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Do not fill this in! == 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" /> 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) Discuss this page