JPC SYSTEMIC PATHOLOGY

REPRODUCTIVE SYSTEM

DECEMBER 2024

R-B01

 

Signalment (JPC #1946318): An aborted Angus bull calf. 

 

HISTORY: The fetus aborted at approximately 6 months of gestation. This was the second first-time heifer to have aborted on this previously non-grazed ranch. The liver was markedly enlarged with rounded margins and had a cobblestone appearance with multiple pinpoint, white foci scattered throughout; the spleen, thymus, and lymph nodes were markedly enlarged.

 

HISTOPATHOLOGIC DESCRIPTION: Thymus: The thymic medulla is diffusely expanded by many epithelioid macrophages admixed with fewer lymphocytes, plasma cells, and rare eosinophils. Macrophages have abundant amphophilic, granular cytoplasm, and often contain phagocytosed cellular debris or, less frequently, erythrocytes (erythrophagocytosis) or hemosiderin. There is marked lymphoid depletion of the thymic cortex characterized by thinning and pallor, frequent lytic lymphocytes, and many tingible body macrophages. There is multifocal mild hemorrhage of the cortex and medulla. The interlobular connective tissue contains scant hemorrhage, fibrin, edema, and low numbers of previously mentioned inflammatory cells.

 

Heart with valve: The mural endocardium is mildly expanded by macrophages and few lymphocytes and plasma cells. Similar inflammatory infiltrates are scattered throughout the myocardium, primarily perivascular, as well as within the epicardium and pericardial adipose tissue.

 

MORPHOLOGIC DIAGNOSES: 1. Thymus: Thymitis, granulomatous, diffuse, marked, with marked lymphoid depletion.

2. Heart: Pancarditis, granulomatous, diffuse, mild.

 

ETIOLOGIC DIAGNOSIS: Deltaproteobacterial thymitis and pancarditis

 

ETIOLOGY: Pajaroellobacter abortibovis (a deltaproteobacterium)

 

CONDITION: Epizootic bovine abortion (EBA), Foothills abortion

 

GENERAL DISCUSSION: 

• EBA is a tick-borne infection of cattle that produces chronic fetal disease and late term abortion 
• “EBA” is a poor name, as the disease is endemic and provincial; additionally, EBA was originally the common name for bovine brucellosis
• Disease distribution is limited to the range of the argasid tick vector, Ornithodoros coriaceus, an ectoparasite of deer and cattle; region includes the foothills of California, and adjacent Nevada, Oregon, and northern Mexico, hence the name ‘Foothills abortion’

 

PATHOGENESIS:

• The etiologic agent is a novel deltaproteobacterium that is detected in the salivary gland of the adult Ornithodoros coriaceus 
  • The deltaproteobacterium has recently been named Pajaroellobacter abortibovis  
• Deer may be reservoir since disease can occur where no cattle have grazed
• Pregnant cattle, especially at 2-6 months of gestation, that have not been previously exposed to the tick vector (no prior immunity) are bitten by infected O. coriaceus à P. abortibovis is transmitted to the cow where it causes no clinical signs à transplacental fetal infection à chronic disease in fetus (3+ month incubation period) à fetal distress/death à fetus triggers abortion, or birth of weak calf
  • Fetal abortion if infection is prior to 7-8 months of gestation, before development of a functional immune system
  • Birth of weak calf if infection is after 7-8 months of gestation, once the fetus has a functional immune system; these are common in abortion outbreaks
• Diagnostic lesions develop late in disease course: 50 days post-infection for notable histologic lesions, with diagnostic specificity in fetuses of at least 100 days of gestation
• Fetal lesions of ascites and nodular enlarged liver are presumably due to heart failure secondary to myocarditis

 

TYPICAL CLINICAL FINDINGS:

• Key clinical features are late term abortion, chronic fetal disease, and weak calves
• At-risk population: Pregnant cattle exposed to vector ticks for the first time
  • Major abortions in a herd only occur when pregnant non-immune cattle are moved into an endemic area
• Cow: 
  • No clinical signs, placenta is shed easily, the only recognizable sign is late-term abortion (6-8 months) or birth of weak calves with failure to thrive in those exposed to the vector tick predominantly at 2-6 months of gestation
  • Cattle develop immunity and usually do not abort again even if re-exposed
• Aborted fetus/weak calf:
  • Fetus triggers its own delivery, most often during the last trimester
  • Fetus often dies during delivery or soon thereafter, or rarely dies in utero with resultant autolysis
  • Weak calves are often seen in association with outbreaks of abortion 

 

TYPICAL GROSS FINDINGS:

• Cow: Typically no gross lesions
• Calf/fetus: 
  • Lymph nodes: Generalized, often marked, lymphadenopathy
  • Liver: Hepatomegaly and an impressively coarsely nodular liver (not always present)
  • Peritoneal cavity: Ascites with abdominal distension, which is characteristic and striking (not always present)
  • Spleen: Splenomegaly
  • Thymus: Small (atrophic), edematous, hemorrhagic thymus surrounded by abundant hemorrhage and edema; lesions not present until late in the disease course
  • Mucosae: Petechial hemorrhages of oral mucosa, larynx, trachea, and conjunctiva
  • Multiple organs: Small gray foci of inflammation in many tissues, especially kidney and heart

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Calf/fetus: Notable lesions are present 50 days after exposure of the dam
  • Thymus (distinctive/pathognomonic lesion): The most distinctive lesion of this disease is remarkable inflammation characterized by infiltration of the medulla by large numbers of macrophages; extensive loss of cortical T cells; fibrinocellular exudation; septal hemorrhage, fibrin, and lymphohistiocytic inflammation 
  • Lymph nodes: Marked lymphoid and mononuclear cell hyperplasia; secondary follicles develop in cortical and paracortical areas; multinuclear giant cells and macrophages filling sinuses and medullary cords
  • Spleen: Marked lymphoid and mononuclear hyperplasia; reactive lymphoid hyperplasia of lymphoid follicles and periarteriolar lymphoid sheaths
  • Liver: Dilated central veins, thinned liver plates, periportal mononuclear cell infiltration, granulomatous inflammatory foci up to 100um in diameter 
  • Lungs: Alveolar septa thickened, with alveolar septal histiocytic inflammatory foci
  • Brain: Granulomatous meningitis and multifocal vasculitis
  • Placental lesions: Absent or mild, often of the loose (fetal) connective tissue, in contrast to other bacterial and fungal causes of abortion
  • Widespread foci of necrosis that often develop into pyogranulomas with a vascular orientation in most organs, including brain, lung, and liver
  • +/- vasculitis of small and large caliber vessels

 

ADDITIONAL DIAGNOSTIC TESTS:

• Steiner silver stain and immunohistochemistry reveal intracytoplasmic bacterial rods in thymuses of aborted calves
• Confirmation requires identification of the 16S RNA of the deltaproteobacteria
• Vascular lesions often contain deposits of IgG and IgM
• This disease can only be diagnosed confidently in animals exposed before the last trimester due to the slow manifestation of disease-specific lesions

 

DIFFERENTIAL DIAGNOSIS:

Bovine abortion:

• Mycoses (R-F01; Absidia sp., Mucor sp., Aspergillus sp., Rhizopus sp.): Necrotic cotyledons; dry, leathery placenta; ringworm-like dermal lesions on fetus; lower rate of abortion
• Tritrichomonas fetus: Early term abortion; infertility or pyometra and fetal maceration 
• Campylobacter fetus (R-B10): Late term abortion; lower abortion rate; infertility; placental edema and petechia
• Neospora caninum (N-P03): Abortions at 3-8 months of gestation and mummification; fetal pathognomonic discrete 100-300um foci of nonsuppurative necrotizing encephalitis with protozoal cysts and zoites, pancarditis/myocarditis also
• Leptospirosis (U-B03; L. pomona and L. hardjo): Late term abortions; brown gelatinous edema between amnion and allantois; yellow-brown cotyledons 
• Brucella abortus (R-B03, P-B14): Necrotizing placentitis; fetal lesions include bronchopneumonia, necrotizing arteritis, hepatitis, splenitis, and nephritis
• Listeria monocytogenes (N-B04): Late term abortion; vasculitis in chorioallantoic stroma; foci of necrosis in liver and other organs
• Ureaplasma diversum (R-B06): Necrotizing placentitis, amnionitis, with fibrosis, mineralization, heavy mononuclear cell infiltrate, foci of necrosis and hemorrhage, mild vasculitis; fetal conjunctivitis and nonsuppurative pneumonia
• Other bacterial causes: Salmonella sp., Staphylococcus sp., Streptococcus sp., and Histophilus somni
• Infectious bovine rhinotracheitis (R-V02; bovine herpesvirus-1): Late term abortions; hepatic necrosis with intranuclear inclusions in fetus 
• Bovine viral diarrhea virus (D-V09, N-V01; bovine pestivirus): Early term abortions or weak calves with cerebellar hypoplasia

 

Fetus, grossly nodular liver:

 

COMPARATIVE PATHOLOGY:

 

REFERENCES:

1. Foster RA, Premanandan C. Female Reproductive System and Mammae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1295-1296.
2. Schlafer DH, Foster RA. Female genital system. In: Maxie MG, ed. Jubb Kennedy and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:419-420.
3. Valli VEO, Kiupel M, Bienzle H. The hematopoietic system. In: Maxie MG, ed. Jubb Kennedy and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:148, 149.

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