JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

October 2024

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 7 µm, 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, mouse, murine.

 

ETIOLOGIC DIAGNOSIS: Intestinal spironucleosis

 

CAUSE: Spironucleus muris

 

GENERAL DISCUSSION:

• An elongate, 7-9 x 2-3 µm, flagellated, binucleate protozoan found in the small intestine (primarily in the crypts of the duodenum) or cecum of clinically normal mice, rats, hamsters 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 mouse hepatitis virus (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 sp. 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:

• Frequently found in the intestines of clinically normal mice, rats, and hamsters
• In rats and hamsters, infection is usually considered opportunistic; clinical disease is rare
• Can cause acute, chronic, or subclinical infection unless young or immunosupresssed mice,or those coinfected with mouse hepatitis virus
• 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 mice
• Chronically affected mice show stunted growth, hunched posture, and lethargy
• 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 2-3µm, 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 “falling leaf” motion (as opposed to fast straight or spiral motion) on direct smears
• Eimeria sp. (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 sp. (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:

• Hexamita pitheci and other Hexamita sp. (diplomonads) are described in the cecum and colon of old world monkeys and apes
• Spironucleus meleagridis: Infectious catarrhal enteritis of turkey poults, upland game birds, peafowl, and ducks; watery to catarrhal inflammation and atony with bulbous dilation of the upper intestine (especially duodenum); characteristically in the lumen of intestinal crypts carrier state facilitates transmission 
• Spironucleus meleagridis: Disseminated spironucleosis reported in immunocompromised rhesus macaques (Bailey, Vet Pathol. 2010)
• Spironucleus meleagridis: Identified in cockatiels with diarrhea and death; concurrent infection with Macrorhabdus ornithogaster and young age are associated with worse disease
• Spironucleus columbae causes a similar catarrhal enteritis to S. meleagridis, but in pigeons
•  Spironucleus elegans/S. vortens: Gastroenteritis in aquarium fish, often in mixed infections, may have amphibian vectors
• Spironucleus salmonis: Primarily freshwater salmonids, usually anterior intestine and pyloric ceca; can spread to gallbladder and other organs, causing high mortality
• Spironucleus barkhanus: Cage-cultured salmonids, proliferates in the blood and localizes to internal organs, muscle, and skin (Not GI)

 

REFERENCES:

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