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tuberculosis

 
Medical Encyclopedia: Tuberculosis

Definition

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

Description

Overview

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

Tuberculosis spread much more widely in Europe when the industrial revolution began in the late nineteenth century. The disease became widespread somewhat later in the United States, because the movement of the population to large cities made overcrowded housing so common. When streptomycin, the first antibiotic effective against M. tuberculosis, was discovered in the early 1940s, the infection began to come under control. Although other more effective anti-tuberculosis drugs were developed in the following decades, the number of cases of TB in the United States began to rise again in the mid-1980s. This upsurge was in part again a result of overcrowding and unsanitary conditions in the poor areas of large cities, prisons, and homeless shelters. Infected visitors and immigrants to the United States 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 to 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. As the end of the century approaches, 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 1992, the risk of TB was still increasing in all these groups.

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.

— David A. Cramer, MD



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Dictionary: tu·ber·cu·lo·sis   (tʊ-bûr'kyə-lō'sĭs, tyʊ-) pronunciation
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n. (Abbr. TB)
  1. An infectious disease of humans and animals caused by the tubercle bacillus and characterized by the formation of tubercles on the lungs and other tissues of the body, often developing long after the initial infection.
  2. Tuberculosis of the lungs, characterized by the coughing up of mucus and sputum, fever, weight loss, and chest pain.

[Latin tūberculum, tubercle; see tubercle + -OSIS.]



Bacterial disease caused by some species of mycobacterium (tubercle bacillus). Mentioned in ancient Egyptian records and by Hippocrates, it has occurred throughout history worldwide. In the 18th – 19th centuries it reached near-epidemic proportions in the rapidly industrializing and urbanizing Western world, where it was the leading cause of death until the early 20th century. TB resurged in the 1980s, spreading from AIDS patients to others, especially in prisons, homeless shelters, and hospitals, since enclosed settings promote spread. It occurs worldwide and is still a major cause of death in many countries. The body isolates the bacilli by forming tiny tubercles (nodules) around them. This often arrests TB's progress and no symptoms occur, but if the disease is not treated, it may become active — and contagious — later in life, most often when the immunity of the infected individual is suppressed (e.g., AIDS, after organ transplant). The original tubercle breaks down, releasing still viable bacilli into the bloodstream to cause a new infection, which starts with loss of energy and weight and persistent cough. Health deteriorates, with increasing cough and possibly pleurisy (see thoracic cavity) and spitting up blood. Growing tubercle masses may destroy so much lung tissue that respiration cannot supply the body with enough oxygen. Other organs can be affected, with complications including meningitis. A vaccine with weakened bacteria has helped control infection, but preventing exposure by recognizing and treating active TB early is more effective. Because many strains are resistant to drugs, treatment requires at least two drugs to which the patient's strain is sensitive and at least six months; inadequate treatment lets resistant bacilli multiply. The acute disease caused by multidrug-resistant strains is very hard to cure and usually fatal.

For more information on tuberculosis, visit Britannica.com.

Sci-Tech Encyclopedia: Tuberculosis
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An infectious disease caused by the bacillus Mycobacterium tuberculosis. It is primarily an infection of the lungs, but any organ system is susceptible, so its manifestations may be varied. Effective therapy and methods of control and prevention of tuberculosis have been developed, but the disease remains a major cause of mortality and morbidity throughout the world. The treatment of tuberculosis has been complicated by the emergence of drug-resistant organisms, including multiple-drug-resistant tuberculosis, especially in those with HIV infection. See also Acquired immune deficiency syndrome (AIDS).

Mycobacterium tuberculosis is transmitted by airborne droplet nuclei produced when an individual with active disease coughs, speaks, or sneezes. When inhaled, the droplet nuclei reach the alveoli of the lung. In susceptible individuals the organisms may then multiply and spread through lymphatics to the lymph nodes, and through the bloodstream to other sites such as the lung apices, bone marrow, kidneys, and meninges.

The development of acquired immunity in 2 to 10 weeks results in a halt to bacterial multiplication. Lesions heal and the individual remains asymptomatic. Such an individual is said to have tuberculous infection without disease, and will show a positive tuberculin test. The risk of developing active disease with clinical symptoms and positive cultures for the tubercle bacillus diminishes with time and may never occur, but is a lifelong risk. Only 5% of individuals with tuberculous infection progress to active disease. Progression occurs mainly in the first 2 years after infection; household contacts and the newly infected are thus at risk.

Many of the symptoms of tuberculosis, whether pulmonary disease or extrapulmonary disease, are nonspecific. Fatigue or tiredness, weight loss, fever, and loss of appetite may be present for months. A fever of unknown origin may be the sole indication of tuberculosis, or an individual may have an acute influenzalike illness. Erythema nodosum, a skin lesion, is occasionally associated with the disease.

The lung is the most common location for a focus of infection to flare into active disease with the acceleration of the growth of organisms. There may be complaints of cough, which can produce sputum containing mucus, pus- and, rarely, blood. Listening to the lungs may disclose rales or crackles and signs of pleural effusion (the escape of fluid into the lungs) or consolidation if present. In many, especially those with small infiltration, the physical examination of the chest reveals no abnormalities.

Miliary tuberculosis is a variant that results from the blood-borne dissemination of a great number of organisms resulting in the simultaneous seeding of many organ systems. The meninges, liver, bone marrow, spleen, and genitourinary system are usually involved. The term miliary refers to the lung lesions being the size of millet seeds (about 0.08 in. or 2 mm). These lung lesions are present bilaterally. Symptoms are variable.

Extrapulmonary tuberculosis is much less common than pulmonary disease. However, in individuals with AIDS, extrapulmonary tuberculosis predominates, particularly with lymph node involvement. Fluid in the lungs and lung lesions are other common manifestations of tuberculosis in AIDS. The lung is the portal of entry, and an extrapulmonary focus, seeded at the time of infection, breaks down with disease occurring.

Development of renal tuberculosis can result in symptoms of burning on urination, and blood and white cells in the urine; or the individual may be asymptomatic. The symptoms of tuberculous meningitis are nonspecific, with acute or chronic fever, headache, irritability, and malaise.

A tuberculous pleural effusion can occur without obvious lung involvement. Fever and chest pain upon breathing are common symptoms.

Bone and joint involvement results in pain and fever at the joint site. The most common complaint is a chronic arthritis usually localized to one joint. Osteomyelitis is also usually present.

Pericardial inflammation with fluid accumulation or constriction of the heart chambers secondary to pericardial scarring are two other forms of extrapulmonary disease.

The principal methods of diagnosis for pulmonary tuberculosis are the tuberculin skin test (an intracutaneous injection of purified protein derivative tuberculin is performed, and the injection site examined for reactivity), sputum smear and culture, and the chest x-ray. Culture and biopsy are important in making the diagnosis in extrapulmonary disease.

A combination of two or more drugs is used in the initial therapy of tuberculous disease. Drug combinations are used to lessen the chance of drug-resistant organisms surviving. The preferred treatment regimen for both pulmonary and extrapulmonary tuberculosis is a 6-month regimen of the antibiotics isoniazid, rifampin, and pyrazinamide given for 2 months, followed by isoniazid and rifampin for 4 months. Because of the problem of drug-resistant cases, ethambutol can be included in the initial regimen until the results of drug susceptibility studies are known. Once treatment is started, improvement occurs in almost all individuals. Any treatment failure or individual relapse is usually due to drug-resistant organisms. See also Drug resistance.

The community control of tuberculosis depends on the reporting of all new suspected cases so case contacts can be evaluated and treated appropriately as indicated. Individual compliance with medication is essential. Furthermore, measures to enhance compliance, such as directly observed therapy, may be necessary. See also Mycobacterial diseases.


World of the Body: tuberculosis
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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.

Thesaurus: tuberculosis
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noun

    An infectious disease producing lesions especially of the lungs: consumption (no longer in scientific use), phthisic (no longer in scientific use), phthisis (no longer in scientific use), white plague. See health/sickness.

Dental Dictionary: tuberculosis
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(tōōbur′kyōōlō′sis)
n

An infectious disease caused by Mycobacterium tuberculosis and characterized by the formation of tubercles in the tissues.

Tuberculosis of tongue. (Regezi/Sciubba/Pogrel, 2000)

Tuberculosis of tongue. (Regezi/Sciubba/Pogrel, 2000)

Definition

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

Description

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

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

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

Causes & Symptoms

Transmission

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

Once inhaled, water in the droplets evaporates and the tubercle bacilli may reach the small breathing sacs in the lungs (the alveoli), then spread through the lymph vessels to nearby lymph nodes. Sometimes the bacilli move through blood vessels to distant organs. At this point they may either remain alive but inactive (quiescent), or they may cause active disease. The likelihood of acquiring the disease increases with the concentration of bacilli in the air, and the seriousness of the disease is determined by the number of bacteria with which a patient is infected.

Ninety percent of patients who harbor M. tuberculosis do not develop symptoms or physical evidence of the disease, and their x rays remain negative. They are not contagious; however, these individuals may get sick at a later date and then pass on TB to others. Though it is impossible to predict whether a person's disease will become active, researchers surmise that more than 90% of cases of active tuberculosis come from this pool of people. An estimated 5% of infected persons get sick within 12-24 months of being infected. Another 5% heal initially but, after years or decades, develop active tuberculosis. This form of the disease is called reactivation TB, or post-primary disease. On rare occasions a previously infected person gets sick again after a second exposure to the tubercle bacillus.

Pulmonary Tuberculosis

Pulmonary tuberculosis is TB that affects the lungs, and represents about 85% of new cases diagnosed. It usually presents with a cough, which may or may not produce sputum. In time, more sputum is produced that is streaked with blood. The cough may be present for weeks or months and may be accompanied by chest pain and shortness of breath. Persons with pulmonary TB often run a low-grade fever and suffer from night-sweats. The patient often loses interest in food and may lose weight. If the infection allows air to escape from the lungs into the chest cavity (pneumothorax) or if fluid collects in the pleural space (pleural effusion), the patient may have difficulty breathing. The TB bacilli may travel from the lungs to lymph nodes in the sides and back of the neck. Infection in these areas can break through the skin and discharge pus.

Extrapulmonary Tuberculosis

Although the lungs are the major site of damage caused by tuberculosis, many other organs and tissues in the body may be affected. Abut 15% of newly diagnosed cases of TB are extrapulmonary, with a higher proportion of these being HIV-infected persons. The usual progression of the disease is to begin in the lungs and spread to locations outside the lungs (extrapulmonary sites). In some cases, however, the first sign of disease appears outside the lungs. The many tissues or organs that tuberculosis may affect include:

  • Bones. TB is particularly likely to attack the spine and the ends of the long bones.
  • Kidneys. Along with the bones, the kidneys are probably the most common site of extrapulmonary TB. There may, however, be few symptoms even though part of a kidney is destroyed.
  • Female reproductive organs. The ovaries in women may be infected; TB can spread from them to the peritoneum, which is the membrane lining the abdominal cavity.
  • Abdominal cavity. Tuberculous peritonitis may cause pain ranging from the mild discomfort of stomach cramps to intense pain that may mimic the symptoms of appendicitis.
  • Joints. Tubercular infection of joints causes a form of arthritis that most often affects the hips and knees.
  • Meninges. The meninges are tissues that cover the brain and the spinal cord. Infection of the meninges by the TB bacillus causes tuberculous meningitis, a condition that is most common in young children and the elderly. It is extremely dangerous. Patients develop headaches, become drowsy, and eventually comatose. Permanent brain damage can result without prompt treatment.
  • Skin, intestines, adrenal glands, and blood vessels. All these parts of the body can be infected by M. tuberculosis. Infection of the wall of the body's main artery (the aorta), can cause it to rupture with catastrophic results. Tuberculous pericarditis occurs when the membrane surrounding the heart (the pericardium) is infected and fills up with fluid that interferes with the heart's ability to pump blood.
  • Miliary tuberculosis. Miliary TB is a life-threatening condition that occurs when large numbers of tubercle bacilli spread throughout the body. Huge numbers of tiny tubercular lesions develop that cause marked weakness and weight loss, severe anemia, and gradual wasting of the body.

Diagnosis

TB is diagnosed through laboratory test results. The standard test for tuberculosis infection, the tuberculin skin test, detects the presence of infection, not of active TB. Skin testing has been done for more than 100 years. In this process, tuberculin is an extract prepared from cultures of M. tuberculosis. It contains substances belonging to the bacillus (antigens) to which an infected person has been sensitized. When tuberculin is injected into the skin of an infected person, the area around the injection becomes hard, swollen, and red within one to three days.

Today skin tests utilize a substance called purified protein derivative (PPD) that has a standard chemical composition and is therefore a good measure of the presence of tubercular infection. The PPD test, also called the Mantoux test, is not always 100% accurate; it can produce false positive as well as false negative results. The test may indicate that some people who have a skin reaction are not infected (false positive) and that some who do not react are in fact infected (false negative). The PPD test is, however, useful as a screener and can be used on people who have had a suspicious chest x ray, on those who have had close contact with a TB patient, and persons who come from a country where TB is common.

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

One important new advance in the diagnosis of TB is the use of molecular techniques to speed the diagnostic process as well as improve its accuracy. As of late 2002, four molecular techniques are increasingly used in laboratories around the world. They include polymerase chain reaction to detect mycobacterial DNA in patient specimens; nucleic acid probes to identify mycobacteria in culture; restriction fragment length polymorphism analysis to compare different strains of TB for epidemiological studies; and genetic-based susceptibility testing to identify drug-resistant strains of mycobacteria.

Treatment

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

Supportive treatments include:

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

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

Allopathic Treatment

Drug Therapy

Five drugs are most commonly used today to treat tuberculosis: isoniazid (INH), rifampin, pyrazinamide, streptomycin, and ethambutol. Of the five medications, INH is the most frequently used drug for both treatment and prevention. The first three drugs may be given in the same capsule to minimize and treat active TB the number of pills in the dosage. As of 1998, many patients are given INH and rifampin together for six months, with pyrazinamide added for the first two months. Hospitalization is rarely necessary because many patients are no longer infectious after about two weeks of combination treatment. A physician must monitor side effects and conduct monthly sputum tests. In 2002, the Centers for Disease Control (CDC) worked with medical organizations to release new guidelines that better individualize the drug regimens received by TB patients depending on their disease symptoms and severity. Many can now receive once-weekly doses of rifapentine in the continuation phase of treatment.

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

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

Surgery

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

Expected Results

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

Modern surgical methods are usually effective when necessary. Miliary tuberculosis is still fatal in many cases but is rarely seen today in developed countries. Even in cases in which the bacillus proves resistant to all of the commonly used medications, other seldom-used drugs may be tried because the tubercle bacilli have not yet developed resistance to them.

Prevention

Vaccination is widely used as a prevention measure for TB. A vaccine called BCG (Bacillus Calmette-Guérin, named after its French developers) is made from a weakened mycobacterium that infects cattle. Vaccination with BCG does not prevent infection, but it does strengthen the immune system of first-time TB patients. As a result, serious complications are less likely to develop. BCG is used more widely in developing countries than in the United States. Though the vaccine has been proven beneficial and fairly safe, its use is still controversial. It is not clear whether the vaccine's effectiveness depends on the population in which it is used or on variations in its formulation. Recently, efforts have been focused on developing a new vaccine.

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

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

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

Resources

Books

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

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

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

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

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

Periodicals

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

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

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

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

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

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

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

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

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

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

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

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

Organizations

American Lung Association. 432 Park Avenue South, New York, NY 10016. (800) LUNG-USA. .

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

Other

New York State Department of Health. Communicable Disease Fact Sheet. nyhealth@health.state.ny.us.

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

[Article by: Amy Cooper; Teresa G. Odle; Rebecca J. Frey, PhD]

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 15–24-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 24–72 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.

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: .

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

[Article by: Mary McNulty Stephanie Dionne Sherk]



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.

(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.

— RAJITA R. BHAVARAJU; LEE B. REICHMAN



US History Encyclopedia: Tuberculosis
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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 names—including consumption and phthisis—were 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 centers—living 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, 1876–1938. 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 Won—And Lost. Boston: Little, Brown, 1993.

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

 
Columbia Encyclopedia: tuberculosis
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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 from the 1950s until 1984; sanatoriums were closed and routine screening was abandoned in the United States. 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 declared TB a global health emergency. Approximately one third of the world's population is infected, and an estimated 1.6 million die each year. 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.

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 is usually used in combination with other antituberculosis drugs such as rifampin, pyrazinamide, and ethambutol. 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 drug 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).


Health Dictionary: tuberculosis
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(tuh-bur-kyuh-loh-sis)

An infectious disease caused by bacteria that mainly attack the lungs. The disease is characterized by the formation of patches, called tubercles, that appear in the lungs and, in later stages, the bones, joints, and other parts of the body. Tuberculosis is treated with combinations of antibiotics and is no longer considered a major health problem in industrialized countries. It was formerly called consumption.

  • Years ago, tuberculosis (consumption) was a major killer; it often figures in literature and drama.
  • In recent years, the incidence of tuberculosis has been on the increase in the United States, particularly in large cities, mainly because the strains of the bacterium have developed resistance to antibiotics.

  • Veterinary Dictionary: tuberculosis
    Top

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

    • atypical mycobacterial t. — see atypical mycobacteriosis.
    • avian t. — see Mycobacterium avium tuberculosis (below).
    • bovine t. — see Mycobacterium bovis tuberculosis (below).
    • cutaneous t. — infection with Mycobacterium tuberculosis uncommonly involves the skin; in dogs and cats it can occur as cutaneous ulcers, abscesses, plaques and nodules. More often, the term is used to describe infection with atypical mycobacteria.
    • fish t. — see fish tuberculosis.
    • Mycobacterium avium t. — causes a significant disease only in birds. In birds it is a chronic disease characterized by loss of body weight, poor egg production and eventual death. There are characteristic large gray, yellow or white tubercles in liver, spleen and intestinal wall. The disease is very persistent in a flock. In mammals it causes nonprogressive lesions, especially in lymph nodes, causing the animals to be positive to the tuberculin test.
    • Mycobacterium bovis t. — a chronic disease characterized by the development of tubercles or discrete nodular lesions in any organ. These may develop a necrotic center containing yellow-orange pus, often caseous. Diffuse involvement of lungs causing bronchopneumonia, and of uterus causing metritis, and of the udder also occur. The common clinical syndrome is wasting with localizing signs dependent on the organs involved. A common lesion in horses is osteomyelitis of a cervical vertebra.
    • Mycobacterium tuberculosis t. — infection with the human mycobacteria causes transient, usually lesionless infections in animals.
    • open t. — 1. that in which there are lesions from which tubercle bacilli are being discharged out of the body.
    • — 2. tuberculosis of the lungs with cavitation.
    • skin t. — is characterized by chronic indurated lesions on the skin of the lower limbs of cattle. There are nodules on the path of corded lymphatics. Nonpathogenic acid-fast bacteria are present in the lesions and affected cattle are positive to the tuberculin test. Also occurs uncommonly in dogs and cats as single or multiple nodules, ulcers, abscesses or plaques in the skin. See also mycobacteriosis.
    • t. testing — tuberculin testing.
    Wikipedia: Tuberculosis
    Top
    Tuberculosis
    Classification and external resources

    Chest X-ray of a patient with far-advanced tuberculosis
    ICD-10 A15.A19.
    ICD-9 010018
    OMIM 607948
    DiseasesDB 8515
    MedlinePlus 000077 000624
    eMedicine med/2324 emerg/618 radio/411
    MeSH D014376

    Tuberculosis (TB) is a common and often deadly infectious disease caused by mycobacteria, primarily Mycobacterium tuberculosis in humans.[1] Tuberculosis usually attacks the lungs but can also affect other parts of the body. It is spread through the air, when people who have the disease cough, sneeze, or spit. Most infections in humans result in asymptomatic, latent infection, and about one in ten latent infections eventually progresses to active disease, which, if left untreated, kills more than half of its victims.

    The classic symptoms are a chronic cough with blood-tinged sputum, fever, night sweats, and weight loss. Infection of other organs causes a wide range of symptoms. Diagnosis relies on radiology (commonly chest X-rays), a tuberculin skin test, blood tests, as well as microscopic examination and microbiological culture of bodily fluids. Treatment is difficult and requires long courses of multiple antibiotics. Contacts are also screened and treated if necessary. Antibiotic resistance is a growing problem in (extensively) multi-drug-resistant tuberculosis. Prevention relies on screening programs and vaccination, usually with Bacillus Calmette-Guérin vaccine.

    A third of the world's population has been infected with M. tuberculosis. New infections occur at a rate of one per second.[2] The proportion of people who become sick with tuberculosis each year is stable or falling worldwide but, because of population growth, the absolute number of new cases is still increasing.[3] In 2007 there were an estimated 13.7 million chronic active cases, 9.3 million new cases, and 1.8 million deaths, mostly in developing countries.[4] In addition, more people in the developed world are contracting tuberculosis because their immune systems are compromised by immunosuppressive drugs, substance abuse, or AIDS. The distribution of tuberculosis is not uniform across the globe; about 80% of the population in many Asian and African countries test positive in tuberculin tests, while only 5-10% of the US population test positive.[1]

    Contents

    Classification

    The current clinical classification system for tuberculosis (TB) is based on the pathogenesis of the disease.[citation needed]

    Classification System for TB
    Class Type Description
    0 No TB exposure
    Not infected
    No history of exposure
    Negative reaction to tuberculin skin test
    1 TB exposure
    No evidence of infection
    History of exposure
    Negative reaction to tuberculin skin test
    2 TB infection
    No disease
    Positive reaction to tuberculin skin test
    Negative bacteriologic studies (if done)
    No clinical, bacteriologic, or radiographic evidence of TB
    3 TB, clinically active M. tuberculosis cultured (if done)
    Clinical, bacteriologic, or radiographic evidence of current disease
    4 TB
    Not clinically active
    History of episode(s) of TB
    or
    Abnormal but stable radiographic findings
    Positive reaction to the tuberculin skin test
    Negative bacteriologic studies (if done)
    and
    No clinical or radiographic evidence of current disease
    5 TB suspect Diagnosis pending
    TB disease should be ruled in or out within 3 months

    Signs and symptoms

    Main symptoms of variants and stages of tuberculosis,[5][6] with many symptoms overlapping with other variants, while others are more (but not entirely) specific for certain variants. Multiple variants may be present simultaneously.

    When the disease becomes active, 75% of the cases are pulmonary TB, that is, TB in the lungs. Symptoms include chest pain, coughing up blood, and a productive, prolonged cough for more than three weeks. Systemic symptoms include fever, chills, night sweats, appetite loss, weight loss, pallor, and often a tendency to fatigue very easily.[2]

    In the other 25% of active cases, the infection moves from the lungs, causing other kinds of TB, collectively denoted extrapulmonary tuberculosis.[7] This occurs more commonly in immunosuppressed persons and young children. Extrapulmonary infection sites include the pleura in tuberculosis pleurisy, the central nervous system in meningitis, the lymphatic system in scrofula of the neck, the genitourinary system in urogenital tuberculosis, and bones and joints in Pott's disease of the spine. An especially serious form is disseminated TB, more commonly known as miliary tuberculosis. Extrapulmonary TB may co-exist with pulmonary TB as well.[8]

    Causes

    Scanning electron micrograph of Mycobacterium tuberculosis

    The primary cause of TB, Mycobacterium tuberculosis, is a small aerobic non-motile bacillus. High lipid content of this pathogen accounts for many of its unique clinical characteristics.[9] It divides every 16 to 20 hours, an extremely slow rate compared with other bacteria, which usually divide in less than an hour.[10] (For example, one of the fastest-growing bacteria is a strain of E. coli that can divide roughly every 20 minutes.) Since MTB has a cell wall but lacks a phospholipid outer membrane, it is classified as a Gram-positive bacterium. However, if a Gram stain is performed, MTB either stains very weakly Gram-positive or does not retain dye due to the high lipid & mycolic acid content of its cell wall.[11] MTB can withstand weak disinfectants and survive in a dry state for weeks. In nature, the bacterium can grow only within the cells of a host organism, but M. tuberculosis can be cultured in vitro.[12]

    Using histological stains on expectorate samples from phlegm (also called sputum), scientists can identify MTB under a regular microscope. Since MTB retains certain stains after being treated with acidic solution, it is classified as an acid-fast bacillus (AFB).[1][11] The most common acid-fast staining technique, the Ziehl-Neelsen stain, dyes AFBs a bright red that stands out clearly against a blue background. Other ways to visualize AFBs include an auramine-rhodamine stain and fluorescent microscopy.

    The M. tuberculosis complex includes three other TB-causing mycobacteria: M. bovis, M. africanum, and M. microti. M. africanum is not widespread, but in parts of Africa it is a significant cause of tuberculosis.[13][14] M. bovis was once a common cause of tuberculosis, but the introduction of pasteurized milk has largely eliminated this as a public health problem in developed countries.[1][15] M. microti is mostly seen in immunodeficient people, although it is possible that the prevalence of this pathogen has been underestimated.[16]

    Other known pathogenic mycobacteria include Mycobacterium leprae, Mycobacterium avium and M. kansasii. The last two are part of the nontuberculous mycobacteria (NTM) group. Nontuberculous mycobacteria cause neither TB nor leprosy, but they do cause pulmonary diseases resembling TB.[17]

    Risk factors

    Persons with silicosis have an approximately 30-fold greater risk for developing TB. Persons with chronic renal failure who are on hemodialysis also have an increased risk: 10—25 times greater than the general population. Persons with diabetes mellitus have a risk for developing active TB that is two to four times greater than persons without diabetes mellitus, and this risk is likely greater in persons with insulin-dependent or poorly controlled diabetes. Other clinical conditions that have been associated with active TB include gastrectomy with attendant weight loss and malabsorption, jejunoileal bypass, renal and cardiac transplantation, carcinoma of the head or neck, and other neoplasms (e.g., lung cancer, lymphoma, and leukemia) [1].

    Given that silicosis greatly increases the risk of tuberculosis, more research about the effect of various (indoor) air pollutants on the disease would be necessary. Some possible indoor source of silica includes paint, concrete and Portland cement.

    Low body weight is associated with risk of tuberculosis as well. A body mass index (BMI) below 18.5 increases the risk by 2—3 times. On the other hand, an increase in body weight lowers the risk [2], [3]. Patients with diabetes mellitus are at increased risk of contracting tuberculosis,[18] and they have a poorer response to treatment, possibly due to poorer drug absorption[19]

    Other conditions that increase risk include IV drug abuse; recent TB infection or a history of inadequately treated TB; chest X-ray suggestive of previous TB, showing fibrotic lesions and nodules; prolonged corticosteroid therapy and other immunosuppressive therapy;Immunocompromised patients (30-40% of AIDS patients in the world also have TB) hematologic and reticuloendothelial diseases, such as leukemia and Hodgkin's disease; end-stage kidney disease; intestinal bypass; chronic malabsorption syndromes; vitamin D deficiency;[20] and low body weight.[1][8]

    Twin studies in the 1940s showed that susceptibility to TB was heritable. If one of a pair of twins got TB, then and the other was more likely to get TB if he was identical than if he was not.[21] Since then, specific gene polymorphisms in IL12B have been linked to tuberculosis susceptibility.[22]

    Some drugs, including rheumatoid arthritis drugs that work by blocking tumor necrosis factor-alpha (an inflammation-causing cytokine), raise the risk of activating a latent infection due to the importance of this cytokine in the immune defense against TB.[23]

    Mechanism

    Transmission

    When people suffering from active pulmonary TB cough, sneeze, speak, or spit, they expel infectious aerosol droplets 0.5 to 5 µm in diameter. A single sneeze can release up to 40,000 droplets.[24] Each one of these droplets may transmit the disease, since the infectious dose of tuberculosis is very low and the inhalation of just a single bacterium can cause a new infection.[25]

    People with prolonged, frequent, or intense contact are at particularly high risk of becoming infected, with an estimated 22% infection rate. A person with active but untreated tuberculosis can infect 10–15 other people per year.[2] Others at risk include people in areas where TB is common, people who inject drugs using unsanitary needles, residents and employees of high-risk congregate settings, medically under-served and low-income populations, high-risk racial or ethnic minority populations, children exposed to adults in high-risk categories, patients immunocompromised by conditions such as HIV/AIDS, people who take immunosuppressant drugs, and health care workers serving these high-risk clients.[26]

    Transmission can only occur from people with active — not latent — TB [1]. The probability of transmission from one person to another depends upon the number of infectious droplets expelled by a carrier, the effectiveness of ventilation, the duration of exposure, and the virulence of the M. tuberculosis strain.[8] The chain of transmission can, therefore, be broken by isolating patients with active disease and starting effective anti-tuberculous therapy. After two weeks of such treatment, people with non-resistant active TB generally cease to be contagious. If someone does become infected, then it will take at least 21 days, or three to four weeks, before the newly infected person can transmit the disease to others.[27] TB can also be transmitted by eating meat infected with TB. Mycobacterium bovis causes TB in cattle. (See details below.)

    Pathogenesis

    About 90% of those infected with Mycobacterium tuberculosis have asymptomatic, latent TB infection (sometimes called LTBI), with only a 10% lifetime chance that a latent infection will progress to TB disease.[1] However, if untreated, the death rate for these active TB cases is more than 50%.[28]

    TB infection begins when the mycobacteria reach the pulmonary alveoli, where they invade and replicate within the endosomes of alveolar macrophages.[1][29] The primary site of infection in the lungs is called the Ghon focus, and is generally located in either the upper part of the lower lobe, or the lower part of the upper lobe[1]. Bacteria are picked up by dendritic cells, which do not allow replication, although these cells can transport the bacilli to local (mediastinal) lymph nodes. Further spread is through the bloodstream to other tissues and organs where secondary TB lesions can develop in other parts of the lung (particularly the apex of the upper lobes), peripheral lymph nodes, kidneys, brain, and bone.[1][30] All parts of the body can be affected by the disease, though it rarely affects the heart, skeletal muscles, pancreas and thyroid.[31]

    Tuberculosis is classified as one of the granulomatous inflammatory conditions. Macrophages, T lymphocytes, B lymphocytes and fibroblasts are among the cells that aggregate to form a granuloma, with lymphocytes surrounding the infected macrophages. The granuloma functions not only to prevent dissemination of the mycobacteria, but also provides a local environment for communication of cells of the immune system. Within the granuloma, T lymphocytes secrete cytokines such as interferon gamma, which activates macrophages to destroy the bacteria with which they are infected.[32] Cytotoxic T cells can also directly kill infected cells, by secreting perforin and granulysin.[29]

    Importantly, bacteria are not always eliminated within the granuloma, but can become dormant, resulting in a latent infection.[1] Another feature of the granulomas of human tuberculosis is the development of cell death, also called necrosis, in the center of tubercles. To the naked eye this has the texture of soft white cheese and was termed caseous necrosis.[33]

    If TB bacteria gain entry to the bloodstream from an area of damaged tissue they spread through the body and set up many foci of infection, all appearing as tiny white tubercles in the tissues. This severe form of TB disease is most common in infants and the elderly and is called miliary tuberculosis. Patients with this disseminated TB have a fatality rate of approximately 20%, even with intensive treatment.[34]

    In many patients the infection waxes and wanes. Tissue destruction and necrosis are balanced by healing and fibrosis.[33] Affected tissue is replaced by scarring and cavities filled with cheese-like white necrotic material. During active disease, some of these cavities are joined to the air passages bronchi and this material can be coughed up. It contains living bacteria and can therefore pass on infection. Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.[33]

    If untreated, infection with Mycobacterium tuberculosis can become lobar pneumonia.[35]

    Diagnosis

    Mycobacterium tuberculosis (stained red) in sputum

    Tuberculosis is diagnosed definitively by identifying the causative organism (Mycobacterium tuberculosis) in a clinical sample (for example, sputum or pus). When this is not possible, a probable diagnosis may be made using imaging (X-rays or scans) and/or a tuberculin skin test.

    The main problem with tuberculosis diagnosis is the difficulty in culturing this slow-growing organism in the laboratory (it may take 4 to 12 weeks for blood or sputum culture). A complete medical evaluation for TB must include a medical history, a physical examination, a chest X-ray, microbiological smears, and cultures. It may also include a tuberculin skin test, a serological test. The interpretation of the tuberculin skin test depends upon the person's risk factors for infection and progression to TB disease, such as exposure to other cases of TB or immunosuppression.[8]

    Currently, latent infection is diagnosed in a non-immunized person by a tuberculin skin test, which yields a delayed hypersensitivity type response to an extract made from M. tuberculosis.[1] Those immunized for TB or with past-cleared infection will respond with delayed hypersensitivity parallel to those currently in a state of infection, so the test must be used with caution, particularly with regard to persons from countries where TB immunization is common.[36] Tuberculin tests have the disadvantage in that they may produce false negatives, especially when the patient is co-morbid with sarcoidosis, Hodgkins lymphoma, malnutrition, or most notably active tuberculosis disease.[1] New TB tests are being developed that offer the hope of cheap, fast and more accurate TB testing. These include polymerase chain reaction detection of bacterial DNA, and assays to detect the release of interferon gamma in response to mycobacterial proteins such as ESAT-6.[37] These are not affected by immunization or environmental mycobacteria, so generate fewer false positive results.[38] The development of a rapid and inexpensive diagnostic test would be particularly valuable in the developing world.[39]

    Prevention

    TB prevention and control takes two parallel approaches. In the first, people with TB and their contacts are identified and then treated. Identification of infections often involves testing high-risk groups for TB. In the second approach, children are vaccinated to protect them from TB. No vaccine is available that provides reliable protection for adults. However, in tropical areas where the levels of other species of mycobacteria are high, exposure to nontuberculous mycobacteria gives some protection against TB.[40]

    The World Health Organization (W.H.O.) declared TB a global health emergency in 1993, and the Stop TB Partnership developed a Global Plan to Stop Tuberculosis that aims to save 14 million lives between 2006 and 2015.[41] Since humans are the only host of Mycobacterium tuberculosis, eradication would be possible: a goal that would be helped greatly by an effective vaccine.[42]

    Vaccines

    Many countries use Bacillus Calmette-Guérin (BCG) vaccine as part of their TB control programs, especially for infants. According to the W.H.O., this is the most often used vaccine worldwide, with 85% of infants in 172 countries immunized in 1993.[43] This was the first vaccine for TB and developed at the Pasteur Institute in France between 1905 and 1921.[44] However, mass vaccination with BCG did not start until after World War II.[45] The protective efficacy of BCG for preventing serious forms of TB (e.g. meningitis) in children is greater than 80%; its protective efficacy for preventing pulmonary TB in adolescents and adults is variable, ranging from 0 to 80%.[46]

    In South Africa, the country with the highest prevalence of TB, BCG is given to all children under age three.[47] However, BCG is less effective in areas where mycobacteria are less prevalent; therefore BCG is not given to the entire population in these countries. In the USA, for example, BCG vaccine is not recommended except for people who meet specific criteria:[8]

    • Infants or children with negative skin test results who are continually exposed to untreated or ineffectively treated patients or will be continually exposed to multidrug-resistant TB.
    • Healthcare workers considered on an individual basis in settings in which a high percentage of MDR-TB patients has been found, transmission of MDR-TB is likely, and TB control precautions have been implemented and were not successful.

    BCG provides some protection against severe forms of pediatric TB, but has been shown to be unreliable against adult pulmonary TB, which accounts for most of the disease burden worldwide. Currently, there are more cases of TB on the planet than at any other time in history and most agree there is an urgent need for a newer, more effective vaccine that would prevent all forms of TB—including drug resistant strains—in all age groups and among people with HIV.[48]

    Several new vaccines to prevent TB infection are being developed. The first recombinant tuberculosis vaccine rBCG30, entered clinical trials in the United States in 2004, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID).[49] A 2005 study showed that a DNA TB vaccine given with conventional chemotherapy can accelerate the disappearance of bacteria as well as protect against re-infection in mice; it may take four to five years to be available in humans.[50] A very promising TB vaccine, MVA85A, is currently in phase II trials in South Africa by a group led by Oxford University,[51] and is based on a genetically modified vaccinia virus. Many other strategies are also being used to develop novel vaccines,[52] including both subunit vaccines (fusion molecules composed of two recombinant proteins delivered in an adjuvant) such as Hybrid-1, HyVac4 or M72, and recombinant adenoviruses such as Ad35.[53][54][55][56] Some of these vaccines can be effectively administered without needles, making them preferable for areas where HIV is very common.[57] All of these vaccines have been successfully tested in humans and are now in extended testing in TB-endemic regions. In order to encourage further discovery, researchers and policymakers are promoting new economic models of vaccine development including prizes, tax incentives and advance market commitments.[58][59]

    The Bill and Melinda Gates Foundation has been a strong supporter of new TB vaccine development. Most recently, it announced a $200 million grant to the Aeras Global TB Vaccine Foundation for clinical trials on up to six different TB vaccine candidates currently in the pipeline.[60]

    Screening

    Mantoux tuberculin skin tests are often used for routine screening of high risk individuals.[61]

    Interferon-γ release assays are blood tests used in the diagnosis of some infectious diseases. There are currently two interferon-γ release assays available for the diagnosis of tuberculosis:

    Chest photofluorography has been used in the past for mass screening for tuberculosis.

    Treatment

    Treatment for TB uses antibiotics to kill the bacteria. Effective TB treatment is difficult, due to the unusual structure and chemical composition of the mycobacterial cell wall, which makes many antibiotics ineffective and hinders the entry of drugs. [62][63][64] The two antibiotics most commonly used are rifampicin and isoniazid. However, instead of the short course of antibiotics typically used to cure other bacterial infections, TB requires much longer periods of treatment (around 6 to 24 months) to entirely eliminate mycobacteria from the body.[8] Latent TB treatment usually uses a single antibiotic, while active TB disease is best treated with combinations of several antibiotics, to reduce the risk of the bacteria developing antibiotic resistance.[65] People with latent infections are treated to prevent them from progressing to active TB disease later in life.

    Drug resistant tuberculosis is transmitted in the same way as regular TB. Primary resistance occurs in persons who are infected with a resistant strain of TB. A patient with fully susceptible TB develops secondary resistance (acquired resistance) during TB therapy because of inadequate treatment, not taking the prescribed regimen appropriately, or using low quality medication.[65] Drug-resistant TB is a public health issue in many developing countries, as treatment is longer and requires more expensive drugs. Multi-drug-resistant tuberculosis (MDR-TB) is defined as resistance to the two most effective first-line TB drugs: rifampicin and isoniazid. Extensively drug-resistant TB (XDR-TB) is also resistant to three or more of the six classes of second-line drugs.[66] The DOTS (Directly Observed Treatment Short-course) strategy of tuberculosis treatment recommended by WHO was based on clinical trials done in the 1970s by Tuberculosis Research Centre, Chennai, India.

    Recurrence

    Studies utilizing DNA fingerprinting of M. tuberculosis strains have shown that reinfection contributes more substantially to recurrent TB than previously thought,[67] with between 12% and 77% of cases attributable to reinfection (instead of reactivation).[68]

    Prognosis

    Progression from TB infection to TB disease occurs when the TB bacilli overcome the immune system defenses and begin to multiply. In primary TB disease—1–5% of cases—this occurs soon after infection.[1] However, in the majority of cases, a latent infection occurs that has no obvious symptoms[1]. These dormant bacilli can produce tuberculosis in 2–23% of these latent cases, often many years after infection.[69] The risk of reactivation increases with immunosuppression, such as that caused by infection with HIV. In patients co-infected with M. tuberculosis and HIV, the risk of reactivation increases to 10% per year.[1][28]

    Epidemiology

    Disability-adjusted life year for tuberculosis per 100,000 inhabitants.
         no data      ≤ 10      10-25      25-50      50-75      75-100      100-250      250-500      500-750      750-1000      1000-2000      2000-3000      ≥ 3000
    World TB incidence. Cases per 100,000; Red => 300, orange = 200–300, yellow = 100–200, green = 50–100, blue =< 50 and grey = n/a. Data from WHO, 2006.[70]
    Annual number of new reported TB cases. Data from WHO.[71]

    According to the World Health Organization (WHO), nearly 2 billion people—one third of the world's population—have been exposed to the tuberculosis pathogen.[2] However, not all infections with M. tuberculosis cause TB disease and many infections are asymptomatic. Annually, 8 million people become ill with tuberculosis, and 2 million people die from the disease worldwide.[72] In 2007, an estimated 13.7 million people had active TB disease with 9.3 million new cases. The annual incidence rate varies from 363 per 100,000 in Africa to 32 per 100,000 in the Americas.[4] Tuberculosis is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with HIV/AIDS.[73]

    The rise in HIV infections and the neglect of TB control programs have enabled a resurgence of tuberculosis.[74] The emergence of drug-resistant strains has also contributed to this new epidemic with, from 2000 to 2004, 20% of TB cases being resistant to standard treatments and 2% resistant to second-line drugs.[66] The rate at which new TB cases occur varies widely, even in neighboring countries, apparently because of differences in health care systems.[75]

    In 2005, the country with the highest estimated incidence of TB was Swaziland, with 1262 cases per 100,000 people. India has the largest number of infections, with over 1.8 million cases.[76] In developed countries, tuberculosis is less common and is mainly an urban disease. In the United Kingdom, TB incidences range from 40 per 100,000 in London to less than 5 per 100,000 in the rural South West of England;[77] the national average is 13 per 100,000. The highest rates in Western Europe are in Portugal (31.1 per 100,000 in 2005) and Spain (20 per 100,000). These rates compare with 113 per 100,000 in China and 64 per 100,000 in Brazil. In the United States, the overall tuberculosis case rate was 4.9 per 100,000 persons in 2004.[72] In Canada tuberculosis is still endemic in some rural areas.[78]

    The incidence of TB varies with age. In Africa, TB primarily affects adolescents and young adults.[79] However, in countries where TB has gone from high to low incidence, such as the United States, TB is mainly a disease of older people, or of the immunocompromised [1][80].

    There are a number of known factors that make people more susceptible to TB infection: worldwide the most important of these is HIV. Co-infection with HIV is a particular problem in Sub-Saharan Africa, due to the high incidence of HIV in these countries.[70][81] Smoking more than 20 cigarettes a day also increases the risk of TB by two to four times.[82][83] Diabetes mellitus is also an important risk factor that is growing in importance in developing countries.[84] Other disease states that increase the risk of developing tuberculosis are Hodgkin lymphoma, end-stage renal disease, chronic lung disease, malnutrition, and alcoholism.[1]

    Diet may also modulate risk. For example, among immigrants in London from the Indian subcontinent, vegetarian Hindu Asians were found to have an 8.5 fold increased risk of tuberculosis, compared to Muslims who ate meat and fish daily.[85] Although a causal link is not proved by this data,[86] this increased risk could be caused by micronutrient deficiencies: possibly iron, vitamin B12 or vitamin D.[85] Further studies have provided more evidence of a link between vitamin D deficiency and an increased risk of contracting tuberculosis.[87][88] Globally, the severe malnutrition common in parts of the developing world causes a large increase in the risk of developing active tuberculosis, due to its damaging effects on the immune system.[89][90] Along with overcrowding, poor nutrition may contribute to the strong link observed between tuberculosis and poverty.[91][92]

    History

    Tuberculosis has been present in humans since antiquity. The earliest unambiguous detection of Mycobacterium tuberculosis is in the remains of bison dated 18,000 years before the present.[93] Whether tuberculosis originated in cattle and then transferred to humans, or diverged from a common ancestor infecting a different species, is currently unclear.[94] However, it is clear that M. tuberculosis is not directly descended from M. bovis, which seems to have evolved relatively recently.[95]

    Tubercular decay has been found in the spines of Egyptian mummies. Pictured: Egyptian mummy in the British Museum

    Skeletal remains from a Neolithic Settlement in the Eastern Mediterranean show prehistoric humans (7000 BC) had TB,[96] and tubercular decay has been found in the spines of mummies from 3000–2400 BC.[97] Phthisis is a Greek term for tuberculosis; around 460 BC, Hippocrates identified phthisis as the most widespread disease of the times involving coughing up blood and fever, which was almost always fatal.[98] In South America, the earliest evidence of tuberculosis is associated with the Paracas-Caverna culture (circa 750 BC to circa 100 AD).[99][100]

    Other names

    In the past, tuberculosis has been called consumption, because it seemed to consume people from within, with a bloody cough, fever, pallor, and long relentless wasting. Other names included phthisis (Greek for consumption) and phthisis pulmonalis; scrofula (in adults), affecting the lymphatic system and resulting in swollen neck glands; tabes mesenterica, TB of the abdomen and lupus vulgaris, TB of the skin; wasting disease; white plague, because sufferers appear markedly pale; king's evil, because it was believed that a king's touch would heal scrofula; and Pott's disease, or gibbus of the spine and joints.[101][102]

    Dr. Robert Koch discovered the tuberculosis bacillus.

    Miliary tuberculosis—now commonly known as disseminated TB—occurs when the infection invades the circulatory system, resulting in lesions which have the appearance of millet seeds on X-ray.[101][103] TB is also called Koch's disease, after the scientist Robert Koch.[104]

    Folklore

    Before the Industrial Revolution, tuberculosis may sometimes have been regarded as vampirism. When one member of a family died from it, the other members that were infected would lose their health slowly. People believed that this was caused by the original victim draining the life from the other family members. Furthermore, people who had TB exhibited symptoms similar to what people considered to be vampire traits. People with TB often have symptoms such as red, swollen eyes (which also creates a sensitivity to bright light), pale skin, extremely low body heat, a weak heart and coughing blood, suggesting the idea that the only way for the afflicted to replenish this loss of blood was by sucking blood.[105] Another folk belief told that the affected individual was being forced, nightly, to attend fairy revels, so that the victim wasted away owing to lack of rest; this belief was most common when a strong connection was seen between the fairies and the dead.[106] Similarly, but less commonly, it was attributed to the victims being "hagridden"—being transformed into horses by witches (hags) to travel to their nightly meetings, again resulting in a lack of rest.[106]

    TB was romanticized in the nineteenth century. Many people believed TB produced feelings of euphoria referred to as Spes phthisica ("hope of the consumptive"). It was believed that TB sufferers who were artists had bursts of creativity as the disease progressed. It was also believed that TB sufferers acquired a final burst of energy just before they died which made women more beautiful and men more creative.[107] In the early 20th century, some believed TB to be caused by masturbation.[108]

    Study and treatment

    The study of tuberculosis, sometimes known as phthisiatry, dates back to The Canon of Medicine written by Ibn Sina (Avicenna) in the 1020s. He was the first physician to identify pulmonary tuberculosis as a contagious disease, the first to recognise the association with diabetes, and the first to suggest that it could spread through contact with soil and water.[109][110] He developed the method of quarantine in order to limit the spread of tuberculosis.[111] In ancient times, treatments focused on sufferers' diets. Pliny the Elder described several methods in his Natural History: "wolf's liver taken in thin wine, the lard of a sow that has been fed upon grass, or the flesh of a she-ass taken in broth".[112]

    Although it was established that the pulmonary form was associated with "tubercles" by Dr Richard Morton in 1689,[113][114] due to the variety of its symptoms, TB was not identified as a single disease until the 1820s and was not named "tuberculosis" until 1839 by J. L. Schönlein.[115] During the years 1838 – 1845, Dr. John Croghan, the owner of Mammoth Cave, brought a number of tuberculosis sufferers into the cave in the hope of curing the disease with the constant temperature and purity of the cave air; they died within a year.[116] The first TB sanatorium opened in 1854 in Görbersdorf, Germany (today Sokołowsko, Poland) by Hermann Brehmer.[117]

    The bacillus causing tuberculosis, Mycobacterium tuberculosis, was identified and described on 24 March 1882 by Robert Koch. He received the Nobel Prize in physiology or medicine in 1905 for this discovery.[118] Koch did not believe that bovine (cattle) and human tuberculosis were similar, which delayed the recognition of infected milk as a source of infection. Later, this source was eliminated by the pasteurization process. Koch announced a glycerine extract of the tubercle bacilli as a remedy for tuberculosis in 1890, calling it "tuberculin". It was not effective, but was later adapted as a test for pre-symptomatic tuberculosis.[119]

    The first genuine success in immunizing against tuberculosis was developed from attenuated bovine-strain tuberculosis by Albert Calmette and Camille Guérin in 1906. It was called "BCG" (Bacillus of Calmette and Guérin). The BCG vaccine was first used on humans in 1921 in France,[44] but it was not until after World War II that BCG received widespread acceptance in the USA, Great Britain, and Germany.[45]

    Tuberculosis, or "consumption" as it was commonly known, caused the most widespread public concern in the 19th and early 20th centuries as an endemic disease of the urban poor.[120] In 1815, one in four deaths in England was of consumption; by 1918 one in six deaths in France were still caused by TB. In the 20th century, tuberculosis killed an estimated 100 million people.[121] After the establishment in the 1880s that the disease was contagious, TB was made a notifiable disease in Britain; there were campaigns to stop spitting in public places, and the infected poor were pressured to enter sanatoria that resembled prisons; the sanatoria for the middle and upper classes offered excellent care and constant medical attention.[117] Whatever the purported benefits of the fresh air and labor in the sanatoria, even under the best conditions, 50% of those who entered were dead within five years (1916).[117]

    Public health campaigns tried to halt the spread of TB

    The promotion of Christmas Seals began in Denmark during 1904 as a way to raise money for tuberculosis programs. It expanded to the United States and Canada in 1907 – 1908 to help the National Tuberculosis Association (later called the American Lung Association).

    In the United States, concern about the spread of tuberculosis played a role in the movement to prohibit public spitting except into spittoons.

    In Europe, deaths from TB fell from 500 out of 100,000 in 1850 to 50 out of 100,000 by 1950. Improvements in public health were reducing tuberculosis even before the arrival of antibiotics. The disease remained such a significant threat to public health, that when the Medical Research Council was formed in Britain in 1913, its initial focus was tuberculosis research.[122]

    It was not until 1946 with the development of the antibiotic streptomycin that effective treatment and cure became possible. Prior to the introduction of this drug, the only treatment besides sanatoria were surgical interventions, including the pneumothorax or plombage technique — collapsing an infected lung to "rest" it and allow lesions to heal — a technique that was of little benefit and was mostly discontinued by the 1950s.[123] The emergence of multidrug-resistant TB has again introduced surgery as part of the treatment for these infections. Here, surgical removal of chest cavities will reduce the number of bacteria in the lungs, as well as increasing the exposure of the remaining bacteria to drugs in the bloodstream. It is therefore thought to increase the effectiveness of the chemotherapy.[124]

    Hopes that the disease could be completely eliminated have been dashed since the rise of drug-resistant strains in the 1980s. For example, tuberculosis cases in Britain, numbering around 117,000 in 1913, had fallen to around 5,000 in 1987, but cases rose again, reaching 6,300 in 2000 and 7,600 cases in 2005.[125] Due to the elimination of public health facilities in New York and the emergence of HIV, there was a resurgence of TB in the late 1980s.[126] The number of patients failing to complete their course of drugs is high. New York had to cope with more than 20,000 TB patients with multidrug-resistant strains (resistant to, at least, both Rifampin and Isoniazid).

    The resurgence of tuberculosis resulted in the declaration of a global health emergency by the World Health Organization (WHO) in 1993.[127] Every year, nearly half a million new cases of multidrug-resistant tuberculosis (MDR-TB) are estimated to occur worldwide.[128]

    Evolution

    Tuberculosis has co-evolved with humans for many thousands of years, and perhaps for several million years.[129] The oldest known human remains showing signs of tuberculosis infection are 9,000 years old.[130] During this evolution, M. tuberculosis has lost numerous coding and non-coding regions in its genome, losses that can be used to distinguish between strains of the bacteria. The implication is that M. tuberculosis strains differ geographically, so their genetic differences can be used to track the origins and movement of each strain.[131]

    Society and culture

    Through its affecting important historical figures, tuberculosis has influenced particularly European history, and become a theme in art – mostly literature, music, and film.

    Public health

    Tuberculosis is one of the three primary diseases of poverty along with AIDS and malaria.[132] The Global Fund to Fight AIDS, Tuberculosis and Malaria was started in 2002 to raise finances to address these infectious diseases. Globalization has lead to increased opportunities for disease spread. In 2007, a tuberculosis scare occurred when Andrew Speaker flew on a transatlantic flight infected with multi-drug-resistant tuberculosis.[133]

    The National Center for HIV, STD, and TB Prevention as part of the Center for Disease Control and Prevention (CDC) is responsible for public health surveillance and prevention research in the United States.

    Notable victims

    Research

    The Mycobacterium Tuberculosis Structural Genomics Consortium is a global consortium of scientists conducting research regarding the diagnosis and treatment of tuberculosis. They are attempting to determine the 3-dimensional structures of proteins from M. Tuberculosis.[citation needed]

    Infection of other animals

    Tuberculosis can be carried by mammals; domesticated species, such as cats and dogs, are generally free of tuberculosis, but wild animals may be carriers.

    Mycobacterium bovis causes TB in cattle. An effort to eradicate bovine tuberculosis from the cattle and deer herds of New Zealand is underway. It has been found that herd infection is more likely in areas where infected natural reservoir such as Australian brush-tailed possums come into contact with domestic livestock at farm/bush borders.[134] Controlling the vectors through possum eradication and monitoring the level of disease in livestock herds through regular surveillance are seen as a "two-pronged" approach to ridding New Zealand of the disease.

    In the Republic of Ireland and the United Kingdom, badgers have been identified as one vector species for the transmission of bovine tuberculosis. As a result, governments have come under pressure from some quarters, primarily dairy farmers, to mount an active campaign of eradication of badgers in certain areas with the purpose of reducing the incidence of bovine TB. The effectiveness of culling on the incidence of TB in cattle is a contentious issue, with proponents and opponents citing their own studies to support their position.[135][136][137] For instance, a study by an Independent Study Group on badger culling reported on 18 June 2007 that it was unlikely to be effective and would only make a “modest difference” to the spread of TB and that "badger culling cannot meaningfully contribute to the future control of cattle TB"; in contrast, another report concluded that this policy would have a significant impact.[138] On July 4, 2008, the UK government decided against a proposed random culling policy.[139]

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