JPC SYSTEMIC PATHOLOGY
SIGNALMENT (NCAH08-1): 6-year-old multiparous Holstein cow (Bos taurus)
HISTORY: Four days after calving the cow developed watery stool that continued for 2 weeks, accompanied by weight loss and decreased in body condition. 20 days after calving it was unable to rise from sternal recumbence and was euthanized.
HISTOPATHOLOGIC DESCRIPTION: Heart: The endocardium is diffusely expanded up to 1mm by collagen and fibroblasts (fibrosis) with multifocal accumulation of basophilic, granular material (mineral) and mineralized collagen fibers, which multifocally extend into the subendocardial myocardium, separating and surrounding bundles of cardiac myocytes. Subendocardial myocytes are occasionally swollen with sarcoplasmic vacuolation and enlarged, rectangular nuclei (degeneration), or rarely shrunken and hypereosinophilic with fragmented sarcoplasm, loss of cross striations and occasional mineralization (necrosis). Multifocally, myocytes are expanded by an intracytoplasmic, round to oval protozoal cyst measuring up to 40 um in diameter with a 4 um thick, eosinophilic capsule, containing numerous, up to 10 um, basophilic, crescent-shaped bradyzoites.
- Heart: Endocardial mineralization and fibrosis, diffused, marked, with myocardial degeneration, necrosis and mineralization, Holstein, bovine (Bos taurus).
- Heart, myocardium: Sarcocysts, multifocal.
DISEASE NAME: Paratuberculosis or Johne’s disease
ETIOLOGIC DIAGNOSIS: Mycobacterial associated endocardial mineralization
CAUSE: Mycobacterium avium subspecies paratuberculosis (Map)
- Two main pathological forms described:
- Paucibacillary form, inflammatory infiltrate composed of lymphocytes with some macrophages but few mycobacteria
- Multibacillary form, mostly macrophages filled with numerous mycobacteria
- In sheep or goats with no clinical signs focal intestinal granulomatous lesions in the intestinal lymphoid tissue
- There are no tests with high specificity as well as high sensitivity are available for subclinically infected animals
- Infection of newborn and young animals can be followed by a latent period that may last for years, with intermittent bacterial shedding
- Transmitted via feces, milk, semen, urine and transplacental
- Fecal-oral route in the first months of life, but clinical disease appears in animals older than one year (usually 2 to 5 years)
- Bacteria invade via tonsils, Peyer’s patches M cells and enterocytes, mainly in jejunum and ileocecal valve > disseminate to mucosal lamina propria and local lymph nodes
- After entering the intestine through Peyer’s patches the bacteria reaches the lymph nodes, escaping the initial local immune defenses in the gut, before inducing lesions in the intestine (in sheep and goat)
- Goats may control the bacterial multiplication resulting in regression and healing of lesions, or an uncontrolled bacterial multiplication leading to clinical disease
- Multibacillary lesions correspond to borderline lepromatous forms, associated with marked humoral peripheral responses
- M2 macrophages predominate
- Paucibacillary lesions, show strong cellular immune responses, correspond to borderline tuberculoid forms
- M1 macrophages predominate (high iNOS; low TNF-a)
- Focal intestinal granulomatous lesions have a high cellular immune response (tuberculoid)
- Cell-mediated immunity is thought to be essential in controlling the progression of infection
- Aortic wall mineralization occurs spontaneously
TYPICAL CLINICAL FINDINGS:
- Weight loss and cachexia
- Decreased milk production and diarrhea
TYPICAL GROSS LESIONS:
- Thickening of the intestinal wall, granulomatous enteritis, lymphangitis, and lymphadenitis of regional lymph nodes
- Intestinal ulcers and strictures
- Crater-like lesions in the small intestine that occasionally coalesce
- Focal lesions are more common in lymph nodes in initial/latent forms of the disease
TYPICAL LIGHT MICROSCOPIC LESIONS:
- Diffuse granulomatous infiltrates in jejunal Peyer’s patches and the patch at the ileocecal valve to severe diffuse lesions throughout the intestine.
- Granulomas or giant cells in intestinal villi and lymph nodes
- Peyer’s patches lymphoid depletion
- Dilation of intestinal glands associated with infiltrates in the lamina propria, causing occlusion
- Intestinal mucosal ulceration with transmural inflammation and serositis > may heal or perforate
- Foci of necrosis and calcification in mesenteric lymph nodes
- Granulomas in the ileal and jejunal lymph nodes
- Granulomatous arteritis in small to medium-sized vessels in the submucosa (may require IHC to be observed)
- Acid fast bacilli within macrophages and dilated intestinal lymphatics
- Minimal lesions in lung
- Lymphocytic inflammation of submucosal nervous plexuses rarely observed
- Multinucleated Langhans giant cells are common in cattle (not sheep/goat)
- Loss of CD4+ T cells and an increased frequency of gamma–delta T cells in the ileum of cattle has been observed in multibacillary lesions
- Lymphangiectasis is most common/severe in small ruminants
- Microscopic granulomas in the liver
- Mineralization of the aortic wall
ADDITIONAL DIAGNOSTIC TESTS:
- Bacterial culture and PCR (from blood, feces, milk, semen, urine and tissues)
- IHC and Acid-fast: Low numbers of bacteria in lesions
- Antibody to lysozyme is useful in immunolabelling of macrophages or giant cells
- Labelling by MAP antibody is more efficient than Ziehl–Neelsen (ZN) staining for organisms detection
- Wall-deficient bacterial forms are usually negative to ZN and difficult to
- culture, but can be demonstrated by in-situ hybridization
- Liver biopsy is a useful diagnostic tool in sheep
- MAP has 15-20 copies of the insertion sequence IS900 which differentiates it from M. avium subspecies avium
- Fallow Deer: Focal, multifocal and diffused forms (both multibacillary and paucibacillary) have been described
- Spontaneous disease occurs in ruminants, camelids, equids and primates
- Natural infection occurs in lagomorphs, rodents, carnivores and birds
- Experimentally induced in mice, rabbits, guinea pigs, hamsters and macaques
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