Editing Tuberculosis (section)

== 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="Adkinson-2010"/> It [[cell division|divides]] every 16 to 20 hours, which is slow 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 a complex, [[lipid]]-rich [[cell envelope]], with the high lipid content of the outer membrane acting as a robust barrier contributing to their [[drug resistance]].<ref>{{cite book |title=Infectious Diseases: A Clinical Short Course, 2nd ed. |vauthors=Southwick F |publisher=McGraw-Hill Medical Publishing Division |year=2007 |isbn=978-0-07-147722-2 |pages=104, 313–14 |chapter=Chapter 4: Pulmonary Infections}}</ref><ref>{{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>{{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>

The term [[Mycobacterium tuberculosis complex|''M. tuberculosis'' complex]] describes a genetically related group of ''[[Mycobacterium]]'' species that can cause tuberculosis in humans or other animals. It  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 |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. bovis'' causes bovine TB and was once a common cause of human TB, but the introduction of [[pasteurisation|pasteurized milk]] has almost eliminated this as a public health problem in developed countries.<ref name="Kumar-2007">{{Cite book |title=Robbins Basic Pathology |vauthors=Kumar V, Robbins SL |date=2007 |publisher=Elsevier |isbn=978-1-4160-2973-1 |edition=8th |location=Philadelphia |oclc=69672074}}</ref><ref>{{cite journal |vauthors=Thoen C, Lobue P, de Kantor I |date=February 2006 |title=The importance of Mycobacterium bovis as a zoonosis |journal=Veterinary Microbiology |volume=112 |issue=2–4 |pages=339–45 |doi=10.1016/j.vetmic.2005.11.047 |pmid=16387455}}</ref> ''M. africanum'' is not widespread, but it is a significant cause of human TB 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 | 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 | 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. 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'' appears to have a [[natural reservoir]] in small [[Rodent|rodents]] such as mice and voles, but can infect larger mammals. It is rare in humans 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 | 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><ref>{{cite journal | vauthors = Smith NH, Crawshaw T, Parry J, Birtles RJ | title = Mycobacterium microti: More diverse than previously thought | journal = Journal of Clinical Microbiology | volume = 47 | issue = 8 | pages = 2551–2559 | date = August 2009 | pmid = 19535520 | pmc = 2725668 | doi = 10.1128/jcm.00638-09 }}</ref>

There are other known [[Mycobacterium|mycobacteria]] which cause lung disease resembling TB. ''[[Mycobacterium avium complex|M. avium complex]]'' is an environmental microorganism found in soil and water sources worldwide, which tends to present as an [[opportunistic infection]] in immunocompromised people.<ref>{{Cite web |title=MAC Lung Disease |url=https://www.lung.org/lung-health-diseases/lung-disease-lookup/mac-lung-disease |access-date=2025-03-18 |website=American Lung Association |language=en}}</ref><ref>{{cite journal | vauthors = Busatto C, Vianna JS, da Silva LV, Ramis IB, da Silva PE | title = Mycobacterium avium: an overview | journal = Tuberculosis | volume = 114 | pages = 127–134 | date = January 2019 | pmid = 30711152 | doi = 10.1016/j.tube.2018.12.004 }}</ref> The natural reservoir of ''[[Mycobacterium kansasii|M. kansasii]]'' is unknown, but it has been found in tap water; it is most likely to infect humans with lung disease or who smoke.<ref>{{cite journal | vauthors = Johnston JC, Chiang L, Elwood K | title = Mycobacterium kansasii | journal = Microbiology Spectrum | volume = 5 | issue = 1 | pages = 10.1128/microbiolspec.tnmi7–0011–2016 | date = January 2017 | pmid = 28185617 | pmc = 11687434 | doi = 10.1128/microbiolspec.tnmi7-0011-2016 }}</ref> These two species are classified as "[[nontuberculous mycobacteria]]".<ref>{{cite journal | 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–S25 | 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 ===

Tuberculosis spreads through the air when people with active pulmonary TB cough, sneeze, speak, or sing, releasing tiny airborne [[Respiratory droplet|droplets]] containing the bacteria. Anyone nearby can breathe in these droplets and become infected. The droplets can remain airborne and infective for several hours, and are more likely to persist in poorly ventilated areas.<ref>{{Cite web |date=2025-02-05 |title=Tuberculosis: Causes and How It Spreads |url=https://www.cdc.gov/tb/causes/index.html |access-date=2025-03-18 |website=Centers for Disease Control and Prevention |language=en-us}}</ref>

=== Risk factors ===
{{Main|Risk factors for tuberculosis}}
Risk factors for TB include exposure to droplets from people with active TB and environmental-related and health-condition related factors that decrease a person's immune system response such as HIV or taking immunosuppressant medications.<ref name="PHA_Canada_2024" />

==== Close contact ====
Prolonged, frequent, or close contact with people who have active TB is a high high risk factor for becoming infected; this group includes health care workers and children where a family member is infected.<ref>{{Cite web |date=2024-12-10 |title=Clinical Overview of Latent Tuberculosis Infection |url=https://www.cdc.gov/tb/hcp/clinical-overview/latent-tuberculosis-infection.html |access-date=2025-03-19 |website=Centers for Disease Control and Prevention |language=en-us}}</ref><ref name="Ahmed_2011">{{cite journal |vauthors=Ahmed N, Hasnain SE |date=September 2011 |title=Molecular epidemiology of tuberculosis in India: moving forward with a systems biology approach |journal=Tuberculosis |volume=91 |issue=5 |pages=407–13 |doi=10.1016/j.tube.2011.03.006 |pmid=21514230}}</ref> Transmission is most likely to occur from only people with active TB – those with latent infection are not thought to be contagious.<ref name="Kumar-2007" /> Environmental risk factors which put a person at closer contact with infective droplets from a person infected with TB are overcrowding, poor ventilation, or close proximity to a potentially infective person.<ref name="Schmidt-2008">{{Cite journal |last=Schmidt |first=Charles W. |date=November 2008 |title=Linking TB and the Environment: An Overlooked Mitigation Strategy |journal=Environmental Health Perspectives |volume=116 |issue=11 |pages=A478–A485 |doi=10.1289/ehp.116-a478 |pmc=2592293 |pmid=19057686}}</ref><ref name="Narasimhan_2013">{{cite journal |vauthors=Narasimhan P, Wood J, Macintyre CR, Mathai D |date=2013 |title=Risk factors for tuberculosis |journal=Pulmonary Medicine |volume=2013 |page=828939 |doi=10.1155/2013/828939 |pmc=3583136 |pmid=23476764 |doi-access=free}}</ref> 

==== Immunodeficiencies ====

The most important risk factor globally for developing active TB is concurrent human immunodeficiency virus ([[HIV]]) infection; in 2023, 6.1% of those becoming infected with TB were also infected with HIV.<ref name="Who_Global_2024" /> [[Sub-Saharan Africa]] has a particularly high burden of HIV-associated TB.<ref name="WHO_Factsheet_2025" /> Of those without HIV infection who are infected with tuberculosis, about 5–15% develop active disease during their lifetimes;<ref name="Price_2024" /> in contrast, 30% of those co-infected with HIV develop the active disease.<ref name="Gibson_BMJ_2005" /> People living with HIV are estimated 16 times more likely to fall ill with TB than people without HIV; TB is the leading cause of death among people with HIV.<ref name="WHO_Factsheet_2025" />

Another important risk factor is use of medications which suppress the immune system; these include, [[chemotherapy]], medication for [[lupus]] or [[rheumatoid arthritis]], and medication after an [[Organ transplantation|organ transplant]].<ref name="PHA_Canada_2024">{{Cite web |date=2024-02-21 |title=Tuberculosis (TB): Prevention and risks |url=https://www.canada.ca/en/public-health/services/diseases/tuberculosis/prevention-risks.html |access-date=2025-03-20 |website=Public Health Agency of Canada}}</ref> Other risk factors include: [[alcoholism]], [[diabetes mellitus]], [[silicosis]], [[cigarette|tobacco smoking]], recreational drug use, severe kidney disease, head and neck cancer, low body weight.<ref name="PHA_Canada_2024" /><ref name="CDC_Risk_2016">{{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> Children, especially those under age five, have undeveloped immune systems and are at higher risk.<ref name="CDC_Risk_2016" />

Environmental factors which weaken the body's protective mechanisms and may put a person at additional risk of contracting TB include [[air pollution]], exposure to smoke (including [[tobacco smoke]]), and exposure (often [[Occupational safety and health|occupational]]) to dust or [[Particulate pollution|particulates]].<ref name="Schmidt-2008" />