Signalment (JPC #2015661): Ovine fetus
HISTORY: One of two crossbred ovine fetuses that were aborted approximately 3-4 weeks prior to the expected date of parturition
HISTOPATHOLOGIC DESCRIPTION: Lung: There are multifocal, randomly distributed foci of necrosuppurative inflammation that affect approximately 25% of the section; these are composed of a central necrotic area of eosinophilic cellular and karyorrhectic debris and large colonies of 1 x 2 um bacilli surrounded by high numbers of viable and degenerate neutrophils, fewer macrophages and lymphocytes. Multifocally, bacterial colonies are present within capillaries. Diffusely, the remaining alveolar spaces, septa, vasculature, and bronchioles contain scattered inflammatory cells, eosinophilic, fibrillar material (fibrin), few erythrocytes (hemorrhage), necrotic cellular debris, and rarely globular yellow material (meconium). There are widely dilated lymphatics and amorphic, homogenous, eosinophilic material (edema) that expands the perivascular space. Diffusely, there is atelectasis and congestion.
MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, necrosuppurative, subacute, severe, with meconium and numerous large bacterial colonies, crossbred sheep, ovine
ETIOLOGIC DIAGNOSIS: Pulmonary yersiniosis
CAUSE: Yersinia pseudotuberculosis
- Pathogenic species of the genus Yersinia, which includes Yersinia pestis (causative agent of plague), pseudotuberculosis, and Y. enterocolitica
- Yersinia pseudotuberculosis is a zoonotic agent that occurs worldwide and causes disease in a wide variety of wild, laboratory, and domestic mammals, as well as birds
- It is also widely distributed in soil, water, and food (milk and meat products, vegetables)
- Facultative anaerobic, oxidase-negative, gram negative, coccobacillus
- Can survive and replicate in the soil and in aquatic environments outside of host for months to years
- Latent infections are common; asymptomatic carriers can break with disease during periods of stress (cold and wet weather, overcrowding, capture, etc.), resulting in herd or flock outbreaks
- Lesions of pseudotuberculosis and Y. enterocolitica cannot be differentiated reliably grossly or macroscopically
- Transmission: ingestion of fecal contaminated food/water or ingestion of infected prey by carnivores
- After ingestion, bacteria attach to and penetrate the mucus layer overlying mucosal epithelial cells via M cells then adhere to and colonize intestinal cell brush border membranes
- Once bacteria reach the terminal ileum, they present the outer membrane protein invasion on their surface; invasion facilitates translocation of the bacteria across the intestinal epithelium
- Invasin then binds to B1 integrins in the host tissue, which induces production of chemokines (IL-8)
- After penetrating the epithelium, the bacteria are phagocytized by neutrophils and macrophages in the mucosa and submucosa
- In the Peyer’s patches, bacteria replicate and express YadA (adhesin), which, together with another protein called Ail, down regulates invasin and protects bacteria against phagocytosis; t-cell-mediated immunity is required to clear infection
- The intracellular environment of the phagocyte (37˚C, low calcium) activates the low calcium response (lcr) plasmid which leads to the production of surface proteins: V antigen and Yersinia outer membrane proteins (Yops)
- These surface proteins confer resistance to killing by phagocytosis by interfering with phagocytic intracellular signaling, inducing host cell apoptosis, and, once out of the phagocyte, inhibiting complement opsonization
- Microcolonies form in the lamina propria, around necks of the crypts in the jejunum and ileum, and in Peyer’s patches and the superficial mucosa in the large intestine
- From the Peyer’s patches, the organism can extend to the regional lymph nodes, causing lymphadenitis, and into the circulatory system leading to septicemia with spread to the liver, spleen, nervous system and lungs
- Abortion can occur after localization of bacteria in maternal caruncle, followed by passage to the chorioallantois and the fetus
TYPICAL CLINICAL FINDINGS:
- Fibrinous to fibrinohemorrhagic enterocolitis, mesenteric lymphadenitis +/- septicemia
- In acute infections, animals may be found dead without showing clinical signs
- Clinical signs: Malaise, depression, anorexia, vomiting, abdominal discomfort, diarrhea, icterus, swollen lymph nodes, dyspnea, emaciation, and sudden death
TYPICAL GROSS FINDINGS:
- Caseonecrotic foci in mesenteric nodes, spleen, liver, occasionally lungs, kidneys, and bone marrow
- Multifocal to diffuse, often transmural, hemorrhage and necrosis of the small and large intestine (ulcerative enterocolitis) with marked neutrophil infiltration
- With abortion, fetus is well preserved and cotyledons are tan-red and thickened; some caruncles may still be attached with fibrin and fibrosis surrounding affected cotyledons
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Necrosis with large colonies of gram-negative bacilli and fragmented neutrophils surrounded by macrophages; multinucleated giant cells are usually absent
- Necrotic placental villi with infiltrates of granulocytes, macrophages, and mononuclear cells in the interstitium of the chorioallantois with fibrinoid necrosis of placental vessels
- Aberrant forms possible: globular bodies, spherules, filaments
- Fetus: Numerous large bacterial colonies and multifocal areas of necrosis with infiltration of mononuclear cells and neutrophils, fibrin and edema in the lungs; also hepatic, myocardial and lymph node necrosis
- Peritrichous flagella when organism is cultured at 20-30°C
- Aberrant forms
- Globular bodies: The cell wall of globular bodies is partly detached from the cytoplasmic membrane
- Globular bodies with decreased ribosomes compared with rod-shaped bacteria
ADDITIONAL DIAGNOSTIC TESTS:
- Cold enrichment and culture at temperatures below 37ºC
Bacteria that appear histologically as large colonies:
- Yersinia enterocolitica and pestis: Differentiate by culture and PCR
- Actinomyces gram (+)
- Actinobacillus gram (-)
- Corynebacterium gram (+)
- Staphylococcus gram (+)
- Streptococcus gram (+)
- Nocardia sp. Partial AFB
- Hamsters: Necrotic caseous nodules in intestine, mesenteric lymph nodes, liver, spleen, and lungs
- Guinea pigs: Acutely-- miliary cream-colored nodules in intestinal wall, enteritis, mucosal ulceration (esp. terminal ileum and cecum); subacutely to chronically-- miliary to caseous lesions in mesenteric lymph nodes, spleen, liver and lung
- Rabbits: Acute to chronic granulomatous infections with focal caseous necrosis of liver, spleen, cecum, lymph nodes and reproductive tract
- Beavers: Acute necrotizing hepatitis and splenitis, intravascular septic emboli in lungs, small intestine, and kidneys, ulcers of tail and hind feet
- Rats: Scattered raised nodules in liver, spleen, and other organs
- Birds: Acute septicemia followed by either sudden death or chronic focal infections in liver, spleen, lungs, intestines, mesentery, pectoral muscles
- Bats: Mesenteric lymphadenopathy, hepatic abscessation, and/or splenomegaly
- Non-human primates: Focal suppurative necrotizing enteritis with serositis, suppurative mesenteric lymphadenitis, necropurulent hepatitis (liver abscesses), suppurative splenitis, myelitis, abortion
- Spontaneous lesions in wild, captive-bred, and zoo-housed nonhuman primates and in nonhuman primate species used in drug safety studies
- Squirrel monkeys in Japan: Aberrant forms of Yersinia pseudotuberculosis as spheroplasts and filaments in Yersiniosis
- The monkeys had systemic necrotizing and hemorrhagic lesions with gram-negative rod-shaped bacilli and microthromboembolism in the kidneys
- Some lesions contained filaments, globular bodies, and other pleomorphic forms of bacteria
- Cattle: Enterocolitis; mesenteric lymphadenitis; septicemia with foci of necrosis in liver, spleen, lungs; abortion; and pneumonia
- Sheep and Goats: Enterocolitis; caseous mesenteric lymphadenitis; septicemia with foci of necrosis in liver, spleen, lungs; placentitis with abortion or perinatal mortality; epididymitis/orchitis; oculoglandular syndrome; and mastitis
- Swine: Necrotic foci surrounded by a thin layer of granulation tissue in lung, liver, spleen, mesenteric lymph nodes, and lymphoid follicles in large intestine; Y. enterocolitica more common than pseudotuberculosis
- Cats: Most often secondarily involved by outbreaks of the disease due to their contact with rodents and birds; infection is usually fatal
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