JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2023

N-B07 (NP)

 

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 necrotic and fewer viable neutrophils, lymphocytes and plasma cells admixed with eosinophilic cellular and karyorrhectic debris (necrosis), eosinophilic beaded to fibrillar material (fibrin), and extravasated erythrocytes (hemorrhage). Multifocally, previously described inflammatory cells occasionally minimally infiltrate into the subjacent superficial neuropil.   

 

MORPHOLOGIC DIAGNOSIS: Cerebrum: Meningitis, suppurative, diffuse, marked, breed unspecified, bovine.

 

ETIOLOGIC DIAGNOSIS: Meningeal brucellosis

 

CAUSE: Brucella abortus

 

CONDITION: Bovine Brucellosis

 

GENERAL DISCUSSION:  

• Gram negative, bacilli to coccobacilli, facultative intracellular; zoonotic; cause systemic infection with recurrent bacteremia that typically manifests in abortion 
• Bovine brucellosis (Brucella abortus) occurs in cattle worldwide, though the incidence of it varies depending on availability of control programs 
• Brucella sp. cause late gestational abortions, orchitis, epididymitis (R-B03), and fetal bronchopneumonia (P-B14) 
• Smooth strains (B. abortus, B. melitensis) express O side chain on its LPS, rough strains (B. ovis, B. suis, B. canis) do not

 

PATHOGENESIS:  

• Infection typically occurs through the alimentary tract via contact with an aborted fetus, placenta, and uterine discharge; lesser routes are through the vagina, conjunctiva, skin (broken or intact), or consumption of milk (especially colostrum)
• Calves and young cattle are more resistant and will eliminate the infection within a few months
• Sexually mature animals, especially females, tend to develop persistent infections
• Typical course: Point of entry à spread to regional lymph nodes via leukocyte trafficking in macrophages and dendritic cells à acute lymphadenitis à if infection persists, hematogenous spread/bacteremia à bacterial localize in the spleen, mammary glands, mammary lymph nodes, gravid uterus (endometrium, fetus; the non-pregnant uterus isn’t particularly susceptible), testis, accessory sex glands à additional bacteremic episodes may recur irregularly for at least 2 years, especially at parturition
• Within the placenta, the chorionic trophoblasts either phagocytose the organisms or the organism invades them à invade the chorionic villi à spread to the fetus 
• Entry into macrophages occurs via endocytosis through a phagosome, which it rapidly acidifies using a type IV secretion system; this, in addition to other virulence factors block phagosome-lysosome fusion, allowing it to persist and replicate 
• Virulence of Brucella spp is related to its capsular LPS composition; smooth phenotypes (that have LPA O-polysaccharide side chains) are more virulent and have enhanced replication 

 

TYPICAL CLINICAL FINDINGS:

• Retained placentas, metritis, late term abortions (most commonly in 7th and 8th month of gestation)
• Scrotal swelling
• Mastitis 
• Synovitis/arthritis

 

TYPICAL GROSS FINDINGS:  

• Fetus: Often autolyzed and somewhat edematous; bronchopneumonia (most important fetal lesion), pleuritis, pericarditis, meningitis, splenitis; umbilicus edematous 
• Placenta: Characteristic, but not pathognomonic; non-uniform; cotyledon necrosis covered in yellow-brown, odorless, sticky exudate; intercotyledonary placenta is thickened, opaque yellow to gray and resembles moroccan leather with  patchy covering of yellow inflammatory exudate
• Testicle/epididymis: Chronic orchitis and epididymitis
• Carpal hygromas

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Fetal lesions:

• Granulomatous lesions with giant cells 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

• Placenta: numerous intra-cellular bacteria within chorionic epithelial cells, trophoblasts, especially at the placentome (base of the chorionic villi); edematous stroma with increased leukocytes (predominantly mononuclear); vasculitis
• Necrotizing orchitis/epididymitis, epididymal tail most commonly affected
• Carpus: Nonsuppurative synovitis and hygromas in cattle

 

ADDITIONAL DIAGNOSTIC TESTS:  

• Multiple diagnostic tests may be needed to reach a definitive diagnosis 
• Culture, immunofluorescence, immunohistochemistry, PCR
• Serology (low sensitivity/specificity; antibodies of B abortus may cross react with Leptospira spp) – AGID, RSAT, TAT, MAT, CFT, ELISA

 

DIFFERENTIAL DIAGNOSIS: 

 

COMPARATIVE PATHOLOGY:  

• Cats are the only domestic animal resistant to natural infection by Brucella sp.
• Pigs (wild and domestic): B suis - predilection for bones and joints; infection may occur in non-pregnant uterus; abortion occurs between month 2 to 3 of pregnancy, but is less frequent than in cattle; high incidence of weak or stillborn piglets 
• Dogs:  B canis – transmission via ingestion of vaginal discharge or venereally via seminal fluids; late term abortions (after 50 days), testicular degeneration, epididymitis 
• Sheep: B ovis – epididymitis with sperm granulomas; pregnant uterus and placental lesions similar to B. abortus; coital transmission most important route (organism present in large numbers in semen) 
• Sheep and goats: Brucella melitensis – similar to bovine brucellosis; late term abortion may be only sign
• Horses: B abortus or B suis cause poll evil or fistulous withers 
• Guinea pigs: Brucellosis model; natural infection rare and occurs by feed contaminated with animal by-products containing B abortus, B melitensis, and B suis
• Rabbits: Rare in domestic rabbits (B intermedia); wild hares are an important reservoir of B suis; pyogranulomatous lesions in the reproductive organs 
• Non-human primates: A novel Brucella isolate was reported in baboons with stillbirth and retained placenta 
• Non-domestic ruminants and camelids: B abortus, B suis, B melitensis most common; significant endemic pathogen in American bison and African buffalo; similar lesions as described in cattle 
• Pinnipeds: B pinnipedialis; unknown transmission (possibly via fish or lungworms); typically subclinical 
• Cetaceans: B. ceti; world-wide; common in stranded animals; cause septicemia, abscessation, and lesions in the reproductive tract, CNS (meningoencephalitis), and musculoskeletal system (discospondylitis, DJD, fibrinopurulent osteoarthritis)

• A recent paper (Davison, et al, J Comp Pathol 2021) reported three cases of fatal lymphocytic meningoencephalitis in three juvenile male Sowerby’s beaked whales due to neurobrucellosis; histologic findings suggested that B ceti replicates in the cerebrospinal fluid

 

References:  

1. Agnew D. Camelidae. In: Terio KA, McAloose D, St Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, MO: Academic Press; 2018:197.
2. Barreto JP, Oliveria PAM, Pertile SFN, et al. Non-agreement between 2 serologic techniques for detecting antibody to Brucella ovis in naturally infected sheep. J Vet Diagn Invest. 2022:34(1):164-166. 
3. Barthold SW, Griffey SM, Percy DH, eds. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA, MO:John Wiley and Sons, Inc.; 2016:223, 272.
4. Branscom LA, Cornish TE, Sondgeroth KS. Evaluation of serologic testing of rams in the management of Brucella ovis in a domestic sheep flock. J Vet Diagn Invest. 2019:31(1):86-89. 
5. Camargo-Castaneda AM, Stranahan LW, Edwards JF, et al. Characterization of epididymal and testicular histologic lesions and use of immunohistochemistry and PCR on formalin-fixed tissues to detect Brucella canis in male dogs. J Vet Diagn Invest. 2021:33(2):352-356. 
6. Cline JM, Brignolo L, Ford EW. Urogenital system. In: Abee CR, Mansfield K, Tardif S, et al, eds. Nonhuman Primates in Biomedical Research, Volume 2: Diseases; 2nd ed. San Diego, CA: Elsevier; 2022:526.
7. Colegrove KM, Burek-Huntington KA, Roe W, et al. Pinnipediae. In: Terio KA, McAloose D, St Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, MO: Academic Press; 2018:582.
8. Davison NJ, Brownlow A, Doeschate MT, et al. Neurobrucellosis due to Brucella ceti ST26 in three Sowerby’s beaked whales (Mesoplodon bidens). J Comp Path. 2021:182:182-188. 
9. Foster RA. Male genital system. In: Maxie MG, ed. Jubb, Kennedy, and Palmers Pathology of Domestic Animals. Vol 3. 6th ed. St Louis, MO: Elsevier; 2016:483-499.
10. Foster RA, Premanandan C. Female reproductive system and mammae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease.  7th ed. St. Louis, MO: Mosby Inc.; 2022:1295-1297.
11. Howerth EW, Nemeth NM, Ryser-Degiorgis MP. Cervidae. In: Terio KA, McAloose D, St Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, MO: Academic Press; 2018:164.
12. Jimenez Martinez MA, Gasper DJ, Mucino MdCC, et al. Suidae and Tayassuidae. In: Terio KA, McAloose D, St Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, MO: Academic Press; 2018:216.
13. Jones MEB, Gasper DJ, Mitchell E. Bovidae, Antilocapridae, Giraffidae, Tragulidae, Hippopotamidae. In: Terio KA, McAloose D, St Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, MO: Academic Press; 2018:136.
14. Kakooza S, Wauwa J, Ipola P, et al. Seromonitoring of brucellosis in goats and sheep slaughtered at an abattoir in Kampala, Uganda. J Vet Diagn Invest. 2022:34(6):964-967. 
15. Krecic MR. Antibodies produced by dogs successfully changed with live Leptospira spp did not cross-react to Brucella antigen in a commercial rapid slide agglutination test that detects antibodies to Brucella canis. J Vet Diagn Invest. 2022:34(6):964-967. 
16. Leger J, Raverty S, Mena A. Cetacea. In: Terio KA, McAloose D, St Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, MO: Academic Press; 2018:556-557.
17. Mol JPS, Guedes ACB, Eckstein C, et al. Diagnosis of canine brucellosis: comparison of various serologic tests and PCR. J Vet Diagn Invest. 2020:32(1):77-86. 
18. Norman SA, Delaney MA, Haman KH, et al. Application of real-time quantitative PCR assays for detecting marine Brucella spp in fish. J Vet Diagn Invest. 2018:30(1):150-154. 
19. Schlafer DH, Foster RA. Female genital system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals.  Vol 3. 6^th ed. Philadelphia, PA: Elsevier Saunders; 2016:402-406.
20. Stanton JB, Zachary JF. Mechanisms of microbial infection. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease.  7th ed. St. Louis, MO: Mosby Inc.; 2022:226-227, 236.

 

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