Difference between revisions of "Sheep Pulmonary Adenomatosis"

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{{unfinished}}
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== Synonyms  ==
  
====Antigenicity====
+
Jaagsiekte (driving sickness in Afrikaans)
*The virus cannot be grown in culture, although it can be seen by EM on tumor cells of infected sheep
 
  
====Pathogenesis====
+
Pulmonary carcinomatosis
*Causes a proliferation of alveolar lining cells, producing massive amounts of fluid
 
*Proliferative foci project into alveoli and bronchi and from slow-growing tumors
 
*Death occurs between 3-4 years of age
 
  
Clinical signs:
+
<br>
*Low exercise tolerance
 
*Gradual weight loss
 
*Dyspnoea
 
*Coughing
 
*Nasal fluid discharges during wheelbarrow test
 
*Secondary bacterial infection by ''Pasteurella hemolytica'' often precipitates death
 
*PM reveals fawn-gray tumor (for more see [[Pulmonary Neoplasia#Sheep pulmonary adenomatosis (SPA/ Jaagsiekte)|here]])
 
  
====Epidemiology====
+
== Introduction<br>  ==
*Found in 25% of pneumonia cases in Scotland
 
*Absent in USA, common in UK
 
  
====Diagnosis====
+
This is a progressive disease in sheep caused by the Retrovirus family. The virus causes an infectious, bronchiolar- alveolar lung tumour of sheep, it killed Dolly, the famous cloned ewe, at 6 years old. The virus works by causing a proliferation of the alveolar lining cells in the lungs, causing mass amounts of fluid to be produced. The proliferative foci project into the alveoli and bronchi and then form slow-growing tumours with death at 3-4 years of age or older. The virus is found in around 25% of cases of pneumonia in sheep in Scotland and is prevalent throughout the rest of the British Isles. It is absent from the United States. The virus is found to be commonest under intensive management systems, which favour aerosol transmission and close contact of disease.<br>
*Electron microscopy on lung biopsy
 
  
====Control====
+
<br>
*Cull clinically affected animals
 
  
 +
== Clinical Signs  ==
  
 +
Low exercise tolerance, gradual weight loss, dyspnoea, coughing and the presence of nasal discharges, bilaterally. Secondary bacterial infection by Pasteurella haemolytica often precipitates death.
  
 +
<br>
  
*Also called '''pulmonary carcinomatosis'''
+
== Diagnosis ==
*Infectious [[Bronchitis#Infectious causes of bronchitis or bronchiolitis|bronchiolar]]-[[Pneumonia Overview#Infectious causes of pneumonia|alveolar]] carcinoma caused by a [[Retroviridae|retrovirus]]
 
*Commonest under intensive management systems which favour aerosol transmission and close contact of disease
 
*Behaves like chronic pneumonia
 
*Takes months to years to express itself clinically as coughing and exercise intolerance
 
*Gross pathology:
 
**Heavy lungs which fail to collapse
 
**The lesions progress from small firm grey/white nodular lesions to extensive confluent areas with replacement by neoplastic tissue
 
**Cut surface oozes fluid
 
**There is often coexistent infection present
 
**Occasional metastases to bronchial and mediastinal lymph nodes can occur
 
*Histopathology:
 
**Widespread proliferation of alveolar (Type 2) and terminal bronchiolar epithelium, lining the alveoli and lower airways
 
**Multiple neoplastic foci of cuboidal/columnar cells forming papillary projections into the lumen
 
**Metastases of the same in the bronchial and mediastinal lymph nodes
 
*There is no serological test, and diagnosis depends upon raising the animal by the hind limbs whereupon a clear fluid issues from the nose = "Wheelbarrow test"
 
<big>'''More information'''</big>
 
  
==Overview==
+
Clinical signs plus the age of the sheep can often be indicative of the disease. A 'wheelbarrow test', where the sheep is lifted by its hind legs so its head drops down can be used to detect any nasal discharge seeping out when the test is performed.
Etiology:  Type B/D Retrovirus (also known as the jaagziekte retrovirus‑‑JSRV)
 
  
Condition:  Pulmonary carcinomatosis.
+
At post mortem the tumour is fawn-grey in colour but may be obscured by autolysis or pneumonia. The lungs will appear heavy and fail to collapse. The cut surface will ooze fluid and there is often secondary bacterial infection present concurrently. There may occasionally be metastasis to bronchial and mediastinal lymph nodes. The virus cannot be grown in cultures, but it can be seen on electron microscopy of tumour cells of infected sheep. PCR on blood is being developed at Moredun.  
  
Synonyms:  Jaagsiekte,  sheep pulmonary adenomatosis, ovine pulmonary carcinoma.
+
<br>
  
==General==
+
== Control  ==
*Pulmonary carcinomatosis (OPC) is an infectious form of bronchioalveolar tumor with behavior of a low-grade carcinoma.
 
*Associated with (and strong evidence that is caused by) a type B/D retrovirus of family Retroviridae (single-stranded RNA).
 
*Occurs in Africa, Europe and the Americas.
 
*Susceptibility among breeds varies; Merino sheep are highly susceptible.
 
*The condition is considered to be a transmissible neoplasm with uncommon metastasis to regional lymph nodes and rare metastasis to other sites.  Most growth is by local expansion and infiltration.
 
*The disease spreads via aerosol transmission and  is less common in areas where the sheep are dispersed.
 
  
==Pathogenesis==
+
All affected animals should be culled. There is no vaccine to the disease, as the disease is progressive and no specific antibodies have yet been detected.
*The retrovirus associated with OPC is generally referred to as the jaagsiekte retrovirus (JSRV). This virus is morphologically distinct from all known retroviruses but has yet to be cultured.  
+
 
*The target cells are type II alveolar epithelial cells and, less frequently, nonciliated bronchiolar epithelium.
+
<br>
*The virus-transformed epithelial cells proliferate, filling alveoli, spilling into adjacent airways and compressing and invading pulmonary parenchyma.
+
<br>
*The exact mechanism of carcinogenesis is unknown.
+
*Pulmonary carcinomatosis (OPC) is an infectious form of bronchioalveolar tumor with behavior of a low-grade carcinoma.
 +
*Associated with (and strong evidence that is caused by) a type B/D retrovirus of family Retroviridae (single-stranded RNA).
 +
*Occurs in Africa, Europe and the Americas.
 +
*Susceptibility among breeds varies; Merino sheep are highly susceptible.
 +
*The condition is considered to be a transmissible neoplasm with uncommon metastasis to regional lymph nodes and rare metastasis to other sites. Most growth is by local expansion and infiltration.
 +
*The disease spreads via aerosol transmission and is less common in areas where the sheep are dispersed.
 +
 
 +
== Pathogenesis ==
 +
 
 +
*The retrovirus associated with OPC is generally referred to as the jaagsiekte retrovirus (JSRV). This virus is morphologically distinct from all known retroviruses but has yet to be cultured.  
 +
*The target cells are type II alveolar epithelial cells and, less frequently, nonciliated bronchiolar epithelium.  
 +
*The virus-transformed epithelial cells proliferate, filling alveoli, spilling into adjacent airways and compressing and invading pulmonary parenchyma.  
 +
*The exact mechanism of carcinogenesis is unknown.  
 
*Naturally occurring ovine pulmonary carcinomatosis has a long incubation period (months to up to 2 years), but experimentally, the time course of the disease can be reduced to a few weeks by inoculating lung tumor or lung fluid from affected sheep into neonatal lambs.
 
*Naturally occurring ovine pulmonary carcinomatosis has a long incubation period (months to up to 2 years), but experimentally, the time course of the disease can be reduced to a few weeks by inoculating lung tumor or lung fluid from affected sheep into neonatal lambs.
  
==Clinical Signs==
+
== Clinical Signs ==
*Coughing
+
 
*Exercise intolerance (thus the Afrikaan name jaagsiekte, “driving sickness”).
+
*Coughing  
*Crackles and wheezes.
+
*Exercise intolerance (thus the Afrikaan name jaagsiekte, “driving sickness”).  
*Abundant watery exudate which is discharged from the nose, especially when the head is lowered. The discharge is an important diagnostic clinical feature.
+
*Crackles and wheezes.  
 +
*Abundant watery exudate which is discharged from the nose, especially when the head is lowered. The discharge is an important diagnostic clinical feature.  
 
*Dyspnea.
 
*Dyspnea.
==Findings==
+
 
===Gross Findings===
+
== Findings ==
*Lung parenchymal masses ranging from 1 – 20 mm dia. gray-blue-white nodules (early) to large gray nodular and confluent masses (later). The larger masses often have fibrotic centers.
+
 
*The lungs are enlarged, heavy, and fail to collapse.
+
=== Gross Findings ===
*Coexisting bronchopneumonia, verminous pneumonia, chronic progressive pneumonia, or combinations of the three.
+
 
*Right ventricular hypertrophy and dilation.
+
*Lung parenchymal masses ranging from 1 – 20 mm dia. gray-blue-white nodules (early) to large gray nodular and confluent masses (later). The larger masses often have fibrotic centers.  
 +
*The lungs are enlarged, heavy, and fail to collapse.  
 +
*Coexisting bronchopneumonia, verminous pneumonia, chronic progressive pneumonia, or combinations of the three.  
 +
*Right ventricular hypertrophy and dilation.  
 
*Deaths result from heart failure, hypoxia or secondary bacterial pneumonias.
 
*Deaths result from heart failure, hypoxia or secondary bacterial pneumonias.
  
Laser Disc: 2395; 2396; 11702; 15547.
+
Laser Disc: 2395; 2396; 11702; 15547.  
===Microscopic Findings===
+
 
*Multiple proliferative foci of cuboidal or columnar cells which line alveoli and form papillary projections into their lumina (i.e., adenomatous hyperplasia, adenomas and adenocarcinomas).
+
=== Microscopic Findings ===
*In larger masses the pattern is obscured and fibroplasia often occurs in more disorganized and degenerative areas.
+
 
 +
*Multiple proliferative foci of cuboidal or columnar cells which line alveoli and form papillary projections into their lumina (i.e., adenomatous hyperplasia, adenomas and adenocarcinomas).  
 +
*In larger masses the pattern is obscured and fibroplasia often occurs in more disorganized and degenerative areas.  
 
*Early or uncomplicated lesions may have little to no accumulation of inflammatory cells; however, there are usually low to moderate aggregations of alveolar macrophages in alveolar lumina.
 
*Early or uncomplicated lesions may have little to no accumulation of inflammatory cells; however, there are usually low to moderate aggregations of alveolar macrophages in alveolar lumina.
==Ultrastructure==
+
 
 +
== Ultrastructure ==
 +
 
 
Some cells have cytoplasmic lamellar bodies characteristic of alveolar type II epithelial cells; others have secretory granules and glycogen compatable with secretory bronchiolar epithelial (Clara) cell origin.  
 
Some cells have cytoplasmic lamellar bodies characteristic of alveolar type II epithelial cells; others have secretory granules and glycogen compatable with secretory bronchiolar epithelial (Clara) cell origin.  
==Differential Diagnosis==
+
 
# Chronic progressive pneumonia (maedi - lentivirus) --lymphofollicular interstitial pneumonia (with little to no significant alveolar epithelial hyperplasia).
+
== Differential Diagnosis ==
# Remember, bacterial bronchopneumonias and verminous pneumonias may be present in addition to OPC.
+
 
==Comparative Pathology==
+
#Chronic progressive pneumonia (maedi - lentivirus) --lymphofollicular interstitial pneumonia (with little to no significant alveolar epithelial hyperplasia).  
 +
#Remember, bacterial bronchopneumonias and verminous pneumonias may be present in addition to OPC.
 +
 
 +
== Comparative Pathology ==
 +
 
 
*Human bronchio‑alveolar carcinoma shares many histologic and behavioral characteristics with OPC.  
 
*Human bronchio‑alveolar carcinoma shares many histologic and behavioral characteristics with OPC.  
 
*Type D retroviruses have been implicated in caprine and ovine nasal adenocarcinomas.
 
*Type D retroviruses have been implicated in caprine and ovine nasal adenocarcinomas.
==References==
 
1.  Hecht SJ, Sharp JM, and Demartini JC:  Retroviral Aetiopathogenesis of Ovine Pulmonary Carcinoma:  A Critical Appraisal.  Br Vet J  (1996) 152:395-406.
 
2.  Dungworth DL: The Respiratory System, In:Pathology of Domestic Animals, 4th edition, ed. Jubb KVF, Kennedy PC, and Palmer N, pp.690-2, Academic Press, San Diego, CA, 1993.
 
3.  Fenner FJ, Gibbs EPJ, Murphy FA, Rott R, Studdert MJ, and White DO: Retroviridae, In: Veterinary Virology, 2nd edition, pp. 578-9, Academic Press, Inc., San Diego CA, 1993.
 
4.  Kimberling CV:  Diseases of Adult Sheep, In: Jensen and Swift’s Diseases of Sheep, 3rd edition, pp. 270-3, 1988.
 
  
Written and revised by GD Young, 1988; BH Williams, 1991; WD Fall, 1994; TO Johnson, 1999.
+
== References ==
  
 +
1. Hecht SJ, Sharp JM, and Demartini JC: Retroviral Aetiopathogenesis of Ovine Pulmonary Carcinoma: A Critical Appraisal. Br Vet J (1996) 152:395-406. 2. Dungworth DL: The Respiratory System, In:Pathology of Domestic Animals, 4th edition, ed. Jubb KVF, Kennedy PC, and Palmer N, pp.690-2, Academic Press, San Diego, CA, 1993. 3. Fenner FJ, Gibbs EPJ, Murphy FA, Rott R, Studdert MJ, and White DO: Retroviridae, In: Veterinary Virology, 2nd edition, pp. 578-9, Academic Press, Inc., San Diego CA, 1993. 4. Kimberling CV: Diseases of Adult Sheep, In: Jensen and Swift’s Diseases of Sheep, 3rd edition, pp. 270-3, 1988.
  
 +
Written and revised by GD Young, 1988; BH Williams, 1991; WD Fall, 1994; TO Johnson, 1999.
  
[[Category:Mammalian Type D retrovirus ]][[Category:Sheep Viruses]]
+
[[Category:Mammalian_Type_D_retrovirus]] [[Category:Sheep_Viruses]] [[Category:To_Do_-_Clinical/Viruses]] [[Category:Respiratory_Viral_Infections]] [[Category:Respiratory_Diseases_-_Sheep]] [[Category:Lungs_-_Pathology]] [[Category:Respiratory_System_-_Hyperplastic/Neoplastic_Pathology]]
[[Category:To_Do_-_Clinical/Viruses]]
 
[[Category:Respiratory_Viral_Infections]]
 
[[Category:Respiratory Diseases - Sheep]]
 
[[Category:Lungs - Pathology]]
 
[[Category:Respiratory System - Hyperplastic/Neoplastic Pathology]]
 

Revision as of 16:11, 16 March 2011

Synonyms

Jaagsiekte (driving sickness in Afrikaans)

Pulmonary carcinomatosis


Introduction

This is a progressive disease in sheep caused by the Retrovirus family. The virus causes an infectious, bronchiolar- alveolar lung tumour of sheep, it killed Dolly, the famous cloned ewe, at 6 years old. The virus works by causing a proliferation of the alveolar lining cells in the lungs, causing mass amounts of fluid to be produced. The proliferative foci project into the alveoli and bronchi and then form slow-growing tumours with death at 3-4 years of age or older. The virus is found in around 25% of cases of pneumonia in sheep in Scotland and is prevalent throughout the rest of the British Isles. It is absent from the United States. The virus is found to be commonest under intensive management systems, which favour aerosol transmission and close contact of disease.


Clinical Signs

Low exercise tolerance, gradual weight loss, dyspnoea, coughing and the presence of nasal discharges, bilaterally. Secondary bacterial infection by Pasteurella haemolytica often precipitates death.


Diagnosis

Clinical signs plus the age of the sheep can often be indicative of the disease. A 'wheelbarrow test', where the sheep is lifted by its hind legs so its head drops down can be used to detect any nasal discharge seeping out when the test is performed.

At post mortem the tumour is fawn-grey in colour but may be obscured by autolysis or pneumonia. The lungs will appear heavy and fail to collapse. The cut surface will ooze fluid and there is often secondary bacterial infection present concurrently. There may occasionally be metastasis to bronchial and mediastinal lymph nodes. The virus cannot be grown in cultures, but it can be seen on electron microscopy of tumour cells of infected sheep. PCR on blood is being developed at Moredun.


Control

All affected animals should be culled. There is no vaccine to the disease, as the disease is progressive and no specific antibodies have yet been detected.



  • Pulmonary carcinomatosis (OPC) is an infectious form of bronchioalveolar tumor with behavior of a low-grade carcinoma.
  • Associated with (and strong evidence that is caused by) a type B/D retrovirus of family Retroviridae (single-stranded RNA).
  • Occurs in Africa, Europe and the Americas.
  • Susceptibility among breeds varies; Merino sheep are highly susceptible.
  • The condition is considered to be a transmissible neoplasm with uncommon metastasis to regional lymph nodes and rare metastasis to other sites. Most growth is by local expansion and infiltration.
  • The disease spreads via aerosol transmission and is less common in areas where the sheep are dispersed.

Pathogenesis

  • The retrovirus associated with OPC is generally referred to as the jaagsiekte retrovirus (JSRV). This virus is morphologically distinct from all known retroviruses but has yet to be cultured.
  • The target cells are type II alveolar epithelial cells and, less frequently, nonciliated bronchiolar epithelium.
  • The virus-transformed epithelial cells proliferate, filling alveoli, spilling into adjacent airways and compressing and invading pulmonary parenchyma.
  • The exact mechanism of carcinogenesis is unknown.
  • Naturally occurring ovine pulmonary carcinomatosis has a long incubation period (months to up to 2 years), but experimentally, the time course of the disease can be reduced to a few weeks by inoculating lung tumor or lung fluid from affected sheep into neonatal lambs.

Clinical Signs

  • Coughing
  • Exercise intolerance (thus the Afrikaan name jaagsiekte, “driving sickness”).
  • Crackles and wheezes.
  • Abundant watery exudate which is discharged from the nose, especially when the head is lowered. The discharge is an important diagnostic clinical feature.
  • Dyspnea.

Findings

Gross Findings

  • Lung parenchymal masses ranging from 1 – 20 mm dia. gray-blue-white nodules (early) to large gray nodular and confluent masses (later). The larger masses often have fibrotic centers.
  • The lungs are enlarged, heavy, and fail to collapse.
  • Coexisting bronchopneumonia, verminous pneumonia, chronic progressive pneumonia, or combinations of the three.
  • Right ventricular hypertrophy and dilation.
  • Deaths result from heart failure, hypoxia or secondary bacterial pneumonias.

Laser Disc: 2395; 2396; 11702; 15547.

Microscopic Findings

  • Multiple proliferative foci of cuboidal or columnar cells which line alveoli and form papillary projections into their lumina (i.e., adenomatous hyperplasia, adenomas and adenocarcinomas).
  • In larger masses the pattern is obscured and fibroplasia often occurs in more disorganized and degenerative areas.
  • Early or uncomplicated lesions may have little to no accumulation of inflammatory cells; however, there are usually low to moderate aggregations of alveolar macrophages in alveolar lumina.

Ultrastructure

Some cells have cytoplasmic lamellar bodies characteristic of alveolar type II epithelial cells; others have secretory granules and glycogen compatable with secretory bronchiolar epithelial (Clara) cell origin.

Differential Diagnosis

  1. Chronic progressive pneumonia (maedi - lentivirus) --lymphofollicular interstitial pneumonia (with little to no significant alveolar epithelial hyperplasia).
  2. Remember, bacterial bronchopneumonias and verminous pneumonias may be present in addition to OPC.

Comparative Pathology

  • Human bronchio‑alveolar carcinoma shares many histologic and behavioral characteristics with OPC.
  • Type D retroviruses have been implicated in caprine and ovine nasal adenocarcinomas.

References

1. Hecht SJ, Sharp JM, and Demartini JC: Retroviral Aetiopathogenesis of Ovine Pulmonary Carcinoma: A Critical Appraisal. Br Vet J (1996) 152:395-406. 2. Dungworth DL: The Respiratory System, In:Pathology of Domestic Animals, 4th edition, ed. Jubb KVF, Kennedy PC, and Palmer N, pp.690-2, Academic Press, San Diego, CA, 1993. 3. Fenner FJ, Gibbs EPJ, Murphy FA, Rott R, Studdert MJ, and White DO: Retroviridae, In: Veterinary Virology, 2nd edition, pp. 578-9, Academic Press, Inc., San Diego CA, 1993. 4. Kimberling CV: Diseases of Adult Sheep, In: Jensen and Swift’s Diseases of Sheep, 3rd edition, pp. 270-3, 1988.

Written and revised by GD Young, 1988; BH Williams, 1991; WD Fall, 1994; TO Johnson, 1999.