JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

August 2023

P-B14

 

Signalment (JPC #1713947): Bovine neonate

 

HISTORY: Tissue from a bovine neonate that was born premature between 220 to 235 days of gestation; the calf was weak and experienced respiratory difficulty and died shortly after birth. The lungs failed to collapse and were uniformly firmer than normal. All lymph nodes examined were 2-2.5x normal size.  

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Multifocally obscuring 30% of the pulmonary architecture, expanding and occasionally obliterating alveolar lumina and septa are numerous macrophages, moderate numbers of lymphocytes and plasma cells, few neutrophils, and multinucleate macrophages (Langhans and foreign body type) admixed with areas of eosinophilic cellular and karyorrhectic debris (necrosis), hemorrhage, fibrin, and edema. Multifocally, bronchioles contain necrotic cellular exudate. Diffusely the less affected alveolar septa are expanded up to 5 times normal by macrophages, lymphocytes, plasma cells, fibrin, and edema. Perivascular, peribronchial, and peribronchiolar adventitia, interlobular septa, and pleura are mildly expanded by similar inflammatory cells, ectatic lymphatics (edema), fibrin, and hemorrhage.  

 

Liver: Essentially normal tissue.

 

MORPHOLOGIC DIAGNOSIS: Lung: Bronchopneumonia, granulomatous and necrotizing, multifocal to coalescing, moderate, breed unspecified, bovine.

 

ETIOLOGIC DIAGNOSIS: Pulmonary brucellosis

 

CAUSE: Brucella abortus

 

CONDITION: Brucellosis

 

SYNONYMS: Bang’s disease

 

GENERAL DISCUSSION: 

• Major zoonotic disease worldwide, a leading cause of abortion and sterility (R-B03)
• Gram negative, small (0.4-1.5µm long), unencapsulated, facultatively intracellular coccobacillus that is the archetype bacterial cause of placentitis
• Secreted in colostrum and intermittently in milk
• Eradicated from livestock in the U.S. but endemic in bison and elk of the Greater Yellowstone Area with occasional spread to cattle in the area
• Smooth strains (B. abortus, B. melitensis) express O side chain on its LPS, rough strains (B. ovis, B. suis, B. canis) do not

 

PATHOGENESIS: 

• Ingestion (inhalation less common) of infected exudates from abortus, placenta or uterine discharge → phagocytosis by mucosal epithelial tissue macrophages/ dendritic cells or endocytosis through epithelium or M cells à leukocyte trafficking to lymph nodes → leukocyte trafficking or hematogenous spread → organ systems (e.g., spleen, liver, bone marrow, mammary glands, reproductive organs)
• Placental trophoblasts produce erythritol, which is theorized to contribute to tropism for the pregnant uterus/placenta due to an unknown effect
• LPS composition of capsule associated with virulence:
  • Smooth strains (more pathogenic, capable of intracellular replication): Cellular entry through interaction with lipid rafts in the plasma membrane via the Brucella LPS O-polysaccharide (O side chain)
  • Rough strains: Different mechanism of cellular entry (don’t interact with lipid rafts, rather are phagocytized following TLR4 or mannose receptor interactions), more readily invade, are LPS deficient; defective at intracellular replication
• LPS (a PAMP), a type IV secretion system, and other virulence factors such as cyclic β-1,2- glucan and heat shock proteins also be involved in blocking phagosome-lysosome fusion and promoting bacterial growth and replication 

 

TYPICAL CLINICAL FINDINGS:

• Chronic infections with persistent or recurrent bacteremia
• Late-term/third trimester abortion; retained placenta; abortion may be the only sign observed
• Orchitis/epididymitis, sterility (orchitis is generally rare; other than B. abortus orchitis in bulls, the vast majority of cases are actually epididymitis)
• Osteoarticular disease (arthritis, spondylitis)

 

TYPICAL GROSS FINDINGS:  

• Placenta: Characteristic but not pathognomonic yellow flocculent exudate in the intercotyledonary area between the chorion and endometrium with “Moroccan leather” surface appearance; variable nonuniform yellow/gray necrotic cotyledons  covered by thick brown “caramel” exudate; hematomas at the ends of maternal septa; edematous fetal membranes and umbilical cord
• Fetus: The important fetal lesion is pneumonia characterized by firm, enlarged, reddened lungs with fibrin strands on pleura (if severely affected), bronchitis and bronchopneumonia (may not be grossly apparent); autolysis; edema; subcutaneous, pleural, peritoneal, and retroperitoneal blood-tinged fluid; turbid yellow, flaky abomasal content; the most commonly infected fetal organ is the spleen
• Pyogranulomatous orchitis/epididymitis, prostatitis, placentitis, discospondylitis

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Fetus:  

• Catarrhal to fibrinous bronchopneumonia with predominantly mononuclear cellular infiltrate and foci of bronchitis, edematous interlobular septa
• Necrotizing arteritis especially of pulmonary vessels
• Edema of the subcutis and skeletal muscles 
• Necrosis and granulomatous inflammation in various organs (liver, spleen, kidney, lymph nodes)
• Hyperplasia of adrenal cortex and lymph nodes
• Thymic cortical lymphoid depletion
• Bacteria in macrophages and neutrophils in the lung and also free in vascular lumina

• Placenta: Extensive necrosis, edema, and leukocytic infiltrate in intervillous areas; abundant bacteria “stuffed” in chorionic epithelial cells that often desquamate into the intercotyledonary space; abundant bacteria within trophoblasts predominantly in intercotyledonary areas; necrotic syncytial trophoblasts; vasculitis of maternal and fetal tissues; maternal portions much less affected
• Testicular atrophy and/or infarction; necrotizing orchitis is characteristic but not pathognomonic for brucellosis

 

ADDITIONAL DIAGNOSTIC TESTS 

• PCR, culture, immunofluorescence, immunohistochemistry
• Serum agglutination and complement fixation to detect antibodies; false positives in vaccinated cattle  

 

DIFFERENTIAL DIAGNOSIS: 

Fetal bronchopneumonia:

• Trueperella pyogenes: Also produces suppurative placentitis and fetal lung lesions, but fetal pneumonia is often accompanied by large colonies of bacteria within airways and alveolar spaces
• Campylobacter fetus ssp. venerealis: Abortion usually between the 4th and 6th month of gestation; placenta not retained; diffuse purulent pneumonia
• Aspergillus fumigatus: Mycotic hyphae in necrotic tissue, especially around necrotic and thrombosed vessels

 

COMPARATIVE PATHOLOGY:

• Humans: Susceptible to all Brucella species (primarily B. abortus, B. melitensis, and B. suis) 

• Transmission by infected milk products or direct contact with infected tissues
• Symptoms include prolonged or recurrent fever, weakness, impotence

• Swine: B. suis (also B. abortus and B. melitensis) chiefly transmitted via coitus; incites granuloma formation, sterility, abortion, arthritis, and vertebral osteomyelitis; uterine lesion of pale yellow miliary foci is NOT dependent on pregnancy; orchitis is characterized by multiple abscesses rather than confluent necrosis
• Sheep & goats: B. melitensis is the principal cause of brucellosis in sheep and goats; in goats disease is similar to B. abortus in cattle, but disease is generally less severe in sheep
• Sheep: B. ovis causes epididymitis with resultant periorchitis and rarely placentitis and abortion; primarily coital transmission; epididymitis predisposes sheep to spermiostasis and extravasation with characteristic spermatic granulomas; nonpregnant uterus is not affected; fetus: calcified plaques on hooves (nonspecific)
• Dogs: B. canis causes epididymitis, periorchitis, prostatitis, scrotal dermatitis (licking due to pain), testicular atrophy, late-term abortion (usually after 50 days gestation), discospondylitis, may cause chronic lymphocytic endophthalmitis (immune mediated); B. suis may cause spontaneous granulomatous epididymitis and prostatitis; infected fetuses: pneumonia, endocarditis, hepatitis
• Horse: B. abortus or B. suis causes bursitis (fistulous withers, poll-evil), or other suppurative skeletal or synovial lesions, commonly present with Actinomyces bovis
• Wild ungulates: B. abortus infections are described in a wide variety of mammals, including bison, elk, and reindeer; B. suis reported in a muskox
• Wood rats: B. neotomae
• Cats: Naturally resistant
• Camelids: Susceptible to  B. abortus and B. melitensis, develop orchitis and epididymitis
• Cervids: B. ovis causes epididymitis, reduced semen quality in red deer; B suis causes orchitis, epidymitis, synovitis, and metritis abortion in reindeer and caribou
• Camelids: B. melitensis and B. abortus less commonly causes epididymitis and metritis abortion in camels
• Dolphins: B ceti causes endometritis, placentitis, abortions, epididymitis, and orchitis in dolphins
• Sowerby’s beaked whales: Brucella ceti

 

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