JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
September 2021
D-P07 (NP)

 

SIGNALMENT (JPC #2317379):  Mouse

 

HISTORY:  Tissue from a mouse

 

HISTOPATHOLOGIC DESCRIPTION:  Small intestine:  Multifocally, crypts are mildly ectatic and contain numerous eosinophilic, piriform to spindled, flagellated, 2 x 7um, protozoal trophozoites that contain two indistinct, basophilic nuclei.  Smaller numbers of similar protozoa are present in the intestinal lumen and lining villar epithelium.

 

MORPHOLOGIC DIAGNOSIS:  Small intestine, crypts and lumen:  Extracellular piriform flagellated protozoa, numerous, etiology consistent with Spironucleus muris, mouse, murine.

 

ETIOLOGIC DIAGNOSIS:  Intestinal spironucleosis

 

CAUSE:  Spironucleus muris

 

GENERAL DISCUSSION:

• An elongate, 7-9 x 2-3um, flagellated, binucleate protozoan found in the small intestine (primarily in the crypts of the duodenum) or cecum of clinically normal mice, rats, amsters and various wild rodents worldwide
• Member of the Hexamitidae family (with Giardia, Pentatrichomonas, and Trichomonas)
• Found in up to 80% of healthy, adult mice
• Animals 3-6 weeks of age are particularly at risk for developing clinical disease
• May cause disease in juveniles or adults who are stressed, immunosuppressed, or immunodeficient; also occurs as a concurrent infection with viruses, such as enterotropic MHV
• Infected mice may be unsuitable for immunologic experiments since they may respond poorly to antigens; cultured macrophages from infected mice are sometimes incapable of normal RNA synthesis
• Frequently found in hamster stocks from commercial suppliers; Giardia is a reported finding with S. muris (larger numbers in crypts of jejunum) in addition to flagellates in the peripheral blood of hamsters with enteritis
• European hamsters were shown to transmit infection to Syrian hamsters
• Transmission between mice, rats, and hamsters can occur although some references say it cannot be transmitted from mice and hamsters to rats

LIFE CYCLE:

·  Direct

• Fecal/oral through food, water, or bedding
• Organisms inhabit intestinal crypts and absorb nutrients from the host's ingesta
• They do not attach to the mucosa, but “graze” along the epithelium
• Reproduction is by longitudinal binary fission
• Flagellated form can encyst and be passed in the feces

 

PATHOGENESIS:

• 4-7 day incubation period
• Infection in a clean colony usually follows introduction of asymptomatic carriers
• Recovered adults can be source of infection
• Several proposed theories for diarrhea:
  • Epithelial blanketing by massive numbers of trophozoites, blocking absorption
  • Competition between parasite and host for nutrients
  • Parasitic toxins interfere with microvillar functions or enzyme activity
  • Mucosal irritation leading to excessive mucous secretion

 

TYPICAL CLINICAL FINDINGS:

• Can cause acute, chronic, or subclinical infection unless young or immunosupresssed
• Acute disease occurs in mice 3 - 6 weeks old; may die with diarrhea or with a distended abdomen and no diarrhea
• Depression, weight loss, dehydration, hunched posture, diarrhea
• Mortality rates up to 50% in young animals
• Chronically affected mice show stunted growth, hunched posture, and lethargy
• Deaths are sporadic
• Most adults are subclinically infected
• In rats, infection is usually considered opportunistic; clinical disease is rare
• Spironucleus muris is apparently non-pathogenic in hamsters but has been isolated from lesions of proliferative ileitis

 

TYPICAL GROSS FINDINGS:

• Small intestine is distended with dark red to brown watery contents and gas

 

TYPICAL MICROSCOPIC FINDINGS:

• Often no associated inflammation
• In acute infections, the lamina propria and submucosa may be edematous and contain neutrophils
• Pale eosinophilic trophozoites (7-9 x 2-3um, elongated, pear-shaped) are present in the crypts and intervillous spaces
• In chronic infections, ectatic crypts contain lymphocytes, plasma cells, cellular debris, and numerous parasites
• Rarely, the organisms may invade the mucosa (between enterocytes) and lamina propria

 

ULTRASTRUCTURAL FINDINGS:

• Piriform to ellipsoid organism
• Eight flagella originating from the anterior portion
• Two anterior, slightly spiral nuclei that resemble eyes
• Lacks an undulating membrane

 

ADDITIONAL DIAGNOSTIC TESTS:

• Observation of the organism in direct smears of feces or ingesta; fast straight or spiral (zig zag) motion; banded “Easter egg” cysts in intestinal contents
• Must have rapid tissue fixation (within 1 hour) for histologic identification; can also use PAS to stain trophozoites

 

DIFFERENTIAL DIAGNOSIS:

Gastrointestinal protozoa in mice:

• Giardia muris (Hexamitidae family): Usually in the lumen; has a rolling motion (as opposed to fast straight or spiral motion) on direct smears
• Eimeria (E. falciformis, E. musculi, E. schueffneri, E. krijgsmanni, E. keilini, E. hindlei): Oocysts in mucosa; more common in wild mice; inapparent infection in adults and marked colitis in juveniles
• Cryptosporidium (C. parvum, C. muris): Attach to the brush border of gastric (muris) or small intestinal (C. parvum) epithelium; C. muris usually nonpathogenic; C. parvum associated with cholangiohepatitis with focal hepatic necrosis in nude and SCID mice

 

COMPARATIVE PATHOLOGY:

• Spironucleus meleagridis: Infectious catarrhal enteritis of poults; watery to catarrhal inflammation and atony of the upper intestine 
• Spironucleus meleagridis: Disseminated spironucleosis reported in immunocompromised rhesus macaques (Bailey, Vet Pathol. 2010)
• Spironucleus columbae: Catarrhal enteritis in pigeons
• Spironucleus elegans: Enteritis in fish

 

 

REFERENCES:

1. Bailey C, Kramer J, Mejia A, et al. Systemic spironucleosis in 2 immunodeficient rhesus macaques (Macaca Mulatta). Vet Pathol. 2010; 47(3):488-494.
2. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: John Wiley & Sons; 2016: 83-84,151,189-190.
3. Delaney MA, Treuting PM, Rothenburger JL. In: Terio KA, McAloose D, Judy St. Leger J, ed. Pathology of Wildlife and Zoo Animals. Cambridge, MA Academic Press; 2018: 513.e9.
4. Gardiner CH, Fayer R, Dubey JP. An Atlas of Protozoan Parasites in Animal Tissues. 2nd ed. Washington, DC: Armed Forces Institute of Pathology; 1998:6-7.
5. Sheppard BJ, Stockdale Walden HD, Kondo H. Syrian hamsters (Mesocricetus auratus) with simultaneous intestinal Giardia, Spironucleus sp., and trichomonad infections. J Vet Diag Invest. 2013; 25(6): 785-790.

 

 

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