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Mycobacterium avium subsp. paratuberculosis
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==Pathophysiology== MAP causes [[Johne's disease]] in [[cattle]] and other [[ruminant]]s. It has long been suspected as a causative agent in [[Crohn's disease]] in humans,<ref name=Hermon_2009>{{cite journal|author=Hermon-Taylor, J|title=''Mycobacterium avium'' subspecies ''paratuberculosis'', Crohn's disease and the Doomsday scenario|year=2009|journal=Gut Pathogens|volume=1|issue=15|doi=10.1186/1757-4749-1-15|pmid=19602288|pages=15|pmc=2718892 |doi-access=free }}.</ref><ref name=Freeman_2005>{{cite journal |vauthors=Freeman H, Noble M |title=Lack of evidence for ''Mycobacterium avium'' subspecies ''paratuberculosis'' in Crohn's disease regulation of immunity |journal=Inflammatory Bowel Diseases |year=2005 |volume=11 |issue=8 |pages=782β3 |url=http://www3.interscience.wiley.com/cgi-bin/fulltext/113522086/HTMLSTART |archive-url=https://archive.today/20110813032552/http://www3.interscience.wiley.com/cgi-bin/fulltext/113522086/HTMLSTART |url-status=dead |archive-date=2011-08-13 |doi=10.1097/01.MIB.0000179317.27132.24 |pmid=16043998|doi-access=free }}</ref> but studies have been unable to show definite correlation.<ref name="Feller">{{cite journal |doi=10.1016/S1473-3099(07)70211-6|pmid=17714674|title=Mycobacterium avium subspecies paratuberculosis and Crohn's disease: A systematic review and meta-analysis|journal=The Lancet Infectious Diseases|volume=7|issue=9|pages=607β613|year=2007|last1=Feller|first1=Martin|last2=Huwiler|first2=Karin|last3=Stephan|first3=Roger|last4=Altpeter|first4=Ekkehardt|last5=Shang|first5=Aijing|last6=Furrer|first6=Hansjakob|last7=Pfyffer|first7=Gaby E|last8=Jemmi|first8=Thomas|last9=Baumgartner|first9=Andreas|last10=Egger|first10=Matthias}}</ref> One study has argued that the presence of antibodies against ''Mycobacterium avium'' subspecies ''paratuberculosis'' is associated with increased propensity of patients with Crohn's disease to receive biological therapy.<ref>{{cite journal | vauthors = Proietti E, Fuhler GM, Peppelenbosch MP | title = Mycobacterium Avium Subspecies Paratuberculosis Infection and Biological Treatment of IBD: Cause or Consequence? | journal = J Crohns Colitis | volume = 15 | issue = 8 | pages = 1247β1249| date = 2021-08-02 | pmid = 33735385 | pmc = 8328286 | doi = 10.1093/ecco-jcc/jjab027 | doi-access = free }}</ref> Recent studies have shown that MAP present in [[milk]] can survive [[pasteurization]], which has raised human health concerns due to the widespread nature of MAP in modern dairy herds. MAP survival during [[pasteurization]] is dependent on the D<sub>72C</sub>-value of the strains present and their concentration in milk.<ref>Mullan, W.M.A. (2015). HTST pasteurization. Is it time to raise statutory time / temperature conditions to destroy Mycobacterium avium subsp. paratuberculosis (MAP)?. [On-line]. Available from: https://www.dairyscience.info/index.php/food-model/277-htst-pasteurization.html . Accessed: 30 July 2018. Updated October, 2017; April 2018. [https://www.dairyscience.info/index.php/food-model/277-htst-pasteurization.html]</ref> It is heat resistant and is capable of sequestering itself inside white blood cells, which may contribute to its persistence in milk. It has also been reported to survive [[Water chlorination|chlorination]] in municipal water supplies. MAP is a slow growing organism and is difficult to culture. Bacterial cultures were regarded as Gold standards for detection of MAP. Detection is very limited in fresh tissues, food, and water. Recently, John Aitken and Otakaro Pathways have discovered a method to culture MAP from human blood. Testing is ongoing. Professor John Hermon-Taylor of King's College London is developing a new vector type anti MAP vaccine which he claims is both curative and preventative. Stage 1 human trials began in January 2017 and concluded successfully in September 2019. He is also developing a companion MAP blood test.{{Citation needed|date=December 2022}}{{Primary source inline|date=December 2022}} It is not susceptible to antituberculosis drugs (which can generally kill ''[[Mycobacterium tuberculosis]]''). MAP is susceptible to [[antibiotics]] used to treat Mycobacterium avium disease, such as [[rifabutin]] and [[clarithromycin]], however the capacity of these antibiotics to eradicate MAP infection in vivo has not been established.{{Citation needed|date=December 2022}}{{Primary source inline|date=December 2022}} ===Crohn's disease=== MAP is recognized as a multi-host mycobacterial pathogen with a proven specific ability to initiate and maintain systemic infection and [[chronic inflammation]] of the intestine of a range of histopathological types in many animal species, including primates.<ref name="Johnes">{{cite web |title=Johne's Information Center |url=http://www.johnes.org/ |access-date=2008-06-13}}</ref> MAP has been found in larger numbers within the intestines of Crohn's disease patients<ref name="pmid16443282">{{cite journal|year=1992|title=Mycobacterium paratuberculosis DNA in Crohn's disease tissue|journal=Gut|volume=33|issue=7|pages=890β6|doi=10.1136/gut.33.7.890|pmc=1379400|pmid=1644328|vauthors=Sanderson JD, Moss MT, Tizard ML, Hermon-Taylor J}}</ref> and in significant amount of [[irritable bowel syndrome]] patients<ref>{{Cite journal|last1=Scanu|first1=Antonio M.|last2=Bull|first2=Tim J.|last3=Cannas|first3=Sara|last4=Sanderson|first4=Jeremy D.|last5=Sechi|first5=Leonardo A.|last6=Dettori|first6=Giuseppe|last7=Zanetti|first7=Stefania|last8=Hermon-Taylor|first8=John|date=December 2007|title=Mycobacterium avium Subspecies paratuberculosis Infection in Cases of Irritable Bowel Syndrome and Comparison with Crohn's Disease and Johne's Disease: Common Neural and Immune Pathogenicities|journal=Journal of Clinical Microbiology|volume=45|issue=12|pages=3883β3890|doi=10.1128/JCM.01371-07|issn=0095-1137|pmc=2168579|pmid=17913930|quote=Mycobacterium avium subsp. paratuberculosis was detected in 15 of 20 (75%) patients with irritable bowel syndrome, 3 of 20 (15%) healthy controls, and 20 of 23 (87%) people with Crohn's disease}}</ref> compared to those with [[ulcerative colitis]] or otherwise healthy controls. One study concluded that MAP "may act as a causative agent, have a role in the context of secondary infection, which may exacerbate the disease, or represent non-pathogenic colonisation."<ref name="Feller"/> The [[Crohns MAP Vaccine]] is an experimental vaccine based on this hypothesis.<ref>{{Cite web|title=The Crohn's Vaccine|url=https://crohnsmapvaccine.com/vaccine/|access-date=2021-06-19|website=Crohn's MAP Vaccine|language=en-GB}}</ref>
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