Tuberculosis

Tuberculosis
Tuberculosis
Specialty	Infectious diseases, pulmonology
Frequency	0.043—0.045% (Suriname), 0.00033—0.00053% (Iceland), 0.077—0.079% (Ecuador), -0.99—1.01% (Norway), -0.00088—0.00112% (France), 0.0029% (United States of America), 0.0028%

Tuberculosis (commonly abbreviated as TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis, which most commonly affects the lungs (pulmonary TB) but can also affect the central nervous system (meningitis), lymphatic system, circulatory system (miliary tuberculosis), genitourinary system, bones and joints. Tuberculosis is one of the deadliest and most common major infectious diseases today. In 2004, the prevalence (number of existing cases) of active TB disease was 14.6 million people with an incidence (number of new cases) of 8.9 million people and mortality (number of deaths) of 1.7 million people ^[1] mostly in developing countries. However, developing countries are not the only places with tuberculosis. There is a rising number of people in the developed world who contract tuberculosis because they have compromised immune systems, typically as a result of immunosuppressive drugs or HIV/AIDS. These people are at particular risk of tuberculosis infection and active tuberculosis disease.

Most of those infected (90%) have asymptomatic latent TB infection (LTBI). There is a 10% lifetime chance that LTBI will progress to TB disease which, if left untreated, will kill more than 50% of its victims. TB is one of the top four infectious killing diseases in the world: TB kills 1.7 million, and malaria kills 2-3 million[footnote needed].

HIV/AIDS, the neglect of TB control programs, and immigration have caused a resurgence of tuberculosis. Multidrug-resistant strains of TB (MDR-TB) and Extreme Drug-Resistance in Tuberculosis (XDR-TB) are emerging. The World Health Organization declared TB a global health emergency in 1993, and the Stop TB Partnership proposed a Global Plan to Stop Tuberculosis which aims to save an additional 14 million lives between 2006 and 2015.

Other names for the disease

TB (short for tuberculosis and also for Tubercle Bacillus)
Consumption (TB seemed to consume people from within with its symptoms of bloody cough, fever, pallor, and long relentless wasting)
Wasting disease
White plague (TB sufferers appear markedly pale)
Phthisis (Greek for consumption) and phthisis pulmonalis
Scrofula (swollen neck glands)
King's evil (so called because it was believed that a king's touch would heal scrofula)
Pott's disease of the spine
Miliary TB (x-ray lesions look like millet seeds)
Tabes mesenterica (TB of the abdomen)
Lupus vulgaris (the common wolf - TB of the skin)
Prosector's wart, also a kind of TB of the skin, transmitted by contact with contaminated cadavers to anatomists, pathologists, veterinarians, surgeons, butchers, etc.
Koch's Disease named after Robert Koch who discovered the tuberculosis bacilli.

The bacterium

File:TB AFB smear.jpg

Acid-fast bacilli (AFB) (shown in red) are tubercle bacilli Mycobacterium tuberculosis.

The cause of tuberculosis, Mycobacterium tuberculosis (MTB), is a slow-growing aerobic bacterium that divides every 16 to 20 hours. This is extremely slow compared to other bacteria (although not the slowest), which tend to have division times measured in minutes (among the fastest growing bacteria is a strain of E. coli that can divide roughly every 20 minutes; by contrast, Mycobacterium leprae divides every 20 days). MTB is not classified as either Gram-positive or Gram-negative because it does not have the chemical characteristics of either. If a Gram stain is performed, it stains very weakly Gram-positive or not at all (ghost cells). It is a small rod-like bacillus which can withstand weak disinfectants and can survive in a dry state for weeks but, spontaneously, can only grow within a host organism (in vitro culture of M. tuberculosis took a long time to be achieved, but is nowadays a routine laboratory procedure).

MTB is identified microscopically by its staining characteristics: it retains certain stains after being treated with acidic solution, and is thus classified as an "acid-fast bacillus" or AFB. In the most common staining technique, the Ziehl-Neelsen stain, AFB are stained a bright red which stands out clearly against a blue background. Acid-fast bacilli can also be visualized by fluorescent microscopy, and by an auramine-rhodamine stain.

The M. tuberculosis complex includes 3 other mycobacteria which can cause tuberculosis: M. bovis, M. africanum and M. microti. The first two are very rare causes of disease and the last one does not cause human disease.

Nontuberculous mycobacteria (NTM) are other mycobacteria (besides M. leprae which causes leprosy) which may cause pulmonary disease resembling TB, lymphadenitis, skin disease, or disseminated disease. These include Mycobacterium avium, M. kansasii, and others.

The disease

Epidemiology

One-third of the world population (2 billion people) have latent TB infection; in 2004, around 14.6 million people have active TB disease with 9 million new cases. The annual incidence rate varies enormously, from 356 per 100,000 in Africa to 41 per 100,000 in the Americas.^[1] In the UK, incidence ranges from 90 per 100,000 in the centre of Birmingham to less than 5 per 100,000 in rural Hertfordshire. Approximately 1.7 million people died from TB in 2004.

The incidence of TB is known to vary with age. In endemic areas, TB is a disease that primarily affects adolescents and young adults (hence the UK policy until recently was to vaccinate with BCG at the age of 12). However, in countries where TB has gone from high to low incidence, TB is mainly a disease of older people, because of the re-activation of latent TB acquired many decade before (as is the situation in the native population of the UK currently).

There are a number of known factors that make people more susceptible to TB infection: worldwide the most important of these is HIV. Smoking more than 20 cigarettes a day also increases the risk of TB by two- to four-times.^[2]

Transmission

TB is spread by aerosol droplets expelled by people with active TB disease of the lungs when they cough, sneeze, speak, or spit. Each droplet is 5 µm in diameter and contains 1 to 3 bacilli. Close contacts (people with prolonged, frequent, or intense contact) are at highest risk of becoming infected (typically a 22% infection rate). A person with untreated, active tuberculosis can infect an estimated 20 other people per year. Others at risk include foreign-born from areas where TB is common, immunocompromised patients (eg. HIV/AIDS), residents and employees of high-risk congregate settings, health care workers who serve high-risk clients, medically underserved, low-income populations, high-risk racial or ethnic minority populations, children exposed to adults in high-risk categories, and people who inject illicit drugs.

Transmission can only occur from people with active TB disease (not latent TB infection).

The probability of transmission depends upon infectiousness of the person with TB (quantity expelled), environment of exposure, duration of exposure, and virulence of the organism.

The chain of transmission can be stopped by isolating patients with active disease and starting effective anti-tuberculous therapy.

Pathogenesis

While only 10% of TB infection progresses to TB disease, if untreated the death rate is 51%.

TB infection begins when MTB bacilli reach the pulmonary alveoli, where the mycobacteria replicate at an exponential rate and infect alveolar macrophages. The primary site of infection in the lungs is called the Ghon focus. Bacteria are picked up by dendritic cells, which can transport the bacilli to local (mediastinal) lymph nodes, and then through the bloodstream to the more distant tissues and organs where TB disease could potentially develop: lung apices, peripheral lymph nodes, kidneys, brain, and bone.

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 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 (CD4+) secrete a cytokine such as interferon gamma, which activates macrophages to destroy the bacteria with which they are infected, making them better able to fight infection. T lymphocytes (CD8+) can also directly kill infected cells.

Importantly, bacteria are not eliminated with the granuloma, but can become dormant, resulting in a latent infection. Latent infection can only be diagnosed in a non-immunized person by a tuberculin skin test, which yields a delayed hypersensitivity type response to purified protein derivatives of M. tuberculosis. Those immunized for TB or with past-cleared infection will respond with parallel delayed hypersensitivity to those currently in a state of infection and thus must be used with caution, particularly with regard to persons from countries where TB immunization is common.

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.

If TB bacteria gain entry to the blood stream from an area of tissue damage they spread through the body and set up myriad foci of infection, all appearing as tiny white tubercles in the tissues. This is called miliary tuberculosis and has a high rate of fatality.

In many patients the infection waxes and wanes. Tissue destruction and necrosis are balanced by healing and fibrosis. Affected tissue is replaced by scarring and cavities filled with cheese-like white necrotic material. During active disease, some of these cavities are in continuity with the air passages bronchi. This material may therefore be coughed up. It contains living bacteria and can pass on infection.

Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Affected areas are eventually replaced by scar tissue.

Progression

In those people in whom TB bacilli overcome the immune system defenses and begin to multiply, there is progression from TB infection to TB disease. This may occur soon after infection (primary TB disease – 1 to 5%) or many years after infection (post primary TB, secondary TB, reactivation TB disease of dormant bacilli – 5 to 9%). The risk of reactivation increases with immune compromise, 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, while in immune competent individuals, the risk is between 5 and 10% in a lifetime.

About five percent of infected persons will develop TB disease in the first two years, and another five percent will develop disease later in life. In other words, about 10% of infected persons with normal immune systems will develop TB disease in their lifetime.

Some medical conditions increase the risk of progression to TB disease. In HIV infected persons with TB infection, the risk increases to 10% each year instead of 10% over a lifetime. Other such conditions include drug injection (mainly because of the life style of IV Drug users), substance abuse, recent TB infection (within two years) or history of inadequately treated TB, chest X-ray suggestive of previous TB (fibrotic lesions and nodules), diabetes mellitus, silicosis, prolonged corticosteroid therapy and other immunosuppressive therapy, head and neck cancers, hematologic and reticuloendothelial diseases (leukemia and Hodgkin's disease), end-stage renal disease, intestinal bypass or gastrectomy, chronic malabsorption syndromes, or low body weight (10% or more below the ideal).

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

Symptoms

TB most commonly affects the lungs (75% or more), where it is called pulmonary TB. Symptoms may include a productive, prolonged cough of more than three weeks duration, chest pain, and hemoptysis. Systemic symptoms include fever, chills, night sweats, appetite loss, weight loss, and easy fatigability. The term consumption arose because sufferers appeared as if they were "consumed" from within by the disease. People from Asian and African descent may have lymph node TB more often than Caucasians. Lymph node TB is not contagious.

Extrapulmonary sites include the pleura, central nervous system (meningitis), lymphatic system (scrofula of the neck), genitourinary system, and bones and joints (Pott's disease of the spine). An especially serious form is disseminated, or miliary TB, so named because the lung lesions so-formed resemble millet seeds on x-ray. These are more common in immunosuppressed persons and in young children. Pulmonary TB may co-exist with extrapulmonary TB.

Drug resistance

Drug-resistant Tuberculosis is transmitted in the same way as regular TB. Primary resistance develops in persons initially infected with resistant organisms. Secondary resistance (acquired resistance) may develop during TB therapy due to inadequate treatment regimen, i.e. not taking the prescribed regimen appropriately or using low quality medication.

Drug-resistant TB is an important public health issue in many developing countries, as treatment of drug-resistant TB requires the use of more expensive drugs and treatment is longer.

Multidrug-resistant TB is defined as resistance to the two most effective first line TB drugs - Rifampicin and Isoniazid (INH).

Extreme drug resistant TB (XDR TB) is defined as resistance to the front-line drugs as well as three or more of the second-line drugs.^[3]

Diagnosis

A complete medical evaluation for TB includes a medical history, a physical examination, a tuberculin skin test, a serological test, a chest X-ray, and microbiologic smears and cultures. The measurement of a positive skin test depends upon the person's risk factors for progression of TB infection to TB disease. Bacteriophage-based assays are among a few new testing procedures that offer the hope of cheap, fast and accurate TB testing for the impoverished countries that need it most.

Treatment

For all practical purposes, only patients with tuberculosis of the lungs can spread TB to other people. People may become infected with TB but not have active disease: such people are said to have latent TB infection (LTBI) and are not capable of passing the infection on to other people. The reason for treating people with LTBI is to prevent them from progressing to active TB disease later in life (approximately 10% lifetime risk). The distinction is important because treatment options are different for the two groups.

Prevention of Tuberculosis

Prevention and control efforts include three priority strategies:

identifying and treating all people who have TB
finding and evaluating persons who have been in contact with TB patients to determine whether they have TB infection or disease, and treating them appropriately, and
testing high-risk groups for TB infection to identify candidates for treatment of latent infection and to ensure the completion of treatment.

In tropical areas where the incidence of atypical mycobacteria is high, exposure to nontuberculous mycobacteria gives some protection against TB.

BCG vaccine

Many countries use BCG vaccine as part of their TB control programs, especially for infants. The protective efficacy of BCG for preventing serious forms of TB (e.g. meningitis) in children is high (greater than 80%). However, the protective efficacy for preventing pulmonary TB in adolescents and adults is variable, from 0 to 80%. In the United Kingdom, children aged 10-14 were typically immunized during school until 2005. (Routine BCG vaccination was stopped as it was no longer cost-effective. The incidence of TB in people born in the UK, and with parents and grandparents who were born in the UK, was at an all time low, and falling. Others continue to be offered BCG vaccination.)

The effectiveness of BCG is much lower in areas where mycobacteria are less prevalent. In the USA, BCG vaccine is not routinely recommended except for selected persons who meet specific criteria:

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

Tuberculosis vaccine

The first recombinant Tuberculosis vaccine entered clinical trials in the United States in 2004 sponsored by the National Institute of Allergy and Infectious Diseases (NIAID).^[4]

A 2005 studyshowed that a DNA TB vaccine given with conventional chemotherapy can accelerate the disappearance of bacteria as well as protecting against re-infection in mice; it may take four to five years to be available in humans.^[5]

Because of the limitations of current vaccines, researchers and policymakers are promoting new economic models of vaccine development including prizes, tax incentives and advance market commitments.

Animals

Tuberculosis can be carried by many mammals. Domesticated species, such as cats and dogs, are generally free of tuberculosis, but wild animals may be carriers. As a result, many places have regulations restricting the ownership of novelty pets, possibly including such partially domesticated species as pet skunks; for example, the American state of California forbids the ownership of pet gerbils. The strictness of such restrictions generally depends on the public health policies adopted for fighting tuberculosis.

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 vector species such as Australian brush-tailed possums come into contact with domestic livestock at farm/bush borders. 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 both the Republic of Ireland and Northern Ireland, badgers have been identified as a vector species for the transmission of bovine tuberculosis. As a result, the government in both regions has mounted an active campaign of eradication of the species in an effort to reduce the incidence of the disease. Badgers have been culled primarily by snaring and gassing. It remains a contentious issue, with proponents and opponents of the scheme citing their own studies to support their position.^[6]^[7]^[8]

History

Tuberculosis has been present in humans since antiquity. The origins of the disease are in the first domestication of cattle (which also gave humanity viral poxes). Skeletal remains show prehistoric humans (4000 BCE) had TB, and tubercular decay has been found in the spines of Egyptian mummies from 3000-2400 BCE. There were references to TB in India around 2000 BCE, and indications of lung scarring identical to that of modern-day TB sufferers in preserved bodies (such as mummies) suggests that TB was present in The Americas from about 2000 BCE.

Phthisis is a Greek term for consumption. Around 460 BCE, Hippocrates identified phthisis as the most widespread disease of the times which was almost always fatal.

During the Industrial Revolution, tuberculosis was more commonly thought of 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 the cause of this was the original victim draining the life from the other family members. To cure this, people would dig up the body of what they thought was the vampire, open the chest and burn the heart, sometimes with the rest of the body. Furthermore, people who had TB exhibited symptoms similar to what people considered to be vampire traits. People with TB often had symptoms such as red, swollen eyes (which also creates a sensitivity to bright light), pale skin and coughing blood (which people often thought needed to be replenished, so they figured the only way for the afflicted to get blood back was by sucking blood). This may be how much of the common mythology of the vampire originated.

Although it was established that the pulmonary form was associated with 'tubercles' by Dr Richard Morton in 1689,^[9]^[10] 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. 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. The first TB sanatorium opened in 1859 in Poland, with another opening in the United States in 1885.

The bacillus causing tuberculosis, Mycobacterium tuberculosis, was identified and described on March 24, 1882 by Robert Koch. He received the Nobel Prize in physiology or medicine in 1905 for this discovery. Koch did not believe that bovine (cattle) and human tuberculosis were similar, which held back 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 by von Pirquet in a test for pre-symptomatic tuberculosis.

The first genuine success in immunizing against tuberculosis developed from attenuated bovine-strain tuberculosis by Albert Calmette and Camille Guerin in 1906. It was called 'BCG' (Bacillus of Calmette and Guerin). The BCG vaccine was first used on humans on July 18, 1921 in France. It wasn't until after World War II that BCG received widespread acceptance in the USA, Great Britain, and Germany.

Tuberculosis caused the most widespread public concern in the 19th and early 20th centuries as the endemic disease of the urban poor. In 1815, one in four deaths in England was of consumption; by 1918 one in six deaths in France were still caused by TB. 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 "encouraged" to enter sanatoria that rather resembled prisons. Whatever the purported benefits of the fresh air and labor in the sanatoria, 75% of those who entered were dead within five years (1908).

The promotion of Christmas Seals was started in 1904 in Denmark as a way to raise money for tuberculosis programs. It expanded to the United States and Canada in 1907-08 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, although the disease's significance was still such that when the Medical Research Council was formed in Britain in 1913 its first project was tuberculosis.

It was not until 1946 with the development of the antibiotic streptomycin that treatment rather than prevention became a possibility. Prior to then only surgical intervention was possible as supposed treatment (other than sanatoria), including the pneumothorax technique: collapsing an infected lung to "rest" it and allow lesions to heal, which was an accomplished technique but was of little benefit and was discontinued after 1946.

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 50,000 in 1955, had fallen to around 5,500 in 1987, but in 2000 there were over 7,000 confirmed cases. Due to the elimination of public health facilities in New York in the 1970s, there was a resurgence in the 1980s [citation needed]. The number of those failing to complete their course of drugs was very high. NY had to cope with more than 20,000 "unnecessary" TB-patients with many multidrug-resistant strains (i.e., 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 in 1993.

Incidence

According to the World Health Organization (WHO), nearly 2 billion people, one-third of the world's population, have tuberculosis. [1] In the United Kingdom, the rate of tuberculosis in London is 40 per 100,000 - three times the national average of 13 per 100,000, according to the Public Health Laboratory Service and WHO. The highest rates in Western Europe are in Portugal (42 per 100,000) and Spain (20 per 100,000). These rates compare with 113 per 100,000 in China and 64 per 100,000 in Brazil. Tuberculosis is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with HIV/AIDS. Globally more than 23 000 people develop active TB and almost 5 000 die from the disease every day. [2]. The highly urbanized region centered in Porto, northern Portugal, is placed among the European Union's largest metropolitan areas having the highest rates of tuberculosis positive cases - 53 per 100,000 (in 2004).

Tuberculosis in art, literature, history and film

Historical people

Due to the high prevalence of tuberculosis in the pre-antibiotic era, many historically prominent people developed or died from the condition, often in the prime of their productive period.

Theology:

Saint Maria Faustina Kowalska, the Roman Catholic nun and mystic from Poland, is the patron saint of mercy, and the Apostle of The Divine Mercy. She suffered greatly from tuberculosis and succumbed to it on October 5, 1938. She was canonized by the Church on April 30, 2000.^[11]
David Brainerd (born: April 20, 1718, died: October 9, 1747) only lived 29 years. His diary has been published and reflects his reliance upon God's faithfulness amidst his battle with consumption. Brainerd's diary has proven historically very influential, particularly to the modern Christian missionary movement.^[12] He was a close friend of Theologian and Pastor Jonathan Edwards in New England.^[13]
The Catholic Church canonized Saint Therese of the Child Jesus (1873-1897) in 1925, who died of tuberculosis.
Cardinal Richelieu of France died of tuberculosis in 1642

Music:

Frédéric Chopin (born: March 1st, 1810, died: October 17th, 1849) died of consumption in 1849 at age 39. Historical records indicate episodes of hemoptysis during performances.
Legendary father of country music, Jimmie Rodgers (1897 - 1933) sang the woes of having tuberculosis in the song T.B. Blues (co-written with Raymond E. Hall). Rodgers ultimately died of the disease days after a New York city recording session.
Luigi Boccherini, Italian cellist and composer, died in 1805 of pulmonary tuberculosis.
Tom Jones, the Welsh singing legend, spent about a year recovering from TB in his parents basement around the age of 12.
Cat Stevens contracted tuberculosis. After several months in the hospital and a year of convalescence, Stevens returned to recording.
Van Morrison's "T.B. Sheets", from the album of the same name, is a 9-minute song to a lover dying of the disease.

Mathematics:

Bernhard Riemann, died on July 20, 1866 at the age of 39 years.
Niels Henrik Abel, died on April 6, 1829 at the age of 26 years.

Literature and poetry:

English Romantic poet John Keats (1795-1821) and some of his family were taken by tuberculosis.
The Brontë family of writers, poets and painters was particularly struck by TB, with Anne, Branwell, and Emily all dying of it within 2 years of each other. Charlotte's death in 1855 was stated as due to TB at the time, although there is some controversy over this today.
In A Moveable Feast, Ernest Hemingway (1899-1961) recounts meeting Ernest Walsh, an Irish poet suffering from TB. "... I looked at him and his marked-for-death look and I thought, you con man conning me with your con."
Neo-romantic Scottish essayist, novelist and poet Robert Louis Stevenson (1850-1894) is thought to have suffered from tuberculosis during much of his life. He spent the winter of 1887–1888 recuperating from a presumed bout of tuberculosis at Dr. E.L. Trudeau's world-renowned Adirondack Cottage Sanatarium in Saranac Lake, New York.
The 20th century French writer, playwright, activist, and existentialist philosopher, Albert Camus also suffered from TB during his life time, although he died in a car accident.
Edward Bellamy (1850-1898), a fiction writer who was made famous from his book "Looking Backward", died from tuberculosis.
Franz Kafka (1883-1924), a German-language novelist who was made famous from his novel (The Metamorphosis), died from tuberculosis.
Masaoka Shiki (1867-1902), a Japanese poet famous for revitalizing the haiku, died after a long struggle with tuberculosis.
George Orwell (1903-1950), British author of 1984, Animal Farm and Homage to Catalonia suffered from the diease in bouts from the early 1930s until his death from the illness.
Dashiell Hammett (1894–1961), American author and creator of the "hard boiled" detective novel (notably, Sam Spade in the Maltese Falcon), contracted tuberculosis during WWI.
Fyodor Dostoyevsky (1821-1881), author of Crime and Punishment (1866) and The Brothers Karamazov (1880) lost his first wife, Marya Dimitryevna, to consumption.
Charles Bukowski (1920-1994), American author and poet contracted TB in 1988; he recovered, losing 60 pounds.
Sir Arthur Conan Doyle (1859–1930), lost his first wife, Louisa Hawkins, to tuberculosis in 1906.
Poet Elizabeth Barrett Browning died of tuberculosis in 1861

Military:

Okita Soji (1844-1868), a young and famous captain of the Shinsengumi, was rumored to have discovered his disease when he coughed blood and fainted during the Ikedaya Affair. He died of it in his mid-20's, on July 19th (lunar calendar May 30th), 1868.

Painters:

Edvard Munch (1863-1944), The famous painter who painted (The Scream), lost two members of his family, his mother, and his beloved sister both to tuberculosis. The loss of his sister was immortalized in the painting "The Sick Child."

Others:

Famous gambler and gunslinger John "Doc" Holliday suffered from tuberculosis until his death in 1887.
Arline Greenbaum, the first wife of famed physicist Richard Feynman died from tuberculosis while he was working on the Manhattan Project.
Juliet Hulme, a girl who help her friend murder her mother suffered from tuberculosis.
Tulasa Thapa, a kidnapped Nepali girl, died of tuberculosis in 1995.
Celebrated British actress of stage and screen Vivien Leigh (1913-1967) died from complications of tuberculosis.
It has been said that King Tutankhamen, Pharoah of Egypt, had TB, but there is debate as to whether it was the cause of his death.
Simon Bolivar, the man who many South American countries consider their liberator, died in 1830 of TB.

Portrayals

It has been speculated that the real-life ubiquity of illness and death due to tuberculosis affected the portrayal of these issues in European art and literature as well as history. The pale, "haunted" appearance of tuberculosis sufferers was fashionable at times, and has been seen as an influence on the works of Edgar Allan Poe who lost loved ones to this disease. In recent years, this aesthetic has been revived by the "Goth" subculture. In 1680 John Bunyan referred to TB as "the captain of all these men of death".

Opera and theatre:

Mimi, the heroine of Puccini's opera, La bohème suffers from tuberculosis . Violetta Valéry, heroine of Verdi's La Traviata, also dies of the disease (a theme carried over in the modern film adaptation Moulin Rouge!).
The character of Jody in the play Hollywood Arms (by Carrie Hamilton and Carol Burnett) suffers from TB.

Novels:

In Dan Simmons' novel The Fall of Hyperion (from the Hyperion Cantos), an artificially recreated John Keats suffers and dies from tuberculosis; several chapters in the book describe his agony and personal thoughts during his final days.
In "Magic the Gathering: The Thran", the entire city of Halcyon is infected with Tuberculosis or "Phthisis", and through that disease that Yawgmoth says he shall cure is how he gains power. The disease infects also the great Genius Glacian.
The Life and Death of Mr. Badman (1680) by John Bunyan - "Yet the captain of all these men of death that came against him to take him away, was the consumption, for it was that that brought him down to the grave."
The protagonist's mother in "Angela's Ashes" by Frank McCourt dies of the consumption.
Tuberculosis is portrayed at least twice in the Sherlock Holmes stories by Sir Arthur Conan Doyle, himself a medical doctor. In 'The Final Problem', Dr. Watson gets a message saying that a lady was in 'the final stages of consumption'. In the story 'The Missing Three-Quarter', Godfrey Staunton's young wife dies of 'consumption of the most villianed kind'. 'Consumption' was a common name for 'tuberculosis' in the 19th and early 20th centuries.
Tuberculosis patients were frequent characters in 19th century Russian literature, and even inspired a character type; the consumptive nihilist, examples of which include Bazarov from Ivan Turgenev's Fathers and Sons, Katerina Ivanovna from Fyodor Dostoevsky's Crime and Punishment, Kirillov from Dostoevsky's Demons (aka The Possessed), and Ippolit and Marie from Dostoevsky's The Idiot.
In the novel The Constant Gardener by John Le Carré, as well as in the movie adaptation directed by Fernando Meirelles, the plot largely revolves around TB drugs beings tested on unwitting subjects in Africa, and dire predictions about a global pandemic of a drug-resistant form of the disease appear repeatedly.
In Sylvia Plath's novel The Bell Jar, the protagonist Esther's boyfriend Buddy Willard suffers from tuberculosis, much to her liking.
Celestine, the heroine of Octave Mirbeau's Diary of a Chambermaid, attempts to contract tuberculosis from her dying lover, Monsieur Georges.
In Nicholas Nickleby, by Charles Dickens, Nickleby's faithful companion Smike is beset by tuberculosis.
Extensively, in The Magic Mountain, by Thomas Mann, where a three week visit to a sanitarium turns into a seven year sabbatical and additionally in the novelle "Tristan" which is set in an alpine sanatorium.
In Hocus Pocus by Kurt Vonnegut, the protagonist contracts TB later in his lifetime.
In the Swedish novel "Körkarlen" by Selma Lagerlöf, the protagonist David Holm is sick with TB, and so are his younger brother Bernard and his friend Sister Edith.
In the Australian novel Seven Little Australians, Judy becomes consumptive after walking from the Blue Mountains to her home.
In the 2002 film The Twilight Samurai, the leading character Seibei Iguchi's wife dies of consumption at the beginning of the story. At the end, his opponent tells of the death of his own wife and daughter of consumption.
In Winter's Tale, by Mark Helprin, Beverly Penn is dying of consumption.
In the Henry James novel Portrait of a Lady(and the film based on it, starring Nicole Kidman), Isabel Archer's cousin Ralph is progressively suffering from TB, and finally dies of it.
Richard Yates, (1926-1992), the American writer, suffered from TB shortly after WWII, and wrote about the disease in a number of his short stories, including "No Pain Whatsoever"
"In the Year Of My Indian Prince", by Ella Thorp Ellis, she contracts TB and is in a TB treatment hospital where she meets, and falls in love with a young Indian prince, who also has TB.
In A Tree Grows in Brooklyn Frances Nolan's friend dies of TB.
In the "Anne of Green Gables" series by L.M. Montgomery, Anne's friend Ruby Gillis dies of tuberculosis.

Nonfiction

Illness as Metaphor by Susan Sontag compares the metaphorical portrayal of TB to cancer.

Theatre:

The play The Cripple of Inishmaan has themes of TB involving the protagonist and another character.

Film:

The hospitalized mother in the movie My Neighbor Totoro is thought to be suffering from tuberculosis (her ailment is not specifically named in the film, but tuberculosis is cited in the film's novelization). This is an autobiographical reference to the fact that writer/director Hayao Miyazaki's own mother spent several years of his childhood hospitalized with TB.
In the period picture Camille MGM 1936, consort Greta Garbo (Camille) tragically contracts TB (known then as "consumption") and dies in Robert Taylor's arms.
In the biographical film, A Time for Miracles starring Kate Mulgrew. Saint Mother Elizabeth Bayley Seton dies of TB at the age of 46 after founding the American Sisters of Charity order in Maryland. Seton's husband and one of her five children also died of TB.
Doc Holliday and his bloody cough were portrayed by Val Kilmer in the 1993 film Tombstone, Dennis Quaid in the 1994 film Wyatt Earp and by Kirk Douglas in the film "Gunfight at O.K Corral".
In the Swedish Film My Life as a Dog the protagonist Ingemar deals with his mother suffering from TB.
In the film Heavenly Creatures, directed by Peter Jackson, Juliet Hulme had TB, and her fear of being sent away 'for the good of her health' played a large role in determining the subsequent actions of herself and Pauline Parker.
In Finding Neverland, Kate Winslet's character suffers and later dies of TB.
In Moulin Rouge the prostitute Satine, played by Nicole Kidman, contracts TB and dies.
In The Others, the servants of the house died of tuberculosis.

Television:

In season three of Deadwood (TV series), the fictional character Doc Cochran contracts TB, which interferes with his duties about the camp. When the symptoms of his disease become apparent to other residents of the camp, they colloquially refer to him as a "lunger."
In one episode of the animated series Drawn Together, Princess Clara suffers from "the consumption."
In Fullmetal Alchemist: Conqueror of Shamballa, Alphonse Heiderich suffers from what seems to be TB.
In the popular manga and anime Naruto, Sound Five member Kaguya Kimimaro suffers to what is believed TB due to his bloody coughing and later dies during his battle between Rock Lee and Gaara.
In the popular manga and anime Bleach, Gotei 13 member Ukitake Jyuushiro suffers from what is referred to as Consumption, as witnessed in flashbacks fighting his lieutenant and coughing up blood.

Graphic art:

The Sick Child (1886) by Edvard Munch, portrait of his sister Sophie, who died of TB at 16.^[14]^[15]
Alice Neel (1900-1984), T.B. Harlem, 1940, American. Oil on canvas. JAMA cover June 8, 2005.