Tuberculosis Warning: You are not logged in. Your IP address will be publicly visible if you make any edits. If you log in or create an account, your edits will be attributed to your username, along with other benefits.Anti-spam check. Do not fill this in! {{Short description|Infectious disease}} {{Good article}} {{Pp-semi-indef}} {{Pp-move-indef}} {{Use dmy dates|date=January 2023}} {{Infobox medical condition (new) | name = Tuberculosis | image = Tuberculosis-x-ray-1.jpg | caption = [[Chest radiograph|Chest X-ray]] of a person with advanced tuberculosis: Infection in both lungs is marked by white arrow-heads, and the formation of a cavity is marked by black arrows. | field = [[Infectious disease (medical specialty)|Infectious disease]], [[pulmonology]] | synonyms = Phthisis, phthisis pulmonalis, consumption, great white plague | symptoms = [[Chronic cough]], [[fever]], [[hemoptysis|cough with bloody mucus]], weight loss<ref name=WHO2015Fact/> | onset = | duration = | causes = ''[[Mycobacterium tuberculosis]]''<ref name=WHO2015Fact/> | risks = Smoking, [[HIV/AIDS]]<ref name=WHO2015Fact/> | diagnosis = [[Chest X-ray|CXR]], [[microbial culture|culture]], [[tuberculin skin test]], [[QuantiFERON]]<ref name=WHO2015Fact/> | differential = [[Pneumonia]], [[histoplasmosis]], [[sarcoidosis]], [[coccidioidomycosis]]<ref>{{cite book | vauthors = Ferri FF |title=Ferri's differential diagnosis : a practical guide to the differential diagnosis of symptoms, signs, and clinical disorders|date=2010|publisher=Elsevier/Mosby|location=Philadelphia, PA|isbn=978-0-323-07699-9|page=Chapter T|edition=2nd}}</ref> | prevention = Screening those at high risk, treatment of those infected, [[vaccination]] with [[bacillus Calmette-Guérin]] (BCG)<ref name=Haw2014/><ref name=TBCon2008/><ref name=Harr2013/> | treatment = [[Antibiotic]]s<ref name=WHO2015Fact/> | medication = | frequency = 25% of people (latent TB)<ref name=WHO2018Fact/> | deaths = 1.3 million (2022)<ref name=WHO2018Fact/> }} '''Tuberculosis''' ('''TB'''), also known colloquially as the "'''white death'''", or historically as '''consumption''',<ref name=Cha1998>{{cite book|title=The Chambers Dictionary.|year=1998|publisher=Allied Chambers India Ltd.|location=New Delhi|isbn=978-81-86062-25-8|page=352|url=https://books.google.com/books?id=pz2ORay2HWoC&pg=RA1-PA352|url-status=live|archive-url=https://web.archive.org/web/20150906201311/https://books.google.com/books?id=pz2ORay2HWoC&pg=RA1-PA352|archive-date=6 September 2015}}</ref> is an [[infectious disease]] usually caused by ''[[Mycobacterium tuberculosis]]'' (MTB) [[bacteria]].<ref name=WHO2015Fact/> Tuberculosis generally affects the [[lung]]s, but it can also affect other parts of the body.<ref name=WHO2015Fact/> Most infections show no symptoms, in which case it is known as [[latent tuberculosis]].<ref name=WHO2015Fact/> Around 10% of latent infections progress to active disease which, if left untreated, kill about half of those affected.<ref name=WHO2015Fact/> Typical symptoms of active TB are chronic [[cough]] with [[hemoptysis|blood-containing]] [[sputum|mucus]], [[fever]], [[night sweats]], and [[weight loss]].<ref name=WHO2015Fact/> [[Infection]] of other organs can cause a wide range of symptoms.<ref name=ID10>{{cite book | vauthors = Adkinson NF, Bennett JE, Douglas RG, Mandell GL |title=Mandell, Douglas, and Bennett's principles and practice of infectious diseases|year=2010|publisher=Churchill Livingstone/Elsevier|location=Philadelphia, PA|isbn=978-0-443-06839-3|page=Chapter 250|edition=7th}}</ref> Tuberculosis is [[Human-to-human transmission|spread from one person to the next]] [[Airborne disease|through the air]] when people who have active TB in their lungs cough, spit, speak, or [[sneeze]].<ref name=WHO2015Fact/><ref name=CDC2012B>{{cite web|title=Basic TB Facts|url=https://www.cdc.gov/tb/topic/basics/default.htm|publisher=[[Centers for Disease Control and Prevention]] (CDC)|access-date=11 February 2016|date=13 March 2012|url-status=live|archive-url=https://web.archive.org/web/20160206032136/http://www.cdc.gov/tb/topic/basics/default.htm|archive-date=6 February 2016}}</ref> People with latent TB do not spread the disease.<ref name=WHO2015Fact/> Active infection occurs more often in people with [[HIV/AIDS]] and in those who [[Tobacco smoking|smoke]].<ref name=WHO2015Fact/> [[Diagnosis]] of active TB is based on [[chest X-ray]]s, as well as [[microscopic]] examination and [[microbiological culture|culture]] of body fluids.<ref name=AP/> Diagnosis of latent TB relies on the [[Mantoux test|tuberculin skin test]] (TST) or blood tests.<ref name=AP>{{cite journal | vauthors = Konstantinos A |year=2010 |title=Testing for tuberculosis |journal=Australian Prescriber |volume=33 |issue=1 |pages=12–18 |doi=10.18773/austprescr.2010.005 |doi-access=free }}</ref> Prevention of TB involves screening those at high risk, early detection and treatment of cases, and [[vaccination]] with the [[bacillus Calmette-Guérin]] (BCG) vaccine.<ref name=Haw2014>{{cite journal | vauthors = Hawn TR, Day TA, Scriba TJ, Hatherill M, Hanekom WA, Evans TG, Churchyard GJ, Kublin JG, Bekker LG, Self SG | display-authors = 6 | title = Tuberculosis vaccines and prevention of infection | journal = Microbiology and Molecular Biology Reviews | volume = 78 | issue = 4 | pages = 650–71 | date = December 2014 | pmid = 25428938 | pmc = 4248657 | doi = 10.1128/MMBR.00021-14 }}</ref><ref name=TBCon2008>{{cite book |title=Implementing the WHO Stop TB Strategy: a handbook for national TB control programmes|date=2008|publisher=[[World Health Organization]] (WHO)|location=Geneva|isbn=978-92-4-154667-6|page=179|url=https://books.google.com/books?id=EUZXFCrlUaEC&pg=PA179|access-date=17 September 2017|archive-date=2 June 2021|archive-url=https://web.archive.org/web/20210602232631/https://books.google.com/books?id=EUZXFCrlUaEC&pg=PA179|url-status=live}}</ref><ref name=Harr2013>{{cite book|vauthors=Harris RE|chapter=Epidemiology of Tuberculosis|title=Epidemiology of chronic disease: global perspectives|date=2013|publisher=Jones & Bartlett Learning|location=Burlington, MA|isbn=978-0-7637-8047-0|page=682|chapter-url=https://books.google.com/books?id=KJLEIvX4wzoC&pg=PA682|access-date=17 September 2017|archive-date=7 February 2024|archive-url=https://web.archive.org/web/20240207093803/https://books.google.com/books?id=KJLEIvX4wzoC&pg=PA682#v=onepage&q&f=false|url-status=live}}</ref> Those at high risk include household, workplace, and social contacts of people with active TB.<ref name=TBCon2008/> Treatment requires the use of multiple [[antibiotic]]s over a long period of time.<ref name=WHO2015Fact/> [[Antibiotic resistance]] is a growing problem, with increasing rates of [[multi-drug-resistant tuberculosis|multiple drug-resistant tuberculosis]] (MDR-TB).<ref name=WHO2015Fact/> In 2018, one quarter of the world's population was thought to have a latent infection of TB.<ref name=WHO2018Fact>{{cite web |title=Tuberculosis (TB) |url=https://www.who.int/en/news-room/fact-sheets/detail/tuberculosis |publisher=[[World Health Organization]] (WHO) |access-date=15 September 2018 |date=16 February 2018 |archive-date=30 December 2013 |archive-url=https://web.archive.org/web/20131230232509/http://www.who.int/mediacentre/factsheets/fs104/en/index.html |url-status=live }}</ref><!-- Quote = About one-quarter of the world's population has latent TB --> New infections occur in about 1% of the population each year.<ref name=WHO2002>{{cite web|title=Tuberculosis|url=https://www.who.int/mediacentre/factsheets/who104/en/print.html|publisher=World Health Organization (WHO)|year=2002|url-status=dead|archive-url=https://web.archive.org/web/20130617193438/http://www.who.int/mediacentre/factsheets/who104/en/print.html|archive-date=17 June 2013}}</ref> In 2022, an estimated 10.6 million people developed active TB, resulting in 1.3 million deaths, making it the second leading [[List of causes of death by rate|cause of death from an infectious disease]] after [[COVID-19]].<ref name="WHO2020">{{cite web | title=Tuberculosis (TB) | website=WHO | url=https://www.who.int/news-room/fact-sheets/detail/tuberculosis | access-date=16 October 2021 | archive-date=30 July 2020 | archive-url=https://web.archive.org/web/20200730165218/https://www.who.int/news-room/fact-sheets/detail/tuberculosis | url-status=live }}</ref> 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 seven countries: India (27%), China (9%), Indonesia (8%), the Philippines (6%), Pakistan (6%), Nigeria (4%), and Bangladesh (4%).<ref name=WHO2017Report>{{Cite web|url=https://www.who.int/tb/publications/global_report/en/|title=Global tuberculosis report|publisher=World Health Organization (WHO)|access-date=9 November 2017|archive-date=30 December 2013|archive-url=https://web.archive.org/web/20131230020808/http://www.who.int/tb/publications/global_report/en/index.html|url-status=live}}</ref> By 2021, the number of new cases each year was decreasing by around 2% annually.<ref name="WHO2020"/><ref name=WHO2015Fact>{{Cite web|title=Tuberculosis (TB)|url=https://www.who.int/news-room/fact-sheets/detail/tuberculosis|website=who.int|language=en|access-date=8 May 2020|archive-date=30 July 2020|archive-url=https://web.archive.org/web/20200730165218/https://www.who.int/news-room/fact-sheets/detail/tuberculosis|url-status=live}}</ref> About 80% of people in many Asian and African countries test positive, while 5–10% of people in the United States test positive via the tuberculin test.<ref name=Robbins>{{Cite book|title=Robbins Basic Pathology|date=2007|publisher=Elsevier| vauthors = Kumar V, Robbins SL |isbn=978-1-4160-2973-1|edition=8th|location=Philadelphia|oclc=69672074}}</ref> Tuberculosis has been present in humans since [[Ancient history|ancient times]].<ref name=Lancet11>{{cite journal | vauthors = Lawn SD, Zumla AI | s2cid = 208791546 | title = Tuberculosis | journal = Lancet | volume = 378 | issue = 9785 | pages = 57–72 | date = July 2011 | pmid = 21420161 | doi = 10.1016/S0140-6736(10)62173-3 }}</ref> [[File:En.Wikipedia-VideoWiki-Tuberculosis.webm|thumb|thumbtime=1:00|Video summary ([[Wikipedia:VideoWiki/Tuberculosis|script]])|303x303px]] {{TOC limit}} == History == {{Main|History of tuberculosis}} [[File:Mummy at British Museum.jpg|thumb|[[Egyptian mummy]] in the [[British Museum]] – tubercular decay has been found in the spine.]] <!-- Ancient history --> Tuberculosis has existed since [[Ancient history|antiquity]].<ref name=Lancet11/> 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.<ref>{{cite journal | vauthors = Rothschild BM, Martin LD, Lev G, Bercovier H, Bar-Gal GK, Greenblatt C, Donoghue H, Spigelman M, Brittain D | display-authors = 6 | title = Mycobacterium tuberculosis complex DNA from an extinct bison dated 17,000 years before the present | journal = Clinical Infectious Diseases | volume = 33 | issue = 3 | pages = 305–11 | date = August 2001 | pmid = 11438894 | doi = 10.1086/321886 | doi-access = free }}</ref> However, whether tuberculosis originated in bovines, then transferred to humans, or whether both bovine and human tuberculosis diverged from a common ancestor, remains unclear.<ref>{{cite journal | vauthors = Pearce-Duvet JM | title = The origin of human pathogens: evaluating the role of agriculture and domestic animals in the evolution of human disease | journal = Biological Reviews of the Cambridge Philosophical Society | volume = 81 | issue = 3 | pages = 369–82 | date = August 2006 | pmid = 16672105 | doi = 10.1017/S1464793106007020 | s2cid = 6577678 }}</ref> A comparison of the [[gene]]s 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]].<ref>{{cite journal | vauthors = Comas I, Gagneux S | title = The past and future of tuberculosis research | journal = PLOS Pathogens | volume = 5 | issue = 10 | page = e1000600 | date = October 2009 | pmid = 19855821 | pmc = 2745564 | doi = 10.1371/journal.ppat.1000600 | veditors = Manchester M | doi-access = free }}</ref> Skeletal remains show some prehistoric humans (4000 [[Common Era|BC]]) had TB, and researchers have found tubercular decay in the spines of [[Ancient Egypt|Egyptian]] [[mummy|mummies]] dating from 3000 to 2400 BC.<ref>{{cite journal | vauthors = Zink AR, Sola C, Reischl U, Grabner W, Rastogi N, Wolf H, Nerlich AG | display-authors = 6 | title = Characterization of Mycobacterium tuberculosis complex DNAs from Egyptian mummies by spoligotyping | journal = Journal of Clinical Microbiology | volume = 41 | issue = 1 | pages = 359–67 | date = January 2003 | pmid = 12517873 | pmc = 149558 | doi = 10.1128/JCM.41.1.359-367.2003 }}</ref> Genetic studies suggest the presence of TB in [[the Americas]] from about AD 100.<ref>{{cite journal | vauthors = Konomi N, Lebwohl E, Mowbray K, Tattersall I, Zhang D | title = Detection of mycobacterial DNA in Andean mummies | journal = Journal of Clinical Microbiology | volume = 40 | issue = 12 | pages = 4738–40 | date = December 2002 | pmid = 12454182 | pmc = 154635 | doi = 10.1128/JCM.40.12.4738-4740.2002 }}</ref> Before the [[Industrial Revolution]], folklore often associated tuberculosis with [[vampire]]s. 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.<ref name=sledzik>{{cite journal | vauthors = Sledzik PS, Bellantoni N | title = Brief communication: bioarcheological and biocultural evidence for the New England vampire folk belief | journal = American Journal of Physical Anthropology | volume = 94 | issue = 2 | pages = 269–74 | date = June 1994 | pmid = 8085617 | doi = 10.1002/ajpa.1330940210 | url = http://www.yorku.ca/kdenning/+++2150%202007-8/sledzik%20vampire.pdf | archive-url = https://web.archive.org/web/20170218082115/http://www.yorku.ca/kdenning/+++2150%202007-8/sledzik%20vampire.pdf | url-status=live | archive-date = 18 February 2017 }}</ref> ===Identification=== Although [[Dr Richard Morton|Richard Morton]] established the pulmonary form associated with [[tubercle (anatomy)|tubercles]] as a pathology in 1689,<ref name="WhoNamedIt-Calmette">{{WhoNamedIt|doctor|2413|Léon Charles Albert Calmette}}</ref><ref name="MedHist1970-Trail">{{cite journal | vauthors = Trail RR | title = Richard Morton (1637-1698) | journal = Medical History | volume = 14 | issue = 2 | pages = 166–74 | date = April 1970 | pmid = 4914685 | pmc = 1034037 | doi = 10.1017/S0025727300015350 }}</ref> due to the variety of its symptoms, TB was not identified as a single disease until the 1820s. [[Benjamin Marten]] conjectured in 1720 that consumptions were caused by microbes which were spread by people living close to each other.<ref>{{cite book |vauthors=Marten B |title=A New Theory of Consumptions—More Especially a Phthisis or Consumption of the Lungs |date=1720 |publisher=T. Knaplock |location=London, England |url=https://babel.hathitrust.org/cgi/pt?id=ucm.5320214800&view=1up&seq=7 |access-date=8 December 2020 |archive-date=26 March 2023 |archive-url=https://web.archive.org/web/20230326205015/https://babel.hathitrust.org/cgi/pt?id=ucm.5320214800&view=1up&seq=7 |url-status=live }} P. 51: "The ''Original'' and ''Essential Cause'' ... may possibly be some certain Species of ''Animalcula'' or wonderfully minute living Creatures, ... " P. 79: "It may be therefore very likely, that by an habitual lying in the same Bed with a Consumptive Patient, constantly Eating and Drinking with him, or by very frequently conversing so nearly, as to draw in part of the Breath he emits from his Lungs, a Consumption may be caught by a sound Person; ... "</ref> In 1819, [[René Laennec]] claimed that tubercles were the cause of pulmonary tuberculosis.<ref>{{cite book |vauthors=Laennec RT |title=De l'auscultation médiate ... |date=1819 |publisher=J.-A. Brosson et J.-S Chaudé |location=Paris, France |volume=1 |page=20 |url=https://books.google.com/books?id=LcZEAAAAcAAJ&pg=PA20 |language=fr |access-date=6 December 2020 |archive-date=2 June 2021 |archive-url=https://web.archive.org/web/20210602212549/https://books.google.com/books?id=LcZEAAAAcAAJ&pg=PA20 |url-status=live }} From p. 20: ''"L'existence des tubercules dans le poumon est la cause et constitue le charactère anatomique propre de la phthisie pulmonaire (a). (a) ... l'effet dont cette maladie tire son nom, c'est-à-dire, la consumption."'' (The existence of tubercles in the lung is the cause and constitutes the unique anatomical characteristic of pulmonary tuberculosis (a). (a) ... the effect from which this malady [pulmonary tuberculosis] takes its name, that is, consumption.)</ref> [[Johann Lukas Schönlein|J. L. Schönlein]] first published the name "tuberculosis" (German: ''Tuberkulose'') in 1832.<ref>{{cite book |vauthors=Schönlein JL |title=Allgemeine und specielle Pathologie und Therapie |trans-title=General and Special Pathology and Therapy |date=1832 |publisher=C. Etlinger |location=Würzburg, (Germany) |volume=3 |page=103 |url=https://books.google.com/books?id=zAtbAAAAcAAJ&pg=PA103 |language=de |access-date=6 December 2020 |archive-date=2 June 2021 |archive-url=https://web.archive.org/web/20210602233224/https://books.google.com/books?id=zAtbAAAAcAAJ&pg=PA103 |url-status=live }}</ref><ref>The word "tuberculosis" first appeared in Schönlein's clinical notes in 1829. See: {{cite journal | vauthors = Jay SJ, Kırbıyık U, Woods JR, Steele GA, Hoyt GR, Schwengber RB, Gupta P | title = Modern theory of tuberculosis: culturomic analysis of its historical origin in Europe and North America | journal = The International Journal of Tuberculosis and Lung Disease | volume = 22 | issue = 11 | pages = 1249–1257 | date = November 2018 | pmid = 30355403 | doi = 10.5588/ijtld.18.0239 | s2cid = 53027676 }} See especially Appendix, p. iii.</ref> Between 1838 and 1845, 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.<ref>{{cite web | url = http://edition.cnn.com/2004/TRAVEL/DESTINATIONS/02/26/mammoth.cave.ap/index.html | title = Kentucky: Mammoth Cave long on history. | archive-url = https://web.archive.org/web/20060813140746/http://edition.cnn.com/2004/TRAVEL/DESTINATIONS/02/26/mammoth.cave.ap/index.html | archive-date= 13 August 2006| work = [[CNN]] | date = 27 February 2004 | access-date = 8 October 2006 }}</ref> Hermann Brehmer opened the first TB [[sanatorium]] in 1859 in Görbersdorf (now [[Sokołowsko]]) in [[Silesia]].<ref name =sanatoria>{{cite journal | vauthors = McCarthy OR | title = The key to the sanatoria | journal = Journal of the Royal Society of Medicine | volume = 94 | issue = 8 | pages = 413–17 | date = August 2001 | pmid = 11461990 | pmc = 1281640 | url = http://www.jrsm.org/cgi/pmidlookup?view=long&pmid=11461990 | doi = 10.1177/014107680109400813 | access-date = 28 September 2011 | archive-date = 3 August 2012 | archive-url = https://archive.today/20120803180504/http://www.jrsm.org/cgi/pmidlookup?view=long&pmid=11461990 | url-status = live }}</ref> In 1865, [[Jean Antoine Villemin]] demonstrated that tuberculosis could be transmitted, via inoculation, from humans to animals and among animals.<ref>{{cite journal |vauthors=Villemin JA |title=Cause et nature de la tuberculose |journal=Bulletin de l'Académie Impériale de Médecine |date=1865 |volume=31 |pages=211–216 |url=https://babel.hathitrust.org/cgi/pt?id=hvd.32044103060562&view=1up&seq=215 |trans-title=Cause and nature of tuberculosis |language=fr |access-date=6 December 2020 |archive-date=9 December 2021 |archive-url=https://web.archive.org/web/20211209200251/https://babel.hathitrust.org/cgi/pt?id=hvd.32044103060562&view=1up&seq=215 |url-status=live }} * See also: {{cite book |vauthors=Villemin JA |title=Etudes sur la tuberculose: preuves rationnelles et expérimentales de sa spécificité et de son inoculabilité |trans-title=Studies of tuberculosis: rational and experimental evidence of its specificity and inoculability |date=1868 |publisher=J.-B. Baillière et fils |location=Paris, France |url=https://books.google.com/books?id=JFg7AAAAcAAJ&pg=PP7 |language=fr |access-date=6 December 2020 |archive-date=7 February 2024 |archive-url=https://web.archive.org/web/20240207093804/https://books.google.com/books?id=JFg7AAAAcAAJ&pg=PP7#v=onepage&q&f=false |url-status=live }}</ref> (Villemin's findings were confirmed in 1867 and 1868 by [[John Burdon-Sanderson]].<ref>Burdon-Sanderson, John Scott. (1870) "Introductory Report on the Intimate Pathology of Contagion." Appendix to: Twelfth Report to the Lords of Her Majesty's Most Honourable Privy Council of the Medical Officer of the Privy Council [for the year 1869], Parliamentary Papers (1870), vol. 38, 229–256.</ref>) [[File:RobertKoch.jpg|upright|thumb|Robert Koch discovered the tuberculosis bacillus.]] [[Robert Koch]] identified and described the bacillus causing tuberculosis, ''M. tuberculosis'', on 24 March 1882.<ref>{{cite book | vauthors = Koch R | title = Robert Koch: Zentrale Texte | chapter = Die Ätiologie der Tuberkulose (1882) |series=Klassische Texte der Wissenschaft |date=24 March 1882|trans-title=The Etiology of Tuberculosis| chapter-url = http://edoc.rki.de/docviews/abstract.php?id=610|volume=19|pages=221–30|doi=10.1007/978-3-662-56454-7_4|isbn=978-3-662-56454-7|access-date=15 June 2021|archive-date=6 November 2018|archive-url= https://web.archive.org/web/20181106191545/https://babel.hathitrust.org/cgi/pt?id=mdp.39015020075001;view=1up;seq=235|url-status=live|publisher=Springer Spektrum|location=Berlin, Heidelberg}}</ref><ref name="discoverydate">{{cite web|url=https://www.cdc.gov/tb/worldtbday/history.htm|title=History: World TB Day|publisher=[[Centers for Disease Control and Prevention]] (CDC)|url-status=live|access-date=23 March 2019|date=12 December 2016|archive-date=7 December 2018|archive-url=https://web.archive.org/web/20181207112253/https://www.cdc.gov/tb/worldtbday/history.htm}}</ref> In 1905, he was awarded the [[Nobel Prize in Physiology or Medicine]] for this discovery.<ref>{{Cite web|title=The Nobel Prize in Physiology or Medicine 1905|url=https://www.nobelprize.org/prizes/medicine/1905/summary/|access-date=7 October 2006|archive-url=https://web.archive.org/web/20061210184150/http://nobelprize.org/nobel_prizes/medicine/laureates/1905/|archive-date=10 December 2006|url-status=live|website=www.nobelprize.org|language=en-US}}</ref> ===Development of treatments=== 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.<ref>{{cite book| vauthors = Bloom BR |title= Tuberculosis: pathogenesis, protection, and control|year= 1994|publisher= ASM Press|location= Washington, DC|isbn= 978-1-55581-072-6|url-access= registration|url= https://archive.org/details/tuberculosispath0000unse}}</ref> In the 18th and 19th century, [[History of tuberculosis#Epidemic tuberculosis|tuberculosis had become epidemic in Europe]], showing a seasonal pattern.<ref name=":02">{{Cite web| vauthors = Frith J |title=History of Tuberculosis. Part 1 – Phthisis, consumption and the White Plague|url=https://jmvh.org/article/history-of-tuberculosis-part-1-phthisis-consumption-and-the-white-plague/|url-status=live|access-date=26 February 2021|website=Journal of Military and Veterans' Health|archive-date=8 April 2021|archive-url=https://web.archive.org/web/20210408050305/https://jmvh.org/article/history-of-tuberculosis-part-1-phthisis-consumption-and-the-white-plague/}}</ref><ref name=":5">{{cite journal | vauthors = Zürcher K, Zwahlen M, Ballif M, Rieder HL, Egger M, Fenner L | title = Influenza Pandemics and Tuberculosis Mortality in 1889 and 1918: Analysis of Historical Data from Switzerland | journal = PLOS ONE | volume = 11 | issue = 10 | pages = e0162575 | date = 5 October 2016 | pmid = 27706149 | pmc = 5051959 | doi = 10.1371/journal.pone.0162575 | doi-access = free | bibcode = 2016PLoSO..1162575Z }}</ref> 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.{{Citation needed|date=August 2020}} After TB was determined to be contagious, in the 1880s, it was put on a [[List of notifiable diseases|notifiable-disease]] list in Britain; campaigns started to stop people from spitting in public places, and the infected poor were "encouraged" to enter [[sanatorium|sanatoria]] that resembled prisons (the sanatoria for the middle and upper classes offered excellent care and constant medical attention).<ref name =sanatoria/> 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).<ref name =sanatoria/> Robert 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". Although it was not effective, it was later successfully adapted as a screening test for the presence of pre-symptomatic tuberculosis.<ref>{{cite journal | vauthors = Waddington K | title = To stamp out 'so terrible a malady': bovine tuberculosis and tuberculin testing in Britain, 1890–1939 | journal = Medical History | volume = 48 | issue = 1 | pages = 29–48 | date = January 2004 | pmid = 14968644 | pmc = 546294 | doi = 10.1017/S0025727300007043 }}</ref> [[World Tuberculosis Day]] is marked on 24 March each year, the anniversary of Koch's original scientific announcement. When the [[Medical Research Council (UK)|Medical Research Council]] formed in Britain in 1913, it initially focused on tuberculosis research.<ref>{{cite book | vauthors = Hannaway C |title= Biomedicine in the twentieth century: practices, policies, and politics|year= 2008|publisher= IOS Press|location= Amsterdam|isbn=978-1-58603-832-8|page= 233|url= https://books.google.com/books?id=o5HBxyg5APIC&pg=PA233|url-status=live|archive-url= https://web.archive.org/web/20150907185226/https://books.google.com/books?id=o5HBxyg5APIC&pg=PA233|archive-date= 7 September 2015}}</ref> [[Albert Calmette]] and [[Camille Guérin]] achieved the first genuine success in immunization against tuberculosis in 1906, using attenuated bovine-strain tuberculosis. It was called [[BCG vaccine|bacille Calmette–Guérin]] (BCG). The BCG vaccine was first used on humans in 1921 in France,<ref name=Bonah>{{cite journal | vauthors = Bonah C | title = The 'experimental stable' of the BCG vaccine: safety, efficacy, proof, and standards, 1921–1933 | journal = Studies in History and Philosophy of Biological and Biomedical Sciences | volume = 36 | issue = 4 | pages = 696–721 | date = December 2005 | pmid = 16337557 | doi = 10.1016/j.shpsc.2005.09.003 }}</ref> but achieved widespread acceptance in the US, Great Britain, and Germany only after World War II.<ref name=Comstock>{{cite journal | vauthors = Comstock GW | title = The International Tuberculosis Campaign: a pioneering venture in mass vaccination and research | journal = Clinical Infectious Diseases | volume = 19 | issue = 3 | pages = 528–40 | date = September 1994 | pmid = 7811874 | doi = 10.1093/clinids/19.3.528 }}</ref> <!-- Effective management --> By the 1950s mortality in Europe had decreased about 90%.<ref name=Per2010>{{cite book| vauthors = Persson S |title= Smallpox, Syphilis and Salvation: Medical Breakthroughs That Changed the World|year= 2010|publisher= ReadHowYouWant.com|isbn= 978-1-4587-6712-7|page= 141|url= https://books.google.com/books?id=-W7ch1d6JOoC&pg=PA141|url-status=live|archive-url= https://web.archive.org/web/20150906192102/https://books.google.com/books?id=-W7ch1d6JOoC&pg=PA141|archive-date= 6 September 2015}}</ref> 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.<ref name=Per2010/> 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.<ref>{{cite book| vauthors = Shields T |title= General thoracic surgery|year= 2009|publisher= Wolters Kluwer Health/Lippincott Williams & Wilkins|location= Philadelphia|isbn= 978-0-7817-7982-1|page= 792|url= https://books.google.com/books?id=bVEEHmpU-1wC&pg=PA792|edition= 7th|url-status=live|archive-url= https://web.archive.org/web/20150906212146/https://books.google.com/books?id=bVEEHmpU-1wC&pg=PA792|archive-date= 6 September 2015}}</ref> ===Current reemergence=== Because of the emergence of [[multidrug-resistant tuberculosis]] (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.<ref>{{cite journal | vauthors = Lalloo UG, Naidoo R, Ambaram A | s2cid = 24221563 | title = Recent advances in the medical and surgical treatment of multi-drug resistant tuberculosis | journal = Current Opinion in Pulmonary Medicine | volume = 12 | issue = 3 | pages = 179–85 | date = May 2006 | pmid = 16582672 | doi = 10.1097/01.mcp.0000219266.27439.52 }}</ref> Hopes of eliminating TB ended with the rise of [[Antibiotic resistant|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.<ref>{{cite web |title= Frequently asked questions about TB and HIV |url=https://www.who.int/tb/hiv/faq/en/index.html |publisher=World Health Organization (WHO) |access-date= 15 April 2012 |archive-url= https://web.archive.org/web/20110808115404/http://www.who.int/tb/hiv/faq/en/ |archive-date= 8 August 2011 |url-status=dead }}</ref> == Signs and symptoms == [[File:Tuberculosis symptoms.svg|thumb|upright=1.5|The main symptoms of variants and stages of tuberculosis are given,<ref>{{cite web|url=http://www.emedicinehealth.com/tuberculosis/page3_em.htm|title=Tuberculosis Symptoms|publisher=eMedicine Health| vauthors = Schiffman G |date=15 January 2009|url-status=live|archive-url=https://web.archive.org/web/20090516075020/http://www.emedicinehealth.com/tuberculosis/page3_em.htm|archive-date=16 May 2009}}</ref> 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).<ref name=ID10/> Extrapulmonary TB occurs when tuberculosis develops outside of the lungs, although extrapulmonary TB may coexist with pulmonary TB.<ref name=ID10/> General signs and symptoms include fever, [[chills]], night sweats, [[Anorexia (symptom)|loss of appetite]], weight loss, and [[fatigue (medical)|fatigue]].<ref name=ID10/> Significant [[nail clubbing]] may also occur.<ref name="Pet2005">{{cite book|url=http://www.wiley.com/WileyCDA/WileyTitle/productCd-072791605X.html|title=Evidence-Based Respiratory Medicine|date=2005|publisher=BMJ Books|isbn=978-0-7279-1605-1|veditors=Gibson PG, Abramson M, Wood-Baker R, Volmink J, Hensley M, Costabel U|edition=1st|page=321|archive-url=https://web.archive.org/web/20151208072842/http://www.wiley.com/WileyCDA/WileyTitle/productCd-072791605X.html|archive-date=8 December 2015|url-status=live}}</ref> === Pulmonary === If a tuberculosis infection does become active, it most commonly involves the lungs (in about 90% of cases).<ref name=Lancet11/><ref>{{cite book| vauthors = Behera D |title=Textbook of Pulmonary Medicine|year=2010|publisher=Jaypee Brothers Medical Publishers|location=New Delhi|isbn=978-81-8448-749-7|page=457|url=https://books.google.com/books?id=0TbJjd9eTp0C&pg=PA457|edition=2nd|url-status=live|archive-url=https://web.archive.org/web/20150906185549/https://books.google.com/books?id=0TbJjd9eTp0C&pg=PA457|archive-date=6 September 2015}}</ref> Symptoms may include [[chest pain]] and a prolonged cough producing sputum.<!-- <ref name=Lancet11/> --> About 25% of people may not have any symptoms (i.e., they remain asymptomatic).<ref name=Lancet11/> Occasionally, people may [[hemoptysis|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.<ref name=ID10/><ref>{{cite journal | vauthors = Halezeroğlu S, Okur E | title = Thoracic surgery for haemoptysis in the context of tuberculosis: what is the best management approach? | journal = Journal of Thoracic Disease | volume = 6 | issue = 3 | pages = 182–85 | date = March 2014 | pmid = 24624281 | pmc = 3949181 | doi = 10.3978/j.issn.2072-1439.2013.12.25 }}</ref> Tuberculosis may become a chronic illness and cause extensive scarring in the upper lobes of the lungs.<!-- <ref name=ID10/> --> The upper lung lobes are more frequently affected by tuberculosis than the lower ones.<ref name=ID10/> The reason for this difference is not clear.<ref name="Robbins" /> It may be due to either better air flow,<ref name="Robbins" /> or poor [[lymph]] drainage within the upper lungs.<ref name=ID10/> === Extrapulmonary === {{Main|Extrapulmonary tuberculosis}} In 15–20% of active cases, the infection spreads outside the lungs, causing other kinds of TB.<ref>{{cite book| veditors = Jindal SK |title=Textbook of Pulmonary and Critical Care Medicine|publisher=Jaypee Brothers Medical Publishers|location=New Delhi|isbn=978-93-5025-073-0|page=549|url=https://books.google.com/books?id=EvGTw3wn-zEC&pg=PA549|year=2011|url-status=live|archive-url=https://web.archive.org/web/20150907185434/https://books.google.com/books?id=EvGTw3wn-zEC&pg=PA549|archive-date=7 September 2015}}</ref> These are collectively denoted as extrapulmonary tuberculosis.<ref name=Extra2005>{{cite journal | vauthors = Golden MP, Vikram HR | title = Extrapulmonary tuberculosis: an overview | journal = American Family Physician | volume = 72 | issue = 9 | pages = 1761–68 | date = November 2005 | pmid = 16300038 }}</ref> Extrapulmonary TB occurs more commonly in people with a [[Immunosuppression|weakened immune system]] and young children. In those with HIV, this occurs in more than 50% of cases.<ref name=Extra2005/> Notable extrapulmonary infection sites include the [[Pleural cavity|pleura]] (in tuberculous pleurisy), the [[central nervous system]] (in [[tuberculous meningitis]]), the [[lymphatic system]] (in [[Tuberculous cervical lymphadenitis|scrofula]] of the neck), the [[genitourinary system]] (in [[urogenital tuberculosis]]), and the [[bone]]s and joints (in [[Pott disease]] of the spine), among others. A potentially more serious, widespread form of TB is called "disseminated tuberculosis"; it is also known as [[miliary tuberculosis]].<ref name=ID10/> Miliary TB currently makes up about 10% of extrapulmonary cases.<ref name=Gho2008/> == Causes == === Mycobacteria === {{Main| Mycobacterium tuberculosis}} [[File:Mycobacterium tuberculosis.jpg|thumb|[[Scanning electron micrograph]] of ''M. tuberculosis'']] The main cause of TB is ''[[Mycobacterium tuberculosis]]'' (MTB), a small, [[aerobic organism|aerobic]], nonmotile [[bacillus]].<ref name=ID10/> The high [[lipid]] content of this [[pathogen]] accounts for many of its unique clinical characteristics.<ref>{{cite book | vauthors = Southwick F |title=Infectious Diseases: A Clinical Short Course, 2nd ed. |publisher=McGraw-Hill Medical Publishing Division |year=2007 |pages=104, 313–14 |chapter=Chapter 4: Pulmonary Infections |isbn=978-0-07-147722-2}}</ref> It [[cell division|divides]] every 16 to 20 hours, which is an extremely slow rate compared with other bacteria, which usually divide in less than an hour.<ref>{{cite book| vauthors = Jindal SK |title=Textbook of Pulmonary and Critical Care Medicine|publisher=Jaypee Brothers Medical Publishers|location=New Delhi|isbn=978-93-5025-073-0|page=525|url=https://books.google.com/books?id=rAT1bdnDakAC&pg=PA525|year=2011|url-status=live|archive-url=https://web.archive.org/web/20150906211342/https://books.google.com/books?id=rAT1bdnDakAC&pg=PA525|archive-date=6 September 2015}}</ref> Mycobacteria have an [[Bacterial cell structure|outer membrane]] lipid bilayer.<ref name=Niederweis2010>{{cite journal | vauthors = Niederweis M, Danilchanka O, Huff J, Hoffmann C, Engelhardt H | title = Mycobacterial outer membranes: in search of proteins | journal = Trends in Microbiology | volume = 18 | issue = 3 | pages = 109–16 | date = March 2010 | pmid = 20060722 | pmc = 2931330 | doi = 10.1016/j.tim.2009.12.005 }}</ref> 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.<ref name=Madison_2001>{{cite journal | vauthors = Madison BM | title = Application of stains in clinical microbiology | journal = Biotechnic & Histochemistry | volume = 76 | issue = 3 | pages = 119–25 | date = May 2001 | pmid = 11475314 | doi = 10.1080/714028138 }}</ref> MTB can withstand weak [[disinfectant]]s and survive in a [[Endospore|dry state]] for weeks. In nature, the bacterium can grow only within the cells of a [[host (biology)|host]] organism, but ''M. tuberculosis'' can be cultured [[in vitro|in the laboratory]].<ref name=Parish_1999>{{cite journal | vauthors = Parish T, Stoker NG | s2cid = 28960959 | title = Mycobacteria: bugs and bugbears (two steps forward and one step back) | journal = Molecular Biotechnology | volume = 13 | issue = 3 | pages = 191–200 | date = December 1999 | pmid = 10934532 | doi = 10.1385/MB:13:3:191 | doi-access = free }}</ref> Using [[histology|histological]] stains on [[expectorate]]d 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]].<ref name=Robbins/><ref name="Madison_2001"/> The most common acid-fast staining techniques are the [[Ziehl–Neelsen stain]]<ref name=Stain2000>{{cite book |title=Medical Laboratory Science: Theory and Practice |publisher=Tata McGraw-Hill |location=New Delhi |year=2000 |page=473 |isbn=978-0-07-463223-9 |url=https://books.google.com/books?id=lciNs3VQPLoC&pg=PA473 |url-status=live |archive-url=https://web.archive.org/web/20150906213737/https://books.google.com/books?id=lciNs3VQPLoC&pg=PA473 |archive-date=6 September 2015 }}</ref> and the [[Kinyoun stain]], which dye acid-fast bacilli a bright red that stands out against a blue background.<ref>{{cite web |title=Acid-Fast Stain Protocols |url=http://www.microbelibrary.org/component/resource/laboratory-test/2870-acid-fast-stain-protocols |access-date=26 March 2016 |date=21 August 2013 |url-status=dead |archive-url=https://web.archive.org/web/20111001132818/http://www.microbelibrary.org/component/resource/laboratory-test/2870-acid-fast-stain-protocols |archive-date=1 October 2011 }}</ref> [[Auramine-rhodamine stain]]ing<ref name=Kommareddi_1984>{{cite journal | vauthors = Kommareddi S, Abramowsky CR, Swinehart GL, Hrabak L | title = Nontuberculous mycobacterial infections: comparison of the fluorescent auramine-O and Ziehl-Neelsen techniques in tissue diagnosis | journal = Human Pathology | volume = 15 | issue = 11 | pages = 1085–9 | date = November 1984 | pmid = 6208117 | doi = 10.1016/S0046-8177(84)80253-1 }}</ref> and [[Fluorescence microscope|fluorescence microscopy]]<ref>{{cite book | vauthors = van Lettow M, Whalen C |title=Nutrition and health in developing countries|year=2008|publisher=Humana Press|location=Totowa, N.J. | veditors = Semba RD, Bloem MW |isbn=978-1-934115-24-4 |page=291 |url=https://books.google.com/books?id=RhH6uSQy7a4C&pg=PA291 |edition=2nd|url-status=live|archive-url=https://web.archive.org/web/20150906215906/https://books.google.com/books?id=RhH6uSQy7a4C&pg=PA291|archive-date=6 September 2015}}</ref> are also used. The [[Mycobacterium tuberculosis complex|''M. tuberculosis'' complex]] (MTBC) includes four other TB-causing [[mycobacterium|mycobacteria]]: ''[[Mycobacterium bovis|M. bovis]]'', ''[[Mycobacterium africanum|M. africanum]]'', ''[[Mycobacterium canettii|M. canettii]]'', and ''[[Mycobacterium microti|M. microti]]''.<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = A novel pathogenic taxon of the Mycobacterium tuberculosis complex, Canetti: characterization of an exceptional isolate from Africa | journal = International Journal of Systematic Bacteriology | volume = 47 | issue = 4 | pages = 1236–45 | date = October 1997 | pmid = 9336935 | doi = 10.1099/00207713-47-4-1236 | doi-access = free }}</ref> ''M. africanum'' is not widespread, but it is a significant cause of tuberculosis in parts of Africa.<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Mycobacterium africanum subtype II is associated with two distinct genotypes and is a major cause of human tuberculosis in Kampala, Uganda | journal = Journal of Clinical Microbiology | volume = 40 | issue = 9 | pages = 3398–405 | date = September 2002 | pmid = 12202584 | pmc = 130701 | doi = 10.1128/JCM.40.9.3398-3405.2002 }}</ref><ref>{{cite journal | vauthors = Niobe-Eyangoh SN, Kuaban C, Sorlin P, Cunin P, Thonnon J, Sola C, Rastogi N, Vincent V, Gutierrez MC | display-authors = 6 | title = Genetic biodiversity of Mycobacterium tuberculosis complex strains from patients with pulmonary tuberculosis in Cameroon | journal = Journal of Clinical Microbiology | volume = 41 | issue = 6 | pages = 2547–53 | date = June 2003 | pmid = 12791879 | pmc = 156567 | doi = 10.1128/JCM.41.6.2547-2553.2003 }}</ref> ''M. bovis'' was once a common cause of tuberculosis, but the introduction of [[pasteurisation|pasteurized milk]] has almost eliminated this as a public health problem in developed countries.<ref name=Robbins/><ref>{{cite journal | vauthors = Thoen C, Lobue P, de Kantor I | title = The importance of Mycobacterium bovis as a zoonosis | journal = Veterinary Microbiology | volume = 112 | issue = 2–4 | pages = 339–45 | date = February 2006 | pmid = 16387455 | doi = 10.1016/j.vetmic.2005.11.047 }}</ref> ''M. canettii'' is rare and seems to be limited to the [[Horn of Africa]], although a few cases have been seen in African emigrants.<ref>{{cite book| vauthors = Acton QA |title=Mycobacterium Infections: New Insights for the Healthcare Professional|year=2011|publisher=ScholarlyEditions|isbn=978-1-4649-0122-5|page=1968|url=https://books.google.com/books?id=g2iFfV6uEuAC&pg=PA1968|url-status=live|archive-url=https://web.archive.org/web/20150906201531/https://books.google.com/books?id=g2iFfV6uEuAC&pg=PA1968|archive-date=6 September 2015}}</ref><ref>{{cite journal | vauthors = Pfyffer GE, Auckenthaler R, van Embden JD, van Soolingen D | title = Mycobacterium canettii, the smooth variant of M. tuberculosis, isolated from a Swiss patient exposed in Africa | journal = Emerging Infectious Diseases | volume = 4 | issue = 4 | pages = 631–4 | date = 1998 | pmid = 9866740 | pmc = 2640258 | doi = 10.3201/eid0404.980414 }}</ref> ''M. microti'' is also rare and is seen almost only in immunodeficient people, although its [[prevalence]] may be significantly underestimated.<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Pulmonary tuberculosis due to Mycobacterium microti: a study of six recent cases in France | journal = Journal of Medical Microbiology | volume = 59 | issue = Pt 8 | pages = 984–989 | date = August 2010 | pmid = 20488936 | doi = 10.1099/jmm.0.019372-0 | doi-access = free }}</ref> Other known pathogenic mycobacteria include ''[[Mycobacterium leprae|M. leprae]]'', ''[[Mycobacterium avium complex|M. avium]]'', and ''[[Mycobacterium kansasii|M. kansasii]]''. The latter two species are classified as "[[nontuberculous mycobacteria]]" (NTM) or atypical mycobacteria. NTM cause neither TB nor [[leprosy]], but they do cause lung diseases that resemble TB.<ref name=ALA_1997>{{cite journal | author = American Thoracic Society | title = Diagnosis and treatment of disease caused by nontuberculous mycobacteria | journal = American Journal of Respiratory and Critical Care Medicine | volume = 156 | issue = 2 Pt 2 | pages = S1–25 | date = August 1997 | pmid = 9279284 | doi = 10.1164/ajrccm.156.2.atsstatement }}</ref>[[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.<ref name=Cole_1998>{{cite journal | vauthors = Cole EC, Cook CE | title = Characterization of infectious aerosols in health care facilities: an aid to effective engineering controls and preventive strategies | journal = American Journal of Infection Control | volume = 26 | issue = 4 | pages = 453–64 | date = August 1998 | pmid = 9721404 | doi = 10.1016/S0196-6553(98)70046-X | pmc = 7132666 }}</ref> 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).<ref>{{cite journal | vauthors = Nicas M, Nazaroff WW, Hubbard A | title = Toward understanding the risk of secondary airborne infection: emission of respirable pathogens | journal = Journal of Occupational and Environmental Hygiene | volume = 2 | issue = 3 | pages = 143–54 | date = March 2005 | pmid = 15764538 | doi = 10.1080/15459620590918466 | pmc = 7196697 }}</ref> ==== Risk of transmission ==== 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.<ref name="Ahmed_2011">{{cite journal | vauthors = Ahmed N, Hasnain SE | title = Molecular epidemiology of tuberculosis in India: moving forward with a systems biology approach | journal = Tuberculosis | volume = 91 | issue = 5 | pages = 407–13 | date = September 2011 | pmid = 21514230 | doi = 10.1016/j.tube.2011.03.006 }}</ref> A person with active but untreated tuberculosis may infect 10–15 (or more) other people per year.<ref name="WHO2012data" /> Transmission should occur from only people with active TB – those with latent infection are not thought to be contagious.<ref name="Robbins" /> 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 (biology)|strain]], the level of immunity in the uninfected person, and others.<ref name="CDCcourse">{{cite web|publisher=[[Centers for Disease Control and Prevention]] (CDC), Division of Tuberculosis Elimination|url=https://www.cdc.gov/tb/education/corecurr/pdf/corecurr_all.pdf|title=Core Curriculum on Tuberculosis: What the Clinician Should Know|page=24|edition=5th|year=2011|url-status=live|archive-url=https://web.archive.org/web/20120519141115/http://www.cdc.gov/tb/education/corecurr/pdf/corecurr_all.pdf|archive-date=19 May 2012}}</ref> 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 [[Antibiotic resistance|nonresistant]] active infections generally do not remain contagious to others.<ref name="Ahmed_2011" /> 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.<ref>{{cite web|url=http://www.mayoclinic.com/health/tuberculosis/DS00372/DSECTION=3|title=Causes of Tuberculosis|access-date=19 October 2007|date=21 December 2006|publisher=[[Mayo Clinic]]|url-status=live|archive-url=https://web.archive.org/web/20071018051807/http://www.mayoclinic.com/health/tuberculosis/DS00372/DSECTION%3D3|archive-date=18 October 2007}}</ref> === Risk factors === {{Main|Risk factors for tuberculosis}} A number of factors make individuals more susceptible to TB infection and/or disease.<ref name=":0">{{cite journal | vauthors = Narasimhan P, Wood J, Macintyre CR, Mathai D | title = Risk factors for tuberculosis | journal = Pulmonary Medicine | volume = 2013 | pages = 828939 | date = 2013 | pmid = 23476764 | pmc = 3583136 | doi = 10.1155/2013/828939 | doi-access = free }}</ref> ==== Active disease risk ==== The most important risk factor globally for developing active TB is concurrent HIV infection; 13% of those with TB are also infected with HIV.<ref name="WHO2011">{{cite web|year=2011|title=The sixteenth global report on tuberculosis|url=https://www.who.int/tb/publications/global_report/2011/gtbr11_executive_summary.pdf|url-status=dead|archive-url=https://web.archive.org/web/20120906223650/http://www.who.int/tb/publications/global_report/2011/gtbr11_executive_summary.pdf|archive-date=6 September 2012|publisher=World Health Organization (WHO)}}</ref> This is a particular problem in [[sub-Saharan Africa]], where HIV infection rates are high.<ref>{{cite web |title = Global tuberculosis control–surveillance, planning, financing WHO Report 2006 |url= https://www.who.int/tb/publications/global_report/en/index.html |url-status=live |archive-url= https://web.archive.org/web/20061212123736/http://www.who.int/tb/publications/global_report/en/index.html|archive-date=12 December 2006|access-date=13 October 2006|publisher=World Health Organization (WHO) }}</ref><ref>{{cite journal|vauthors=Chaisson RE, Martinson NA|date=March 2008|title=Tuberculosis in Africa – combating an HIV-driven crisis|journal=The New England Journal of Medicine|volume=358|issue=11|pages=1089–92|doi=10.1056/NEJMp0800809|pmid=18337598|doi-access=free}}</ref> Of those without HIV infection who are infected with tuberculosis, about 5–10% develop active disease during their lifetimes;<ref name="Pet2005" /> in contrast, 30% of those co-infected with HIV develop the active disease.<ref name="Pet2005" /> Use of certain medications, such as [[corticosteroids]] and [[infliximab]] (an anti-αTNF monoclonal antibody), is another important risk factor, especially in the [[developed world]].<ref name="Lancet11" /> Other risk factors include: [[alcoholism]],<ref name="Lancet11" /> [[diabetes mellitus]] (3-fold increased risk),<ref>{{cite journal|vauthors=Restrepo BI|date=August 2007|title=Convergence of the tuberculosis and diabetes epidemics: renewal of old acquaintances|journal=Clinical Infectious Diseases|volume=45|issue=4|pages=436–38|doi=10.1086/519939|pmc=2900315|pmid=17638190}}</ref> [[silicosis]] (30-fold increased risk),<ref name="table3">{{cite journal|date=June 2000|title=Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/rr4906a1.htm#tab3|url-status=live|journal=MMWR. Recommendations and Reports|volume=49|issue=RR-6|pages=1–51|pmid=10881762|archive-url=https://web.archive.org/web/20041217172736/http://www.cdc.gov/MMWR/preview/mmwrhtml/rr4906a1.htm#tab3|archive-date=17 December 2004}}</ref> [[cigarette|tobacco smoking]] (2-fold increased risk),<ref>{{cite journal|display-authors=6|vauthors=van Zyl Smit RN, Pai M, Yew WW, Leung CC, Zumla A, Bateman ED, Dheda K|date=January 2010|title=Global lung health: the colliding epidemics of tuberculosis, tobacco smoking, HIV and COPD|journal=The European Respiratory Journal|volume=35|issue=1|pages=27–33|doi=10.1183/09031936.00072909|pmc=5454527 |doi-access=free |pmid=20044459|quote=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.}}</ref> [[indoor air quality|indoor air pollution]], malnutrition, young age,<ref name=":0" /> recently acquired TB infection, recreational drug use, severe kidney disease, low body weight, organ transplant, head and neck cancer,<ref>{{Cite web|date=March 18, 2016 |title=TB Risk Factors |url=https://www.cdc.gov/tb/topic/basics/risk.htm|access-date=25 August 2020|website=CDC |language=en-us|archive-date=30 August 2020|archive-url=https://web.archive.org/web/20200830234002/https://www.cdc.gov/tb/topic/basics/risk.htm|url-status=live}}</ref> and [[genetic susceptibility]]<ref>{{cite journal|vauthors=Möller M, Hoal EG|date=March 2010|title=Current findings, challenges and novel approaches in human genetic susceptibility to tuberculosis|journal=Tuberculosis|volume=90|issue=2|pages=71–83|doi=10.1016/j.tube.2010.02.002|pmid=20206579}}</ref> (the overall importance of genetic risk factors remains undefined<ref name="Lancet11" />). ==== Infection susceptibility ==== Tobacco smoking increases the risk of infections (in addition to increasing the risk of active disease and death). Additional factors increasing infection susceptibility include young age.<ref name=":0" /> == Pathogenesis == [[File:Carswell-Tubercle.jpg|thumb|upright|[[Robert Carswell (pathologist)|Robert Carswell]]'s illustration of tubercle<ref name="GoodCooper1835">{{cite book| vauthors = Good JM, Cooper S, Doane AS |title=The Study of Medicine|url=https://books.google.com/books?id=K906AQAAMAAJ&pg=PA32|year=1835|publisher=Harper|page=32|url-status=live|archive-url=https://web.archive.org/web/20160810194616/https://books.google.com/books?id=K906AQAAMAAJ&pg=PA32|archive-date=10 August 2016}}</ref>]] About 90% of those infected with ''M. tuberculosis'' have [[asymptomatic]], latent TB infections (sometimes called LTBI),<ref name=Book90>{{cite book| vauthors = Skolnik R |title=Global health 101|year=2011|publisher=Jones & Bartlett Learning|location=Burlington, MA|isbn=978-0-7637-9751-5|page=[https://archive.org/details/globalhealth1010000skol/page/253 253]|url=https://archive.org/details/globalhealth1010000skol|url-access=registration|edition=2nd}}</ref> with only a 10% lifetime chance that the latent infection will progress to overt, active tuberculous disease.<ref name=Arch2009>{{cite book | vauthors = Mainous III AR, Pomeroy C |title=Management of antimicrobials in infectious diseases: impact of antibiotic resistance|year=2009|publisher=Humana Press|location=Totowa, NJ|isbn=978-1-60327-238-4|page=74|url=https://books.google.com/books?id=hwVFAPLYznsC&pg=PA74|edition=2nd rev.|url-status=live|archive-url=https://web.archive.org/web/20150906224212/https://books.google.com/books?id=hwVFAPLYznsC&pg=PA74|archive-date=6 September 2015}}</ref> In those with HIV, the risk of developing active TB increases to nearly 10% a year.<ref name=Arch2009/> If effective treatment is not given, the death rate for active TB cases is up to 66%.<ref name=WHO2012data>{{cite web|url=https://www.who.int/mediacentre/factsheets/fs104/en/index.html|title=Tuberculosis Fact sheet N°104|publisher=[[World Health Organization]] (WHO)|date=November 2010|access-date=26 July 2011|url-status=live|archive-url=https://web.archive.org/web/20061004013508/http://www.who.int/mediacentre/factsheets/fs104/en/index.html|archive-date=4 October 2006}}</ref> [[File:Tuberculous epididymitis Low Power.jpg|thumb|Microscopy of tuberculous epididymitis. [[H&E]] stain]] TB infection begins when the mycobacteria reach the [[Pulmonary alveolus|alveolar air sacs]] of the lungs, where they invade and replicate within [[endosomes]] of alveolar [[macrophages]].<ref name=Robbins/><ref name=Houben>{{cite journal | vauthors = Houben EN, Nguyen L, Pieters J | title = Interaction of pathogenic mycobacteria with the host immune system | journal = Current Opinion in Microbiology | volume = 9 | issue = 1 | pages = 76–85 | date = February 2006 | pmid = 16406837 | doi = 10.1016/j.mib.2005.12.014 }}</ref><ref>{{cite journal | vauthors = Queval CJ, Brosch R, Simeone R | title = Mycobacterium tuberculosis | journal = Frontiers in Microbiology | volume = 8 | page= 2284 | year = 2017 | pmid = 29218036 | pmc = 5703847 | doi = 10.3389/fmicb.2017.02284 | doi-access = free }}</ref> 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 [[lung|upper lobe]].<ref name=Robbins/> 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.<ref>{{cite book| vauthors = Khan MR |title=Essence of Paediatrics|year=2011|publisher=Elsevier India|isbn=978-81-312-2804-3|page=401|url=https://books.google.com/books?id=gERCc6KTxwoC&pg=PA401|url-status=live|archive-url=https://web.archive.org/web/20150906193259/https://books.google.com/books?id=gERCc6KTxwoC&pg=PA401|archive-date=6 September 2015}}</ref> This hematogenous transmission can also spread infection to more distant sites, such as peripheral lymph nodes, the kidneys, the brain, and the bones.<ref name=Robbins/><ref name=Herrmann_2005>{{cite journal | vauthors = Herrmann JL, Lagrange PH | title = Dendritic cells and Mycobacterium tuberculosis: which is the Trojan horse? | journal = Pathologie-Biologie | volume = 53 | issue = 1 | pages = 35–40 | date = February 2005 | pmid = 15620608 | doi = 10.1016/j.patbio.2004.01.004 }}</ref> All parts of the body can be affected by the disease, though for unknown reasons it rarely affects the [[heart]], [[skeletal muscle]]s, [[pancreas]], or [[thyroid]].<ref>{{cite journal | vauthors = Agarwal R, Malhotra P, Awasthi A, Kakkar N, Gupta D | title = Tuberculous dilated cardiomyopathy: an under-recognized entity? | journal = BMC Infectious Diseases | volume = 5 | issue = 1 | pages = 29 | date = April 2005 | pmid = 15857515 | pmc = 1090580 | doi = 10.1186/1471-2334-5-29 | doi-access = free }}</ref> Tuberculosis is classified as one of the [[granuloma]]tous inflammatory diseases. [[Macrophage]]s, [[epithelioid cell]]s, [[T cell|T lymphocytes]], [[B cell|B lymphocytes]], and [[fibroblast]]s <!-- are among the cells that --> 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.<ref name=Grosset /> However, more recent evidence suggests that the bacteria use the granulomas to avoid destruction by the host's immune system. Macrophages and [[dendritic cell]]s in the granulomas are unable to present antigen to lymphocytes; thus the immune response is suppressed.<ref>{{cite journal | vauthors = Bozzano F, Marras F, De Maria A | title = Immunology of tuberculosis | journal = Mediterranean Journal of Hematology and Infectious Diseases | volume = 6 | issue = 1 | page= e2014027 | year = 2014 | pmid = 24804000 | pmc = 4010607 | doi = 10.4084/MJHID.2014.027 }}</ref> 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 [[Tubercle (anatomy)|tubercles]]. To the naked eye, this has the texture of soft, white cheese and is termed [[caseous necrosis]].<ref name=Grosset>{{cite journal | vauthors = Grosset J | title = Mycobacterium tuberculosis in the extracellular compartment: an underestimated adversary | journal = Antimicrobial Agents and Chemotherapy | volume = 47 | issue = 3 | pages = 833–36 | date = March 2003 | pmid = 12604509 | pmc = 149338 | doi = 10.1128/AAC.47.3.833-836.2003 }}</ref> 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.<ref>{{cite book| vauthors = Crowley LV |title=An introduction to human disease: pathology and pathophysiology correlations|year=2010|publisher=Jones and Bartlett|location=Sudbury, MA|isbn=978-0-7637-6591-0|page=374|url=https://books.google.com/books?id=TEiuWP4z_QIC&pg=PA374|edition=8th|url-status=live|archive-url=https://web.archive.org/web/20150906193726/https://books.google.com/books?id=TEiuWP4z_QIC&pg=PA374|archive-date=6 September 2015}}</ref> This severe form of TB disease, most common in young children and those with HIV, is called miliary tuberculosis.<ref>{{cite book| vauthors = Harries AD, Maher D, Graham S |title=TB/HIV a Clinical Manual|year=2005|publisher=World Health Organization (WHO)|location=Geneva|isbn=978-92-4-154634-8|page=75|url=https://books.google.com/books?id=8dfhwKaCSxkC&pg=PA75|edition=2nd|url-status=live|archive-url=https://web.archive.org/web/20150906195514/https://books.google.com/books?id=8dfhwKaCSxkC&pg=PA75|archive-date=6 September 2015}}</ref> People with this disseminated TB have a high fatality rate even with treatment (about 30%).<ref name=Gho2008>{{cite book| vauthors = Habermann TM, Ghosh A |title=Mayo Clinic internal medicine: concise textbook|year=2008|publisher=Mayo Clinic Scientific Press|location=Rochester, MN|isbn=978-1-4200-6749-1|page=789|url=https://books.google.com/books?id=YJtodBwNxokC&pg=PA789|url-status=live|archive-url=https://web.archive.org/web/20150906190055/https://books.google.com/books?id=YJtodBwNxokC&pg=PA789|archive-date=6 September 2015}}</ref><ref>{{cite journal | vauthors = Jacob JT, Mehta AK, Leonard MK | title = Acute forms of tuberculosis in adults | journal = The American Journal of Medicine | volume = 122 | issue = 1 | pages = 12–17 | date = January 2009 | pmid = 19114163 | doi = 10.1016/j.amjmed.2008.09.018 }}</ref> In many people, the infection waxes and wanes. Tissue destruction and necrosis are often balanced by healing and [[fibrosis]].<ref name=Grosset/> 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 [[antibiotic]]s kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.<ref name=Grosset/> {{Clear}} == Diagnosis == {{Main|Tuberculosis diagnosis}} [[File:TB in sputum.png|thumb|''M. tuberculosis'' ([[Ziehl-Neelsen stain|stained red]]) in [[sputum]]]] === Active tuberculosis === Diagnosing active tuberculosis based only on signs and symptoms is difficult,<ref name=DiagP2011>{{cite journal | vauthors = Bento J, Silva AS, Rodrigues F, Duarte R | title = [Diagnostic tools in tuberculosis] | journal = Acta Médica Portuguesa | volume = 24 | issue = 1 | pages = 145–54 | date = 2011 | doi = 10.20344/amp.333 | pmid = 21672452 | s2cid = 76156550 | doi-access = free }}</ref> as is diagnosing the disease in those who have a weakened immune system.<ref name=Clinic2009>{{cite journal | vauthors = Escalante P | s2cid = 639982 | title = In the clinic. Tuberculosis | journal = Annals of Internal Medicine | volume = 150 | issue = 11 | pages = ITC61-614; quiz ITV616 | date = June 2009 | pmid = 19487708 | doi = 10.7326/0003-4819-150-11-200906020-01006 }}</ref> A diagnosis of TB should, however, be considered in those with signs of lung disease or [[constitutional symptoms]] lasting longer than two weeks.<ref name=Clinic2009/> A [[chest X-ray]] and multiple [[sputum culture]]s for [[acid-fast bacilli]] are typically part of the initial evaluation.<ref name=Clinic2009/> [[Interferon gamma release assay|Interferon-γ release assays]] (IGRA) and tuberculin skin tests are of little use in most of the developing world.<ref>{{cite journal | vauthors = Metcalfe JZ, Everett CK, Steingart KR, Cattamanchi A, Huang L, Hopewell PC, Pai M | title = Interferon-γ release assays for active pulmonary tuberculosis diagnosis in adults in low- and middle-income countries: systematic review and meta-analysis | journal = The Journal of Infectious Diseases | volume = 204 | issue = suppl_4 | pages = S1120-9 | date = November 2011 | pmid = 21996694 | pmc = 3192542 | doi = 10.1093/infdis/jir410 }}</ref><ref name="Sester 100–11">{{cite journal | vauthors = 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 | display-authors = 6 | title = Interferon-γ release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis | journal = The European Respiratory Journal | volume = 37 | issue = 1 | pages = 100–11 | date = January 2011 | pmid = 20847080 | doi = 10.1183/09031936.00114810 | doi-access = free }}</ref> IGRA have similar limitations in those with HIV.<ref name="Sester 100–11"/><ref>{{cite journal | vauthors = Chen J, Zhang R, Wang J, Liu L, Zheng Y, Shen Y, Qi T, Lu H | display-authors = 6 | title = Interferon-gamma release assays for the diagnosis of active tuberculosis in HIV-infected patients: a systematic review and meta-analysis | journal = PLOS ONE| volume = 6 | issue = 11 | pages = e26827 | year = 2011 | pmid = 22069472 | pmc = 3206065 | doi = 10.1371/journal.pone.0026827 | veditors = Vermund SH |editor1-link=Sten H. Vermund | bibcode = 2011PLoSO...626827C | doi-access = free }}</ref> A definitive diagnosis of TB is made by identifying ''M. tuberculosis'' in a clinical sample (e.g., sputum, [[pus]], or a [[Tissue (biology)|tissue]] [[biopsy]]). However, the difficult culture process for this slow-growing organism can take two to six weeks for blood or sputum culture.<ref>{{cite book | author = Special Programme for Research & Training in Tropical Diseases |title=Diagnostics for tuberculosis: global demand and market potential|year=2006|publisher=World Health Organization (WHO)|location=Geneva|isbn=978-92-4-156330-7|page=36|url=https://books.google.com/books?id=CFPpcCef4yQC&pg=PA36|url-status=live|archive-url=https://web.archive.org/web/20150906202315/https://books.google.com/books?id=CFPpcCef4yQC&pg=PA36|archive-date=6 September 2015}}</ref> Thus, treatment is often begun before cultures are confirmed.<ref name=NICE2011/> [[Nucleic acid amplification test]]s and [[adenosine deaminase]] testing may allow rapid diagnosis of TB.<ref name=DiagP2011/> Blood tests to detect antibodies are not [[sensitivity and specificity|specific or sensitive]], so they are not recommended.<ref>{{cite journal | vauthors = Steingart KR, Flores LL, Dendukuri N, Schiller I, Laal S, Ramsay A, Hopewell PC, Pai M | display-authors = 6 | title = Commercial serological tests for the diagnosis of active pulmonary and extrapulmonary tuberculosis: an updated systematic review and meta-analysis | journal = PLOS Medicine | volume = 8 | issue = 8 | page= e1001062 | date = August 2011 | pmid = 21857806 | pmc = 3153457 | doi = 10.1371/journal.pmed.1001062 | doi-access = free | veditors = Evans C }}</ref> === Latent tuberculosis === {{Main|Latent tuberculosis}} [[File:Mantoux tuberculin skin test.jpg|thumb|left|Mantoux tuberculin skin test]] The [[Mantoux test|Mantoux tuberculin skin test]] is often used to screen people at high risk for TB.<ref name=Clinic2009/> Those who have been previously immunized with the Bacille Calmette-Guerin vaccine may have a false-positive test result.<ref name=Rothel_2005>{{cite journal | vauthors = Rothel JS, Andersen P | s2cid = 25423684 | title = Diagnosis of latent Mycobacterium tuberculosis infection: is the demise of the Mantoux test imminent? | journal = Expert Review of Anti-Infective Therapy | volume = 3 | issue = 6 | pages = 981–93 | date = December 2005 | pmid = 16307510 | doi = 10.1586/14787210.3.6.981 }}</ref> The test may be falsely negative in those with [[sarcoidosis]], [[Hodgkin's lymphoma]], [[malnutrition]], and most notably, active tuberculosis.<ref name=Robbins/> [[Interferon gamma release assay]]s, on a blood sample, are recommended in those who are positive to the Mantoux test.<ref name=NICE2011>{{NICE|117|Tuberculosis|2011}}</ref> These are not affected by immunization or most [[environmental mycobacteria]], so they generate fewer [[false-positive]] results.<ref>{{cite journal | vauthors = Pai M, Zwerling A, Menzies D | title = Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update | journal = Annals of Internal Medicine | volume = 149 | issue = 3 | pages = 177–84 | date = August 2008 | pmid = 18593687 | pmc = 2951987 | doi = 10.7326/0003-4819-149-3-200808050-00241 }}</ref> However, they are affected by ''M. szulgai'', ''M. marinum'', and ''M. kansasii''.<ref>{{cite book| veditors = Jindal SK |title=Textbook of Pulmonary and Critical Care Medicine|publisher=Jaypee Brothers Medical Publishers|location=New Delhi|isbn=978-93-5025-073-0|page=544|url=https://books.google.com/books?id=rAT1bdnDakAC&pg=PA544|year=2011|url-status=live|archive-url=https://web.archive.org/web/20150906185238/https://books.google.com/books?id=rAT1bdnDakAC&pg=PA544|archive-date=6 September 2015}}</ref> IGRAs may increase sensitivity when used in addition to the skin test, but may be less sensitive than the skin test when used alone.<ref>{{cite journal | vauthors = Amicosante M, Ciccozzi M, Markova R | title = Rational use of immunodiagnostic tools for tuberculosis infection: guidelines and cost effectiveness studies | journal = The New Microbiologica | volume = 33 | issue = 2 | pages = 93–107 | date = April 2010 | pmid = 20518271 }}</ref> 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 assay]]s.<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Screening for Latent Tuberculosis Infection in Adults: US Preventive Services Task Force Recommendation Statement | journal = JAMA | volume = 316 | issue = 9 | pages = 962–9 | date = September 2016 | pmid = 27599331 | doi = 10.1001/jama.2016.11046 | doi-access = free }}</ref> While some have recommend testing health care workers, evidence of benefit for this is poor {{as of|2019|lc=yes}}.<ref>{{cite journal | vauthors = Gill J, Prasad V | title = Testing Healthcare Workers for Latent Tuberculosis: Is It Evidence Based, Bio-Plausible, Both, Or Neither? | journal = The American Journal of Medicine | volume = 132 | issue = 11 | pages = 1260–1261 | date = November 2019 | pmid = 30946831 | doi = 10.1016/j.amjmed.2019.03.017 | doi-access = free }}</ref> The [[Centers for Disease Control and Prevention]] (CDC) stopped recommending yearly testing of health care workers without known exposure in 2019.<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Tuberculosis Screening, Testing, and Treatment of U.S. Health Care Personnel: Recommendations from the National Tuberculosis Controllers Association and CDC, 2019 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 68 | issue = 19 | pages = 439–443 | date = May 2019 | pmid = 31099768 | pmc = 6522077 | doi = 10.15585/mmwr.mm6819a3 }}</ref> == Prevention == [[File:Notice Do not spit - National Association for the Prevention of Tuberculosis Dublin Branch.jpg|thumb|Tuberculosis public health campaign in Ireland, c. 1905]] Tuberculosis prevention and control efforts rely primarily on the vaccination of infants and the detection and appropriate treatment of active cases.<ref name=Lancet11/> The [[World Health Organization]] (WHO) has achieved some success with improved treatment regimens, and a small decrease in case numbers.<ref name=Lancet11/> Some countries have legislation to involuntarily detain or examine those suspected to have tuberculosis, or [[Involuntary treatment|involuntarily treat]] them if infected.<ref>{{cite journal | vauthors = Coker R, Thomas M, Lock K, Martin R | title = Detention and the evolving threat of tuberculosis: evidence, ethics, and law | journal = The Journal of Law, Medicine & Ethics | volume = 35 | issue = 4 | pages = 609–15, 512 | date = 2007 | pmid = 18076512 | doi = 10.1111/j.1748-720X.2007.00184.x | s2cid = 19924571 }}</ref> === Vaccines === {{Main|Tuberculosis vaccines|BCG vaccine}} The only available [[vaccine]] {{as of|2021|lc=yes}} is [[bacillus Calmette-Guérin]] (BCG).<ref name=McS2011>{{cite journal | vauthors = McShane H | title = Tuberculosis vaccines: beyond bacille Calmette-Guerin | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 366 | issue = 1579 | pages = 2782–89 | date = October 2011 | pmid = 21893541 | pmc = 3146779 |doi-access=free | doi = 10.1098/rstb.2011.0097 }}</ref><ref>{{cite web |title=Vaccines {{!}} Basic TB Facts |url=https://www.cdc.gov/tb/topic/basics/vaccines.htm |date=16 June 2021 |publisher=CDC |access-date=30 December 2021 |archive-date=30 December 2021 |archive-url=https://web.archive.org/web/20211230115301/https://www.cdc.gov/tb/topic/basics/vaccines.htm |url-status=live }}</ref> In children it decreases the risk of getting the infection by 20% and the risk of infection turning into active disease by nearly 60%.<ref>{{cite journal | vauthors = Roy A, Eisenhut M, Harris RJ, Rodrigues LC, Sridhar S, Habermann S, Snell L, Mangtani P, Adetifa I, Lalvani A, Abubakar I | display-authors = 6 | title = Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis |doi-access=free | journal = BMJ | volume = 349 | page= g4643 | date = August 2014 | pmid = 25097193 | pmc = 4122754 | doi = 10.1136/bmj.g4643 }}</ref> It is the most widely used vaccine worldwide, with more than 90% of all children being vaccinated.<ref name=Lancet11/> The immunity it induces decreases after about ten years.<ref name=Lancet11/> As tuberculosis is uncommon in most of Canada, Western Europe, and the United States, BCG is administered to only those people at high risk.<ref>{{cite web|url=https://www.cdc.gov/tb/topic/vaccines/|title=Vaccine and Immunizations: TB Vaccine (BCG)|publisher=Centers for Disease Control and Prevention|year=2011|access-date=26 July 2011|url-status=dead|archive-url=https://web.archive.org/web/20111117140855/http://www.cdc.gov/tb/topic/vaccines/|archive-date=17 November 2011}}</ref><ref>{{cite web|title=BCG Vaccine Usage in Canada – Current and Historical|url=http://www.phac-aspc.gc.ca/tbpc-latb/bcgvac_1206-eng.php|work=Public Health Agency of Canada|access-date=30 December 2011|date=September 2010|url-status=dead|archive-url=https://web.archive.org/web/20120330042719/http://www.phac-aspc.gc.ca/tbpc-latb/bcgvac_1206-eng.php|archive-date=30 March 2012}}</ref><ref name=UK06>{{cite journal | vauthors = Teo SS, Shingadia DV | title = Does BCG have a role in tuberculosis control and prevention in the United Kingdom? | journal = Archives of Disease in Childhood | volume = 91 | issue = 6 | pages = 529–31 | date = June 2006 | pmid = 16714729 | pmc = 2082765 | doi = 10.1136/adc.2005.085043 }}</ref> 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.<ref name=UK06/> Several vaccines are being developed.<ref name=Lancet11/> Intradermal MVA85A vaccine in addition to BCG injection is not effective in preventing tuberculosis.<ref>{{cite journal | vauthors = Kashangura R, Jullien S, Garner P, Johnson S | title = MVA85A vaccine to enhance BCG for preventing tuberculosis | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | pages = CD012915 | date = April 2019 | issue = 4 | pmid = 31038197 | pmc = 6488980 | doi = 10.1002/14651858.CD012915.pub2 | collaboration = Cochrane Infectious Diseases Group }}</ref> === Public health === Public health campaigns which have focused on overcrowding, public spitting and regular sanitation (including hand washing) during the 1800s helped to either interrupt or slow spread which when combined with contact tracing, isolation and treatment helped to dramatically curb the transmission of both tuberculosis and other airborne diseases which led to the [[Tuberculosis elimination|elimination of tuberculosis]] as a major public health issue in most developed economies.<ref>{{cite journal | vauthors = Clark M, Riben P, Nowgesic E | title = The association of housing density, isolation and tuberculosis in Canadian First Nations communities | journal = International Journal of Epidemiology | volume = 31 | issue = 5 | pages = 940–945 | date = October 2002 | pmid = 12435764 | doi = 10.1093/ije/31.5.940 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Barberis I, Bragazzi NL, Galluzzo L, Martini M | title = The history of tuberculosis: from the first historical records to the isolation of Koch's bacillus | journal = Journal of Preventive Medicine and Hygiene | volume = 58 | issue = 1 | pages = E9–E12 | date = March 2017 | pmid = 28515626 | pmc = 5432783 }}</ref> Other risk factors which worsened TB spread such as malnutrition were also ameliorated, but since the emergence of HIV a new population of immunocompromised individuals was available for TB to infect. The World Health Organization (WHO) declared TB a "global health emergency" in 1993,<ref name="Lancet11" /> 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.<ref>{{cite web|url=http://www.stoptb.org/global/plan/|title=The Global Plan to Stop TB|publisher=[[World Health Organization]] (WHO)|year=2011|access-date=13 June 2011|url-status=live|archive-url=https://web.archive.org/web/20110612030924/http://www.stoptb.org/global/plan/|archive-date=12 June 2011}}</ref> 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.<ref name="Lancet11" /> A [[tuberculosis classification]] system developed by the [[American Thoracic Society]] is used primarily in public health programs.<ref>{{cite book| vauthors = Warrell DA, Cox TM, Firth JD, Benz EJ |title=Sections 1–10|year=2005|publisher=Oxford Univ. Press|location=Oxford [u.a.]|isbn=978-0-19-857014-1|page=560|url=https://books.google.com/books?id=EhjX517cGVsC&pg=PA560|edition=4. ed., paperback|url-status=live|archive-url=https://web.archive.org/web/20150906210011/https://books.google.com/books?id=EhjX517cGVsC&pg=PA560|archive-date=6 September 2015}}</ref> In 2015, it launched the [[End TB Strategy]] to reduce deaths by 95% and incidence by 90% before 2035. The goal of tuberculosis elimination is hampered by the lack of rapid testing, of short and effective treatment courses, and of [[tuberculosis vaccine|completely effective vaccines]].<ref>{{cite journal | vauthors = Uplekar M, Weil D, Lonnroth K, Jaramillo E, Lienhardt C, Dias HM, Falzon D, Floyd K, Gargioni G, Getahun H, Gilpin C, Glaziou P, Grzemska M, Mirzayev F, Nakatani H, Raviglione M | display-authors = 6 | title = WHO's new end TB strategy | journal = Lancet | volume = 385 | issue = 9979 | pages = 1799–1801 | date = May 2015 | pmid = 25814376 | doi = 10.1016/S0140-6736(15)60570-0 | s2cid = 39379915 }}</ref> The benefits and risks of giving anti-tubercular drugs in those exposed to MDR-TB is unclear.<ref>{{cite journal | vauthors = Fraser A, Paul M, Attamna A, Leibovici L | title = Drugs for preventing tuberculosis in people at risk of multiple-drug-resistant pulmonary tuberculosis | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD005435 | date = April 2006 | volume = 2006 | pmid = 16625639 | pmc = 6532726 | doi = 10.1002/14651858.CD005435.pub2 | collaboration = Cochrane Infectious Diseases Group }}</ref> Making HAART therapy available to HIV-positive individuals significantly reduces the risk of progression to an active TB infection by up to 90% and can mitigate the spread through this population.<ref>{{cite journal | vauthors = Piggott DA, Karakousis PC | title = Timing of antiretroviral therapy for HIV in the setting of TB treatment | journal = Clinical & Developmental Immunology | volume = 2011 | pages = 103917 | date = 27 December 2010 | pmid = 21234380 | pmc = 3017895 | doi = 10.1155/2011/103917 | doi-access = free }}</ref> == Treatment == {{Main|Tuberculosis management}} [[File:Tubi - 1234,0186.jpg|thumb|Tuberculosis phototherapy treatment on 3 March 1934, in [[Kuopio]], [[Finland]]]] 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 [[Cord factor|cell wall]], which hinders the entry of drugs and makes many antibiotics ineffective.<ref>{{cite journal | vauthors = Brennan PJ, Nikaido H | title = The envelope of mycobacteria | journal = Annual Review of Biochemistry | volume = 64 | pages = 29–63 | year = 1995 | pmid = 7574484 | doi = 10.1146/annurev.bi.64.070195.000333 }}</ref> Active TB is best treated with combinations of several antibiotics to reduce the risk of the bacteria developing [[antibiotic resistance]].<ref name=Lancet11/> The routine use of [[rifabutin]] instead of [[rifampicin]] in HIV-positive people with tuberculosis is of unclear benefit {{as of|2007|lc=yes}}.<ref>{{cite journal | vauthors = Davies G, Cerri S, Richeldi L | title = Rifabutin for treating pulmonary tuberculosis | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD005159 | date = October 2007 | volume = 2007 | pmid = 17943842 | pmc = 6532710 | doi = 10.1002/14651858.CD005159.pub2 }}</ref> Acetylsalicylic acid (aspirin) at a dose of 100 mg per day has been shown to improve clinical signs and symptoms, reduce cavitary lesions, lower inflammatory markers, and increase the rate of sputum-negative conversion in patients with pulmonary tuberculosis.<ref>{{cite journal | vauthors = Di Bella S, Luzzati R, Principe L, Zerbato V, Meroni E, Giuffrè M, Crocè LS, Merlo M, Perotto M, Dolso E, Maurel C, Lovecchio A, Dal Bo E, Lagatolla C, Marini B, Ippodrino R, Sanson G | display-authors = 6 | title = Aspirin and Infection: A Narrative Review | journal = Biomedicines | volume = 10 | issue = 2 | pages = 263 | date = January 2022 | pmid = 35203473 | pmc = 8868581 | doi = 10.3390/biomedicines10020263 | doi-access = free }}</ref> === Latent TB === Latent TB is treated with either [[isoniazid]] or [[rifampin]] alone, or a combination of isoniazid with either rifampicin or rifapentine.<ref name="WHOlatent2018">{{cite book | publisher=[[World Health Organization]] (WHO) | title=Latent tuberculosis infection | year=2018 | page=23 | isbn=978-92-4-155023-9 | url=http://apps.who.int/iris/bitstream/handle/10665/260233/9789241550239-eng.pdf;jsessionid=E08401544A59BE3F84C645C9A9A7B0E5?sequence=1 | access-date=25 July 2018 | archive-date=2 June 2021 | archive-url=https://web.archive.org/web/20210602215123/http://apps.who.int/iris/bitstream/handle/10665/260233/9789241550239-eng.pdf;jsessionid=E08401544A59BE3F84C645C9A9A7B0E5?sequence=1 | url-status=live }}</ref><ref>{{cite journal | vauthors = Borisov AS, Bamrah Morris S, Njie GJ, Winston CA, Burton D, Goldberg S, Yelk Woodruff R, Allen L, LoBue P, Vernon A | display-authors = 6 | title = Update of Recommendations for Use of Once-Weekly Isoniazid-Rifapentine Regimen to Treat Latent Mycobacterium tuberculosis Infection | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 67 | issue = 25 | pages = 723–726 | date = June 2018 | pmid = 29953429 | pmc = 6023184 | doi = 10.15585/mmwr.mm6725a5 }}</ref><ref name=Ste2020>{{cite journal | vauthors = Sterling TR, Njie G, Zenner D, Cohn DL, Reves R, Ahmed A, Menzies D, Horsburgh CR, Crane CM, Burgos M, LoBue P, Winston CA, Belknap R | display-authors = 6 | title = Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020 | language = en-us | journal = MMWR. Recommendations and Reports | volume = 69 | issue = 1 | pages = 1–11 | date = February 2020 | pmid = 32053584 | pmc = 7041302 | doi = 10.15585/mmwr.rr6901a1 }}</ref> The treatment takes three to nine months depending on the medications used.<ref name=CDCcourse/><ref name="WHOlatent2018"/><ref>{{cite journal | vauthors = Njie GJ, Morris SB, Woodruff RY, Moro RN, Vernon AA, Borisov AS | title = Isoniazid-Rifapentine for Latent Tuberculosis Infection: A Systematic Review and Meta-analysis | journal = American Journal of Preventive Medicine | volume = 55 | issue = 2 | pages = 244–252 | date = August 2018 | pmid = 29910114 | pmc = 6097523 | doi = 10.1016/j.amepre.2018.04.030 }}</ref><ref name=Ste2020/> People with latent infections are treated to prevent them from progressing to active TB disease later in life.<ref name=Latent2011>{{cite journal | vauthors = Menzies D, Al Jahdali H, Al Otaibi B | title = Recent developments in treatment of latent tuberculosis infection | journal = The Indian Journal of Medical Research | volume = 133 | issue = 3 | pages = 257–66 | date = March 2011 | pmid = 21441678 | pmc = 3103149 }}</ref> Education or counselling may improve the latent tuberculosis treatment completion rates.<ref>{{cite journal | vauthors = M'imunya JM, Kredo T, Volmink J | title = Patient education and counselling for promoting adherence to treatment for tuberculosis | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD006591 | date = May 2012 | volume = 2012 | pmid = 22592714 | pmc = 6532681 | doi = 10.1002/14651858.CD006591.pub2 | collaboration = Cochrane Infectious Diseases Group }}</ref> === 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.<ref name=Lancet11/> Where resistance to isoniazid is high, ethambutol may be added for the last four months as an alternative.<ref name="Lancet11" /> 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. Shorter treatment regimen may be recommended for those with compliance issues.<ref name="Gelband_1999">{{cite journal | vauthors = Gelband H | title = Regimens of less than six months for treating tuberculosis | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD001362 | date = 25 October 1999 | volume = 1999 | pmid = 10796641 | pmc = 6532732 | doi = 10.1002/14651858.CD001362 | collaboration = Cochrane Infectious Diseases Group }}</ref> There is also no evidence to support shorter anti-tuberculosis treatment regimens when compared to a 6-month treatment regimen.<ref>{{cite journal | vauthors = Grace AG, Mittal A, Jain S, Tripathy JP, Satyanarayana S, Tharyan P, Kirubakaran R | title = Shortened treatment regimens versus the standard regimen for drug-sensitive pulmonary tuberculosis | journal = The Cochrane Database of Systematic Reviews | volume = 12 | pages = CD012918 | date = December 2019 | issue = 12 | pmid = 31828771 | pmc = 6953336 | doi = 10.1002/14651858.CD012918.pub2 | collaboration = Cochrane Infectious Diseases Group }}</ref> However recently, results from an international, randomized, controlled clinical trial indicate that a four-month daily treatment regimen containing high-dose, or "optimized", rifapentine with moxifloxacin (2PHZM/2PHM) is as safe and effective as the existing standard six-month daily regimen at curing drug-susceptible tuberculosis (TB) disease.<ref>{{cite web |title=Landmark TB Trial Identifies Shorter-Course Treatment Regimen |url=https://www.cdc.gov/nchhstp/newsroom/2020/landmark-tb-trial-media-statement.html |website=CDC |date=20 October 2020 |publisher=NCHHSTP Media Team Centers for Disease Control and Prevention |access-date=27 November 2021 |archive-date=27 November 2021 |archive-url=https://web.archive.org/web/20211127171700/https://www.cdc.gov/nchhstp/newsroom/2020/landmark-tb-trial-media-statement.html |url-status=live }}</ref> === Recurrent disease === If tuberculosis recurs, testing to determine which antibiotics it is sensitive to is important before determining treatment.<ref name="Lancet11" /> If [[Multidrug-resistant TB|multiple drug-resistant TB]] (MDR-TB) is detected, treatment with at least four effective antibiotics for 18 to 24 months is recommended.<ref name="Lancet11" /> === 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.<ref>{{cite book |vauthors = Mainous III AB |title=Management of Antimicrobials in Infectious Diseases: Impact of Antibiotic Resistance |publisher=Humana Press |location=Totowa, NJ |year=2010 |page=69 |isbn=978-1-60327-238-4 |url=https://books.google.com/books?id=hwVFAPLYznsC&pg=PA69 |url-status=live |archive-url=https://web.archive.org/web/20150906215558/https://books.google.com/books?id=hwVFAPLYznsC&pg=PA69 |archive-date=6 September 2015 }}</ref> The evidence to support this practice over people simply taking their medications independently is of poor quality.<ref name=Karumbi2015 /> 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.<ref name=Karumbi2015>{{cite journal | vauthors = Karumbi J, Garner P | title = Directly observed therapy for treating tuberculosis | journal = The Cochrane Database of Systematic Reviews | issue = 5 | page= CD003343 | date = May 2015 | volume = 2015 | pmid = 26022367 | pmc = 4460720 | doi = 10.1002/14651858.CD003343.pub4 }}</ref> 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.<ref name=Karumbi2015 /> Methods to remind people of the importance of treatment and appointments may result in a small but important improvement.<ref>{{cite journal | vauthors = Liu Q, Abba K, Alejandria MM, Sinclair D, Balanag VM, Lansang MA | title = Reminder systems to improve patient adherence to tuberculosis clinic appointments for diagnosis and treatment | journal = The Cochrane Database of Systematic Reviews | issue = 11 | pages = CD006594 | date = November 2014 | volume = 2014 | pmid = 25403701 | pmc = 4448217 | doi = 10.1002/14651858.CD006594.pub3 | collaboration = Cochrane Infectious Diseases Group }}</ref> 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.<ref>{{cite journal | vauthors = Mwandumba HC, Squire SB | title = Fully intermittent dosing with drugs for treating tuberculosis in adults | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD000970 | date = 23 October 2001 | pmid = 11687088 | pmc = 6532565 | doi = 10.1002/14651858.CD000970 | collaboration = Cochrane Infectious Diseases Group }}</ref> 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.<ref>{{cite journal | vauthors = Bose A, Kalita S, Rose W, Tharyan P | title = Intermittent versus daily therapy for treating tuberculosis in children | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD007953 | date = January 2014 | volume = 2014 | pmid = 24470141 | pmc = 6532685 | doi = 10.1002/14651858.CD007953.pub2 | collaboration = Cochrane Infectious Diseases Group }}</ref> === Medication resistance === Primary resistance occurs when a person becomes infected with a resistant strain of TB. A person with fully susceptible [[Mycobacterium tuberculosis|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.<ref name=OBrien>{{cite journal | vauthors = O'Brien RJ | title = Drug-resistant tuberculosis: etiology, management and prevention | journal = Seminars in Respiratory Infections | volume = 9 | issue = 2 | pages = 104–12 | date = June 1994 | pmid = 7973169 }}</ref> 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.<ref name="MMWR2006">{{cite journal | author = Centers for Disease Control and Prevention (CDC) | title = Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs--worldwide, 2000-2004 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 55 | issue = 11 | pages = 301–5 | date = March 2006 | pmid = 16557213 | url = https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5511a2.htm | url-status = live | archive-url = https://web.archive.org/web/20170522030229/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5511a2.htm | archive-date = 22 May 2017 }}</ref> Totally drug-resistant TB is resistant to all currently used drugs.<ref name="TR2012">{{Cite magazine|title=Totally Resistant TB: Earliest Cases in Italy|magazine=Wired|url=https://www.wired.com/wiredscience/2012/01/tdr-first-Italy/| vauthors = McKenna M |date=12 January 2012|access-date=12 January 2012|url-status=live|archive-url=https://web.archive.org/web/20120114214156/http://www.wired.com/wiredscience/2012/01/tdr-first-Italy/|archive-date=14 January 2012}}</ref> It was first observed in 2003 in Italy,<ref>{{cite journal | vauthors = Migliori GB, De Iaco G, Besozzi G, Centis R, Cirillo DM | title = First tuberculosis cases in Italy resistant to all tested drugs | journal = Euro Surveillance | volume = 12 | issue = 5 | pages = E070517.1 | date = May 2007 | pmid = 17868596 | doi = 10.2807/esw.12.20.03194-en | doi-access = free }}</ref> but not widely reported until 2012,<ref name="TR2012" /><ref>{{cite web|title=Totally Drug-Resistant TB: a WHO consultation on the diagnostic definition and treatment options|url=https://www.who.int/tb/challenges/xdr/Report_Meeting_totallydrugresistantTB_032012.pdf?ua=1|publisher=World Health Organization (WHO)|access-date=25 March 2016|url-status=live|archive-url=https://web.archive.org/web/20161021151601/http://www.who.int/tb/challenges/xdr/Report_Meeting_totallydrugresistantTB_032012.pdf?ua=1|archive-date=21 October 2016}}</ref> and has also been found in Iran and India.<ref name="EIU 2014">{{cite news | title = Ancient enemy, modern imperative – A time for greater action against tuberculosis | newspaper = The Economist |url=http://www.economistinsights.com/sites/default/files/Ancient%20enemy%20modern%20imperative.pdf |publisher=[[Economist Intelligence Unit]]|access-date=22 January 2022|date=30 June 2014| vauthors = Kielstra P | veditors = Tabary Z |url-status=dead|archive-url=https://web.archive.org/web/20140810101716/http://www.economistinsights.com/sites/default/files/Ancient%20enemy%20modern%20imperative.pdf |archive-date=10 August 2014}}</ref> There is some efficacy for [[linezolid]] to treat those with XDR-TB but side effects and discontinuation of medications were common.<ref>{{cite journal | vauthors = Singh B, Cocker D, Ryan H, Sloan DJ | title = Linezolid for drug-resistant pulmonary tuberculosis | journal = The Cochrane Database of Systematic Reviews | volume = 3 | pages = CD012836 | date = March 2019 | issue = 3 | pmid = 30893466 | pmc = 6426281 | doi = 10.1002/14651858.CD012836.pub2 | collaboration = Cochrane Infectious Diseases Group }}</ref><ref>{{cite journal | vauthors = Velayati AA, Masjedi MR, Farnia P, Tabarsi P, Ghanavi J, ZiaZarifi AH, Hoffner SE | title = Emergence of new forms of totally drug-resistant tuberculosis bacilli: super extensively drug-resistant tuberculosis or totally drug-resistant strains in Iran | journal = Chest | volume = 136 | issue = 2 | pages = 420–425 | date = August 2009 | pmid = 19349380 | doi = 10.1378/chest.08-2427 }}</ref> [[Bedaquiline]] is tentatively supported for use in multiple drug-resistant TB.<ref>{{cite web|title=Provisional CDC Guidelines for the Use and Safety Monitoring of Bedaquiline Fumarate (Sirturo) for the Treatment of Multidrug-Resistant Tuberculosis|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6209a1.htm?s_cid=rr6209a1_x|url-status=live|archive-url=https://web.archive.org/web/20140104204359/http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6209a1.htm?s_cid=rr6209a1_x|archive-date=4 January 2014}}</ref> 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.<ref name="EIU 2014"/> For those with known rifampicin or MDR-TB, molecular tests such as the Genotype MTBDRsl Assay (performed on culture isolates or smear positive specimens) may be useful to detect second-line anti-tubercular drug resistance.<ref>{{cite journal | vauthors = Theron G, Peter J, Richardson M, Warren R, Dheda K, Steingart KR | title = ® MTBDRsl assay for resistance to second-line anti-tuberculosis drugs | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | pages = CD010705 | date = September 2016 | issue = 9 | pmid = 27605387 | pmc = 5034505 | doi = 10.1002/14651858.CD010705.pub3 | collaboration = Cochrane Infectious Diseases Group }}</ref><ref>{{cite web |url=https://www.who.int/tb/WHOPolicyStatementSLLPA.pdf |title=The use of molecular line probe assays for the detection of resistance to second-line anti-tuberculosis drugs |website=World Health Organization |access-date=18 June 2021 |archive-date=22 September 2021 |archive-url=https://web.archive.org/web/20210922003541/https://www.who.int/tb/WHOPolicyStatementSLLPA.pdf |url-status=live }}</ref> == Prognosis == [[File:Tuberculosis world map - DALY - WHO2004.svg|thumb|upright=1.4|[[Age adjustment|Age-standardized]] [[disability-adjusted life year]]s caused by tuberculosis per 100,000 inhabitants in 2004.<ref>{{cite web |url=https://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |title=WHO Disease and injury country estimates |year=2004 |publisher=World Health Organization (WHO) |access-date=11 November 2009 |url-status=live |archive-url=https://web.archive.org/web/20091111101009/http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |archive-date=11 November 2009 }}</ref> {{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.<ref name=Robbins/> However, in the majority of cases, a [[Latent tuberculosis|latent infection]] occurs with no obvious symptoms.<ref name=Robbins/> These dormant bacilli produce active tuberculosis in 5–10% of these latent cases, often many years after infection.<ref name=Pet2005/> 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.<ref name=Robbins/> Studies using [[DNA fingerprinting]] of ''M. tuberculosis'' strains have shown reinfection contributes more substantially to recurrent TB than previously thought,<ref>{{cite journal | vauthors = Lambert ML, Hasker E, Van Deun A, Roberfroid D, Boelaert M, Van der Stuyft P | title = Recurrence in tuberculosis: relapse or reinfection? | journal = The Lancet. Infectious Diseases | volume = 3 | issue = 5 | pages = 282–7 | date = May 2003 | pmid = 12726976 | doi = 10.1016/S1473-3099(03)00607-8 }}</ref> with estimates that it might account for more than 50% of reactivated cases in areas where TB is common.<ref>{{cite journal | vauthors = Wang JY, Lee LN, Lai HC, Hsu HL, Liaw YS, Hsueh PR, Yang PC | title = Prediction of the tuberculosis reinfection proportion from the local incidence | journal = The Journal of Infectious Diseases | volume = 196 | issue = 2 | pages = 281–8 | date = July 2007 | pmid = 17570116 | doi = 10.1086/518898 | doi-access = free }}</ref> The chance of death from a case of tuberculosis is about 4% {{as of|2008|lc=yes}}, down from 8% in 1995.<ref name=Lancet11/> 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). TB is almost always fatal in those with untreated HIV co-infection and death rates are increased even with antiretroviral treatment of HIV.<ref>{{Cite web|title=1.4 Prognosis - Tuberculosis|url=https://medicalguidelines.msf.org/viewport/TUB/latest/1-4-prognosis-20320185.html|access-date=25 August 2020|website=medicalguidelines.msf.org|archive-date=2 June 2021|archive-url=https://web.archive.org/web/20210602215007/https://medicalguidelines.msf.org/viewport/TUB/latest/1-4-prognosis-20320185.html|url-status=live}}</ref> == Epidemiology == Roughly one-quarter of the world's population has been infected with ''M. tuberculosis'',<ref name=WHO2018Fact/> with new infections occurring in about 1% of the population each year.<ref name=WHO2002/> However, most infections with ''M. tuberculosis'' do not cause disease,<ref name=CDC>{{cite web|publisher=[[Centers for Disease Control and Prevention]] (CDC)|url=https://www.cdc.gov/tb/publications/factsheets/general/LTBIandActiveTB.htm|title=Fact Sheets: The Difference Between Latent TB Infection and Active TB Disease|date=20 June 2011|access-date=26 July 2011|url-status=live|archive-url=https://web.archive.org/web/20110804005502/http://www.cdc.gov/tb/publications/factsheets/general/LTBIandActiveTB.htm|archive-date=4 August 2011}}</ref> and 90–95% of infections remain asymptomatic.<ref name=Book90/> In 2012, an estimated 8.6 million chronic cases were active.<ref>{{cite web|title=Global tuberculosis report 2013|url=https://www.who.int/tb/publications/global_report/en/index.html|publisher=World Health Organization (WHO)|year=2013|url-status=live|archive-url=https://web.archive.org/web/20061212123736/http://www.who.int/tb/publications/global_report/en/index.html|archive-date=12 December 2006}}</ref> In 2010, 8.8 million new cases of tuberculosis were diagnosed, and 1.20–1.45 million deaths occurred (most of these occurring in [[Developing nation|developing countries]]).<ref name=WHO2011/><ref name=Loz2012>{{cite journal | vauthors = Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, etal | s2cid = 1541253 | title = 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 | journal = Lancet | volume = 380 | issue = 9859 | pages = 2095–128 | date = December 2012 | pmid = 23245604 | doi = 10.1016/S0140-6736(12)61728-0 | pmc = 10790329 | hdl = 10536/DRO/DU:30050819 | url = https://zenodo.org/record/2557786 | hdl-access = free | access-date = 18 March 2020 | archive-date = 19 May 2020 | archive-url = https://web.archive.org/web/20200519152712/https://zenodo.org/record/2557786 | url-status = live }}</ref> Of these, about 0.35 million occur in those also infected with HIV.<ref name=WHO2011Control>{{cite web|title=Global Tuberculosis Control 2011 |url=https://www.who.int/tb/publications/global_report/2011/gtbr11_full.pdf |publisher=World Health Organization (WHO) |access-date=15 April 2012 |url-status=dead |archive-url=https://web.archive.org/web/20120617064025/http://www.who.int/tb/publications/global_report/2011/gtbr11_full.pdf |archive-date=17 June 2012 }}</ref> In 2018, tuberculosis was the leading cause of death worldwide from a single infectious agent.<ref>{{cite web |title=Tuberculosis |url=https://www.who.int/news-room/fact-sheets/detail/tuberculosis |website=WHO |date=24 March 2020 |access-date=31 May 2020 |archive-date=30 July 2020 |archive-url=https://web.archive.org/web/20200730165218/https://www.who.int/news-room/fact-sheets/detail/tuberculosis |url-status=live }}</ref> The total number of tuberculosis cases has been decreasing since 2005, while new cases have decreased since 2002.<ref name="WHO2011" /> Tuberculosis{{Clarify|reason=Which one? Pulmonary?|date=December 2022}} incidence is seasonal, with peaks occurring every spring and summer.<ref>{{cite journal | vauthors = Douglas AS, Strachan DP, Maxwell JD | title = Seasonality of tuberculosis: the reverse of other respiratory diseases in the UK | journal = Thorax | volume = 51 | issue = 9 | pages = 944–946 | date = September 1996 | pmid = 8984709 | pmc = 472621 | doi = 10.1136/thx.51.9.944 }}</ref><ref>{{cite journal | vauthors = Martineau AR, Nhamoyebonde S, Oni T, Rangaka MX, Marais S, Bangani N, Tsekela R, Bashe L, de Azevedo V, Caldwell J, Venton TR, Timms PM, Wilkinson KA, Wilkinson RJ | display-authors = 6 | title = Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 47 | pages = 19013–19017 | date = November 2011 | pmid = 22025704 | pmc = 3223428 | doi = 10.1073/pnas.1111825108 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Parrinello CM, Crossa A, Harris TG | title = Seasonality of tuberculosis in New York City, 1990-2007 | journal = The International Journal of Tuberculosis and Lung Disease | volume = 16 | issue = 1 | pages = 32–37 | date = January 2012 | pmid = 22236842 | doi = 10.5588/ijtld.11.0145 }}</ref><ref name="Korthals2012">{{cite journal | vauthors = Korthals Altes H, Kremer K, Erkens C, van Soolingen D, Wallinga J | title = Tuberculosis seasonality in the Netherlands differs between natives and non-natives: a role for vitamin D deficiency? | journal = The International Journal of Tuberculosis and Lung Disease | volume = 16 | issue = 5 | pages = 639–644 | date = May 2012 | pmid = 22410705 | doi = 10.5588/ijtld.11.0680 }}</ref> The reasons for this are unclear, but may be related to vitamin D deficiency during the winter.<ref name="Korthals2012"/><ref>{{cite journal | vauthors = Koh GC, Hawthorne G, Turner AM, Kunst H, Dedicoat M | title = Tuberculosis incidence correlates with sunshine: an ecological 28-year time series study | journal = PLOS ONE | volume = 8 | issue = 3 | pages = e57752 | year = 2013 | pmid = 23483924 | pmc = 3590299 | doi = 10.1371/journal.pone.0057752 | doi-access = free | bibcode = 2013PLoSO...857752K }}</ref> There are also studies linking tuberculosis to different weather conditions like low temperature, low humidity and low rainfall. It has been suggested that tuberculosis incidence rates may be connected to climate change.<ref>{{cite journal | vauthors = Kuddus MA, McBryde ES, Adegboye OA | title = Delay effect and burden of weather-related tuberculosis cases in Rajshahi province, Bangladesh, 2007-2012 | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 12720 | date = September 2019 | pmid = 31481739 | pmc = 6722246 | doi = 10.1038/s41598-019-49135-8 | bibcode = 2019NatSR...912720K }}</ref> === At-risk groups === Tuberculosis is closely linked to both overcrowding and [[malnutrition]], making it one of the principal [[diseases of poverty]].<ref name="Lancet11" /> 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.<ref name="Griffith_1996">{{cite journal|vauthors=Griffith DE, Kerr CM|date=August 1996|title=Tuberculosis: disease of the past, disease of the present|journal=Journal of PeriAnesthesia Nursing|volume=11|issue=4|pages=240–45|doi=10.1016/S1089-9472(96)80023-2|pmid=8964016}}</ref> The rate of tuberculosis varies with age. In Africa, it primarily affects adolescents and young adults.<ref>{{cite web|title=Global Tuberculosis Control Report, 2006 – Annex 1 Profiles of high-burden countries|url=https://www.who.int/tb/publications/global_report/2006/pdf/full_report_correctedversion.pdf|url-status=dead|archive-url=https://web.archive.org/web/20090726124358/http://www.who.int/tb/publications/global_report/2006/pdf/full_report_correctedversion.pdf|archive-date=26 July 2009|access-date=13 October 2006|publisher=World Health Organization (WHO)}}</ref> However, in countries where incidence rates have declined dramatically (such as the United States), tuberculosis is mainly a disease of the elderly and [[immunocompromise]]d (risk factors are listed above).<ref name="Robbins" /><ref>{{cite web|date=12 September 2006|title=2005 Surveillance Slide Set|url=https://www.cdc.gov/nchstp/tb/pubs/slidesets/surv/surv2005/default.htm|url-status=live|archive-url=https://web.archive.org/web/20061123122326/http://www.cdc.gov/nchstp/tb/pubs/slidesets/surv/surv2005/default.htm|archive-date=23 November 2006|access-date=13 October 2006|publisher=Centers for Disease Control and Prevention}}</ref> Worldwide, 22 "high-burden" states or countries together experience 80% of cases as well as 83% of deaths.<ref name="EIU 2014" /> In Canada and Australia, tuberculosis is many times more common among the [[Indigenous peoples]], especially in remote areas.<ref>{{cite journal|vauthors=FitzGerald JM, Wang L, Elwood RK|date=February 2000|title=Tuberculosis: 13. Control of the disease among aboriginal people in Canada|journal=[[Canadian Medical Association Journal]]|volume=162|issue=3|pages=351–55|pmc=1231016|pmid=10693593}}</ref><ref>{{cite book| vauthors = Quah SR, Carrin G, Buse K, Heggenhougen K |url=https://books.google.com/books?id=IEXUrc0tr1wC&pg=PA424|title=Health Systems Policy, Finance, and Organization|publisher=Academic Press|year=2009|isbn=978-0-12-375087-7|location=Boston|page=424|name-list-style=vanc|archive-url=https://web.archive.org/web/20150906220918/https://books.google.com/books?id=IEXUrc0tr1wC&pg=PA424|archive-date=6 September 2015|url-status=live}}</ref> Factors contributing to this include higher prevalence of predisposing health conditions and behaviours, and overcrowding and poverty. In some Canadian Indigenous groups, genetic susceptibility may play a role.<ref name=":0" /> Socioeconomic status (SES) strongly affects TB risk. People of low SES are both more likely to contract TB and to be more severely affected by the disease. 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. 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.<ref name=":0" /> === Geographical epidemiology === 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.<ref name="Robbins" /> Hopes of totally controlling the disease have been dramatically dampened because of many 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.<ref name="Lancet11" /> In developed countries, tuberculosis is less common and is found mainly in urban areas. In Europe, deaths from TB fell from 500 out of 100,000 in 1850 to 50 out of 100,000 by 1950. Improvements in public health were reducing tuberculosis even before the arrival of antibiotics, although the disease remained a significant threat to public health, such that when the [[Medical Research Council (UK)|Medical Research Council]] was formed in Britain in 1913 its initial focus was tuberculosis research.<ref>{{cite web | work = [[Medical Research Council (UK)|Medical Research Council]] | url = http://www.mrc.ac.uk/index/about/about-history/about-history-2.htm | title = Origins of the MRC. | archive-url = https://web.archive.org/web/20080411164838/http://www.mrc.ac.uk/index/about/about-history/about-history-2.htm | archive-date=11 April 2008 | access-date = 7 October 2006 }}</ref> 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.<ref name="WHO2011Control" /> ==== Russia ==== Russia has achieved particularly dramatic progress with a decline in its TB mortality rate—from 61.9 per 100,000 in 1965 to 2.7 per 100,000 in 1993;<ref>{{Cite book |vauthors=Shkolnikov VM, Meslé F |chapter=The Russian Epidemiological Crisis as Mirrored by Mortality Trends |page=142 |year=1996 |url=https://www.rand.org/pubs/conf_proceedings/CF124.html |language=en |veditors=DaVanzo J, Farnsworth G |title=Russia's Demographic "Crisis" |publisher=RAND Corporation |isbn=0-8330-2446-9 |access-date=20 February 2023 |archive-date=20 February 2023 |archive-url=https://web.archive.org/web/20230220171629/https://www.rand.org/pubs/conf_proceedings/CF124.html |url-status=live }}</ref><ref name=WHO2011a>{{cite web | url = https://www.who.int/tb/publications/global_report/en/index.html | title = Global Tuberculosis Control | archive-url = https://web.archive.org/web/20061212123736/http://www.who.int/tb/publications/global_report/en/index.html | archive-date=12 December 2006 | publisher = World Health Organization | date = 2011 }}</ref> however, mortality rate increased to 24 per 100,000 in 2005 and then recoiled to 11 per 100,000 by 2015.<ref>{{Cite web|url=https://extranet.who.int/sree/Reports?op=Replet&name=%2FWHO_HQ_Reports%2FG2%2FPROD%2FEXT%2FTBCountryProfile&ISO2=RU&LAN=EN&outtype=html|title=WHO global tuberculosis report 2016. Annex 2. Country profiles: Russian Federation|access-date=22 August 2020|archive-date=14 July 2017|archive-url=https://web.archive.org/web/20170714043942/https://extranet.who.int/sree/Reports?op=Replet&name=%2FWHO_HQ_Reports%2FG2%2FPROD%2FEXT%2FTBCountryProfile&ISO2=RU&LAN=EN&outtype=html|url-status=dead}}</ref> ==== China ==== China has achieved particularly dramatic progress, with about an 80% reduction in its TB mortality rate between 1990 and 2010.<ref name=WHO2011Control/> The number of new cases has declined by 17% between 2004 and 2014.<ref name="EIU 2014"/> ==== Africa ==== In 2007, the country with the highest estimated incidence rate of TB was [[Eswatini]], with 1,200 cases per 100,000 people. In 2017, the country with the highest estimated [[Incidence (epidemiology)|incidence rate]] as a % of the population was [[Lesotho]], with 665 cases per 100,000 people.<ref name="Global tuberculosis report 2018">{{cite web|title=Global Tuberculosis Report 2018|url=http://apps.who.int/iris/bitstream/handle/10665/274453/9789241565646-eng.pdf?ua=1|access-date=27 September 2019|archive-date=7 August 2020|archive-url=https://web.archive.org/web/20200807121356/https://apps.who.int/iris/bitstream/handle/10665/274453/9789241565646-eng.pdf?ua=1|url-status=live}}</ref> In South Africa, 54 200 people died in 2022 from TB. The incidence rate was 468 per 100 000 people; in 2015, this was 988 per 100 000. The total incidence was 280 000 in 2022; in 2015, this was 552 000.<ref>{{Cite web |last=Tomlinson |first=Catherine |date=2023-11-10 |title=In-depth: What new WHO TB numbers mean for South Africa |url=https://www.spotlightnsp.co.za/2023/11/10/in-depth-what-new-who-tb-numbers-mean-for-sa/ |access-date=2024-03-27 |website=Spotlight |language=en-US}}</ref> ==== India ==== As of 2017, India had the largest total incidence, with an estimated 2,740,000 cases.<ref name="Global tuberculosis report 2018"/> 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.<ref>{{Cite web|url=https://extranet.who.int/sree/Reports?op=Replet&name=%2FWHO_HQ_Reports%2FG2%2FPROD%2FEXT%2FTBCountryProfile&ISO2=IN&LAN=EN&outtype=html|title=WHO Global tuberculosis report 2016: India|access-date=22 August 2020|archive-date=6 February 2018|archive-url=https://web.archive.org/web/20180206193815/https://extranet.who.int/sree/Reports?op=Replet&name=%2FWHO_HQ_Reports%2FG2%2FPROD%2FEXT%2FTBCountryProfile&ISO2=IN&LAN=EN&outtype=html|url-status=dead}}</ref><ref>{{cite web|url=http://www.dnaindia.com/health/report-govt-revisits-strategy-to-combat-tuberculosis-nadda-2388967|title=Govt revisits strategy to combat tuberculosis|work=Daily News and Analysis|date=8 April 2017|access-date=22 August 2020|archive-date=3 June 2021|archive-url=https://web.archive.org/web/20210603072417/https://www.dnaindia.com/health/report-govt-revisits-strategy-to-combat-tuberculosis-nadda-2388967|url-status=live}}</ref> In India a major proportion of tuberculosis patients are being treated by private partners and private hospitals. Evidence indicates that the tuberculosis national survey does not represent the number of cases that are diagnosed and recorded by private clinics and hospitals in India.<ref>{{cite journal | vauthors = Mahla RS | title = Prevalence of drug-resistant tuberculosis in South Africa | journal = The Lancet. Infectious Diseases | volume = 18 | issue = 8 | pages = 836 | date = August 2018 | pmid = 30064674 | doi = 10.1016/S1473-3099(18)30401-8 | doi-access = free }}</ref> ==== North America ==== In the United States, [[Native Americans in the United States|Native Americans]] have a fivefold greater mortality from TB,<ref>{{cite book | vauthors = Birn AE |title= Textbook of International Health: Global Health in a Dynamic World |year= 2009 |page= 261 |publisher= Oxford University Press |isbn= 978-0-19-988521-3 |url= https://books.google.com/books?id=2XBB4-eYGZIC&pg=PT261 |url-status=live |archive-url= https://web.archive.org/web/20150906213750/https://books.google.com/books?id=2XBB4-eYGZIC&pg=PT261 |archive-date= 6 September 2015 }}</ref> and racial and ethnic minorities accounted for 84% of all reported TB cases.<ref>{{cite web|publisher=Centers for Disease Control and Prevention|url=https://www.cdc.gov/tb/statistics/surv/surv2012/slides/surv12.htm|title=CDC Surveillance Slides 2012 – TB|url-status=dead|archive-url=https://web.archive.org/web/20131109150519/http://www.cdc.gov/tb/statistics/surv/surv2012/slides/surv12.htm|archive-date=9 November 2013|date=24 October 2018|access-date=17 September 2017}}</ref> The overall tuberculosis case rate in the United States was 3 per 100,000 persons in 2017.<ref name="Global tuberculosis report 2018"/> In Canada, tuberculosis was endemic in some rural areas as of 1998.<ref>{{cite journal|url=http://gateway.nlm.nih.gov/MeetingAbstracts/ma?f=102188560.html|title=Rural outbreaks of ''Mycobacterium tuberculosis'' in a Canadian province|journal=Abstr Intersci Conf Antimicrob Agents Chemother|year=1998|volume=38|page=555 |id=abstract no. L-27|vauthors=Al-Azem A, Kaushal Sharma M, Turenne C, Hoban D, Hershfield E, MacMorran J, Kabani A|url-status=dead|archive-url=https://web.archive.org/web/20111118161808/http://gateway.nlm.nih.gov/MeetingAbstracts/ma?f=102188560.html |archive-date=18 November 2011 }}</ref> ==== Western Europe ==== 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. <gallery widths="300" heights="210"> File:Tuberculosis incidence (per 100,000 people), OWID.svg|alt=Number of new cases of tuberculosis per 100,000 people in 2016.|Number of new cases of tuberculosis per 100,000 people in 2016<ref>{{cite web |title=Tuberculosis incidence (per 100,000 people) |url=https://ourworldindata.org/grapher/incidence-of-tuberculosis-sdgs |website=Our World in Data |access-date=7 March 2020 |archive-date=26 September 2019 |archive-url=https://web.archive.org/web/20190926041419/https://ourworldindata.org/grapher/incidence-of-tuberculosis-sdgs |url-status=live }}</ref> File:Tuberculosis world map-Deaths per million persons-WHO2012.svg|Tuberculosis deaths per million persons in 2012 File:Tuberculosis deaths by region, OWID.svg|alt=Tuberculosis deaths by region, 1990 to 2017.|Tuberculosis deaths by region, 1990 to 2017<ref>{{cite web |title=Tuberculosis deaths by region |url=https://ourworldindata.org/grapher/tuberculosis-deaths-region |website=Our World in Data |access-date=7 March 2020 |archive-date=8 May 2020 |archive-url=https://web.archive.org/web/20200508204644/https://ourworldindata.org/grapher/tuberculosis-deaths-region |url-status=live }}</ref> </gallery> == Society and culture == === Names === Tuberculosis has been known by many names from the technical to the familiar.<ref name=Lawlor/> {{Lang|grc-latn|Phthisis}} ({{Lang|grc|Φθισις}}) is a Greek word for consumption, an old term for pulmonary tuberculosis;<ref name=Cha1998/> around 460 BCE, [[Hippocrates]] described phthisis as a disease of dry seasons.<ref>{{cite web |title=Hippocrates 3.16 Classics, MIT |url=http://classics.mit.edu/Hippocrates/aphorisms.mb.txt |access-date=15 December 2015 |url-status=unfit |archive-url=https://web.archive.org/web/20050211173218/http://classics.mit.edu/Hippocrates/aphorisms.mb.txt |archive-date=11 February 2005}}</ref> The abbreviation ''TB'' is short for ''tubercle [[Bacillus (shape)|bacillus]]''. ''Consumption'' was the most common nineteenth century English word for the disease, and was also in use well into the twentieth century. The Latin root {{Lang|la|con}} meaning 'completely' is linked to {{Lang|la|sumere}} meaning 'to take up from under'.<ref>{{cite book| vauthors = Caldwell M |title=The Last Crusade|date=1988|publisher=Macmillan|location=New York|isbn=978-0-689-11810-4|page=[https://archive.org/details/isbn_9780689118104/page/21 21]|url-access=registration|url=https://archive.org/details/isbn_9780689118104/page/21}}</ref> In ''[[The Life and Death of Mr Badman]]'' by [[John Bunyan]], the author calls consumption "the captain of all these men of death."<ref>{{cite book| vauthors = Bunyan J |date=1808 |title=The Life and Death of Mr. Badman|url=https://archive.org/details/lifeanddeathmrb01bunygoog |quote=captain. |page=[https://archive.org/details/lifeanddeathmrb01bunygoog/page/n238 244] |location=London |publisher=W. Nicholson |via=Internet Archive |access-date=28 September 2016}}</ref> "Great white plague" has also been used.<ref name=Lawlor/> === Art and literature === [[File:Munch Det Syke Barn 1885-86.jpg|thumb|Painting ''[[The Sick Child (Munch)|The Sick Child]]'' by [[Edvard Munch]], 1885–1886, depicts the illness of his sister Sophie, who died of tuberculosis when Edvard was 14; his mother also died of the disease.]] {{main|Cultural depictions of tuberculosis}} Tuberculosis was for centuries associated with [[poet]]ic and [[art]]istic qualities among those infected, and was also known as "the romantic disease".<ref name=Lawlor>{{cite web| vauthors = Lawlor C |title=Katherine Byrne, Tuberculosis and the Victorian Literary Imagination|url=http://www.bsls.ac.uk/reviews/romantic-and-victorian/katherine-byrne-tuberculosis-and-the-victorian-literary-imagination/|publisher=British Society for Literature and Science|access-date=11 June 2017|archive-date=6 November 2020|archive-url=https://web.archive.org/web/20201106070752/http://www.bsls.ac.uk/reviews/romantic-and-victorian/katherine-byrne-tuberculosis-and-the-victorian-literary-imagination/|url-status=live}}</ref><ref>{{cite book | vauthors = Byrne K | title=Tuberculosis and the Victorian Literary Imagination |publisher=Cambridge University Press |year=2011 |isbn=978-1-107-67280-2}}</ref> Major artistic figures such as the poets [[John Keats]], [[Percy Bysshe Shelley]], and [[Edgar Allan Poe]], the composer [[Frédéric Chopin]],<ref name=IOE>{{cite web|title=About Chopin's illness|url=http://www.iconsofeurope.com/chopin.tuberculosis.htm|publisher=Icons of Europe|access-date=11 June 2017|archive-date=28 September 2017|archive-url=https://web.archive.org/web/20170928150213/http://www.iconsofeurope.com/chopin.tuberculosis.htm|url-status=live}}</ref> the playwright [[Anton Chekhov]], the novelists [[Franz Kafka]], [[Katherine Mansfield]],<ref name="Vilaplana2017">{{cite journal | vauthors = Vilaplana C | title = A literary approach to tuberculosis: lessons learned from Anton Chekhov, Franz Kafka, and Katherine Mansfield | journal = International Journal of Infectious Diseases | volume = 56 | pages = 283–85 | date = March 2017 | pmid = 27993687 | doi = 10.1016/j.ijid.2016.12.012 | doi-access = free }}</ref> [[Charlotte Brontë]], [[Fyodor Dostoevsky]], [[Thomas Mann]], [[W. Somerset Maugham]],<ref name=Rogal1997>{{cite book |vauthors=Rogal SJ |title=A William Somerset Maugham Encyclopedia |url=https://books.google.com/books?id=H0MqigagKTkC&pg=PA245 |year=1997 |publisher=Greenwood Publishing |isbn=978-0-313-29916-2 |page=245 |access-date=4 October 2017 |archive-date=2 June 2021 |archive-url=https://web.archive.org/web/20210602212607/https://books.google.com/books?id=H0MqigagKTkC&pg=PA245 |url-status=live }}</ref> [[George Orwell]],<ref>{{cite web | vauthors = Eschner K |title=George Orwell Wrote '1984' While Dying of Tuberculosis |url=https://www.smithsonianmag.com/smart-news/george-orwell-wrote-1984-while-dying-tuberculosis-180962608/ |website=Smithsonian |access-date=25 March 2019 |archive-date=24 March 2019 |archive-url=https://web.archive.org/web/20190324161820/https://www.smithsonianmag.com/smart-news/george-orwell-wrote-1984-while-dying-tuberculosis-180962608/ |url-status=live }}</ref> and [[Robert Louis Stevenson]], and the artists [[Alice Neel]],<ref name=JAMA2005>{{cite journal |journal=Journal of the American Medical Association |url=http://jamanetwork.com/journals/jama/issue/293/22 |page=cover |date=8 June 2005 |volume=293 |issue=22 |title=Tuberculosis (whole issue) |access-date=4 October 2017 |archive-date=24 August 2020 |archive-url=https://web.archive.org/web/20200824105736/https://jamanetwork.com/journals/jama/issue/293/22 |url-status=live }}</ref> [[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.<ref name=Lemlein1981>{{cite journal |vauthors=Lemlein RF |s2cid=191371443 |title=Influence of Tuberculosis on the Work of Visual Artists: Several Prominent Examples |journal=Leonardo |date=1981 |volume=14 |issue=2 |pages=114–11 |jstor=1574402 |doi=10.2307/1574402 }}</ref><ref name=Wilsey>{{cite thesis | vauthors = Wilsey AM | title = 'Half in Love with Easeful Death:' Tuberculosis in Literature | date = May 2012 | work = Humanities Capstone Projects | degree = PhD Thesis | publisher = Pacific University | ref = Paper 11 | url = http://commons.pacificu.edu/cgi/viewcontent.cgi?article=1010&context=cashu | access-date = 28 September 2017 | archive-url = https://web.archive.org/web/20171011220904/http://commons.pacificu.edu/cgi/viewcontent.cgi?article=1010&context=cashu | archive-date = 11 October 2017 | url-status = dead }}</ref><ref name="Morens2002">{{cite journal | vauthors = Morens DM | title = At the deathbed of consumptive art | journal = Emerging Infectious Diseases | volume = 8 | issue = 11 | pages = 1353–8 | date = November 2002 | pmid = 12463180 | pmc = 2738548 | doi = 10.3201/eid0811.020549 }}</ref> Tuberculosis formed an often-reused theme in [[literature]], as in [[Thomas Mann]]'s ''[[The Magic Mountain]]'', set in a [[sanatorium]];<ref name=McMasterUni>{{cite web |url=http://hsl.mcmaster.libguides.com/c.php?g=306775&p=2045587 |title=Pulmonary Tuberculosis/In Literature and Art| publisher=McMaster University History of Diseases |access-date=9 June 2017}}</ref> in [[music]], as in [[Van Morrison]]'s song "[[T.B. Sheets]]";<ref>{{cite news| vauthors = Thomson G |title=Van Morrison – 10 of the best|url=https://www.theguardian.com/music/musicblog/2016/jun/01/van-morrison-10-of-the-best|work=[[The Guardian]]|date=1 June 2016|access-date=28 September 2017|archive-date=14 August 2020|archive-url=https://web.archive.org/web/20200814152313/https://www.theguardian.com/music/musicblog/2016/jun/01/van-morrison-10-of-the-best|url-status=live}}</ref> in [[opera]], as in [[Giacomo Puccini|Puccini]]'s ''[[La bohème]]'' and [[Giuseppe Verdi|Verdi]]'s ''[[La Traviata]]'';<ref name="Morens2002"/> in [[art]], as in [[Edvard Munch|Munch]]'s painting of his ill sister;<ref name=USAID>{{cite web|title=Tuberculosis Throughout History: The Arts|url=https://www.usaid.gov/sites/default/files/documents/1864/art_poster.pdf|publisher=[[United States Agency for International Development]] (USAID)|access-date=12 June 2017|archive-date=30 June 2017|archive-url=https://web.archive.org/web/20170630123411/https://www.usaid.gov/sites/default/files/documents/1864/art_poster.pdf|url-status=live}}</ref> and in [[film]], such as the 1945 ''[[The Bells of St. Mary's]]'' starring [[Ingrid Bergman]] as a nun with tuberculosis.<ref name=Corliss2008>{{Cite magazine | vauthors = Corliss R |title=Top 10 Worst Christmas Movies |magazine=Time |url=http://entertainment.time.com/2011/12/20/top-10-worst-christmas-movies/ |date=22 December 2008 |quote='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.' |access-date=28 September 2017 |archive-date=22 September 2020 |archive-url=https://web.archive.org/web/20200922042323/https://entertainment.time.com/2011/12/20/top-10-worst-christmas-movies/ |url-status=live }}</ref> === Public health efforts === {{Further information|Tuberculosis elimination}} In 2014, the WHO adopted the "End TB" strategy which aims to reduce TB incidence by 80% and TB deaths by 90% by 2030.<ref name="who_end_tb">{{Cite web|url=https://www.who.int/teams/global-tuberculosis-programme/the-end-tb-strategy|title=The End TB Strategy|website=who.int|access-date=22 July 2021|archive-date=22 July 2021|archive-url=https://web.archive.org/web/20210722170507/https://www.who.int/teams/global-tuberculosis-programme/the-end-tb-strategy|url-status=live}}</ref> The strategy contains a milestone to reduce TB incidence by 20% and TB deaths by 35% by 2020.<ref name="2020_TB_report">{{Cite book |url=https://apps.who.int/iris/rest/bitstreams/1312164/retrieve |title=Global tuberculosis report 2020 |year=2020 | publisher = World Health Organization | isbn = 978-92-4-001313-1 |access-date=22 July 2021 |archive-date=22 July 2021 |archive-url= https://web.archive.org/web/20210722172009/https://apps.who.int/iris/rest/bitstreams/1312164/retrieve |url-status=live }}</ref> However, by 2020 only a 9% reduction in incidence per population was achieved globally, with the European region achieving 19% and the African region achieving 16% reductions.<ref name="2020_TB_report"/> Similarly, the number of deaths only fell by 14%, missing the 2020 milestone of a 35% reduction, with some regions making better progress (31% reduction in Europe and 19% in Africa).<ref name="2020_TB_report"/> Correspondingly, also treatment, prevention and funding milestones were missed in 2020, for example only 6.3 million people were started on TB prevention short of the target of 30 million.<ref name="2020_TB_report"/> 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.<ref name=PressRelease2012/><ref name=Xpert2011>{{cite journal | vauthors = Lawn SD, Nicol MP | title = Xpert® MTB/RIF assay: development, evaluation and implementation of a new rapid molecular diagnostic for tuberculosis and rifampicin resistance | journal = Future Microbiology | volume = 6 | issue = 9 | pages = 1067–82 | date = September 2011 | pmid = 21958145 | pmc = 3252681 | doi = 10.2217/fmb.11.84 }}</ref><ref>{{cite news |url=https://www.reuters.com/article/idUSTRE6B71RF20101208 |title=WHO says Cepheid rapid test will transform TB care |work=[[Reuters]] |date=8 December 2010 |url-status=live |archive-url=https://web.archive.org/web/20101211140847/http://www.reuters.com/article/idUSTRE6B71RF20101208 |archive-date=11 December 2010 }}</ref> 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.<ref name=PressRelease2012>{{cite web|title=Public–Private Partnership Announces Immediate 40 Percent Cost Reduction for Rapid TB Test|url=https://www.who.int/tb/features_archive/GeneXpert_press_release_final.pdf|publisher=World Health Organization (WHO)|date=6 August 2012|url-status=live|archive-url=https://web.archive.org/web/20131029234310/http://www.who.int/tb/features_archive/GeneXpert_press_release_final.pdf|archive-date=29 October 2013}}</ref><ref>{{cite web|title=The Stop TB Partnership, which operates through a secretariat hosted by the World Health Organization (WHO) in Geneva, Switzerland|url=http://www.stoptb.org/wg/gli/assets/documents/map/XpertPublications.pdf|author=STOPTB|date=5 April 2013|url-status=live|archive-url=https://web.archive.org/web/20140124041952/http://www.stoptb.org/wg/gli/assets/documents/map/XpertPublications.pdf|archive-date=24 January 2014}}</ref> Many resource-poor places {{as of|2011|lc=yes}} have access to only sputum microscopy.<ref>{{cite journal | vauthors = Lienhardt C, Espinal M, Pai M, Maher D, Raviglione MC | title = What research is needed to stop TB? Introducing the TB Research Movement | journal = PLOS Medicine | volume = 8 | issue = 11 | pages = e1001135 | date = November 2011 | pmid = 22140369 | pmc = 3226454 | doi = 10.1371/journal.pmed.1001135 | doi-access = free }}</ref> 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.<ref>{{Cite journal| vauthors = Sandhu GK |date=2011|title=Tuberculosis: Current Situation, Challenges and Overview of its Control Programs in India|journal=Journal of Global Infectious Diseases|volume=3|issue=2|pages=143–150|doi=10.4103/0974-777X.81691|issn=0974-777X|pmc=3125027|pmid=21731301 |doi-access=free }}</ref> Programs such as the [[Revised National Tuberculosis Control Program]] are working to reduce TB levels among people receiving public health care.<ref name="Bhargava">{{cite journal | vauthors = Bhargava A, Pinto L, Pai M |title=Mismanagement of tuberculosis in India: Causes, consequences, and the way forward |journal=Hypothesis |volume=9 |issue=1 |page=e7 |year=2011 |url=http://www.hypothesisjournal.com/wp-content/uploads/2011/09/vol9no1-hj009.pdf |archive-url=https://web.archive.org/web/20160314104924/http://www.hypothesisjournal.com/wp-content/uploads/2011/09/vol9no1-hj009.pdf |archive-date=14 March 2016 |url-status=unfit }}</ref><ref>{{cite journal | vauthors = Amdekar Y | s2cid = 41788291 | title = Changes in the management of tuberculosis | journal = Indian Journal of Pediatrics | volume = 76 | issue = 7 | pages = 739–42 | date = July 2009 | pmid = 19693453 | doi = 10.1007/s12098-009-0164-4 }}</ref> A 2014 [[Economist Intelligence Unit|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."<ref name="EIU 2014"/> 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."<ref name="EIU 2014"/> 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.<ref name="EIU 2014"/> The government of Brazil provides universal TB care, which reduces this problem.<ref name="EIU 2014"/> Conversely, falling rates of TB infection may not relate to the number of programs directed at reducing infection rates but may be tied to an increased level of education, income, and health of the population.<ref name="EIU 2014"/> Costs of the disease, as calculated by the [[World Bank]] in 2009 may exceed US$150 billion per year in "high burden" countries.<ref name="EIU 2014"/> Lack of progress eradicating the disease may also be due to lack of patient follow-up – as among the 250 million [[migration in China|rural migrants in China]].<ref name="EIU 2014"/> There is insufficient data to show that active contact tracing helps to improve case detection rates for tuberculosis.<ref>{{cite journal | vauthors = Fox GJ, Dobler CC, Marks GB | title = Active case finding in contacts of people with tuberculosis | journal = The Cochrane Database of Systematic Reviews | issue = 9 | pages = CD008477 | date = September 2011 | volume = 2011 | pmid = 21901723 | pmc = 6532613 | doi = 10.1002/14651858.CD008477.pub2 }}</ref> Interventions such as house-to-house visits, educational leaflets, mass media strategies, educational sessions may increase tuberculosis detection rates in short-term.<ref>{{cite journal | vauthors = Mhimbira FA, Cuevas LE, Dacombe R, Mkopi A, Sinclair D | title = Interventions to increase tuberculosis case detection at primary healthcare or community-level services | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | pages = CD011432 | date = November 2017 | issue = 11 | pmid = 29182800 | pmc = 5721626 | doi = 10.1002/14651858.CD011432.pub2 | collaboration = Cochrane Infectious Diseases Group }}</ref> There is no study that compares new methods of contact tracing such as social network analysis with existing contact tracing methods.<ref>{{cite journal | vauthors = Braganza Menezes D, Menezes B, Dedicoat M | title = Contact tracing strategies in household and congregate environments to identify cases of tuberculosis in low- and moderate-incidence populations | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | pages = CD013077 | date = August 2019 | issue = 8 | pmid = 31461540 | pmc = 6713498 | doi = 10.1002/14651858.CD013077.pub2 | collaboration = Cochrane Infectious Diseases Group }}</ref> === Stigma === Slow progress in preventing the disease may in part be due to [[social stigma|stigma]] associated with TB.<ref name="EIU 2014"/> 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 [[AIDS in Africa|Africa, AIDS]].<ref name="EIU 2014"/> Such stigmatization may be both real and perceived; for example, in Ghana, individuals with TB are banned from attending public gatherings.<ref name="Courtwright 2010">{{cite journal | vauthors = Courtwright A, Turner AN | title = Tuberculosis and stigmatization: pathways and interventions | journal = Public Health Reports | volume = 125 | issue = 4_suppl | pages = 34–42 | date = Jul–Aug 2010 | pmid = 20626191 | pmc = 2882973 | doi = 10.1177/00333549101250S407 }}</ref> Stigma towards TB may result in delays in seeking treatment,<ref name="EIU 2014"/> lower treatment compliance, and family members keeping cause of death secret<ref name="Courtwright 2010"/> – allowing the disease to spread further.<ref name="EIU 2014"/> In contrast, in Russia stigma was associated with increased treatment compliance.<ref name="Courtwright 2010"/> TB stigma also affects socially marginalized individuals to a greater degree and varies between regions.<ref name="Courtwright 2010"/> 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.<ref name="Courtwright 2010"/> Some studies have shown TB education programs to be effective in decreasing stigma, and may thus be effective in increasing treatment adherence.<ref name="Courtwright 2010"/> 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.<ref name="Courtwright 2010"/> 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.<ref name="EIU 2014"/> A greater understanding of the social and cultural dimensions of tuberculosis may also help with stigma reduction.<ref>{{cite journal | vauthors = Mason PH, Roy A, Spillane J, Singh P | title = Social, Historical and Cultural Dimensions of Tuberculosis | journal = Journal of Biosocial Science | volume = 48 | issue = 2 | pages = 206–32 | date = March 2016 | pmid = 25997539 | doi = 10.1017/S0021932015000115 | doi-access = free }}</ref> == Research == {{see also|International Congress on Tuberculosis}} The BCG vaccine has limitations, and research to develop new TB vaccines is ongoing.<ref name=VacRes2011>{{cite journal | vauthors = Martín Montañés C, Gicquel B | title = New tuberculosis vaccines | journal = Enfermedades Infecciosas y Microbiologia Clinica | volume = 29 | pages = 57–62 | date = March 2011 | issue = Suppl 1 | pmid = 21420568 | doi = 10.1016/S0213-005X(11)70019-2 }}</ref> A number of potential candidates are currently in [[clinical trial|phase I and II clinical trials]].<ref name=VacRes2011/><ref>{{cite journal | vauthors = Zhu B, Dockrell HM, Ottenhoff TH, Evans TG, Zhang Y | title = Tuberculosis vaccines: Opportunities and challenges | journal = Respirology | volume = 23 | issue = 4 | pages = 359–368 | date = April 2018 | pmid = 29341430 | doi = 10.1111/resp.13245 | doi-access = free | hdl = 1887/77156 | hdl-access = free }}</ref> 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.<ref name=VacRes2011/> [[MVA85A]], an example of a subunit vaccine, is in trials in South Africa as of 2006, is based on a genetically modified [[vaccinia]] virus.<ref name=Ibanga_2006>{{cite journal | vauthors = Ibanga HB, Brookes RH, Hill PC, Owiafe PK, Fletcher HA, Lienhardt C, Hill AV, Adegbola RA, McShane H | display-authors = 6 | title = Early clinical trials with a new tuberculosis vaccine, MVA85A, in tuberculosis-endemic countries: issues in study design | journal = The Lancet. Infectious Diseases | volume = 6 | issue = 8 | pages = 522–8 | date = August 2006 | pmid = 16870530 | doi = 10.1016/S1473-3099(06)70552-7 }}</ref> Vaccines are hoped to play a significant role in treatment of both latent and active disease.<ref>{{cite journal | vauthors = Kaufmann SH | title = Future vaccination strategies against tuberculosis: thinking outside the box | journal = Immunity | volume = 33 | issue = 4 | pages = 567–77 | date = October 2010 | pmid = 21029966 | doi = 10.1016/j.immuni.2010.09.015 | doi-access = free }}</ref> 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]].<ref>{{cite journal| vauthors = Webber D, Kremer M |url=https://www.who.int/bulletin/archives/79(8)735.pdf |title=Stimulating Industrial R&D for Neglected Infectious Diseases: Economic Perspectives|journal=Bulletin of the World Health Organization|volume=79|issue=8|year=2001|pages=693–801|url-status=live|archive-url=https://web.archive.org/web/20070926012031/http://www.who.int/bulletin/archives/79(8)735.pdf|archive-date=26 September 2007}}</ref><ref>{{cite journal| vauthors = Barder O, Kremer M, Williams H |s2cid=154454583|url=http://www.bepress.com/ev/vol3/iss3/art1|title=Advance Market Commitments: A Policy to Stimulate Investment in Vaccines for Neglected Diseases|journal=The Economists' Voice|volume=3|year=2006|issue=3|doi=10.2202/1553-3832.1144|url-status=dead|archive-url=https://web.archive.org/web/20061105083659/http://www.bepress.com/ev/vol3/iss3/art1|archive-date=5 November 2006}}</ref> A number of groups, including the [[Stop TB Partnership]],<ref>{{cite book | author = Department of Economic and Social Affairs |title=Achieving the global public health agenda: dialogues at the Economic and Social Council|year=2009|publisher=[[United Nations]]|location=New York|isbn=978-92-1-104596-3|page=103|url=https://books.google.com/books?id=VeF9dv74C4MC&pg=PA103 |url-status=live|archive-url=https://web.archive.org/web/20150906212013/https://books.google.com/books?id=VeF9dv74C4MC&pg=PA103|archive-date=6 September 2015}}</ref> the South African Tuberculosis Vaccine Initiative, and the Aeras Global TB Vaccine Foundation, are involved with research.<ref>{{cite book| vauthors = Jong EC, Zuckerman JN |title=Travelers' vaccines|year=2010|publisher=People's Medical Publishing House|location=Shelton, CT|isbn=978-1-60795-045-5|page=319|url=https://books.google.com/books?id=BKRpWFEy66wC&pg=PA319|edition=2nd|url-status=live|archive-url=https://web.archive.org/web/20150906203627/https://books.google.com/books?id=BKRpWFEy66wC&pg=PA319|archive-date=6 September 2015}}</ref> 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.<ref>{{Cite web|last=Bill and Melinda Gates Foundation Announcement |title=Gates Foundation Commits $82.9 Million to Develop New Tuberculosis Vaccines |date=12 February 2004 |url=http://www.globalhealth.org/news/article/4134 |url-status=dead |archive-url=https://web.archive.org/web/20091010163118/http://www.globalhealth.org/news/article/4134 |archive-date=10 October 2009 }}</ref><ref>{{Cite web| vauthors = Nightingale K |title=Gates foundation gives US$280 million to fight TB|date=19 September 2007|url=http://www.scidev.net/en/news/gates-foundation-gives-us280-million-to-fight-tb.html|url-status=live|archive-url=https://web.archive.org/web/20081201175618/http://www.scidev.net/en/news/gates-foundation-gives-us280-million-to-fight-tb.html|archive-date=1 December 2008}}</ref> In 2012 a new medication regimen was approved in the US for multidrug-resistant tuberculosis, using [[bedaquiline]] as well as existing drugs. There were initial concerns about the safety of this drug,<ref name="Zumla2012">{{cite journal |vauthors=Zumla A, Hafner R, Lienhardt C, Hoelscher M, Nunn A |date=March 2012 |title=Advancing the development of tuberculosis therapy |url=http://www.nature.com/articles/nrd3694 |url-status=live |journal=Nature Reviews. Drug Discovery |volume=11 |issue=3 |pages=171–2 |doi=10.1038/nrd3694 |pmid=22378254 |s2cid=7232434 |archive-url=https://web.archive.org/web/20200112192759/https://www.nature.com/articles/nrd3694 |archive-date=12 January 2020 |access-date=8 May 2020}}</ref><ref>{{cite news |date=31 December 2012 |title=J&J Sirturo Wins FDA Approval to Treat Drug-Resistant TB |url=https://www.bloomberg.com/news/2012-12-31/j-j-sirturo-wins-fda-approval-to-treat-drug-resistant-tb.html |url-status=live |archive-url=https://web.archive.org/web/20130104110903/http://www.bloomberg.com/news/2012-12-31/j-j-sirturo-wins-fda-approval-to-treat-drug-resistant-tb.html |archive-date=4 January 2013 |access-date=1 January 2013 |newspaper=[[Bloomberg News]]}}</ref><ref name="Avorn 2013 1349–1350">{{cite journal |vauthors=Avorn J |date=April 2013 |title=Approval of a tuberculosis drug based on a paradoxical surrogate measure |journal=JAMA |volume=309 |issue=13 |pages=1349–50 |doi=10.1001/jama.2013.623 |pmid=23430122}}</ref><ref name="US Food and Drug Administration website">{{cite web |last=US Food and Drug Administration |title=Briefing Package: NDA 204–384: Sirturo |url=https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti-%20InfectiveDrugsAdvisoryCommittee/UCM329258.pdf |url-status=live |archive-url=https://web.archive.org/web/20140104212835/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti-%20InfectiveDrugsAdvisoryCommittee/UCM329258.pdf |archive-date=4 January 2014 |website=[[Food and Drug Administration]]}}</ref><ref>{{cite journal |vauthors=Zuckerman D, Yttri J |date=January 2013 |title=Antibiotics: When science and wishful thinking collide |url=https://www.healthaffairs.org/do/10.1377/forefront.20130125.027503 |url-status=live |journal=Health Affairs |doi=10.1377/forefront.20130125.027503 |archive-url=https://web.archive.org/web/20220329211404/https://www.healthaffairs.org/do/10.1377/forefront.20130125.027503 |archive-date=29 March 2022 |access-date=29 March 2022}}</ref> but later research on larger groups found that this regimen improved health outcomes.<ref>{{Cite journal |last1=Mbuagbaw |first1=Lawrence |last2=Guglielmetti |first2=Lorenzo |last3=Hewison |first3=Catherine |last4=Bakare |first4=Nyasha |last5=Bastard |first5=Mathieu |last6=Caumes |first6=Eric |last7=Fréchet-Jachym |first7=Mathilde |last8=Robert |first8=Jérôme |last9=Veziris |first9=Nicolas |last10=Khachatryan |first10=Naira |last11=Kotrikadze |first11=Tinatin |last12=Hayrapetyan |first12=Armen |last13=Avaliani |first13=Zaza |last14=Schünemann |first14=Holger J. |last15=Lienhardt |first15=Christian |date=May 2019 |title=Outcomes of Bedaquiline Treatment in Patients with Multidrug-Resistant Tuberculosis |journal=Emerging Infectious Diseases |volume=25 |issue=5 |pages=936–943 |doi=10.3201/eid2505.181823 |issn=1080-6040 |pmc=6478224 |pmid=31002070}}</ref> By 2017 the drug was used in at least 89 countries.<ref>{{Cite journal |last1=Khoshnood |first1=Saeed |last2=Taki |first2=Elahe |last3=Sadeghifard |first3=Nourkhoda |last4=Kaviar |first4=Vahab Hassan |last5=Haddadi |first5=Mohammad Hossein |last6=Farshadzadeh |first6=Zahra |last7=Kouhsari |first7=Ebrahim |last8=Goudarzi |first8=Mehdi |last9=Heidary |first9=Mohsen |date=2021-10-07 |title=Mechanism of Action, Resistance, Synergism, and Clinical Implications of Delamanid Against Multidrug-Resistant Mycobacterium tuberculosis |journal=Frontiers in Microbiology |volume=12 |pages=717045 |doi=10.3389/fmicb.2021.717045 |doi-access=free |issn=1664-302X |pmc=8529252 |pmid=34690963}}</ref> Another new drug is [[delamanid]], which was first approved by the European Medicines Agency in 2013 to be used in multidrug-resistant tuberculosis patients,<ref>{{Cite web |date=2013-12-03 |title=European Medicines Agency - News and Events - European Medicines Agency recommends two new treatment options for tuberculosis |url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/11/news_detail_001972.jsp&mid=WC0b01ac058004d5c1 |access-date=2024-04-09 |archive-url=https://web.archive.org/web/20131203022613/http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/11/news_detail_001972.jsp&mid=WC0b01ac058004d5c1 |archive-date=3 December 2013 }}</ref> and by 2017 was used in at least 54 countries.<ref>{{Cite journal |last1=Khoshnood |first1=Saeed |last2=Taki |first2=Elahe |last3=Sadeghifard |first3=Nourkhoda |last4=Kaviar |first4=Vahab Hassan |last5=Haddadi |first5=Mohammad Hossein |last6=Farshadzadeh |first6=Zahra |last7=Kouhsari |first7=Ebrahim |last8=Goudarzi |first8=Mehdi |last9=Heidary |first9=Mohsen |date=2021-10-07 |title=Mechanism of Action, Resistance, Synergism, and Clinical Implications of Delamanid Against Multidrug-Resistant Mycobacterium tuberculosis |journal=Frontiers in Microbiology |volume=12 |pages=717045 |doi=10.3389/fmicb.2021.717045 |doi-access=free |issn=1664-302X |pmc=8529252 |pmid=34690963}}</ref> Steroids add-on therapy has not shown any benefits for active pulmonary tuberculosis infection.<ref>{{cite journal | vauthors = Critchley JA, Orton LC, Pearson F | title = Adjunctive steroid therapy for managing pulmonary tuberculosis | journal = The Cochrane Database of Systematic Reviews | issue = 11 | pages = CD011370 | date = November 2014 | volume = 2014 | pmid = 25387839 | pmc = 6532561 | doi = 10.1002/14651858.CD011370 }}</ref> == Other animals == Mycobacteria infect many different animals, including birds,<ref>{{cite journal | vauthors = Shivaprasad HL, Palmieri C | title = Pathology of mycobacteriosis in birds | journal = The Veterinary Clinics of North America. Exotic Animal Practice | volume = 15 | issue = 1 | pages = 41–55, v–vi | date = January 2012 | pmid = 22244112 | doi = 10.1016/j.cvex.2011.11.004 }}</ref> fish, rodents,<ref>{{cite journal | vauthors = Reavill DR, Schmidt RE | title = Mycobacterial lesions in fish, amphibians, reptiles, rodents, lagomorphs, and ferrets with reference to animal models | journal = The Veterinary Clinics of North America. Exotic Animal Practice | volume = 15 | issue = 1 | pages = 25–40, v | date = January 2012 | pmid = 22244111 | doi = 10.1016/j.cvex.2011.10.001 }}</ref> and reptiles.<ref>{{cite journal | vauthors = Mitchell MA | title = Mycobacterial infections in reptiles | journal = The Veterinary Clinics of North America. Exotic Animal Practice | volume = 15 | issue = 1 | pages = 101–11, vii | date = January 2012 | pmid = 22244116 | doi = 10.1016/j.cvex.2011.10.002 }}</ref> The subspecies ''Mycobacterium tuberculosis'', though, is rarely present in wild animals.<ref>{{cite book| vauthors = Wobeser GA |title=Essentials of disease in wild animals|year=2006|publisher=Blackwell Publishing|location=Ames, IO [u.a.]|isbn=978-0-8138-0589-4|page=170|url=https://books.google.com/books?id=JgyS6fxVasYC&pg=PA170|edition=1st|url-status=live|archive-url=https://web.archive.org/web/20150906172856/https://books.google.com/books?id=JgyS6fxVasYC&pg=PA170|archive-date=6 September 2015}}</ref> An effort to eradicate bovine tuberculosis caused by ''[[Mycobacterium bovis]]'' from the cattle and deer herds of [[New Zealand]] has been relatively successful.<ref>{{cite journal | vauthors = Ryan TJ, Livingstone PG, Ramsey DS, de Lisle GW, Nugent G, Collins DM, Buddle BM | display-authors = 6 | title = Advances in understanding disease epidemiology and implications for control and eradication of tuberculosis in livestock: the experience from New Zealand | journal = Veterinary Microbiology | volume = 112 | issue = 2–4 | pages = 211–19 | date = February 2006 | pmid = 16330161 | doi = 10.1016/j.vetmic.2005.11.025 }}</ref> Efforts in Great Britain have been less successful.<ref>{{cite journal | vauthors = White PC, Böhm M, Marion G, Hutchings MR | title = Control of bovine tuberculosis in British livestock: there is no 'silver bullet' | journal = Trends in Microbiology | volume = 16 | issue = 9 | pages = 420–7 | date = September 2008 | pmid = 18706814 | doi = 10.1016/j.tim.2008.06.005 | citeseerx = 10.1.1.566.5547 }}</ref><ref>{{cite journal | vauthors = Ward AI, Judge J, Delahay RJ | title = Farm husbandry and badger behaviour: opportunities to manage badger to cattle transmission of Mycobacterium bovis? | journal = Preventive Veterinary Medicine | volume = 93 | issue = 1 | pages = 2–10 | date = January 2010 | pmid = 19846226 | doi = 10.1016/j.prevetmed.2009.09.014 }}</ref> {{As of|2015}}, tuberculosis appears to be widespread among captive [[elephant]]s 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 [[circus]]es and [[zoo]]s.<ref name="Holt">{{cite web | vauthors = Holt N |title=The Infected Elephant in the Room |url= http://www.slate.com/blogs/wild_things/2015/03/24/elephant_tuberculosis_epidemic_zoo_and_circus_animals_passing_tb_to_humans.html|website=[[Slate (magazine)|Slate]]|access-date=5 April 2016|date=24 March 2015|url-status=live|archive-url=https://web.archive.org/web/20160414151050/http://www.slate.com/blogs/wild_things/2015/03/24/elephant_tuberculosis_epidemic_zoo_and_circus_animals_passing_tb_to_humans.html|archive-date=14 April 2016}}</ref><ref name="Mikota">{{cite web| vauthors = Mikota SK |title=A Brief History of TB in Elephants |url= https://www.aphis.usda.gov/animal_welfare/downloads/elephant/A%20Brief%20History%20of%20TB%20in%20Elephants.pdf|publisher=[[Animal and Plant Health Inspection Service]] (APHIS)|access-date=5 April 2016|url-status=live|archive-url=https://web.archive.org/web/20161006125349/https://www.aphis.usda.gov/animal_welfare/downloads/elephant/A%20Brief%20History%20of%20TB%20in%20Elephants.pdf|archive-date=6 October 2016}}</ref> == See also == * [[List of deaths due to tuberculosis]] == Notes == {{notelist}} == References == {{Reflist}} == External links == <!-- Please DO ''not'' add new external links! Instead please submit them on the Talk page for discussion about their proposed inclusion. Thank you. --> {{Sisterlinks|d=Q12204|wikt=tuberculosis|q=Tuberculosis|c=Category:Tuberculosis|n=no|b=no|v=no|voy=no|m=no|mw=no|s=no|species=Mycobacterium tuberculosis}} {{Offline|med}} * {{curlie|Health/Conditions_and_Diseases/Infectious_Diseases/Mycobacterial/Tuberculosis/}} * {{cite web |url=https://www.cdc.gov/tb/default.htm |publisher=Centers for Disease Control and Prevention (CDC) |title=Tuberculosis (TB)|date=24 October 2018 }} * {{cite web |url=http://www.hpa.org.uk/infections/topics_az/tb/menu.htm |publisher=[[Health Protection Agency]] |location=London |title=Tuberculosis (TB) |url-status=dead |archive-url=https://web.archive.org/web/20070705100742/http://www.hpa.org.uk/infections/topics_az/tb/menu.htm |archive-date=5 July 2007 }} * [https://www.who.int/tb/global-tb-report-infographic.pdf?ua=1 WHO global 2016 TB report (infographic)] * [https://www.who.int/tb/country/data/profiles/en/ WHO tuberculosis country profiles] * [https://americanarchive.org/catalog/cpb-aacip_529-1c1td9p67s "Tuberculosis Among African Americans"], 1990-11-01, ''[[In Black America]]''; [[KUT|KUT Radio]], [[American Archive of Public Broadcasting]] ([[WGBH Educational Foundation|WGBH]] and the Library of Congress) * [https://www.newtbdrugs.org/ Working Group on New TB drugs], tracking clinical trials and drug candidates {{Medical condition classification and resources | DiseasesDB = 8515 | ICD11 = {{ICD11|1B10}}-{{ICD11|1B1Z}} | ICD10 = {{ICD10|A15-A19}} | ICD9 = {{ICD9|010}}–{{ICD9|018}} | OMIM = 607948 | MedlinePlus = 000077 | MedlinePlus_mult = {{MedlinePlus2|000624}} | eMedicineSubj = med | eMedicineTopic = 2324 | eMedicine_mult = {{eMedicine2|emerg|618}} {{eMedicine2|radio|411}} | MeshID = D014376 | Orphanet=3389 | Scholia=Q12204 }} {{Gram-positive actinobacteria diseases}} {{Tuberculosis}} {{Diseases of Poverty}} {{Portal bar | Medicine}} {{Authority control}} [[Category:Tuberculosis| ]] [[Category:Airborne diseases]] [[Category:Articles containing video clips]] [[Category:Health in Africa]] [[Category:Healthcare-associated infections]] [[Category:Infectious causes of cancer]] [[Category:Mycobacterium-related cutaneous conditions]] [[Category:Vaccine-preventable diseases]] [[Category:Wikipedia infectious disease articles ready to translate]] [[Category:Wikipedia medicine articles ready to translate (full)]] Summary: Please note that all contributions to Christianpedia may be edited, altered, or removed by other contributors. If you do not want your writing to be edited mercilessly, then do not submit it here. You are also promising us that you wrote this yourself, or copied it from a public domain or similar free resource (see Christianpedia:Copyrights for details). Do not submit copyrighted work without permission! Cancel Editing help (opens in new window) Templates used on this page: Tuberculosis (edit) Template:As of (edit) Template:Authority control (edit) Template:Circa (edit) Template:Citation needed (edit) Template:Cite book (edit) Template:Cite journal (edit) Template:Cite magazine (edit) Template:Cite news (edit) Template:Cite thesis (edit) Template:Cite web (edit) Template:Clarify (edit) Template:Clear (edit) Template:Col-begin (edit) Template:Col-break (edit) Template:Col-end (edit) Template:Curlie (edit) Template:DMCA (edit) Template:Diseases of Poverty (edit) Template:Fix (edit) Template:Fix-span (edit) Template:Further information (edit) Template:Good article (edit) Template:Gram-positive actinobacteria diseases (edit) Template:Infobox medical condition (new) (edit) Template:Lang (edit) Template:Legend (edit) Template:Main (edit) Template:Main other (edit) Template:Medical condition classification and resources (edit) Template:NICE (edit) Template:Notelist (edit) Template:Offline (edit) Template:Portal bar (edit) Template:Pp-move (edit) Template:Pp-move-indef (edit) Template:Pp-semi-indef (edit) Template:Reflist (edit) Template:Reflist/styles.css (edit) Template:See also (edit) Template:Short description (edit) Template:Sisterlinks (edit) Template:TOC limit (edit) Template:Tuberculosis (edit) Template:Use dmy dates (edit) Template:WhoNamedIt (edit) Template:Yesno (edit) Module:Arguments (edit) Module:Check for unknown parameters (edit) Module:Citation/CS1 (edit) Module:Citation/CS1/COinS (edit) Module:Citation/CS1/Configuration (edit) Module:Citation/CS1/Date validation (edit) Module:Citation/CS1/Identifiers (edit) Module:Citation/CS1/Utilities (edit) Module:Citation/CS1/Whitelist (edit) Module:Citation/CS1/styles.css (edit) Module:Format link (edit) Module:Hatnote (edit) Module:Hatnote/styles.css (edit) Module:Hatnote list (edit) Module:Labelled list hatnote (edit) Module:Portal bar (view source) Module:Protection banner (view source) Module:Unsubst (edit) Module:Yesno (edit) Discuss this page