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.

FLORENCE B. SEIBERT (1897–1991)

Florence Barbara Seibert was born on October 6, 1897, in Easton, Pennsylvania, the second of three children. She was the daughter of George Peter Seibert, a rug manufacturer and merchant, and Barbara (Memmert) Seibert. At the age of three she contracted polio. Despite her resultant handicaps, she completed high school, with the help of her highly supportive parents, and entered Goucher College in Baltimore, where she studied chemistryand zoology. She graduated in 1918, then worked under the direction of one of her chemistry teachers, Jessie E. Minor, at the Chemistry Laboratory of the Hammersley Paper Mill in Garfield, New Jersey. She and her professor, having responded to the call for women to fill positions vacated by men fighting in World War I, coauthored scientific papers on the chemistry of cellulose and wood pulps.

A biochemist who received her Ph.D. from Yale University in 1923, Florence B. Seibert is best known for her research in the biochemistry of tuberculosis. She developed the protein substance used for the tuberculosis skin test. The substance was adopted as the standard in 1941 by the United States and a year later by the World Health Organization. In addition, in the early 1920s, Seibert discovered that the sudden fevers that sometimes occurred during intravenous injections were caused by bacteria in the distilled water that was used to make the protein solutions. She invented a distillation apparatus that prevented contamination. This research had great practical significance later when intravenous blood transfusions became widely used in surgery. Seibert authored or coauthored more than a hundred scientific papers. Her later research involved the study of bacteria associated with certain cancers. Her many honors include five honorary degrees, induction into the National Women's Hall of Fame in Seneca Falls, New York (1990), the Garvan Gold Medal of the American Chemical Society (1942), and the John Elliot Memorial Award of the American Association of Blood Banks (1962).

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:

• 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 segments (vertebrae) may collapse and cause paralysis in one or both legs.

• Kidneys. Along with the bones, the kidneys are probably the commonest 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 be infected; 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 the TB bacillus causes tuberculous meningitis, a condition that is most common in young children but is especially dangerous in the elderly. Patients develop headaches, become drowsy, and eventually comatose. Permanent brain damage is the rule unless prompt treatment is given. Some patients with tuberculous meningitis develop a tumor-like brain mass called a tuberculoma that can cause stroke-like symptoms.
• 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 that cause 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 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:

• 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 remains positive afterfive 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 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 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.

KEY TERMS

Bacillus Calmette-Guérin (BCG)— A vaccine made from a damaged bacillus akin to the tubercle bacillus, which may help prevent serious pulmonary TB and its complications.

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.

Pneumothorax— Air inside the chest cavity, which may cause the 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— Referring 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 "learned" how to survive in its presence.

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

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

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

• close contacts of TB patients, 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 the 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 with positive PPD results and evidence of old disease on the chest x-ray who have never been treated for TB
• patients 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

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."

Tuberculosis

Definition

Tuberculosis (TB) is a contagious and potentially fatal disease that can affect almost any part of the body but manifests mainly as an infection of the lungs. It is caused by a bacterial microorganism, the tubercle bacillus or Mycobacterium tuberculosis. TB infection can either be acute and short-lived or chronic and long-term.

Description

Although TB can be prevented, treated, and cured with proper treatment and medications, scientists have never been able to eliminate it entirely. The organism that causes tuberculosis, popularly known as consumption, was discovered in 1882. Because antibiotics were unknown, the only means of controlling the spread of infection was to isolate patients in private sanatoria or hospitals limited to patients with TB—a practice that continues to this day in many countries. TB spread very quickly and was a leading cause of death in Europe. At the turn of the twentieth century more than 80% of the people in the United States were infected before age 20, and tuberculosis was the single most common cause of death. Streptomycin was developed in the early 1940s and was the first antibiotic effective against the disease. The number of cases declined until the mid- to late-1980s, when overcrowding, homelessness, immigration, decline in public health inspections, decline in funding, and the AIDS epidemic caused a slight resurgence of the disease. The increase in TB in the United States peaked in 1992, and new cases reported in the United States continue to decrease as of 2004. Yet the number of cases in foreign-born individuals is rising, and the number of deaths from TB has been rising, making TB a leading cause of death from infection throughout the world. It is estimated that in the next 10 years 90 million new cases of TB will be reported, with the result of 30 million deaths, or about 3 million deaths per year.

Several demographic groups are at a higher risk of contracting tuberculosis. Tuberculosis is more common in elderly persons. More than one-fourth of the nearly 23,000 cases of TB in the United States in 1995 were reported in people above age 65. TB also is more common in populations where people live under conditions that promote infection, such as homelessness and injection drug use. In the late 1990s, two-thirds of all cases of TB in the United States affected African Americans, Hispanics, Asians, and persons from the Pacific Islands. Finally, the high risk of TB includes people who have a depressed immune system. High-risk groups include alcoholics, people suffering from malnutrition, diabetics, and AIDS patients — and those infected by human immunodeficiency virus (HIV) — who have not yet developed clinical signs of AIDS. TB is the number one killer of women of childbearing age worldwide. In poor countries, women with TB often don't know they have the disease until symptoms become severe.

As of late 2002, TB is a major health problem in certain 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 healthcare 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 for all new immigrants and refugees.

Causes & symptoms

Transmission

Tuberculosis spreads by droplet infection, in which a person breathes in the bacilli released into the air when a TB patient exhales, coughs, or sneezes. However, TB is not considered highly contagious compared to other infectious diseases. Only about one in three people who have close contact with a TB patient, and fewer than 15% of more remote contacts, are likely to become infected. Unlike many other infections , TB is not passed on by contact with a patient's clothing, bed linens, or dishes and cooking utensils. Yet if a woman is pregnant, her fetus may contract TB through blood or by inhaling or swallowing the bacilli present in the amniotic fluid.

Once inhaled, water in the droplets evaporates and the tubercle bacilli may reach the small breathing sacs in the lungs (the alveoli), 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. The likelihood of acquiring the disease increases with the concentration of bacilli in the air, and the seriousness of the disease is determined by the number of bacteria with which a patient is infected.

Ninety percent of patients who harbor M. tuberculosis do not develop symptoms or physical evidence of the disease, and their x rays remain negative. They are not contagious; however, these individuals may get sick at a later date and then pass on TB to others. Though it is impossible to predict whether a person's disease will become active, researchers surmise that more than 90% of cases of active tuberculosis come from this pool of people. 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. 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 second exposure to the tubercle bacillus.

Pulmonary tuberculosis

Pulmonary tuberculosis is TB that affects the lungs, and represents about 85% of new cases diagnosed. It usually presents with a cough , which may or may not produce sputum. In time, more sputum is produced that is streaked with blood. The cough may be present for weeks or months and may be accompanied by chest pain and shortness of breath. Persons with pulmonary TB often run a low-grade fever and suffer from night-sweats. The patient often loses interest in food and may lose weight. 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. 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.

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. Abut 15% of newly diagnosed cases of TB are extrapulmonary, with a higher proportion of these being HIV-infected persons. The usual progression of the disease is to begin in the lungs and spread 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.
• Kidneys. Along with the 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.
• Female reproductive organs. The ovaries in women may be infected; 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 mild 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.
• Meninges. The meninges are tissues that cover the brain and the spinal cord. Infection of the meninges by the TB bacillus causes tuberculous meningitis , a condition that is most common in young children and the elderly. It is extremely dangerous. Patients develop headaches, become drowsy, and eventually comatose. Permanent brain damage can result without prompt treatment.
• 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 that cause marked weakness and weight loss, severe anemia , and gradual wasting of the body.

Diagnosis

TB is diagnosed through laboratory test results. The standard test for tuberculosis infection, the tuberculin skin test, detects the presence of infection, not of active TB. Skin testing has been done for more than 100 years. In this process, 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 a good measure of the presence of tubercular infection. The PPD test, also called the Mantoux test, is not always 100% accurate; it can produce false positive as well as false negative results. The test may indicate 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 and can be used on people who have had a suspicious chest x ray, on those who have had close contact with a TB patient, and persons who come from a country where TB is common.

Because of the multiple and varied symptoms of TB, diagnosis on the basis of external symptoms is not always possible. TB is often discovered by an abnormal chest x ray or other test result rather than by a claim of physical discomfort by the patient. After an irregular x ray, a PPD test is always done to show whether the patient has been infected. To verify the test results, the physician obtains a sample of sputum or a tissue sample (biopsy) for culture. In cases where other areas of the body might be infected, such as the kidney or the brain, body fluids other than sputum (urine or spinal fluid, for example) can be used for culture.

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 2002, 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 drug-resistant strains of mycobacteria.

Treatment

Because of the nature of tuberculosis, the disease should never be treated by alternative methods alone. Alternative treatments can help support healing, but treatment of TB must include drugs and will require the care of a physician. Any alternative treatments should be discussed with a medical practitioner before they are applied.

Supportive treatments include:

• Diet. Nutritionists recommend a whole food diet including raw foods, fluids, and particularly pears and pear products (pear juice, pear sauce), since pears may help heal the lungs. Other helpful foods include fenugreek, alfalfa sprouts, garlic , pomegranate, and yogurt or kefir. Four tablespoons of pureed steamed asparagus at breakfast and dinner taken for a few months may also be helpful.
• Nutritional therapy. Nutritionists may recommend one or many of the following vitamins and minerals: vitamin A at 300,000 IU for the first three days, 200,000 IU for the next two days, then 50,000 IU for several weeks; beta-carotene at 25,000-50,000 IU; vitamin E at up to 1,000 IU daily unless the patient is a premenopausal woman with premenstrual symptoms; lipotrophic formula (one daily); deglycerolized licorice ; citrus seed extract; vitamin C ; lung glandular; essential fatty acids ; vitamin B complex ; multiminerals; and zinc.
• Herb therapy may use the tinctures of echinacea , elecampane, and mullein taken three times per day, along with three garlic capsules three times per day.
• Hydrotherapy may be used up to five times weekly. Dr. Benedict Lust , the founder of naturopathy, supposedly cured himself of tuberculosis by using hydrotherapy.
• Juice therapy. Raw potato juice, may be taken three times daily with equal parts of carrot juice plus one teaspoon of olive or almond oil, one teaspoon of honey, beaten until it foams. Before using the potato juice, starch should be allowed to settle from the juice.
• Topical treatment may use eucalyptus oil packs, grape packs or grain alcohol packs.

Professional practitioners may also treat tuberculosis using cell therapy , magnetic field therapy, or traditional Chinese medicine . Fasting may be undertaken, but only with a doctor's supervision.

Allopathic treatment

Drug therapy

Five drugs are most commonly used today to treat tuberculosis: isoniazid (INH), rifampin, pyrazinamide, streptomycin, and ethambutol. Of the five medications, INH is the most frequently used drug for both treatment and prevention. The first three drugs may be given in the same capsule to minimize and treat active TB 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. A physician must monitor side effects and conduct monthly sputum tests. In 2002, the Centers for Disease Control (CDC) worked with medical organizations to release new guidelines that better individualize the drug regimens received by TB patients depending on their disease symptoms and severity. Many can now receive once-weekly doses of rifapentine in the continuation phase of treatment.

The first large scale trial of a new agent to treat TB began in 2002. The promising new drug, called moxifloxacin, may mean a shorter treatment course for TB sufferers in the near future. It will also be tested in combination with rifapentine, and researchers believe that using the drugs together will mean a less frequent dosing schedule for patients.

Drug resistance has become a problem in treating TB. When patients do not take medication properly or for long enough periods of time, the TB organisms may become drug resistant. This makes the patient vulnerable to further infection and allows the TB organism to develop resistance.

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.

Expected results

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 are usually effective when necessary. 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, other seldom-used drugs may be tried because the tubercle bacilli have not yet developed resistance to them.

Prevention

Vaccination is widely used as a prevention measure for 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, 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. Though the vaccine has been proven beneficial and fairly safe, its use is still controversial. It is not clear whether the vaccine's effectiveness depends on the population in which it is used or on variations in its formulation. Recently, efforts have been focused on developing a new vaccine.

Generally, prevention focuses on the prevention of transmission, skin-testing high-risk persons and providing preventive drug therapy to people at risk. Measures such as avoidance of overcrowded and unsanitary conditions are necessary aspects of prevention. Hospital emergency rooms and similar locations can be treated with ultraviolet light, which has an antibacterial effect.

INH is also given to prevent TB, and decreases the incidence of TB by about 60% over the life of the patient. INH is effective when taken daily for 6 to 12 months by people in high-risk categories who are under 35 years of age. About 1% of patients in preventive treatment develop toxicity. Because INH carries the risk of side effects (liver inflammation, nerve damage, changes in mood and behavior), it is important for its use to be monitored and to give it only to persons at special risk.

Unfortunately, failure of TB patients to complete the full course of their drugs adds to TB incidence and encourages development of drug-resistant strains of the disease. As scientists try to develop drugs that require shorter courses, physicians must work with patients to encourage compliance with their treatments. Even if symptoms go away, patients often have to continue their drug treatment for six months to be sure to stop the spread of their TB infection to others.

Resources

BOOKS

Burton-Goldberg Group. Alternative Medicine: The Definitive Guide. Puyallup, WA: Future Medicine Publishing, Inc., 1994.

"Infectious Diseases Caused by Mycobacteria." Section 13, Chapter 157 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 2001.

Merck Manual of Medical Information: Home Edition. Edited by Robert Berkow, et al. Whitehouse Station, NJ: Merck Research Laboratories, 1997.

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

Smolley, Lawrence A., and Debra F. Bryse. Breathe Right Now: A Comprehensive Guide to Understanding and Treating the Most Common Breathing Disorders. New York: W. W. Norton & Co., 1998.

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-Out-break 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 (Fall 2002) (3 Suppl.): 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. 432 Park Avenue South, New York, NY 10016. (800) LUNG-USA. <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. nyhealth@health.state.ny.us.

University of Wisconsin-Madison Health Sciences Libraries. "Pulmonary Medicine" Healthweb. http://www.biostat.wisc.edu/chslib/hw/pulmonar.

Amy Cooper

Teresa G. Odle

Rebecca J. Frey, PhD

Tuberculosis

Introduction

Disease History, Characteristics, and Transmission

Scope and Distribution

Treatment and Prevention

Impacts and Issues

Primary Source Connection

BIBLIOGRAPHY

Introduction

Tuberculosis, often known as TB, is a disease caused by infection with the bacterium called Mycobacterium tuberculosis. A few other types of mycobacterium are capable of causing a tuberculosislike illness, but are only rarely encountered. Most commonly, the infection affects the lungs. However, along with the pulmonary form of tuberculosis, the infection can become extrapulmonary, affecting other parts of the body, including the central nervous system, kidneys, joints, spine, and skin.

In a tuberculosis infection, symptoms may be absent initially. Sometime later, in about 10% of those who are infected, this so-called latent tuberculosis, which cannot be spread from person to person, becomes active and more serious, killing up to 50% of those who are infected. The presence of the latent form of tuberculosis is especially dangerous in people whose immune systems are not functioning properly, such as those with acquired immunodeficiency syndrome (AIDS, also cited as acquired immune deficiency syndrome).

Disease History, Characteristics, and Transmission

Tuberculosis is an ancient disease. In about 400 BC, the Greek physician Hippocrates (460–377 BC) described a disease that is thought to have been tuberculosis. Then the disease was called phthisis, a name derived from the Greek word meaning “to waste away”. This description was apt, since, then, as now, a hallmark feature of tuberculosis is weight loss and physical deterioration that occurs over the often considerable length of time that the infection persists. In more recent times, the characteristic physical wasting associated with the disease led to its popular name—consumption.

A fragment of M. tuberculosis DNA was found in lung tissue from an Egyptian mummy approximately 3,000 years old. It has been argued that diseases like tuberculosis were unknown in South America until being introduced by European explorers hundreds of years ago. However, this may not be true, since preserved remains of people with tuberculosislike lung damage have been dated to hundreds of years before the time of Columbus. (There is no evidence that the Viking explorations, which pre-date Columbus, took them south of the equator.) It seems likely that tuberculosis may have been globally common even centuries ago.

The name tuberculosis was coined in 1839 by Johann Schönlein. At that time, the pathogen responsible for the disease had not been discovered. M. tuberculosis was finally identified in 1882 by Robert Koch (1843–1910), one of the pioneers of the study of bacteria (bacteriology). In 1890, Koch reported on the extraction of a bacterial protein from dead bacteria recovered from tuberculosis infections. The protein, which he called tuberculin, is still important as a means of detecting the presence of the bacteria. With the discovery and use of x rays at the end of the nineteenth century, the presence of the lung infection that is a consequence of the growth of M. tuberculosis was revealed. On x-ray images, the masses of bacteria that develop are seen as more opaque regions in the lungs.

Lung infection with M. tuberculosis results from inhaling droplets of moisture that contain the bacteria. Most commonly this occurs when someone who has the infection expels droplets from their lungs by coughing. The droplets, which tend to be 0.5–5 microns in diameter (a micron is a millionth of a meter) can contain more than 40,000 living M. tuberculosis bacteria. M. tuberculosis also can be transmitted in milk that has not been pasteurized to kill the bacteria. Symptoms of this form of tuberculosis, which is called active tuberculosis, include a feeling of tiredness, loss of weight, a fever that tends to occur during sleep, chills, and a cough that persists for weeks. The coughing can dislodge and expel sputum, which may be tinged with blood, as the infection can damage cells lining the lungs. In some people, the infection can spread beyond the lungs to other parts of the body. If not treated, this extrapulmonary tuberculosis is fatal in up to 50% of the cases. The extrapulmonary form cannot be spread from person to person.

Scope and Distribution

Tuberculosis is a common disease with a global distribution. About 30% of the world's population—some 2 billion people—have tuberculosis, according to the World Health Organization (WHO). The organization has estimated that new infections are occurring at the rate of one every second. In 2004, almost 15 million people had the active form of tuberculosis, according to the WHO, and about 1.7 million people died of the disease, most in developing countries. Nearly 9 million of these cases had developed during that year.

Some people are at increased risk for contracting tuberculosis. These include children, whose immune systems are not fully developed, and elderly people, whose immune function may have deteriorated. The immune system can also deteriorate due to diseases (for example, acquired immunodeficiency syndrome, or AIDS), poor nutrition, and the physical consequences of chronic alcohol or drug abuse. In addition, immune function may be deliberately suppressed in transplant patients to help minimize the chance of rejection of the transplanted organ. Health care providers may also be at risk of contracting tuberculosis, since they are exposed more frequently to people with the infection. Other risk factors include diabetes, various cancers, kidney disease, and abnormally low body weight.

While present in every country, tuberculosis can be especially prevalent in regions where health care is substandard and poverty affects the overall health of the inhabitants. Traditionally, this has been a more significant problem in underdeveloped and developing countries. However, even in the United States, increasing poverty has contributed to a resurgence of tuberculosis. More than 14,000 cases of tuberculosis were reported in the United States in 2004, according to the CDC.

Treatment and Prevention

The diagnosis of tuberculosis relies of the recognition of the symptoms and the detection of the infection. The presence of the lung infection can be visualized using a chest x ray. M. tuberculosis also can be detected, either by obtaining sputum samples and growing the organism or by isolating protein components of the bacterium. The latter test can be faster, since the bacterium can be difficult to grow in laboratory conditions. For example, the length of time for M. tuberculosis to grow and divide in the nutritionally rich conditions of a laboratory culture dish can be 16–20 hours, which is far longer than the 15–20 minutes required by the common intestinal bacterium Escherichia coli. Thus, identification of the tuberculosis bacterium by laboratory culturing can take days.

A well-known test for tuberculosis is called a skin test. In this test, the tuberculin protein from M. tuberculosis is injected just under the skin of the forearm. The development of redness and swelling at the injection site within several days indicates that the person has at least been exposed to the infection. The test does not necessarily show that the infection is active, and so is valuable in the detection of the latent form of tuberculosis.

In May 2005, the U.S. Food and Drug Administration approved the QuantiFERON -TB Gold test for use in the diagnosis of M. tuberculosis infection in the United States. The test detects the release of a compound called interferon-gamma from blood cells in those who have tuberculosis. The test has been approved as a replacement for the skin test, and to confirm the results of the skin test. As of 2007, the test is not widely available, and can still be beyond the budget of smaller health care centers.

In the past, the treatment of tuberculosis was associated with images of hospital wards filled with bedridden patients or images of people slowly recovering from the infection while at sanatoriums located in the countryside. Even into the 1960s, sanatoriums that were located in areas with clean, dry air were a popular part of treatment for tuberculosis.

Sanatoriums did aid recovery, but their usefulness was supplanted during the 1960s by the introduction of antibiotics that were effective against M. tuberculosis. The antibiotic treatment needs to be carried out for up to six months to be effective, in part because of the slow growth of the bacteria (many antibiotics are effective only on bacteria that are growing). It can be tempting to stop taking the antibiotics before the end of the prescribed period of treatment, since the patient begins to feel better after only a few weeks. But, as with other bacterial infections, discontinuing treatment prematurely is dangerous, since it can allow surviving bacteria to reestablish the infection. In fact, the surviving bacteria may be resistant to the antibiotics used, making treatment more difficult and more expensive.

The first few decades of the antibiotic therapy were resoundingly successful. Over 90% of tuberculosis infections were cured. However, in the early years of the twenty-first century, resistance to the antibiotics emerged and became more prevalent.

A tuberculosis vaccine does exist. It was developed during World War I (1914–1918) by French scientists Albert Calmette (1863–1933) and Camille Guérin, (1872–1961) and was first used in 1921. The vaccine uses a live, but weakened, strain of the bacterium Mycobacterium bovis. BCG (for Bacillus-Calmette-Guérin) is still the only vaccine for tuberculosis, although researchers are continuing to investigate new vaccine candidates.

The vaccine is not recommended for use in the United States by the CDC. This is due to a combination of factors—the relatively low number of cases of the disease in the United States, the vaccine's 80% success rate, and the risks associated with the use of live bacteria in a vaccine. Health care providers and others at higher risk to acquire the infection are vaccinated, however, as are people who have the multidrug-resistant form of tuberculosis. People who come to the United States from areas of the world where tuberculosis is prevalent are required to be examined for the presence of the active and latent forms of the infection and to be treated if necessary.

Efforts to develop new tuberculosis vaccines are ongoing. Several vaccine candidates have been developed using recombinant genetic techniques. These techniques involve splicing genetic material into an organism that can then ferry the recombined genetic material into animals or humans to generate antibodies to combat the infection. As of 2007, the U.S. National Institute of Allergy and Infectious Diseases and other agencies around the world continue to sponsor trials to evaluate the effectiveness and safety of the recombinant vaccines.

IN CONTEXT: EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS (XDR TB)

In May 2007 a Centers for Disease Control and Prevention (CDC) investigation of a suspected case of Extensively Drug-Resistant Tuberculosis (XDR TB) made news headlines around the world and heightened public awareness of XDR TB. The case involved a U.S. citizen that the CDC publicly asserted had a “potentially infectious XDR TB who traveled to and from Europe on commercial flights between May 12 and May 24, (2007) and then re-entered the United States at the Canada-U.S. border via automobile.”

Because of the international travel implications, for the first time in more than 40 years, CDC issued a Federal isolation order under authority of the U.S. Public Health Service Act. Such are orders are rare because state and local health departments usually order isolation (in fact, in early June 2007, the Denver Health Authority Public Health Department issued an order that the patient be detained for treatment at the Denver area hospital where the patient had ultimately been transferred for treatment and so the federal order was lifted).

Although the patient was asymptomatic and physicians later stated that he did not appear to be highly infectious, the case came under intense media scrutiny. At the time of the printing of this book, many issues existed concerning the facts and timeline of events related to the case, including the investigation of how the patient may have initially contracted the disease and the events surrounding the response by a number of health and security agencies to his infection and subsequent travel. Intense media coverage was also fueled by initial disinformation about the nature of transmission, with reports failing to specify that transmission of the bacterium responsible usually takes prolonged contact.

The CDC states that Extensively drug-resistant tuberculosis (XDR TB) is “a relatively rare type of multidrug-resistant tuberculosis (MDR TB). It is resistant to almost all drugs used to treat TB, including the two best first-line drugs: isoniazid and rifampin. XDR TB is also resistant to the best second-line medications: fluoroquinolones and at least one of three injectable drugs (i.e., amikacin, kanamycin, or capreomycin).”

“Because XDR TB is resistant to the most powerful first-line and second-line drugs, patients are left with treatment options that are much less effective and often have worse treatment outcomes.”

“XDR TB is of special concern for persons with HIV infection or other conditions that can weaken the immune system. These persons are more likely to develop TB disease once they are infected, and also have a higher risk of death once they develop TB disease.”

“The risk of acquiring XDR TB in the United States appears to be relatively low. However, it is important to acknowledge the ease at which TB can spread. As long as XDR TB exists, the United States is at risk and must address the threat.”

SOURCE: Centers for Disease Control and Prevention, Division of Tuberculosis Elimination National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention

Impacts and Issues

Throughout history, tuberculosis has been a threat to health and life. For example, in the mid-nineteenth century, about 25% of all deaths were due to tuberculosis. The devastation caused to families and the economic consequences of the loss of so many wage-earners were immense. At that time, the disease was especially prevalent in children, adolescents, and young adults; whole generations of people were affected.

This situation changed during the 1940s with the introduction of antibiotics that were effective against M. tuberculosis. There was a steep drop in the number of cases of tuberculosis worldwide. This fueled optimism that the disease had been controlled. But, as with other bacterial diseases that were initially suppressed by anti-biotic therapy, this optimism was premature. Several factors have fueled the return of tuberculosis, including the increasing incidence of immunosuppressive diseases (primarily AIDS), the impact of growing gap in health care between the richer and poorer nations, and the emergence of a type of tuberculosis infection that is resistant to multiple antibiotics.

Currently, the impact of tuberculosis is most severe in the poorest regions of the world. For example, South Africa had the highest incidence of tuberculosis in the world in 2004, according to the WHO, and India had the most infections. WHO statistics show that more than 80% of the new cases of tuberculosis in 2004 were found among people living in Africa, Southeast Asia (including India), and the Western Pacific.

In other countries, including the United States, tuberculosis is less common and is mainly found in cities among the poor and homeless. In the United States, a program called Directly Observed Therapy (DOT) is being used by some states to help deal with the rising prevalence of tuberculosis. The program, which focuses on the poor and homeless in cities such as New York, involves direct meetings between the patient and a health care provider and the delivery of every scheduled dose of tuberculosis medication by that health care provider. DOT has been successful in reducing the number of reported cases of the disease.

DOT is also used in 182 other nations. It is estimated that this surveillance program, which relies on the microscopic detection of M. tuberculosis in blood samples, detected over 60% of the cases of tuberculosis worldwide in 2005.

In 1990, there were 7,537,000 tuberculosis cases worldwide, according to the WHO, with approximately 30,000 of those cases reported in the United States. The 14,097 reported cases in the United States in 2005 represent a 47% decline from 1990. However, in some states and among certain ethnic groups in the country, the prevalence of tuberculosis is still increasing. Furthermore, the situation elsewhere in the world is bleak. During the decade from 2000–2009, the WHO projects that 30 million people will die of tuberculosis. Since many cases are never reported, the actual death toll likely will be much higher.

In 2004, there were almost 9 million new cases of tuberculosis around the world, according to the WHO. Of these, 740,000 infections arose in people already infected with the human immunodeficiency virus (HIV). The immunocompromised condition of these patients makes it more likely that their cases of tuberculosis will be more serious, life threatening, and costly to treat.

IN CONTEXT: SCIENTIFIC, POLITICAL, AND ETHICAL ISSUES

The interplay of complex ethical and social considerations is also evident when considering the general rise of infectious diseases that sometimes occurs as an unintended side effect of the otherwise beneficial use of medications. Nearly half the world's population, for example, is infected with the bacterium causing TB (although for most people the infection is inactive) yet the organism causing some new cases of TB is evolving toward a greater resistance to the antibiotics that were once effective in treating TB. Such statistics also take on added social dimension when considering that TB disproportionately impacts certain social groups (the elderly, minority groups, and people infected with HIV).

The resurgence of tuberculosis has resulted in part from the increasing prevalence of immunodeficiency diseases, but also from a lack of attention to the control of tuberculosis. As with diseases such as polio, the early success in combating the disease led to complacency regarding control programs, with the result that the disease rebounded.

The emergence of antibiotic-resistant forms of M. tuberculosis is especially troubling. From 2000–2004, according to the CDC, 20% of tuberculosis cases in the United States were resistant to commonly used antibiotics and approximately 2% were resistant to the more potent and more expensive drugs employed as a next step. MDR-TB (multidrug-resistant TB) includes strains of tuberculosis that are resistant to at least two first-line drugs—isoniazid and rifampicin—used to treat TB.

Extremely drug-resistant tuberculosis (XDR-TB) is another emerging threat, according to the WHO. The disease is initially latent; when the symptoms appear and treatment is initiated, the resistance of the infection to virtually all antibiotics makes XDR-TB extremely difficult to treat.

As of 2007, identified XDR-TB is rare. Yet, the WHO estimates that in 2004 there were over 500,000 cases worldwide and that this number will rise in the coming years. The increased expense of treating XDRTB will become a significant issue for poorer nations. By 2015, according to the WHO, the treatment of tuberculosis will cost $650 million each year, in part due to elaborate airborne precautions in hospitals that include isolation rooms with specialized air exchanges and N-95 masks that can serve as a barrier for the extra-small bacteria that cause tuberculosis. More than $600 million will also be needed for programs aimed at curbing the spread of the multidrug-resistant bacteria. As of 2007, the funds budgeted by various governments around the world to battle tuberculosis total $250 million—$400 million less than the projected $650 million needed. In 2006, the WHO spearheaded the Stop TB Partnership, an initiative that aims to save 14 million lives by 2015, partly by encouraging nations worldwide to commit the needed money. The campaign also seeks to increase access to treatment for nations most in need, and to reduce the economic burden associated with the costs of tuberculosis health care and the work force losses due to the disease.

Primary Source Connection

The World Care Council (WCC), based in France, is a non-governmental organization (NGO) dedicated to mobilizing public and private forces together worldwide in the fight against AIDS, malaria, and tuberculosis. The Patients Charter for Tuberculosis Care, developed by the WCC, aims to empower people with tuberculosis by describing their rights and responsibilities regarding the disease. WCC intends for the charter to become the catalyst for effective collaboration between health providers, authorities, and persons with TB. The charter is the first global patient-powered standard for care.

The Patients’ Charter for Tuberculosis Care

The Patients’ Charter outlines the Rights and Responsibilities of People with Tuberculosis. It empowers people with the disease and their communities through this knowledge. Initiated and developed by patients from around the world, the Charter makes the relationship with health care providers a mutually beneficial one.

The Charter sets out the ways in which patients, the community, health providers, both private and public, and governments can work as partners in a positive and open relationship with a view to improving tuberculosis care and enhancing the effectiveness of the health care process. It allows for all parties to be held more accountable to each other, fostering mutual interaction and a ‘positive partnership’.

Developed in tandem with the International Standards for Tuberculosis Care to promote a ‘patient-centered’ approach, the Charter bears in mind the principles on health and human rights of the United Nations, UNESCO, WHO, Council of Europe, as well as other local and national charters and conventions.

The Patients Charter for Tuberculosis Care practices the principle of Greater Involvement of People with TB. This affirms that the empowerment of people with the disease is the catalyst for effective collaboration with health providers and authorities, and is essential to victory in the fight to stop TB. The Patients’ Charter, the first global ‘patient-powered’ standard for care, is a cooperative tool, forged from common cause, for the entire TB Community.

PATIENTS’ RIGHTS

You have the right to:

Care

• The right to free and equitable access to tuberculosis care, from diagnosis through treatment completion, regardless of resources, race, gender, age, language, legal status, religious beliefs, sexual orientation, culture or having another illness.
• The right to receive medical advice and treatment which fully meets the new International Standards for Tuberculosis Care, centering on patient needs, including those with MDR-TB or TB-HIV coinfections, and preventative treatment for young children and others considered to be at high risk.
• The right to benefit from proactive health sector community outreach, education and prevention campaigns as part of comprehensive care programs.

Dignity

• The right to be treated with respect and dignity, including the delivery of services without stigma, prejudice or discrimination by health providers and authorities.
• The right to quality health care in a dignified environment, with moral support from family, friends and the community.

Information

• The right to information about what health care services are available for tuberculosis, and what responsibilities, engagements, and direct or indirect costs, are involved.
• The right to receive a timely, concise and clear description of the medical condition, with diagnosis, prognosis (an opinion as to the likely future course of the illness), and treatment proposed, with communication of common risks and appropriate alternatives.
• The right to know the names and dosages of any medication or intervention to be prescribed, its normal actions and potential side-effects, and its possible impact on other conditions or treatments.
• The right of access to medical information which relates to the patient's condition and treatment, and a copy of the medical record if requested by the patient or a person authorized by the patient.
• The right to meet, share experiences with peers and other patients, and to voluntary counseling at any time from diagnosis through treatment completion.

Choice

• The right to a second medical opinion, with access to previous medical records.
• The right to accept or refuse surgical interventions if chemotherapy is possible, and to be informed of the likely medical and statutory consequences within the context of a communicable disease.
• The right to choose whether or not to take part in research programs without compromising care.

Confidence

• The right to have personal privacy, dignity, religious beliefs and culture respected.
• The right to have information relating to the medical condition kept confidential, and released to other authorities contingent upon the patient's consent.

Justice

• The right to make a complaint through channels provided for this purpose by the health authority, and to have any complaint dealt with promptly and fairly.
• The right to appeal to a higher authority if the above is not respected, and to be informed in writing of the outcome.

Organization

• The right to join, or to establish, organizations of people with or affected by tuberculosis, and to seek support for the development of these clubs and community based associations through the health providers, authorities, and civil society.
• The right to participate as ‘stakeholders’ in the development, implementation, monitoring and evaluation of TB policies and programs with local, national and international health authorities.

Security

• The right to job security after diagnosis or appropriate rehabilitation upon completion of treatment.
• The right to nutritional security or food supplements if needed to meet treatment requirements.

PATIENTS’ RESPONSIBILITIES

You have the responsibility to:

Share Information

• The responsibility to provide the health care giver as much information as possible about present health, past illnesses, any allergies and any other relevant details.
• The responsibility to provide information to the health provider about contacts with immediate family, friends and others who may be vulnerable to tuberculosis or may have been infected by contact.

WORDS TO KNOW

ACTIVE INFECTION: An active infection is one which is currently producing symptoms or in which the infective agent is multiplying rapidly. In contrast, a latent infection is one in which the infective agent is present, but not causing symptoms or damage to the body, nor reproducing at a significant rate.

AIRBORNE PRECAUTIONS: Airborne precautions are procedures that are designed to reduce the chance that certain disease-causing (pathogenic) microorganisms will be transmitted through the air.

AIRBORNE TRANSMISSION: Airborne transmission refers to the ability of a disease-causing (pathogenic) microorganism to be spread through the air by droplets expelled during sneezing or coughing.

ANTIBIOTIC RESISTANCE: The ability of bacteria to resist the actions of antibiotic drugs.

LATENT INFECTION: An infection already established in the body but not yet causing symptoms, or having ceased to cause symptoms after an active period, is a latent infection.

Follow Treatment

• The responsibility to follow the prescribed and agreed treatment plan, and to conscientiously comply with the instructions given to protect the patient's health, and that of others.
• The responsibility to inform the health provider of any difficulties or problems with following treatment, or if any part of the treatment is not clearly understood.

Contribute to Community Health

• The responsibility to contribute to community well being by encouraging others to seek medical advice if they exhibit the symptoms of tuberculosis.
• The responsibility to show consideration for the rights of other patients and health care providers, understanding that this is the dignified basis and respectful foundation of the TB Community.

Show Solidarity

• The moral responsibility of showing solidarity with other patients, marching together towards cure.
• The moral responsibility to share information and knowledge gained during treatment, and to pass this expertise to others in the community, making empowerment contagious.
• The moral responsibility to join in efforts to make the community TB Free.

World Care Council

WORLD CARE COUNCIL. “THE PATIENTS’ CHARTER FOR TUBERCULOSIS CARE.” 2006. AVAILABLE ONLINE AT< HTTP://WWW.WHO.INT/TB/PUBLICATIONS/2006/ISTC_CHARTER.PDF> (ACCESSED APRIL 10, 2007).

See AlsoAirborne Precautions; Antibiotic Resistance; Developing Nations and Drug Delivery; Re-emerging Infectious Diseases; Resistant Organisms.

BIBLIOGRAPHY

Books

Daniel Thomas M. Captain of Death: The Story of Tuberculosis. Rochester, NY: University of Rochester Press, 2005.

Gandy, Matthew, and Alimuddin Zumla. The Return of the White Plague: Global Poverty and the ‘New’ Tuberculosis. New York: Verso, 2003.

Mayho, Paul, and Richard Coker. The Tuberculosis Survival Handbook. West Palm Beach, FL: Merit Publishing International, 2006.

Periodicals

Hoffman, Michelle. “New Medicine for Old Mummies: Diagnosing Disease in Some Very Old ‘Patients'”. American Scientist 86 (May–June 1998).

Web Sites

World Health Organization. “World TB Day—March 24th.” <http://www.stoptb.org/events/world_tb_day/> (accessed April 10, 2007).

Brian Hoyle

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.

GEM_sbtuberculosis.sgm

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 States have 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.

Demographics

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.

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.

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.

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:

• Bones. TB is particularly likely to attack the spine and the ends of the long bones. If not treated, the spinal segments (vertebrae) may collapse and cause paralysis in one or both legs.
• Kidneys. Along with the bones, the kidneys are probably the commonest 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 be infected; 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 the TB bacillus causes tuberculous meningitis, a condition that is most common in young children but is especially dangerous in the elderly. Patients develop headaches, become drowsy, and eventually comatose. Permanent brain damage is the rule unless prompt treatment is given. Some patients with tuberculous meningitis develop a tumor-like brain mass called a tuberculoma that can cause stroke-like symptoms.
• 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 that cause marked weakness and weight loss, severe anemia, and gradual wasting of the body.

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 MantouxPPDskin 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.

KEY TERMS

Bacillus Calmette-Guérin (BCG) —A vaccine made from a damaged bacillus akin to the tubercle bacillus, which may help prevent serious pulmonary TB and its complications.

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.

Pneumothorax —Air inside the chest cavity, which may cause the 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 —Referring 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 “learned” how to survive in its presence.

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

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

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 2007, 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 drug-resistant 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:

• 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 remains 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 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 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:

• close contacts of TB patients, 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 the 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 with positive PPD results and evidence of old disease on the chest x-ray who have never been treated for TB
• patients 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

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.

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.

David A. Cramer MD

Rebecca J. Frey Ph.D.

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〉.

OTHER

Centers for Disease Control and Prevention. August 2001. 〈http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/rr4906a1.htm〉.

Columbia Presbyterian Medical Center. August 2001. 〈http://www.cpmc.columbia.edu/tbcpp〉.

Department of Health Services: Australia. August 2001. 〈http://www.dhs.vic.gov.au/phb/hprot/tb/tbm/tb2.html〉.

State Tuberculosis Control Offices. August 2001. 〈http://www.cdc.gov/nchstp/tb/tboffices.htm〉.

World Health Organization. August 2001. 〈http://www.who.int/gtb〉.