JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
August 2021
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:  The superficial 1/4 to 1/3 of the mucosa is diffusely characterized by necrosis (lytic and coagulative) admixed with a variable amount of hemorrhage, fibrin, and edema, and occasionally overlain by a thin pseudomembrane of fibrin with enmeshed cellular and karyorrhectic debris, degenerate neutrophils, and colonies of thin, 0.5um wide, variably elongate, occasionally spiral, basophilic bacteria.  Coagulative necrosis multifocally extends into crypts and is characterized by retention of architecture with loss of differential staining.  Crypts are diffusely elongated up to 2-3 times normal (crypt hyperplasia), are multifocally lined by increased numbers of goblet cells (goblet cells hyperplasia), are multifocally ectatic, containing amphophilic to pale basophilic fibrillar material (mucus), and occasionally also contain neutrophils and necrotic cellular debris (crypt abscess).  There are multiple ectatic, mucus-filled crypts located within a Peyer’s patch (focal crypt herniation).  Small caliber blood vessels within the lamina propria and submucosa multifocally are occluded by fibrillar to hyalinized eosinophilic material (fibrin thrombi).  Blood vessels within the lamina propria, submucosa, and mesentery are congested. 

 

MORPHOLOGIC DIAGNOSIS:  Colon:  Colitis, necrohemorrhagic, acute, diffuse, moderate, with crypt hyperplasia, 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)
• Lesions can be multifocal, patchy, or involve the entire large intestine; usually limited to the colon and cecum
• Multiple Brachyspira 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 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 for successful colonization of colonic epithelium) 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 and degeneration with necrosis of epithelial cells and hemorrhage (thought to be mediated by cytotoxins and endotoxin), edema and hemorrhage of the lamina propria with pseudomembrane production > death from dehydration (diarrhea due to malabsorption of fluids and electrolytes in colon)
• Thrombosis (capillaries and venules) may occur due to absorption of bacterial endotoxins from gram-negative bacteria through the damaged mucosal epithelium
• Initial bacterial replication in mucigen droplets of goblet cells causes increased mucus production by goblet cells; bacteria colonize the thickened mucus layer
• Subfamilies of mucins include secreted gel-forming mucins, secreted nongel-forming mucins, and cell-surface mucins
  • An increased expression of mucin 2 (MUC2, secreted gel forming), de novo expression of mucin 5 AC (MUC5AC, secreted gel-forming), and a decrease in mucin 4 (MUC4, cell-surface) has been reported in pigs with SD (Je-Han Lin, Vet Pathol. 2021)
  • Pro-inflammatory cytokine IL-1b was not significantly increased in pigs with SD and thus may not be a major regulator of MUC5AC and MUC2 secretion; expression of the immune-regulatory cytokine TGF-b was significantly suppressed in pigs with SD (Je-Han Lin, Vet Pathol. 2021)
• 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 (rodents) 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 hyodysenteriae, B. hampsonii, and B. suanatina.

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Significant lesions limited to cecum, colon; can occur in rectum
• Discrete areas of epithelial erosion and necrosis of the superficial mucosa
• Elongated hyperplastic crypts lined by proliferative basophilic epithelial cells or and few differentiated goblet cells and later may be dilated with necrotic debris and abundant mucus
• Goblet cell hyperplasia and copious mucus production later
• 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 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:

• Detection of subclinical infection is difficult: Ingesta from the colon and lesions of slaughtered pigs is useful material for detection of hyodysenteriae – Zeeh JVDI 2017
• 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 hyodysenteriae

 

DIFFERENTIAL DIAGNOSIS: 

Bloody diarrhea in swine:

• Brachyspira hampsonii and suanatina: Identified in 2012 and 2007 respectively, cause disease identical to Brachyspira hyodysenteriae (Aller-Morán, J Vet Diagn Invest 2016)
• Porcine colonic spirochetosis: Caused by the weakly beta-hemolytic intestinal spirochete (WBHIS) Brachyspira pilosicoli; mild diarrhea and reduced growth rate in weanling pigs (5 to 12 weeks); causes distinctive microscopic lesions as it colonizes the apex of surface epithelium
• 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
• Salmonella enterocolitis mainly resulting from Typhimurium

• S. Typhimurium:  Yellow watery diarrhea; acute enterocolitis with pseudodiphtheritic membrane; fibrinous, erosive to focally ulcerative condition with lesions mainly of cecum, colon, but occasional involvement of terminal ileum; intestinal content is fluid not usually bloody; prominent mesenteric lymph nodes  
• S. Choleraesuis:  Primarily septicemia (host-adapted strain) 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 the ileum (terminal ileum > adenomatosis) 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
• Report of coinfection with Entamoeba polecki – (Cuvertoret-Sanz J Vet Diagn Invest 2019)

 

COMPARATIVE PATHOLOGY:

• Experimental oral inoculation of Brachyspira hyodysenteriae results in lesions of swine dysentery in mice, young chicks, and Guinea pigs
• Natural infection:
  • Necrotizing typhlocolitis in naturally infected rheas
  • Fibrinonecrotic typhlocolitis in ducks
  • Has been isolated from a dog on a farm where swine dysentery was present

 

REFERENCES:

1. Aller-Morán LM, Martínez-Lobo FJ, Rubio P, Carvajal A. Cross-reactions in specific Brachyspira spp. PCR assays caused by “Brachyspira hampsonii” isolates: implications for detection. JVDI. 2016;28(6):755-759.
2. Burrough ER. Swine Dysentery: Etiopathogenesis and Diagnosis of a Reemerging Disease. Vet Pathol. 2017;54(1):22-31.
3. 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.
4. Cuvertoret-Sanz M, et. al. Coinfection with Entamoeba polecki and Brachyspira hyodysenteriae in a pig with severe diarrhea. JVDI 2019;31(2):298-302.
5. 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.
6. Glavits R, Ivanics E, Thuma A, et al. Typhlocolitis associated with spirochaetes in duck flocks. Avian Pathol. 2011;40(1):23-31.
7. Je-Han Lin S, Arruda B, Burrough E. Alteration of Colonic Mucin Composition and Cytokine Expression in Acute Swine Vet Pathol. 2021;58(3):531-541.
8. 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.
9. Smith DA. Palaeognathae: Apterygiformes, Casuariiformes, Rheiformes, Struthioniformes; Tinamiformes. In: Terio KA, McAloose D, Judy St. Leger J, ed. Pathology of Wildlife and Zoo Animals, Cambridge, MA Academic Press; 2018:644, 648.e13.
10. 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; 2016:100, 115-116; 181-183.
11. 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.
12. 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.
13. 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.
14. Zachary JF. Mechanisms of microbial infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. St. Louis, MO: Elsevier; 2017:165-166.
15. Zeeh F, De Luca S, Nicholson P, et al. Brachyspira hyodysenteriae detection in the large intestine of slaughtered pigs. J Vet Diagn Invest. 2018;30(1): 56-63.

 

 

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