.

Purified protein derivative (PPD)— An extract of tubercle bacilli that is injected into the skin to find out whether a person presently has or has ever had tuberculosis.

Resistance— A property of some bacteria that have been exposed to a particular antibiotic and have changed sufficiently to survive in its presence.

Sputum— Secretions produced in an infected lung and coughed up. A sign of illness, sputum is routinely used as a specimen for culturing the tubercle bacillus in a laboratory.

Tuberculoma— A tumor-like mass in the brain that sometimes develops as a complication of tuberculous meningitis.

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 widely in developing countries but is not used in the United States. This is because it protects only 75% of recipients, and because everyone who receives the vaccine reacts positively to future TB screening tests. The problem is identifying the one person in four who has a false negative test result. 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

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

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

Close contacts of persons with active TB, including health care workers.
Newly infected patients whose skin test has turned positive in the past two years.
Anyone who is HIV-positive with a positive PPD skin test. Isoniazid may be given even if PPD results are negative if there is a risk of exposure to active tuberculosis.
Intravenous drug users, even if they are negative for HIV.
Persons who have never been treated for TB, have positive PPD results, and show evidence of old disease on a chest x ray.
People who have an illness or are taking a drug that can suppress the immune system.
Persons with positive PPD results who have had intestinal surgery, have diabetes or chronic kidney failure, have any type of cancer, or are more than 10% below their ideal body weight.
People from countries with high rates of TB who have positive PPD results.
People from low-income groups with positive skin test results.
Persons with a positive PPD reaction who belong to high-risk ethnic groups (African-Americans, Hispanics, Native Americans, Asians, and Pacific Islanders).

Resources

BOOKS

Dormandy, Thomas. The White Death: A History of Tuberculosis. New York: New York University Press, 2000.

Friedman, Lloyd N. Tuberculosis: Current Concepts and Treatment, 2nd ed. Boca Raton, FL: CRC Press, 2000.

Geiter, Lawrence. Ending Neglect: The Elimination of Tuberculosis in the United States. Washington, DC: National Academy Press, 2000.

Rom, William N. and Stewart M. Garay. Tuberculosis. Philadelphia: Lippincott Williams & Wilkins, 1993.

Ryan, Frank. The Forgotten Plague: How the Battle Against Tuberculosis Was Won and Lost. Philadelphia: Lippincott Williams & Wilkins, 1993.

PERIODICALS

Ebrahim, G.J."Multi-drug Resistant Tuberculosis." Journal of Tropical Pediatrics 46, no. 6 (2000): 320-1.

Hamilton, CD. "Recent Developments in Epidemiology, Treatment, and Diagnosis of Tuberculosis." Current Infectious Disease Reports 1, no. 1 (1999): 80-8.

Jones, T.F. and W. Moore. "The Phthisis Still With Us. Tuberculosis: The White Plague is Not Yet a Ghost of the Past." Tennessee Medicine 94, no. 2 (2001): 62-3.

Kochi, A. "The Global Tuberculosis Situation and the New Control Strategy of the World Health Organization." Bulletin of the World Health Organization 79, no. 1 (2001): 71-5.

Williamson, J. "Tuberculosis revisited or how we nearly conquered tuberculosis." Scottish Medical Journal 45, no. 6 (2000):183-185.

ORGANIZATIONS

American Lung Association. 1740 Broadway, New York, NY 10019. (212) 315-8700. ?http://www.lungusa.org/diseases/lungtb.html?.

Centers for Disease Control and Prevention. 1600 Clifton Rd., Atlanta, GA 30333. (404) 639-3534 or (800) 311-3435. ?http://www.cdc.gov/nchstp/tb/faqs/qa.htm?.

Francis J. Curry National Tuberculosis Center. 3180 18th St., Suite 101, San Francisco, CA 94110-2028. (415) 502-4600. ?http://www.nationaltbcenter.edu?.

National Tuberculosis Center, University of Medicine and Dentistry of New Jersey. 65 Bergen St., Newark, NJ 07107-3001. (973) 972-3270 or (800) 482-3627. ?http://www.umdnj.edu/ntbcweb?.

World Health Organization, Communicable Diseases. 20 Avenue Appia, 1211 Geneva 27, Switzerland. +41 (22) 791 4140. ?http://www.who.int/gtb?.