JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
August 2018
D-B16

SIGNALMENT (JPC #2329499):  A 3-month-old male Yorkshire crossbred feeder pig

HISTORY:  Eight pigs died acutely in a pen of 50 pigs which were experiencing bloody diarrhea, dehydration and weight loss which was refractory to antibiotic therapy.

HISTOPATHOLOGIC DESCRIPTION:  Colon:  There are multifocal to coalescing areas of hemorrhage and necrosis (lytic and coagulative) of superficial mucosal epithelium admixed with thin mat of fibrin, cellular and karyorrhectic debris, degenerate neutrophils, and colonies of basophilic bacteria.  Coagulative necrosis multifocally extends into crypts and is characterized by retention of architecture with more brightly eosinophilic cytoplasm of enterocytes.  Crypts are diffusely elongated up to 2-3 times normal, mutlifocally ectatic, containing an amphophilic to pale basophilic fibrillary material (mucus) (crypt hyperplasia).  Multifocally, crypts also contain hyperplastic goblet cells, and occasionally are ectatic and contain mucus, neutrophils and necrotic cellular debris (crypt abscess)  Blood vessels within the lamina propria, submucosa, and mesentery are congested, and multifocally, small vessels within the mucosa and submucosa contain a fibrillar to finely granular to hyalinized eosinophilic material (fibrin thrombi).  There are multiple ectactic, mucus filled crypts located within a Peyer’s patch (focal crypt herniation).

MORPHOLOGIC DIAGNOSIS:  Colon:  Colitis, necrohemorrhagic, acute, diffuse, moderate, with crypt and goblet cell hyperplasia and fibrin thrombi, Yorkshire cross (Sus scrofa domestica), porcine.

ETIOLOGIC DIAGNOSIS:  Brachyspiral colitis

CAUSE:  Brachyspira hyodysenteriae

CONDITION:  Swine dysentery

SYNONYMS:  Vibriotic dysentery, bloody scours, bloody dysentery, black scours, mucohemorrhagic diarrhea

GENERAL DISCUSSION:

• Gram-negative, strongly beta hemolytic, oxygen tolerant, anaerobic, loosely coiled, motile spirochete, 8-10 microns long, 0.3-0.4 microns in diameter with 7-13 periplasmic flagella per cell
• Acute to chronic highly infectious disease, most commonly found in grower and finisher pigs (8-14 weeks)
• Multiple Brachyspira spp. can colonize the porcine colon and cause disease typical of swine dysentery (B. hyodysenteriae, “B. hampsonii”, and “B. suanatina”)

PATHOGENESIS:

• Transmission is fecal-oral
• Pathogenesis is incompletely understood 
• There is synergistic action between B. hyodysenteriae and other anaerobes normally found in the swine colon and cecum (mainly Bacteroides spp. and Fusobacterium spp.) required for clinical disease; erosion of the mucosa can lead to secondary invaders into the lamina propria (e.g., Balantidium coli)
• Various virulence traits (i.e., hemolysin, cytotoxins, outer membrane proteins, motility factors such as flagella, NADH oxidase activity) believed to play a role in infection 
• Motile Brachyspira hyodysenteriae is chemotactically attracted to hog mucin (fucose and L-serine) > invades intestinal crypts and disrupts colonic epithelium > progressive erosion of superficial epithelium, excess mucus production, edema and hemorrhage of the lamina propria with pseudomembrane production > death from dehydration (diarrhea due to malabsorption of fluids and electrolytes in colon)
• Thrombosis may occur due to absorption of bacterial endotoxins from gram-negative bacteria through the damaged mucosal epithelium
• Initial replication in mucigen droplets of goblet cells by bacteria cause increased mucus production by goblet cells; colonize the thickened mucosal layer
• Decreased expression of sulphated mucins and MUC4, but increased expression in MUC5AC and MUC2 in pigs infected with B. hyodysenteriae and B. hampsonii compared to control groups
• Increased protein:carbohydrate ratio in hindgut can enhance pathogenicity
• Asymptomatic carrier pigs are the most important mode of transmission from farm to farm; mechanical vectors are also important

TYPICAL CLINICAL FINDINGS:

• Anorexia, fever, moderate to severe mucohemorrhagic to fibrinous colitis
• Abdominal pain, dehydration, emaciation; the abdominal skin may be cyanotic
• Morbidity 90%, mortality 30% with rapid spread through herd
• Metabolic acidosis with decreased sodium, chloride and bicarbonate levels; terminal hyperkalemia; marked left shift
• Rarely, peracute death with no diarrhea; unknown pathogenesis
• Chronic form:  Persistent diarrhea and failure to thrive

TYPICAL GROSS FINDINGS:

• Lesions in the large intestine only (cecum, colon, spiral colon, and rectum); multifocal, patchy, or diffuse involvement of large intestine
• Mucohemorrhagic and fibrinonecrotic pseudomembranous colitis with a granular and hyperemic mucosa in advanced cases
• Opaque spots (i.e., enlarged submucosal glands) are visible through the colonic serosa
• Mucus, fibrin and blood in the lumen
• Lesions are similar in pigs infected with B. hyodysenteriae, B. hampsonii, and B. suanatina.

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Elongated hyperplastic crypts may be dilated with necrotic debris and abundant mucus;  
• Goblet cell hyperplasia
• Significant lesions limited to cecum, colon and rectum
• Discrete epithelial erosion and necrosis of the superficial mucosa with a fibrinocellular exudate early in the disease process
• Fibrin thrombi in the vessels of the superficial lamina propria
• Transmural edema
• Mucosal and submucosal thickening from vascular congestion and extravasation of fluids and electrolytes
• Experimentally, histologic findings of neutrophilic inflammation, colonic crypt death, mucosal ulceration and hemorrhage are similar in infections with B. hyodysenteriae, B. hampsonii, and B. suanatina.

ULTRASTRUCTURAL FINDINGS:

• Spirochetes at the luminal surface of epithelial cells (in mucus layer), in crypts and in the lamina propria 
• Sparse and shortened microvilli of colonic epithelial cells, swollen mitochondria, reduced number of organelles

ADDITIONAL DIAGNOSTIC TESTS:

• Culture of feces, colonic contents with identification via PCR has been gold standard
• Matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) increasingly used – quick, precise, inexpensive
• Silver stains (Warthin-Starry) and in situ hybridization demonstrate spirochetes in superficial erosions and crypt lumina, goblet cells, luminal mucus and epithelial cells
• Restriction endonuclease analysis, Southern blot hybridization and PCR for species-specific and strain-specific identification of B. hyodysenteriae

DIFFERENTIAL DIAGNOSIS:  (bloody diarrhea in swine)

• Brachyspira hampsonii and B. suanatina:  Causes disease identical to Brachyspira hyodysenteriae; novel Brachyspira spp. identified in 2012 and 2007 respectively
• Porcine colonic spirochetosis:  Caused by the weakly beta-hemolytic intestinal spirochetes (WBHIS) Brachyspira pilosicoli; mild diarrhea and reduced growth rate in weanling pigs (5 to 12 weeks)
• Coliform gastroenteritis:  Deep red gastric venous infarcts; flaccid small intestine and enlarged mesenteric lymph nodes
• Postweaning colibacillosis: Catarrhal to mild fibrinohemorrhagic enterocolitis in piglets after weaning
• Salmonellosis:
  • S. Typhimurium:  Yellow watery diarrhea; acute enterocolitis  with pseudodiphtheritic membrane; lesions in colon and rectum
  • S. Choleraesuis:  Primarily septicemia with enteritis
• Classical swine fever (swine pestivirus):  Sudden death; weak pigs; anorexia; watery diarrhea; hypertrophy and ulceration of mucosa of stomach, cecum and colon; colonic button ulcers
• Trichuris suis:  Concurrent infections are possible, which can cause bloody diarrhea
• Acute hemorrhagic, proliferative enteropathy (Lawsonia intracellularis)
  • Affects terminal ileum and colon; rapidly fatal with severe hemorrhagic diarrhea
  • May be proliferative, necrotizing and hemorrhagic, or both
  • Intracytoplasmic bacteria in apical cytoplasm identified with silver stain
  • Areas of hyperplasia often appear irregular / adenomatous
  • Often effects ileum (unlike B. hyodysenteriae) but may also be in colon
  • Hemorrhagic form more common in young adults (4-12 months)
• Gastric ulceration:  Melena rather than frank blood

COMPARATIVE PATHOLOGY:

• Experimentally, lesions of swine dysentery have been induced in mice, young chicks and Guinea pigs by oral inoculation of Brachyspira hyodysenteriae
• The organism has been isolated from a dog on a farm where swine dysentery was present
• Necrotizing typhlocolitis in naturally infected rheas
• Fibrinonecrotic typhlocolitis in ducks

REFERENCES:

1. Burrough ER. Swine Dysentery: Etiopathogenesis and Diagnosis of a Reemerging Disease. Vet Pathol. 2017;54(1): 22-31.
2. Chander Y, Primus A, Oliveira S, Gebhart CJ. Phenotypic and molecular characterization of a novel strongly hemolytic Brachyspira species, provisionally designated “Brachyspira hampsonii”. J Vet Diagn Invest. 2012;24(5):903-10.
3. Gelberg HB. Alimentary system and the peritoneum, omentum, mesentery, and peritoneal cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. St. Louis, MO: Elsevier; 2017:403-404.
4. Glavits R, Ivanics E, Thuma A, et al. Typhlocolitis associated with spirochaetes in duck flocks. Avian Pathol. 2011;40(1):23-31.
5. Rohde F, Majzoub-Altweck M, Falkenau A, et al. Occurrence of dysentery-like diarrhoea associated with Brachyspira suanatina infection on a German fattening pig farm. Vet Rec. 2018;1: 1-5.
6. Uzal, FA, Plattner 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; 2016:115-116; 181-183.
7. Warneke HL, Kinyon JM, Power LP, Burrough ER, Frana TS. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for rapid identification of Brachyspira species isolated from swine, including the newly described “Brachyspira hampsonii.” J Vet Diagn Invest. 2014;26(5):635-639.
8. Wilberts BL, Arruda PH, Kinyon JM, Madson DM, Frana TS, Burrough ER. Comparison of lesion severity, distribution, and colonic mucin expression in pigs with acute swine dysentery following oral inoculation with “Brachyspira hampsonii” or Brachyspira hyodysenteriae. Vet Pathol. 2014;51(6):1096-1108.
9. Wilberts BL, Warneke HL, Power LP, Kinyon JM, Burrough ER. Comparison of culture, polymerase chain reaction, and fluorescent in situ hybridization for detection of Brachyspira hyodysenteriae and “Brachyspira hampsonii” in pig feces. J Vet Diagn Invest. 2014;27(1):41-46.
10. Zachary JF. Mechanisms of microbial infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. St. Louis, MO: Elsevier; 2017:165-166.
11. Zeeh F, De Luca S, Nicholson P, et al. Brachyspira hyodysenteriae detection in the large intestine of slaughtered pigs. J Vet Diagn Invest. 2018 Jan(1): 56-63.

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