AFIP SYSTEMIC PATHOLOGY

 JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2017

N-B05 (NP)

 

Signalment (JPC #1143949):  Young calf

 

HISTORY: This calf was from Oklahoma. The animal experienced a sudden onset of disease characterized by high fever, anorexia, depression, decreased activity, excessive salivation with drooling, and nasal discharge. These signs were followed by dyspnea, cough and severe diarrhea. Towards the end of the illness, the calf had difficulty walking and exhibited stiffness and knuckling in the fetlock joints. The animal was seen to move aimlessly in circles, stagger and fall with the head extended in opisthotonus. In the final stages, the limbs appeared weak or paralyzed, and death occurred 7 days after the onset of signs.

 

HISTOPATHOLOGIC DESCRIPTION:  Brainstem:  Multifocally expanding Virchow-Robin space and extending into the meninges and adjacent neuropil are moderate numbers of lymphocytes and macrophages with fewer neutrophils and necrotic debris. Affected small caliber blood vessels are lined by hypertrophied (reactive) endothelial cells and vessel walls are often obscured by previously described inflammatory cells admixed with small amounts of necrotic debris and fibrin (necrotizing vasculitis). There is multifocal spongiosis within the neuropil adjacent to affected vessels.  Within the white matter myelin sheaths are often dilated with swollen axons (spheroids) up to 30 um in diameter or rarely contain a gitter cell (ellipsoid) (axonal degeneration).  Within the gray matter there are rare foci of neuronal necrosis and central chromatolysis (degeneration).

 

MORPHOLOGIC DIAGNOSIS: Brainstem:  Meningoencephalitis, lymphohistiocytic and neutrophilic, multifocal, moderate, with necrotizing vasculitis, breed unspecified, bovine.

 

CAUSE: Chlamydophila pecorum

 

ETIOLOGIC DIAGNOSIS:  Chlamydophilial meningoencephalitis

 

CONDITION:  Sporadic bovine encephalomyelitis

 

CONDITION SYNONYMS:  Buss disease, transmissible serositis

 

GENERAL DISCUSSION:

·       Chlamydophila pecorum is an obligate intracellular gram-negative  coccobacillus associated with abortion, conjunctivitis, encephalitis, enteritis, pneumonia and polyarthritis in ruminants

·       Chlamydiaceae are incapable of autonomous survival and replication and rely on host mitochondrial ATP for metabolic functions

·       A recent taxonomic change in the family Chlamydiaceae created two genera, Chlamydia and Chlamydophila; the genera are distinguished by rRNA sequences and production of detectable glycogen by Chlamydia; the genus Chlamydia contains three recognized species, C trachomatis, C muridarum, C suis, and within Chylamydophila there are six species, C pecorum, C. pneumoniae, C. psittaci, C. abortus, C. felis, C. caviae; these species are discussed in the comparative section

 

PATHOGENESIS:

·       Chlamydia exists in two forms:  Elementary bodies and reticulate bodies

·       Elementary bodies are small (0.3um) particles with rigid cell walls that can survive outside the host cell but are metabolically inactive and incapable of replication; they are the infectious form; attach to the host cell by adhesins on their surface and enter the host cell via phagocytosis

·       Elementary bodies shed their cell wall and grow larger (0.6-1.5um), forming reticulate bodies that replicate by binary fission; this form is metabolically active, utilizing ATP from host mitochondria; reticulate bodies are incapable of infecting other cells; reticulate bodies condense and reform elementary bodies that are released during cell lysis to infect other cells

·       Chlamydiae persist as commensal flora on the conjunctiva and respiratory, GI, and genitourinary mucosae, often with no clinical signs

·       They are shed in saliva, milk, urine, and feces

·       The disease does not seem to be highly transmissible and mild or inapparent cases can occur.; the incubation period varies from 4-27 days

·       The organism has a tropism for blood vessels, mesenchymal tissue, and serous membranes

·       Replication in serous membranes and vascular endothelium leads to serofibrinous serositis and vasculitis

·       Encephalitis is secondary to vasculitis

 

TYPICAL CLINICAL FINDINGS:

·       Calves less than 6-months of age

·       Sudden onset of high fever, depression

·       Catarrhal nasal discharge, excessive salivation and drooling

·       Diarrhea

·       Dyspnea and cough

·       Stiff gait, staggering, knuckling, circling, falling, muscle tremors

·       5-50% morbidity (highest in calves); 31% mortality (highest in adults)

·       No neurologic sequelae in survivors

 

TYPICAL GROSS FINDINGS:

·       Serofibrinous polyserositis and synovitis with congestion and petechiation

·       Approximately 50% of fatal cases also have pleuritis and pericarditis

·       Meningoencephalomyelitis

·       Leptomeningeal congestion and edema

·       Exudative meningitis especially on ventral surface of brain stem

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·       Fibrinous serositis of pleural, peritoneal, pericardial cavities

·       Vasculitis +/- endothelial proliferation in many organs

·       Severe, diffuse mononuclear meningoencephalitis especially affecting medulla and cerebellum

·       Degeneration and necrosis of the grey matter may be severe and are believed to be secondary to vascular lesions

·       Elementary bodies in cytoplasm of mononuclear cells of affected tissues and exudates

 

ULTRASTRUCTURAL FINDINGS:

·       Elementary bodies are round and dark with a bilayered cell wall and a unique dense core of condensed chromatin (nucleoid)

·       Reticulate bodies are larger with more dispersed chromatin

·       Intermediate forms (intermediate body) resemble reticulate bodies but contain a central electron dense core

·       All three forms occur together, within membrane-bound vacuoles (phagosomes); host mitochondria are closely associated with these vacuoles

 

ADDITIONAL DIAGNOSTIC TESTS:

·       Giemsa, Castaneda, Gimenez, and Macchiavello stain reticulate and elementary bodies

·       Neutralizing antibody and complement fixation tests

·       PCR and In Situ hybridization are available

 

DIFFERENTIAL DIAGNOSIS:

·       For histologic findings:

o  Histophilus somni (Haemophilus somnus)(TME): Diffuse severe vasculitis with more hemorrhage and thrombi

o  Listeria monocytogenes: Localized signs; facial paralysis and circling; encephalitis with perivascular cuffs and microabscesses

o  Alcelaphine herpesvirus 1, ovine herpesvirus 2 (MCF): No serositis; higher mortality; ocular and mucosal lesions; necrotizing arteritis; plasma exudation into Virchow-Robins space; lymphocytic inflammation

o  Bovine herpes virus type 5: Encephalitis with perivascular cuffs and neuronal necrosis

·       Other causes of bovine neurological disease

o  Rabies (Lyssavirus, Rhabdoviridae): Negri bodies, mild perivascular cuffs

o  Lead toxicity: Absence of fever, severe motor disease, lead inclusions, cortical laminar necrosis

·       Other causes of respiratory disease (without encephalitis)

o  Pasteurella multocida: Similar lung lesions

 

COMPARATIVE PATHOLOGY:

·       Chlamydophila pecorum causes encephalomyelitis in buffalo, reproductive and urinary tract disease/orchitis in koalas

·       Chlamydophila pneumoniae is a human pathogen causing bronchitis and pneumonia; affects also frogs and snakes

·       Chlamydophila psittaci is a common avian pathogen with zoonotic potential

·       Chlamydophila abortus is endemic in ruminants causing abortion, especially in ewes; affects rabbit, guinea pig, mice and human

·       Chlamydophila felis is endemic in cats, producing conjunctivitis and rhinitis

·       Chlamydophila caviae is specific pathogen of guinea pigs causing conjunctivitis

·       Chlamydia trachomatis is a human pathogen causing trachoma, sexually transmitted disease and arthritis

·       Chlamydia muridarum causes pneumonia in mice and hamsters

·       Chlamydia suis causes conjunctivitis, enteritis and pneumonia in swine

 

References:

1.      Cheville NF. Ultrastructural Pathology. 2nd ed. Ames, IA: Wiley-Blackwell; 2009:485-496.

2.      Cantile C, Youssef S. The nervous system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed., Philadelphia, PA: Elsevier Ltd.; 2016:391-392.

3.      Ganta RR. Chlamydiae. In: McVey DS, Kennedy M, Chengappa MM. Veterinary Microbiology. 3rd ed. Ames, IA: Blackwell Publishing, LTD; 2004:279-281.

4.      Giannitti F, Anderson M, Miller M, et al. Chlamydia pecorum: Fetal and placental lesions in sporadic caprine abortion. J Vet Diagn Invest. 2016; 28(2): 184-189.

5.      Johnston SD, Deif HH, McKinnon A, Theilemann P, Griffith JE, Higgins DP. Orchitis and epididymitis in koalas (Phascolarctos cinereus) infected with Chlamydia pecorum. Vet Pathol. 2015; 52(6): 1254-1257.

6.      McAdam AJ, Sharpe AH. Infectious diseases. In: Cotran RS, Kumar V, Collins T, eds. Pathological Basis of Disease. 9th ed. Philadelphia, PA: Elsevier Saunders; 2015:383-384.

7.      Radostits OM, Gay CC, Blood DC, Hinchcliff KW. Veterinary Medicine: A Textbook of the Diseases of Cattle, Sheep, Pigs, Goats and Horses. 10th ed. New York, NY: W.B. Saunders Company; 2007:1433-1437.

8.      Summers BA, Cummings JF, De Lahunta A. Veterinary Neuropathology. St Louis, MO: Mosby; 1995:144.

 

 

 


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