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Also known as: '''''Paratuberculosis
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| '''Paratuberculosis
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Johne's Disease is caused by ''[[Mycobacterium avium subsp. paratuberculosis]]''.  This chronic mycobacterial infection primarily affects the small intestine, and is most commonly seen in cattle, sheep and goats.
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Caused by '''''M avium'' subsp. ''paratuberculosis''
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Johne's disease refers to the condition caused by the mycrobacterial infection. Calves are most commonly affected by this condition, and can be infected via a number of routes. They may be infected by ingestion of infected manure, or via transmammary infection. In addition, calves may also be infected in vitro, or may ingest the bacteria via colostrum.
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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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There are three stages of infection in Johne's disease.
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==Pathogenesis==
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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.  
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'''Stage 1''':  This often goes unnoticed, as it is subclinical. It typically affects animals less than two years of age, and will advance to stage II, only a few months later.
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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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'''Stage 2''':  This is again a subclinical infection, usually affecting older heifers, or young adults.  Infected animals are apparently healthy, but are shedding infection within their manure, infecting the environment.
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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.
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'''Stage 3''': Advanced infection. Animals will show clear clinical signs, including weight loss, decreased milk production, and a severe reduction in appetite.
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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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Animals with advanced '''stage 3''' will appear gaunt, and the meat is no longer deemed fit for human consumption.  Once the disease is present in the herd, it is ver difficult to get rid of it.
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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.
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===Clinical===
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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.
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* Clinical signs develop in older cows after calving i.e. 3 to 4 years of age. 
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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.  
* '''BUT''' animals are infected as calves less than 6 months old
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It may be rapidly fatal with weight loss and diarrhoea in some '''deer'''.
** 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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==Diagnosis==  
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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.
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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 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.
* 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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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.
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====Gross====
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Other possible tests include:
[[Image:johnes disease proliferative enteritis.jpg|thumb|right|150px|Johnes Disease (Courtesy of Bristol BioMed Image Archive)]]
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*Serology of serum including complement fixation tests  
* Quite typical
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*Histopathology of intestines and lymph nodes
* Cows appear very emaciated.
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*Isolation and identification of mycobacteria from faeces and tissues
** Depends on how long the disease has been there.
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*Ziehl-Neelson-positive smears
** Not very much to see!
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*Intradermal tuberculin test
*** Fat is pale and oedematous, and there is not much of it.  
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*DNA probes for detection in faeces
* 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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==Gross Pathology==
[[Image:johnes disease histological.jpg|thumb|right|150px|Histological appearance of Johnes disease (Courtesy of Bristol BioMed Image Archive)]]
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[[Image:johnes disease proliferative ileitis.jpg|thumb|right|150px|Proliferative ileitis in Johnes disease (Courtesy of Bristol BioMed Image Archive)]]
* Many large macrophages (epithelioid macrophages) in mucosa, submucosa and lymph nodes.
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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 .
** 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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Infected animals may also have enlarged mesenteric lymph nodes.
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* Diagnosis is by
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==Treatment==
** Histology
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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.
** Serological tests
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*** ELISA & AGID
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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.
** 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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Inactivated adjuvanted vaccines are available and reduce shedding of mycobacteria but do not eliminate infection.
[[Category:Enteritis,_Granulomatous]]
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[[Category:To_Do_-_Clinical]]
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{{Learning
[[Category:To_Do_-_Max]]
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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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