JPC SYSTEMIC PATHOLOGY
REPRODUCTIVE SYSTEM
JANUARY 2022
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 high numbers of epithelioid macrophages admixed with fewer lymphocytes, plasma cells, and rare eosinophils.  Macrophages have abundant amphophilic, granular cytoplasm, and often contain phagocytosed cellular debris or occasionally contain erythrocytes (erythrophagocytosis) or hemosiderin.  The thymic cortex demonstrates marked lymphoid depletion characterized by marked thinning and pallor, frequent karyorrhectic lymphocytes, and high numbers of tingible body macrophages.  There is multifocal mild hemorrhage of the cortex and medulla, and 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 moderate numbers of infiltrating macrophages and few lymphocytes and plasma cells.  Similar moderate numbers of inflammatory infiltrates are scattered throughout the myocardium, primarily in perivascular areas, 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:

• Epizootic bovine abortion, or foothill abortion, is an endemic, tick-borne infection of range cattle in the western US (especially California) and Mexico that causes late term abortion, chronic fetal disease, and weak calves
• “EBA” is a poor name, as the disease is endemic and provincial, and 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

PATHOGENESIS:

• The etiologic agent is a novel deltaproteobacterium with unique 16S deltaproteobacterial rDNA gene sequence detected in a high proportion of affected calf thymus tissue and a high percentage of adult Ornithodoros coriaceus salivary gland and other tissues
  • The deltaproteobacterium has recently been named Pajaroellobacter abortibovis (this is not yet published in ACVP required reading sources)
• Deer may be reservoir since disease can occur where no cattle have grazed
• Pregnant cattle, especially at 2-6 months of gestation, predominantly those exposed to the tick vector for the first time (no prior immunity) 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:

• At-risk population: 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

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

DIFFERENTIAL DIAGNOSIS:

Bovine abortion:

• Mycoses (R-F01; Absidia , 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, 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:

• Fetal cardiac disease

COMPARATIVE PATHOLOGY:

• Lawsonia intracellularis (D-B15), the causative agent of porcine proliferative enteropathy, is the only other animal pathogen in the class Deltaproteobacteria

REFERENCES:

1. Blanchard MT, Anderson ML, Hoar BR, et. al. Assessment of a fluorescent antibody test for the detection of antibodies against epizootic bovine abortion.  J Vet Diagn Invest.  2014;26(5):622-630.
2. Brooks RS, Blanchard MT, Clothier KA, et. al. Characterization of Pajaroellobacter abortibovis, the etiologic agent of epizootic bovine abortion.  Vet Microbiol.  2016;192:73-80.
3. Clothier K, Anderson, M. Evaluation of bovine abortion cases and tissue suitability for identification of infectious agents in California diagnostic laboratory cases from 2007 to 2012. Theriogenology. 2016;85(5):933-938.
4. Foster RA. Female reproductive system and mammae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2016: 1181.
5. 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.
6. 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.
7. Welly BT, Miller MR, Scott JL, et al. Genome Report: Identification and Validation of Antigenic Proteins from Pajaroellobacter abortibovis Using De Novo Genome Sequence Assembly and Reverse Vaccinology. G3; 7(2):321-331.

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