AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

April 2017

N-V12 (NP)

 

Signalment (JPC 2359294):  An adult seal

 

HISTORY:  This animal was found dead along the shore.  Gross inspection revealed severe bronchopneumonia.

 

HISTOPATHOLOGIC DESCRIPTION:  Cerebrum:  Multifocally within the gray matter, there are multiple small foci of spongiosis with minimal eosinophilic debris and glial nodules.  Multifocally neuronal cell bodies are degenerate (swollen and round with central chromatolysis) or are necrotic (shrunken, hypereosinophilic cytoplasm with pyknotic nuclei).  There is occasional satellitosis and rare multinucleated syncytial cells.  There are few gemistocytes (astrocytes with abundant eosinophilic cytoplasm with eccentric nuclei).  Rarely, neurons and astrocytes contain round to oval, 1-5 um diameter eosinophilic intranuclear or intracytoplasmic inclusion bodies.  Multifocally within the white matter, myelin sheaths are dilated and contain a spheroid (round, swollen, hypereosinophilic axon).  In more severely affected areas, blood vessels are occasionally lined by hypertrophied reactive endothelial cells and surrounded by mild hemorrhage.  Diffusely, there is mild expansion of Virchow Robin space by few lymphocytes, plasma cells and rare macrophages (perivascular cuffing).  The meninges contain a similar but reduced inflammatory infiltrate.

 

MORPHOLOGIC DIAGNOSIS:  Cerebrum:  Encephalitis, nonsuppurative, multifocal, moderate, with rare neuronal degeneration, syncytia, spongiosis, gliosis, spheroids, and intranuclear and intracytoplasmic eosinophilic inclusion bodies, seal, pinniped.

 

ETIOLOGIC DIAGNOSIS:  Morbilliviral encephalitis

 

CAUSE:  Phocine morbillivirus [Phocine distemper virus (PDV)]

 

GENERAL DISCUSSION:

·       Family Paramyxoviridae, genus Morbillivirus; single-stranded, enveloped, RNA viruses

·       Canine distemper virus is the closest relative of PDV and has a wide host range including all terrestrial carnivores; has also caused epidemics among pinnipeds

·       PDV is a highly contagious aerosolized virus that causes epizootics in naive populations; evidence also suggests transmission by direct and indirect contact due to sociable behavior of pinnipeds

·       Clinical signs and lesions in lung, CNS, and lymphoid tissue are comparable to canine distemper virus (CDV)

·       PDV has cause very large, very-well-documented epizootics in seals in Europe; serologic surveys have detected anti-morbilliviral antibodies from pinnipeds from the Antarctic to the Canadian artic

·       Secondary bacterial infections can be common:  Bordetella bronchiseptica and Streptococcus equi subsp. zooepidemicus were significantly associated with the seal die-offs from phocine distemper in 2002

 

PATHOGENESIS:

·       Proposed similarity to CDV:  Inhalation > virus replicates in lymphoid tissue > viremia 5-12 days post-infection > lymphocytolysis and lymphoid depletion > dissemination to multiple tissues, including respiratory, GI tract, CNS and lymphoid tissues > immunosuppression > increased susceptibility to secondary infections

·       CNS white matter is demyelinated following the direct spread of virus into cerebrospinal fluid

 

TYPICAL CLINICAL FINDINGS:

·       Abortion, sudden death

·       Lethargy, weakness, ventral pressure sores, severe edematous conjunctivitis, serous to mucopurulent oculonasal discharge, cutaneous lesions, gastroenteritis, neurologic signs

·       Pneumonia, anorexia, respiratory distress, cyanosis, coughing terminally

 

TYPICAL GROSS FINDINGS:

·       CNS:  No gross lesions

·       Respiratory:  Bronchointerstitial pneumonia, pulmonary edema and congestion, atelectasis, emphysema, occasionally exudative pleuritis

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·       Intranuclear or intracytoplasmic viral inclusion bodies are single to multiple, eosinophilic, distinct, round to oval, and up to 20 um in diameter

·       Multinucleated “Warthin-Finkeldey” syncytial cells in bronchi, and bronchiolar and alveolar lumina, which often contain inclusion bodies

·       CNS:  Non-suppurative demyelinating meningoencephalitis, neuronal and glial necrosis, perivascular cuffing, gliosis, neuronophagia and inclusion bodies within astrocytes, neurons, and ependymal cells

·       Respiratory:  Bronchointerstitial pneumonia, edema, congestion, and interlobular, subpleural and mediastinal emphysema; intracytoplasmic and intranuclear (less frequent) inclusion bodies in respiratory epithelium, alveolar macrophages, and type II pneumocytes

·       Lymphoid tissue:  Lymphocytolysis, lymphoid depletion of lymph nodes, spleen, gut-associated lymphoid tissue, and thymus; rare intracytoplasmic inclusion bodies

·       Other tissues:  Intracytoplasmic inclusion bodies can be found within epithelium of the urinary tract including urinary bladder and renal pelvis, and the gastrointestinal tract including biliary and pancreatic ductules

 

ULTRASTRUCTURAL FINDINGS:

·       Virions are enveloped, pleomorphic (spherical and filamentous), 150-300 nm in diameter and have a herringbone-shaped nucleocapsid with helical symmetry

 

ADDITIONAL DIAGNOSTIC TESTS: 

·       Reverse transcriptase polymerase chain reaction (RT-PCR)

·       Immunohistochemistry

·       Immunofluorescence

 

DIFFERENTIAL DIAGNOSIS:

·       Combined mycoplasma and influenza infections can cause deadly epizootics in seals

 

COMPARATIVE PATHOLOGY:

·       Cetacean morbillivirus:  Interstitial pneumonia, lymphoid depletion, syncytial cells, 3-8 um diameter eosinophilic intranuclear or intracytoplasmic inclusion bodies of lung, lymph node, spleen, epidermis and urinary bladder; demyelination is NOT recognized in CMV-infected cetaceans; poses a significant risk to endangered species of aquatic mammals

·       Rinderpest:  Infects ruminants and wild ungulates, dehydration, diarrhea, depression and death, oral/esophageal erosion and ulceration, inflammation and necrosis of gastrointestinal tract, Peyer"s patch necrosis; currently classified as eradicated

·       Canine distemper virus:  Infects animals of the families Ailuridae (red panda), Canidae (fox, wolf), Hyaenidae (hyena), Mustelidae (ferret, mink), Procyonidae (raccoon, panda), Ursidae (bear), Viverridae (civet, mongoose), and Felidae (exotic felids including lions, tigers, and leopards) are susceptible; causes bronchointerstitial pneumonia with syncytia, inclusion bodies, lymphoid depletion, optic neuritis, retinal degeneration, anterior uveitis, defective enamel development, hyperkeratosis, demyelination, neuronal degeneration and perivascular cuffs in CNS

·       Peste des petits ruminants:  Infects sheep and goats, acute onset, inflammation and necrosis of mouth and gastrointestinal tract, and inconsistent involvement of the respiratory tract

·       Measles (rubeola) virus:  Infectious disease of primates characterized by blotchy red-brown rash, and sometimes pneumonia, diarrhea, keratitis, blindness, encephalitis, and hemorrhage

 

REFERENCES:

1.      DiGuardo G, Marruchella G, Agrimi U, Kennedy S. Morbillivirus infections in aquatic mammals: A brief overview. J Vet Med. 2005;52:88-93.

2.      Duignan PJ, Nielsen O, House C, et al. Epizootiology of morbillivirus infection in harp, hooded, and ringed seals from the Canadian Arctic and Western Atlantic. J Wildl Dis. 1997;33(1):7-19.

3.      Kennedy S. Morbillivirus infections in aquatic mammals. J Comp Path. 1998;119:201-225.

4.      Lipscomb TP, Kennedy S, Moffett D, et al. Morbilliviral epizootic in bottlenose dolphins of the Gulf of Mexico. J Vet Diagn Invest. 1996;8:283-290.

5.      Lipscomb TP, Kennedy S, Moffett D, Ford BK. Morbilliviral disease in Atlantic bottlenose dolphins (Tursiops truncatus) from the Gulf of Mexico. J Wildl Dis. 1994;30(4):562-576.

6.      Lipscomb TP, Mense MG, Habecker PL, Taubenberger JK, Schoelkopf R. Morbilliviral dermatitis in seals. Vet Pathol. 2001;38:724-726.

7.      Lipscomb TP, Schulman FY, Moffett D, Kennedy S. Morbilliviral disease in Atlantic bottlenose dolphins (Tursiops truncatus) from the 1987-1988 epizootic. J Wildl Dis. 1994;30(4):567-571.

8.      MacLachlan NJ, Dubovi EJ.  Paramyxoviridae. In: MacLachlan NJ, Dubovi EJ, eds.  Fenner’s Veterinary Virology.  4th ed. Oxford, UK: Elsevier; 2011:320-321.

9.      Muller G, Wohlsein P, Beineke A, et al. Phocine distemper in German seals, 2002. Emerg Infect Dis. 2004;10(4):723-725.

10.   Peste des petits ruminants. In: Committee on Foreign Animal Diseases of the United States Animal Health Association. Foreign Animal Diseases. Richmond, VA: Pat Campbell & Associates and Carter Printing Company; 1998:344-351.

11.   Philippa JD, van de Bildt MW, Kuiken T, Hart P, Osterhaus AD. Neurological signs in juvenile harbour seals (Phoca vitulina) with fatal phocine distemper. Vet Rec. 2009;164(11)327-331.

12.   Rinderpest. In: Committee on Foreign Animal Diseases of the United States Animal Health Association. Foreign Animal Diseases. Richmond, VA: Pat Campbell & Associates and Carter Printing Company; 1998:362-369.

13.   Schulman FY, Lipscomb TP, Moffett D, et al. Histologic, immunohistochemical, and polymerase chain reaction studies of bottlenose dolphins from the 1987-1988 United States Atlantic coast epizootic. Vet Pathol. 1997;34:288-295.

14.   Siebert U, Rademaker M, Ulrich SA, et al. Bacterial microbiota in harbor seals (Phoca vitulina) from the north sea of Schleswig-Holstein, Germany, around the time of morbillivirus and influenza epidemics.  J Wildl Dis. 2017 Jan 31. doi: 10.7589/2015-11-320. [Epub ahead of print]

15.   Van Bonn WG.  Pinnipedia.  In: Miller RE, Fowler ME, eds.  Fowler’s Zoo and Wild Animal Medicine. Vol 8.  St. Louis, MO: Elsevier; 2015:446.

 

 

 


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