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tuberculosis
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{{pp-semi-indef}}{{pp-move-indef}}{{short description|Infectious disease caused by the bacterium Mycobacterium tuberculosis}}{{good article}}{{Use dmy dates|date=March 2014}}







factoids
| prevention = Screening those at high risk, treatment of those infected, vaccination with bacillus Calmette-Guérin (BCG)| treatment = Antibiotics| medication = | frequency = 25% of people (latent TB)| deaths = 1.6 million (2017)}}Tuberculosis (TB) is an infectious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria. Tuberculosis generally affects the lungs, but can also affect other parts of the body. Most infections do not have symptoms, in which case it is known as latent tuberculosis. About 10% of latent infections progress to active disease which, if left untreated, kills about half of those affected. The classic symptoms of active TB are a chronic cough with blood-containing mucus, fever, night sweats, and weight loss. It was historically called "consumption" due to the weight loss.BOOK, The Chambers Dictionary., 1998, Allied Chambers India Ltd., New Delhi, 978-81-86062-25-8, 352,weblink live,weblink 6 September 2015, dmy-all, Infection of other organs can cause a wide range of symptoms.BOOK, Dolin, [edited by] Gerald L. Mandell, John E. Bennett, Raphael, Mandell, Douglas, and Bennett's principles and practice of infectious diseases, 2010, Churchill Livingstone/Elsevier, Philadelphia, PA, 978-0-443-06839-3, Chapter 250, 7th, Tuberculosis is spread through the air when people who have active TB in their lungs cough, spit, speak, or sneeze.WEB, Basic TB Facts,weblink Centers for Disease Control and Prevention (CDC), 11 February 2016, 13 March 2012, live,weblink" title="web.archive.org/web/20160206032136weblink">weblink 6 February 2016, dmy-all, People with latent TB do not spread the disease. Active infection occurs more often in people with HIV/AIDS and in those who smoke. Diagnosis of active TB is based on chest X-rays, as well as microscopic examination and culture of body fluids. Diagnosis of latent TB relies on the tuberculin skin test (TST) or blood tests.JOURNAL, Konstantinos A, 2010, Testing for tuberculosis, Australian Prescriber, 33, 1, 12–18, dmy-all, 10.18773/austprescr.2010.005, Prevention of TB involves screening those at high risk, early detection and treatment of cases, and vaccination with the bacillus Calmette-Guérin (BCG) vaccine.JOURNAL, Hawn TR, Day TA, Scriba TJ, Hatherill M, Hanekom WA, Evans TG, Churchyard GJ, Kublin JG, Bekker LG, Self SG, 3, Tuberculosis vaccines and prevention of infection, Microbiology and Molecular Biology Reviews, 78, 4, 650–71, December 2014, 25428938, 4248657, 10.1128/MMBR.00021-14, BOOK, Organization, World Health, Implementing the WHO Stop TB Strategy: a handbook for national TB control programmes, 2008, World Health Organization (WHO), Geneva, 978-92-4-154667-6, 179,weblink dmy-all, BOOK, Harris, Randall E., Epidemiology of chronic disease: global perspectives, 2013, Jones & Bartlett Learning, Burlington, MA, 978-0-7637-8047-0, 682,weblink Those at high risk include household, workplace, and social contacts of people with active TB. Treatment requires the use of multiple antibiotics over a long period of time. Antibiotic resistance is a growing problem with increasing rates of multiple drug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB).As of 2018 one-quarter of the world's population is thought to be infected with TB.WEB, Tuberculosis (TB),weblink World Health Organization (WHO), 15 September 2018, 16 February 2018, New infections occur in about 1% of the population each year.WEB, Tuberculosis,weblink World Health Organization (WHO), 2002, dead,weblink" title="web.archive.org/web/20130617193438weblink">weblink 17 June 2013, dmy-all, In 2017, there were more than 10 million cases of active TB which resulted in 1.6 million deaths.WEB,weblink Global tuberculosis report, World Health Organization (WHO), 2017-11-09, This makes it the number one cause of death from an infectious disease. More than 95% of deaths occurred in developing countries, and more than 50% in India, China, Indonesia, Pakistan, and the Philippines. The number of new cases each year has decreased since 2000.WEB, Tuberculosis Fact sheet N°104,weblink World Health Organization (WHO), 11 February 2016, October 2015, live,weblink" title="web.archive.org/web/20120823143802weblink">weblink 23 August 2012, dmy-all, 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.BOOK, Kumar V, Abbas AK, Fausto N, Mitchell RN, 3, 2007, Robbins Basic Pathology, 8th, Saunders Elsevier, 516–22, 978-1-4160-2973-1, Tuberculosis has been present in humans since ancient times.JOURNAL, Lawn SD, Zumla AI, Tuberculosis, Lancet, 378, 9785, 57–72, July 2011, 21420161, 10.1016/S0140-6736(10)62173-3, File:Wikipedia-VideoWiki-Tuberculosis.webm|thumb|thumbtime=1:33|upright=1.3|Video summary (script)]]{{TOC limit}}

Signs and symptoms

(File:Tuberculosis symptoms.svg|thumb|upright=1.5|The main symptoms of variants and stages of tuberculosis are given,WEB,weblink Tuberculosis Symptoms, eMedicine Health, Schiffman, G, 15 January 2009, live,weblink" title="web.archive.org/web/20090516075020weblink">weblink 16 May 2009, dmy-all, with many symptoms overlapping with other variants, while others are more (but not entirely) specific for certain variants. Multiple variants may be present simultaneously.)Tuberculosis may infect any part of the body, but most commonly occurs in the lungs (known as pulmonary tuberculosis). Extrapulmonary TB occurs when tuberculosis develops outside of the lungs, although extrapulmonary TB may coexist with pulmonary TB.General signs and symptoms include fever, chills, night sweats, loss of appetite, weight loss, and fatigue. Significant nail clubbing may also occur.

Pulmonary

If a tuberculosis infection does become active, it most commonly involves the lungs (in about 90% of cases).BOOK, Behera, D., Textbook of Pulmonary Medicine, 2010, Jaypee Brothers Medical Publishers, New Delhi, 978-81-8448-749-7, 457,weblink 2nd, live,weblink 6 September 2015, dmy-all, Symptoms may include chest pain and a prolonged cough producing sputum. About 25% of people may not have any symptoms (i.e. they remain "asymptomatic"). 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.JOURNAL, Halezeroğlu S, Okur E, Thoracic surgery for haemoptysis in the context of tuberculosis: what is the best management approach?, Journal of Thoracic Disease, 6, 3, 182–85, March 2014, 24624281, 3949181, 10.3978/j.issn.2072-1439.2013.12.25, Tuberculosis may become a chronic illness and cause extensive scarring in the upper lobes of the lungs. The upper lung lobes are more frequently affected by tuberculosis than the lower ones. The reason for this difference is not clear. It may be due to either better air flow, or poor lymph drainage within the upper lungs.

Extrapulmonary

In 15–20% of active cases, the infection spreads outside the lungs, causing other kinds of TB.BOOK, Jindal, editor-in-chief SK, Textbook of Pulmonary and Critical Care Medicine, Jaypee Brothers Medical Publishers, New Delhi, 978-93-5025-073-0, 549,weblink 2011, live,weblink 7 September 2015, dmy-all, These are collectively denoted as "extrapulmonary tuberculosis".JOURNAL, Golden MP, Vikram HR, Extrapulmonary tuberculosis: an overview, American Family Physician, 72, 9, 1761–68, November 2005, 16300038, Extrapulmonary TB occurs more commonly in people with a weakened immune system and young children. In those with HIV, this occurs in more than 50% of cases. 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. A potentially more serious, widespread form of TB is called "disseminated tuberculosis", also known as miliary tuberculosis. Miliary TB currently makes up about 10% of extrapulmonary cases.

Causes

Mycobacteria

File:Mycobacterium tuberculosis.jpg|thumb|Scanning electron micrographScanning electron micrographThe main cause of TB is Mycobacterium tuberculosis (MTB), a small, aerobic, nonmotile bacillus. The high lipid content of this pathogen accounts for many of its unique clinical characteristics.BOOK, Southwick F, Infectious Diseases: A Clinical Short Course, 2nd ed., McGraw-Hill Medical Publishing Division, 2007, 104, 313–14, Chapter 4: Pulmonary Infections, 978-0-07-147722-2, 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.BOOK, Jindal, editor-in-chief SK, Textbook of Pulmonary and Critical Care Medicine, Jaypee Brothers Medical Publishers, New Delhi, 978-93-5025-073-0, 525,weblink 2011, live,weblink 6 September 2015, dmy-all, Mycobacteria have an outer membrane lipid bilayer.JOURNAL, Niederweis M, Danilchanka O, Huff J, Hoffmann C, Engelhardt H, 3, Mycobacterial outer membranes: in search of proteins, Trends in Microbiology, 18, 3, 109–16, March 2010, 20060722, 2931330, 10.1016/j.tim.2009.12.005, 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.JOURNAL, Madison BM, Application of stains in clinical microbiology, Biotechnic & Histochemistry, 76, 3, 119–25, May 2001, 11475314, 10.1080/714028138, 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.JOURNAL, Parish T, Stoker NG, Mycobacteria: bugs and bugbears (two steps forward and one step back), Molecular Biotechnology, 13, 3, 191–200, December 1999, 10934532, 10.1385/MB:13:3:191, Using histological stains on expectorated samples from phlegm (also called "sputum"), scientists can identify MTB under a microscope. Since MTB retains certain stains even after being treated with acidic solution, it is classified as an acid-fast bacillus. The most common acid-fast staining techniques are the Ziehl–Neelsen stainBOOK, Medical Laboratory Science: Theory and Practice, Tata McGraw-Hill, New Delhi, 2000, 473, 978-0-07-463223-9,weblink live,weblink 6 September 2015, dmy-all, and the Kinyoun stain, which dye acid-fast bacilli a bright red that stands out against a blue background.WEB, Acid-Fast Stain Protocols,weblink 26 March 2016, 21 August 2013, dead,weblink" title="web.archive.org/web/20111001132818weblink">weblink 1 October 2011, Auramine-rhodamine stainingJOURNAL, Kommareddi S, Abramowsky CR, Swinehart GL, Hrabak L, 3, Nontuberculous mycobacterial infections: comparison of the fluorescent auramine-O and Ziehl-Neelsen techniques in tissue diagnosis, Human Pathology, 15, 11, 1085–89, November 1984, 6208117, 10.1016/S0046-8177(84)80253-1, and fluorescence microscopyBOOK, van Lettow, Monique, Whalen, Christopher, Nutrition and health in developing countries, 2008, Humana Press, Totowa, N.J. (Richard D. Semba and Martin W. Bloem, eds.), 978-1-934115-24-4, 291,weblink 2nd, live,weblink 6 September 2015, dmy-all, are also used.The M. tuberculosis complex (MTBC) includes four other TB-causing mycobacteria: M. bovis, M. africanum, M. canetti, and M. microti.JOURNAL, van Soolingen D, Hoogenboezem T, de Haas PE, Hermans PW, Koedam MA, Teppema KS, Brennan PJ, Besra GS, Portaels F, Top J, Schouls LM, van Embden JD, 3, A novel pathogenic taxon of the Mycobacterium tuberculosis complex, Canetti: characterization of an exceptional isolate from Africa, International Journal of Systematic Bacteriology, 47, 4, 1236–45, October 1997, 9336935, 10.1099/00207713-47-4-1236, M. africanum is not widespread, but it is a significant cause of tuberculosis in parts of Africa.JOURNAL, Niemann S, Rüsch-Gerdes S, Joloba ML, Whalen CC, Guwatudde D, Ellner JJ, Eisenach K, Fumokong N, Johnson JL, Aisu T, Mugerwa RD, Okwera A, Schwander SK, 3, Mycobacterium africanum subtype II is associated with two distinct genotypes and is a major cause of human tuberculosis in Kampala, Uganda, Journal of Clinical Microbiology, 40, 9, 3398–405, September 2002, 12202584, 130701, 10.1128/JCM.40.9.3398-3405.2002, JOURNAL, Niobe-Eyangoh SN, Kuaban C, Sorlin P, Cunin P, Thonnon J, Sola C, Rastogi N, Vincent V, Gutierrez MC, 3, Genetic biodiversity of Mycobacterium tuberculosis complex strains from patients with pulmonary tuberculosis in Cameroon, Journal of Clinical Microbiology, 41, 6, 2547–53, June 2003, 12791879, 156567, 10.1128/JCM.41.6.2547-2553.2003, 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.JOURNAL, Thoen C, Lobue P, de Kantor I, The importance of Mycobacterium bovis as a zoonosis, Veterinary Microbiology, 112, 2–4, 339–45, February 2006, 16387455, 10.1016/j.vetmic.2005.11.047, M. canetti is rare and seems to be limited to the Horn of Africa, although a few cases have been seen in African emigrants.BOOK, Acton, Q. Ashton, Mycobacterium Infections: New Insights for the Healthcare Professional, 2011, ScholarlyEditions, 978-1-4649-0122-5, 1968,weblink live,weblink 6 September 2015, dmy-all, JOURNAL, Pfyffer GE, Auckenthaler R, van Embden JD, van Soolingen D, 3, Mycobacterium canettii, the smooth variant of M. tuberculosis, isolated from a Swiss patient exposed in Africa, Emerging Infectious Diseases, 4, 4, 631–34, Oct–Dec 1998, 9866740, 2640258, 10.3201/eid0404.980414, M. microti is also rare and is seen almost only in immunodeficient people, although its prevalence may be significantly underestimated.JOURNAL, Panteix G, Gutierrez MC, Boschiroli ML, Rouviere M, Plaidy A, Pressac D, Porcheret H, Chyderiotis G, Ponsada M, Van Oortegem K, Salloum S, Cabuzel S, Bañuls AL, Van de Perre P, Godreuil S, 3, Pulmonary tuberculosis due to Mycobacterium microti: a study of six recent cases in France, Journal of Medical Microbiology, 59, Pt 8, 984–89, August 2010, 20488936, 10.1099/jmm.0.019372-0, Other known pathogenic mycobacteria include M. leprae, M. avium, and M. kansasii. The latter two species are classified as "nontuberculous mycobacteria" (NTM). NTM cause neither TB nor leprosy, but they do cause lung diseases that resemble TB.JOURNAL, American Thoracic Society, Diagnosis and treatment of disease caused by nontuberculous mycobacteria. This official statement of the American Thoracic Society was approved by the Board of Directors, March 1997. Medical Section of the American Lung Association, American Journal of Respiratory and Critical Care Medicine, 156, 2 Pt 2, S1–25, August 1997, 9279284, 10.1164/ajrccm.156.2.atsstatement,

Risk factors

A number of factors make people more susceptible to TB infections. The most important risk factor globally is HIV; 13% of all people with TB are infected by the virus.WEB, The sixteenth global report on tuberculosis, World Health Organization (WHO),weblink 2011, dead,weblink" title="web.archive.org/web/20120906223650weblink">weblink 6 September 2012, This is a particular problem in sub-Saharan Africa, where rates of HIV are high.WEB, World Health Organization (WHO),weblink Global tuberculosis control–surveillance, planning, financing WHO Report 2006, 13 October 2006, live,weblink" title="web.archive.org/web/20061212123736weblink">weblink 12 December 2006, dmy-all, JOURNAL, Chaisson RE, Martinson NA, Tuberculosis in Africa – combating an HIV-driven crisis, The New England Journal of Medicine, 358, 11, 1089–92, March 2008, 18337598, 10.1056/NEJMp0800809, Of people without HIV who are infected with tuberculosis, about 5–10% develop active disease during their lifetimes;BOOK, Gibson, Peter G. (ed.), Abramson, Michael (ed.), Wood-Baker, Richard (ed.), Volmink, Jimmy (ed.), Hensley, Michael (ed.), Costabel, Ulrich (ed.), Evidence-Based Respiratory Medicine, 2005, BMJ Books, 978-0-7279-1605-1, 321, 1st,weblink live,weblink" title="web.archive.org/web/20151208072842weblink">weblink 8 December 2015, dmy-all, in contrast, 30% of those coinfected with HIV develop the active disease.Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of the principal diseases of poverty. 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.JOURNAL, Griffith DE, Kerr CM, Tuberculosis: disease of the past, disease of the present, Journal of Perianesthesia Nursing, 11, 4, 240–45, August 1996, 8964016, 10.1016/S1089-9472(96)80023-2, Chronic lung disease is another significant risk factor. Silicosis increases the risk about 30-fold.JOURNAL, Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society, MMWR. Recommendations and Reports, 49, RR-6, 1–51, June 2000, 10881762,weblinkweblink" title="web.archive.org/web/20041217172736weblink">weblink dmy-all, live, 17 December 2004, Those who smoke cigarettes have nearly twice the risk of TB compared to nonsmokers.JOURNAL, van Zyl Smit RN, Pai M, Yew WW, Leung CC, Zumla A, Bateman ED, Dheda K, 3, Global lung health: the colliding epidemics of tuberculosis, tobacco smoking, HIV and COPD, The European Respiratory Journal, 35, 1, 27–33, January 2010, 20044459, 5454527, 10.1183/09031936.00072909, These analyses indicate that smokers are almost twice as likely to be infected with TB and to progress to active disease (RR of about 1.5 for latent TB infection (LTBI) and RR of ∼2.0 for TB disease). Smokers are also twice as likely to die from TB (RR of about 2.0 for TB mortality), but data are difficult to interpret because of heterogeneity in the results across studies., Other disease states can also increase the risk of developing tuberculosis. These include alcoholism and diabetes mellitus (three-fold increase).JOURNAL, Restrepo BI, Convergence of the tuberculosis and diabetes epidemics: renewal of old acquaintances, Clinical Infectious Diseases, 45, 4, 436–38, August 2007, 17638190, 2900315, 10.1086/519939, Certain medications, such as corticosteroids and infliximab (an anti-αTNF monoclonal antibody), are other important risk factors, especially in the developed world.Genetic susceptibility also exists,JOURNAL, Möller M, Hoal EG, Current findings, challenges and novel approaches in human genetic susceptibility to tuberculosis, Tuberculosis, 90, 2, 71–83, March 2010, 20206579, 10.1016/j.tube.2010.02.002, for which the overall importance remains undefined.

Mechanism

(File:TB poster.jpg|thumb|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 5.0 µm in diameter. A single sneeze can release up to 40,000 droplets.JOURNAL, Cole EC, Cook CE, Characterization of infectious aerosols in health care facilities: an aid to effective engineering controls and preventive strategies, American Journal of Infection Control, 26, 4, 453–64, August 1998, 9721404, 10.1016/S0196-6553(98)70046-X, 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).JOURNAL, Nicas M, Nazaroff WW, Hubbard A, Toward understanding the risk of secondary airborne infection: emission of respirable pathogens, Journal of Occupational and Environmental Hygiene, 2, 3, 143–54, March 2005, 15764538, 10.1080/15459620590918466, 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.JOURNAL, Ahmed N, Hasnain SE, Molecular epidemiology of tuberculosis in India: moving forward with a systems biology approach, Tuberculosis, 91, 5, 407–13, September 2011, 21514230, 10.1016/j.tube.2011.03.006, A person with active but untreated tuberculosis may infect 10–15 (or more) other people per year. Transmission should occur from only people with active TB – those with latent infection are not thought to be contagious. 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.WEB, Centers for Disease Control and Prevention (CDC), Division of Tuberculosis Elimination,weblink Core Curriculum on Tuberculosis: What the Clinician Should Know, 24, 5th, 2011, live,weblink" title="web.archive.org/web/20120519141115weblink">weblink 19 May 2012, dmy-all, 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. After about two weeks of effective treatment, subjects with nonresistant active infections generally do not remain contagious to others. 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.WEB,weblink Causes of Tuberculosis, 19 October 2007, 21 December 2006, Mayo Clinic, live,weblink" title="web.archive.org/web/20071018051807weblink">weblink 18 October 2007, dmy-all,

Pathogenesis

File:Tuberculous epididymitis Low Power.jpg|thumb|Microscopy of tuberculous epididymitis. H&EH&EAbout 90% of those infected with M. tuberculosis have asymptomatic, latent TB infections (sometimes called LTBI),BOOK, Skolnik, Richard, Global health 101, 2011, Jones & Bartlett Learning, Burlington, MA, 978-0-7637-9751-5, 253,weblink 2nd, live,weblink 6 September 2015, dmy-all, with only a 10% lifetime chance that the latent infection will progress to overt, active tuberculous disease.BOOK, editors, Arch G. Mainous III, Claire Pomeroy, Management of antimicrobials in infectious diseases: impact of antibiotic resistance, 2009, Humana Press, Totowa, NJ, 978-1-60327-238-4, 74,weblink 2nd rev., live,weblink 6 September 2015, dmy-all, In those with HIV, the risk of developing active TB increases to nearly 10% a year. If effective treatment is not given, the death rate for active TB cases is up to 66%.WEB,weblink Tuberculosis Fact sheet N°104, World Health Organization (WHO), November 2010, 26 July 2011, live,weblink" title="web.archive.org/web/20061004013508weblink">weblink 4 October 2006, dmy-all, TB infection begins when the mycobacteria reach the alveolar air sacs of the lungs, where they invade and replicate within endosomes of alveolar macrophages.JOURNAL, Houben EN, Nguyen L, Pieters J, Interaction of pathogenic mycobacteria with the host immune system, Current Opinion in Microbiology, 9, 1, 76–85, February 2006, 16406837, 10.1016/j.mib.2005.12.014, JOURNAL, Queval CJ, Brosch R, Simeone R, Mycobacterium tuberculosis, Frontiers in Microbiology, 8, 2284, 2017, 29218036, 5703847, 10.3389/fmicb.2017.02284, Macrophages identify the bacterium as foreign and attempt to eliminate it by phagocytosis. During this process, the bacterium is enveloped by the macrophage and stored temporarily in a membrane-bound vesicle called a phagosome. The phagosome then combines with a lysosome to create a phagolysosome. In the phagolysosome, the cell attempts to use reactive oxygen species and acid to kill the bacterium. However, M. tuberculosis has a thick, waxy mycolic acid capsule that protects it from these toxic substances. M. tuberculosis is able to reproduce inside the macrophage and will eventually kill the immune cell.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 of the lungs may also occur via infection from the blood stream. This is known as a Simon focus and is typically found in the top of the lung.BOOK, Khan, Essence of Paediatrics, 2011, Elsevier India, 978-81-312-2804-3, 401,weblink live,weblink 6 September 2015, dmy-all, This hematogenous transmission can also spread infection to more distant sites, such as peripheral lymph nodes, the kidneys, the brain, and the bones.JOURNAL, Herrmann JL, Lagrange PH, Dendritic cells and Mycobacterium tuberculosis: which is the Trojan horse?, Pathologie-Biologie, 53, 1, 35–40, February 2005, 15620608, 10.1016/j.patbio.2004.01.004, 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.JOURNAL, Agarwal R, Malhotra P, Awasthi A, Kakkar N, Gupta D, 3, Tuberculous dilated cardiomyopathy: an under-recognized entity?, BMC Infectious Diseases, 5, 1, 29, April 2005, 15857515, 1090580, 10.1186/1471-2334-5-29, File:Carswell-Tubercle.jpg|thumb|left|upright=90%|(Robert Carswell (pathologist)|Robert Carswell]]'s illustration of tubercleBOOK, John Mason Good, Samuel Cooper, Augustus Sidney Doane, The Study of Medicine,weblink 1835, Harper, 32, live,weblink 10 August 2016, dmy-all, )Tuberculosis is classified as one of the granulomatous inflammatory diseases. Macrophages, T lymphocytes, B lymphocytes, and fibroblasts aggregate to form granulomas, with lymphocytes surrounding the infected macrophages. When other macrophages attack the infected macrophage, they fuse together to form a giant multinucleated cell in the alveolar lumen. The granuloma may prevent dissemination of the mycobacteria and provide a local environment for interaction of cells of the immune system. However, more recent evidence suggests that the bacteria use the granulomas to avoid destruction by the host's immune system. Macrophages and dendritic cells in the granulomas are unable to present antigen to lymphocytes; thus the immune response is suppressed.JOURNAL, Bozzano F, Marras F, De Maria A, Immunology of tuberculosis, Mediterranean Journal of Hematology and Infectious Diseases, 6, 1, e2014027, 2014, 24804000, 4010607, 10.4084/MJHID.2014.027, Bacteria inside the granuloma can become dormant, resulting in latent infection. Another feature of the granulomas 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.JOURNAL, Grosset J, Mycobacterium tuberculosis in the extracellular compartment: an underestimated adversary, Antimicrobial Agents and Chemotherapy, 47, 3, 833–36, March 2003, 12604509, 149338, 10.1128/AAC.47.3.833-836.2003, 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.BOOK, Crowley, Leonard V., An introduction to human disease: pathology and pathophysiology correlations, 2010, Jones and Bartlett, Sudbury, MA, 978-0-7637-6591-0, 374,weblink 8th, live,weblink 6 September 2015, dmy-all, This severe form of TB disease, most common in young children and those with HIV, is called miliary tuberculosis.BOOK, Anthony, Harries, TB/HIV a Clinical Manual, 2005, World Health Organization (WHO), Geneva, 978-92-4-154634-8, 75,weblink 2nd, live,weblink 6 September 2015, dmy-all, People with this disseminated TB have a high fatality rate even with treatment (about 30%).BOOK, Ghosh, editors-in-chief, Thomas M. Habermann, Amit K., Mayo Clinic internal medicine: concise textbook, 2008, Mayo Clinic Scientific Press, Rochester, MN, 978-1-4200-6749-1, 789,weblink live,weblink 6 September 2015, dmy-all, JOURNAL, Jacob JT, Mehta AK, Leonard MK, Acute forms of tuberculosis in adults, The American Journal of Medicine, 122, 1, 12–17, January 2009, 19114163, 10.1016/j.amjmed.2008.09.018, In many people, the infection waxes and wanes. Tissue destruction and necrosis are often balanced by healing and fibrosis. 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, and thus 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.{{Clear}}

Diagnosis

File:TB in sputum.png|thumb|M. tuberculosis (stained red) in sputumsputum

Active tuberculosis

Diagnosing active tuberculosis based only on signs and symptoms is difficult,JOURNAL, Bento J, Silva AS, Rodrigues F, Duarte R, 3, [Diagnostic tools in tuberculosis], Acta Medica Portuguesa, 24, 1, 145–54, Jan–Feb 2011, 21672452, as is diagnosing the disease in those who have a weakened immune system.JOURNAL, Escalante P, In the clinic. Tuberculosis, Annals of Internal Medicine, 150, 11, ITC61–614; quiz ITV616, June 2009, 19487708, 10.7326/0003-4819-150-11-200906020-01006, A diagnosis of TB should, however, be considered in those with signs of lung disease or constitutional symptoms lasting longer than two weeks. A chest X-ray and multiple sputum cultures for acid-fast bacilli are typically part of the initial evaluation. Interferon-γ release assays and tuberculin skin tests are of little use in the developing world.JOURNAL, Metcalfe JZ, Everett CK, Steingart KR, Cattamanchi A, Huang L, Hopewell PC, Pai M, 3, Interferon-γ release assays for active pulmonary tuberculosis diagnosis in adults in low- and middle-income countries: systematic review and meta-analysis, The Journal of Infectious Diseases, 204 Suppl 4, suppl_4, S1120–29, November 2011, 21996694, 3192542, 10.1093/infdis/jir410, JOURNAL, Sester M, Sotgiu G, Lange C, Giehl C, Girardi E, Migliori GB, Bossink A, Dheda K, Diel R, Dominguez J, Lipman M, Nemeth J, Ravn P, Winkler S, Huitric E, Sandgren A, Manissero D, 3, Interferon-γ release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis, The European Respiratory Journal, 37, 1, 100–11, January 2011, 20847080, 10.1183/09031936.00114810, Interferon gamma release assays (IGRA) have similar limitations in those with HIV.JOURNAL, Chen J, Zhang R, Wang J, Liu L, Zheng Y, Shen Y, Qi T, Lu H, 3, Interferon-gamma release assays for the diagnosis of active tuberculosis in HIV-infected patients: a systematic review and meta-analysis, PLOS ONE, 6, 11, e26827, 2011, 22069472, 3206065, 10.1371/journal.pone.0026827, Vermund, Sten H, 2011PLoSO...626827C, {{open access}}A definitive diagnosis of TB is made by identifying M. tuberculosis in a clinical sample (e.g., sputum, pus, or a tissue biopsy). However, the difficult culture process for this slow-growing organism can take two to six weeks for blood or sputum culture.BOOK, Diseases, Special Programme for Research & Training in Tropical, Diagnostics for tuberculosis: global demand and market potential, 2006, World Health Organization (WHO), Geneva, 978-92-4-156330-7, 36,weblink live,weblink 6 September 2015, dmy-all, Thus, treatment is often begun before cultures are confirmed.Nucleic acid amplification tests and adenosine deaminase testing may allow rapid diagnosis of TB. These tests, however, are not routinely recommended, as they rarely alter how a person is treated. Blood tests to detect antibodies are not specific or sensitive, so they are not recommended.JOURNAL, Steingart KR, Flores LL, Dendukuri N, Schiller I, Laal S, Ramsay A, Hopewell PC, Pai M, 3, Commercial serological tests for the diagnosis of active pulmonary and extrapulmonary tuberculosis: an updated systematic review and meta-analysis, PLoS Medicine, 8, 8, e1001062, August 2011, 21857806, 3153457, 10.1371/journal.pmed.1001062, Evans, Carlton, {{open access}}

Latent tuberculosis

File:Mantoux tuberculin skin test.jpg|thumb|left|Mantoux tuberculin skin test ]]The Mantoux tuberculin skin test is often used to screen people at high risk for TB. Those who have been previously immunized with the Bacille Calmette-Guerin vaccine may have a false-positive test result.JOURNAL, Rothel JS, Andersen P, Diagnosis of latent Mycobacterium tuberculosis infection: is the demise of the Mantoux test imminent?, Expert Review of Anti-Infective Therapy, 3, 6, 981–93, December 2005, 16307510, 10.1586/14787210.3.6.981, The test may be falsely negative in those with sarcoidosis, Hodgkin's lymphoma, malnutrition, and most notably, active tuberculosis. Interferon gamma release assays, on a blood sample, are recommended in those who are positive to the Mantoux test.{{NICE|117|Tuberculosis|2011}} These are not affected by immunization or most environmental mycobacteria, so they generate fewer false-positive results.JOURNAL, Pai M, Zwerling A, Menzies D, Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update, Annals of Internal Medicine, 149, 3, 177–84, August 2008, 18593687, 2951987, 10.7326/0003-4819-149-3-200808050-00241, However, they are affected by M. szulgai, M. marinum, and M. kansasii.BOOK, Jindal, editor-in-chief SK, Textbook of Pulmonary and Critical Care Medicine, Jaypee Brothers Medical Publishers, New Delhi, 978-93-5025-073-0, 544,weblink 2011, live,weblink 6 September 2015, dmy-all, IGRAs may increase sensitivity when used in addition to the skin test, but may be less sensitive than the skin test when used alone.JOURNAL, Amicosante M, Ciccozzi M, Markova R, Rational use of immunodiagnostic tools for tuberculosis infection: guidelines and cost effectiveness studies, The New Microbiologica, 33, 2, 93–107, April 2010, 20518271, 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.JOURNAL, Bibbins-Domingo K, Grossman DC, Curry SJ, Bauman L, Davidson KW, Epling JW, García FA, Herzstein J, Kemper AR, Krist AH, Kurth AE, Landefeld CS, Mangione CM, Phillips WR, Phipps MG, Pignone MP, 3, Screening for Latent Tuberculosis Infection in Adults: US Preventive Services Task Force Recommendation Statement, JAMA, 316, 9, 962–69, September 2016, 27599331, 10.1001/jama.2016.11046, While some have recommend testing health care workers, evidence of benefit for this is poor {{as of|2019|lc=yes}}.JOURNAL, Gill, Jennifer, Prasad, Vinay, Testing Healthcare Workers for Latent Tuberculosis: Is It Evidence Based, Bio-Plausible, Both, Or Neither?, The American Journal of Medicine, April 2019, 10.1016/j.amjmed.2019.03.017, 30946831, The Centers for Disease Control and Prevention (CDC) stopped recommending yearly testing of health care workers without known exposure in 2019.JOURNAL, Sosa, LE, Njie, GJ, Lobato, MN, Bamrah Morris, S, Buchta, W, Casey, ML, Goswami, ND, Gruden, M, Hurst, BJ, Khan, AR, Kuhar, DT, Lewinsohn, DM, Mathew, TA, Mazurek, GH, Reves, R, Paulos, L, Thanassi, W, Will, L, Belknap, R, Tuberculosis Screening, Testing, and Treatment of U.S. Health Care Personnel: Recommendations from the National Tuberculosis Controllers Association and CDC, 2019., MMWR. Morbidity and Mortality Weekly Report, 17 May 2019, 68, 19, 439–443, 10.15585/mmwr.mm6819a3, 31099768, 6522077,

Prevention

(File:3f05369r (8435815214).jpg|thumb|Tuberculosis prevention poster from the United States, c. 1940)Tuberculosis prevention and control efforts rely primarily on the vaccination of infants and the detection and appropriate treatment of active cases. The World Health Organization (WHO) has achieved some success with improved treatment regimens, and a small decrease in case numbers.

Vaccines

The only available vaccine {{as of|2011|lc=yes}} is Bacillus Calmette-Guérin (BCG).JOURNAL, McShane H, Tuberculosis vaccines: beyond bacille Calmette-Guerin, Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 366, 1579, 2782–89, October 2011, 21893541, 3146779, 10.1098/rstb.2011.0097, In children it decreases the risk of getting the infection by 20% and the risk of infection turning into active disease by nearly 60%.JOURNAL, Roy A, Eisenhut M, Harris RJ, Rodrigues LC, Sridhar S, Habermann S, Snell L, Mangtani P, Adetifa I, Lalvani A, Abubakar I, 3, Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis, BMJ, 349, g4643, August 2014, 25097193, 4122754, 10.1136/bmj.g4643, It is the most widely used vaccine worldwide, with more than 90% of all children being vaccinated. The immunity it induces decreases after about ten years. As tuberculosis is uncommon in most of Canada, the United Kingdom, and the United States, BCG is administered to only those people at high risk.WEB,weblink Vaccine and Immunizations: TB Vaccine (BCG), Centers for Disease Control and Prevention, 2011, 26 July 2011, live,weblink" title="web.archive.org/web/20111117140855weblink">weblink 17 November 2011, dmy-all, WEB, BCG Vaccine Usage in Canada – Current and Historical,weblink Public Health Agency of Canada, 30 December 2011, September 2010, dead,weblink" title="web.archive.org/web/20120330042719weblink">weblink 30 March 2012, dmy-all, JOURNAL, Teo SS, Shingadia DV, Does BCG have a role in tuberculosis control and prevention in the United Kingdom?, Archives of Disease in Childhood, 91, 6, 529–31, June 2006, 16714729, 2082765, 10.1136/adc.2005.085043, 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. A number of new vaccines in development as of 2011.

Public health

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.WEB,weblink The Global Plan to Stop TB, World Health Organization (WHO), 2011, 13 June 2011, live,weblink" title="web.archive.org/web/20110612030924weblink">weblink 12 June 2011, dmy-all, 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. A tuberculosis classification system developed by the American Thoracic Society is used primarily in public health programs.BOOK, Warrell, ed. by D.J. Weatherall ... [4. + 5. ed.] ed. by David A., Sections 1–10, 2005, Oxford Univ. Press, Oxford [u.a.], 978-0-19-857014-1, 560,weblink 4. ed., paperback, live,weblink 6 September 2015, dmy-all,

Management

Treatment of 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 hinders the entry of drugs and makes many antibiotics ineffective.JOURNAL, Brennan PJ, Nikaido H, The envelope of mycobacteria, Annual Review of Biochemistry, 64, 29–63, 1995, 7574484, 10.1146/annurev.bi.64.070195.000333, Latent TB is treated with either isoniazid alone, or a combination of isoniazid with either rifampicin or rifapentine.BOOK, World Health Organization (WHO), Latent tuberculosis infection, 2018, 23, 978-92-4-155023-9,weblink JOURNAL, Borisov, AS, Bamrah Morris, S, Njie, GJ, Winston, CA, Burton, D, Goldberg, S, Yelk Woodruff, R, Allen, L, LoBue, P, Vernon, A, Update of Recommendations for Use of Once-Weekly Isoniazid-Rifapentine Regimen to Treat Latent Mycobacterium tuberculosis Infection., MMWR. Morbidity and Mortality Weekly Report, 29 June 2018, 67, 25, 723–26, 10.15585/mmwr.mm6725a5, 29953429, 6023184, The treatment takes at least three months.JOURNAL, Njie, GJ, Morris, SB, Woodruff, RY, Moro, RN, Vernon, AA, Borisov, AS, Isoniazid-Rifapentine for Latent Tuberculosis Infection: A Systematic Review and Meta-analysis., American Journal of Preventive Medicine, August 2018, 55, 2, 244–52, 10.1016/j.amepre.2018.04.030, 29910114, 6097523, People with latent infections are treated to prevent them from progressing to active TB disease later in life.JOURNAL, Menzies D, Al Jahdali H, Al Otaibi B, Recent developments in treatment of latent tuberculosis infection, The Indian Journal of Medical Research, 133, 3, 257–66, March 2011, 21441678, 3103149, Active TB disease is best treated with combinations of several antibiotics to reduce the risk of the bacteria developing antibiotic resistance.

New onset

The recommended treatment of new-onset pulmonary tuberculosis, {{as of|2010|lc=yes}}, 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. Where resistance to isoniazid is high, ethambutol may be added for the last four months as an alternative.

Recurrent disease

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

Medication administration

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.BOOK, Arch G., III Mainous, Management of Antimicrobials in Infectious Diseases: Impact of Antibiotic Resistance, Humana Press, Totowa, NJ, 2010, 69, 978-1-60327-238-4,weblink live,weblink 6 September 2015, dmy-all, The evidence to support this practice over people simply taking their medications independently is of poor quality. 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.JOURNAL, Karumbi J, Garner P, Directly observed therapy for treating tuberculosis, The Cochrane Database of Systematic Reviews, 5, CD003343, May 2015, 26022367, 4460720, 10.1002/14651858.CD003343.pub4, 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. Methods to remind people of the importance of treatment and appointments may result in a small but important improvement.JOURNAL, Liu Q, Abba K, Alejandria MM, Sinclair D, Balanag VM, Lansang MA, 3, Reminder systems to improve patient adherence to tuberculosis clinic appointments for diagnosis and treatment, The Cochrane Database of Systematic Reviews, 11, CD006594, November 2014, 25403701, 4448217, 10.1002/14651858.CD006594.pub3,

Medication resistance

Primary resistance occurs when a person becomes infected with a resistant strain of TB. 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.JOURNAL, O'Brien RJ, Drug-resistant tuberculosis: etiology, management and prevention, Seminars in Respiratory Infections, 9, 2, 104–12, June 1994, 7973169, Drug-resistant TB is a serious 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.JOURNAL, Centers for Disease Control and Prevention (CDC), Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs – worldwide, 2000–2004, MMWR. Morbidity and Mortality Weekly Report, 55, 11, 301–05, March 2006, 16557213,weblinkweblink dmy-all, live, 22 May 2017, Totally drug-resistant TB is resistant to all currently used drugs.JOURNAL, Totally Resistant TB: Earliest Cases in Italy, Wired,weblink Maryn McKenna, 12 January 2012, 12 January 2012, live,weblink" title="web.archive.org/web/20120114214156weblink">weblink 14 January 2012, dmy-all, It was first observed in 2003 in Italy,JOURNAL, Migliori GB, De Iaco G, Besozzi G, Centis R, Cirillo DM, 3, First tuberculosis cases in Italy resistant to all tested drugs, Euro Surveillance, 12, 5, E070517.1, May 2007, 17868596, 10.2807/esw.12.20.03194-en, but not widely reported until 2012,WEB, Totally Drug-Resistant TB: a WHO consultation on the diagnostic definition and treatment options,weblink World Health Organization (WHO), 25 March 2016, live,weblink" title="web.archive.org/web/20161021151601weblink">weblink 21 October 2016, dmy-all, and has also been found in Iran and India.JOURNAL, Velayati AA, Masjedi MR, Farnia P, Tabarsi P, Ghanavi J, ZiaZarifi AH, Hoffner SE, 3, Emergence of new forms of totally drug-resistant tuberculosis bacilli: super extensively drug-resistant tuberculosis or totally drug-resistant strains in Iran, Chest, 136, 2, 420–25, August 2009, 19349380, 10.1378/chest.08-2427, Bedaquiline is tentatively supported for use in multiple drug-resistant TB.WEB, Provisional CDC Guidelines for the Use and Safety Monitoring of Bedaquiline Fumarate (Sirturo) for the Treatment of Multidrug-Resistant Tuberculosis,weblink live,weblink" title="web.archive.org/web/20140104204359weblink">weblink 4 January 2014, dmy-all, XDR-TB is a term sometimes used to define extensively resistant TB, and constitutes one in ten cases of MDR-TB. Cases of XDR TB have been identified in more than 90% of countries.JOURNAL, Ancient enemy, modern imperative – A time for greater action against tuberculosis,weblink Economist Intelligence Unit, 1 August 2014, 30 June 2014, Paul Kielstra, Zoe Tabary, live,weblink" title="web.archive.org/web/20140731145650weblink">weblink 31 July 2014, dmy-all,

Prognosis

File:Tuberculosis world map - DALY - WHO2004.svg|thumb|upright=1.4|left|Age-standardized weblink WHO Disease and injury country estimates, 2004, World Health Organization (WHO), 11 November 2009, live,weblink" title="web.archive.org/web/20091111101009weblink">weblink 11 November 2009, dmy-all, {{Col-begin}}{{Col-break}}{{legend">#b3b3b3|no data|size=60%}}{{legend|#ffff65|≤10|size=60%}}{{legend|#fff200|10–25|size=60%}}{{legend|#ffdc00|25–50|size=60%}}{{legend|#ffc600|50–75|size=60%}}{{legend|#ffb000|75–100|size=60%}}{{legend|#ff9a00|100–250|size=60%}}{{Col-break}}{{legend|#ff8400|250–500|size=60%}}{{legend|#ff6e00|500–750|size=60%}}{{legend|#ff5800|750–1000|size=60%}}{{legend|#ff4200|1000–2000|size=60%}}{{legend|#ff2c00|2000–3000|size=60%}}{{legend|#cb0000|≥ 3000|size=60%}}{{col-end}}Progression from TB infection to overt TB disease occurs when the bacilli overcome the immune system defenses and begin to multiply. In primary TB disease (some 1–5% of cases), this occurs soon after the initial infection. However, in the majority of cases, a latent infection occurs with no obvious symptoms. These dormant bacilli produce active tuberculosis in 5–10% of these latent cases, often many years after infection.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. Studies using DNA fingerprinting of M. tuberculosis strains have shown reinfection contributes more substantially to recurrent TB than previously thought,JOURNAL, Lambert ML, Hasker E, Van Deun A, Roberfroid D, Boelaert M, Van der Stuyft P, 3, Recurrence in tuberculosis: relapse or reinfection?, The Lancet. Infectious Diseases, 3, 5, 282–87, May 2003, 12726976, 10.1016/S1473-3099(03)00607-8, with estimates that it might account for more than 50% of reactivated cases in areas where TB is common.JOURNAL, Wang JY, Lee LN, Lai HC, Hsu HL, Liaw YS, Hsueh PR, Yang PC, 3, Prediction of the tuberculosis reinfection proportion from the local incidence, The Journal of Infectious Diseases, 196, 2, 281–88, July 2007, 17570116, 10.1086/518898, The chance of death from a case of tuberculosis is about 4% {{as of|2008|lc=yes}}, down from 8% in 1995.

Epidemiology

File:Tuberculosis-prevalence-WHO-2009.svg|thumb|upright=1.4|alt=World map with (sub-Saharan Africa]] in various shades of yellow, marking prevalences above 300 per 100,000, and with the U.S., Canada, Australia, and northern Europe in shades of deep blue, marking prevalences around 10 per 100,000. Asia is yellow but not quite so bright, marking prevalences around 200 per 100,000 range. South America is a darker yellow.|In 2007, the number of cases of TB per 100,000 people was highest in sub-Saharan Africa, and was also relatively high in Asia.BOOK, Global tuberculosis control: epidemiology, strategy, financing, World Health Organization (WHO), 2009, 978-92-4-156380-2, The Stop TB Strategy, case reports, treatment outcomes and estimates of TB burden,weblink 14 November 2009, 187–300, dead,weblinkweblink" title="web.archive.org/web/20091119022738weblink">weblink 19 November 2009, dmy-all, )(File:Tuberculosis world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.4|Tuberculosis deaths per million persons in 2012{{legend|#ffff20|0–3}}{{legend|#ffe820|4–7}}{{legend|#ffd820|8–16}}{{legend|#ffc020|17–26}}{{legend|#ffa020|27–45}}{{legend|#ff9a20|46–83}}{{legend|#f08015|84–137}}{{legend|#e06815|138–215}}{{legend|#d85010|216–443}}{{legend|#d02010|444-1,359}})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. However, most infections with M. tuberculosis do not cause TB disease,WEB, Centers for Disease Control and Prevention (CDC),weblink Fact Sheets: The Difference Between Latent TB Infection and Active TB Disease, 20 June 2011, 26 July 2011, live,weblink" title="web.archive.org/web/20110804005502weblink">weblink 4 August 2011, dmy-all, and 90–95% of infections remain asymptomatic. In 2012, an estimated 8.6 million chronic cases were active.WEB, Global tuberculosis report 2013,weblink World Health Organization (WHO), 2013, live,weblink" title="web.archive.org/web/20061212123736weblink">weblink 12 December 2006, dmy-all, 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.JOURNAL, Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M, Burney P, Carapetis J, Chen H, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahodwala N, De Leo D, Degenhardt L, Delossantos A, Denenberg J, Des Jarlais DC, Dharmaratne SD, Dorsey ER, Driscoll T, Duber H, Ebel B, Erwin PJ, Espindola P, Ezzati M, Feigin V, Flaxman AD, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabriel SE, Gakidou E, Gaspari F, Gillum RF, Gonzalez-Medina D, Halasa YA, Haring D, Harrison JE, Havmoeller R, Hay RJ, Hoen B, Hotez PJ, Hoy D, Jacobsen KH, James SL, Jasrasaria R, Jayaraman S, Johns N, Karthikeyan G, Kassebaum N, Keren A, Khoo JP, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lipnick M, Lipshultz SE, Ohno SL, Mabweijano J, MacIntyre MF, Mallinger L, March L, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGrath J, Mensah GA, Merriman TR, Michaud C, Miller M, Miller TR, Mock C, Mocumbi AO, Mokdad AA, Moran A, Mulholland K, Nair MN, Naldi L, Narayan KM, Nasseri K, Norman P, O'Donnell M, Omer SB, Ortblad K, Osborne R, Ozgediz D, Pahari B, Pandian JD, Rivero AP, Padilla RP, Perez-Ruiz F, Perico N, Phillips D, Pierce K, Pope CA 3rd, Porrini E, Pourmalek F, Raju M, Ranganathan D, Rehm JT, Rein DB, Remuzzi G, Rivara FP, Roberts T, De León FR, Rosenfeld LC, Rushton L, Sacco RL, Salomon JA, Sampson U, Sanman E, Schwebel DC, Segui-Gomez M, Shepard DS, Singh D, Singleton J, Sliwa K, Smith E, Steer A, Taylor JA, Thomas B, Tleyjeh IM, Towbin JA, Truelsen T, Undurraga EA, Venketasubramanian N, Vijayakumar L, Vos T, Wagner GR, Wang M, Wang W, Watt K, Weinstock MA, Weintraub R, Wilkinson JD, Woolf AD, Wulf S, Yeh PH, Yip P, Zabetian A, Zheng ZJ, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA, 3, Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010, Lancet, 380, 9859, 2095–128, December 2012, 23245604, 10.1016/S0140-6736(12)61728-0, 10536/DRO/DU:30050819, Of these 1.45 million deaths, about 0.35 million occur in those also infected with HIV.WEB, Global Tuberculosis Control 2011,weblink World Health Organization (WHO), 15 April 2012, dead,weblink" title="web.archive.org/web/20120617064025weblink">weblink 17 June 2012, Tuberculosis is the second-most common cause of death from infectious disease (after those due to HIV/AIDS). The total number of tuberculosis cases has been decreasing since 2005, while new cases have decreased since 2002. China has achieved particularly dramatic progress, with about an 80% reduction in its TB mortality rate between 1990 and 2010. The number of new cases has declined by 17% between 2004 and 2014. 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. 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.In 2007, the country with the highest estimated incidence rate of TB was Swaziland, with 1,200 cases per 100,000 people. India had the largest total incidence, with an estimated 2.0 million new cases.BOOK, Global tuberculosis control: epidemiology, strategy, financing, World Health Organization (WHO), 2009, 978-92-4-156380-2, Epidemiology,weblink 6–33, {{dead link|date=March 2018 |bot=InternetArchiveBot |fix-attempted=yes }} In developed countries, tuberculosis is less common and is found mainly in urban areas. 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 in 2010. In Canada and Australia, tuberculosis is many times more common among the aboriginal peoples, especially in remote areas.JOURNAL, FitzGerald JM, Wang L, Elwood RK, Tuberculosis: 13. Control of the disease among aboriginal people in Canada, Canadian Medical Association Journal, 162, 3, 351–55, February 2000, 10693593, 1231016, BOOK, Quah, Stella R., Carrin, Guy, Buse, Kent, Kristian Heggenhougen, Health Systems Policy, Finance, and Organization, Academic Press, Boston, 2009, 424, 978-0-12-375087-7,weblink live,weblink 6 September 2015, dmy-all, In the United States Native Americans have a fivefold greater mortality from TB,BOOK, Anne-Emanuelle Birn, Textbook of International Health: Global Health in a Dynamic World, 2009, 261, 978-0-19-988521-3,weblink live,weblink 6 September 2015, dmy-all, and racial and ethnic minorities accounted for 84% of all reported TB cases.WEB, Centers for Disease Control and Prevention,weblink CDC Surveillance Slides 2012 – TB, live,weblink" title="web.archive.org/web/20131109150519weblink">weblink 9 November 2013, dmy-all, 2018-10-24, The rate of TB varies with age. In Africa, it primarily affects adolescents and young adults.WEB, World Health Organization (WHO),weblink Global Tuberculosis Control Report, 2006 – Annex 1 Profiles of high-burden countries, 13 October 2006, dead,weblink" title="web.archive.org/web/20090726124358weblink">weblink 26 July 2009, 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).WEB, Centers for Disease Control and Prevention,weblink 2005 Surveillance Slide Set, 12 September 2006, 13 October 2006, live,weblink" title="web.archive.org/web/20061123122326weblink">weblink 23 November 2006, dmy-all, Worldwide, 22 "high-burden" states or countries together experience 80% of cases as well as 83% of deaths.The routine use of rifabutin instead of rifampicin in HIV-positive people with tuberculosis is of unclear benefit {{as of|2007|lc=yes}}.JOURNAL, Davies, G., Cerri, S., Richeldi, L., 2007-10-17, Rifabutin for treating pulmonary tuberculosis, The Cochrane Database of Systematic Reviews, 4, CD005159, 10.1002/14651858.CD005159.pub2, 1469-493X, 17943842, 6532710,

History

File:Mummy at British Museum.jpg|thumb|Egyptian mummy in the British MuseumBritish MuseumTuberculosis has existed since antiquity. 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.JOURNAL, Rothschild BM, Martin LD, Lev G, Bercovier H, Bar-Gal GK, Greenblatt C, Donoghue H, Spigelman M, Brittain D, 3, Mycobacterium tuberculosis complex DNA from an extinct bison dated 17,000 years before the present, Clinical Infectious Diseases, 33, 3, 305–11, August 2001, 11438894, 10.1086/321886,weblink However, whether tuberculosis originated in bovines, then transferred to humans, or whether both bovine and human tuberculosis diverged from a common ancestor, remains unclear.JOURNAL, Pearce-Duvet JM, The origin of human pathogens: evaluating the role of agriculture and domestic animals in the evolution of human disease, Biological Reviews of the Cambridge Philosophical Society, 81, 3, 369–82, August 2006, 16672105, 10.1017/S1464793106007020, 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. Both strains of the tuberculosis bacteria share a common ancestor, which could have infected humans even before the Neolithic Revolution.JOURNAL, Comas I, Gagneux S, The past and future of tuberculosis research, PLoS Pathogens, 5, 10, e1000600, October 2009, 19855821, 2745564, 10.1371/journal.ppat.1000600, Manchester, Marianne, 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.JOURNAL, Zink AR, Sola C, Reischl U, Grabner W, Rastogi N, Wolf H, Nerlich AG, 3, Characterization of Mycobacterium tuberculosis complex DNAs from Egyptian mummies by spoligotyping, Journal of Clinical Microbiology, 41, 1, 359–67, January 2003, 12517873, 149558, 10.1128/JCM.41.1.359-367.2003, Genetic studies suggest the presence of TB in the Americas from about 100 AD.JOURNAL, Konomi N, Lebwohl E, Mowbray K, Tattersall I, Zhang D, 3, Detection of mycobacterial DNA in Andean mummies, Journal of Clinical Microbiology, 40, 12, 4738–40, December 2002, 12454182, 154635, 10.1128/JCM.40.12.4738-4740.2002, Before the Industrial Revolution, folklore often associated tuberculosis with vampires. When one member of a family died from the disease, the other infected members would lose their health slowly. People believed this was caused by the original person with TB draining the life from the other family members.JOURNAL, Sledzik PS, Bellantoni N, Brief communication: bioarcheological and biocultural evidence for the New England vampire folk belief, American Journal of Physical Anthropology, 94, 2, 269–74, June 1994, 8085617, 10.1002/ajpa.1330940210,weblinkweblink" title="web.archive.org/web/20170218082115weblink">weblink dmy-all, live, 18 February 2017, Although Richard Morton established the pulmonary form associated with tubercles as a pathology in 1689,{{WhoNamedIt|doctor|2413|Léon Charles Albert Calmette}}JOURNAL, Trail RR, Richard Morton (1637-1698), Medical History, 14, 2, 166–74, April 1970, 4914685, 1034037, 10.1017/S0025727300015350, due to the variety of its symptoms, TB was not identified as a single disease until the 1820s. J. L. Schönlein coined the name "tuberculosis" in 1839.Zur Pathogenie der Impetigines. Auszug aus einer brieflichen Mitteilung an den Herausgeber. [Müller's] Archiv für Anatomie, Physiologie und wissenschaftliche Medicin. 1839, p. 82. 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.Kentucky: Mammoth Cave long on history. {{webarchive|url=weblink" title="web.archive.org/web/20060813140746weblink">weblink |date= 13 August 2006 }} CNN. 27 February 2004. Accessed 8 October 2006. Hermann Brehmer opened the first TB sanatorium in 1859 in Görbersdorf (now Sokołowsko) in Silesia.JOURNAL, McCarthy OR, The key to the sanatoria, Journal of the Royal Society of Medicine, 94, 8, 413–17, August 2001, 11461990, 1281640,weblink 10.1177/014107680109400813, (File:RobertKoch.jpg|upright|thumb|left|Robert Koch discovered the tuberculosis bacillus.)Robert Koch identified and described the bacillus causing tuberculosis, M. tuberculosis, on 24 March 1882.WEB,weblink History: World TB Day, Centers for Disease Control and Prevention (CDC), live, 23 March 2019, 12 December 2016, 7 December 2018,weblink He received the Nobel Prize in physiology or medicine in 1905 for this discovery.Nobel Foundation. The Nobel Prize in Physiology or Medicine 1905. {{webarchive|url=weblink" title="web.archive.org/web/20061210184150weblink">weblink |date= 10 December 2006 }} Accessed 7 October 2006. Koch did not believe the cattle and human tuberculosis diseases were similar, which delayed the recognition of infected milk as a source of infection. During the first half of the 1900s the risk of transmission from this source was dramatically reduced after the application of the pasteurization process. Koch announced a glycerine extract of the tubercle bacilli as a "remedy" for tuberculosis in 1890, calling it "tuberculin". While it was not effective, it was later successfully adapted as a screening test for the presence of pre-symptomatic tuberculosis.JOURNAL, Waddington K, To stamp out 'so terrible a malady': bovine tuberculosis and tuberculin testing in Britain, 1890–1939, Medical History, 48, 1, 29–48, January 2004, 14968644, 546294, 10.1017/S0025727300007043, World Tuberculosis Day is marked on 24 March each year, the anniversary of Koch's original scientific announcement.Albert Calmette and Camille Guérin achieved the first genuine success in immunization against tuberculosis in 1906, using attenuated bovine-strain tuberculosis. It was called bacille Calmette–Guérin (BCG). The BCG vaccine was first used on humans in 1921 in France,JOURNAL, Bonah C, The 'experimental stable' of the BCG vaccine: safety, efficacy, proof, and standards, 1921–1933, Studies in History and Philosophy of Biological and Biomedical Sciences, 36, 4, 696–721, December 2005, 16337557, 10.1016/j.shpsc.2005.09.003, but achieved widespread acceptance in the US, Great Britain, and Germany only after World War II.JOURNAL, Comstock GW, The International Tuberculosis Campaign: a pioneering venture in mass vaccination and research, Clinical Infectious Diseases, 19, 3, 528–40, September 1994, 7811874, 10.1093/clinids/19.3.528, Tuberculosis caused widespread public concern in the 19th and early 20th centuries as the disease became common among the urban poor. In 1815 one in four deaths in England was due to "consumption". By 1918, TB still caused one in six deaths in France. 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). 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 ({{circa}} 1916). When the Medical Research Council formed in Britain in 1913, it initially focused on tuberculosis research.BOOK, editor, Caroline Hannaway, Biomedicine in the twentieth century: practices, policies, and politics, 2008, IOS Press, Amsterdam, 978-1-58603-832-8, 233,weblink live,weblink 7 September 2015, dmy-all, 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.BOOK, Bloom, editor, Barry R., Tuberculosis: pathogenesis, protection, and control, 1994, ASM Press, Washington, DC, 978-1-55581-072-6, By the 1950s mortality in Europe had decreased about 90%.BOOK, Persson, Sheryl, Smallpox, Syphilis and Salvation: Medical Breakthroughs That Changed the World, 2010, ReadHowYouWant.com, 978-1-4587-6712-7, 141,weblink live,weblink 6 September 2015, dmy-all, 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. In 1946 the development of the antibiotic streptomycin made effective treatment and cure of TB a reality. 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.BOOK, Shields, Thomas, General thoracic surgery, 2009, Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia, 978-0-7817-7982-1, 792,weblink 7th, live,weblink 6 September 2015, dmy-all, Because of the emergence of MDR-TB, surgery has been re-introduced for certain cases of TB infections. 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.JOURNAL, Lalloo UG, Naidoo R, Ambaram A, Recent advances in the medical and surgical treatment of multi-drug resistant tuberculosis, Current Opinion in Pulmonary Medicine, 12, 3, 179–85, May 2006, 16582672, 10.1097/01.mcp.0000219266.27439.52, Hopes of completely eliminating TB ended with the rise of drug-resistant strains in the 1980s. The subsequent resurgence of tuberculosis resulted in the declaration of a global health emergency by the World Health Organization (WHO) in 1993.WEB, Frequently asked questions about TB and HIV,weblink World Health Organization (WHO), 15 April 2012,weblink" title="web.archive.org/web/20110808115404weblink">weblink 8 August 2011, dead,

Society and culture

Names

Tuberculosis has been known by many names from the technical to the familiar. 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.WEB, Hippocrates 3.16 Classics, MIT,weblink 15 December 2015, unfit,weblink" title="web.archive.org/web/20050211173218weblink">weblink 11 February 2005, The abbreviation "TB" is short for tubercle bacillus. "Consumption" was the most common nineteenth century English word for the disease. The Latin root "con" meaning "completely" is linked to "sumere" meaning "to take up from under."BOOK, Caldwell, Mark, The Last Crusade, 1988, Macmillan, New York, 978-0-689-11810-4, 21, registration,weblink In The Life and Death of Mr Badman by John Bunyan, the author calls consumption "the captain of all these men of death."BOOK, Bunyan, John, 1808, The Life and Death of Mr. Badman,weblink 244, London, W. Nicholson, Google Books, 28 September 2016, live,weblink 10 September 2017, dmy-all, "Great white plague" has also been used.

Art and literature

File:Munch Det Syke Barn 1885-86.jpg|thumb|Painting The Sick Child by Edvard MunchEdvard MunchTuberculosis was for centuries associated with poetic and artistic qualities among those infected, and was also known as "the romantic disease".WEB, Lawlor, Clark, Katherine Byrne, Tuberculosis and the Victorian Literary Imagination,weblink British Society for Literature and Science, 11 June 2017, BOOK, Byrne, Katherine, Tuberculosis and the Victorian Literary Imagination, Cambridge University Press, 2011, 978-1-107-67280-2, Major artistic figures such as the poets John Keats, Percy Bysshe Shelley, and Edgar Allan Poe, the composer Frédéric Chopin,WEB, About Chopin's illness,weblink Icons of Europe, 11 June 2017, the playwright Anton Chekhov, the novelists Franz Kafka, Katherine Mansfield,JOURNAL, Vilaplana C, A literary approach to tuberculosis: lessons learned from Anton Chekhov, Franz Kafka, and Katherine Mansfield, International Journal of Infectious Diseases, 56, 283–85, March 2017, 27993687, 10.1016/j.ijid.2016.12.012, Charlotte Brontë, Fyodor Dostoevsky, Thomas Mann, W. Somerset Maugham,BOOK, Rogal, Samuel J., A William Somerset Maugham Encyclopedia,weblink 1997, Greenwood Publishing, 978-0-313-29916-2, 245, George Orwell,WEB, Eschner, Kat, George Orwell Wrote '1984' While Dying of Tuberculosis,weblink Smithsonian, 25 March 2019, and Robert Louis Stevenson, and the artists Alice Neel,JOURNAL, Journal of the American Medical Association,weblink cover, 8 June 2005, 293, 22, Tuberculosis (whole issue), 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. A widespread belief was that tuberculosis assisted artistic talent. 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.JOURNAL, Lemlein, Rhoda F., Influence of Tuberculosis on the Work of Visual Artists: Several Prominent Examples, Leonardo, 1981, 14, 2, 114–11, 1574402, 10.2307/1574402, WEB, Wilsey, Ashley M., 'Half in Love with Easeful Death:' Tuberculosis in Literature, May 2012, Humanities Capstone Projects (PhD Thesis), Pacific University, Paper 11,weblink JOURNAL, Morens DM, At the deathbed of consumptive art, Emerging Infectious Diseases, 8, 11, 1353–8, November 2002, 12463180, 2738548, 10.3201/eid0811.020549, Tuberculosis formed an often-reused theme in literature, as in Thomas Mann's The Magic Mountain, set in a sanatorium;WEB,weblink Pulmonary Tuberculosis/In Literature and Art, McMaster University History of Diseases, 9 June 2017, in music, as in Van Morrison's song "T.B. Sheets";NEWS, Thomson, Graeme, Van Morrison – 10 of the best,weblink The Guardian, 1 June 2016, 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;WEB, Tuberculosis Throughout History: The Arts,weblink United States Agency for International Development (USAID), 12 June 2017, and in film, such as the 1945 The Bells of St. Mary's starring Ingrid Bergman as a nun with tuberculosis.JOURNAL, Corliss, Richard, Top 10 Worst Christmas Movies, Time,weblink 22 December 2008, 'If you don't cry when Bing Crosby tells Ingrid Bergman she has tuberculosis', Joseph McBride wrote in 1973, 'I never want to meet you, and that's that.',

Public health efforts

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.JOURNAL, Lawn SD, Nicol MP, Xpert® MTB/RIF assay: development, evaluation and implementation of a new rapid molecular diagnostic for tuberculosis and rifampicin resistance, Future Microbiology, 6, 9, 1067–82, September 2011, 21958145, 3252681, 10.2217/fmb.11.84, NEWS,weblink WHO says Cepheid rapid test will transform TB care, Reuters, 8 December 2010, live,weblink" title="web.archive.org/web/20101211140847weblink">weblink 11 December 2010, dmy-all, 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.WEB, Public–Private Partnership Announces Immediate 40 Percent Cost Reduction for Rapid TB Test,weblink World Health Organization (WHO), 6 August 2012, live,weblink" title="web.archive.org/web/20131029234310weblink">weblink 29 October 2013, dmy-all, WEB, The Stop TB Partnership, which operates through a secretariat hosted by the World Health Organization (WHO) in Geneva, Switzerland,weblink STOPTB, 5 April 2013, live,weblink" title="web.archive.org/web/20140124041952weblink">weblink 24 January 2014, dmy-all, Many resource-poor places {{as of|2011|lc=yes}} have access to only sputum microscopy.JOURNAL, Lienhardt C, Espinal M, Pai M, Maher D, Raviglione MC, 3, What research is needed to stop TB? Introducing the TB Research Movement, PLoS Medicine, 8, 11, e1001135, November 2011, 22140369, 3226454, 10.1371/journal.pmed.1001135, 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.JOURNAL, Mishra, G, Tuberculosis Prescription Practices in Private And Public Sector in India, NJIRM, 2013, 4, 2, 71–78,weblink live,weblink" title="web.archive.org/web/20130510025039weblink">weblink 10 May 2013, dmy-all, Programs such as the Revised National Tuberculosis Control Program are working to reduce TB levels among people receiving public health care.JOURNAL, Anurag Bhargava, Lancelot Pinto, Madhukar Pai, Mismanagement of tuberculosis in India: Causes, consequences, and the way forward, Hypothesis, 9, 1, e7, 2011, 10.5779/hypothesis.v9i1.214, dmy-all, JOURNAL, Amdekar Y, Changes in the management of tuberculosis, Indian Journal of Pediatrics, 76, 7, 739–42, July 2009, 19693453, 10.1007/s12098-009-0164-4, A 2014 the EIU-healthcare report finds there is a need to address apathy and urges for increased funding. The report cites among others Lucica Ditui "[TB] is like an orphan. It has been neglected even in countries with a high burden and often forgotten by donors and those investing in health interventions."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." 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. Commercial treatment providers may at times overprescribe second-line drugs as well as supplementary treatment, promoting demands for further regulations. The government of Brazil provides universal TB-care, which reduces this problem. 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. Costs of the disease, as calculated by the World Bank in 2009 may exceed US$150 billion per year in "high burden" countries. Lack of progress eradicating the disease may also be due to lack of patient follow-up – as among the 250M rural migrants in China.

Stigma

Slow progress in preventing the disease may in part be due to stigma associated with TB. Stigma may be due to the fear of transmission from affected individuals. This stigma may additionally arise due to links between TB and poverty, and in Africa, AIDS. Such stigmatization may be both real and perceived; for example, in Ghana individuals with TB are banned from attending public gatherings.JOURNAL, Courtwright A, Turner AN, Tuberculosis and stigmatization: pathways and interventions, Public Health Reports, 125 Suppl 4, 4_suppl, 34–42, Jul–Aug 2010, 20626191, 2882973, 10.1177/00333549101250S407, 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. In contrast, in Russia stigma was associated with increased treatment compliance. TB stigma also affects socially marginalized individuals to a greater degree and varies between regions.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. Some studies have shown TB education programs to be effective in decreasing stigma, and may thus be effective in increasing treatment adherence. Despite this, studies on the relationship between reduced stigma and mortality are lacking {{as of|2010|lc=yes}}, and similar efforts to decrease stigma surrounding AIDS have been minimally effective. 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. A greater understanding of the social and cultural dimensions of tuberculosis may also help with stigma reduction.JOURNAL, Mason PH, Roy A, Spillane J, Singh P, 3, Social, Historical and Cultural Dimensions of Tuberculosis, Journal of Biosocial Science, 48, 2, 206–32, March 2016, 25997539, 10.1017/S0021932015000115,

Research

The BCG vaccine has limitations, and research to develop new TB vaccines is ongoing.JOURNAL, Martín Montañés C, Gicquel B, New tuberculosis vaccines, Enfermedades Infecciosas y Microbiologia Clinica, 29 Suppl 1, 57–62, March 2011, 21420568, 10.1016/S0213-005X(11)70019-2, A number of potential candidates are currently in phase I and II clinical trials.JOURNAL, Zhu B, Dockrell HM, Ottenhoff TH, Evans TG, Zhang Y, 3, Tuberculosis vaccines: Opportunities and challenges, Respirology, 23, 4, 359–68, April 2018, 29341430, 10.1111/resp.13245, Two main approaches are used to attempt to improve the efficacy of available vaccines. One approach involves adding a subunit vaccine to BCG, while the other strategy is attempting to create new and better live vaccines. MVA85A, an example of a subunit vaccine, is in trials in South Africa as of 2006, is based on a genetically modified vaccinia virus.JOURNAL, Ibanga HB, Brookes RH, Hill PC, Owiafe PK, Fletcher HA, Lienhardt C, Hill AV, Adegbola RA, McShane H, 3, Early clinical trials with a new tuberculosis vaccine, MVA85A, in tuberculosis-endemic countries: issues in study design, The Lancet. Infectious Diseases, 6, 8, 522–28, August 2006, 16870530, 10.1016/S1473-3099(06)70552-7, Vaccines are hoped to play a significant role in treatment of both latent and active disease.JOURNAL, Kaufmann SH, Future vaccination strategies against tuberculosis: thinking outside the box, Immunity, 33, 4, 567–77, October 2010, 21029966, 10.1016/j.immuni.2010.09.015, 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.JOURNAL, Webber D., Kremer M.,weblink Stimulating Industrial R&D for Neglected Infectious Diseases: Economic Perspectives, Bulletin of the World Health Organization, 79, 8, 2001, 693–801, live,weblink" title="web.archive.org/web/20070926012031weblink">weblink 26 September 2007, dmy-all, JOURNAL, Barder O., Kremer M., Williams H.,weblink Advance Market Commitments: A Policy to Stimulate Investment in Vaccines for Neglected Diseases, The Economists' Voice, 3, 2006, 3, 10.2202/1553-3832.1144, dead,weblink" title="web.archive.org/web/20061105083659weblink">weblink 5 November 2006, dmy-all, A number of groups, including the Stop TB Partnership,BOOK, Economic, Department of, Achieving the global public health agenda: dialogues at the Economic and Social Council, 2009, United Nations, New York, 978-92-1-104596-3, 103,weblink Affairs, Social, live,weblink 6 September 2015, dmy-all, the South African Tuberculosis Vaccine Initiative, and the Aeras Global TB Vaccine Foundation, are involved with research.BOOK, Jong, [edited by] Jane N. Zuckerman, Elaine C., Travelers' vaccines, 2010, People's Medical Publishing House, Shelton, CT, 978-1-60795-045-5, 319,weblink 2nd, live,weblink 6 September 2015, dmy-all, 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.WEB, Bill and Melinda Gates Foundation Announcement, Gates Foundation Commits $82.9 Million to Develop New Tuberculosis Vaccines, 12 February 2004,weblink dead,weblink" title="web.archive.org/web/20091010163118weblink">weblink 10 October 2009, WEB, Nightingale, Katherine, Gates foundation gives US$280 million to fight TB, 19 September 2007,weblink live,weblink" title="web.archive.org/web/20081201175618weblink">weblink 1 December 2008, dmy-all, A number of medications are being studied as of 2012 for multidrug-resistant tuberculosis, including bedaquiline and delamanid.JOURNAL, Zumla A, Hafner R, Lienhardt C, Hoelscher M, Nunn A, 3, Advancing the development of tuberculosis therapy, Nature Reviews. Drug Discovery, 11, 3, 171–72, March 2012, 22378254, 10.1038/nrd3694, Bedaquiline received U.S. Food and Drug Administration (FDA) approval in late 2012.NEWS, J&J Sirturo Wins FDA Approval to Treat Drug-Resistant TB,weblink 1 January 2013, Bloomberg News, 31 December 2012, live,weblink" title="web.archive.org/web/20130104110903weblink">weblink 4 January 2013, dmy-all, The safety and effectiveness of these new agents are uncertain as of 2012, because they are based on the results of relatively small studies.JOURNAL, Avorn J, Approval of a tuberculosis drug based on a paradoxical surrogate measure, JAMA, 309, 13, 1349–50, April 2013, 23430122, 10.1001/jama.2013.623, 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,WEB, US Food and Drug Administration, Briefing Package: NDA 204–384: Sirturo,weblink live,weblink" title="web.archive.org/web/20140104212835weblink">weblink 4 January 2014, dmy-all, 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.JOURNAL, Zuckerman, Diana, Jennifer Yttri, Antibiotics: When science and wishful thinking collide, Health Affairs, January 2013,weblink live,weblink" title="web.archive.org/web/20130210154447weblink">weblink 10 February 2013, dmy-all,

Other animals

Mycobacteria infect many different animals, including birds,JOURNAL, Shivaprasad HL, Palmieri C, Pathology of mycobacteriosis in birds, The Veterinary Clinics of North America. Exotic Animal Practice, 15, 1, 41–55, v–vi, January 2012, 22244112, 10.1016/j.cvex.2011.11.004, rodents,JOURNAL, Reavill DR, Schmidt RE, Mycobacterial lesions in fish, amphibians, reptiles, rodents, lagomorphs, and ferrets with reference to animal models, The Veterinary Clinics of North America. Exotic Animal Practice, 15, 1, 25–40, v, January 2012, 22244111, 10.1016/j.cvex.2011.10.001, and reptiles.JOURNAL, Mitchell MA, Mycobacterial infections in reptiles, The Veterinary Clinics of North America. Exotic Animal Practice, 15, 1, 101–11, vii, January 2012, 22244116, 10.1016/j.cvex.2011.10.002, The subspecies Mycobacterium tuberculosis, though, is rarely present in wild animals.BOOK, Wobeser, Gary A., Essentials of disease in wild animals, 2006, Blackwell Publishing, Ames, IO [u.a.], 978-0-8138-0589-4, 170,weblink 1st, live,weblink 6 September 2015, dmy-all, An effort to eradicate bovine tuberculosis caused by Mycobacterium bovis from the cattle and deer herds of New Zealand has been relatively successful.JOURNAL, Ryan TJ, Livingstone PG, Ramsey DS, de Lisle GW, Nugent G, Collins DM, Buddle BM, 3, Advances in understanding disease epidemiology and implications for control and eradication of tuberculosis in livestock: the experience from New Zealand, Veterinary Microbiology, 112, 2–4, 211–19, February 2006, 16330161, 10.1016/j.vetmic.2005.11.025, Efforts in Great Britain have been less successful.JOURNAL, White PC, Böhm M, Marion G, Hutchings MR, 3, Control of bovine tuberculosis in British livestock: there is no 'silver bullet', Trends in Microbiology, 16, 9, 420–7, September 2008, 18706814, 10.1016/j.tim.2008.06.005,weblink 10.1.1.566.5547, JOURNAL, Ward AI, Judge J, Delahay RJ, Farm husbandry and badger behaviour: opportunities to manage badger to cattle transmission of Mycobacterium bovis?, Preventive Veterinary Medicine, 93, 1, 2–10, January 2010, 19846226, 10.1016/j.prevetmed.2009.09.014, {{As of|2015}}, tuberculosis appears to be widespread among captive elephants in the US. It is believed that the animals originally acquired the disease from humans, a process called reverse zoonosis. 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.WEB, Holt, Nathalia, The Infected Elephant in the Room,weblink Slate (magazine), Slate, 2016-04-05, 24 March 2015, live,weblink" title="web.archive.org/web/20160414151050weblink">weblink 14 April 2016, dmy-all, WEB, Mikota, Susan K., A Brief History of TB in Elephants,weblink Animal and Plant Health Inspection Service (APHIS), 2016-04-05, live,weblink 6 October 2016, dmy-all,

References

{{Reflist}}

External links

{{Medical condition classification and resources|DiseasesDB = 8515A15-A19}}010}}–{{ICD9|018}}|OMIM = 607948|MedlinePlus = 000077000624}}|eMedicineSubj = med|eMedicineTopic = 2324emergradio|411}}|MeshID = D014376|Orphanet=3389|Scholia=Q12204}}{{offline|med}}{{Commons category|Tuberculosis}}
  • {{curlie|Health/Conditions_and_Diseases/Infectious_Diseases/Mycobacterial/Tuberculosis/}}
  • WEB,weblink Centers for Disease Control and Prevention (CDC), Tuberculosis (TB), 2018-10-24,
  • WEB,weblink Health Protection Agency, London, Tuberculosis (TB), dead,weblink" title="web.archive.org/web/20070705100742weblink">weblink 5 July 2007, dmy-all,
{{Gram-positive actinobacteria diseases}}{{Tuberculosis}}{{Diseases of Poverty}}{{Arthritis in children}}{{Authority control}}

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