JPC SYSTEMIC PATHOLOGY
REPRODUCTIVE SYSTEM
January 2022
R-B10 (NP)

Signalment (JPC #3124326):  Newborn polypay lamb

HISTORY:  This lamb was one of hundreds of stillborn lambs delivered during an abortion storm at an experimental sheep research facility.

HISTOPATHOLOGIC DESCRIPTION:  Liver:  Randomly affecting 50% of hepatic parenchyma are multifocal to coalescing variably sized foci of lytic necrosis characterized by loss of cellular architecture and replacement by abundant eosinophilic cellular and karryorhectic debris admixed with numerous necrotic and fewer viable neutrophils, macrophages, eosinophilic fibrillar material (fibrin), edema, and moderate hemorrhage.  Within and surrounding foci of lytic necrosis are necrotic hepatocytes that are shrunken and hypereosinophilic with pyknotic nuclei.  Degenerate hepatocytes surrounding areas of necrosis are swollen with vacuolated cytoplasm.  Multifocally, portal areas are moderately expanded by lymphocytes, plasma cells, and fewer neutrophils and macrophages.  Multifocally, lymphatic vessels are mildly ectatic with increased clear space (edema). Multifocally, there are small aggregates of myeloid and erythroid precursors (extramedullary hematopoiesis, normal in a fetus). 

MORPHOLOGIC DIAGNOSIS: Liver: Hepatitis, necrotizing and suppurative, multifocal to coalescing, random, acute, severe, polypay, ovine.

ETIOLOGIC DIAGNOSIS: Campylobacterial hepatitis

CAUSE: Campylobacter fetus subsp. Fetus

SYNONYM: Ovine campylobacteriosis, vibriosis

GENERAL DISCUSSION:

• Gram-negative, spiral (“gull-wing” shaped), motile bacteria previously grouped under title “vibriosis” in sheep and cattle
• Campylobacter infections are seen in humans, cattle, sheep, swine, and chickens and generally result in either reproductive or gastrointestinal disease
• The chief manifestations of infection in sheep are late term abortion, premature birth, and the birth of weak lambs; causes nonsuppurative placentitis affecting multiple organs in the fetus
• 3 types of Campylobacter cause disease in ruminants:
  • C. fetus subsp. fetus: Common resident of the ovine and bovine intestinal tract, resulting in abortion in both species but with higher incidence in sheep; not associated with venereal transmission
  • C. fetus subsp. venerealis: True genital specific infection and is an important cause of abortion in cattle and sheep (enzootic infertility)
  • C. jejuni: Common commensal organism of the intestinal tract of cattle, sheep, and swine results in intestinal disease in humans and animals, frequent cause of abortion in sheep and less so in cattle; also found as an intestinal tract inhabitant of poultry, dogs, cats, and rodents

PATHOGENESIS:

• C. jejuni or C. fetus subsp fetus: Fecal/oral or direct contact inoculation > transient bacteremia > localization in the intestine and bile > uterine infection is an accidental outcome of a brief bacteremic phase in nonimmune sheep
  • Surface (S) layer proteins are essential for colonization and/or translocation across intestinal mucosa to blood stream to the placenta and fetus
  • Incubation period is usually from 14 to 21 days, but can typically have a long duration from 13 to 113 days which is influenced by time of infection
• C. fetus subsp venerealis: transmitted by coitus,
• Infected male is an indefinite carrier; bacteria carried in preputial cavity, may also live on surface of bovine vagina
  • C. fetus subsp venerealis organisms are commonly found in the epithelial crypts in penile mucosa
  • C. sputorum subsp. bubulus is nonpathogenic and typically found as a surface contaminant with C. fetus subsp venerealis
• Outstanding feature: temporary sterility or repeated breeding, rather than the abortion itself

TYPICAL CLINICAL FINDINGS:

• Most significant manifestations in sheep are late term abortions (typically occurs between 4 and 6 months of gestation), premature births, and births of weak lambs; however, infected sheep may deliver clinically normal lambs
• Occasional maternal death secondary to metritis
• Abortion rate in natural outbreaks ranges between 5% and 70% but is usually 25%
• Fetus may have a pot belly appearance

TYPICAL GROSS FINDINGS:

• C. fetus subsp fetus or C. jejuni:
  • Fetal hepatic lesions are characteristic (if present):
    • Multifocal 1 mm to 2 cm diameter, tan, umbilicated/targetoid areas of hepatic necrosis (not pathognomonic, but diagnostic) with a slightly raised outer rim and a depressed tan inner zone
  • Fetal lesions may be only non-specific edematous changes
  • Placenta: enlarged, yellow and pale cotyledons, covered with brown exudate
• C. fetus subsp venerealis:
  • Placental lesions (placentitis): are similar to those associated with brucellosis, but less severe
    • Cotyledons: Enlarged, friable, pale- yellow to tan necrotic cotyledons covered in a brown exudate
    • Intercotyledonary areas: Edematous and opaque
    • Placental lesions are more severe over the cotyledons than the intercotyledonary areas
    • Placenta is usually not retained
• Can have necrotizing bronchopneumonia, renal hemorrhages, serositis, and fibrinous peritonitis

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• C. fetus subsp fetus or C. jejuni:
  • Aborted fetus can have no changes aside from edema
  • Multifocal to coalescing necrotizing hepatitis, with outer rim of pyogranulomatous inflammation
    • Diagnosis based on hepatic lesions and demonstration of organism
  • Bronchopneumonia in the fetus
• C. fetus subsp venerealis:
  • Edematous intercotyledonary placenta
  • Diffuse predominantly histiocytic inflammation in placenta
  • Yellow necrotic villi at the margins
  • Desquamated trophoblasts mat contain few bacteria

ADDITIONAL DIAGNOSTIC TESTS:

• Special stains: Gram-negative organisms may be present in smears of abomasal contents or affected cotyledons
• Dark field microscopy
• Phase-contrast microscopy
• Fluorescence in situ hybridization: Beneficial in detecting the organism in lesions that may be culture negative (i.e. may be more sensitive than culture) (Wolf-Jäckel GA. et al., J Vet Diagn Invest. 2020)

DIFFERENTIAL DIAGNOSIS:

Placental lesions / causes of abortion in sheep:

• Brucella ovis; B. melitensis; B. abortus: Late term abortions; large, visible bacilli
• Flexispira rappini: Very similar lesions to Campylobacter; fetal

mummification, abortion, lambs born weak

• Listeria monocytogenes: Usually pinpoint hepatic necrosis
• Leptospira bratislava; L. ballum, L. pomona, and hardjo: Stillbirth and abortion
• Trueperella (formerly Arcanobacter, Actinomyces, Corynebacterium) pyogenes: Causes less frequent abortions in sheep; large colonies of bacteria
• Salmonella abortus ovis
• Coxiella burnetti: Small colonies of bacteria within trophoblasts (characteristic foamy cells); rare; no vasculitis or fibrin
• Chlamydia: Abundant fibrin due to vasculitis; abundant bacteria (characteristic chlamydial inclusions) within trophoblasts

Hepatic lesions:

• Clostridium novyi type B strain (Black disease)
• Fusobacterium necrophorum: Causes omphalophlebitis in lambs and calves; can result in foci of hepatic necrosis

COMPARATIVE PATHOLOGY:

Selected Campylobacter spp. in other species:

• Campylobacter are common pathogens causing disease in humans, cattle, sheep, swine, chickens, occasionally in dogs, and non-human primates
• Nonhuman primates: fetus, C. jejuni, and C. coli cause campylobacteriosis or multifactorial chronic colitis syndrome with abortions in primates; animals have mild secretory watery diarrhea or severe dysentery; C. fetus, C. laridis, C. sputorum, and C. hyointestinalis are less common isolates
• Poultry: jejuni, and C. coli are both isolated from the intestine with C. jejuni more commonly causing colonization in the cecum
• Guinea pigs: Have been used as experimental models for Campylobacter isolates known to cause abortion in humans and animals
• Humans: Zoonotic agents causing fatal septicemia in newborns and immunocompromised individuals

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents & Rabbits. 4th ed. Ames, IA: John Wiley & Sons, Inc.; 2016: 224.
2. Bidwell CA, Woodger NGA, Cook AJC, et al. Campylobacter fetus subspecies fetus abortion in alpacas (Vicugna pacos). Vet Rec. 2010:167(12):457-8.
3. Fulton R, Boulianne M. Bacterial Diseases. In: Boulianne M. ed. Avian Disease Manual. 8^th Jacksonville, FL.: American Association of Avian Pathologists, Inc.; 2019:76-77, 200.
4. Schlafer DH, Foster RA. Female genital system. In: Maxie MG ed., Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals, Vol 3. 6th ed. St Louis, MO: Elsevier; 2016:406-408.
5. Simmons J, Gibson S. Bacterial and Mycotic Diseases of Nonhuman Primates. In: Abee CR, Mansfield K, Tardiff S, Morris T, ed. Nonhuman Primates in Biomedical Research. Vol 2. Waltham, MA: Elsevier; 2012:141.
6. Smith BP, Van Metre DC, Pusterla N. In: Large Animal Internal Medicine, 6^th St. Louis, MO: Elsevier; 2020: 1495t, 1503-1504, 1633-1634.
7. Uzal FA, Platter BL, Hostetter JM. Alimentary System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St Louis, MO: Elsevier; 2016:314, 316.
8. Wolf-Jäckel GA, Boye M, Angen Ø, Müller M, Jensen TK. Fluorescence in situ hybridization in species-specific diagnosis of ovine Campylobacter abortions. J Vet Diagn Invest. 2020; 32(3):413-419.

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