JPC SYSTEMIC PATHOLOGY

REPRODUCTIVE SYSTEM

December 2024

R-B07

 

Signalment (JPC #1758839): African pygmy goat

 

HISTORY: Multiple near-term abortions occurred in a research herd of African pygmy goats. Placentas were covered with tan, mucoid exudates, cotyledons were hemorrhagic, and necrotic villi were noted. Cultures of fetal stomach contents were negative for bacterial growth.

 

Slide A: HISTOPATHOLOGIC DESCRIPTION: Placenta (chorioallantois), cotyledon and intercotyledonary area: Diffusely affecting the cotyledon, there is effacement of the chorioallantoic villar architecture with degeneration, necrosis, and loss (ulceration) of the chorionic epithelium with replacement by abundant necrotic debris (lytic necrosis), hemorrhage, fibrin, edema, and scattered sloughed cytotrophoblasts and syncytiotrophoblasts, admixed with numerous degenerate neutrophils and fewer macrophages, lymphocytes, and plasma cells. Multifocally the intervillous space is expanded by abundant necrotic debris, degenerate neutrophils, fibrin, hemorrhage, and edema. Multifocally, trophoblasts are hypertrophic and distended, with foamy, pale blue cytoplasm and numerous ~1 µm indistinct bacteria. The nucleus of affected trophoblasts is occasionally peripheralized and crescent-shaped. Macrophages occasionally contain the previously described intracytoplasmic bacilli. Near the base of the cotyledon are multifocal areas of basophilic finely granular to fragmented material (mineral). The chorioallantoic stroma is multifocally expanded by clear space (edema), ectatic lymphatics, and moderate numbers of lymphocytes, plasma cells, and fewer macrophages. The chorionic epithelium of the intercotyledonary chorioallantois is diffusely thickened and ulcerated with epithelial replacement by degenerate neutrophils, bacteria-laden trophoblasts, fibrin, hemorrhage, edema, and necrotic debris.

 

Slide B: Giemsa: Innumerable intratrophoblastic ~1µm blue to purple staining coccobacilli.

 

MORPHOLOGIC DIAGNOSIS: Placenta (chorioallantois), cotyledon and intercotyledonary area: Placentitis, necrotizing and suppurative, subacute, diffuse, severe, with trophoblast hypertrophy and numerous intratrophoblastic and intrahistiocytic bacilli, African pygmy goat, caprine.

 

ETIOLOGIC DIAGNOSIS: Coxiella placentitis

 

CAUSE: Coxiella burnetii

 

CONDITION: Q (query) Fever in humans, coxiellosis

 

GENERAL DISCUSSION:

• Gram negative, obligate intracellular, intracytoplasmic bacterium of the order Legionellales (formerly Rickettsiales); worldwide distribution; causes reproductive losses (typically late gestational abortion) in ruminants
  • Phylogenetically related to Legionella, Francisella, and Rickettsia spp.
• Reported to cause placentitis, abortion, and stillbirth in captive Bovidae
• Dairy cows, goats, sheep are the most common reservoirs; other hosts include cats, wild ruminants, pigs, rodents, humans, birds, Pacific harbor seals, and arthropods 
  • Infection persists indefinitely in sheep and cattle
  • Sheep and goats often co-infected with Chlamydia and Toxoplasma 
• Usually transmitted by inhalation, ingestion, direct contact with body fluids, and vectors
• Zoonotic, OIE reportable; very low infectious dose

 

PATHOGENESIS:

• Acquired via ingestion or inhalation, shed in vaginal discharges at parturition and in the milk
• C. burnetii infects cells of the macrophage lineage and trophoblasts  
• Abortions usually follow initial exposure; abortions are less common in endemically infected herds/flock
• Transmitted to the fetus either hematogenously, affecting mainly the liver, or transplacentally via contaminated amniotic fluid, causing pneumonia and enteritis

 

TYPICAL CLINICAL FINDINGS:

• Inapparent infection in most animals
• Abortions in last trimester, usually following initial exposure
• Weak and stillborn neonates

 

TYPICAL GROSS FINDINGS:

• Generally confined to the placenta
• Placenta may be grossly normal, or may be thickened and leathery, with discoloration or mineralization of cotyledons
• Copious, off-white exudate covers intercotyledonary areas
• Cotyledons may have white outer ring with central scattered white flecks
• Aborted fetus may have nonspecific lesions 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Acute diffuse suppurative placentitis with extensive necrosis of cotyledonary villi and intercotyledonary trophoblasts (i.e. both cotyledonary and intercotyledonary areas affected)
• Suppurative inflammation most severe in intercotyledonary areas and cotyledon periphery
• Mononuclear (primarily plasma cells) inflammation in the chorioallantoic interstitium
• Vasculitis is not usually a feature (vs. Chlamydia infection)
• Trophoblast hypertrophy with microcolonies of Coxiella organisms that distend the cytoplasm
  • Cells containing organisms frequently have a characteristic foamy appearance with multiple unstained vacuoles within finely granular pale blue cytoplasm and the nucleus is peripheralized/crescent-shaped 
• Fetal lesions are usually mild and include a granulomatous hepatitis and nonsuppurative pneumonia with occasional focal peribronchiolar lymphoid accumulations

Cytology: Smears of placental exudate contain large numbers of organisms 

 

ADDITIONAL DIAGNOSTIC TESTS:

•  Organisms stain well with modified Ziehl-Neelsen, Stamp, Gimenez, or Macchiavello stains on impression smears
• Culture (BSL-3 lab required because of zoonotic potential) 
• Placental immunohistochemistry: Antigen present in cytoplasmic vacuoles of trophoblasts, especially along the base of the chorionic villi and in neutrophils, degenerate cells, and extracellularly in the intervillous spaces
• Fluorescent antibody staining of tissue or smears of placental exudate
• Serologic titers from dam; complement‑fixation; indirect fluorescent antibody; ELISA
• PCR assays

 

DIFFERENTIAL DIAGNOSIS:

Abortions in small ruminants:

• Necrotizing placentitis associated with intra-trophoblastic organisms:
  • Brucella ovis: Caramel colored, sticky exudate on the placenta, thick leathery placenta, and vasculitis 
  • Chlamydia abortus (R-B08): Vasculitis common; coccoid organisms form intracytoplasmic “inclusions” that stain poorly and appear homogeneous
  • Toxoplasma gondii: Affects primarily cotyledons
• Campylobacter fetus: Placental lesions are more severe over the placentomes; vasculitis; characteristic targetoid lesions on fetal liver (hepatic necrosis)
• Listeria monocytogenes: Severe placental lesions; necrotic tips of villi covered by purulent exudate in which many bacteria are present
• Sarcocystis cruzi: Abortion in cattle, goats, sheep; acute necrotizing endometritis; zoite-containing cysts; multiple foci of necrosis in fetal soft tissues

 

COMPARATIVE PATHOLOGY:

C. burnetti in other species:

• Cattle: Abortion and placental lesions similar to sheep and goats, however severe lesions are rare (bovids usually subclinical)
• Non-domestic ruminants (waterbuck, sable antelope, dama gazelle, Cuvier’s gazelle, greater kudu, bongo, and giraffe): Coxiella-associated placentitis, abortion, and stillbirth have been reported 
• Mice: C. burnetii infection documented in C.B-17-scid/beige mice xenotransplanted with fetal bovine tissue, developed multifocal necrotizing hepatitis with intracytoplasmic organisms within Kupffer cells 
• Humans: Variety of nonspecific signs; chronic infection may result in endocarditis 
• Birds: 
  • C. burnetii: Non-clinical infection 
  • Other Coxiella spp. (Avian Coxiellosis): more pathogenic; non-specific clinical signs, emaciation, splenomegaly, hepatomegaly, granulomatous encephalitis and myocarditis, and Coxiella-like organisms within macrophages of the spleen, liver, bone marrow, kidneys, and adrenal glands 

 

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: John Wiley and Sons; 2016:61-62.
2. Delaney MA, Hartigh AD, Carpentier SJ, et al. Avoidance of the NLRP3 inflammasome by the stealth pathogen, Coxiella burnetii. Vet Pathol. 2021; 58(4):624-642. 
3. Flanders AJ, Speer B, Reavill DR, et al. Development and validation of 2 probe-hybridization quantitative PCR assays for rapid detection of a pathogenic Coxiella species in captive psittacines. J Vet Diagn Invest. 2020; 32(3):423-428. 
4. Foster RA, Premanandan C. Female Reproductive System and Mammae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1296-1298.
5. Jones MEB, Gasper DJ, Mitchell E. Bovidae, Antilocapridae, Giraffidae, Tragulidae, Hippopotamidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Academic Press; 2018:136-137
6. 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; 2016:416-417.

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