Editing Paratuberculosis

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| field           = [[Veterinary medicine]]
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'''Paratuberculosis''' is a contagious, chronic and sometimes fatal [[infection]] that primarily affects the [[small intestine]] of [[ruminant]]s.<ref name="bcrcj">{{cite web |last1=Hendrick |first1=Steve |last2=Waldner |first2=Cheryl |title=HOME» RESEARCH » JOHNE'S DISEASE |url=https://www.beefresearch.ca/research-topic.cfm/johnes-disease-51 |publisher=Beef Cattle Research Council |date=2 October 2019}}</ref>  It is caused by the [[bacterium]] [[Mycobacterium avium subspecies paratuberculosis|''Mycobacterium avium'' subspecies ''paratuberculosis'']].  Infections normally affect [[ruminant]]s ([[mammal]]s that have four compartments of their stomachs, of which the [[rumen]] is one), but have also been seen in a variety of nonruminant species, including rabbits, foxes, and birds. Horses, dogs, and nonhuman primates have been infected experimentally. Paratuberculosis is found worldwide, with some states in [[Australia]] (where it is usually called bovine [[Heinrich Albert Johne|Johne's disease]] or BJD) being the only areas proven to be free of the disease.<ref>Collins M. and Manning E. "Johne's Information Center" The University of Wisconsin-School of Veterinary Medicine. 13 March 2003.</ref> At least in Canada, the signs of BJD usually start when cattle are four to seven years of age, and then usually only are diagnosed in one animal at a time.<ref name="ccaj">{{cite news |last1=Furber |first1=Debbie |title=When Johne's hits home |url=https://www.canadiancattlemen.ca/features/when-johnes-hits-home/ |publisher=Canadian Cattlemen The Beef Magazine |date=16 December 2016}}</ref> Cattle "with signs of Johne’s disease shed billions of bacteria through their manure and serve as a major source of infection for future calves."<ref name="jded">{{cite news |last1=Hendrick |first1=Steve |title=Johne's Disease And The Ethical Dilemma |url=http://beefresearch.ln2.mdphosting.ca/blog/johnes-disease-and-the-ethical-dilemma/ |publisher=Beef Cattle Research Council |date=19 March 2013}}</ref>

Some sources define "paratuberculosis" by the lack of ''[[Mycobacterium tuberculosis]]'', rather than the presence of any specific infectious agent,<ref>{{DorlandsDict|six/000078685|paratuberculosis}}</ref> leaving ambiguous the appropriateness of the term to describe [[Buruli ulcer]] or [[Lady Windermere syndrome]].

==Bacterium==
The disease, discovered by [[Heinrich A. Johne]], a German bacteriologist and veterinarian, in 1905, is caused by a [[bacterium]] named [[Mycobacterium avium subspecies paratuberculosis|''Mycobacterium avium'' subspecies ''paratuberculosis'']], an [[acid-fast]] [[bacillus]], often abbreviated MAP. MAP is akin to, but distinct from, ''[[Mycobacterium tuberculosis]]'', the main cause of [[tuberculosis]] in humans, and ''[[Mycobacterium bovis]]'', the main cause of tuberculosis in cattle and occasionally also in humans.  MAP is 99% genetically related to ''[[Mycobacterium avium]]'', but has different [[phenotype|phenotypic]] characteristics, such as:{{citation needed|date=June 2020}}
* slower growth
* requires the addition of an iron transport chemical known as [[mycobactin]] when grown ''[[in vitro]]''
* forms a rough colony when grown on a solid [[agar]] medium
* Infects [[mammal]]s instead of [[bird]]s
Also, the environmental distribution of MAP is markedly different from that of ''M. avium'', which can produce mycobactin, so can grow and multiply outside the body.{{citation needed|date=June 2020}}

==Control==
[[Pasteurization]] is used to kill the causal agent, ''M. paratuberculosis'', by heating [[cow's milk]] for a short time and then immediately cooling it.<ref name="holzinger97">{{cite journal |doi=10.20506/rst.16.2.1037|title=Milk pasteurisation and safety: A brief history and update|year=1997|last1=Holsinger|first1=V.H.|last2=Rajkowski|first2=K.T.|last3=Stabel|first3=J.R.|journal=Revue Scientifique et Technique de l'OIE|volume=16|issue=2|pages=441–451|pmid=9501358|url=https://www.oie.int/doc/ged/d9152.pdf}}</ref>{{Obsolete source|date=December 2022}}

== Signs and symptoms ==
In cattle, the main signs of paratuberculosis are [[diarrhea]] and [[wasting]]. Most cases are seen in 2- to 6-year-old animals. The initial signs can be subtle, and may be limited to weight loss, decreased milk production, or roughening of the hair coat. The diarrhea is usually thick, without blood, mucus, or epithelial debris, and may be intermittent.  Several weeks after the onset of diarrhea, a soft swelling may occur under the jaw. Known as "bottle jaw" or intermandibular [[edema]], this symptom is due to [[protein]] loss from the bloodstream into the digestive tract. Paratuberculosis is progressive; affected animals become increasingly emaciated and usually die as the result of [[dehydration]] and severe [[cachexia]].{{citation needed|date=June 2020}}

Signs are rarely evident until two or more years after the initial infection, which usually occurs shortly after birth.  Animals are most susceptible to the infection in the first year of life. Newborns most often become infected by swallowing small amounts of infected [[manure]] from the birthing environment or [[udder]] of the mother.  In addition, newborns may become infected while in the [[uterus]] or by swallowing bacteria passed in [[milk]] and [[colostrum]].  Animals exposed at an older age, or exposed to a very small dose of bacteria at a young age, are not likely to develop clinical disease until they are much older than two years.{{citation needed|date=June 2020}}

The clinical signs are similar in other ruminants. In sheep and goats, the wool or hair is often damaged and easily shed, and diarrhea is uncommon. In deer, paratuberculosis can progress rapidly. Intestinal disease has also been reported in rabbits and nonhuman primates.{{citation needed|date=June 2020}}

Unlike cattle and sheep, infections in deer often present with clinical illness in animals under one year of age.{{citation needed|date=June 2020}}

==Pathophysiology==
The primary site targeted by Johne's disease is the lower part of the intestine known as the [[ileum]].  The wall of the ileum contains a large number of pockets of lymphoid tissue known as [[Peyer's patch]]es that lie just beneath the interior surface of the intestine.  Peyer's patches are clusters of [[macrophage]]s and [[lymphocyte]]s organized much like [[lymph node]]s.  Covering Peyer's patches are a layer of cells called [[Microfold cell|M cells]].  These cells function to sample the content of the lumen of the intestines and pass antigens (bacteria) through to the underlying cells of the Peyer's patch to "show" these antigens to the macrophages and lymphocytes.  This is a means of "educating" the cells in a young animal about its environment, and is a protective mechanism designed to help the animal become immune to pathogens in its environment.{{citation needed|date=June 2020}}

Unfortunately, when M cells bring ''M. paratuberculosis'' to the Peyer's patch, the bacteria find an ideal place for growth.  Macrophages in Peyer's patches engulf ''M. paratuberculosis'' for the purpose of destroying the foreign invader, but for reasons yet unclear, these macrophages fail to do this.  Inside a macrophage, ''M. paratuberculosis'' multiplies until it eventually kills the cell, spreads, and infects other nearby cells.  In time, other parts of the ileum and other regions of the body are teeming with millions of the mycobacteria.  How ''M. paratuberculosis'' neutralizes or evades the normally efficient bacterial killing mechanisms of the macrophages is unknown, although the unusually resistant cell wall of mycobacteria likely plays an important role.{{citation needed|date=June 2020}}

The animal's immune system reacts to the ''M. paratuberculosis'' invasion by  recruiting more macrophages and lymphocytes to the site of the infection.  The lymphocytes release a variety of chemicals signals, called [[cytokine]]s, in an attempt to increase the bacterial killing power of the macrophages.  Macrophages fuse together, forming large cells, called multinucleated giant cells, in an apparent attempt to kill the mycobacteria.  Infiltration of infected tissues with millions of lymphocytes and macrophages leads to visible thickening of the intestines.  This prevents nutrient absorption, and diarrhea results.  Late in the infection, antibody production by the animal occurs to ''M. paratuberculosis'' in serum of animals, and is an indicator that clinical signs of disease and death from the infection will soon follow.{{citation needed|date=June 2020}}

For goats infected with this disease, the most apparent sign of having it is their bodies wasting away, even with a sufficient diet. If a goat develops Johne's and it has diarrhea, it is most likely going to die. When it has diarrhea, the goat is at the last stages of the disease. Herds should be tested once or twice a year to maintain the health and keep out the disease.{{citation needed|date=June 2020}}

==Morbidity and mortality==
In an endemic herd, only a minority of the animals develops clinical signs; most animals either eliminate the infection or become [[asymptomatic]] carriers. The [[mortality rate]] is about 1%, but up to 50% of the animals in the herd can be asymptomatically infected, resulting in losses in production. Once the symptoms appear, paratuberculosis is progressive and affected animals eventually die. The percentage of asymptomatic carriers that develop overt disease is unknown.<ref>Paratuberculosis. In the Merck Veterinary Manual, 8th ed. Edited by S. E. Aiello. Whitehouse Station, NJ: Merck and Co. 1998.</ref>

== Human risks ==

MAP is capable of causing Johne's-like symptoms in humans, though difficulty in testing for MAP infection presents a diagnostic hurdle.<ref>Richter, E., Wessling, J., Lügering, N., Domschke, W., & Rüsch-Gerdes, S. (2002). Mycobacterium avium subsp. paratuberculosis Infection in a Patient with HIV, Germany. Emerging Infectious Diseases, 8(7), 729–731. http://doi.org/10.3201/eid0807.010388</ref>

As of October 2019, neither the [[World Health Organization]] nor any individual nation had declared Johne's disease to be [[zoonotic]].<ref name=bcrcj/>

Clinical similarities are seen between Johne's disease in ruminants and [[inflammatory bowel disease]] in humans,<ref name="pmid18596984">{{cite journal  |vauthors=Juste RA, Elguezabal N, Garrido JM, etal |title=On the prevalence of M. avium subspecies paratuberculosis DNA in the blood of healthy individuals and patients with inflammatory bowel disease |journal=PLOS ONE |volume=3 |issue=7 |pages=e2537 |year=2008 |pmid=18596984 |pmc=2434204 |doi=10.1371/journal.pone.0002537 |bibcode=2008PLoSO...3.2537J |doi-access=free }} {{open access}}</ref> and because of this, some researchers contend the organism is causative factor in [[Crohn's disease]].<ref name="pmid17445316">{{cite journal |vauthors=Uzoigwe JC, Khaitsa ML, Gibbs PS |title=Epidemiological evidence for Mycobacterium avium subspecies paratuberculosis as a cause of Crohn's disease |journal=Epidemiol. Infect. |volume=135 |issue=7 |pages=1057–68 |date=October 2007 |pmid=17445316 |doi=10.1017/S0950268807008448 |pmc=2870686}}</ref><ref>Gitlin L, Borody TJ, Chamberlin W, Campbell J. Mycobacterium avium ss paratuberculosis-associated diseases: piecing the Crohn's puzzle together. J Clin Gastroenterol. 2012 Sep;46(8) 649-55. {{doi|10.1097/MCG.0b013e31825f2bce}}</ref> However, epidemiologic studies have provided variable results; in certain studies, the organism (or an immune response directed against it) has been much more frequently found in patients with Crohn's disease than asymptomatic people.{{Citation needed|date=December 2022}}

==Action and regulations==
Paratuberculosis is a [[reportable disease]] in some states of the US.<ref>[[United States Department of Agriculture]], [http://www.aphis.usda.gov/vs/ceah/ncahs/nahrs/NAHRS_disease_list.htm "National Animal Health Reporting System - Reportable Diseases"] {{webarchive|url=https://web.archive.org/web/20090829222421/http://www.aphis.usda.gov/vs/ceah/ncahs/nahrs/NAHRS_disease_list.htm |date=2009-08-29 }}</ref> US Federal regulations prohibit culture positive or DNA test-positive animals from being moved across state lines except for slaughter.{{Citation needed|date=May 2008}}

==References==
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== External links ==
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*[https://web.archive.org/web/20040928083100/http://www.aphis.usda.gov/vs/nahps/johnes/ USDA Johne's resource page]
*[http://www.johnes.org/ University of Wisconsin School of Veterinary Medicine Johne's Information Center]
*[https://www.paratuberculosis.com/ International Association for Paratuberculosis, Inc.]

{{Gram-positive actinobacteria diseases}}
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[[Category:Bovine diseases]]
[[Category:Sheep and goat diseases]]