AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

April 2017

N-V16 (NP)

 

Signalment (JPC #1902458):  Weaner pig

 

HISTORY:  These pigs were purchased for rearing.  Seven days after arrival on the farm, 27 of the pigs had high fever, anorexia, and cutaneous hyperemia.  Most of the pigs died 7-12 days later.

 

HISTOPATHOLOGIC DESCRIPTION:  Cerebrum and brainstem:  Multifocally, blood vessels within the gray matter, white matter, meninges, and the choroid plexus are surrounded by moderate numbers of lymphocytes, macrophages, plasma cells and a small amount of karyorrhectic and cellular debris (necrosis) that occasionally extends into surrounding neuropil and white matter.  Similar inflammatory cells, minimal necrotic debris and fibrin segmentally expand and disrupt blood vessel walls (vasculitis); these vessels are also surrounded by increased clear space (edema).  There are multifocal glial nodules within areas of grey and white matter, and increased numbers of reactive astrocytes.  Remaining blood vessels are often lined by hypertrophied (reactive) endothelium.    

 

MORPHOLOGIC DIAGNOSIS:  Cerebrum and brainstem: Choriomeningoencephalitis, nonsuppurative, perivascular, multifocal, mild, with vasculitis, gliosis, and glial nodules, breed not specified, porcine.

 

ETIOLOGIC DIAGNOSIS:  Pestiviral choriomeningoencephalitis

 

CAUSE:  Porcine pestivirus

 

CONDITION:  Classical swine fever, hog cholera

 

CONDITION SYNONYMS:  Schweinpest, peste du porc, peste svina

 

GENERAL DISCUSSION:

·       A highly contagious, fatal hemorrhagic disease caused by a small, enveloped ssRNA virus belonging to the genus Pestivirus (Flaviviridae)

·       Peracute, acute, subacute, chronic and persistently infected forms

·       Morbidity and mortality ranges from almost none to 100% depending on strain virulence

 

PATHOGENESIS:

·       Virus is transmitted by direct contact, usually by the oronasal route, and occasionally by fomites and arthropods; virus is eliminated in urine, feces, lacrimal and oronasal secretions, and in semen of infected boars

·       Prime viral targets are monocytes and macrophages, but also epithelial cells, endothelial cells, lymphocytes, neutrophils, fibroblasts and megakaryocytes

·       Primary site of viral replication is tonsillar epithelium > spread to cervical lymph nodes > viremia > secondary replication in cells of the immune system (lymph nodes, bone marrow, spleen, Peyer’s patches) > invasion of endothelial cells and epithelial cells (pharyngeal mucosa, GI tract, gallbladder, pancreas, salivary gland, uterus, adrenal gland, and thyroid gland) > damage to endothelial and other cells > thrombocytopenia > consumption coagulopathy > DIC > hemorrhage

·       Intestinal epithelial necrosis due to release of chemical mediators by activated macrophages, rather than direct viral infection

·       End stages of chronic disease cause lymphoid depletion (indirectly through expression of apoptotic cytokines) and secondary bacterial infection

·       TNF-alpha, and, to a lesser extent, IL-1 alpha and IL-6 synthesized and released by virally-infected macrophages appear to be the major cytokines involved in the pathogenesis of lymphocytopenia and thrombocytopenia

·       Renal hemorrhage results from diapedesis and increased vascular permeability secondary to complement activation, mast cell degranulation and release of chemical mediators from fibroblasts and macrophages

·       Mesangioproliferative glomerulonephritis in chronic cases results from immune-complex (IgM and IgG) and C1q deposition

·       Late-onset disease occurs in persistently infected pigs that are immunotolerant to porcine pestivirus as a result of in utero infection by a low virulent strain

 

TYPICAL CLINICAL FINDINGS:

·       Acute:  Sudden death, depression, anorexia, pyrexia, leukopenia, thrombocytopenia, vomiting, diarrhea, cutaneous erythema and hemorrhage, nervous signs, conjunctivitis

·       Subacute and chronic:  Emaciation, cutaneous erythema and hemorrhage, alopecia, dermatitis, diarrhea

·       In utero infections may result in abortion, stillbirth or mummified fetuses, or congenital tremors type A1 (due to cerebellar hypoplasia and hypomyelinogenesis)

 

TYPICAL GROSS FINDINGS:

·       Acute:  Splenic infarction; hemorrhagic lymph nodes; tonsillar necrosis; renal petechial and ecchymotic hemorrhages (“turkey egg kidney”); petechial and ecchymotic hemorrhages in urinary bladder, larynx, gastric mucosa, lung, and epicardium; and subcutaneous (especially abdomen and inner thighs) and serosal hemorrhage

·       Subacute and chronic:  "Button ulcers" within the intestinal tract, thymic atrophy

·       In utero infection:  Cerebellar hypoplasia, thymic atrophy, deformed head and limbs, edema and petechial hemorrhage in the skin and viscera; or abortion, stillbirths and mummified fetuses

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·       Central nervous system:  Nonsuppurative meningoencephalitis with vasculitis and perivasculitis, primarily in the brainstem, midbrain and thalamus; coexistence of endothelial cell proliferation with swelling that occludes the lumen and endothelial necrosis, perivascular hemorrhage

·       Response of neural parenchyma secondary to vascular lesions and is often non-existent or limited to minimal neuronal degeneration, or may consist of glial nodules around obstructed or destroyed capillaries

·       Vessels of eyes, choroid plexus, and leptomeninges similarly involved

·       Other tissues: Fibrinoid necrosis, vasculitis, hemorrhage, fibrin thrombi and infarction; lymphoid necrosis; membranoproliferative glomerulonephritis

 

ULTRASTRUCTURAL FINDINGS: 

·       Virions bud from the membranes of the endoplasmic reticulum and are spheroidal, enveloped, and 40-50 nm in diameter

·       There are fringelike projections of 6-8 nm on the virion surface

 

ADDITIONAL DIAGNOSTIC TESTS:

·       The direct immunofluorescence test for detection of viral antigen in frozen tissue sections (usually tonsil) is the usual officially accepted test in eradication programs

·       Prescribed test in the OIE manual include the neutralization peroxidase-linked assay, fluorescent antibody virus neutralization, and ELISA

·       CSFV antigen can be detected in formalin-fixed tissue by semi-nested RT-PCR or in situ hybridization

·       RT-PCR can be used to detect CSFV antigen in serum from live pigs, and meat juice and skeletal muscle from both live and dead pigs (lower diagnostic sensitivity than serum).

 

DIFFERENTIAL DIAGNOSIS:

For microscopic findings (nonsuppurative meningoencephalitis in pigs):

·       African swine fever (asfarvirus):  Similar lesion to those of porcine pestivirus

·       Pseudorabies/Aujeszky"s disease (porcine herpesvirus type 1): Nonsuppurative meningoencephalomyelitis with ganglioneuritis, neuronal degeneration and necrosis, and intranuclear inclusion bodies; other lesions may include multifocal necrosis in other organs such as liver, spleen and adrenal gland

·       Water deprivation/salt toxicity:  Laminar cerebrocortical neuronal necrosis with perivascular eosinophilic cuffs in the leptomeninges

·       Teschen disease (porcine enterovirus):  Nonsuppurative polioencephalomyelitis

·       Porcine hemagglutinating encephalomyelitis virus (porcine coronavirus): Vomiting, anorexia, constipation and emaciation in nursing pigs (“vomiting and wasting disease”); nonsuppurative meningoencephalomyelitis and neuronal degeneration, primarily within the gray matter of the caudal brain stem and spinal cord, and nonsuppurative inflammation and neuronal degeneration in peripheral ganglia

·       Rabies (rhabdovirus):  Nonsuppurative encephalomyelitis with perivascular lymphocytic cuffing, gliosis and Negri bodies

·       Swine vesicular disease (porcine enterovirus):  Nonsuppurative encephalomyelitis; vesicles on hoofs, snout, and oral cavity

·       Encephalomyocarditis virus (picornavirus):  Usually sudden death due to myocarditis; a minority of pigs will also have nonsuppurative meningoencephalitis    

 

COMPARATIVE PATHOLOGY:

Bovine viral diarrhea (bovine pestivirus) and border disease (ovine pestivirus) also can cause in utero infection, persistent viremia and congenital abnormalities

 

References:

1.      Buisch WW, Hyde JL, Mebus CA. Foreign Animal Diseases. Richmond, VA: United State Animal Health Association; 1998:273-282.

2.      Gomez-Villamandos JC, Garcia de Leaniz I, Nunez A, et al. Neuropathologic study of experimental classical swine fever. Vet Pathol. 2006;43:530-540.

3.      Gomez-Villamandos JC, Ruiz-Villamor E, Bautista MJ, et al. Pathogenesis of classical swine fever: Renal hemorrhages and erythrodiapedesis. J Comp Path. 2000;123:47-54.

4.      Gomez-Villamandos JC, Ruiz-Villamor E, Bautista MJ, et al. Morphological and immunohistochemical changes in splenic macrophages of pigs infected with classical swine fever. J Comp Path. 2001;125:98-109.

5.      Gomez-Villamandos JC, Ruiz-Villamor E, Salguero FJ, et al. Immunohistochemical and ultrastructural evidence of hog cholera virus infection of megakaryocytes in bone marrow and spleen. J Comp Path. 1998;119:111-119.

6.      Le Potier M-F, Mesplede A, Vannier P. Classical swine fever and other pestiviruses. In: Straw BE, Zimmerman JJ, D’Allaire S, Taylor DJ, eds. Diseases of Swine. 10th ed. Ames, IA: Blackwell Publishing; 2012:539-546.

7.      Lohse L, Uttenthal A, Rasmussen TB, Nielsen J.  Diagnostic value of meat juice in early detection of classical swine fever virus infection.  J Vet Diagn Invest. 2011;23(5):1005-1008.

8.      Miller  LM, Gal A. Cardiovascular system and lymphatic vessels. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:608-609.

9.      Miller AD, Zachary JF. Nervous system. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:862.

10.   Nagai M, Aoki H, Sakoda Y, Kozasa T, et al. Molecular, biological, and antigenic characterization of a Border disease virus isolated from a pig during classical swine fever surveillance in Japan. JVDI. 2014;26(4):547-552.

11.   Narita M, Kawashima K, Kimura K, et al. Comparative immunohistopathology in pigs infected with highly virulent or less virulent strains of hog cholera virus. Vet Pathol. 2000;37:402-408.

12.   Reperant LA, Brown IH, Haenen OL, deJong MD, et al. Companion animals as a source of viruses for human beings and food production animals. J Comp Path. 2016;155:S41-S53.

13.   Sanchez-Cordon PJ, Nunez A, Salguero FJ, Pedrera M, Fernandez de Marco M, Gomez-Villamandos JC. Lymphocyte apoptosis and thrombocytopenia in spleen during classical swine fever: Role of macrophages and cytokines. Vet Pathol. 2005;42:477-488.

14.   Sonnenburg J, Schultz K, Blome S, Staubach C. The challenge of detecting classical swine fever virus circulation in wild boars (Sus scrofa): simulation of sampling options. Journal of Wildlife Diseases. 2016;52(4):828-836.

15.   Summers BA, Cummings JF, de Lahunta A. Veterinary Neuropathology. St. Louis, MO: Mosby; 1995:125-126.

16.   Terpstra C. Hog cholera. In: Coetzer JAW, Thomson GR, Tustin RC, Kriek NPJ, eds. Infectious Diseases of Livestock. Vol 1. Oxford, England: Oxford University Press; 1994: 654-657.

17.   Valli VEO, Kiupel M, Bienzle D. Hematopoietic system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol. 3, 6th ed. Philadelphia, PA: Elsevier Ltd; 2016:178-181.

 

 


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