JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

April 2023

N-V10

 

Signalment (JPC #1498135): A parrot

 

HISTORY: This parrot was inoculated with an agent isolated from another parrot.

 

HISTOPATHOLOGIC DESCRIPTION: Cerebellum and brainstem: Within the periventricular white matter are multiple coalescing 2-3 mm foci of liquefactive necrosis characterized by loss of normal neuroparenchyma with replacement by moderate numbers of gitter cells, reactive astrocytes (gemistocytes), and scattered hemorrhage, fibrin, and edema. Remaining myelin sheaths are frequently dilated and contain swollen hypereosinophilic axons (spheroids). Perivascular spaces are multifocally variably expanded by a lymphoplasmacytic infiltrate (perivascular cuffing), and endothelial cells are hypertrophied (reactive).   Scattered neurons exhibit central chromatolysis characterized by peripheralization of Nissl substance (neuronal degeneration) and rarely contain 2-5 µm, eosinophilic, cytoplasmic or nuclear inclusion bodies. There are decreased numbers of Purkinje cells (loss) and occasional Purkinje cells have hypereosinophilic cytoplasm, angular borders, and pyknotic nuclei (necrosis) and contain the previously described inclusion bodies.  

 

MORPHOLOGIC DIAGNOSIS: Cerebellum and brainstem: Encephalitis, necrotizing, multifocal, moderate, with spheroids, lymphoplasmacytic perivascular cuffing, and intranuclear and intracytoplasmic viral inclusions, parrot, avian.

                                                                                       

ETIOLOGIC DIAGNOSIS: Avulaviral (Paramyxoviral) encephalitis

 

CAUSE: Newcastle disease virus (Avian paramyxovirus serotype 1, APMV-1)

 

CONDITION: Newcastle disease

 

GENERAL DISCUSSION: 

• Causative agent is APMV-1; genus Avulavirus and family Paramyxoviridae; there are many strains that vary in pathogenicity; the four categories are:
  1. Asymptomatic enteric
  2. Lentogenic: Mildly pathogenic
  3. Mesogenic: Moderately pathogenic
  4. Velogenic: Markedly pathogenic; neurotropic and viscerotropic varieties 
• Viral disease; affects poultry, wild, and cage birds; marked variation in morbidity, mortality, clinical signs, and lesions
  1. Virus has been isolated from sparrows, pigeons, doves, crows, owls, and waterfowl; these birds do not play a significant role in spread of ND
• Newcastle disease is defined as “an infection of birds caused by a virus of avian paramyxovirus 1 (AVPM-1) that meets one of the following criteria for virulence:
  1. The virus has an intracerebral pathogenicity index (ICPI) in day-old chicks (Gallus gallus) of 0.7 or greater or
  2. Multiple basic amino acids have been demonstrated in the virus at the C-terminus of the F2 protein and phenylalanine at residue 117, which is the N-terminus of the F1 protein.”
• Common in chickens, less common in turkeys; all ages are susceptible
• Disease occurs worldwide; APMV-1 strains have been in the United States since 1940; extensive outbreaks occurred in 1971 and 2002; generally introduced by illegally imported birds
  1. Reportable disease 

 

PATHOGENESIS:

• Virus is shed in aerosols and fecesàcontaminates feed, water, fomites, and the environment (untreated tissue if not rendered) à transmission via inhalation or ingestion 
• Eggs laid by infected hen may be contaminated and if broken can infect a hatch of chicks à distribution of chicks prior to onset of clinical signs will spread disease
• Vaccines produced from lentogenic viruses have short immunity and revaccination is required; vaccines produced from mesogenic strains have a longer, stronger immunity (may cause mortality in unthrifty chicks)
• Young chicks have a strong pro-inflammatory cytokine response that is proposed as the reason for more severe disease (Brown, Vet Pathol. 2022)

 

TYPICAL CLINICAL FINDINGS: 

1. Asymptomatic enteric: Subclinical enteric infection
2. Lentogenic: Mild respiratory infection
   1. Adult chickens: +/- Clinical signs; mild respiratory signs and decreased egg production; few soft-shelled, roughened, or deformed eggs
   2. Young chicks: Respiratory signs (gasping, sneezing coughing, rales, and nasal and lacrimal discharge); swollen heads
3. Mesogenic: respiratory signs and occasional nervous signs with low mortality 
   1. Adult chickens: Mild depression, anorexia, respiratory signs; mortality low or absent; +/- mild CNS signs; egg production ceases and eggs are low quality (soft-shelled, roughened, or deformed)
   2. Young chicks: Marked depression and prostration; marked respiratory signs; CNS signs (abnormal position of the head and neck (“star gazers”); paralysis, prostration, trampling by pen mates, and death; up to 50% mortality 
4. Velogenic
   1. Neurotropic velogenic: Respiratory and nervous signs with high mortality
   2. Viscerotropic velogenic: Hemorrhagic intestinal lesions and high mortality
   3. Adult birds: Varies based on tropism; marked dyspnea; violent diarrhea, conjunctivitis, paralysis, and death in 2-3 days; swelling/darkening around eyes with sticky ocular and nasal discharge; CNS signs in 0-25% (tremors, twisting of head/neck, circling, paresis, paralysis, terminal clonic spasms); up to 100% mortality 
   4. Young chicks: Similar signs to mesogenic strains, but up to 100% mortality

 

TYPICAL GROSS FINDINGS: 

• Lentogenic and mesogenic: Minimal; mild conjunctivitis, rhinitis, tracheitis, and air sacculitis; complicated by secondary bacterial infection; drop in egg production (mesogenic strains)
• Velogenic: 
  1. Ocular and respiratory lesions: Conjunctival hemorrhage, edema, hemorrhage, congestion and necrosis of the tracheal epithelium with paratracheal edema (near thoracic inlet), air sacculitis +/- catarrhal or fibrinoheterophilic exudate if a secondary bacterial infection is present (e.g. E. coli)
  2. Hemorrhages of mucosal surface of proventriculus, gizzard, Peyer’s patches, and cecal tonsils
  3. Focal splenic necrosis
  4. Mature production birds may have egg yolk in the abdominal cavity and regressing hemorrhagic ovarian follicles 
  5. Minimal gross lesions with peracute mortality 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Lentogenic and mesogenic: Deciliation, necrosis, attenuation of the respiratory epithelium with infiltration of the lamina propria by a mixture of mononuclear cells and fewer heterophils; luminal exudate composed of exfoliating epithelial cells, mucus, and inflammatory cells
• Velogenic: 
  1. CNS: Nonsuppurative encephalomyelitis with neuronal degeneration, perivascular cuffing with lymphocytic cells, multifocal gliosis, and endothelial hypertrophy 
  2. Vascular: Medial degeneration, microvascular hyalinization and thrombosis, endothelial necrosis with widespread congestion, hemorrhage, and edema
  3. Lymphoid organs: Marked lymphocyte necrosis +/- hemorrhage
  4. Respiratory: Widespread deciliation of the tracheal epithelium with mucosal congestion, edema, and hemorrhage and marked lymphohistiocytic cellular infiltrate of the lamina propria 

     

ADDITIONAL DIAGNOSTIC TESTS: 

• Virus isolation in embryos; pathogenicity testing in day-old specified pathogen free (SPF) chicks
• RT-PCR: viral RNA
• Serology: Demonstrate an increasing titer of Newcastle antibody in the flock by ELISA or HI
• Immunochromatographic strip that detects NDV antigen with no cross-reactivity in viruses examined; sensitivity 83.3%; specificity 100% (Qingmei, J Vet Diagn Invest. 2019)

 

DIFFERENTIAL DIAGNOSIS: 

For gross findings:

• Fowl plague (highly pathogenic avian influenza [HPAI], Orthomyxoviridae): Lung lesions predominate
• Eastern equine encephalitis (Togaviridae, Alphavirus)
• West Nile virus (Flaviviridae)

For histologic findings:

• Marek's disease (N-V08, Alphaherpesvirus): Lymphocytic proliferation in meninges and cerebrum – Possible intranuclear inclusion bodies
• Avian encephalomyelitis (N-V03, Enterovirus, Picornaviridae family): Prominent neuronalcentral chromatolysis
• Toxoplasma gondii (N-P02): Necrosis and gliosis, non-suppurative inflammation with tachyzoites

 

COMPARATIVE PATHOLOGY: 

Avian Paramyxoviruses, genus Avulavirus

• Avian paramyxovirus-1 

• Less severe in turkeys (airsacculitis most common lesion) than that in chickens (tracheitis) with respiratory and neurological signs
• Ducks and geese: Infections are usually asymptomatic 
• Game birds – Outbreaks have been reported
• Pigeon – Causes diarrhea, neurological signs; virus produces signs similar to velogenic or neurotropic virus strains in chickens  

• Pigeon paramyxovirus serotype I (PPMV-1) belongs to class II genotype VI of APMV-1; it causes mortality in columbiform and poultry and has caused numerous mortality events in the US in Eurasian collared doves and rock pigeons, causing acute to subacute tubulointerstitial nephritis and necrotizing pancreatitis most commonly with IHC viral labeling in these organs, lymphoid depletion with occasional IHC viral labeling, and lymphocytic meningoencephalitis without IHC viral labeling (Isidoro-Ayza, Vet Pathol. 2017)

• Japanese quail – Recent report indicates that virulent NDV strains have limited replicative potential and mild to moderate disease-inducing ability (Susta,Vet Pathol. 2018)
• Raptors: APMV-1 outbreaks are usually traced back to contact with wild birds, pigeons, and poultry (alive or as food)
• Pet birds: PMV- 1, 2, 3, and 5 have been documented in pet birds

• PMV-3 is the most common cause of encephalitis in psittacine and small passerine birds; commonly affects Australian grass parakeets and cockatiels

• Racing pigeons: Common cause of encephalitis 
• Ostriches: Isolated from ostriches in zoos and commercial operations; may be absent clinical disease and there are no pathognomonic gross or microscopic lesions 

• Chicks and juveniles are most susceptible; sudden death
• Adults can have edema of the head, mucoid sinusitis, tracheitis, and airsacculitis, splenomegaly, epicardial petechial hemorrhages, and neurologic abnormalities

• Double-crested cormorants: Recurrent high rate of mortality; occurs in breeding colonies in the US and Canada; mortality can exceed 90% of juveniles; major clinical sign is an inability to fly and unilateral wing or leg paralysis

• May spillover into white pelicans; can cause large scale mortalities (greater than 5,000 birds); present as weak and unable to fly

• Falcons: Infected via prey; velogenic ND produces neurotrophic (nonsuppurative encephalomyelitis with mild to severe demyelination in the cerebrum) and visceral lesions; clinical signs include anorexia, vomiting, paralytic ileus, and bloody diarrhea; CNS signs include ataxia, head tilt, tremors, and wing and leg paralysis; torticollis develops late in disease; grossly may have a swollen pancreas with petechiae
• Found in one female bearded vulture; found dead; histiocytic hepatitis and duodenal and jejunal mucosal erosions 

Other Paramyxoviruses:  4 other genera:

• Morbillivirus – Includes measles virus, canine distemper and rinderpest viruses
• Respirovirus – Human parainfluenza virus 1, bovine and human parainfluenza 3 and Sendai virus
• Henipavirus – Formed from Nipah virus and Hendra virus
• Rubulavirus  - Mumps virus, includes some other mammalian parainfluenza viruses

• Rubulavirus of pigs: Encephalomyelitis, reproductive failure and corneal opacity (blue eye)

Public Health Significance:

 

References:

1. Abd-Ellatieff HA, Abd El Aziem AN, Elbestawy AR, Goda WM, Belih SS, Ellakany HF, Abd El-Hamid HS, Yanai T, AbouRawash AA, El-Habashi N. Efficacy of Vaccination against Infection with Velogenic Newcastle Disease Virus Genotypes VI and VII 1.1 Strains in Japanese Quails. J Comp Pathol. 2021;186:35-50.
2. Brown C, Zhang J, Pantin-Jackwood M, Dimitrov K, Ferreira HL, Suarez D. In situ cytokine gene expression in early stage of virulent Newcastle disease in chickens. Vet Pathol. 2022;59(1):75-81.
3. Carvallo FR, Moore JD, Nyaoke AC, Huang L, Crossley BM, Uzal FA. Diagnosis of virulent Newcastle disease in southern California, May 2018. J Vet Diagn Invest. 2018;30(4):493-494. 
4. Crespo R, Franca MS, Fenton H, Shivaprasad HL. Galliformes and Columbiformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier; 2018:756. 
5. Fan J, Chen W, Zhang Y, Liu Z, Li X, Ding H, Yi L, Chen J, Zhao M. Development of a reverse-transcription recombinase polymerase amplification assay with a lateral flow assay for rapid detection of avian orthoavulavirus 1. J Ved Diagn Invest. 2021;33(2):308-312.
6. Fenton H, McManamon R, Howerth EW. Anseriformes, Ciconiiformes, Charadriiformes, and Gruiformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier; 2018:709.
7. Igwe AO, Afonso CL, Ezema WS, Brown CC, Okoye JOA. Pathology and Distribution of Velogenic Viscerotropic Newcastle Disease Virus in the Reproductive System of Vaccinated and Unvaccinated Laying Hens (Gallus gallus domesticus) by Immunohistochemical Labelling. J Comp Pathol. 2018;159:36-48.
8. Li Q, Wang L, Sun Y, Liu J, Ma F, Yang J, Zhao D, Zhang Y, Luo J, Guo J, Deng R, Zhang G. Evaluation of an immunochromatographic strip for detection of avian avulavirus 1 (Newcastle disease virus). J Vet Diagn Invest. 2019;31(3):475-480.
9. Li Q, Wang L, Sun Y, et.al. Evaluation of an Immunochromatographic Strip for Detection of Avian Avulavirus 1 (Newcastle Disease Virus).  J Vet Diagn Invest. 2019;31(3):475-480.  
10. Schmidt RE, Reavill DR, Phalen DN. Nervous system. In: Pathology of Pet and Aviary Birds. 2^nd ed. Ames, Iowa; 2015:223.
11. Sellers H, Ojkic D. Viral diseases. In: Boulianne M. Avian Disease Manual. 8^th ed. Jacksonville, FL: American Association of Avian Pathologists; 2019:58-62.          
12. Smith DA. Palaeognathae: Apterygiformes, Casuariiformes, Rheiformes, Struthioniformes; Tinamiformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier; 2018:642. 
13. Stidworthy MF, Denk D. Sphenisciformes, Gaviiformes, Podicipediformes, Procellariiformes, and Pelecaniformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier; 2018:666.
14. Susta L, Segovia D, Oliver T, et.al. Newcastle Disease Virus Infection in Quail.  Vet Pathol. 2018;55(5):682-692.
15. Wunschmann A, Armien AG, Hofle U, Kinne J, Lowenstine LJ, Shivaprasad HL. Birds of Prey. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier; 2018:734. 

 

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