JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2026

N-B05

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, extending into the perivascular parenchyma, and to a lesser extent expanding the leptomeninges are moderate numbers of lymphocytes and macrophages with fewer neutrophils and scant to moderate amounts of necrotic cellular 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). Adjacent to vessels, there is multifocal vacuolation of the neuropil characterized by variably sized, round, clear vacuoles. Within the white matter myelin sheaths are often expanded and contain swollen and hypereosinophilic axons (spheroids) that are up to 30µm in diameter or gitter cells admixed with fragmented axonal debris (digestion chambers). Within the gray matter there are rare neurons with angular borders, hypereosinophilic cytoplasm, and pyknotic or karyorrhectic nuclei (neuronal necrosis) and rare neurons with central chromatolysis (degeneration).

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

CAUSE: Chlamydia pecorum

ETIOLOGIC DIAGNOSIS: Chlamydial meningoencephalitis

CONDITION: Sporadic bovine encephalomyelitis

CONDITION SYNONYMS: Buss disease, transmissible serositis

GENERAL DISCUSSION:

• Chlamydia pecorum is an obligate intracellular faint to poorly staining gram-negative coccobacillus associated with abortion, conjunctivitis, encephalitis, enteritis, metritis, pneumonia, and polyarthritis in ruminants
• C. pecorum is the only Chlamydia species that causes arthritis in domestic animals; responsible for sporadic or epidemic polyarthritis in calves and lambs; severity calves > lambs
• Disease caused by C. pecorum reported in the U.S., Japan, Europe, and Australia; most are asymptomatic
• Sporadic bovine encephalomyelitis (SBE) reported to occur naturally in cattle and buffalo; outbreaks can reach 25% morbididty
• C. pecorum and C. psittaci associated with SBE
• A publication (Borel, Vet Pathol 2018) clarified Chlamydial nomenclature: currently, the family Chlamydiaceae contains only ONE genus, Chlamydia (Chlamydophila is now considered an obsolete genus), with 11 species: C. abortus, C. avium, C. caviae, C.felis, C. gallinacea, C. muridarum, C. pecorum, C. pneumoniae, C. psittaci, C. suis, and C. trachomatis

PATHOGENESIS:

• Chlamydia exists in two forms (biphasic lifecycle): Elementary bodies and reticulate bodies
  • Elementary bodies: small (0.3um) particles with rigid cell walls that lack peptidoglycans and 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
  • Reticulate bodies: elementary bodies shed their cell wall and grow larger (0.6-1.5um) within intracytoplasmic membrane bound vacuoles, 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 infectious elementary bodies that are released during cell lysis
• Chlamydiae persist as commensal flora on the conjunctiva and respiratory, GI, and genitourinary mucosae, often with no clinical signs
• Transmission is through direct contact > infection of oronasal mucosal and pulmonary epithelial and endothelial cells > infection of monocytes and lymphocytes > systemic infection through leukocyte trafficking > CND endothelial cells infected
• 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 (e.g. meninges), and serous membranes; hallmark lesions are serofibrinous polyarthritis and vasculitis
  • Encephalitis is secondary to vasculitis; lesions is nonsuppurative meningoencephalomyelitis

TYPICAL CLINICAL FINDINGS:

• Typically affects calves less than 6-months of age; 5-50% morbidity (highest in calves) and 31% mortality (highest in adults)
• Sudden onset of moderate fever, dullness, and depression
• Catarrhal nasal discharge, excessive salivation and drooling, dyspnea, and cough
• Diarrhea
• Stiff gait, staggering, knuckling, circling, falling, muscle tremors
• Affected animals initially are ataxic but terminally become recumbent and develop opisthotonos

TYPICAL GROSS FINDINGS:

• When present, are limited to active hyperemia and edema of the leptomeninges
• Serofibrinous polyserositis and synovitis with congestion and petechiation
• Approximately 50% of fatal cases also have pleuritis and pericarditis
• Leptomeningeal congestion, edema, and few fibrin tags

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Fibrinous serositis of pleural, peritoneal, pericardial cavities
• Vasculitis +/- endothelial proliferation in many organs; in CNS perivascular cuffing with macrophages and plasma cells
• Severe, diffuse histiocytic and plasmacytic meningoencephalomyelitis
  • Basilar leptomeninges most severely affected
• Widespread reactive microglial nodules
• Degeneration and necrosis of the grey matter with microgliosis may be severe and are believed to be secondary to vascular lesions
• Reticulate bodies, i.e. inclusions, in cytoplasm of mononuclear cells (predominantly histiocytes) of affected tissues and exudates; NOT numerous and easier to see on cytology than histology.
• IHC: antigen detected in cytoplasm of endothelium and macrophages of the brain, spleen, lung, mesothelium (Borel, Vet Pathol 2018)

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:

• Cell culture is the gold standard diagnostic tool
• PCR and In Situ hybridization are available
• Histochemical stains: Giemsa, Gimenez, modified Ziehl-Neelsen, and Macchiavello stain reticulate and elementary bodies

DIFFERENTIAL DIAGNOSIS:

• For histologic findings:
  • Histophilus somni (TME, N-B03): Diffuse severe vasculitis with more hemorrhage and thrombi, may see bacteria in vessels
  • Listeria monocytogenes (N-B04): Localized signs; facial paralysis and circling; encephalitis with perivascular cuffs and microabscesses
  • Alcelaphine herpesvirus 1, ovine herpesvirus 2 (MCF; D-V15, S-V01): No serositis; higher mortality; ocular and mucosal lesions; necrotizing arteritis; plasma exudation into Virchow-Robins space; lymphocytic inflammation
  • Bovine herpes virus type 5: Encephalitis with perivascular cuffs and neuronal necrosis
  • Chlamydia pssittaci can cause identical disease
• Other causes of bovine neurological disease:
  • Rabies (Lyssavirus, Rhabdoviridae; N-V06): Negri bodies, mild perivascular cuffs
  • Lead toxicity (N-T05): Absence of fever, severe motor disease, lead inclusions, cortical laminar necrosis

COMPARATIVE PATHOLOGY:

• Chlamydia pecorum causes polyarthritis and abortion in sheep; meningoencephalitis, vasculitis, spontaneous calf enteritis, and abortion in cattle; sexually transmitted disease in koalas with severe urogenital tract inflammation and infertility issues
• Chlamydia pneumoniae is a human pathogen causing bronchitis and pneumonia in marsupials and horses; affects also frogs, snakes, rabbits and cats
• Chlamydia psittaci (Psittacosis, D-B12) is a common avian pathogen causing conjunctivitis, pneumonia, enteritis, hepatitis, embryonic death, increased mortality in chicks; important human pathogen, zoonotic ; may contribute to enzootic pneumonia in lambs and claves; experimentally infects mice; can infect rabbits.
• Chlamydia abortus (R-B08) is endemic in ruminants causing abortion, especially in ewes and does; affects nondomestic ruminants; can infect wide range of animals; zoonotic
• Chlamydia felis is endemic in cats, producing conjunctivitis and rhinitis; zoonotic
• Chlamydia caviae is pathogen of guinea pigs; zoonotic
  • Causes inclusion body conjunctivitis, rhinitis, urogenital tract infections, abortions and pneumonia
• Chlamydia trachomatis is a human pathogen causing trachoma, sexually transmitted disease and arthritis; a case reorted in pig-tail macaque; causes infertility in African green monkeys; can experimentally infect mice
• Chlamydia muridarum causes pneumonia in mice and hamsters
• Chlamydia suis causes conjunctivitis, enteritis and pneumonia in swine; zoonotic
• Chlamydia avium possibly causes enteritis and respiratory in birds
• Chlamydia gallinacea: in birds, no apparent pathology yet described

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