JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1758403): Full-term bovine fetus
HISTORY: This fetus was found in a field on a small beef cattle farm.
HISTOPATHOLOGIC DESCRIPTION: Cerebrum: Diffusely the meninges are markedly expanded up to ten times normal by high numbers of degenerate neutrophils, fewer lymphocytes and plasma cells admixed with eosinophilic cellular and karyorrhectic debris (necrosis), eosinophilic beaded to fibrillar material (fibrin), and extravasated erythrocytes (hemorrhage). Multifocally subjacent to the meninges, minimally expanding the neuropil, there are small aggregates of lymphocytes, plasma cells, and neutrophils.
MORPHOLOGIC DIAGNOSIS: Cerebrum: Meningitis, suppurative, diffuse, marked, breed unspecified, bovine.
ETIOLOGIC DIAGNOSIS: Meningeal brucellosis
CAUSE: Brucella abortus
SYNONYM: Bang’s disease
· Gram negative, bacilli to coccobacilli, intracellular; cause recurrent bacteremia
· Brucellosis is an important zoonotic disease and was a major cause of bovine abortion in the U.S. but has been largely eradicated through intensive control programs
· Brucella sp. cause late gestational abortions, orchitis, epididymitis, and fetal bronchopneumonia
· Infection persists in sexually mature animals, especially females, with bacteremia recurring especially near the time of parturition
· Transmission by contact with infected tissues, secretions or excretions (milk, urine, fetal tissues, placenta, etc.) > penetration of mucosa > regional lymph node, lymphadenitis, replication within mononuclear phagocytic cells (macrophages are the preferred cell) > bacteremia > dissemination to mammary gland, reproductive organs (both sexes), placenta > massive intracellular replication in the rough endoplasmic reticulum of chorionic trophoblasts > necrosis of trophoblast and ulceration of chorioallantois > invasion of fetal chorionic villi > hematogenous dissemination in fetus; (when Brucella abortus is ingested with feed contamination the initial lesion is a persistent nasopharyngeal lymphadenitis)
· Smooth strains (more pathogenic): Cellular entry through interaction with lipid rafts in the plasma membrane via the Brucella LPS O-polysaccharide (O side chain)
· Opsonization aids entry via IgG and complement (C3b and 4b); smooth strains are capable of intracellular replication;
· After entry, trafficked to phagosome termed “Brucellosome” via endoplasmic reticulum (ER) and requires low pH (<4.5) for intracellular replication in phagosome/brucellosome
· VirB operon controls genes for type IV secretion system/T4SS and interacts with ER to neutralized pH of phagosome and prevents phago-lysosomal fusion (cyclic glucan synthase also plays a role)
· Brucella expresses 2 superoxide dismutases to neutralize oxidative killing and have a requirement for heme as an iron source in the phagosome; smooth strains inhibit macrophage apoptosis
· Rough strains: Different mechanism of cellular entry, more readily invade, are LPS deficient, and don’t interact with lipid rafts
· Phagocytosed following TLR4 or mannose receptor interactions but are defective at intracellular replication
· Evasion of immune response:
· Minimize stimulation of pattern recognition receptors (PRR) resulting in a reduced immune response
· Induces reduced inflammatory response compared to other Gram-negative bacteria due to LPS structure;
· O side chain interferes with MHCII antigen presentation
· Inhibition of apoptosis of infected monocytes/macrophages
· Prevents dendritic cell maturation, antigen presentation and T cell activation
· Subversion of unfolded protein response (UPR) and IRE1α signaling cascade important for intracellular survival
· Affinity for pregnant endometrium and fetal placenta is associated with erythritol, which is produced by the fetus and stimulates growth of the bacteria
· Osteolysis due to IL-17 induced osteoclastogenesis
· Fetal death and abortion are attributed to placental disruption and endotoxemia
TYPICAL CLINICAL FINDINGS:
· Retained placentas, metritis, late term abortions
· Scrotal swelling
· Late term abortions (most commonly in 7th and 8th month of gestation)
TYPICAL GROSS FINDINGS:
· Fetal lesions: Fibrinous bronchopneumonia (most important fetal lesion), pleuritis, pericarditis, meningitis, splenitis
· Placental lesions:
· Cotyledons: Non-uniform necrosis; covered in brown, odorless, sticky exudate (“caramel candy” exudate)
· Intercotyledonary placenta: Thickened, opaque surface, yellow to gray and resembles moroccan leather; patchy covering of yellow inflammatory exudate
· Testicle/epididymis: Chronic orchitis and epididymitis
· Carpal hygromas
TYPICAL LIGHT MICROSCOPIC FINDINGS:
· Granulomatous lesions and focal necrosis in lymph nodes, liver, spleen, kidney, and meninges
· Bronchopneumonia (ranges from catarrhal to fibrinous) or interstitial pneumonia
· Fibrinous pericarditis
· Necrotizing arteritis, especially of pulmonary vessels
· Necrotizing orchitis/epididymitis
· Fibrinopurulent serositis of visceral and parietal tunics
· Necrotic tubular epithelium with numerous organisms; predisposition to sperm granulomas
· In rams with B.ovis infection, the epididymal tail is most commonly affected and there is epithelial hyperplasia, degeneration and the formation of intraepithelial lumina; unlike bulls, ram infections with Brucella spp usually do not have an associated orchitis
· Necrotizing placentitis with periarteritis and arteritis, edema and macrophages and neutrophils
· No granulomas
· Numerous bacteria in the chorionic epithelium, trophoblasts and macrophages
· Most severely affected area is the intervillus portion (placental arcades)
· Focal lymphoplasmacytic and histiocytic interstitial inflammation and occasional lymphoid follicles
· Chronic infection leading to thickened interlobular septa and atrophy of alveoli; often no grossly detectable lesions
Carpus: Nonsuppurative synovitis and hygromas in cattle
ADDITIONAL DIAGNOSTIC TESTS:
· Culture, milk ring test, serum agglutination, complement fixation, ELISA
· Removal of lipid using chloroform and centrifugation increased diagnostic coherency of Rose Bangel Plate Test and ELISA for Alaskan grizzly And Kodiak brown bears
Causes of fetal meningitis:
· Brucella abortus
· Escherichia coli
· Aspergillus sp.
· Cats are the only domestic animal resistant to natural infection by Brucella sp.
· Pigs: Brucella suis - predilection for bones and joints; infection may occur in non-pregnant uterus
· Brucella abortus and B. suis are commonly associated with bursitis in horses (poll evil and fistulous withers)
· Dogs: Brucella canis – epididymitis, placentitis, diskospondylitis
· Sheep: Brucella ovis – epididymitis; placental lesions similar to B. abortus
· Sheep and goats: Brucella melitensis – Mediterranean countries; inflammation in mammary gland and pregnant uterus
· Camelids: Brucella melitensis (Natural infection), lesions consistent with small ruminants
· Wildlife (elk, bison, deer): Brucella abortus
· Recent report in short-beaked common dolphin: Brucella ceti
· Atlanto-occipital joints filled with inspissated, caseous material
· Chronic, nonsuppurative meningoencephalitis, characterized by patchy congestion of meningeal blood vessels and mononuclear cell cuffing of blood vessels in brain and meninges
· Harbor seals: Brucella sp.
· Wood rats: Brucella neotomae
· Hares: Brucella suis type 2
· Humans (Undulant fever):
· Zoonosis associated with B. abortus, B. melitensis, B. suis and B. canis
· Biowarfare agent
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