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Paratuberculosis/ Johne's Disease is caused by ''[[Mycobacterium avium subsp. paratuberculosis]]'', commonly seen in cattle, but known to affect all ruminants.  Common signs include enteritis and diarrhoea.
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Also known as: '''''Paratuberculosis
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** May be seen in zoo ruminants and goat herds.
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Caused by '''''M avium'' subsp. ''paratuberculosis''
** Particularly prevalent in Channel Island breeds.
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** Is now also becoming a problem in Limousin breeds.
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* Produces a chronic proliferative enteritis.
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* Is usually fatal, since the disease cannot be got rid of.
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* Animals may sometimes be carriers without showing clinical signs.
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** Once disease is present in a herd, it is very difficult to get rid of it.
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* Mycobacterium is excreted in urine and milk as well as in the faeces.
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===Clinical===
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==Introduction==
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Johne's Disease is a contagious and chronic disease of ruminants caused by the bacterium ''Mycobacterium avium subsp. paratuberculosis''. Affected species include cattle, sheep, goats and camelids. The disease is present worldwide with the highest prevalence occurring in dairy cattle. In these animals the disease is responsible for severe economic losses due to reduced reproductive performance, increased susceptibility to disease, reduced milk production and culling losses. Subclinical carriers can occur, shedding organisms in their faeces.
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* Clinical signs develop in older cows after calving i.e. 3 to 4 years of age. 
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==Pathogenesis==
* '''BUT'''  animals are infected as calves less than 6 months old
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''Mycobacterium paratuberculosis'' is an intracellular pathogen that is spread through herds via faecal-oral transmission, contaminated water and in utero. Young animals less than a year of age are most susceptible to infection and this usually occurs via ingestion of contaminated milk or colostrum. Environmental factors such as overcrowding and poor husbandry may increase the risk of infection.  
** The disease develops very slowly.
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* Clinical signs include:
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** Ongoing, chronic profuse diarrhoea.
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*** Paint like consistency.
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** Hindquarters and tail-caked with faeces
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** Faeces also splattered on walls.
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** Animal gradually fades away and dies over the course of months.
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===Pathogenesis===
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Following ingestion of ''M. paratuberculosis'' and uptake by the Peyer's patches, infection begins in the ileum. ''M. paratuberculosis'' infects macrophages in the gastrointestinal tract and lymph nodes leading to a granulomatous inflammatory response. This leads to malabsorption and a [[Protein Losing Enteropathy|protein-losing enteropathy]].
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* Organisms get in through the M-cells of [[Peyer's Patches - Anatomy & Physiology|Peyer's patches]].
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The organism is viable in the environment for long periods of time and has a long incubation period with clinical signs appearing in cattle over 2 years of age.
* Mycobacteria invade macrophages and cause a granulomatous inflammatory response.
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* Death results from:
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** Damage to the mucosa.
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*** Nutrients cannot be absorbed.
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** Inflammatory loss of protein
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*** I.e. a [[Protein Losing Enteropathy|protein losing enteropathy]] (hypoalbuminaemia).
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===Pathology===
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==Clinical Signs==
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'''Cattle''' become infected by the bacteria as calves but do not display the clinical signs of disease until between two and five years of age. In addition animals may be affected subclinically before overt clinical signs are displayed.
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====Gross====
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In the early stages, the disease is characterised by reduced milk production, reduced reproductive performance and increased susceptibility to infection or disease. There may be intermittent diarrhoea and weight loss.
[[Image:johnes disease proliferative enteritis.jpg|thumb|right|150px|Johnes Disease (Courtesy of Bristol BioMed Image Archive)]]
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* Quite typical
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* Cows appear very emaciated.
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** Depends on how long the disease has been there.
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** Not very much to see!
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*** Fat is pale and oedematous, and there is not much of it. 
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* Signs are confined to the terminal [[Small Intestine - Anatomy & Physiology|small intestine]] (especially the [[Ileum - Anatomy & Physiology|ileum]]) but are characteristic.
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** Diffusely thickened mucosa
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*** Transverse, corrugated ruggae with reddened crests.
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**** Cannot extend the gut to remove these (i.e. they are permanent ruggae).
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*** Velvety mucosal surface.
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*** Mucosa may take on a 'corn-on-the-cob' appearance in advanced cases.[[Image:johnes disease proliferative ileitis.jpg|thumb|right|150px|Proliferative ileitis in Johnes disease (Courtesy of Bristol BioMed Image Archive)]]
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** Serosal oedema.
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** Distended lymphatics.
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* Enlarged mesenteric lymph nodes.
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* Changes are milder in sheep and goats.
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** Often missed.
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** May produce small areas of necrosis not usually seen in cattle.
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** Sheep may get a pigmented form.
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====Histologically====
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In the later phases of infection, the clinical signs become more severe. The characteristic clinical signs are of watery 'pipe-stem' diarrhoea and severe wasting (despite maintenance of a good appetite). The disease is progressive and advanced cases may develop submandibular or ventral oedema due to a protein losing enteropathy.  
[[Image:johnes disease histological.jpg|thumb|right|150px|Histological appearance of Johnes disease (Courtesy of Bristol BioMed Image Archive)]]
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* Many large macrophages (epithelioid macrophages) in mucosa, submucosa and lymph nodes.
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** Mesenteric lymph nodes are pale and enlarged (though not necrotic).  
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* The lamina propria is infiltrated by sheets of macrophages with some lymphocytes.
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* Acid-fast bacteria are found in the macrophages and giant cells.
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** Detected by Ziehl-Neelson stain.
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** Bacteria act like foreign body producing a type IV hypersensitivity reaction.
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* Sheep have two different forms.
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*# '''Paucibacillary'''
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*#* Many T cells
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*#* Few bacilli
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*# '''Multibacillary'''
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*#* Many macrophages
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*#* Many bacilli in macrophages
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*#* Few lymphocytes
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===Diagnosis===
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The disease is similar in '''goats''' and '''sheep''' except diarrhoea is not a feature. It is characterised mainly by weight loss.
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It may be rapidly fatal with weight loss and diarrhoea in some '''deer'''.
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* Diagnosis is by
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==Diagnosis==
** Histology
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Diagnosis is difficult, particularly in the case of subclinical disease as there is no single test that will detect all stages of the disease. '''Bacterial culture''' is the most definitive test but is time-consuming, requiring up to sixteen weeks for incubation.
** Serological tests
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*** ELISA & AGID
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The most commonly used diagnostic test is the [[ELISA testing|'''ELISA''']] which detects antibodies to ''M. paratuberculosis'' in clinically affected animals. This is typically used in combination with post mortem and identification of the classic pathological lesions of the disease. Other commercially available tests include bacterial culture, '''PCR''' and '''agar gel immunodiffusion'''. Test sensitivity may be increased by using different tests in combination.
** Culture of organisms
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** 60% of cases have lesions in [[Colon - Anatomy & Physiology|colon]] and [[Rectum - Anatomy & Physiology|rectum]] and can be diagnosed by rectal biopsy.[[Category:Enteritis,_Bacterial]][[Category:Enteritis, Proliferative]][[Category:Cattle]]
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Diagnosis in sheep may also be complicated due to the disease occurring in two different types in these animals. Multibacillary disease is associated with large numbers of bacteria in the gut and a high antibody response. Paucibacillary disease is characterised by few or no bacteria within the alimentary tract and is associated with a low antibody response. Due to the different type of immune response occurring with each type of disease, there is no single test available to detect the presence of disease. Definitive diagnosis is provided following post mortem exam, histopathology and culture in order to determine the type of disease present.
[[Category:Enteritis,_Granulomatous]]
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[[Category:To_Do_-_Clinical]]
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Other possible tests include:
[[Category:To_Do_-_Max]]
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*Serology of serum including complement fixation tests
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*Histopathology of intestines and lymph nodes
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*Isolation and identification of mycobacteria from faeces and tissues
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*Ziehl-Neelson-positive smears
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*Intradermal tuberculin test
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*DNA probes for detection in faeces
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==Gross Pathology==
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[[Image:johnes disease proliferative ileitis.jpg|thumb|right|150px|Proliferative ileitis in Johnes disease (Courtesy of Bristol BioMed Image Archive)]]
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Lesions are usually localised to the terminal portion of the ileum. Lymphocytes and macrophages accumulate in the lamina propria and submucosa, resulting in marked thickening and folding of the intestinal wall. The mucosal surface is diffusely thickened with transverse, corrugated rugae which do not disappear when the intestinal wall is stretched. In sheep and goats however, the lesions usually described are nodule formation with necrosis and calcification .
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Infected animals may also have enlarged mesenteric lymph nodes.
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==Treatment==
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Several studies have reported an improvement in clinical signs following antimicrobial treatment of affected animals. However the same studies have shown that faecal shedding of the bacterium still occurs following treatment, therefore such treatment does not appear to be currently viable. Control measures are aimed at providing good hygiene and husbandry, maintaining adequate stocking densities and minimising exposure of young animals to the organism. Current recommendations include providing clean, manure-free areas for cows to calve and only administering pasteurised or test-negative colostrum to new born calves. Separation and isolation of calves from affected dams is also recommended.
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The disease in mainly controlled by slaughter of affected animals, detection and slaughter of subclinical shedders using faecal culture, DNA probes and ELISA.
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Inactivated adjuvanted vaccines are available and reduce shedding of mycobacteria but do not eliminate infection.
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{{Learning
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|literature search = [http://www.cabdirect.org/search.html?it=any&q1=%28title%3A%28%22Johne%27s+disease%22%29+OR+title%3A%28%22Johnes+disease%22%29+OR+title%3A%28Paratuberculosis%29%29+AND+od%3A%28cattle%29&calendarInput=yyyy-mm-dd&occuring1=freetext&show=all&rowId=1&rowId=2&rowId=3&options1=AND&options2=AND&options3=AND&occuring3=freetext&occuring2=freetext&publishedend=yyyy&la=any&publishedstart=2000&fq=sc%3A%22ve%22&y=5&x=67 Johne’s disease in cattle publications since 2000]
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[http://www.cabdirect.org/search.html?rowId=1&options1=AND&q1=%28%28title%3A%28%22Johne%27s+disease%22%29+OR+title%3A%28%22Johnes+disease%22%29+OR+title%3A%28Paratuberculosis%29%29+AND+%28od%3A%28sheep%29+OR+od%3A%28goats%29%29%29+&occuring1=freetext&rowId=2&options2=AND&q2=&occuring2=freetext&rowId=3&options3=AND&q3=&occuring3=freetext&publishedstart=2000&publishedend=yyyy&calendarInput=yyyy-mm-dd&la=any&it=any&show=all&x=40&y=10 Johne’s disease in sheep and goats publications since 2000]
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|full text = [http://www.cabi.org/cabdirect/FullTextPDF/2005/20053177366.pdf ''' Mycobacterium paratuberculosis/Johne's disease: review & update.''' Whitlock, R. H.; Eastern States Veterinary Association, Gainesville, USA, Proceedings of the North American Veterinary Conference. Large animal. Volume 19, Orlando, Florida, USA, 8-12 January, 2005, 2005, pp 79-80]
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}}
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==References==
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* Jones, T. C., Hunt, R. D., King, N. W. (1997) '''Veterinary Pathology''' ''Wiley-Blackwell''
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* Merck & Co (2008) '''The Merck Veterinary Manual (Eighth Edition)''' ''Merial''
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{{review}}
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[[Category:Enteritis,_Bacterial]][[Category:Enteritis, Proliferative]][[Category:Intestinal Diseases - Cattle]][[Category:Alimentary Diseases - Sheep]][[Category:Alimentary Diseases - Goat]]
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[[Category:Enteritis,_Granulomatous]][[Category:Deer]]
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[[Category:Brian Aldridge reviewing]]
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[[Category:Mycobacterium_species]]
Author, Donkey, Bureaucrats, Administrators
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