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Other namesTuberculosis_header_cell_0_1_0 Phthisis, phthisis pulmonalis, consumptionTuberculosis_cell_0_1_1
SpecialtyTuberculosis_header_cell_0_2_0 Infectious disease, pulmonologyTuberculosis_cell_0_2_1
SymptomsTuberculosis_header_cell_0_3_0 Chronic cough, fever, cough with bloody mucus, weight lossTuberculosis_cell_0_3_1
CausesTuberculosis_header_cell_0_4_0 Mycobacterium tuberculosisTuberculosis_cell_0_4_1
Risk factorsTuberculosis_header_cell_0_5_0 Smoking, HIV/AIDSTuberculosis_cell_0_5_1
Diagnostic methodTuberculosis_header_cell_0_6_0 CXR, culture, tuberculin skin testTuberculosis_cell_0_6_1
Differential diagnosisTuberculosis_header_cell_0_7_0 Pneumonia, histoplasmosis, sarcoidosis, coccidioidomycosisTuberculosis_cell_0_7_1
PreventionTuberculosis_header_cell_0_8_0 Screening those at high risk, treatment of those infected, vaccination with bacillus Calmette-Guérin (BCG)Tuberculosis_cell_0_8_1
TreatmentTuberculosis_header_cell_0_9_0 AntibioticsTuberculosis_cell_0_9_1
FrequencyTuberculosis_header_cell_0_10_0 25% of people (latent TB)Tuberculosis_cell_0_10_1
DeathsTuberculosis_header_cell_0_11_0 1.5 million (2018)Tuberculosis_cell_0_11_1

Tuberculosis (TB) is an infectious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria. Tuberculosis_sentence_0

Tuberculosis generally affects the lungs, but can also affect other parts of the body. Tuberculosis_sentence_1

Most infections show no symptoms, in which case it is known as latent tuberculosis. Tuberculosis_sentence_2

About 10% of latent infections progress to active disease which, if left untreated, kills about half of those affected. Tuberculosis_sentence_3

The classic symptoms of active TB are a chronic cough with blood-containing mucus, fever, night sweats, and weight loss. Tuberculosis_sentence_4

It was historically called consumption due to the weight loss. Tuberculosis_sentence_5

Infection of other organs can cause a wide range of symptoms. Tuberculosis_sentence_6

Tuberculosis is spread from one person to the next through the air when people who have active TB in their lungs cough, spit, speak, or sneeze. Tuberculosis_sentence_7

People with latent TB do not spread the disease. Tuberculosis_sentence_8

Active infection occurs more often in people with HIV/AIDS and in those who smoke. Tuberculosis_sentence_9

Diagnosis of active TB is based on chest X-rays, as well as microscopic examination and culture of body fluids. Tuberculosis_sentence_10

Diagnosis of latent TB relies on the tuberculin skin test (TST) or blood tests. Tuberculosis_sentence_11

Prevention of TB involves screening those at high risk, early detection and treatment of cases, and vaccination with the bacillus Calmette-Guérin (BCG) vaccine. Tuberculosis_sentence_12

Those at high risk include household, workplace, and social contacts of people with active TB. Tuberculosis_sentence_13

Treatment requires the use of multiple antibiotics over a long period of time. Tuberculosis_sentence_14

Antibiotic resistance is a growing problem with increasing rates of multiple drug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). Tuberculosis_sentence_15

As of 2018 one quarter of the world's population is thought to have latent infection with TB. Tuberculosis_sentence_16

New infections occur in about 1% of the population each year. Tuberculosis_sentence_17

In 2018, there were more than 10 million cases of active TB which resulted in 1.5 million deaths. Tuberculosis_sentence_18

This makes it the number one cause of death from an infectious disease. Tuberculosis_sentence_19

As of 2018, most TB cases occurred in the regions of South-East Asia (44%), Africa (24%) and the Western Pacific (18%), with more than 50% of cases being diagnosed in eight countries: India (27%), China (9%), Indonesia (8%), the Philippines (6%), Pakistan (6%), Nigeria (4%) and Bangladesh (4%). Tuberculosis_sentence_20

The number of new cases each year has decreased since 2000. Tuberculosis_sentence_21

About 80% of people in many Asian and African countries test positive while 5–10% of people in the United States population test positive by the tuberculin test. Tuberculosis_sentence_22

Tuberculosis has been present in humans since ancient times. Tuberculosis_sentence_23

Signs and symptoms Tuberculosis_section_0

Tuberculosis may infect any part of the body, but most commonly occurs in the lungs (known as pulmonary tuberculosis). Tuberculosis_sentence_24

Extrapulmonary TB occurs when tuberculosis develops outside of the lungs, although extrapulmonary TB may coexist with pulmonary TB. Tuberculosis_sentence_25

General signs and symptoms include fever, chills, night sweats, loss of appetite, weight loss, and fatigue. Tuberculosis_sentence_26

Significant nail clubbing may also occur. Tuberculosis_sentence_27

Pulmonary Tuberculosis_section_1

If a tuberculosis infection does become active, it most commonly involves the lungs (in about 90% of cases). Tuberculosis_sentence_28

Symptoms may include chest pain and a prolonged cough producing sputum. Tuberculosis_sentence_29

About 25% of people may not have any symptoms (i.e. they remain "asymptomatic"). Tuberculosis_sentence_30

Occasionally, people may cough up blood in small amounts, and in very rare cases, the infection may erode into the pulmonary artery or a Rasmussen's aneurysm, resulting in massive bleeding. Tuberculosis_sentence_31

Tuberculosis may become a chronic illness and cause extensive scarring in the upper lobes of the lungs. Tuberculosis_sentence_32

The upper lung lobes are more frequently affected by tuberculosis than the lower ones. Tuberculosis_sentence_33

The reason for this difference is not clear. Tuberculosis_sentence_34

It may be due to either better air flow, or poor lymph drainage within the upper lungs. Tuberculosis_sentence_35

Extrapulmonary Tuberculosis_section_2

Main article: Extrapulmonary tuberculosis Tuberculosis_sentence_36

In 15–20% of active cases, the infection spreads outside the lungs, causing other kinds of TB. Tuberculosis_sentence_37

These are collectively denoted as "extrapulmonary tuberculosis". Tuberculosis_sentence_38

Extrapulmonary TB occurs more commonly in people with a weakened immune system and young children. Tuberculosis_sentence_39

In those with HIV, this occurs in more than 50% of cases. Tuberculosis_sentence_40

Notable extrapulmonary infection sites include the pleura (in tuberculous pleurisy), the central nervous system (in tuberculous meningitis), the lymphatic system (in scrofula of the neck), the genitourinary system (in urogenital tuberculosis), and the bones and joints (in Pott disease of the spine), among others. Tuberculosis_sentence_41

A potentially more serious, widespread form of TB is called "disseminated tuberculosis", it is also known as miliary tuberculosis. Tuberculosis_sentence_42

Miliary TB currently makes up about 10% of extrapulmonary cases. Tuberculosis_sentence_43

Causes Tuberculosis_section_3

Mycobacteria Tuberculosis_section_4

Main article: Mycobacterium tuberculosis Tuberculosis_sentence_44

The main cause of TB is Mycobacterium tuberculosis (MTB), a small, aerobic, nonmotile bacillus. Tuberculosis_sentence_45

The high lipid content of this pathogen accounts for many of its unique clinical characteristics. Tuberculosis_sentence_46

It divides every 16 to 20 hours, which is an extremely slow rate compared with other bacteria, which usually divide in less than an hour. Tuberculosis_sentence_47

Mycobacteria have an outer membrane lipid bilayer. Tuberculosis_sentence_48

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. Tuberculosis_sentence_49

MTB can withstand weak disinfectants and survive in a dry state for weeks. Tuberculosis_sentence_50

In nature, the bacterium can grow only within the cells of a host organism, but M. tuberculosis can be cultured in the laboratory. Tuberculosis_sentence_51

Using histological stains on expectorated samples from phlegm (also called "sputum"), scientists can identify MTB under a microscope. Tuberculosis_sentence_52

Since MTB retains certain stains even after being treated with acidic solution, it is classified as an acid-fast bacillus. Tuberculosis_sentence_53

The most common acid-fast staining techniques are the Ziehl–Neelsen stain and the Kinyoun stain, which dye acid-fast bacilli a bright red that stands out against a blue background. Tuberculosis_sentence_54

Auramine-rhodamine staining and fluorescence microscopy are also used. Tuberculosis_sentence_55

The M. Tuberculosis_sentence_56 tuberculosis complex (MTBC) includes four other TB-causing mycobacteria: M. Tuberculosis_sentence_57 bovis, M. Tuberculosis_sentence_58 africanum, M. Tuberculosis_sentence_59 canetti, and M. Tuberculosis_sentence_60 microti. Tuberculosis_sentence_61

M. africanum is not widespread, but it is a significant cause of tuberculosis in parts of Africa. Tuberculosis_sentence_62

M. bovis was once a common cause of tuberculosis, but the introduction of pasteurized milk has almost completely eliminated this as a public health problem in developed countries. Tuberculosis_sentence_63

M. canetti is rare and seems to be limited to the Horn of Africa, although a few cases have been seen in African emigrants. Tuberculosis_sentence_64

M. microti is also rare and is seen almost only in immunodeficient people, although its prevalence may be significantly underestimated. Tuberculosis_sentence_65

Other known pathogenic mycobacteria include M. Tuberculosis_sentence_66 leprae, M. Tuberculosis_sentence_67 avium, and M. Tuberculosis_sentence_68 kansasii. Tuberculosis_sentence_69

The latter two species are classified as "nontuberculous mycobacteria" (NTM). Tuberculosis_sentence_70

NTM cause neither TB nor leprosy, but they do cause lung diseases that resemble TB. Tuberculosis_sentence_71

Transmission Tuberculosis_section_5

When people with active pulmonary TB cough, sneeze, speak, sing, or spit, they expel infectious aerosol droplets 0.5 to 5.0 µm in diameter. Tuberculosis_sentence_72

A single sneeze can release up to 40,000 droplets. Tuberculosis_sentence_73

Each one of these droplets may transmit the disease, since the infectious dose of tuberculosis is very small (the inhalation of fewer than 10 bacteria may cause an infection). Tuberculosis_sentence_74

Risk of transmission Tuberculosis_section_6

People with prolonged, frequent, or close contact with people with TB are at particularly high risk of becoming infected, with an estimated 22% infection rate. Tuberculosis_sentence_75

A person with active but untreated tuberculosis may infect 10–15 (or more) other people per year. Tuberculosis_sentence_76

Transmission should occur from only people with active TB – those with latent infection are not thought to be contagious. Tuberculosis_sentence_77

The probability of transmission from one person to another depends upon several factors, including the number of infectious droplets expelled by the carrier, the effectiveness of ventilation, the duration of exposure, the virulence of the M. tuberculosis strain, the level of immunity in the uninfected person, and others. Tuberculosis_sentence_78

The cascade of person-to-person spread can be circumvented by segregating those with active ("overt") TB and putting them on anti-TB drug regimens. Tuberculosis_sentence_79

After about two weeks of effective treatment, subjects with nonresistant active infections generally do not remain contagious to others. Tuberculosis_sentence_80

If someone does become infected, it typically takes three to four weeks before the newly infected person becomes infectious enough to transmit the disease to others. Tuberculosis_sentence_81

Risk factors Tuberculosis_section_7

Main article: Risk factors for tuberculosis Tuberculosis_sentence_82

A number of factors make individuals more susceptible to TB infection and/or disease. Tuberculosis_sentence_83

Active disease risk Tuberculosis_section_8

The most important risk factor globally is HIV; 13% of those with TB are also infected with HIV. Tuberculosis_sentence_84

This is a particular problem in sub-Saharan Africa, where rates of HIV are high. Tuberculosis_sentence_85

Of those without HIV who are infected with tuberculosis, about 5–10% develop active disease during their lifetimes; in contrast, 30% of those co-infected with HIV develop the active disease. Tuberculosis_sentence_86

Use of certain medications, such as corticosteroids and infliximab (an anti-αTNF monoclonal antibody), is another important risk factor, especially in the developed world. Tuberculosis_sentence_87

Other risk factors include: alcoholism, diabetes mellitus (3-fold increased risk), silicosis (30-fold increased risk), tobacco smoking (2-fold increased risk), indoor air pollution, malnutrition, young age, recently acquired TB infection, recreational drug use, severe kidney disease, low body weight, organ transplant, head and neck cancer, and genetic susceptibility (of which the overall importance remains undefined). Tuberculosis_sentence_88

Infection susceptibility Tuberculosis_section_9

Tobacco smoking increases the risk of infections (in addition to increasing the risk of active disease and death). Tuberculosis_sentence_89

Additional factors increasing infection susceptibility include: young age (children). Tuberculosis_sentence_90

Pathogenesis Tuberculosis_section_10

About 90% of those infected with M. tuberculosis have asymptomatic, latent TB infections (sometimes called LTBI), with only a 10% lifetime chance that the latent infection will progress to overt, active tuberculous disease. Tuberculosis_sentence_91

In those with HIV, the risk of developing active TB increases to nearly 10% a year. Tuberculosis_sentence_92

If effective treatment is not given, the death rate for active TB cases is up to 66%. Tuberculosis_sentence_93

TB infection begins when the mycobacteria reach the alveolar air sacs of the lungs, where they invade and replicate within endosomes of alveolar macrophages. Tuberculosis_sentence_94

Macrophages identify the bacterium as foreign and attempt to eliminate it by phagocytosis. Tuberculosis_sentence_95

During this process, the bacterium is enveloped by the macrophage and stored temporarily in a membrane-bound vesicle called a phagosome. Tuberculosis_sentence_96

The phagosome then combines with a lysosome to create a phagolysosome. Tuberculosis_sentence_97

In the phagolysosome, the cell attempts to use reactive oxygen species and acid to kill the bacterium. Tuberculosis_sentence_98

However, M. tuberculosis has a thick, waxy mycolic acid capsule that protects it from these toxic substances. Tuberculosis_sentence_99

M. tuberculosis is able to reproduce inside the macrophage and will eventually kill the immune cell. Tuberculosis_sentence_100

The primary site of infection in the lungs, known as the "Ghon focus", is generally located in either the upper part of the lower lobe, or the lower part of the upper lobe. Tuberculosis_sentence_101

Tuberculosis of the lungs may also occur via infection from the blood stream. Tuberculosis_sentence_102

This is known as a Simon focus and is typically found in the top of the lung. Tuberculosis_sentence_103

This hematogenous transmission can also spread infection to more distant sites, such as peripheral lymph nodes, the kidneys, the brain, and the bones. Tuberculosis_sentence_104

All parts of the body can be affected by the disease, though for unknown reasons it rarely affects the heart, skeletal muscles, pancreas, or thyroid. Tuberculosis_sentence_105

Tuberculosis is classified as one of the granulomatous inflammatory diseases. Tuberculosis_sentence_106

Macrophages, epithelioid cells, T lymphocytes, B lymphocytes, and fibroblasts aggregate to form granulomas, with lymphocytes surrounding the infected macrophages. Tuberculosis_sentence_107

When other macrophages attack the infected macrophage, they fuse together to form a giant multinucleated cell in the alveolar lumen. Tuberculosis_sentence_108

The granuloma may prevent dissemination of the mycobacteria and provide a local environment for interaction of cells of the immune system. Tuberculosis_sentence_109

However, more recent evidence suggests that the bacteria use the granulomas to avoid destruction by the host's immune system. Tuberculosis_sentence_110

Macrophages and dendritic cells in the granulomas are unable to present antigen to lymphocytes; thus the immune response is suppressed. Tuberculosis_sentence_111

Bacteria inside the granuloma can become dormant, resulting in latent infection. Tuberculosis_sentence_112

Another feature of the granulomas is the development of abnormal cell death (necrosis) in the center of tubercles. Tuberculosis_sentence_113

To the naked eye, this has the texture of soft, white cheese and is termed caseous necrosis. Tuberculosis_sentence_114

If TB bacteria gain entry to the blood stream from an area of damaged tissue, they can spread throughout the body and set up many foci of infection, all appearing as tiny, white tubercles in the tissues. Tuberculosis_sentence_115

This severe form of TB disease, most common in young children and those with HIV, is called miliary tuberculosis. Tuberculosis_sentence_116

People with this disseminated TB have a high fatality rate even with treatment (about 30%). Tuberculosis_sentence_117

In many people, the infection waxes and wanes. Tuberculosis_sentence_118

Tissue destruction and necrosis are often balanced by healing and fibrosis. Tuberculosis_sentence_119

Affected tissue is replaced by scarring and cavities filled with caseous necrotic material. Tuberculosis_sentence_120

During active disease, some of these cavities are joined to the air passages (bronchi) and this material can be coughed up. Tuberculosis_sentence_121

It contains living bacteria, and thus can spread the infection. Tuberculosis_sentence_122

Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Tuberculosis_sentence_123

Upon cure, affected areas are eventually replaced by scar tissue. Tuberculosis_sentence_124

Diagnosis Tuberculosis_section_11

Main article: Tuberculosis diagnosis Tuberculosis_sentence_125

Active tuberculosis Tuberculosis_section_12

Diagnosing active tuberculosis based only on signs and symptoms is difficult, as is diagnosing the disease in those who have a weakened immune system. Tuberculosis_sentence_126

A diagnosis of TB should, however, be considered in those with signs of lung disease or constitutional symptoms lasting longer than two weeks. Tuberculosis_sentence_127

A chest X-ray and multiple sputum cultures for acid-fast bacilli are typically part of the initial evaluation. Tuberculosis_sentence_128

Interferon-γ release assays and tuberculin skin tests are of little use in most of the developing world. Tuberculosis_sentence_129

Interferon gamma release assays (IGRA) have similar limitations in those with HIV. Tuberculosis_sentence_130

A definitive diagnosis of TB is made by identifying M. tuberculosis in a clinical sample (e.g., sputum, pus, or a tissue biopsy). Tuberculosis_sentence_131

However, the difficult culture process for this slow-growing organism can take two to six weeks for blood or sputum culture. Tuberculosis_sentence_132

Thus, treatment is often begun before cultures are confirmed. Tuberculosis_sentence_133

Nucleic acid amplification tests and adenosine deaminase testing may allow rapid diagnosis of TB. Tuberculosis_sentence_134

These tests, however, are not routinely recommended, as they rarely alter how a person is treated. Tuberculosis_sentence_135

Blood tests to detect antibodies are not specific or sensitive, so they are not recommended. Tuberculosis_sentence_136

Latent tuberculosis Tuberculosis_section_13

Main article: Latent tuberculosis Tuberculosis_sentence_137

The Mantoux tuberculin skin test is often used to screen people at high risk for TB. Tuberculosis_sentence_138

Those who have been previously immunized with the Bacille Calmette-Guerin vaccine may have a false-positive test result. Tuberculosis_sentence_139

The test may be falsely negative in those with sarcoidosis, Hodgkin's lymphoma, malnutrition, and most notably, active tuberculosis. Tuberculosis_sentence_140

Interferon gamma release assays, on a blood sample, are recommended in those who are positive to the Mantoux test. Tuberculosis_sentence_141

These are not affected by immunization or most environmental mycobacteria, so they generate fewer false-positive results. Tuberculosis_sentence_142

However, they are affected by M. szulgai, M. marinum, and M. kansasii. Tuberculosis_sentence_143

IGRAs may increase sensitivity when used in addition to the skin test, but may be less sensitive than the skin test when used alone. Tuberculosis_sentence_144

The US Preventive Services Task Force (USPSTF) has recommended screening people who are at high risk for latent tuberculosis with either tuberculin skin tests or interferon-gamma release assays. Tuberculosis_sentence_145

While some have recommend testing health care workers, evidence of benefit for this is poor as of 2019. Tuberculosis_sentence_146

The Centers for Disease Control and Prevention (CDC) stopped recommending yearly testing of health care workers without known exposure in 2019. Tuberculosis_sentence_147

Prevention Tuberculosis_section_14

Tuberculosis prevention and control efforts rely primarily on the vaccination of infants and the detection and appropriate treatment of active cases. Tuberculosis_sentence_148

The World Health Organization (WHO) has achieved some success with improved treatment regimens, and a small decrease in case numbers. Tuberculosis_sentence_149

Vaccines Tuberculosis_section_15

Main articles: Tuberculosis vaccines and BCG vaccine Tuberculosis_sentence_150

The only available vaccine as of 2011 is Bacillus Calmette-Guérin (BCG). Tuberculosis_sentence_151

In children it decreases the risk of getting the infection by 20% and the risk of infection turning into active disease by nearly 60%. Tuberculosis_sentence_152

It is the most widely used vaccine worldwide, with more than 90% of all children being vaccinated. Tuberculosis_sentence_153

The immunity it induces decreases after about ten years. Tuberculosis_sentence_154

As tuberculosis is uncommon in most of Canada, Western Europe, and the United States, BCG is administered to only those people at high risk. Tuberculosis_sentence_155

Part of the reasoning against the use of the vaccine is that it makes the tuberculin skin test falsely positive, reducing the test's usefulness as a screening tool. Tuberculosis_sentence_156

Several vaccines are being developed. Tuberculosis_sentence_157

Intradermal MVA85A Vaccine in addition to BCG injection is not effective in preventing tuberculosis. Tuberculosis_sentence_158

Public health Tuberculosis_section_16

The World Health Organization (WHO) declared TB a "global health emergency" in 1993, and in 2006, the Stop TB Partnership developed a Global Plan to Stop Tuberculosis that aimed to save 14 million lives between its launch and 2015. Tuberculosis_sentence_159

A number of targets they set were not achieved by 2015, mostly due to the increase in HIV-associated tuberculosis and the emergence of multiple drug-resistant tuberculosis. Tuberculosis_sentence_160

A tuberculosis classification system developed by the American Thoracic Society is used primarily in public health programs. Tuberculosis_sentence_161

The benefits and risks of giving anti-tubercular drugs in those exposed to MDR-TB is unclear. Tuberculosis_sentence_162

Treatment Tuberculosis_section_17

Main article: Tuberculosis management Tuberculosis_sentence_163

Treatment of TB uses antibiotics to kill the bacteria. Tuberculosis_sentence_164

Effective TB treatment is difficult, due to the unusual structure and chemical composition of the mycobacterial cell wall, which hinders the entry of drugs and makes many antibiotics ineffective. Tuberculosis_sentence_165

Active TB is best treated with combinations of several antibiotics to reduce the risk of the bacteria developing antibiotic resistance. Tuberculosis_sentence_166

The routine use of rifabutin instead of rifampicin in HIV-positive people with tuberculosis is of unclear benefit as of 2007. Tuberculosis_sentence_167

Latent Tuberculosis_section_18

Latent TB is treated with either isoniazid or rifampin alone, or a combination of isoniazid with either rifampicin or rifapentine. Tuberculosis_sentence_168

The treatment takes three to nine months depending on the medications used. Tuberculosis_sentence_169

People with latent infections are treated to prevent them from progressing to active TB disease later in life. Tuberculosis_sentence_170

Education or counselling may improve the latent tuberculosis treatment completion rates. Tuberculosis_sentence_171

New onset Tuberculosis_section_19

The recommended treatment of new-onset pulmonary tuberculosis, as of 2010, is six months of a combination of antibiotics containing rifampicin, isoniazid, pyrazinamide, and ethambutol for the first two months, and only rifampicin and isoniazid for the last four months. Tuberculosis_sentence_172

Where resistance to isoniazid is high, ethambutol may be added for the last four months as an alternative. Tuberculosis_sentence_173

Treatment with anti-TB drugs for at least 6 months results in higher success rates when compared with treatment less than 6 months; even though the difference is small. Tuberculosis_sentence_174

Shorter treatment regimen may be recommended for those with compliance issues. Tuberculosis_sentence_175

There is also no evidence to support shorter anti-tubeculosis treatment regimen when compared to 6 months treatment regimen. Tuberculosis_sentence_176

Recurrent disease Tuberculosis_section_20

If tuberculosis recurs, testing to determine which antibiotics it is sensitive to is important before determining treatment. Tuberculosis_sentence_177

If multiple drug-resistant TB (MDR-TB) is detected, treatment with at least four effective antibiotics for 18 to 24 months is recommended. Tuberculosis_sentence_178

Medication administration Tuberculosis_section_21

Directly observed therapy, i.e., having a health care provider watch the person take their medications, is recommended by the World Health Organization (WHO) in an effort to reduce the number of people not appropriately taking antibiotics. Tuberculosis_sentence_179

The evidence to support this practice over people simply taking their medications independently is of poor quality. Tuberculosis_sentence_180

There is no strong evidence indicating that directly observed therapy improves the number of people who were cured or the number of people who complete their medicine. Tuberculosis_sentence_181

Moderate quality evidence suggests that there is also no difference if people are observed at home versus at a clinic, or by a family member versus a health care worker. Tuberculosis_sentence_182

Methods to remind people of the importance of treatment and appointments may result in a small but important improvement. Tuberculosis_sentence_183

There is also not enough evidence to support intermittent rifampicin-containing therapy given two to three times a week has equal effectiveness as daily dose regimen on improving cure rates and reducing relapsing rates. Tuberculosis_sentence_184

There is also not enough evidence on effectiveness of giving intermittent twice or thrice weekly short course regimen compared to daily dosing regimen in treating children with tuberculosis. Tuberculosis_sentence_185

Medication resistance Tuberculosis_section_22

Primary resistance occurs when a person becomes infected with a resistant strain of TB. Tuberculosis_sentence_186

A person with fully susceptible MTB may develop secondary (acquired) resistance during therapy because of inadequate treatment, not taking the prescribed regimen appropriately (lack of compliance), or using low-quality medication. Tuberculosis_sentence_187

Drug-resistant TB is a serious public health issue in many developing countries, as its treatment is longer and requires more expensive drugs. Tuberculosis_sentence_188

MDR-TB is defined as resistance to the two most effective first-line TB drugs: rifampicin and isoniazid. Tuberculosis_sentence_189

Extensively drug-resistant TB is also resistant to three or more of the six classes of second-line drugs. Tuberculosis_sentence_190

Totally drug-resistant TB is resistant to all currently used drugs. Tuberculosis_sentence_191

It was first observed in 2003 in Italy, but not widely reported until 2012, and has also been found in Iran and India. Tuberculosis_sentence_192

Bedaquiline is tentatively supported for use in multiple drug-resistant TB. Tuberculosis_sentence_193

XDR-TB is a term sometimes used to define extensively resistant TB, and constitutes one in ten cases of MDR-TB. Tuberculosis_sentence_194

Cases of XDR TB have been identified in more than 90% of countries. Tuberculosis_sentence_195

There is some efficacy for linezolid to treat those with XDR-TB but side effects and discontinuation of medications were common. Tuberculosis_sentence_196

For those with known rifampicin or MDR-TB, Genotype® MTBDRsl Assay performed on culture isolates or smear positive specimens may be useful to detect second-line anti-tubercular drug resistance. Tuberculosis_sentence_197

Prognosis Tuberculosis_section_23

Progression from TB infection to overt TB disease occurs when the bacilli overcome the immune system defenses and begin to multiply. Tuberculosis_sentence_198

In primary TB disease (some 1–5% of cases), this occurs soon after the initial infection. Tuberculosis_sentence_199

However, in the majority of cases, a latent infection occurs with no obvious symptoms. Tuberculosis_sentence_200

These dormant bacilli produce active tuberculosis in 5–10% of these latent cases, often many years after infection. Tuberculosis_sentence_201

The risk of reactivation increases with immunosuppression, such as that caused by infection with HIV. Tuberculosis_sentence_202

In people coinfected with M. tuberculosis and HIV, the risk of reactivation increases to 10% per year. Tuberculosis_sentence_203

Studies using DNA fingerprinting of M. tuberculosis strains have shown reinfection contributes more substantially to recurrent TB than previously thought, with estimates that it might account for more than 50% of reactivated cases in areas where TB is common. Tuberculosis_sentence_204

The chance of death from a case of tuberculosis is about 4% as of 2008, down from 8% in 1995. Tuberculosis_sentence_205

In people with smear-positive pulmonary TB (without HIV co-infection), after 5 years without treatment, 50-60% die while 20-25% achieve spontaneous resolution (cure). Tuberculosis_sentence_206

TB is almost always fatal in those with untreated HIV co-infection and death rates are increased even with antiretroviral treatment of HIV. Tuberculosis_sentence_207

Epidemiology Tuberculosis_section_24

Roughly one-quarter of the world's population has been infected with M. tuberculosis, with new infections occurring in about 1% of the population each year. Tuberculosis_sentence_208

However, most infections with M. tuberculosis do not cause TB disease, and 90–95% of infections remain asymptomatic. Tuberculosis_sentence_209

In 2012, an estimated 8.6 million chronic cases were active. Tuberculosis_sentence_210

In 2010, 8.8 million new cases of TB were diagnosed, and 1.20–1.45 million deaths occurred (most of these occurring in developing countries). Tuberculosis_sentence_211

Of these, about 0.35 million occur in those also infected with HIV. Tuberculosis_sentence_212

In 2018, tuberculosis was the leading cause of death worldwide from a single infectious agent. Tuberculosis_sentence_213

The total number of tuberculosis cases has been decreasing since 2005, while new cases have decreased since 2002. Tuberculosis_sentence_214

Tuberculosis incidence is seasonal, with peaks occurring every spring/summer. Tuberculosis_sentence_215

The reasons for this are unclear, but may be related to vitamin D deficiency during the winter. Tuberculosis_sentence_216

There are also studies linking Tuberculosis to different weather conditions like low temperature, low humidity and low rainfall. Tuberculosis_sentence_217

It has also been suggested that Tuberculosis incidence rates may be connected to climate change. Tuberculosis_sentence_218

At-risk groups Tuberculosis_section_25

Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of the principal diseases of poverty. Tuberculosis_sentence_219

Those at high risk thus include: people who inject illicit drugs, inhabitants and employees of locales where vulnerable people gather (e.g. prisons and homeless shelters), medically underprivileged and resource-poor communities, high-risk ethnic minorities, children in close contact with high-risk category patients, and health-care providers serving these patients. Tuberculosis_sentence_220

The rate of TB varies with age. Tuberculosis_sentence_221

In Africa, it primarily affects adolescents and young adults. Tuberculosis_sentence_222

However, in countries where incidence rates have declined dramatically (such as the United States), TB is mainly a disease of older people and the immunocompromised (risk factors are listed above). Tuberculosis_sentence_223

Worldwide, 22 "high-burden" states or countries together experience 80% of cases as well as 83% of deaths. Tuberculosis_sentence_224

In Canada and Australia, tuberculosis is many times more common among the aboriginal peoples, especially in remote areas. Tuberculosis_sentence_225

Factors contributing to this include higher prevalence of predisposing health conditions and behaviours, and overcrowding and poverty. Tuberculosis_sentence_226

In some Canadian aboriginal groups, genetic susceptibility may play a role. Tuberculosis_sentence_227

Socioeconomic status (SES) strongly affects TB risk. Tuberculosis_sentence_228

People of low SES are both more likely to contract TB and to be more severely affected by the disease. Tuberculosis_sentence_229

Those with low SES are more likely to be affected by risk factors for developing TB (e.g. malnutrition, indoor air pollution, HIV co-infection, etc.), and are additionally more likely to be exposed to crowded and poorly ventilated spaces. Tuberculosis_sentence_230

Inadequate healthcare also means that people with active disease who facilitate spread are not diagnosed and treated promptly; sick people thus remain in the infectious state and (continue to) spread the infection. Tuberculosis_sentence_231

Geographical epidemiology Tuberculosis_section_26

The distribution of tuberculosis is not uniform across the globe; about 80% of the population in many African, Caribbean, south Asian, and eastern European countries test positive in tuberculin tests, while only 5–10% of the U.S. population test positive. Tuberculosis_sentence_232

Tuberculosis is more common in developing countries; 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. Tuberculosis_sentence_233

Hopes of totally controlling the disease have been dramatically dampened because of a number of factors, including the difficulty of developing an effective vaccine, the expensive and time-consuming diagnostic process, the necessity of many months of treatment, the increase in HIV-associated tuberculosis, and the emergence of drug-resistant cases in the 1980s. Tuberculosis_sentence_234

In developed countries, tuberculosis is less common and is found mainly in urban areas. Tuberculosis_sentence_235

In Europe, deaths from TB fell from 500 out of 100,000 in 1850 to 50 out of 100,000 by 1950. Tuberculosis_sentence_236

Improvements in public health were reducing 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. Tuberculosis_sentence_237

In 2010, rates per 100,000 people in different areas of the world were: globally 178, Africa 332, the Americas 36, Eastern Mediterranean 173, Europe 63, Southeast Asia 278, and Western Pacific 139. Tuberculosis_sentence_238

Russia Tuberculosis_section_27

Russia has achieved particularly dramatic progress with decline in its TB mortality rate—from 61.9 per 100,000 in 1965 to 2.7 per 100,000 in 1993; however, mortality rate increased to 24 per 100,000 in 2005 and then recoiled to 11 per 100,000 by 2015. Tuberculosis_sentence_239

China Tuberculosis_section_28

China has achieved particularly dramatic progress, with about an 80% reduction in its TB mortality rate between 1990 and 2010. Tuberculosis_sentence_240

The number of new cases has declined by 17% between 2004 and 2014. Tuberculosis_sentence_241

Africa Tuberculosis_section_29

In 2007, the country with the highest estimated incidence rate of TB was Eswatini, with 1,200 cases per 100,000 people. Tuberculosis_sentence_242

In 2017, the country with the highest estimated incidence rate as a % of the population was Lesotho, with 665 cases per 100,000 people. Tuberculosis_sentence_243

India Tuberculosis_section_30

As of 2017, India had the largest total incidence, with an estimated 2 740 000 cases. Tuberculosis_sentence_244

According to the World Health Organization (WHO), in 2000–2015, India's estimated mortality rate dropped from 55 to 36 per 100 000 population per year with estimated 480 thousand people died of TB in 2015. Tuberculosis_sentence_245

North America Tuberculosis_section_31

In the United States Native Americans have a fivefold greater mortality from TB, and racial and ethnic minorities accounted for 84% of all reported TB cases. Tuberculosis_sentence_246

In the United States, the overall tuberculosis case rate was 3 per 100,000 persons in 2017. Tuberculosis_sentence_247

In Canada, tuberculosis is still endemic in some rural areas. Tuberculosis_sentence_248

Western Europe Tuberculosis_section_32

In 2017, in the United Kingdom, the national average was 9 per 100,000 and the highest incidence rates in Western Europe were 20 per 100,000 in Portugal. Tuberculosis_sentence_249


  • Tuberculosis_item_0_0
  • Tuberculosis_item_0_1
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History Tuberculosis_section_33

Main article: History of tuberculosis Tuberculosis_sentence_250

Tuberculosis has existed since antiquity. Tuberculosis_sentence_251

The oldest unambiguously detected M. tuberculosis gives evidence of the disease in the remains of bison in Wyoming dated to around 17,000 years ago. Tuberculosis_sentence_252

However, whether tuberculosis originated in bovines, then transferred to humans, or whether both bovine and human tuberculosis diverged from a common ancestor, remains unclear. Tuberculosis_sentence_253

A comparison of the genes of M. tuberculosis complex (MTBC) in humans to MTBC in animals suggests humans did not acquire MTBC from animals during animal domestication, as researchers previously believed. Tuberculosis_sentence_254

Both strains of the tuberculosis bacteria share a common ancestor, which could have infected humans even before the Neolithic Revolution. Tuberculosis_sentence_255

Skeletal remains show some prehistoric humans (4000 BC) had TB, and researchers have found tubercular decay in the spines of Egyptian mummies dating from 3000 to 2400 BC. Tuberculosis_sentence_256

Genetic studies suggest the presence of TB in the Americas from about 100 AD. Tuberculosis_sentence_257

Before the Industrial Revolution, folklore often associated tuberculosis with vampires. Tuberculosis_sentence_258

When one member of a family died from the disease, the other infected members would lose their health slowly. Tuberculosis_sentence_259

People believed this was caused by the original person with TB draining the life from the other family members. Tuberculosis_sentence_260

Although Richard Morton established the pulmonary form associated with tubercles as a pathology in 1689, due to the variety of its symptoms, TB was not identified as a single disease until the 1820s. Tuberculosis_sentence_261

Benjamin Marten conjectured in 1720 that consumptions were caused by microbes which were spread by people living in close proximity to each other. Tuberculosis_sentence_262

In 1819 René Laennec claimed that tubercles were the cause of pulmonary tuberculosis. Tuberculosis_sentence_263

J. Tuberculosis_sentence_264 L. Schönlein first published the name "tuberculosis" (German: Tuberkulose) in 1832. Tuberculosis_sentence_265

Between 1838 and 1845, Dr. John Croghan, the owner of Mammoth Cave in Kentucky from 1839 onwards, 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; each died within a year. Tuberculosis_sentence_266

Hermann Brehmer opened the first TB sanatorium in 1859 in Görbersdorf (now Sokołowsko) in Silesia. Tuberculosis_sentence_267

In 1865 Jean Antoine Villemin demonstrated that tuberculosis could be transmitted, via inoculation, from humans to animals and among animals. Tuberculosis_sentence_268

(Villemin's findings were confirmed in 1867 and 1868 by John Burdon-Sanderson.) Tuberculosis_sentence_269

Robert Koch identified and described the bacillus causing tuberculosis, M. tuberculosis, on 24 March 1882. Tuberculosis_sentence_270

He received the Nobel Prize in physiology or medicine in 1905 for this discovery. Tuberculosis_sentence_271

Koch did not believe the cattle and human tuberculosis diseases were similar, which delayed the recognition of infected milk as a source of infection. Tuberculosis_sentence_272

During the first half of the 1900s the risk of transmission from this source was dramatically reduced after the application of the pasteurization process. Tuberculosis_sentence_273

Koch announced a glycerine extract of the tubercle bacilli as a "remedy" for tuberculosis in 1890, calling it "tuberculin". Tuberculosis_sentence_274

Although it was not effective, it was later successfully adapted as a screening test for the presence of pre-symptomatic tuberculosis. Tuberculosis_sentence_275

World Tuberculosis Day is marked on 24 March each year, the anniversary of Koch's original scientific announcement. Tuberculosis_sentence_276

Albert Calmette and Camille Guérin achieved the first genuine success in immunization against tuberculosis in 1906, using attenuated bovine-strain tuberculosis. Tuberculosis_sentence_277

It was called bacille Calmette–Guérin (BCG). Tuberculosis_sentence_278

The BCG vaccine was first used on humans in 1921 in France, but achieved widespread acceptance in the US, Great Britain, and Germany only after World War II. Tuberculosis_sentence_279

Tuberculosis caused widespread public concern in the 19th and early 20th centuries as the disease became common among the urban poor. Tuberculosis_sentence_280

In 1815 one in four deaths in England was due to "consumption". Tuberculosis_sentence_281

By 1918, TB still caused one in six deaths in France. Tuberculosis_sentence_282

After TB was determined to be contagious, in the 1880s, it was put on a notifiable-disease list in Britain; campaigns started to stop people from 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). Tuberculosis_sentence_283

Whatever the benefits of the "fresh air" and labor in the sanatoria, even under the best conditions, 50% of those who entered died within five years (c. 1916). Tuberculosis_sentence_284

When the Medical Research Council formed in Britain in 1913, it initially focused on tuberculosis research. Tuberculosis_sentence_285

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. Tuberculosis_sentence_286

By the 1950s mortality in Europe had decreased about 90%. Tuberculosis_sentence_287

Improvements in sanitation, vaccination, and other public-health measures began significantly reducing rates of tuberculosis even before the arrival of streptomycin and other antibiotics, although the disease remained a significant threat. Tuberculosis_sentence_288

In 1946 the development of the antibiotic streptomycin made effective treatment and cure of TB a reality. Tuberculosis_sentence_289

Prior to the introduction of this medication, the only treatment was surgical intervention, including the "pneumothorax technique", which involved collapsing an infected lung to "rest" it and to allow tuberculous lesions to heal. Tuberculosis_sentence_290

Because of the emergence of MDR-TB, surgery has been re-introduced for certain cases of TB infections. Tuberculosis_sentence_291

It involves the removal of infected chest cavities ("bullae") in the lungs to reduce the number of bacteria and to increase exposure of the remaining bacteria to antibiotics in the bloodstream. Tuberculosis_sentence_292

Hopes of completely eliminating TB ended with the rise of drug-resistant strains in the 1980s. Tuberculosis_sentence_293

The subsequent resurgence of tuberculosis resulted in the declaration of a global health emergency by the World Health Organization (WHO) in 1993. Tuberculosis_sentence_294

Society and culture Tuberculosis_section_34

Names Tuberculosis_section_35

Tuberculosis has been known by many names from the technical to the familiar. Tuberculosis_sentence_295

Phthisis (Φθισις) is a Greek word for consumption, an old term for pulmonary tuberculosis; around 460 BCE, Hippocrates described phthisis as a disease of dry seasons. Tuberculosis_sentence_296

The abbreviation "TB" is short for tubercle bacillus. Tuberculosis_sentence_297

"Consumption" was the most common nineteenth century English word for the disease. Tuberculosis_sentence_298

The Latin root "con" meaning "completely" is linked to "sumere" meaning "to take up from under." Tuberculosis_sentence_299

In The Life and Death of Mr Badman by John Bunyan, the author calls consumption "the captain of all these men of death." Tuberculosis_sentence_300

"Great white plague" has also been used. Tuberculosis_sentence_301

Art and literature Tuberculosis_section_36

Main article: Tuberculosis in human culture Tuberculosis_sentence_302

Tuberculosis was for centuries associated with poetic and artistic qualities among those infected, and was also known as "the romantic disease". Tuberculosis_sentence_303

Major artistic figures such as the poets John Keats, Percy Bysshe Shelley, and Edgar Allan Poe, the composer Frédéric Chopin, the playwright Anton Chekhov, the novelists Franz Kafka, Katherine Mansfield, Charlotte Brontë, Fyodor Dostoevsky, Thomas Mann, W. Tuberculosis_sentence_304 Somerset Maugham, George Orwell, and Robert Louis Stevenson, and the artists Alice Neel, Jean-Antoine Watteau, Elizabeth Siddal, Marie Bashkirtseff, Edvard Munch, Aubrey Beardsley and Amedeo Modigliani either had the disease or were surrounded by people who did. Tuberculosis_sentence_305

A widespread belief was that tuberculosis assisted artistic talent. Tuberculosis_sentence_306

Physical mechanisms proposed for this effect included the slight fever and toxaemia that it caused, allegedly helping them to see life more clearly and to act decisively. Tuberculosis_sentence_307

Tuberculosis formed an often-reused theme in literature, as in Thomas Mann's The Magic Mountain, set in a sanatorium; in music, as in Van Morrison's song "T.B. Tuberculosis_sentence_308 Sheets"; in opera, as in Puccini's La bohème and Verdi's La Traviata; in art, as in Monet's painting of his first wife Camille on her deathbed; and in film, such as the 1945 The Bells of St. Mary's starring Ingrid Bergman as a nun with tuberculosis. Tuberculosis_sentence_309

Public health efforts Tuberculosis_section_37

The World Health Organization (WHO), the Bill and Melinda Gates Foundation, and the U.S. government are subsidizing a fast-acting diagnostic tuberculosis test for use in low- and middle-income countries as of 2012. Tuberculosis_sentence_310

In addition to being fast-acting, the test can determine if there is resistance to the antibiotic rifampicin which may indicate multi-drug resistant tuberculosis and is accurate in those who are also infected with HIV. Tuberculosis_sentence_311

Many resource-poor places as of 2011 have access to only sputum microscopy. Tuberculosis_sentence_312

India had the highest total number of TB cases worldwide in 2010, in part due to poor disease management within the private and public health care sector. Tuberculosis_sentence_313

Programs such as the Revised National Tuberculosis Control Program are working to reduce TB levels among people receiving public health care. Tuberculosis_sentence_314

A 2014 the EIU-healthcare report finds there is a need to address apathy and urges for increased funding. Tuberculosis_sentence_315

The report cites among others Lucica Ditui "[TB] is like an orphan. Tuberculosis_sentence_316

It has been neglected even in countries with a high burden and often forgotten by donors and those investing in health interventions." Tuberculosis_sentence_317

Slow progress has led to frustration, expressed by the executive director of the Global Fund to Fight AIDS, Tuberculosis and Malaria – Mark Dybul: "we have the tools to end TB as a pandemic and public health threat on the planet, but we are not doing it." Tuberculosis_sentence_318

Several international organizations are pushing for more transparency in treatment, and more countries are implementing mandatory reporting of cases to the government as of 2014, although adherence is often variable. Tuberculosis_sentence_319

Commercial treatment providers may at times overprescribe second-line drugs as well as supplementary treatment, promoting demands for further regulations. Tuberculosis_sentence_320

The government of Brazil provides universal TB-care, which reduces this problem. Tuberculosis_sentence_321

Conversely, falling rates of TB-infection may not relate to the number of programs directed at reducing infection rates but may be tied to increased level of education, income, and health of the population. Tuberculosis_sentence_322

Costs of the disease, as calculated by the World Bank in 2009 may exceed US$150 billion per year in "high burden" countries. Tuberculosis_sentence_323

Lack of progress eradicating the disease may also be due to lack of patient follow-up – as among the 250M rural migrants in China. Tuberculosis_sentence_324

There is insufficient data to show that active contact tracing helps to improve case detection rates for tuberculosis. Tuberculosis_sentence_325

Interventions such as house-to-house visits, educational leaflets, mass media strategies, educational sessions may increase tuberculosis detection rates in short-term. Tuberculosis_sentence_326

There is no study that compare new method of contact tracing such as social network analysis with existing contact tracing methods. Tuberculosis_sentence_327

Stigma Tuberculosis_section_38

Slow progress in preventing the disease may in part be due to stigma associated with TB. Tuberculosis_sentence_328

Stigma may be due to the fear of transmission from affected individuals. Tuberculosis_sentence_329

This stigma may additionally arise due to links between TB and poverty, and in Africa, AIDS. Tuberculosis_sentence_330

Such stigmatization may be both real and perceived; for example, in Ghana individuals with TB are banned from attending public gatherings. Tuberculosis_sentence_331

Stigma towards TB may result in delays in seeking treatment, lower treatment compliance, and family members keeping cause of death secret – allowing the disease to spread further. Tuberculosis_sentence_332

In contrast, in Russia stigma was associated with increased treatment compliance. Tuberculosis_sentence_333

TB stigma also affects socially marginalized individuals to a greater degree and varies between regions. Tuberculosis_sentence_334

One way to decrease stigma may be through the promotion of "TB clubs", where those infected may share experiences and offer support, or through counseling. Tuberculosis_sentence_335

Some studies have shown TB education programs to be effective in decreasing stigma, and may thus be effective in increasing treatment adherence. Tuberculosis_sentence_336

Despite this, studies on the relationship between reduced stigma and mortality are lacking as of 2010, and similar efforts to decrease stigma surrounding AIDS have been minimally effective. Tuberculosis_sentence_337

Some have claimed the stigma to be worse than the disease, and healthcare providers may unintentionally reinforce stigma, as those with TB are often perceived as difficult or otherwise undesirable. Tuberculosis_sentence_338

A greater understanding of the social and cultural dimensions of tuberculosis may also help with stigma reduction. Tuberculosis_sentence_339

Research Tuberculosis_section_39

See also: International Congress on Tuberculosis Tuberculosis_sentence_340

The BCG vaccine has limitations, and research to develop new TB vaccines is ongoing. Tuberculosis_sentence_341

A number of potential candidates are currently in phase I and II clinical trials. Tuberculosis_sentence_342

Two main approaches are used to attempt to improve the efficacy of available vaccines. Tuberculosis_sentence_343

One approach involves adding a subunit vaccine to BCG, while the other strategy is attempting to create new and better live vaccines. Tuberculosis_sentence_344

MVA85A, an example of a subunit vaccine, is in trials in South Africa as of 2006, is based on a genetically modified vaccinia virus. Tuberculosis_sentence_345

Vaccines are hoped to play a significant role in treatment of both latent and active disease. Tuberculosis_sentence_346

To encourage further discovery, researchers and policymakers are promoting new economic models of vaccine development as of 2006, including prizes, tax incentives, and advance market commitments. Tuberculosis_sentence_347

A number of groups, including the Stop TB Partnership, the South African Tuberculosis Vaccine Initiative, and the Aeras Global TB Vaccine Foundation, are involved with research. Tuberculosis_sentence_348

Among these, the Aeras Global TB Vaccine Foundation received a gift of more than $280 million (US) from the Bill and Melinda Gates Foundation to develop and license an improved vaccine against tuberculosis for use in high burden countries. Tuberculosis_sentence_349

A number of medications are being studied as of 2012 for multidrug-resistant tuberculosis, including bedaquiline and delamanid. Tuberculosis_sentence_350

Bedaquiline received U.S. Food and Drug Administration (FDA) approval in late 2012. Tuberculosis_sentence_351

The safety and effectiveness of these new agents are uncertain as of 2012, because they are based on the results of relatively small studies. Tuberculosis_sentence_352

However, existing data suggest that patients taking bedaquiline in addition to standard TB therapy are five times more likely to die than those without the new drug, which has resulted in medical journal articles raising health policy questions about why the FDA approved the drug and whether financial ties to the company making bedaquiline influenced physicians' support for its use. Tuberculosis_sentence_353

Steroids add-on therapy has not shown any benefits for people with active pulmonary tuberculosis infection. Tuberculosis_sentence_354

Other animals Tuberculosis_section_40

Mycobacteria infect many different animals, including birds, fish, rodents, and reptiles. Tuberculosis_sentence_355

The subspecies Mycobacterium tuberculosis, though, is rarely present in wild animals. Tuberculosis_sentence_356

An effort to eradicate bovine tuberculosis caused by Mycobacterium bovis from the cattle and deer herds of New Zealand has been relatively successful. Tuberculosis_sentence_357

Efforts in Great Britain have been less successful. Tuberculosis_sentence_358

As of 2015, tuberculosis appears to be widespread among captive elephants in the US. Tuberculosis_sentence_359

It is believed that the animals originally acquired the disease from humans, a process called reverse zoonosis. Tuberculosis_sentence_360

Because the disease can spread through the air to infect both humans and other animals, it is a public health concern affecting circuses and zoos. Tuberculosis_sentence_361

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