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Tuberculosis
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Tuberculosis
Classification and external resources

Chest X-ray of a person with advanced tuberculosis ICD-10 ICD-9 OMIM A15A19 010018 607948

DiseasesDB 8515 MedlinePlus 000077 000624 eMedicine MeSH med/2324 emerg/618 radio/411 D014376

Tuberculosis, MTB, or TB (short for tubercle bacillus) is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis.[1] Tuberculosis typically attacks the lungs but can also affect other parts of the body. It is spread through the air when people who have an active TB infection cough, sneeze, or otherwise transmit their saliva through the air.[2] Most infections in humans result in an asymptomatic, latent infection, and about one in ten latent infections eventually progresses to active disease, which, if left untreated, kills more than 50% of those so infected. The classic symptoms are a chronic cough with blood-tinged sputum, fever, night sweats, and weight loss (the last giving rise to the formerly prevalent term "consumption"). Infection of other organs causes a wide range of symptoms. Diagnosis of active TB relies on radiology (commonly chest X-rays) as well as microscopic examination and microbiological culture of bodily fluids. Diagnosis of latent TB relies on the tuberculin skin test and/or blood tests. Treatment is difficult and requires long courses of multiple antibiotics. Social contacts are also screened and treated if necessary. Antibiotic resistance is a growing problem in multiple drughttp://en.wikipedia.org/wiki/Tuberculosis 1/15

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resistant tuberculosis. Prevention relies on screening programs and vaccination with the bacillus Calmette-Gurin vaccine. One-third of the world's population is thought to have been infected with M. tuberculosis,[3] and new infections occur at a rate of about one per second.[3] In 2007, there were an estimated 13.7 million chronic active cases,[4] and in 2010, there were 8.8 million new cases, and 1.5 million deaths, mostly in developing countries.[5] The absolute number of tuberculosis cases has been decreasing since 2006, and new cases have decreased since 2002.[5] 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 510% of the United States population test positive.[1] More people in the developing world contract tuberculosis because of compromised immunity due to high rates of AIDS.[6]

Contents
[hide] 1 Signs and symptoms 1.1 Pulmonary 1.2 Extrapulmonary 2 Causes 2.1 Mycobacteria 2.2 Risk factors 3 Mechanism 3.1 Transmission 3.2 Pathogenesis 4 Diagnosis 4.1 Active tuberculosis 4.2 Latent tuberculosis 5 Prevention 5.1 Vaccines 5.2 Public health 6 Management 6.1 New onset 6.2 Recurrent disease 6.3 Medication resistance 7 Prognosis 8 Epidemiology 9 History 10 Society and culture 11 Research 12 In other animals 13 References 14 External links

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Signs and symptoms

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Signs and symptoms

The main symptoms of variants and stages of tuberculosis are given,[7] with many symptoms overlapping with other variants, while others are more (but not entirely) specific for certain variants. Multiple variants may be present simultaneously. About 510% of those without HIV, infected with tuberculosis, develop active disease during their lifetimes.[8] In contrast, 30% of those coinfected with HIV develop active disease.[8] Tuberculosis may infect any part of the body, but most commonly occurs in the lungs (known as pulmonary tuberculosis).[9] Extrapulmonary TB is when tuberculosis occurs outside of the lungs and may coexist with pulmonary TB.[9] General signs and symptoms such as: fever, chills, night sweats, appetite loss, weight loss, fatigue,[9] and finger clubbing may also occur.[8]

Pulmonary
If tuberculosis does become active, it most commonly involves infection in the lungs. Symptoms may include chest pain and a productive, prolonged cough. About a quarter of people, however, may not have any symptoms.[6] Occasionally, people may cough up blood in small amounts and in very rare cases the infection may erode into the pulmonary artery, resulting in massive bleeding known as Rasmussen's aneurysm. Tuberculosis may become chronic, with scarring usually in the upper lobes of the lungs. The upper lungs are believed to be more frequently affected due to their poor lymph supply rather than more air flow.[9]

Extrapulmonary
In the other 25% of active cases, the infection moves from the lungs, causing other kinds of TB, collectively denoted as extrapulmonary tuberculosis.[10] This occurs more commonly in
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immunosuppressed persons and young children. Extrapulmonary infection sites include the

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immunosuppressed persons and young children. Extrapulmonary infection sites include the pleura in tuberculous pleurisy, the central nervous system in meningitis, the lymphatic system in scrofula of the neck, the genitourinary system in urogenital tuberculosis, and the bones and joints in Pott's disease of the spine. When it spreads to the bones, it is also known as "osseous tuberculosis",[11] a form of osteomyelitis.[1] A potentially more serious form is disseminated TB, commonly known as miliary tuberculosis.[9]

Causes
Mycobacteria
Main article: Mycobacterium tuberculosis

Scanning electron micrograph of Mycobacterium tuberculosis The main cause of TB is Mycobacterium tuberculosis, a small, aerobic nonmotile bacillus or less commonly, the closely related Mycobacterium bovis.[9] The high lipid content of this pathogen accounts for many of its unique clinical characteristics.[12] It divides every 16 to 20 hours, an extremely slow rate compared with other bacteria, which usually divide in less than an hour.[13] Mycobacteria have an outer membrane lipid bilayer, yet microbiology textbooks continue to classify them as a Gram-positive bacteria.[14][15] If a Gram stain is performed, MTB either stains very weakly Gram-positive or does not retain dye as a result of the high lipid and mycolic acid content of its cell wall.[16] 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 the laboratory.[17] 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][16] The most common acid-fast staining technique, the ZiehlNeelsen stain, dyes AFBs a bright red that stands out clearly against a blue background. Other ways to visualize AFBs include an
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auramine-rhodamine stain and fluorescent microscopy.

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auramine-rhodamine stain and fluorescent microscopy.

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The M. tuberculosis complex (MTBC) includes four other TB-causing mycobacteria: M. bovis, M. africanum , M. canetti, and M. microti.[18] M. africanum is not widespread, but it is a significant cause of tuberculosis in parts of Africa.[19][20] 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][21] M. canetti is rare and seems to be limited to the Horn of Africa, although a few cases have been seen in African emigrants.[22][23] M. microti is rare and mostly seen in immunodeficient people, although the prevalence of this pathogen possibly has been underestimated.[24] Other known pathogenic mycobacteria include Mycobacterium leprae, Mycobacterium avium , and M. kansasii. The latter two are part of the nontuberculous mycobacteria (NTM) group. NTMs cause neither TB nor leprosy, but they do cause pulmonary diseases resembling TB.[25]

Risk factors
Main article: Risk factors for tuberculosis A a number factors make people more susceptible to TB infections. Worldwide, the most important of these is HIV, with coinfection present in about 13% of cases.[5] This is a particular problem in sub-Saharan Africa, where rates of HIV are high.[26][27] Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of the principal diseases of poverty.[6] Chronic lung disease is a risk factor, with smoking more than 20 cigarettes a day increasing the risk by two to four times[28] and silicosis increasing the risk about 30-fold.[29] Other disease states can increase the risk of developing tuberculosis, including alcoholism[6] and diabetes mellitus (threefold increase).[30] Certain medications, such as corticosteroids and infliximab (an anti-TNF monoclonal antibody) are becoming increasingly important risk factors, especially in the developed world.[6] There is also a genetic susceptibility[31] for which overall importance is still undefined.[6]

Mechanism

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Public health campaigns in the 1920s tried to halt the spread of TB.

Transmission
When people with active pulmonary TB cough, sneeze, speak, sing, or spit, they expel infectious aerosol droplets 0.5 to 5 m in diameter. A single sneeze can release up to 40,000 droplets.[32] Each one of these droplets may transmit the disease, since the infectious dose of tuberculosis is very low, and inhaling fewer than 10 bacteria may cause an infection.[33] People with prolonged, frequent, or close contact are at particularly high risk of becoming infected, with an estimated 22% infection rate.[34] A person with active but untreated tuberculosis can infect 1015 other people per year.[3] Others at risk include people in areas where TB is common, people who inject illicit drugs, inhabitants and employees of locales where vulnerable people gather (eg. prisons, homeless shelters), medically underprivileged and resource-poor populations, high-risk racial or ethnic minorities, children in close contact with high-risk category patients, those who are immunocompromised by conditions such as HIV infection, people who take immunosuppressant drugs, and health care providers serving these clients.[35] Transmission can only occur from people with activenot latentTB.[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.[36] The cascade of person-to-person spread can be circumvented by effective segregation of those with active (overt) TB, and putting them on recommended antiTB drug regimens. After about two weeks of such treatment, subjects with nonresistant active infections generally do not remain as potential sources of infection for contacts.[34] If someone does become infected, then it will take three to four weeks before the newly infected person can transmit the disease to others.[37]

Pathogenesis
About 90% of those infected with M. tuberculosis have asymptomatic, latent TB infections
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(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%.[3] TB infection begins when the mycobacteria reach the pulmonary alveoli, where they invade and replicate within the endosomes of alveolar macrophages.[1][38] The primary site of infection in the lungs, the Ghon focus, is generally located in either the upper part of the lower lobe, or the lower part of the upper lobe.[1] Simon foci may also be present. 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][39] All parts of the body can be affected by the disease, though it rarely affects the heart, skeletal muscles, pancreas and thyroid.[40] 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 granulomas, with lymphocytes surrounding the infected macrophages. The granuloma prevents dissemination of the mycobacteria and provides a local environment for interaction of cells of the immune system. Bacteria inside the granuloma can become dormant, resulting in a latent infection. Another feature of the granulomas of human tuberculosis is the development of abnormal cell death (necrosis) in the center of tubercles. To the naked eye, this has the texture of soft, white cheese and is termed caseous necrosis.[41] 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, most common in infants and the elderly, is called miliary tuberculosis. People with this disseminated TB have a fatality rate near 100% if untreated. However, if treated early, the fatality rate is reduced to about 10%.[42] In many people, the infection waxes and wanes. Tissue destruction and necrosis are balanced by healing and fibrosis.[41] Affected tissue is replaced by scarring and cavities filled with caseous 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, so can spread the infection. Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.[41]

Diagnosis
Main article: Tuberculosis diagnosis
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Mycobacterium tuberculosis (stained red) in sputum

Active tuberculosis
Diagnosing active tuberculosis based on signs and symptoms is difficult.[43] As is diagnosis tuberculosis in those who are immunosuppressed.[44] The diagnosis should be considered, though, in those with signs of lung disease or constitutional symptoms of greater than two weeks.[44] A chest X-ray, and multiple sputum cultures for acid-fast bacilli are typically part of the initial evaluation.[44] Interferon- release assays and tuberculin skin tests are of little use in the developing world.[45] IGRA have similar limitations in those with HIV[46] and questionable utility for diagnosis TB in the developed world.[47] A definitive diagnosis is made by identifying M. tuberculosis in a clinical sample (for example sputum, pus or a tissue biopsy). However, the difficult culture process for this slow-growing organism can take four to 12 weeks for blood or sputum culture. Thus, treatment is often begun before cultures are confirmed.[48] Nucleic acid amplification tests and adenosine deaminase may allow rapid diagnosis.[43] These tests, however, are not routinely recommended, as they may not alter how a person is treated.[48] Blood tests to detect antibodies are not very accurate, so are not recommended.[49]

Latent tuberculosis

Mantoux tuberculin skin test


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The Mantoux tuberculin skin test is often used to screen people at high risk.[44] Those who have been previously immunized may have a false-positive test result.[50] The test may be falsely negative in those with sarcoidosis, Hodgkins lymphoma, malnutrition, or most notably, active tuberculosis disease.[1] Interferon gamma release assays (IGRAs), on a blood sample, are recommended in those who test positive to the Mantoux test.[48] These are not affected by immunization or environmental mycobacteria, so generate fewer false-positive results.[51] There is also evidence IGRAs are more sensitive than the skin test.[52]

Prevention
Tuberculosis prevention and control efforts primarily rely on the vaccination of infants and the detection and appropriate treatment of active cases.[6] The World Health Organization has achieved some success with improved treatment regimens, and a small decrease in case numbers.[6]

Vaccines
The only currently available vaccine as of 2011 is bacillus Calmette-Gurin (BCG), which, while effective against disseminated disease in childhood, confers inconsistent protection against pulmonary disease.[53] It is the most widely used vaccine worldwide, with more than 90% of children vaccinated.[6] However, the immunity it induces decreases after about ten years.[6] As tuberculosis is uncommon in most of Canada, the United Kingdom and the United States, BCG is only administered to people at high risk.[54][55][56] Part of the reason against the use of vaccine is that it makes the tuberculin skin test falsely positive, so of no use in screening.[56] A number of new vaccines are in development.[6]

Public health
The World Health Organization (WHO) declared TB a global health emergency in 1993.[6] and in 2006 the Stop TB Partnership developed a Global Plan to Stop Tuberculosis that aims to save 14 million lives between its launch and 2015.[57] A number of targets they have set are not likely to be achieved by 2015 due to the increase in HIV-associated tuberculosis and multiple drugresistant tuberculosis.[6] A tuberculosis classification system developed by the American Thoracic Society is used primarily in public health programs.[58]

Management
Main article: Tuberculosis management
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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.[59] The two antibiotics most commonly used are isoniazid and rifampicin, and treatments can be prolonged.[36] Latent TB treatment usually uses a single antibiotic,[60] while active TB disease is best treated with combinations of several antibiotics, to reduce the risk of the bacteria developing antibiotic resistance.[6] People with latent infections are treated to prevent them from progressing to active TB disease later in life.[60]

New onset
The recommended treatment of new-onset pulmonary tuberculosis as of 2010 is six months of a combination of antibiotics containing rifampin, isoniazid, pyrazinamide and ethambutol for the first two months, and just rifampin and isoniazid for the last four months.[6] Where resistance to isoniazid is high, ethambutol may be added for the last four months.[6]

Recurrent disease
If tuberculosis recurs, testing to determine to which antibiotics it is sensitive is important before determining treatment.[6] If multiple drug-resistant TB (MDR-TB) is detected, treatment with at least four effective antibiotics for 18 to 24 months is recommended.[6]

Medication resistance
Primary resistance occurs when a persons becomes infected with a resistant strain of TB. A person with fully susceptible TB may develop secondary (acquired) resistance during therapy because of inadequate treatment, not taking the prescribed regimen appropriately, or using lowquality medication.[61] Drug-resistant TB is a public health issue in many developing countries, as its treatment is longer and requires more expensive drugs. MDR-TB is defined as resistance to the two most effective first-line TB drugs: rifampicin and isoniazid. Extensively drug-resistant TB is also resistant to three or more of the six classes of second-line drugs.[62] Totally drugresistant TB, which was first observed in 2003 in Italy, but not widely reported until 2012, is resistant to all currently used drugs.[63]

Prognosis
Progression from TB infection to TB disease occurs when the bacilli overcome the immune system defenses and begin to multiply. In primary TB disease15% of casesthis occurs soon after infection.[1] However, in the majority of cases, a latent infection occurs with no obvious symptoms.[1] These dormant bacilli can produce tuberculosis in two to 23% of these
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symptoms.

Tuberculosis - can produce encycl These dormant bacilliWikipedia, the free tuberculosis in two to 23% of these

latent cases, often many years after infection.[64] The risk of reactivation increases with immunosuppression, such as that caused by infection with HIV. In people coinfected with M. tuberculosis and HIV, the risk of reactivation increases to 10% per year.[1] Studies using DNA fingerprinting of M. tuberculosis strains have shown reinfection contributes more substantially to recurrent TB than previously thought,[65] with estimates that it might account for more than 50% in areas where TB is common.[66] The chance of death from a case of tuberculosis is about 4% as of 2008, down from 8% in 1995.[6]

Epidemiology
Main article: Epidemiology of tuberculosis

In 2007, the prevalence of TB per 100,000 people was highest in sub-Saharan Africa, and was also relatively high in Asia.[67] Roughly a third of the world's population has been infected with M. tuberculosis, and new infections occur at a rate of one per second.[3] However, not all infections with M. tuberculosis cause TB disease, and many infections are asymptomatic.[68] In 2007, there were an estimated 13.7 million chronic active cases,[4] and in 2010 there were 8.8 million new cases, and 1.45 million deaths, mostly in developing countries.[5] 0.35 million of these deaths occur in those coinfected with HIV.[69] Tuberculosis is the second most common cause of death from an infectious disease (after HIV).[9] The absolute number of tuberculosis cases has been decreasing since 2005, and new cases have decreased since 2002.[5] China has achieved particularly dramatic progress, with an 80% decline in its TB mortality rate.[69] 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 510% of the U.S. population test positive.[1] Hopes of controlling the disease have, however ,been dampened because no effective vaccine is available, the diagnosis is expensive and time-consuming, treatment takes many months, and drug-resistant disease began to emerge in the 1980s.[6]

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Annual number of new reported TB cases. Data from WHO.[70] In 2007, the country with the highest estimated incidence rate of TB was Swaziland, with 1200 cases per 100,000 people. India had the largest total incidence, with an estimated 2.0 million new cases.[4] In developed countries, tuberculosis is less common and is mainly an urban disease. In the United Kingdom, the national average was 15 per 100,000 in 2007, and the highest incidence rates in Western Europe were 30 per 100,000 in Portugal and Spain. These rates compared with 98 per 100,000 in China and 48 per 100,000 in Brazil. In the United States, the overall tuberculosis case rate was four per 100,000 persons in 2007.[67] In Canada, tuberculosis is many times more common among the aborigines, especially in remote areas.[71] The incidence of TB varies with age. In Africa, it primarily affects adolescents and young adults.[72] However, in countries where TB has gone from high to low incidence, such as the United States, it is mainly a disease of older people, or of the immunocompromised.[1][73] In Europe, rates of tuberculosis began to rise in the early 1600s to a peak level in the 1800s, when it caused nearly 25% of all deaths.[74] Mortality then decreased nearly 90% by the 1950s from its highs in the 1800s.[75] Improvements in public health reduced rates of tuberculosis even before the arrival of antibiotics, although the disease remained a significant threat to public health, such that when the Medical Research Council was formed in Britain in 1913, its initial focus was tuberculosis research. [76]

History
Main article: History of tuberculosis

Egyptian mummy in the British Museum - tubercular decay has


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Tuberculosis has been present in humans since antiquity.[6] The earliest unambiguous detection of M. tuberculosis is in the remains of bison dated 17,000 years ago.[77] However, whether tuberculosis originated in bovines, then transferred to humans, or diverged from a common ancestor, is currently unclear.[78] Evidence following a comparative genomic approach of M. tuberculosis complex (MTBC) in humans to MTBC in animals suggests humans did not acquire MTBC from animals during animal domestication as previously believed. Both strains of the tuberculosis bacteria are shown to share a common ancestor, which could have infected humans as early as the Neolithic transition.[79] Skeletal remains show prehistoric humans (4000 BCE) had TB, and researchers have found tubercular decay in the spines of Egyptian mummies dating from 3000-2400 BCE.[80] Phthisis is a Greek term for consumption; around 460 BCE, Hippocrates identified phthisis as the most widespread disease of the times involving coughing up blood and fever, which was almost always fatal.[81] Genetic studies suggest TB was present in the Americas from about the year 100 CE.[82] Before the Industrial Revolution, folklore often associated tuberculosis with vampires. When one member of a family died from it, the other infected members would lose their health slowly. People believed this was caused by the original victim draining the life from the other family members.[83] Although the pulmonary form being associated with tubercles was established by Dr Richard Morton in 1689,[84][85] 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. Schnlein.[86] During the years 18381845, Dr. John Croghan, the owner of Mammoth Cave, brought a number of people with tuberculosis 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.[87] Hermann Brehmer opened the first TB sanatorium in 1859 in Sokoowsko, Poland.[88]

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Dr. Robert Koch discovered the tuberculosis bacilli. 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.[89] Koch did not believe the bovine (cattle) and human tuberculosis diseases were similar, which delayed the recognition of infected milk as a source of infection. Later, this source was reduced 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 presymptomatic tuberculosis.[90] Albert Calmette and Camille Guerin achieved the first genuine success in immunizing against tuberculosis in 1906, using attenuated bovine-strain tuberculosis. It was called BCG (bacillus of Calmette and Guerin). The BCG vaccine was first used on humans in 1921 in France,[91] BCG only received widespread acceptance in the USA, Great Britain, and Germany after World War II.[92] Tuberculosis caused the most widespread public concern in the 19th and early 20th centuries as an 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 finding the disease was contagious in the 1880s, TB was made a notifiable disease in Britain; campaigns were started to stop spitting in public places, and the infected poor were "encouraged" to enter sanatoria that resembled prisons; the sanatoria for the middle and upper classes offered excellent care and constant medical attention.[88] 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).[88] In 1946,the development of the antibiotic streptomycin made effective treatment and cure of TB possible. Prior to the introduction of this drug, the only treatment besides sanatoria were surgical interventions, including the pneumothorax techniquecollapsing an infected lung to "rest" it and allow lesions to heala technique that was of little benefit and was largely discontinued by the 1950s.[93] The emergence of MDR-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, and is therefore thought to increase the effectiveness of therapy.[94] Hopes of completely eliminating the disease were dashed following the rise of drug-resistant strains in the 1980s. The resurgence of tuberculosis resulted in the declaration of a global health emergency by the World Health Organization in 1993. [95]
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Society and culture

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Society and culture


One molecular diagnostics test which gives results in 100 minutes is currently being offered to 116 low- and middle-income countries at a discount with support from the World Health Organization and the Bill and Melinda Gates Foundation.[96] Many resource-poor places as of 2011 still only have access to sputum microscopy.[97] In part due to poor disease management within the private health care sector, India had the highest total number of TB cases worldwide in 2010, and implementation is pending for programs similar to the Revised National Tuberculosis Control Program that has helped reduce TB levels amongst patients receiving public health care.[98]

Research
Research to develop new TB vaccines is ongoing to address the limitations of BCG.[99] A number of potential candidates are currently in phase I and II trials.[99] Two main approaches are being attempted to improve the efficacy of available vaccines; one is to add a subunit vaccine to BCG, and the other is to create new, better live vaccines.[99] MVA85A, an example of a subunit vaccine which is currently in trials in South Africa, is based on a genetically modified vaccinia virus.[100] Vaccines are hoped to play a role in treatment of both latent and active disease.[101] To encourage further discovery, researchers and policymakers are promoting new economic models of vaccine development, including prizes, tax incentives, and advance market commitments.[102][103] A number of groups, including the Stop TB Partnership, [104] the South African Tuberculosis Vaccine Initiative, and the Aeras Global TB Vaccine Foundation, are involved with research.[105]

In other animals
Mycobacteria infect many different animals, including birds,[106] rodents,[107] and reptiles.[108] The subspecies Mycobacterium tuberculosis, though, is rarely present in wild animals.[109] An effort to eradicate bovine tuberculosis caused by Mycobacterium bovis from the cattle and deer herds of New Zealand has been relatively successful.[110] Efforts in Great Britain have been less successful.[111][112]

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