Read-Only Case Details

JPC SYSTEMIC PATHOLOGY

REPRODUCTIVE SYSTEM

January 2025

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 karyorrhectic debris admixed with numerous necrotic and viable neutrophils, macrophages, eosinophilic fibrillar material (fibrin), edema, and moderate hemorrhage. Within and surrounding foci of lytic necrosis are hepatocytes that are shrunken and hypereosinophilic with pyknotic nuclei (necrotic) or swollen with vacuolated cytoplasm (degenerate). Multifocally, portal areas are moderately expanded by lymphocytes, plasma cells, and fewer neutrophils and macrophages. Multifocally, lymphatic vessels are 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, acute, random, severe, polypay, ovine.

ETIOLOGIC DIAGNOSIS: Campylobacterial hepatitis

CAUSE: Campylobacter fetus subsp. Fetus

SYNONYM: Ovine campylobacteriosis, vibriosis

GENERAL DISCUSSION:

Gram-negative, spiral (“gull-wing” shaped in feces; or can be bacilli in chains), motile bacteria previously grouped under title “vibriosis” in sheep and cattle
Campylobacter spp. infections are seen in humans, cattle, sheep, swine, and chickens and generally result in either reproductive or gastrointestinal disease
Primary manifestations in sheep are late term abortion, premature birth, and the birth of weak lambs; nonsuppurative placentitis affecting multiple organs in the fetus
3 types of Campylobacter spp. 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): 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, Wright-Giemsa
Culture
PCR
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)
Cytology: Spirochete, “gull wing” appearance on cytology

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 spp.; fetal

mummification, abortion, lambs born weak

Listeria monocytogenes: Usually pinpoint hepatic necrosis
Leptospira bratislava; L. ballum, L. pomona, and L. 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 spp. are common pathogens causing disease in humans, cattle, sheep, swine, chickens (less likely to cause disease in chickens but a carrier for other animals), occasionally in dogs, and non-human primates
Nonhuman primates: C. 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
Dogs: Campylobacter spp. Are bacterial agents associated with diarrhea
Poultry: C. jejuni, and C. coli are both isolated from the intestine with C. jejuni more commonly causing colonization in the cecum and gall bladder.

Campylobacter-induced paralysis with experimental infection of C. jejuni from humans with Guillain-Barre syndrome

Ratites (emu, rhea): Bacterial infection is a common cause of embryonic death and of disease and mortality in young hatched ratite chicks including Campylobacter jejuni can cause yolk sacculitis, typhlocolitis and/or multifocal necrotizing or granulomatous hepatitis
Guinea pigs: Have been used as experimental models for Campylobacter isolates known to cause abortion in humans and animals reported to have developed diarrhea
Humans: Zoonotic agents causing fatal septicemia in newborns and immunocompromised individuals

REFERENCES:

Abdul-Aziz T, Fletcher OJ. Hepatobiliary System. In: Abdul-Aziz T, Fletcher OJ, Barnes HJ Avian Histopathology 4^th ed. J Jacksonville, FL.: American Association of Avian Pathologists, Inc.; 2019: 401-402.
Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents & Rabbits. 4th ed. Ames, IA: John Wiley & Sons, Inc.; 2016: 224.
Carli SD, Dias ME, da Silva MERJ, Breyer GM, Siqueira FM. Survey of beef bulls in Brazil to assess their role as source of infectious agents related to cow infertility. J Vet Diagn Invest. 2022 Jan;34(1):54-60.
Conrado FO. Chapter 10: Fecal and Rectal Cytopathology. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:389.
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