Conference 08 - 2010 Case: 03 20101006

Signalment:

Male, mature, captive bred, Timneh African Grey parrot (Psittacus erithacus timneh).This bird was one member of a research colony that had been created to study fecal virus shedding in psittacine birds with proventricular dilatation disease (PDD). All birds in this colony had a history of exposure to other birds with PDD. This individually caged bird had not shown any signs of neurological or gastrointestinal disease over the course of the study.

Gross Description:

No gross lesions seen at necropsy.

Histopathologic Description:

Brain: Multiple cerebral and meningeal vessels are lined by mildly hypertrophied endothelial cells with partial to complete perivascular cuffs of variable thickness (1- 8 cells thick) composed of predominantly lymphocytes and plasma cells with fewer macrophages.
Crop: Variable numbers of plasma cells and lymphocytes infiltrate around and within blood vessels, nerves and ganglia in the tunica muscularis. Infrequently, a few plasma cells and lymphocytes have infiltrated between smooth muscle fibers of the tunica muscularis. Occasional moderate sized lymphoid aggregates are present in the lamina propria.

Morphologic Diagnosis:

1. Mild to moderate cerebral and meningeal lymphoplasmacytic perivascular cuffing.
2. Mild to moderate multifocal lymphoplasmacytic ganglioneuritis and mild multifocal non-suppurative leiomyositis of the crop compatible with proventricular dilatation disease (PDD)

Lab Results:

Histopathological lesions consistent with PDD were identified in cerebrum, cerebellum, brainstem, spinal cord, brachial nerve, vagus nerve, adrenal gland, crop, proventriculus, ventriculus and heart. Tissues positive for avian bornavirus (ABV) antigen by immunohistochemistry (IHC) include cerebellum, brainstem, spinal cord, adrenal gland and ventriculus. Tissues positive for ABV antigen by RT-PCR include cerebrum, cerebellum, brain stem, spinal cord and adrenal gland.

Condition:

Proventricular dilatation disease

Contributor Comment:

Plasmacytic and lymphocytic infiltrates in the myenteric ganglia of the crop, proventriculus, ventriculus and duodenum are characteristic of proventricular dilatation disease (PDD). This disease has also been called macaw wasting disease, neuropathic gastric dilatation in psittaciformes(7) and myenteric ganglioneuritis(6) and has been reported in many species of psittacine birds. Similar pathological findings have been identified in Canada geese(2) and recently in various Passeriformes.(11) Psittacine birds affected with PDD can exhibit gastrointestinal signs including anorexia, emaciation, weight loss, regurgitation, delayed crop emptying, diarrhea and the presence of undigested seeds in the feces and/ or neurological signs such as ataxia, tremors, seizures and motor or proprioceptive defects.(3) Sudden death with the absence of clinical signs has also been reported. It is now known that the characteristic lymphoplasmacytic infiltrates can occur in many tissues of the central and peripheral nervous system and not all affected birds exhibit nervous signs clinically(1) as demonstrated by this bird. This bird did not show any signs of neurological disease for a year prior to euthanasia but histologically had widespread cerebral and meningeal perivascular lymphoplasmacytic cuffing.

The characteristic cellular infiltrates of PDD are variable in size and distribution as demonstrated by the lesions in the sections of brain and crop provided for this case. In some sections of crop, numerous plasma cells and lymphocytes are present within the nerves and ganglia, while in other sections, only rare plasma cells or lymphocytes can be identified. Historically, examination of multiple sections of biopsied tissues, such as crop, or multiple sections of gastrointestinal tract collected at necropsy was needed to improve diagnostic accuracy.

An avian bornavirus (ABV) has recently been proposed as the etiological agent of PDD, and evidence from bird inoculation studies is strongly supportive.(4,5) Through collaborative efforts of researchers from the University of California, San Francisco, the Ontario Veterinary College and the Animal Health Laboratory, University of Guelph, an ABV specific RT-PCR screening test and immunohistochemistry (IHC) that detects the ABV nucleocapsid protein have been developed and tissues from psittacine birds with and without PDD were tested. Those results were compared with the histopathologic diagnoses and the sensitivity and specificity of IHC for detection of ABV antigens on a bird by bird basis were found to be 100% and 100%, respectively. Many more tissues were positive for ABV RNA by RT-PCR than were positive histopathologically or for viral antigens by IHC. Brain tissues, but not crop tissues, from this bird were positive by RT-PCR for ABV antigen. Similar results were obtained with IHC testing. Overall, brain tissue appears to be the tissue that is most consistently positive with both PCR and IHC testing. It is suggested that IHC and or RT-PCR testing of biopsy specimens, in addition to histopathology, may help increase the sensitivity of diagnosis of PDD allowing for earlier identification of infected birds.(11)

JPC Diagnosis:

1. Brain: Meningoencephalitis, lymphohistiocytic and plasmacytic, perivascular, multifocal, mild.
2. Crop, ganglia: Ganglioneuritis, lymphohistiocytic and plasmacytic, multifocal, mild.

Conference Comment:

Borna disease virus (BDV) is the sole member of the family Bornaviridae, order Mononegavirales. The virus is spherical and enveloped with negative-sense single-stranded RNA.(8) Replication within infected cells occurs in the nucleus; viral inclusions typically are seen only in cell culture. BDV is neurotropic, resulting in persistent, non-cytolytic infection of the central nervous system.(9) The virus is known to naturally infect a wide variety of animals, including horses, sheep, cattle and rabbits.(8) The virus is implicated in human neuropsychoses, such as depression, schizophrenia, obsessive compulsive disorder and chronic fatigue syndrome.(12) The disease is best characterized in equids, where after a four week incubation period the infected horse exhibits non-specific signs of colic, fatigue, coughing and icterus followed by alternating periods of excitability and somnolence. Neurologic signs progress over the next 3-20 days, leading to the death of the animal.(8)

The pathogenesis and persistence of the virus within infected cells is complex. Once infection is established, the virus interferes with many intracellular signaling pathways involved in spread of the virus, maintenance of viral persistence, and modulation of neurotransmitter pathways.(9) Neuronal death is due to effector CD8+ T cells which kill infected cells.(12) Studies in laboratory infected mice demonstrated a positive correlation between lesion severity and increased levels of IL-6, TNF-α, IL-α, and inducible nitric oxide synthase mRNA.(12)

References:

1. Berhane Y, Smith DA, Newman S, et al. Peripheral neuritis in psittacine birds with proventricular dilatation disease. Avian Pathol. 2001;30:563-570.
2. Daoust PY, Julian R, Yason CV, Artsob H. Proventricular impaction associated with nonsuppurative encephalomyelitis and ganglioneuritis in two Canada geese. J Wildlife Dis. 1991; 27:513-517.
3. Degernes LA, Flammer K, Fisher P. Proventricular dilatation syndrome in a Green-Winged Macaw. Proceedings of the Annual Conference of the Association of Avian Veterinarians. 1991;45-49.
4. Gancz AY, Kistler AL, Greninger AL, et al. Experimental induction of proventricular dilatation disease in cockatiels (Nymphicus hollandicus) inoculated with brain homogenates containing avian bornavirus 4. Virol J. 2009;6:100.
5. Gray P, Hoppes S, Suchodolski P, et al. Use of avian bornavirus isolates to induce proventricular dilatation disease in conures. Emerg Infect Dis. 2010;16:473-479.
6. Joyner KL, Kock N, Styles D. Encephalitis, proventricular and ventricular myositis, and myenteric ganglioneuritis in an Umbrella Cockatoo. Avian Dis. 1989;33:379-381.
7. Mannl A, Gerlach H, Leipold R. Neuropathic gastric dilatation in Psittaciformes. Avian Dis. 1987;31:214-221.
8. Murphy FA, Gibbs EPJ, Horzinek MC, Studdert MJ. Bornaviridae. In: Veterinary Virology. 3rd ed. vol.1. San Diego, CA: Elsevier Academic Press; 1999:455-458.
9. Planz O, Pleschka S, Wolff T. Borna disease virus: a unique pathogen and its interaction with intracellular signaling pathways. Cell Microbiol. 2009;11(6):872-879.
10.Perpi+â-¦+â-ín D, Fern+â-índez-Bellon H, L³pez C, Ramis A. Lymphoplasmacytic myenteric, subepicardial and pulmonary ganglioneuritis in four non-psittacine birds. J Avian Med Surg. 2007;21:210-214.
11.Raghav R, Taylor M, Delay J, Kistler A, Smith D. Avian bornavirus is present in many tissues of psittacine birds with histopathologic evidence of proventricular dilatation disease. J Vet Diagn Invest. 2010:22(4):495-508.
12.Thakur R, Sarma S, Sharma B. Role of Borna disease virus in neuropsychiatric illnesses: are we inching closer?. Indian J Med Microbiol. 2009;27(3):191-201.