JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

October 2023

P-V04

 

Signalment (JPC #2295198): 9-month-old, mixed breed goat

 

HISTORY: This goat was found dead 8 days after being inoculated subcutaneously with 1.0 mL of blood product made from a goat with profound respiratory signs. The cranioventral lungs were consolidated and hyperemic. There was accumulation of fibrin on the overlying pleura.

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Approximately 90% of the section is consolidated, characterized by atelectasis, alveolar septal expansion, and/or alveolar exudate obliterating alveolar spaces. Diffusely, alveolar septa are expanded up to three times normal by histiocytes and lymphocytes and there is extensive necrosis and loss of type I pneumocytes with replacement by type II pneumocytes (type II pneumocyte hyperplasia). Multifocally replacing both alveolar pneumocytes and bronchiolar epithelium, there are numerous viral syncytia containing up to 30 nuclei. Multifocally, alveolar and bronchiolar epithelial syncytia, type II pneumocytes, and bronchiolar epithelial cells contain intranuclear and intracytoplasmic, eosinophilic, oval viral inclusions up to 5 microns in diameter. Bronchial and bronchiolar epithelial cells often exhibit one or more of the following changes: Attenuation, necrosis, and hyperplasia, which is often irregular and tortuous. Multifocally, the perivascular and peribronchiolar interstitium, interlobular septa, and pleura are expanded by edema, ectatic lymphatics, few neutrophils, lymphocytes, and rare plasma cells. Alveolar spaces, and occasionally bronchiolar lumina, are filled with an exudate composed of viable and degenerate neutrophils, necrotic cellular debris, and fibrin with fewer macrophages, occasional lymphocytes, hemorrhage, and edema.

 

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, bronchointerstitial, lymphohistiocytic, diffuse, severe, with bronchial and bronchiolar epithelial attenuation, necrosis, and hyperplasia, type II pneumocyte hyperplasia, numerous viral syncytia, and intranuclear and intracytoplasmic eosinophilic viral inclusions, mixed breed, caprine.

 

ETIOLOGIC DIAGNOSIS: Morbilliviral pneumonia

 

CAUSE: Peste des petits ruminants virus (PPRV)

 

SYNONYMS: Goat plague, ovine rinderpest, pseudorinderpest, stomatitis-pneumoenteritis complex, kata

 

GENERAL DISCUSSION:

• This is an acute, rapidly progressive disease of goats and sheep characterized by epithelial necrosis and high morbidity and mortality; goats, especially young, are more severely affected
• Genus Morbillivirus, family Paramyxoviridae
• Occurs in sub-Saharan Africa, Arabian Peninsula, and Indian subcontinent, including Nepal and Bangladesh
• PPRV is closely related to rinderpest virus (RPV) with which it shares common antigenic determinants
• The clinical signs, pathogenesis, and lesions of the disease in sheep and goats in general are similar to those of RPV

 

PATHOGENESIS:

• PPRV is very contagious but transmission requires close contact; ocular, nasal, oral secretions, and feces are infectious
• Virtually all outbreaks can be traced to movement of stock, either migration to new areas or introduction of new animals to the herd
• More acute in onset than RPV with more rapid course and marked involvement of the respiratory tract; pulmonary lesions resemble pneumonia caused by canine distemper virus in dogs
• Infection enters oropharynx > virus replicates in draining lymph nodes > spreads to other lymphoid tissue throughout the body > viremia ensues > spreads throughout the body to susceptible epithelia > virus multiplies > cytopathic effects in epithelial cells, resulting in characteristic erosions and necrosis 
• Incubation period is 3 – 10 days
  • In experimentally inoculated NHP, infected cell numbers from bronchioalveolar lavage fluid peak at 6 days post infection, before or around the time of the eruption of the characteristic skin rash, suggesting that infected animals are capable of aerosol transmission before the onset of suggestive clinical signs

 

TYPICAL CLINICAL FINDINGS:

• Fever, depression, inappetence, and serous nasal/ocular discharge which becomes purulent and more profuse with time
• Oral erosions, necrotic stomatitis, near-term abortions
• Diarrhea begins 2-3 days after onset of fever
• Dyspnea and cough associated with developing pneumonia

 

TYPICAL GROSS FINDINGS:

• Characterized by pseudomembranous oral lesions, fibrinonecrotic tracheitis, fibrinous pleuritis, bronchointerstitial pneumonia, necrotizing tonsillitis, and fibrinohemorrhagic enteritis
• In the lung, bronchointerstitial pneumonia involving the cranioventral lobes with focal to diffuse congestion; pleuritis is variable
• Gastrointestinal tract: Erosion and ulcerations from the buccal cavity (including lips) to the mid-esophagus; necrosis of epithelium overlying Peyer’s patches; marked congestion of apices of mucosal folds (zebra striping) in the large intestine and rectum with occasional ulceration

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Lung: Bronchointerstitial pneumonia with lymphocytes, necrosis, type II pneumocyte hyperplasia, and hyperplastic bronchial and bronchiolar epithelium
• Intracytoplasmic and intranuclear eosinophilic viral inclusions in the epithelial cells of the airways, type II pneumocytes, alveolar and bronchiolar epithelial syncytial cells, and occasionally in alveolar macrophages
• Upper gastrointestinal tract: Erosions arise from hydropic degeneration and necrosis of epithelial cells in the stratum granulosum; syncytial cell formation
• Severe lymphoid necrosis, often apparent in gut-associated lymphoid tissue (GALT), with associated mucosal ulceration overlying Peyer's patches. Also present in lymph nodes and spleen

 

ULTRASTRUCTURAL FINDINGS:

• Paramyxovirus-like particles in degenerating cells in the lungs, particularly alveolar macrophages, and intestinal epithelium
• Intranuclear and intracytoplasmic nucleocapsids in intestinal epithelial cells, with apparent extrusion of extracellular viral particles from microvilli

 

ADDITIONAL DIAGNOSTIC TESTS:

• Immunohistochemical staining for viral antigen
• Monoclonal antibody-based antigen capture ELISA 
• RT-PCR
• Virus isolation (usually difficult in clinical cases)

 

DIFFERENTIAL DIAGNOSIS:

For Pneumonias in small ruminants:

• Small ruminant lentiviruses (P-V17): Caprine Arthritis-Encephalitis (CAE): Chronic lymphocytic interstitial pneumonia, goats; Ovine progressive pneumonia (OPP; maedi): Interstitial pneumonia, sheep, less type II pneumocyte hyperplasia
• Contagious caprine pleuropneumonia (Mycoplasma capricolum ssp. capripneumoniae): Fibrinous bronchopneumonia and pleuritis
• Septicemic pasteurellosis (Bibersteinia trehalosi): Multiple foci of hemorrhage and necrosis scattered throughout the lungs
• Chronic enzootic pneumonia (Pasteurellosis): Early stages, bronchointerstitial, type II pneumocyte hyperplasia
• Shipping fever complex (Mannheimia haemolytica, Pasteurella multocida, Histopholus somni, hemolytic streptococci, and Helcoccus ovis): Acute bronchopneumonia; similar to bovine shipping fever

 

COMPARATIVE PATHOLOGY:

PPRV in other animals:

• Experimental inoculation of PPRV in cattle and pigs protects against rinderpest and does not produce clinical disease
• Wild ungulates diagnosed with PPRV include gemsbok, gazelle, saiga antelopes, and ibex (similar lesions to goats)
• PPR has been reported in dromedary camels in the Middle East and East Africa Other morbilliviral diseases:
  • Canine distemper (canids, mustelids, and raccoons) (I-V12, N-V11, P-V01, U-V07): CDV causes a systemic infection in dogs and wild carnivores, with disease manifestation in multiple organs, including the respiratory tract (rhinitis, tracheobronchitis, interstitial pneumonia), skin (hyperkeratosis of the nose and foot pads), alimentary tract (catarrhal enteritis), central nervous system (necrotizing encephalitis), bones (growth retardation lattices), and eyes (conjunctivitis)

• CDV-associated growth retardation lattice is a metaphyseal sclerosis parallel to the physis resulting from

pathologically cross-linked persistent primary spongiosa that represents a transient impairment of osteoclastic resorption

• Rinderpest (cattle, water buffalo, camels, goats and sheep) (D-V28)
• Measles (humans, apes, and monkeys) (P-V02)
  • Reported mortality rates among captive NHPs are typically around 25% but vary widely, depending on species and concurrent disease processes
  • Old World monkeys: Signs develop at about 1 week postinfection and consist of conjunctivitis, a maculopapular rash (particularly evident on the face and sparsely haired skin of the ventrum), and minute pathognomonic white eruptions in the oral cavity (known as Koplik’s spots)
  • New World monkeys: May lack many of the hallmark signs common to humans and other Old World primates
    • In most cases, they fail to develop conjunctivitis or cutaneous lesions, and death occurs as a result of immune suppression and enterocolitis
    • Encephalitis is observed with intracranial inoculation but not with peripheral inoculation
    • Infection of moustached tamarins with the attenuated Edmonston strain of measles virus, which fails to produce clinical disease in rhesus macaques, has resulted in a 25% mortality in the tamarins
  • Measles virus is immunosuppressive, and the clinical picture may be com-pounded by opportunistic agents such as Shigella, Campylobacter, Candida, cytomegalovirus, and adenovirus
  • Pathogenesis: Measles virus is believed to gain access to the body through tonsils or the respiratory tree via receptors CD46, an inhibitory complement receptor, and CD150, the signaling lymphocyte activation molecule which is broad based > the port of entry may be CD150+ dendritic cells or other leukocyte restricted whereas the former is more broadly expressed (as opposed to epithelial cells as was once thought) > 
    • In blood and lymphoid tissue, CD150+ B lymphocytes and both CD4+ and CD8+ T lymphocytes—but not monocytes, natural killer cells, or neutrophils—harbor infection
    • Infected cells in peripheral tissues are morphologically consistent with lymphocytes and dendritic cells
    • Epithelial cells of the lung and trachea are infected, whereas those of the gastrointestinal tract are not 

• Depletion of lymphocytes, thymic dysinvolution, aberrant cytokine responses, and suppression of peripheral lymphoproliferation all play roles; concurrent measles virus infection may impair immune responses to other agents and interfere with routine diagnostic assays
  • Phocine morbillivirus (seals, sea lions) (N-V12): 
    • Phocine distemper virus causes mass mortality in harbor seals (Phoca vitulina), whereas gray seals (Halichoerus grypus) do not develop clinical signs of disease
  • Cetacean morbillivirus (porpoises and dolphins) (P-V03): 
    • Two strains of cetacean morbillivirus have been reported to infect odontocete cetacean populations worldwide: dolphin morbillivirus (DMV) and porpoise morbillivirus (PMV)

 

REFERENCES:

1. Agnew, D. Camelidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier. 2018:196.
2. Bossart BG. Marine mammals as sentinel species for oceans and human health. Vet Pathol. 2011; 48(3):676-690.
3. Caswell JL, Williams KJ. The respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. Vol. 2. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:557.
4. Jones MEB, Gasper DJ, Mitchell E. Bovidae, Antilocapridae, Giraffidae, Tragulidae, Hippopotamidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier. 2018:130.
5. Kul O, Kabakci N, Atmaca HT, Ozkul A. Natural peste des petits ruminants virus infection: novel pathologic findings resembling other morbillivirus infections. Vet Pathol. 2007; 44:479-786.
6. Lopez, A. and Martinson, SA. Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO:Elsevier; 2022: 621.
7. MacLachlan NJ, Dubovi EJ, eds. Paramyxoviridae and Pneumoviridae. In: Fenner's Veterinary Virology. San Diego, CA: Elsevier. 2017:342-345.
8. Olatunde BA, Franzke K, Adeyinka JA. Peste Des Petits Ruminants Virus and Goatpox Virus Co-Infection in Goats. Vet Pathol. 2020;57(4):550-553. 
9. Spagnoli, ST and Gelberg HB. Alimentary system and the peritoneum, omentum, mesentery, and peritoneal cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO:Elsevier; 2022: 471.
10. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier Limited; 2016: 115, 130-131.
11. United States Animal Health Association. Foreign Animal Diseases, 7^th ed. Boca Raton, FL: Boca Publications Group, Inc. 2008:357-363.
12. Wachtman L, Mansfield K. Viral Disease of Nonhuman Primates. In: Abee CR, Mansfield K, Tardif S, Morris T, eds. Nonhuman Primates in Biomedical Research, Vol 2. Waltham, MA:Elsevier. 2012:42-45.

 

Click the slide to view.

---