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Tuberculosis

Tuberculosis

Definition

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

Description

Overview

Tuberculosis was popularly known as consumption for a long time. Scientists know it as an infection caused by M. tuberculosis. In 1882, the microbiologist Robert Koch discovered the tubercle bacillus, at a time when one of every seven deaths in Europe was caused by TB. Because antibiotics were unknown, the only means of controlling the spread of infection was to isolate patients in private sanitoria or hospitals limited to patients with TBa 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 (18971991)

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 todayat 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 tuberculosiswhich is the so-called tuberculin skin testdetects 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 olderaverage age 62and 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."

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Tuberculosis

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 TBa 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 olderaverage age 62and 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): 171172.

"'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): 11141117.

"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): 255265.

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): 11691172.

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.): 189196.

"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): 879905.

Su, W. J. "Recent Advances in the Molecular Diagnosis of Tuberculosis." Journal of Microbiology, Immunology, and Infection 35 (December 2002): 209214.

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. [email protected]

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

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Tuberculosis

TUBERCULOSIS

TUBERCULOSIS was the leading cause of death in the United States during the nineteenth century, responsible at times for as many as one of every four deaths. Although the death rate from tuberculosis steadily declined beginning in the mid-nineteenth century, it persisted as a major public health problem well into the twentieth century, when programs of public health education, disease surveillance and diagnosis, and the availability of antibiotics and vaccination helped to curb its incidence. After World War II, the death rate was only a small fraction of what it was a century earlier, but by the 1990s, the emergence of tuberculosis strains resistant to antibiotics and the connections between tuberculosis and AIDS again made it a significant health concern.

Before the late nineteenth century, various namesincluding consumption and phthisiswere used to describe the dry, persistent cough, throat irritations, chest and shoulder pains, and difficult breathing accompanied by emaciation that characterized pulmonary tuberculosis. The incidence of tuberculosis grew dramatically in Europe beginning in the eighteenth century, and although its incidence in the United States was less severe, it had grown into the leading cause of death in the United States by the mid-nineteenth century. Other than being slightly more prevalent in women than men, the disease respected no boundaries, afflicting Americans of all ages, races, ethnicities, and social and economic stations.

Tuberculosis in Nineteenth-Century Life

While sudden and dramatic epidemics of cholera, diphtheria, smallpox, and yellow fever commanded public attention, tuberculosis quietly became a regular feature of nineteenth-century American life. Healers diagnosed tuberculosis on the basis of its physical symptoms, but they were at a loss to offer a definitive cause or cure for the disease. For much of the nineteenth century, it was thought that tuberculosis was hereditary, and therefore, that it was noncontagious and could not be transmitted from person to person. It was presumed that there was some familial disposition that made a person susceptible to the disease and that the interaction of the inherited constitution with environmental or behavioral "irritations," such as rich diets, sedentary occupations, and cold, wet climates, brought on the disease. The remedies emphasized changing the irritants, whether to a mild or bland diet, to an active lifestyle with exercise, or to a residence that was mild and dry. Between 1840 and 1890, thousands of Americans with tuberculosis, particularly from New England, became "health seekers," moving to where they believed the wholesome, restorative climates would give them relief. These "lungers," as tuberculosis patients were colloquially called, moved first to Florida, and later to the West and Southwest, settling in the deserts and mountains of Arizona, California, Colorado, and New Mexico. One in four migrants to California and one in three migrants to Arizona during the second half of the nineteenth century went looking to improve their health.

During the 1830s, tuberculosis was responsible for one in every four deaths, but by the 1880s, the mortality rate had declined to one in every eight deaths. In major American cities, the death rate from tuberculosis at the end of the nineteenth century (200 deaths per 100,000 population) was essentially half of what it was a century earlier. Improvements in diets and in living conditions, along with natural selection and genetic resistance in the population, contributed to the declining rates. Even as the mortality rates from tuberculosis declined in the general population, it persisted as a significant health problem among America's growing immigrant population, most of whom lived in the crowded, dank, and dirty tenements of America's urban centersliving conditions that were ripe for the rapid spread of the disease. The incidence of tuberculosis became increasingly associated with immigrants and the impoverished and the overcrowded living conditions they experienced.

Tuberculosis in the Age of Bacteriology

In March 1882, the German bacteriologist Robert Koch announced the discovery of Mycobacterium tuberculosis, the bacillus or bacterium that causes tuberculosis. But medical explanations attributing the cause of tuberculosis to heredity, climate, diet, lifestyle, poor ventilation, and other factors endured through the century and decades would pass before physicians were fully convinced that tuberculosis was contagious and could be transmitted between persons. The medical landmark of Koch's discovery accompanied the growing number of tuberculosis sanatoria being built in Europe and the United States after the 1850s and 1880s, respectively. The sanatorium movement emphasized a therapy regimen based on fresh air, proper diet, and rest, but they also served to remove and to isolate patients with tuberculosis from areas where they might infect others. Among the sanatoria were two founded by America's most prominent physicians of tuberculosis: Edward Livingston Trudeau established a sanatorium at Saranac Lake in the Adirondack Mountains of northeastern New York, and Lawrence Flick established a sanatorium at White Haven, in the Pocono Mountains of eastern Pennsylvania. Trudeau and Flick themselves suffered from tuberculosis, and learned of the benefits of an outdoor life in seeking a cure for their own afflictions. Trudeau's Saranac Lake sanatorium, founded in 1884, became a model for other sanatoria. Flick, believing that tuberculosis was contagious, advocated for a scientific approach to its diagnosis and treatment, as well as the registration of patients and the education of the public about the disease. In 1892, Flick founded the Pennsylvania Society for the Prevention of Tuberculosis, the first state organization in the nation devoted to the control and the elimination of tuberculosis. As other state societies against tuberculosis developed, Flick joined Trudeau, Hermann Biggs, William Welch, William Osler, and others to found in 1904 the National Association for the Study and Prevention of Tuberculosis (NASPT), the forerunner to the American Lung Association, which unified efforts, led public health education campaigns, and raised funds for research.

By the turn of the twentieth century, as the presence of the tubercle bacillus rather than the physical symptoms became the basis for diagnosis, the new understanding of what caused tuberculosis and how it was spread brought important changes in public health and the medical care of patients. The goal of Progressive Era public health work against tuberculosis was to improve social conditions


and to control the behaviors that fostered the disease. Health departments instituted education campaigns that used films, posters, and lectures to dissuade individuals from practices that spread germs, such as spitting and coughing. In addition to maintaining clean, well-ventilated homes, the use of nonporous building materials such as metals, linoleum, and porcelain was encouraged over wood and cloth, which could harbor disease-causing germs. Public health officials inspected and fumigated dwellings that posed health risks, required physicians to report cases of tuberculosis, and forcibly isolated individuals who did not seek treatment. New diagnostic tests such as the tuberculin skin test and radiological examinations were used in mass screenings for tuberculosis, and new surgical therapies involving the collapse or partial section of the lungs were introduced. Infected individuals were required to seek treatment through a sanatorium or through a dispensary that engaged in disease surveillance and patient education.

Tuberculosis after World War II

The result of the far-reaching and aggressive public health campaign was that the incidence of tuberculosis, which had been steadily declining since the 1870s (when the mortality rate exceeded 300 deaths per 100,000 population), fell to unprecedented low levels by the 1930s (when the mortality rate fell below 50 deaths per 100,000 population). Disease mortality fell even lower (to 10 deaths per 100,000 population in 1954) after the development of an antibiotic, streptomycin, by the microbiologist Selman Waksman in 1943. Although other countries in the 1950s instituted vaccination campaigns using the Bacillus-Calmette-Guérin (BCG) vaccine, it was not adopted for wide use in the United States as public health programs emphasized the identification of patients exposed to the bacillus rather than universal vaccination against the disease.

Between 1954 and 1985, the incidence of tuberculosis in the United States declined 75 percent, and by 1989, public health officials confidently predicted its eradication in the United States by 2010 and worldwide by 2025, believing it would no longer pose a public health threat. These expectations were dashed as a worldwide pandemic of tuberculosis began in 1987 and the World Health Organization declared that tuberculosis posed a global emergency in 1993. The displacement of populations through immigration and political conflicts; the emergence of drug-resistant strains; the high rates of incarceration, homelessness, and intravenous drug use; the prevalence of mass air travel; the collapse of medical services in eastern Europe; the persistence of widespread poverty; and the progress of the AIDS pandemic, in which tuberculosis emerged as an opportunistic infection, all contributed to a worldwide public health crisis. By 2002, the World Health Organization reported that tuberculosis was the leading infectious killer of youth and adults and a leading killer of women, and that a third of the world's population was infected with the tuberculosis bacillus. In response, nearly 150 countries, including the United States, agreed to adopt the Directly Observed Treatment Short-Course (DOTS) system in which countries would promote public health programs of case detection, standardized treatment regimens using multiple drugs, patient surveillance to monitor compliance, and the forcible detention of noncompliant patients. Once thought to be on the verge of eradication, in 2002 it was not known if and when the worldwide incidence of tuberculosis would return to levels experienced only a half century before.

BIBLIOGRAPHY

Bates, Barbara. Bargaining for Life: A Social History of Tuberculosis, 18761938. Philadelphia: University of Pennsylvania Press, 1992.

Ellison, David L. Healing Tuberculosis in the Woods: Medicine and Science at the End of the Nineteenth Century. Westport, Conn.: Greenwood Press, 1994.

Feldberg, Georgina. Disease and Class: Tuberculosis and the Shaping of Modern North American Society. New Brunswick, N.J.: Rutgers University Press, 1995.

Lerner, Barron H. Contagion and Confinement: Controlling Tuberculosis Along the Skid Road. Baltimore: Johns Hopkins University Press, 1998.

Ott, Katherine. Fevered Lives: Tuberculosis in American Culture since 1870. Cambridge, Mass.: Harvard University Press, 1996.

Rothman, Sheila. Living in the Shadow of Death: Tuberculosis and the Social Experience of Illness in America. New York: Basic Books, 1994.

Ryan, Frank. The Forgotten Plague: How the Battle against Tuberculosis Was WonAnd Lost. Boston: Little, Brown, 1993.

Teller, Michael. The Tuberculosis Movement: A Public Health Campaign in the Progressive Era. New York: Greenwood Press, 1988.

D. George Joseph

See also Epidemics and Public Health .

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tuberculosis

tuberculosis is caused by the microorganism Mycobacterium tuberculosis, or tubercle bacillus. It was in 1882 that Robert Koch, among his many historic contributions to bacteriology, identified this as the cause of the disease, thus firmly establishing for the first time its infective nature. It has been estimated that one-third of the world's population has been infected by M. tuberculosis but only a minority, probably about 10%, go on to develop disease. Disease manifests in any number of ways, almost all of them chronic, involving practically any part of the body. The most common site involved is the lungs, where cavities are produced. When this occurs patients have a cough with sputum (which sometimes contains blood), weight loss, and fever. Those with this type of disease are the most infectious, because of the presence of the bacillus in the sputum. Animals also carry the disease; although Koch had denied the possibility, it was later realized that the bovine strain of the organism, Mycobacterium bovis, could cause human infection from cow's milk.

Historically, tuberculosis has long ranked among the most feared of diseases. Such dread is reflected in some of its alternative names, including John Bunyan's ‘Captain of all these Men of Death’, and Charles Dickens' ‘dread disease’ which capture something of the prevalence of the disease in their times. Other names conjure up images of the disease process: the term ‘consumption’ describes what happened to an individual — a progressive emaciation and wasting away. Still other terms, such ‘the King's Evil’ describe the lottery of survival (cure arising from the king's touch in medieval England). Yet tuberculosis is not only a disease of the past. Keats' ‘death warrant’ continues to haunt us. Historically tuberculosis conjures up romantic images of pale, wraith-like artists suffering lingering deaths. Literature, art, and music have all recorded and been transformed by the disease. Those who have succumbed to the disease form a veritable who's who of the artistic and political worlds and notions persist that those with artistic leanings are at greater risk from tuberculosis. As Susan Sontag noted in Illness as Metaphor, ‘tuberculosis was thought to come from too much passion, afflicting the reckless and sensual.’ Gradually, however, perceptions changed. In the US, for example, Katherine Ott noted in Fevered Lives that this ‘most flattering of all diseases’ of the 1870s was transformed, as awareness of the social associations grew in the 1880s, into a disease which was seen as the consequence of either acquired or inherited degeneracy and later came to mirror ethnic and racial fears and prejudices. Yet by the turn of the century the enthusiasm for pointing the finger at individual weaknesses was tempered by an increasing awareness that society's strictures were in part responsible. In truth, in past centuries tuberculosis was a frequent killer of people from all walks of life, not only the famous and infamous, the artistic and notorious. Those living in poverty and squalor were always most susceptible.

The sanatorium movement, which promoted wholesome rest and genteel exercise in pleasant surroundings, took off in the second half of the nineteenth century. In Britain, which borrowed the idea from Germany, the first sanatoria opened in the 1890s. Although many sanatoria in Europe catered for a select, affluent, cosmopolitan clientele (an image which persists in the popular imagination conjured up by establishments such as those at Davos in Switzerland), sanatorium treatment also, by the 1920s, became available for those unable to pay, and the average duration of stay shortened. However a decline in the sanatorium movement started with the onset of World War I and was hastened by the Depression which followed. Although there were still thousands of tuberculosis sufferers receiving care in sanatoria by the mid 1940s, the availability of effective drug treatment meant that they soon became obsolete. Removal of infectious sufferers from the community had contributed to a decrease in incidence of the disease, but for the patients in sanatoria or specialized hospitals there was no specific cure. Recovery was sometimes assisted by causing collapse of an infected lung by the introduction of air into the chest (artificial pneumothorax) or by an operation that ‘caved-in’ the overlying ribs (thoracoplasty).

The advent of drug treatment followed the discovery, by Selman Waksman in the US in 1944, that streptomycin was effective, and other drugs shortly followed. When chemotherapy from then on resulted in cure for most tuberculosis sufferers, contemporary commentators told stories largely of hope, of medicine's conquest of nature, and reflected less on societal hindrances to medicine's application. An optimistic faith in the benefits of science shone through such that it seemed merely a matter of time before this ancient scourge would be eradicated. At the time this optimism seemed well-founded: mortality rates in England and Wales, which had been falling by about 1% annually since the 1860s, declined dramatically from the mid 1940s. Death rates for respiratory tuberculosis in England and Wales were about 125/100 000 at the turn of the century, and by the 1960s had fallen to below 10/100 000. Preceding the advent of chemotherapy there had been improvements in social conditions and better identification of those with active disease, along with advances in bacteriology and in X-ray diagnosis. From the 1920s there were attempts to control bovine infection, first by certifying tuberculin tested (TT) herds, and later by heat treatment to kill bacteria in milk. Although this pasteurization had been considered as early as 1913, Britain lagged behind much of Europe and the US by more than a quarter of a century in putting it into consistent effect. A further preventative measure was the introduction in the 1950s of the BCG (Bacille Calmette Guérin) vaccination programme.

Despite the remarkable success in controlling tuberculosis in the West, the overriding optimism which followed the development of effective antituberculosis drugs in the 1940s and 1950s was somewhat premature. The disease continues to target those most marginalized and vulnerable. Each year more than 8 million people acquire tuberculosis (most of them in the developing world), and about 3 million die, including about 100 000 children, annually. In England and Wales there was concern as to why this should be, why Keats' death warrant should still be received by so many, given that we have had at our disposal for over fifty years drugs which are effective in curing the disease? The answer was known half a century ago.

‘Tuberculosis is a social disease, and presents problems that transcend the conventional medical approach. On the one hand, its understanding demands that the impact of social and economic factors on the individual be considered as much as the mechanisms by which tubercle bacilli cause damage to the human body. On the other hand, the disease modifies in a peculiar manner the emotional and intellectual climate of the societies that it attacks.’ Rene Dubos who, with his wife Jean, wrote these words in 1952, was one of the giants of twentieth-century medicine. As well as being a major figure in the development of antibacterial drugs in the US in the 1920s and 1930s, which led to the later successful antituberculous drugs, he was able, unlike so many, to see the place of tuberculosis in society and to recognize the limits of modern medicine. His words resonate through the years and perhaps are more pertinent now than ever. In 1993 the World Health Organization officially called the global threat of tuberculosis an ‘emergency’. New drug-resistant strains of the organism are spreading and modern medical approaches are failing to cure patients. In England and Wales there was a 20% increase in incidence of the disease between 1987 and 1990, weighted towards the underprivileged. Overcrowding, poverty, social alienation, increased incarceration rates in prisons, homelessness, and AIDS (the ‘deadly alliance’) are combining to overwhelm uncoordinated and under-resourced public health responses.

Perhaps nowhere have the consequences of contemporary public health failures been more obvious than in New York City. In the late 1980s and early 1990s an epidemic of this ancient disease killed hundreds of people, forcing politicians to rethink their approaches to those living on the margins of society, and provoking a response which has cost millions of dollars. As Rene Dubos knew all along, tuberculosis is as much a social and political disease as it is a medical condition.

Richard Coker

Bibliography

Coker, R. (2000). From chaos to coercion: detention and the control of tuberculosis. St Martins Press, New York.
Dormandy, T. (1999). The White Death: a history of tuberculosis. The Hambledon Press, London.
Ott, K. (1996). Fevered lives: tuberculosis in American culture since 1870. Harvard University Press, Cambridge MA.
Ryan, F. (1992). Tuberculosis: the greatest story never told. Swift publishers, Bromsgrove, Worcestershire.
Sontag, S. (1978). Illness as metaphor. Farrar, Straus and Giroux, New York.


See also infectious diseases; immunization.

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Tuberculosis

Tuberculosis

Tuberculosis (TB) is an infectious disease of the lungs caused by the bacterium Mycobacterium tuberculosis. In the mid-nineteenth century, about one-fourth of the mortality rate was attributable to tuberculosis. It was particularly rampant in early childhood and young adulthood. Its presence was felt throughout the world, but by the 1940s, with the introduction of antibiotics , there was a sharp decline of cases in developed countries. For less-developed countries with poor public health structures, tuberculosis is still a major problem. Since 1989, however, there has been an increase in reported cases in economically advanced countries due mainly to immunosuppression associated with AIDS , and the emergence of antibiotic-resistant strains of TB.

The bacillus infects the lungs of those who inhale the infected droplets formed during coughing by an individual who has an active case of the disease. It can also be transmitted by unpasteurized milk, as animals can be infected with the bacteria . The disease is dormant in different parts of the body until it becomes active and attacks the lungs, leading to a chronic infection. Symptoms include fatigue, loss of weight, night fevers and chills, and persistent coughing with sputumstreaked blood. The virulent form of the infection can then spread to other parts of the body. Without treatment, the condition is eventually fatal.

Chest x rays and sputum examinations can show the presence of tuberculosis. Tuberculin, a purified protein taken from the tuberculosis bacilli, is placed under the skin of the forearm during a tuberculosis skin test. In two or three days if there is a red swelling at the site, the test is positive, and indicates TB infection, but not necessarily active TB disease. Early detection of the disease facilitates effective treatment to avoid the possibility of it becoming active later on.

Populations at risk of contracting TB are people with certain medical conditions or those using drugs for medical conditions that weaken the immune system . Others at risk are low-income groups, people from undeveloped countries with high TB rates, people who work in or are residents of long-term care facilities (nursing homes, prisons, hospitals), those who are significantly underweight, alcoholics, and intravenous drug users.

Traces of lesions from tuberculosis have been found in the lungs of ancient Egyptian mummies. The recent discovery of a Pre-Columbian mummy has resolved the debate on whether or not European explorers introduced the disease to the New World. Lung samples from a Peruvian woman who lived 500 years before Columbus discovered America show a lump that was identified as tuberculosis by DNA testing. Hippocrates, a Greek physician who lived from 460 to 370 B.C., described the disease. The Greek name for the disease was phthisis, derived from the verb phthinein, meaning to waste away. Tuberculosis was also called consumption because of the wasting away effects (notably, significant losses of weight over a period of time) of the disease.

In 1839, Johann Schonlein is credited with first labeling the disease tuberculosis. In 1882, the tubercle bacillus was discovered by Robert Koch , the German physician who pioneered the science of bacteriology. This landmark discovery was followed eight years later by his extraction of a protein from dead bacilli called tuberculin. This protein is still used to test for the presence of TB infection in a dormant or early stage. Another important diagnostic breakthrough came in 1895 with the discovery of Wilhelm Conrad Roentgen's x rays. The presence of TB lesions was detected on x rays.

Two twentieth century French scientists, Albert Calmette and Camille Guerin, developed a vaccine against tuberculosis from a weakened strain of bovine bacillus. Called BCG for Bacillus-Calmette-Guerin, this vaccine is the only one still in use although some scientists question its effectiveness. Despite doubts about the vaccine, it is still widely used, especially in TB endemic countries where other preventive measures are lacking. The U.S. Public Health Service's policy recommends testing and drug therapy for those infected instead of vaccination . The two factors responsible for this policy are the low incidence of TB in the United States and the doubts raised about BCG. The Centers for Disease Control and Prevention, (CDC), however, in its concern over the rising incidence of TB in the United States and the appearance of multidrug-resistant tuberculosis (MDR TB) which is difficult to treat, reexamined the TB vaccination issue, and released recommendations for its use in limited situations.

The CDC still recommends the use of skin tests and drug therapy as the most important measures in controlling the incidence of TB in the United States. Drug therapy is 90% effective in halting the infection. Since those vaccinated test positive with the skin test, a vaccination program would interfere with skin testing. Mass vaccination would risk giving up a simple test that provides an early warning. Relying on the drug treatment program to stop TB epidemics , however, has one major drawback. The drug therapy takes six months to a year before halting the infection. People infected are often among the homeless, poor, drug addicted, or criminal societies. Unless these people are carefully supervised to make sure they complete a regimen of drug therapy, it is difficult to effect a cure for the disease.

Throughout the nineteenth century and up until the 1960s, physicians sent their TB patients to sanatoriums which were rest homes located in mountains or semi-arid regions such as the American southwest. These locations were supposed to help the breathing process by providing clean and dry air. Physicians assumed that deeper, easier breathing in a work-free environment would help overcome the disease. Prior to the advent of antibiotics, these retreats were the only recourse for chronically ill tubercular patients. Although treatment in sanatoriums did help many, they were phased out before the 1960s, and replaced by antibiotic drug chemotherapy , which could be administered in either a hospital or home environment. Over 90% of TB patients can be cured by a combination of inexpensive antibiotics, but it is necessary they be used for a period of at least six months.

The impact of tuberculosis was evident in the nineteenth and early twentieth centuries in literature, art, and music. Puccini's opera, La Boheme, was created around the tragic death of the tubercular heroine, Mimi. Since TB often attacked the young, many poets, artists and musicians fell prey to the disease before they had a chance to fulfill their creative work. Among them, Amedeo Modigliani, John Keats, Frederic Chopin, and Anton Chekhov were claimed by the disease, along with millions of other young people during the period. In the United States, American playwright Eugene O'Neill was one of the fortunate few who did recover in a sanatorium and went on to write his plays. His early play, The Straw, written in 1919, dramatically shows what life was like in a sanatorium.

In the past, U.S. city and state governments were actively involved in regulations that controlled infected people from spreading the infection. At present, federal, state, and local agencies must again take a leading role in formulating a public policy on this complicated health problem. Several states are using a program called Directly Observed Therapy (DOT) to combat the rising incidence of TB. This program has met with considerable success in lowering reported cases of TB as much as 15% in New York City during the late 1990s.

DOT is offered at soup kitchens, clinics, hospitals, neighborhood health centers, and drug rehabilitation centers. Outreach workers enable those with TB to get help with the least amount of red tape. The wide array of medicines needed to treat the disease are made available, and ample funding has been provided from federal, state, and local agencies. Apartments are located for homeless patients and special provisions are made to help released prison inmates and those on parole. Guidelines for compassionate, supervised medical services are periodically reviewed for the successful implementation of the DOT program.

Despite such measures, the U.S. Department of Health and Human Services predicts tuberculosis, will spread further by the year 2005. In 1990, there were 7,537,000 TB cases worldwide. That number is expected to rise to 11,875,000 in 2005, a 58% increase. Most of the rise in rate is attributed to demographic factors (77%) while 23% accounts for the epidemiological factors, i.e., the rise in HIV infection. Approximately 30 million people around the world will die of TB from 2000 to 2009. These predictions are considered conservative because many cases of TB are never reported.

See also AIDS, recent advances in research and treatment; Bacteria and bacterial infection; Epidemiology, tracking diseases with technology; Public health, current issues

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Tuberculosis

Tuberculosis

Definition

Tuberculosis is a chronic, infectious disease that primarily attacks the lungs.

Description

Tuberculosis (TB) is caused by a bacteria that primarily attacks the lungs. An individual may be "TB infected," meaning the bacteria are in the body but are in an inactive state, walled off behind scab-like structures that are the body's defense mechanism, or have "TB disease," when the bacteria actively spread throughout the body and can cause damage to the lungs or other organs. The severity of the attack depends on whether the bacteria spread from the lungs to other parts of the body. TB infection in the blood, the meninges (membranes around the brain and spinal cord), or the kidneys are the most serious. Children between the ages of six and 24 months are the most susceptible to meningitis ; it is the chief cause of tuberculin death among children.

Transmission

The bacteria that causes TB, Mycobacterium tuberculosis, is transmitted by droplets when an infected person coughs or sneezes. It is not spread through kissing or other physical contact. Children nearly always contract the disease from an infected adult.

Demographics

In 2003, the Centers for Disease Control and Prevention (CDC) reported 14,874 cases of tuberculosis in the United States, or 5.1 cases per 100,000 population. The actual number of TB infections, however, is estimated to be much higher, as high as ten million. In 2002, there were 802 tuberculosis-related deaths. The District of Columbia had the highest rates of TB, with 14 cases per 100,000 people in 2003; Montana and Wyoming had the lowest rate, with 0.8 cases per 100,000 population. Children less than 15 years of age represented 6 percent of reported TB cases, and 1524-year-olds represented 11 percent of all cases. Worldwide, TB cases are the rise, with nearly 8.8 million new cases a year being estimated by the World Health Organization (WHO).

Causes and symptoms

Mycobacterium tuberculosis is a microscopic, rod-shaped bacterium. The majority of individuals who are infected with TB do not go on to have active disease. Active TB can be triggered when a person's immune system is weakened, such as from human immunodeficiency virus (HIV), malnutrition , or alcohol abuse.

Early symptoms of TB include unusual fatigue, fever , loss of weight, headache , coughing, and irritability. An infected child may have night sweats and cough up blood. In advanced stages, the patient will suffer persistent coughing, breathlessness, and fever. Many times TB is not diagnosed and becomes dormant; this is known as initial tuberculosis. In severe cases among young children between the ages of two and four, initial TB can be fatal. The disease can reoccur, or reactivate, during adolescence when resistance is low, and may disappear on its own or develop into serious lung disease.

When to call the doctor

Parents should contact their child's doctor if the child has been in contact with someone who has been diagnosed with or is suspected to have tuberculosis, or if the child exhibits the symptoms of the disease, particularly persistent fever, night sweats, and cough.

Diagnosis

Tuberculosis is nearly always diagnosed by tuberculin skin tests, although one can also be diagnosed by chest x rays and analysis of sputum (matter from the respiratory tract) smears and cultures. The most common tuberculin skin test is the Mantoux test, which consists of injecting a small amount of protein from the TB bacillus into the forearm. A reddening and swelling of the area after 2472 hours signals the presence of TB. A negative result, however, may not necessarily exclude a diagnosis of TB.

Treatment

The disease is treated with a regimen of strong antibiotics such as Rifampin and Isoniazid for six months to two years. Because some strains of the disease are unusually drug-resistant, cultures are grown from the patient's bacteria and tested with a variety of drugs to determine the most effective treatment. In cases of strong drug-resistant strains, the child may undergo surgery to remove the infected areas.

Infants with TB are usually hospitalized but children and teenagers can generally lead active lives within two weeks of beginning medication. It is imperative that the mediation prescribed be taken faithfully.

Prognosis

With treatment, TB infection that is not drug resistant can nearly always be cured as long as patients are consistent with their medications and considerable lung damage as not already occurred. Drug-resistant TB has a lower cure rate. Without treatment, the disease will continue to progress; approximately one-half of untreated TB patients will die of the disease.

Prevention

Stopping the spread of tuberculosis is the most effective way of preventing its incidence among children. All adults who work with children should be screened regularly. In many communities, children are tested when they reach their first birthday and then at one-to-three year intervals throughout the school years. The medical profession is divided on the issue of screening; some physicians believe that the screening should be focused in areas of common occurrence or within high-risk populations such as foreign-born children. The practice of relying on parents to report results of the skin testing has also come under criticism from some members of the medical community.

While a vaccine for TB does exist (Bacille Calmette-Guerin or BCG vaccine), it is not widely available in the United States and has had conflicting reports about its efficacy. Being inoculated with BCG vaccine does not always prevent infection with the disease. The vaccine is only recommended for children in the United States if they live with someone who has active TB that cannot be treated or is drug-resistant.

Nutritional concerns

Poor nutrition is closely related active tuberculosis; children with adequate nutrition are more resistant to the disease than those who suffer from malnutrition.

Parental concerns

If a child has been infected with TB and is prescribed drug therapy to treat the disease, it is imperative that parents closely monitor their child to ensure that the medication is taken as prescribed; if the medication is not taken frequently enough or until it is no longer needed, drug-resistant TB can arise.

KEY TERMS

Mantoux test A tuberculin skin test. Also called the PPD (purified protein derivative) test.

Meningitis An infection or inflammation of the membranes that cover the brain and spinal cord. It is usually caused by bacteria or a virus.

Sputum The substance that is coughed up from the lungs and spit out through the mouth. It is usually a mixture of saliva and mucus, but may contain blood or pus in patients with lung abscess or other diseases of the lungs.

Resources

BOOKS

Landau, Elaine. Tuberculosis. New York: F. Watts, 1995.

PERIODICALS

"TB on the Rise." Patient Care 38, no. 6 (June 2004): 9-10.

Young, Douglas B. and Brian D. Robertson. "TB Vaccines: Global Solutions for Global Problems." Science 284, no. 5419 (May 28, 1999): 1479.

ORGANIZATIONS

American Lung Association. 61 Broadway, 6th Floor, New York, NY 10006. (800) 548-8252. Web site: <www.lungusa.com>.

Centers for Disease Control and Prevention. 1600 Clifton Rd., Atlanta, GA 30333. (404) 639-3311. Web site: <www.cdc.gov>.

WEB SITES

Division of Tuberculosis Elimination. "Reported Tuberculosis in the United States, 2003." Centers for Disease Control and Prevention. [cited September 12, 2004]. Available online at: <http://www.cdc.gov/nchstp/tb/>.

Sharma, Sat. "Tuberculosis." eMedicine. January 14, 2003 [cited September 12, 2004]. Available online at: <www.emedicine.com/aaem/topic464.htm>.

Mary McNulty Stephanie Dionne Sherk

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Tuberculosis

TUBERCULOSIS

Tuberculosis (TB), an infectious disease, has been present throughout ancient and modern history. TB rates in the United States are on the decline after a resurgence from 1985 to 1992. However, TB continues to be a major killer in much of the world. The implications of this epidemic are global, as travel and migration are now part of everyday life.

Although the cause, diagnosis, and treatment and prevention of TB are known, paradoxically, the disease continues to increase as a public health challenge. Caused by a bacterium called Mycobacterium tuberculosis, TB spreads via an airborne route from an infectious person coughing, sneezing, laughing, or singing. The bacteria infect mainly other individuals who have frequent and prolonged contact with a contagious TB case.

HISTORY

TB's existence dates back many centuries. There are references to TB in third-century b.c.e. Chinese and second-century b.c.e. Indian texts; Plato and Hippocrates wrote about it around 400 b.c.e. TB was commonly known as consumption in Europe, a cause of death for hundreds of thousands in the late eighteenth and nineteenth centuries. This is when TB in close groups was first observed and assumed to have a genetic cause, since it was commonly seen in families.

In 1882 Robert Koch's discovery of Mycobacterium tuberculosis led to the recognition of TB as an infectious disease. This discovery also led to interventions for interrupting transmission from person-to-person.

Beginning in the late 1880s, TB patients were treated in sanitoria with various modalities, including exposure to fresh air, exercise, and nourishment. About 50 percent of patients recovered or had long-term remission. However, as is known today, their "cure" was not due to the treatments administered but perhaps to self-healing mechanisms.

In the early twentieth century, public health interventions became key in controlling the spread of TB in the cities, where TB was most prevalent. For example, Herman M. Biggs, General Medical Officer of New York City, actively catalogued lists of TB patients and enforced isolation and environmental mechanisms to control TB, including the opening of a TB hospital to quarantine patients. Between 1914 and 1923, the Metropolitan Life Insurance Company conducted the "Framingham Tuberculosis Project" using community nurses to visit the homes of its clients to do assessments, teach health practices, and collect data for research and policy-making purposes. The project was in response to a high rate of TB-related mortality among Metropolitan customers. As a result, mortality rates for TB in the Metropolitan pool declined by 68 percent.

Beginning in 1921, the Bacille Calmette Guerin (BCG) vaccine was used to prevent TB. Still used in many parts of the world but not in the United States, the vaccine is not effective, except perhaps in infants. The discovery of streptomycin in 1943 brought drug treatment for TB. Between 1943 and 1952, two more TB drugs, para-amino-salicylic acid (PAS) and isoniazid (INH), were discovered. Sanitoria began to close in the early 1970s, as TB could be now be treated on an outpatient basis, as evidenced by success in the decrease in TB rates with combined drug treatment and infection-control mechanisms.

RESURGENCE

By 1985, there were 22,201 cases of TB in the United States, the lowest number recorded since national case reporting began in 1953. However, rates then began to increase, until in 1992 cases peaked at 26,673. The human immunodeficiency virus (HIV) epidemic was a major contributor, as its victims are at higher risk for developing active disease once infected with TB bacteria. Migration from countries with high rates of TB added to the number. Also, improper or inadequate drug treatment for TB has led to drug-resistant strains. Finally, medical education stressed TB to a lesser degree in academic curricula, and funding and interest in TB-control programs had dwindled with decreased cases. Most authorities feel that the latter reason was the most important.

Response to the American TB resurgence resulted in increased funding for TB control programs. This gave greater access to TB treatment through health departments. The health departments were responsible not only for treating cases, but for surveillance, outreach, case management, and treatment for those who had been exposed to infectious TB cases. Directly observed therapy short course (DOTS), the observation of the ingestion of medication, has now become the basis for the worldwide standard of TB care. DOTS includes five elements: government commitment to sustained TB-control activities; case detection and self-reporting to health services; standardized treatment regimen of six to eight months for at least all confirmed infectious cases, with directly observed treatment (DOT) for at least the initial two months; a regular, uninterrupted supply of all essential anti-TB drugs; and a standardized recording and reporting system that allows assessment of treatment results for each patient and of the TB control program overall. DOTS is presently available to 25 percent of the world's TB patients, but its acceptance is slowly increasing. There was also an increase in TB educational interventions via the public health sector and medical schools. New drug trials did not create new drugs but created variations on existing drugs and regimens. TB rates began to decrease again in 1994, and as of 1999, they were at an all-time low of 17,528 cases in the United States. Globally, there are still eight million new cases of TB annually with three million deaths. Clearly, even with the exemplary level of achievement domestically, TB cannot be controlled anywhere unless it is controlled everywhere.

THE FUTURE

Although one of the Healthy People 2010 goals calls for TB elimination from this country, the United States is still far from that goal. Many interventions need to be continued despite falling rates. For other communicable diseases, effective vaccine development and the advent of new drug therapies has been key to disease control approaching elimination. The best course for TB elimination is to develop a vaccine and new drugs while continuing surveillance, treating TB patients who may infect others, treating those who have been infected but are not yet active cases, increasing TB awareness among health professionals, and performing targeted testing for TB infection among high-risk populations. This combination of medical and public health practice can make TB elimination a reality.

Rajita R. Bhavaraju

Lee B. Reichman

(see also: Communicable Disease Control; Drug Resistance; Immunizations; Isolation )

Bibliography

Centers for Disease Control and Prevention (1995). Self-Study Modules on Tuberculosis. Atlanta, GA: Author.

(2000). Core Curriculum on Tuberculosis: What the Clinician Should Know, 4th edition. Atlanta, GA: Author.

Daniel, T. M. (1997). Captain of Death: The Story of Tuberculosis. Rochester, NY: University of Rochester Press.

Dublin, L. I. (1952). A Forty-Year Campaign against Tuberculosis: The Contribution of the Metropolitan Life Insurance Company. New York: Metropolitan Life Insurance Company.

Reichman, L. B. and Tanne J. H. (2001). Time Bomb: The Global Epidemic of Multidrug Resistant Tuberculosis. New York: McGraw Hill.

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tuberculosis

tuberculosis (TB), contagious, wasting disease caused by any of several mycobacteria. The most common form of the disease is tuberculosis of the lungs (pulmonary consumption, or phthisis), but the intestines, bones and joints, the skin, and the genitourinary, lymphatic, and nervous systems may also be affected.

There are three major types of tubercle bacilli that affect humans. The human type (Mycobacterium tuberculosis), first identified in 1882 by Robert Koch, is spread by people themselves. It is the most common one. The bovine type (M. bovis) is spread by infected cattle but is no longer a threat in areas where pasteurization of milk and the health of cattle are strictly supervised. The avian type (M. avis) is carried by infected birds but can occur in humans. The tubercle bacillus can live for a considerable period of time in air or dust. The most common means of acquiring the disease is by inhalation of respiratory droplets.

Course of the Disease

Tuberculosis of the lungs usually results in no or minimal symptoms in its early stages. In most persons the primary infection is contained by the body's immune system, and the lesion, called a tubercle, becomes calcified. In many the infection is permanently arrested. In others the disease may break out again and become active years later, usually when the body's immune defenses are low. Untreated, the infection can progress until large areas of the lung and other organs are destroyed. Symptoms of the disease include cough, sputum, bleeding from the lungs, fever, night sweats, loss of weight, and weakness.

Incidence

The incidence of tuberculosis of the lungs, the "white plague" that formerly affected millions of people, declined in the United States from the 1950s until 1984; sanatoriums were closed and routine screening was abandoned. Then, between 1984 and 1992, the incidence increased by 20%, chiefly because of immigration from countries where it is common and because of AIDS, which leaves people particularly vulnerable to the disease. Renewed efforts at control and advances in treatment have been rewarded with incidence declines each year, amounting to a total decline of 31% from 1992 to 1998.

Worldwide the outlook has been far less encouraging. In 1993 the World Health Organization (WHO) declared TB a global health emergency. Approximately one third of the world's population is infected; an estimated 1.3 million died in 2012. The vast majority of new cases occur in sub-Saharan Africa. Spread of TB is especially rapid in areas with poor public health services and crowded living conditions. In homeless shelters and prisons, crowded conditions and inadequate treatment often go together. Areas where living conditions are disrupted by wars, famine, and natural disasters also are heavily affected.

Especially alarming has been the spread of drug-resistant strains of TB. By the late 1990s scientific experts and international health officials warned that drug-resistant strains were spreading faster than had been anticipated. Bacteria can survive and become drug resistant in patients whose treatment is not properly monitored and seen to completion. Multidrug resistant (MDR) TB strains are resistant to two or more of the commonly prescribed first-line drugs, while extensively drug resistant (XDR) strains are also resistant to three or classes of the more toxic second-line drugs. Some believe that unless major new treatment strategies are initiated in source countries, drug-resistant TB will eventually become epidemic even in areas with good control programs, such as Europe and America. In 2011, WHO estimated that there were more than 80,000 cases, many of them undiagnosed, of drug-resistant TB in Europe.

Diagnosis and Treatment

Diagnosis is made by a tuberculin skin test. It can be confirmed by X rays of the chest and sputum examination. Ideally, treatment begins after a skin test signals exposure but before active disease has developed. The treatment of choice for prevention and for active cases is the antimicrobial drug isoniazid (INH), available since 1956. In infected individuals it now is usually used in combination with other antituberculosis drugs such as rifampin, pyrazinamide, and ethambutol. Bedaquiline is used to treat multidrug resistant and extensively drug resistant TB.

Tuberculosis drugs have to be taken regularly, typically for 6 to 12 months. Many patients abandon their treatment when they feel better; similarly, preventive treatment is often abandoned because of the inconvenience. Such noncompliance is believed to be the main reason for the upsurge in drug-resistant strains of the TB bacilli, many of which are resistant to more than one drug. Drug-resistant TB is difficult to treat and has a much higher death rate; extensively resistant TB is especially worrisome because it can be essentially untreatable.

The combination drug rifater (rifampin, isoniazid, and pyrazinamide) has simplified drug administration. Directly observed treatment, where health-care workers watch patients take each dose of medicine, has proved effective in eliminating the problem of noncompliance in the United States, but monitoring has been less effective in many other parts of the world.

Prevention of Tuberculosis

Preventive measures include strict standards for ventilation, air filtration, and isolation methods in hospitals, medical and dental offices, nursing homes, and prisons. If someone is believed to have been in contact with another person who has TB, preventive antibiotic treatment may have to be given. Infected persons need to be identified as soon as possible so that they can be isolated from others and treated.

An antituberculosis vaccine, bacille Calmette-Guérin, or BCG vaccine, was developed in France in 1908. Although there is conflicting evidence as to its efficacy (it appears to be effective in 50% of those vaccinated), it is given to over 80% of the world's children, mostly in countries where TB is common; it is not generally given in the United States. Federal health officials in the United States have stated (1999) that a new vaccine is essential to TB prevention. It is hoped that the determination of the complete DNA (genome) sequence of Mycobacterium tuberculosis, achieved in 1998, will hasten the development of an effective vaccine.

Bibliography

See R. Dubos, The White Plague (1955); S. A. Waksman, The Conquest of Tuberculosis (1964).

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tuberculosis

tuberculosis (TB) (tew-ber-kew-loh-sis) n. an infectious disease caused by the bacillus Mycobacterium tuberculosis and characterized by the formation of nodular lesions (tubercles) in the tissues. In the most common form of the disease (pulmonary t.) the bacillus is inhaled into the lungs where it sets up a primary tubercle and spreads to the nearest lymph nodes (the primary complex). Many people become infected but show no symptoms. Others develop a chronic infection and can transmit the bacillus by coughing and sneezing. Symptoms of the active disease include fever, night sweats, weight loss, and the spitting of blood. In some cases the bacilli spread from the lungs to the bloodstream, setting up millions of tiny tubercles throughout the body (miliary t.). Bacilli entering by the mouth, usually in infected cows' milk, set up a primary complex in abdominal lymph nodes, leading to peritonitis, and sometimes spread to other organs, joints, and bones (see Pott's disease). Tuberculosis is curable by various combinations of the antibiotics streptomycin, ethambutol, isoniazid (INH), rifampicin, and pyrazinamide. Preventive measures in the UK include the detection of cases by X-ray screening of vulnerable populations and vaccination with BCG vaccine. See also direct observed therapy.


www.hpa.org.uk/infections/topics_az/tb/menu.htm Explanation of TB from the Health Protection Agency

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Tuberculosis

TUBERCULOSIS

DEFINITION


Tuberculosis (pronounced too-BUR-kyoo-LOH-siss), or TB, is a contagious disease of the lungs that can spread to other parts of the body and may be fatal. TB is caused by a microorganism known as the tubercle bacillus, or Mycobacterium tuberculosis. The disease can now be treated, cured, and prevented. However, scientists have never come closing to wiping it out and TB remains one of the most serious diseases worldwide.

DESCRIPTION


Some parts of the population are at higher risk of getting TB than others. For instance, tuberculosis is more common among elderly people. Typically, more than one-fourth of the TB cases reported in the United States occur among people above age sixty-five.

Elderly people are especially vulnerable for a number of reasons. First, the disease can take years to become active, so an older person may have gotten the disease earlier in life and only discovered it after it became active. Second, people who live in nursing homes and similar facilities are often in close contact with each other and the disease can spread more easily in such conditions. Third, the body's immune system becomes weaker as a person grows older and older people may find it more difficult to hold off an attack of the tubercle bacillus. The immune system is the body's network system for fighting off disease and infection.

Race also can be a factor in determining the risk of getting tuberculosis. TB occurs most commonly among African Americans. Other minorities are also at higher risk. Currently about two-thirds of all TB cases in the United States affect African Americans, Hispanics, Asians, and people from the Pacific Islands. Another one-fourth of cases in the United States affect people born outside the country.

People who are infected with the human immunodeficiency virus (HIV) are also at high risk for tuberculosis (see AIDS entry). HIV can damage a person's immune system, making it difficult for the body to fight off the TB bacterium. People who abuse alcohol and illegal drugs are also at high risk for the disease.

CAUSES


The most common method by which TB is transmitted is coughing or sneezing. When a person coughs or sneezes, he or she releases a fine mist of water droplets. If the person carries the tubercle bacillus, those droplets may contain thousands of the bacteria. A person nearby may inhale those water droplets and the bacteria they contain. The bacteria can then travel to that person's respiratory system and cause a new infection.

About a third of the people standing close to a person with TB are likely to develop the disease. Tuberculosis is not transmitted by contact with a person's clothing, bed linens, or dishes and cooking utensils. A fetus may become infected, however, by taking in bacilli from the mother.

Progression

The tubercle bacilli a person inhales may or may not cause tuberculosis. The human immune system has a variety of ways to capture and kill these bacteria. If the immune system is successful in doing so, the person will not become ill with TB.

Inhaled bacilli, however, may survive the immune system. They may travel throughout the body to organs other than the lungs. In some cases, the bacilli remain active enough to cause tuberculosis. In about 5 percent of all cases, a person develops tuberculosis within twelve to twenty-four months of being exposed to TB bacteria.

Tuberculosis: Words to Know

Bacillus Calmette-Guérin (BCG):
A vaccine made from weakened mycobacterium that infects cattle. It is used to protect humans against pulmonary tuberculosis and its complications.
Extrapulmonary:
Outside of the lungs.
Lesion:
Any change in the structure or appearance of a part of the body as the result of an injury or infection.
Mantoux test:
Another name for the PPD test, which is used to determine whether a person has been infected with the tuberculosis bacterium.
Miliary tuberculosis:
A form of tuberculosis in which the bacillus spreads throughout the body producing many thousands of tubercular lesions.
Mycobacteria:
A group of bacteria that includes Mycobacterium tuberculosis, the bacterium that causes tuberculosis.
Pericardium:
the membrane surrounding the heart.
Pulmonary:
Relating to the lungs.
Purified protein derivative (PPD):
A substance injected beneath the skin to see whether a person presently has or has ever had the tubercle bacillus.
Sputum:
Secretions produced inside an infected lung. When the sputum is coughed up it can be studied to determine what kinds of infection are present in the lung.
Vaccine:
A substance that causes the body's immune system to build up resistance to a particular disease.

By contrast, less than 10 percent of all people who inhale the tubercle bacillus actually become ill. The rest develop no symptoms of the disease and have negative X rays for the disease. In such cases, the disease is said to be inactive. The bacilli remain alive in cells, but they are not active enough to actually cause disease. They may become more active later in life, however.

In such cases, a person may become ill with tuberculosis long after being exposed to the TB bacteria.

Scientists believe that anywhere from ten to fifteen million Americans are carrying inactive tubercle bacilli in their bodies.

SYMPTOMS


Cases of tuberculosis are often classified as to whether they occur in the lung (pulmonary tuberculosis) or elsewhere in the body (extrapulmonary tuberculosis). Pulmonary tuberculosis is often confused with other diseases of the respiratory system. A person with TB may feel slightly sick or develop a mild cough. The person may also cough up small amounts of greenish or yellow sputum in the morning; the sputum can sometimes contain blood.

Other symptoms include a low-grade fever, a loss of interest in food, mild chest pain, difficulty in breathing, and night sweats. If the TB bacilli travel from the lungs to the lymph nodes, which help fight off illness, other symptoms, such as skin infections, may develop. More serious symptoms can also develop, including severe weight loss. Modern antibiotics, however, can prevent patients from reaching that stage of the disease.

THE FIGHT AGAINST TUBERCULOSIS THEN AND NOW

In the mid-seventeenth and eighteenth centuries, many countries underwent an Industrial Revolution. Because of inventions such as the steam engine, cities saw an increase of factory and industrial jobs, and more and more people moved from farms in the country to work in the city. Once there, workers often lived in very close contact with relatives and neighbors. Under those crowded and unsanitary conditions, tuberculosis was able to spread easily among the population.

Before scientists knew what caused tuberculosis, the disease was commonly referred to as consumption.

Until recently, there was no way of treating the disease. Instead, people with "consumption" were isolated in private hospitals or sanitariums. The purpose of isolation was to prevent the disease from spreading to uninfected people. Because of this practice, the study of tuberculosis also became separated from other fields of medicines. Entire organizations were created to study the disease, its effects on patients, and its impact on society as a whole.

In 1885 the German microbiologist Robert Koch discovered the tubercle bacillus and showed that this microorganism was responsible for tuberculosis. At the time, TB was responsible for one out of every seven deaths that occurred in Europe.

At the turn of the twentieth century, more than 80 percent of all Americans had been infected with TB before the age of twenty. Most of these people did not become ill since their bodies were able to fight off the disease. However, tuberculosis was still the most common cause of death among Americans. Even as late as 1938 there were more than seven hundred TB hospitals in the United States.

The first step in the conquest of TB occurred with the discovery of streptomycin in the early 1940s. Streptomycin is an antibiotic that kills the tubercle bacillus. Eventually, a number of other anti-tuberculosisdrugs were developed and progress was made in overcoming the disease.

By 1985 a conference was held to develop plans to eliminate tuberculosis forever. The number of cases of TB had been dropping for many years and many experts thought that TB was no longer going to be a serious disease. Then, in the late 1980s, the number of TB cases began to rise, both in the United States and around the world. Why did this change come about? At least five factors are thought to play a role in the return of TB as a major health problem:

  • Education. Efforts to educate people about the disease may have lessened as the perceived threat of TB decreased.
  • AIDS/HIV epidemic. As HIV weakens a person's immune system, a patient can become more prone to developing infectious diseases, such as tuberculosis.
  • Living conditions. People who are poor, or homeless, or who live in crowded and unsanitary conditions may also develop weakened immune systems, or increase their chances of coming in contact with the disease. Drug users often have weakened immune systems as well. As the number of people in these categories increases, so does the rate of tuberculosis.
  • Population movement. The increased movement of people across national boundaries is another factor. When people take vacations, conduct business, or move to new countries, they may take TB with them.
  • Drug Resistance. TB bacteria have become resistant to many of the drugs once used to treat the disease.

Experts estimate that eight to ten million new cases of tuberculosis develop worldwide every year. The disease is thought to be responsible for about three million deaths annually. While there are various ways to fight the disease, if root problems, such as homelessness, poverty, drug use, and drug resistance are not solved, tuberculosis may once again become a major health problem.

Extrapulmonary Tuberculosis

Some of the tissues and organs in which extrapulmonary tuberculosis may appear are the following:

  • Bones. TB is particularly likely to infect the spine and the ends of the long bones. Children are especially susceptible to spinal tuberculosis. If the disease is not treated, it may cause collapse of the vertebrae and paralysis in one or both legs.
  • Kidneys. The kidneys are another common location for extrapulmonary tuberculosis. Although there are few signs of TB kidney infections, the disease may spread to the bladder, the prostate gland (in men), and other nearby organs and tissues.
  • Female reproductive organs. In women, TB bacilli may spread to the ovaries and the peritoneum (pronounced per-i-tuh-NEE-uhm), the membrane lining the abdominal cavity.
  • Abdominal cavity. Peritonitis (pronounced per-i-tuh-NIE-tiss), infection of the peritoneum, produces symptoms similar to those of stomach cramps and appendicitis (see appendicitis entry).
  • Joints. Infection of the joints results in a form of arthritis (see arthritis entry) that most commonly affects the hips and knees. Less commonly, the wrist, hand, and elbow joints may become painful and inflamed.
  • Meninges (pronounced mu-NIHN-jeez). The meninges are tissues that cover the brain and the spinal cord. Infection of the meninges by the TB bacillus causes tubercular meningitis (see meningitis entry). This condition is most common among children, but most dangerous among the elderly. Symptoms of tubercular meningitis include headaches and drowsiness. If left untreated, a person with tubercular meningitis may lose consciousness and suffer permanent brain damage.
  • Skin, intestines, adrenal glands, and blood vessels. The TB bacterium can infect all of these body parts. One serious result can occur when the body's main artery, the aorta, becomes infected. The infection may cause the aorta to rupture, resulting in the person's death. Infection of the pericardium, the membrane surrounding the heart, can cause pericarditis (pronounced per-i-kar-DIE-tiss) which interferes with the heart's ability to pump blood.
  • Miliary tuberculosis. Miliary tuberculosis occurs when very large numbers of tubercle bacilli spread throughout the body. Huge numbers of tiny lesions (pronounced LEE-zhuns) develop throughout the body causing severe anemia, weakness, weight loss, and wasting. Lesions are any change in the structure or appearance of a part of the body as the result of an injury or infection.

DIAGNOSIS


The first sign of tuberculosis may be the presence of one or more of the symptoms described. For example, someone who experiences persistent cold-like systems might seek medical advice. In such cases, a medical worker can take samples of a person's sputum. The sputum can then be cultured (grown and studied) to look for tubercle bacilli. Standard chemical tests are available for the detection of these bacilli.

Body fluids other than sputum can also be collected and cultured. For example, studies of the urine will indicate whether the kidneys or bladder have been infected.

Perhaps the most common warning sign for tuberculosis is an abnormal chest X ray. The X ray of a person with pulmonary tuberculosis will show numerous white, irregular areas against a dark background and/or enlarged lymph nodes. Chest X rays are recommended for anyone who has close contact with a TB patient. For example, health care workers who have contact with people at risk for the disease should have regular chest X rays.

The most common method for diagnosing TB has traditionally been a tuberculin skin test. Tuberculin consists of antigens, substances produced by an M. tuberculosis culture. In a tuberculin skin test, these antigens are injected beneath the skin. If TB bacteria are present, the injection becomes hard, swollen, and red within one to three days. This change is generally a good indication that infection has occurred.

Today, skin tests generally use a substance called purified protein derivative (PPD). The PPD test, also called the Mantoux test, tends to provide more accurate results than the traditional tuberculin test. However, both false positives and false negatives do occur. A false positive is a test that suggests infection has occurred when it really has not. A false negative is a test that shows that no infection has occurred when, in fact, it actually has.

TREATMENT


In the past, treatment of tuberculosis was primarily supportive. Patients were kept in isolation, away from the healthy population. They were encouraged to rest and to eat well. If these measures failed, surgery was used. Today, surgical procedures are used much less often. Instead, drug therapy has become the primary means of treatment. Patients with TB can now safely rest at home; they pose no threat to other members of the household.

Drug Therapy

Drugs provide the most effective treatment for TB patients. Three principles govern the use of drug treatment for tuberculosis:

  • First, the number of bacilli must be lowered as quickly as possible. By so doing, the risk of transmitting the disease to other people is reduced.
  • Second, efforts must be made to prevent the development of drug resistance. If a person develops a resistance to a drug, it will no longer be helpful in curing the disease. As a result, most patients are given a combination of two or three different drugs at first.
  • Third, drug treatment must be continued to prevent reoccurrence of the disease.

Five drugs are used today to treat tuberculosis. They are isoniazid (also known as INH; pronounced eye-suh-NY-uh-zid, trade names Laniazid, Nydrazid); rifampin (pronounced ry-FAM-puhn, trade names Rifadin, Rimactane); pyrazinamide (pronounced pir-uh-ZIN-uh-mide, trade name Tebrazid); streptomycin (pronounced strep-tuh-MYS-uhn); and ethambutol (pronounced eth-AM-byoo-tol, trade name Myambutol). The first three drugs are often combined into a single capsule so that patients have fewer pills to take.

Surgery

Surgery is sometimes used to treat tuberculosis when medication is not effective. One form of surgery involves the introduction of air into the chest. This procedure causes the lung to collapse. In a second procedure, one or more ribs may be removed. A third procedure involves the removal of all or part of a diseased lung. Other forms of surgery may be used in cases of extrapulmonary tuberculosis.

PROGNOSIS


The prognosis for recovery from TB is good for most patients. The key to success is early diagnosis of the disease followed by a careful program of medication. The most serious form of tuberculosis, miliary tuberculosis, is still fatal in many cases, but it is seldom seen in developed countries today.

PREVENTION


Probably the most important form of prevention is to reduce the over-crowded and unsanitary conditions in which many people live. This action reduces the risk of transmitting TB from infected to uninfected people.

Vaccinations

The Bacillus Calmette-Guérin vaccine (BCG) is available for use against tuberculosis. A vaccine is a substance that causes the body's immune system to build up resistance to a particular disease. BCG is made from a type of mycobacterium that infects cattle. When injected into humans, it stimulates the immune system against M. tuberculosis. The vaccine, however, is more effective in some groups of people than in others. Scientists are conducting studies to better understand why the vaccine is not as effective in some parts of the population.

Preventative Use of Isoniazid

Isoniazid can be used to prevent the development of TB as well as to treat it. There is no point in giving the drug to everyone, however, since most people never come into contact with someone who has tuberculosis, so their risk of infection is small. However, some people encounter TB carriers often. These people can benefit from taking isoniazid on a regular basis. The treatment involves receiving a dose of isoniazid once every six to twelve months.

Among the groups that should consider the use of isoniazid as a preventative against TB are: health care workers who have contact with TB patients; people who are HIV positive; intravenous drug users; anyone who has had positive PPD results and abnormal chest X rays in the past; people with depressed immune systems; and members of high-risk groups who have had positive PPD tests.

FOR MORE INFORMATION


Books

Hyde, Margaret O. Know About Tuberculosis. New York: Walker & Company, 1994.

Landau, Elaine. Tuberculosis. New York: Franklin Watts, Inc., 1995.

Silverstein, Alvin, Virginia Silverstein, and Robert Silverstein. Tuberculosis. Hillside, NJ: Enslow Publishers, Inc., 1994.

Organizations

National Institute of Allergy and Infectious Diseases. Building 31, Room 7A-50, 31 Center Drive, MSC 2520, Bethesda, MD 208922520. http://www.niaid.nih.gov.

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tuberculosis

tuberculosis (TB) Infectious disease caused by the bacillus Mycobacterium tuberculosis. It most often affects the lungs (pulmonary tuberculosis), but may involve the bones and joints, skin, lymph nodes, intestines, and kidneys. One-third of the world's population is infected, and up to 5% of those infected eventually develop TB. Poor urban living conditions have lead to a resurgence of the disease in the USA and much of Europe, where previously it had been in decline. The BCG vaccine against tuberculosis developed in the 1920s and the first effective treatment drug, streptomycin, became available in 1944. However, the bacillus shows increasing resistance to drugs and some strains are multi-resistant.

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Tuberculosis

Tuberculosis

What Is Tuberculosis?

Is TB Common?

How Is TB Spread?

What Are the Signs and Symptoms of TB?

How Do Doctors Diagnose and Treat TB?

What Are Some Complications of TB?

Can TB Be Prevented?

Resources

Tuberculosis (too-ber-kyoo-LO-sis) is a bacterial infection that primarily attacks the lungs but can spread to other parts of the body.

KEYWORDS

for searching the Internet and other reference sources

Consumption

Directly observed therapy (DOT)

Lung diseases

Mantoux test

MDR tuberculosis

Mycobacterium tuberculosis

PPD test

Tuberculin skin test

What Is Tuberculosis?

A germ known as Mycobacterium (my-ko-bak-TEER-e-um) tuberculosis causes tuberculosis (TB). Being infected with the bacterium and actually having the disease tuberculosis are very different. When most people breathe in M. tuberculosis bacteria, the immune system quickly seals off the invading bacteria in the lungs and protects the body from illness. These people are said to have latent, or inactive, TB (also called primary infection): their bodies carry the germs, but they have no symptoms and are not contagious. However, latent TB germs sometimes escape the immune systems barriers and cause disease.

HIV and TB: A Lethal Combination

One of the reasons for the surge in TB cases in the 1980s was the rapid increase in the number of HIV cases. Because HIV/AIDS weakens the immune system, patients who have HIV/AIDS are at high risk for contracting TB when the germ first is breathed in. Approximately 11 million people around the globe are infected with both HIV and TB. TB is more likely to spread to other areas of the body in people with HIV, and multidrug-resistant (MDR) TB is much more dangerous in these patients. TB infection in patients who have HIV/AIDS can be cured if found and treated early.

When a persons immune system is no longer able to contain the bacteria, or if latent TB activates for other reasons, tuberculosis disease, or active TB, develops (also called secondary infection). Patients may feel sick quickly or develop symptoms gradually over weeks or months, and they may be highly contagious until treated. If TB travels through the blood to invade organs outside the lungs, it is known as disseminated TB. Many organs and bones, including the brain, pericardium (sac surrounding the heart), kidneys*, gastrointestinal* tract, and spine, can become involved and be damaged by the infection.

*kidneys
are the pair of organs that filter blood and remove waste products and excess water from the body in the form of urine.
*gastrointestinal
(gas-tro-in-TES-tih-nuhl) means having to do with the organs of the digestive system, the system that processes food. It includes the stomach, intestines, and other organs involved in digestion, including the liver and pancreas.

Is TB Common?

TB is one of the most common causes of death due to infection in the world. About 2 million people around the world die from TB each year. In the nineteenth century, TB was a major cause of death, especially among young children. Drugs to treat the disease were first developed in the 1940s, and they dramatically lowered the number of TB cases over the next few decades. Unfortunately, TB began to resurface in the 1980s, but the number of cases has been declining in recent years. Between 10 and 15 million Americans are believed to have latent TB.

There are several reasons why TB made a comeback:

  • HIV/AIDS* has weakened the immune systems of many people, increasing their likelihood of contracting TB.
*AIDS ,
or acquired immunodeficiency (ih-myoo-no-dih-FIH-shen-see) syndrome, is an infection that severely weakens the immune system; it is caused by the human immunodeficiency virus (HIV).
  • Increased numbers of malnourished, poor, or homeless people live in crowded, unclean conditions and are vulnerable to infection.
  • TB bacteria become more resistant to medications when patients do not take the drugs as prescribed. Multidrug-resistant (MDR) TB is difficult to treat and spreads easily.
  • Immigration to the United States from countries with high rates of TB has increased.

TB can affect anyone, but it is most common among immigrants from countries with high levels of TB and people whose immune systems are weak because of chronic* illness, medications that affect the immune system, infancy, old age, poor nutrition, unclean or crowded living areas (including prisons), alcoholism, or intravenous* (IV) drug use.

*chronic
(KRAH-nik) means continuing for a long period of time.
*intravenous
(in-tra-VEE-nus) means within or through a vein. For example, medications, fluid, or other substances can be given through a needle or soft tube inserted through the skins surface directly into a vein.

In the twenty-first century, the number of TB cases is falling once again in the United States thanks to effective public health measures, including finding contacts of anyone known to have TB so that they may be treated as well, and directly observing that patients take medication as prescribed.

How Is TB Spread?

Active TB involving the lungs is highly contagious if untreated. Like the flu, TB is spread through the air. When a person with active TB sneezes, coughs, or talks closely to others, bacteria are passed through tiny drops of fluid from the mouth and nose that are unknowingly breathed in by others. Spending lots of time in close quarters with a person who has untreated active TB is the most common way to become infected. A brief encounter with an infected person usually does not spread TB. Touching an infected person or his or her belongings does not put a person at risk for TB. Within a few weeks of the start of effective treatment, patients are no longer contagious.

What Are the Signs and Symptoms of TB?

People with latent TB have no symptoms, but they need to be aware of signs of active TB. Active TB may begin with mild symptoms like those of the flu but quickly worsens. Possible symptoms include:

  • cough that lasts a long time
  • coughing up blood or lots of mucus*
*mucus
(MYOO-kus) is a thick, slippery substance that lines the insides of many body parts.
  • chest pain
  • loss of appetite and weight loss
  • weakness and exhaustion
  • fever and chills
  • night sweats

If TB spreads to other parts of the body, additional serious symptoms may occur, depending on the organs involved.

How Do Doctors Diagnose and Treat TB?

TB infection is detected through a skin test known as the Mantoux test or PPD (purified protein derivative) test. A tiny amount of tuberculin (too-BER-kyoo-lin) substance, a protein taken from M. tuberculosis, is injected into the skin of an arm. A few days later a health professional will check to see if a bump has formed at the site of the injection. If the bump is wider than a certain size (for most people, 10 to 15 millimeters or a half inch), the patient most likely has been infected by TB bacteria; this is known as a positive skin test.

Next, a doctor will determine if the patient has active TB through a physical exam and by asking about symptoms and people the patient has had close contact with recently. The doctor may hear crackles when listening to the lungs with a stethoscope if a person has active TB. A chest X ray will be done, and samples of sputum*, blood, and urine may be tested. It can take weeks to confirm a diagnosis, although treatment can begin based on the skin test results and the persons symptoms.

*sputum
(SPYOO-tum) is a substance that contains mucus and other matter coughed out from the lungs, bronchi, and trachea.

MDR TB

Multidrug-resistant tuberculosis (MDR TB) occurs when TB patients stop taking their prescribed medications or do not take them as directed. Patients often stop taking the drugs when they begin to feel better or to avoid side effects. However, TB bacteria can survive inside the body for several months during treatment and are ready to spring back into activity when the medication disappears.

Symptoms return with a vengeance, and infected people become highly contagious again, putting those close to them at risk. In MDR TB, germs become stronger than the antibiotics, making the drugs less effective. Patients with MDR TB need special medications, but they may not work as well. In addition, patients can spread this highly dangerous form of the disease to others.

One way to fight this problem is through directly observed therapy (DOT). In DOT, patients must take their medications regularly in the presence of a health professional. Home visits by health professionals to supervise the taking of medications or free transportation and meals often are provided to encourage patients to take part in this type of program.

Both latent and active TB can be cured if patients closely follow their doctors orders. Antibiotics must be taken by mouth every day for 6 months to 1 year. Hospitalization and isolation may be required in the early stages of active disease for people who are highly contagious or who have severe symptoms. Patients must continue to take medications even if they begin to feel better. If they do not, the germs that are still in the body can cause symptoms to return and drugs to stop working properly due to the development of MDR TB.

Once treatment begins, TB symptoms disappear within a few weeks. People with TB can lead normal, active lives while taking their medications over the course of several months.

What Are Some Complications of TB?

Complications of TB include:

  • side effects of the drugs used to treat TB, which range from mild to severe
  • lung damage and difficulty breathing
  • damage to other organs from disseminated TB
  • development of MDR TB
  • other bacterial infections
  • death

Can TB Be Prevented?

The Centers for Disease Control and Prevention recommends that people at high risk for TB (such as those with HIV infection or immigrants from areas with high rates of TB) get a skin test yearly so that treatment can begin immediately if they are found to have TB.

A TB vaccine* is given to infants and toddlers in countries with high levels of the disease. The vaccine is not commonly used in the United States because it does not always work and it may cause a positive skin test, making it more difficult to detect true TB infection.

*vaccine
(vak-SEEN) is a preparation of killed or weakened germs, or a part of a germ or product it produces, given to prevent or lessen the severity of the disease that can result if a person is exposed to the germ itself. Use of vaccines for this purpose is called immunization.

Practical prevention tips include:

  • avoiding close contact with people infected with TB until they are no longer contagious
  • wearing a special type of facemask (called a respirator) that can prevent the spread of TB if close contact with someone who has TB is necessary

See also

AIDS and HIV Infection

Pneumonia

Public Health

Resources

Organizations

American Lung Association, 61 Broadway, 6th Floor, New York, NY 10006. The American Lung Association offers information about tuberculosis and other diseases that affect the lungs at its website. Telephone 212-315-8700 http://www.lungusa.org

National Institute of Allergy and Infectious Diseases (NIAID), Building 31, Room 7A-50, 31 Center Drive MSC 2520, Bethesda, MD 20892. The NIAID, part of the National Institutes of Health, posts information about tuberculosis at its website.

http://www.niaid.nih.gov

U.S. Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, Atlanta, GA 30333. The CDC is the U.S. government authority for information about infectious and other diseases. It provides information about tuberculosis at its website.

Telephone 800-311-3435 http://www.cdc.gov

World Health Organization (WHO), Avenue Appia 20, 1211 Geneva 27, Switzerland. WHO posts information about tuberculosis and tracks TB cases worldwide on its website.

Telephone 011-41-22-791-2111 http://www.who.int

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tuberculosis

tu·ber·cu·lo·sis / təˌbərkyəˈlōsis; t(y)oō-/ (abbr.: TB) • n. an infectious disease characterized by the growth of nodules (tubercles) in the tissues, esp. the lungs, caused chiefly by the bacterium Mycobacterium tuberculosis.

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tuberculosis

tuberculosisglacis, Onassis •abscess •anaphylaxis, axis, praxis, taxis •Chalcis • Jancis • synapsis • catharsis •Frances, Francis •thesis • Alexis • amanuensis •prolepsis, sepsis, syllepsis •basis, oasis, stasis •amniocentesis, anamnesis, ascesis, catechesis, exegesis, mimesis, prosthesis, psychokinesis, telekinesis •ellipsis, paralipsis •Lachesis •analysis, catalysis, dialysis, paralysis, psychoanalysis •electrolysis • nemesis •genesis, parthenogenesis, pathogenesis •diaeresis (US dieresis) • metathesis •parenthesis •photosynthesis, synthesis •hypothesis, prothesis •crisis, Isis •proboscis • synopsis •apotheosis, chlorosis, cirrhosis, diagnosis, halitosis, hypnosis, kenosis, meiosis, metempsychosis, misdiagnosis, mononucleosis, myxomatosis, necrosis, neurosis, osmosis, osteoporosis, prognosis, psittacosis, psychosis, sclerosis, symbiosis, thrombosis, toxoplasmosis, trichinosis, tuberculosis •archdiocese, diocese, elephantiasis, psoriasis •anabasis • apodosis •emphasis, underemphasis •anamorphosis, metamorphosis •periphrasis • entasis • protasis •hypostasis, iconostasis

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Tuberculosis

Tuberculosis

Definition

Tuberculosis (TB) is a potentially fatal contagious disease that can affect almost any part of the body but is mainly an infection of the lungs. It is caused by a bacterial microorganism: the tubercle bacillus or Mycobacterium tuberculosis. Although TB can be treated 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〉.

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Tuberculosis

Tuberculosis

Resources

Tuberculosis is a disease caused by the bacterium Mycobacterium tuberculosis. The organism infects the lungs and causes a debilitating condition that historically was known as consumption. In the 1970s, scientists considered tuberculosis as largely defeated following the widespread use of antibiotics. Today, multi-drug resistant Mycobacterium tuberculosis has developed, and tuberculosis has reemerged as a worldwide public health problem.

Tuberculosis is not a new disease. Egyptian mummies that are over 4,000 years old have shown symptoms of tuberculosis. The Greek physician Hippocrates (ca. 470410 BC) described a condition that he termed pthisis. His account makes it clear that he was observing a person with tuberculosis.

The term consumption reflected the progression of tuberculosis. Patients became lethargic, weak, and seemed to waste away. The role of bacteria in tuberculosis became clear in 1882, when the German physician Robert Koch (18431910) discovered a staining technique that allowed bacteria to be visible using a lightmicroscope. In Kochs time, and even into the middle of the twentieth century, the main treatment for tuberculosis was the isolation of patients in facilities called sanitoriums. Here, patients spent much of their time exposed to the dry, fresh outdoor air, which lessened the spread of the bacteria.

Tuberculosis is infectious, and is spread from person to person via inhaling contaminated droplets in the air. Often, someone can be infected with Mycobacterium tuberculosis yet not feel ill. This is also called latent tuberculosis. An active infection can appear at a later time. A person with tuberculosis cannot spread the germ to others until the infection becomes active.

In the twentieth century, specific chemical treatments for tuberculosis were developed. French bacteriologists Leon Calmette and Camille Guèrin found a way to grow Mycobacterium tuberculosis so that its ability to cause disease was weakened. This weakened, or attenuated, microbe eventually formed the basis of a vaccine. The bacille Calmette-Guérin (BCG) vaccine, which was first given to people in 1921, is still in use today.

Unfortunately, the potential of BCG has not been realized because the vaccine is protective against the form of tuberculosis that occurs in children rather than in adults. Also, because samples of the original vaccine were kept, the development of numerous formulations of BCG have made it difficult to establish which of the many variations of the vaccine is effective.

One variant of BCG, called Evans BCG, was withdrawn from use in July 2002 because of concerns that it was not protective against infection. Every vaccine, particularly those that use attenuated microorganisms, carries some risk. In the case of Evans BCG, the risks of its use were deemed to be greater than any benefit resulting from its use.

Beginning in the 1940s, antibiotics were discovered and chemically synthesized. An antibiotic called streptomycin was an immediate success against the tuberculosis bacteria. Unfortunately, resistance to the antibiotic soon developed. A succession of antibiotics was able to keep tuberculosis at bay for some decades. However, beginning in the 1980s, the number of cases of tuberculosis once again began to rise.

Part of this increase has paralleled the emergence and spread of Acquired Immunodeficiency Syndrome (AIDS). AIDS devastates the immune system, which gives other infections, including tuberculosis, a better chance to flourish. Another factor contributing to the spread of tuberculosis is the emergence of strains of Mycobacterium tuberculosis that are resistant to many antibiotics.

The World Health Organization (WHO) now estimates that about 15 million people worldwide have active TB, and that almost two million people die from the disease each year, mostly in developing countries. An initiative set in motion by the WHO and the Stop Tuberculosis Partnership proposes to treat 50 million people with tuberculosis and save 14 million lives during the decade from 20062015.

See also Epidemiology.

Resources

BOOKS

Reichman, L.B., and J.H. Tanne. Time Bomb: The Global
Epidemic of Multi-Drug Resistant Tuberculosis.
New
York: McGraw-Hill, 2001.

PERIODICALS

Naqui, H., et al. Tuberculosis and Human Rights. Kekkaku 80(1) (January 2005):3145.

OTHER

Centers for Disease Control and Prevention. Division of Tuberculosis Elimination. 1600 Clifton Road, NE Mailstop E-10, Atlanta, GA 30333. (404) 6398135. <http://www.cdc.gov/nchstp/tb/> (accessed March 29, 2007).

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Tuberculosis

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

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Tuberculosis

Tuberculosis

Definition

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

Description

Overview

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

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

Tuberculosis cases, percentages, and case rates per 100,000 population by age group: United States, 1993–2006
  45–64 ≤65
Year Total
cases
No. (%) Rate No. (%) Rate
source: Reported Tuberculosis in the United States, 2006. Centers for Disease Control and Prevention, U.S. Department of Health and Human
Services
(Illustration by GGS Information Services. Cengage Learning, Gale)
199312,0176,197(25)12.45,820(23)17.7
199411,6646,125(25)11.95,539(23)16.6
199511,2285,960(26)11.35,328(23)15.8
199610,6485,572(26)10.25,076(24)14.9
19979,9405,277(27)9.44,663(24)13.6
19989,3334,956(27)8.54,377(24)12.6
19998,8784,858(28)8.04,020(23)11.6
20008,1534,637(28)7.43,516(22)10.0
20017,8084,515(28)7.03,293(21)9.3
20027,3234,182(28)6.33,141(21)8.8
20037,2774,283(29)6.22,994(20)8.3
20047,0054,194(29)5.92,811(19)7.7
20056,9404,125(29)5.72,815(20)7.7
20066,7294,053(29)5.42,676(19)7.2

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.

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Tuberculosis

TUBERCULOSIS


Tuberculosis (TB) is a disease that played a major role in mortality decline in developed countries, and it remains a major cause of morbidity (illness) and mortality in developing countries. Tuberculosis is caused by infection with the bacterium Mycobacterium tuberculosis, discovered in 1882 by the German scientist Robert Koch (1843–1910). The related germ Mycobacterium africanum also causes TB in sub-Saharan Africa, but even in this region Mycobacterium tuberculosis predominates. The bovine form of TB, caused by Mycobacterium bovis, can also be transmitted to humans, but pasteurization of milk has reduced the chances of this. In historical texts, TB is sometimes referred to as consumption or pthisis. A notable aspect of TB is that it is an infectious disease of adults, not primarily of youth or the elderly.

Both historically and at present, tuberculosis of the lungs, called pulmonary tuberculosis, accounts for the major portion of TB morbidity and mortality. But tuberculosis can assume many forms, including tuberculosis meningitis, Pott's disease (TB of the vertebral column), and infection of any internal organ. Tuberculosis is a notable example of the difference between infection and disease. Those infected with TB (i.e., harboring the bacilli in their bodies) may develop clinical signs of the disease either immediately or sometimes many years after the first infection. Person-to-person spread occurs when someone with active tuberculosis coughs, producing droplets containing bacilli, which can infect someone nearby. Not all active cases are contagious (i.e., produce bacilli when coughing), however.

A tuberculosis vaccine, BCG (bacille Calmette-Guerin), exists, but its protective efficacy against TB in adults is variable; it is more effective in protecting children. In some populations, vaccination with BCG also protects against leprosy, which is caused by Mycobacterium leprae, a cousin of the TB-causing bacterium. The first antibiotic against TB was streptomycin, first used widely in 1947. Before the introduction of antibiotics, TB patients were treated in specialized sanatoriums, reflecting the belief that fresh air was curative. While this is not true, the sanatoriums did diminish the chances of TB transmission by removing the infected from the general population.

Figure 1 shows age-specific death rates, by sex, for TB (all forms), for the United States. Death rates are shown for 1900, when TB as a cause of death was of overwhelming importance; for 1939, by which time TB mortality had declined markedly but was still fairly high; and for 1998, after a half-century of antibiotic use. The figure depicts four key facets of the demography of TB. First, the data highlight the radical decline of tuberculosis mortality during the twentieth century, with most of the drop occurring before the introduction of antibiotics. Second, they show that TB is as much a disease of middle age as it is of the young and the elderly. This is in contrast to most other infectious diseases of similar importance: Diseases such as measles or pertussis are concentrated in childhood; other diseases such as influenza cause morbidity at all ages, but mortality is typically concentrated at the youngest and oldest ages. Third, death rates for males and females exhibit distinctly different patterns, with males having on average significantly higher TB mortality rates, yet at some ages female mortality is higher. Finally, when TB death rates decline, they do not fall evenly at all ages; both the shape and the level of the age-mortality curves change. The figure is broadly representative of the decline of TB in other developed countries.

Worldwide, there is great variability across nations in TB death rates. In 2002, the following nations had the highest TB death rates in their respective world regions (deaths per 100,000 population): Zambia, 290; Djibouti, 164; Haiti, 137; Cambodia, 90; Indonesia, 68; Russia, 17. Estimates for other nations include: South Africa, 166; India, 46; China, 21; Mexico, 6; Portugal, 5; United Kingdom, 2; United States, 1. These are crude death rates, not adjusted for population age composition, but they do correctly

FIGURE 1

reflect overall tuberculosis disease burden in terms of deaths per capita. Compare these data to the following sample of historical estimates of pulmonary TB death rates (listed by country, year, and death rate per 100,000 population), in chronological order: England and Wales in 1861, 258; Japan in 1899, 127; United States in 1900, 168; Chile in 1904, 270; Australia in 1911, 67; Portugal in 1920, 125; England and Wales in 1921, 89; France in 1926, 143; and South Africa (nonwhite population) in 1951, 300.

Tuberculosis is central to the story of what was one of the great debates in population studies. The British epidemiologist Thomas McKeown (1911–1988) maintained that the standard of living in general, and improved nutrition in particular, played a more important role than did medicine and public-health measures in the historical decline of mortality. He used the case of TB in support of the thesis, noting, among other things, that much of the decline in TB mortality occurred before the introduction of antibiotics. While improved nutrition was certainly a factor in the decline of TB, a number of objections have been raised against McKeown's general argument. His analysis rested mainly on data from England and Wales, in which the decline of TB in the nineteenth century played an idiosyncratically large role in the decline of mortality overall, thus exaggerating the importance of the decline of TB. And the use of sanitariums to reduce TB transmission is best viewed as a public-health measure, not a factor reflecting improved living standards.

In the 1990s TB strains resistant to multiple antibiotics became a significant problem in several countries, most notably in the former Soviet Union–a worrisome development. In any region where such strains become prevalent, reversal of progress against TB cannot be ruled out. This is of particular concern in developing countries, where TB prevalence, transmission, and mortality are still relatively high and where historical declines have been much less rapid than in the advanced industrialized countries. Infection with human immunodeficiency virus (HIV) is a major risk factor for developing active TB disease, with initial HIV-positive status followed by TB exposure being more severe in most cases than the reverse order of infection. In regions where prevalence of TB and HIV/AIDS are both high, most notably in sub-Saharan Africa, HIVTB coinfection is a strong contributing factor to the lack of progress in reducing tuberculosis morbidity and mortality.

See also: AIDS; Diseases: Infectious; Health Transition; Mortality Decline; Mortality Reversals.

bibliography

Dormandy, Thomas. 1999. The White Death: A History of Tuberculosis. London: Hambledon Press; New York: New York University Press.

Dye, Christopher, Suzanne Scheele, Paul Dolin, Vikram Pathania, and Mario C. Raviglione.1999. "Global Burden of Tuberculosis: Estimated Incidence, Prevalence, and Mortality by Country." Journal of the American Medical Association 282: 677–686.

Espinal, Marcos A., Adalbert Laszlo, Lone Simonsen, Fadila Boulahbal, Sang Jae Kim, Ana Reniero, Sven Hoffner, Hans L. Rieder, Nancy Binkin, Christopher Dye, Rosamund Williams, and Mario C. Raviglione. 2001. "Global Trends in Resistance to Antituberculosis Drugs." New England Journal of Medicine 344: 1,294–1,303.

McKeown, Thomas. 1976. The Modern Rise of Population. London: Edward Arnold; New York: Academic Press.

Preston, Samuel H. 1990. "Sources of Variation in Vital Rates: An Overview." In Convergent Issues in Genetics and Demography, ed. Julian Adams, David A. Lam, Albert I. Hermalin, and Peter E. Smouse. New York: Oxford University Press.

Andrew Noymer

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Tuberculosis

Tuberculosis

Tuberculosis is a disease caused by the bacterium Mycobacterium tuberculosis. The organism infects the lungs and causes a debilitating condition that historically was known as consumption. In the 1970s, scientists considered tuberculosis as largely defeated following the widespread use of antibiotics . Today, multi-drug resistant Mycobacterium tuberculosis has developed, and tuberculosis has reemerged as a worldwide public health problem.

Tuberculosis is not a new disease. Indeed, examinations of Egyptian mummies that are over 4,000 years old have shown symptoms of tuberculosis. Hippocrates, the father of medicine, described a malady in 460 b.c. that he termed pthisis. His description makes it clear that he was describing tuberculosis.

The term consumption reflected the progression of tuberculosis. Patients became lethargic, weak, and seemed to waste away. The role of bacteria in tuberculosis became clear in 1882, when Robert Koch discovered a staining technique that allowed bacteria to be visible using a light microscope . In Koch's time, and even into the middle of the twentieth century, the main treatment for tuberculosis was the isolation of patients in facilities called sanitoriums. Here, patients spent much of their time exposed to the dry, fresh outdoor air, which lessened the spread of the bacteria.

Tuberculosis is infectious, and is spread from person to person via inhaling contaminated droplets in the air. Often, someone can be infected with Mycobacterium tuberculosis yet not feel ill. This is also called latent tuberculosis. The infected person can spread the germ to others, however, by coughing or breathing. An active infection can appear at a later time.

In the twentieth century, specific chemical treatments for tuberculosis were developed. French bacteriologists Leon Calmette and Camille Guérin found a way to grow Mycobacterium tuberculosis so that its ability to cause disease was weakened. This weakened, or attenuated, microbe eventually formed the basis of a vaccine . The bacille Calmette-Guérin (BCG) vaccine, which was first given to people in 1921, is still in use today.

Unfortunately, the potential of BCG has not been realized because the vaccine is protective against the form of tuberculosis that occurs in children rather than in adults. Also, because samples of the original vaccine were kept, the development of numerous formulations of BCG have made it difficult to establish which of the many variations of the vaccine is effective.

One variant of BCG, called Evans BCG, was withdrawn from use in July 2002 because of concerns that it was not protective against infection. Every vaccine, particularly those that use attenuated microorganisms , carries some risk. In the case of Evans BCG, the risks of its use were deemed to be greater than any benefit resulting from its use.

Beginning in the 1940s, antibiotics were discovered and chemically synthesized. An antibiotic called streptomycin was an immediate success against the tuberculosis bacteria. Unfortunately, resistance to the antibiotic soon developed. A succession of antibiotics was able to keep tuberculosis at bay for some decades. However, beginning in the 1980s, the number of cases of tuberculosis once again began to rise.

Some 30 million people around the world died of tuberculosis in the 1990s. The U.S. Department of Health and Human Services predicts tuberculosis, the "forgotten plague," will spread further by the year 2005. In 1990 there were 7,537,000 TB cases worldwide. That number is expected to rise by almost 60%, to 11,875,000 cases by 2005.

Part of this increase has paralleled the emergence and spread of Acquired Immunodeficiency Syndrome (AIDS ). AIDS devastates the immune system , which gives other infections, including tuberculosis, a better chance to flourish. Another factor contributing to the spread of tuberculosis is the emergence of strains of Mycobacterium tuberculosis that are resistant to many antibiotics.

See also Epidemiology.


Resources

books

Reichman, L.B., and J.H. Tanne. Time Bomb: The Global Epidemic of Multi-Drug Resistant Tuberculosis. New York: McGraw-Hill, 2001.

periodicals

Starke, J.R., et al. "The Role of BCG Vaccine in the Prevention and Control of Tuberculosis in the United States: A Joint Statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices." Morbidity and Mortality Weekly Report 45 (April 1996): 1–18.


organizations

Centers for Disease Control and Prevention. Division of Tuberculosis Elimination. 1600 Clifton Road, NE Mailstop E-10, Atlanta, GA 30333. (404) 639–8135. <http://www.cdc.gov/nchstp/tb/>.

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Tuberculosis

TUBERCULOSIS

modern concepts of tuberculosis
treatment
bibliography

The symptoms of tuberculosis, more often called consumption or phthisis in the nineteenth century, have been known in Europe for many hundreds of years. A Dublin physician described consumption of the lungs in 1772 in much the same way as modern medical treatises do—as an obstinate cough, inclination to vomit, oppression of the chest, habitual fever that increases after eating, general paleness, high pulse, night sweats, loss of weight, and coughing up of blood. Infection with the tubercle bacillus was widespread in Europe; some calculations for the early twentieth century suggest an almost 100 percent rate of infection. But though not all who were infected went on to develop the full-blown disease, mortality was high. At the height of the epidemic possibly at least two-thirds to three-quarters of those who had the disease died, most commonly from respiratory failure. Even among the recovered, tuberculosis could return in later life.

Some historians see the high rates of tuberculosis in Europe in the eighteenth and nineteenth centuries as the downward curve of an epidemic that had reached its peak several hundred years before. Others argue that a deteriorating urban environment caused an increased incidence in the early nineteenth century. All agree that in most European countries—Ireland and Norway were the exception—tuberculosis was on the decline in the late nineteenth century. Nonetheless, of all the infectious diseases, tuberculosis was the most important contributor to mortality in the nineteenth century and, while its decline continued into the twentieth, it was still the leading cause of death among young adults. Tuberculosis was more prevalent in the cities and towns. There is some evidence that in the nineteenth century, with important exceptions, mortality from tuberculosis was higher among women than men in rural areas, whereas the reverse was true for the towns; no definitive explanation for this variation is known in the early twenty-first century.

modern concepts of tuberculosis

Modern concepts of the causes of tuberculosis date from 1882, when the German scientist Robert Koch identified the bacteria responsible for the disease. Before then only two significant developments had taken place that affected the understanding of tuberculosis. One was the refinement around 1816 by the French scientist René-Théophile-Hyacinthe Laennec of the stethoscope, which aided better diagnosis; the other was the microscope, which enabled the identification of the characteristic lesions or "tubercles" that were present in the infected organs of sufferers. This established that, although consumption of the lungs was the most prevalent form of the disease, it could be found in other parts of the human body. It also gave the disease its modern name—tuberculosis.

Before Koch it was not known whether tuberculosis was infectious, though some doctors suspected it was. It was widely believed to be hereditary, and this led to families concealing the disease. Innumerable cures were offered in the early nineteenth century, all in retrospect valueless, including inhalation of iodine, a diet rich in fat, water cures, and even starvation. Some doctors attributed its incidence to overindulgence. By the middle of the nineteenth century, climate was considered to be an important influence on tuberculosis, and medical journals of the period are full of investigations of the incidence of tuberculosis in different climates around the world. This led sufferers to take tours or voyages in search of a climate they hoped would improve their health. A significant number of immigrants from Europe to the New World and the colonies were tuberculosis sufferers.

The lingering nature of death from consumption of the lungs and the fact that it seemed to strike the young in their prime led to a romantic iconography growing up around the disease in the nineteenth century. Some symptoms—flushed cheeks, glittering eyes—were considered to enhance beauty. The febrile excitement that sufferers often displayed in their psychological reaction to their illness led to an association between susceptibility to tuberculosis and emotional and artistic temperaments. Thus in operas, novels, and art, death from tuberculosis was used as the climax of a tragic


narrative of unfulfilled promise and youthful hopes dashed. Most famously the theme appears in the death of Mimi in Giacomo Puccini's opera La Bohème (1896), based on Henri Murger's novel of 1849. However, there are many examples in real life of the impact of tuberculosis on promise. The disease claimed the composer Frédéric Chopin at thirty-nine; the Brontë sisters Emily, Anne, and Charlotte at ages thirty, twenty-nine, and thirty-eight respectively; and the playwright Anton Chekhov at forty-four and the poet John Keats at age twenty-five.

treatment

The belief that fresh, uncontaminated air was good for the tuberculosis sufferer gained ground in the nineteenth century and came to dominate treatment of the disease. One product of this was the specialized tuberculosis hospital or sanatorium situated in an area chosen for climate and fresh air. The most famous example was the hospital in the German Black Forest opened by Dr. Otto Walther in 1888, which combined bed rest, medical attendance, and exposure to the air. Sanatoriums based on similar principles, catering initially to the private patient, opened throughout Europe. Isolated mountain retreats in Europe, brought within reach by the railway, experienced burgeoning local economies built on the provision of sanatoriums for the tubercular. The sanatorium led to the development of a specialized form of hospital architecture and to a literature based on the patient's experience. Every European country produced novels of sanatorium life, most now forgotten. However, the most famous is the German novelist Thomas Mann's The Magic Mountain, published in 1924. This was the year that the writer Franz Kafka, whose life and work was also over-shadowed by the disease, died from tuberculosis in an Austrian sanatorium.

The late nineteenth century saw a dramatic change in attitudes toward tuberculosis. Koch's discovery of the infectious nature of tuberculosis opened up the possibility that it could be susceptible to the kind of public health measures that had once been used to combat the "fevers"—the epidemic diseases such as cholera, typhus, and smallpox. These included notification, isolation, and decontamination. Between 1890 and 1914 nongovernmental organizations emerged in Europe, usually initiated and led by medical professionals. They raised consciousness of the disease among the public, advocated hygiene, and strove to bring the benefits of the sanatorium within reach of the poor. The principle they operated under was that the disease could be prevented, contained, and perhaps even cured. Thus tuberculosis became a focus for private charitable and eventually government action. A series of international conferences acted as a vector for the spread of ideas about its treatment across Europe. They encouraged comparisons between national tuberculosis rates, though the figures these comparisons were based on were notoriously unreliable. Nonetheless, this helped to make lowering the national tuberculosis rate a matter of patriotic duty.

There were national styles in the public health treatment of tuberculosis. Germany was the country with strongest adherence to the sanatorium; France to the outpatient clinic dealing exclusively with tuberculosis—the tuberculosis dispensary. Some countries had a system of compulsory notification of sufferers, others resisted. Two significant disparities in tuberculosis policy concerned the use of the antituberculosis vaccine BCG and the treatment of bovine tuberculosis. Koch's discoveries had encouraged the search for a vaccine against tuberculosis and in 1921 two French scientists Albert-Léon-Charles Calmette and Camille Guérin announced the discovery of BCG. By the 1930s it was in use in France and Scandinavian countries but elsewhere, particularly in Britain, its value as a preventative measure was questioned. By the 1940s, however, the use of BCG, particularly for children, had become widespread in Europe.

The second was treatment of bovine tuberculosis. Tubercles similar to those seen in humans were observed in animals, and the bacteria Koch found in affected humans was also present in animals. But he doubted, incorrectly, that tuberculosis could be transmitted between animals and humans. In the first decade of the twentieth century experimental proof that it could be so transmitted was available and generally accepted. The chief vector was in the milk and meat of infected animals, primarily cattle. Tuberculosis transmitted by milk affected the bones and internal organs of children in particular. This led to another familiar figure of the nineteenth century—the severely crippled child. Improved agricultural practices and pasteurization of milk eventually led to decline in tuberculosis of bovine origin, but the politics of agriculture intervened in some countries to slow down reform.

See alsoDisease; Public Health.

bibliography

Barnes, David. The Making of a Social Disease: Tuberculosis in Nineteenth-Century France. Berkeley, Calif., 1995.

Bryder, Lynda. Below the Magic Mountain: A Social History of Tuberculosis in Twentieth-Century Britain. Oxford, U.K., 1988.

Dormandy, Thomas. "The White Death": A History of Tuberculosis. London, 1999.

Jones, Greta. "Captain of All These Men of Death": The History of Tuberculosis in Nineteenth and Twentieth Century Ireland. New York and Amsterdam, 2001.

Smith, Francis Barrymore. The Retreat of Tuberculosis, 1850–1960. London, 1988.

Greta Jones

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Learn more about citation styles

Citation styles

Encyclopedia.com gives you the ability to cite reference entries and articles according to common styles from the Modern Language Association (MLA), The Chicago Manual of Style, and the American Psychological Association (APA).

Within the “Cite this article” tool, pick a style to see how all available information looks when formatted according to that style. Then, copy and paste the text into your bibliography or works cited list.

Because each style has its own formatting nuances that evolve over time and not all information is available for every reference entry or article, Encyclopedia.com cannot guarantee each citation it generates. Therefore, it’s best to use Encyclopedia.com citations as a starting point before checking the style against your school or publication’s requirements and the most-recent information available at these sites:

Modern Language Association

http://www.mla.org/style

The Chicago Manual of Style

http://www.chicagomanualofstyle.org/tools_citationguide.html

American Psychological Association

http://apastyle.apa.org/

Notes:
  • Most online reference entries and articles do not have page numbers. Therefore, that information is unavailable for most Encyclopedia.com content. However, the date of retrieval is often important. Refer to each style’s convention regarding the best way to format page numbers and retrieval dates.
  • In addition to the MLA, Chicago, and APA styles, your school, university, publication, or institution may have its own requirements for citations. Therefore, be sure to refer to those guidelines when editing your bibliography or works cited list.