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Rodent Infections

The infections included in our rodent serology panels are described below. Diagnosis of these infections is facilitated by serology. Since serology measures immunoglobulins, that take time and an intact immune system to develop, it may be negative at the time of clinical disease, and in immature, immunodeficient and immunocompromised rodents. The occurrence of the agents is based on the published references and may not be indicative of all populations of mice and rats.

Viruses

Ectromelia

Host species: Mice

Type of agent: Orthopoxvirus

Occurrence: Rare

Significance: Important systemic pathogen.

Epidemiology:
• Virus is shed in the feces for about 3 weeks.
• Transmission is primarily by direct contact and fomites.
• Skin abrasions serve as the portal of entry.
• Moderately infectious.
• May contaminate biological materials, e.g., serum, cell and tumor lines.

Clinical disease:
• Pathogenicity varies with the strain of mice.
• In susceptible strains, foot swelling, pocks, lethargy, depression and sudden death.
• Distal portions of the tail and limbs may necrose and slough.

Pathology:
• Widespread necrosis in the spleen, lymph nodes, thymus and liver.
• Erosions of the mucosa of the small intestine.
• Cytoplasmic inclusions in the skin and liver.

Diagnosis:
• Clinical signs.
• Serology.
• Histopathology, particularly inclusion bodies in epithelial cells of skin or mucous membranes.
 

Kilham’s rat virus

Host species: Rats

Type of agent:
• Parvovirus.
• Other currently recognized parvoviruses of rats include rat parvovirus (RPV) and Toolan’s H-1 virus.

Occurrence: Common

Significance: Infection is persistent.

Epidemiology:
• Transmission is by exposure to urine, feces, nasal secretions and milk; or by contact with contaminated fomites.
• Transplacental transmission.
• Infection is persistent.
• Contaminant of cell lines and transplantable tumors.
• Highly resistant to environmental conditions, hence, persists in the environment for long periods.

Clinical disease:
• Infection usually asymptomatic.
• Fetal and neonatal loss and abnormalities.
• Mortality in athymic infant rats.
• Jaundice and ataxia in young rats.
• Clinical disease with mortality in older rats.

Pathology:
• Necrosis, hemorrhage and infarction in the central nervous system.
• Necrosis, inflammation, fibrosis and nodular hyperplasia in the liver.
• Intranuclear inclusions in cerebellar external germinal cells and various cells of the liver, e.g., hepatocytes, Kupffer cells.

Diagnosis:
• Serology.
• Histopathology, particularly histologic evidence of inclusions in cells.
 

Lymphocytic choriomenigitis virus

Host species: Mice, rats

Type of agent: Arenavirus

Occurrence: Rare

Significance: Transmissible to humans.

Epidemiology:
• Shed in saliva, nasal secretions and urine.
• Transmission is by exposure of mucous membranes and broken skin to urine, saliva and milk, and possibly by ingestion.
• Transovarian and transplactental transmission in mice.
• Highly infectious.
• Contaminant of cell lines and transplantable tumors.
• Humans can also be infected resulting in a flu-like illness with meningeal involvement.
• Hamsters are an amplifying host for the virus and should also be considered a source of infection for humans.

Clinical disease:
• Perinatal (in utero or neonatal) infection – persistent infection with wasting (emaciation, ruffled fur, hunched posture, ascites) at 7-10 months old.
• Adult infection – asymptomatic acute infection.

Pathology:
• Perinatal infection – immune-mediated glomerulonephritis.

Diagnosis: Serology
 

Mouse adenovirus

Host species: Mice, rats

Type of agent: Adenovirus (two strains – MAd-1 [polytropic] and MAd-2 [enterotropic])

Occurrence: Rare

Significance: Not usually a pathogen.

Epidemiology:
• Mad-1: Shed in the urine for prolonged periods.
• Mad-2: Shed in feces for 3 weeks in immunocompetent mice and 6 months in athymic mice.
• Transmission is by direct contact.
• Degree of infectivity unknown.

Clinical disease:
• Asymptomatic in immunocompetent mice and rats.
• Wasting disease in athymic mice.

Pathology:
• Mad-1 – necrotic foci and intranuclear inclusions in myocardium and adrenal glands.
• Mad-2 – intranuclear inclusions in mucosal epithelium of ileum and cecum.

Diagnosis:
• Serology.
• Histopathology, particularly intranuclear inclusions.
 

Mouse hepatitis virus

Host species: Mice

Type of agent: Coronavirus (enterotropic and polytropic [respiratory] strains)

Occurrence: Common

Significance: Important digestive tract pathogen.

Epidemiology:
• Shed in feces and nasopharyngeal exudates.
• Transmission by direct contact, airborne and by fomites.
• Highly infectious.
• Immunodeficient strains of mice may develop persistent infections.
• Contaminant of transplantable tumors.

Clinical disease:
• Infectivity, organotropism and pathogenicity of infection dependent on the strain of virus and strain of mice.
• Asymptomatic in immunocompetent adult mice.
• Diarrhea, poor growth and high mortality in neonatal mice.
• Wasting disease with high mortality in immunodeficient, e.g., athymic mice.

Pathology:
• Enterotropic strains: villus attenuation, enterocytic syncytia and mucosal necrosis in the ileum, cecum and ascending colon.
• Polytropic strains: acute necrosis and syncytia formation in liver, spleen and lymphoid tissues; necrotizing encephalitis with demyelinization and syncytia formation.

Diagnosis:
• PCR assay of fecal pellets and tissues.
• Serology.
• Histopathology.
 

Mouse minute virus

Host species: Mice

Type of agent:
• Parvovirus (two allotropic variants – MMVp and MMVi).
• Another currently recognized parvovirus of mice is mouse parvovirus (MPV).

Occurrence: Common

Significance: Infection may be persistent.

Epidemiology:
• Transmission is primarily by exposure to feces and urine but may also be transmitted by exposure to nasal secretions and by fomites.
• Transplacental transmission.
• Contaminant of cell lines and transplantable tumors.
• Highly resistant to environmental conditions, hence, persists in the environment for long periods.

Clinical disease:
• Infectivity, organotropism and pathogenicity of infection dependent on the strain of virus and strain of mice.
• Infection usually asymptomatic.

Pathology: None reported.

Diagnosis: Serology
 

Mouse parvovirus

Host species: Mice

Type of agent:
• Parvovirus
• Another currently recognized parvovirus of mice is mouse minute virus (MMV).

Occurrence: Common.

Significance: Infection is persistent.

Epidemiology:
• Transmission is most likely by exposure to feces, urine and nasal secretions.
• Infection in mice is persistent.
• Contaminant of cell lines and transplantable tumors.
• Highly resistant to environmental conditions, hence, persists in the environment for long periods.

Clinical disease:
• Infection is asymptomatic, even in neonatal and immunocompromised mice.

Pathology: None reported.

Diagnosis:
• Serology.
• Immunohistochemistry.
 

Pneumonia virus of mice

Host species: Mice, rats

Type of agent: Paramyxovirus (pneumovirus)

Occurrence: More common in rats than mice.

Significance: Not usually a pathogen.

Epidemiology:
• Shed in secretions of the respiratory tract.
• Transmission is by direct contact and aerosol.

Clinical disease:
• Asymptomatic in immunocompetent mice and rats.
• Chronic pneumonia, wasting and mortality in athymic mice.

Pathology:
• Mild necrotizing rhinitis, necrotizing bronchiolitis and non-suppurative interstitial pneumonia.

Diagnosis: Serology
 

Rat coronavirus

Host species: Rats

Type of agent: Coronavirus (two major strains – RCV-P and RCV-SDA).

Occurrence: Common

Significance: Important pathogen of the upper respiratory tract.

Epidemiology:
• Shed in secretions of the respiratory tract and oral cavity.
• Transmission is by direct contact, aerosol and fomites.
• Highly infectious.
• Infection self-limiting.
• Athymic rats develop persistent infections.

Clinical disease:
• Mild conjunctivitis in suckling rats.
• Cervical edema, sneezing, photophobia, conjunctivitis, nasal and ocular discharge, porphyrin staining, exophthalmus, corneal ulceration and keratoconus in rats.
• Lower respiratory tract disease can result with superimposed infections, e.g., Mycoplasma pulmonis.

Pathology:
• Diffuse coagulation necrosis of ducts of the salivary and lacrimal glands.
• Squamous metaplasia of ductal and acinar structures of the salivary and lacrimal glands.
• Patchy necrotizing rhinitis, tracheitis, bronchitis, bronchiolitis and mulifocal pneumonitis.

Diagnosis:
• Clinical signs.
• Histopathology, particularly histologic examination of the Harderian glands and the submaxillary and parotid salivary glands.
• Serology
 

Rat parvovirus

Host species: Rats

Type of agent:
• Parvovirus.
• Other currently recognized parvoviruses of rats include Kilham’s rat virus (KRV) and Toolan’s H-1 virus.

Occurrence: Common

Significance: Infection is persistent.

Epidemiology:
• Virus shed in feces, urine and saliva.
• Transmission is most likely by exposure to feces, urine and nasal secretions; or by contact with contaminated fomites.
• Infection is persistent.
• Contaminant of cell lines and transplantable tumors.
• Highly resistant to environmental conditions, hence, persists in the environment for long periods.

Clinical disease:
• Infection is asymptomatic, even in infant and immunocompromised rats.

Pathology: None reported.

Diagnosis: Serology
 

Reovirus 3

Host species: Mice, rats

Type of agent:
• Reovirus.
• Of the three mammalian reoviruses, serotypes 1, 2 and 3, reovirus 3 is the most pathogenic for rodents.

Occurrence: Uncommon in mice, rare in rats.

Significance: Not usually a pathogen.

Epidemiology:
• Transmission by direct contact.
• Poor infectivity.
• Contaminant of cell lines and transplantable tumors.

Clinical disease:
• Infection usually asymptomatic.
• Stunting, diarrhea, oily coats, abdominal alopecia and jaundice in neonatal mice.

Pathology:
• Enlarged black gall bladders and yellow kidneys.
• Hepatic necrosis with syncytial giant cell formation.

Diagnosis: Serology
 

Rotavirus

Host species: Mice

Type of agent: Reovirus (group A rotavirus)

Occurrence: Not uncommon

Significance: Important digestive tract pathogen.

Epidemiology:
• Virus is shed in the feces.
• Infection is acquired by exposure to feces and contaminated airborne dust.
• Highly infectious.
• Infection self-limiting.

Clinical disease:
• Diarrhea (watery mustard-colored stool), lethargy and distended abdomen in neonatal mice.

Pathology:
• Apical villous enterocytes of small intestine vacuolated and contain pyknotic nuclei.

Diagnosis:
• Clinical signs
• Histopathology
• Serology
 

Sendai virus

Host species: Mice, rats

Type of agent: paramyxovirus (parainfluenza virus type 1)

Occurrence: Uncommon.

Significance: Important respiratory tract pathogen.

Epidemiology:
• Shed in secretions of the respiratory tract.
• Transmission is by direct contact and aerosol.
• Highly infectious.
• Infection self-limiting.
• May be transmissible to humans.

Clinical disease:
• Infection usually asymptomatic.
• Respiratory disease can result with superimposed infections, e.g., Mycoplasma pulmonis, CAR bacillus.

Pathology:
• Pathogenicity dependent on the strain of virus and strain of rodents.
• Necrotizing inflammation of respiratory epithelium.
• Suppurative or necrotizing bronchitis and bronchiolitis.
• Focal interstitial pneumonia.

Diagnosis:
• Serology
• Histopathology
 

Theiler’s murine encephalomyelitis virus

Host species: Mice, rats

Type of agent: Cardiovirus

Occurrence: Not uncommon

Significance: Not usually a pathogen.

Epidemiology:
• Virus is shed in the feces.
• Transmission is fecal-oral.
• Transplacental transmission.
• Poor infectivity.
• Infection self-limiting.
• Contaminant of mouse and rat cell cultures.

Clinical disease:
• Infection is usually asymptomatic.
• Flaccid posterior paralysis in mice.

Pathology:
• Poliomyelitis with necrosis, nonsuppurative meningitis, microgliosis, perivasculitis, neuronophagia of ventral horn cells and demyelination.

Diagnosis: Serology
 

Toolan’s H-1

Host species: Rats

Type of agent:
• Parvovirus.
• Other currently recognized parvoviruses of rats include Kilham’s rat virus (KRV) and rat parvovirus (RPV).

Occurrence: Uncommon

Significance: Infection is persistent.

Epidemiology:
• Transmission is by exposure to urine, feces, nasal secretions and milk.
• Transplacental transmision.
• Infection is persistent.
• Contaminant of cell lines and transplantable tumors.
• Highly resistant to environmental conditions, hence, persists in the environment for long periods.

Clinical disease:
• Infection usually asymptomatic.
• Fetal and neonatal abnormalities.

Pathology: None reported.

Diagnosis: Serology
 

Bacteria

Cilia-associated respiratory bacillus

Host species: Mice, rats

Type of agent: Gram-negative filamentous rod of uncertain classification tentatively placed in a group of bacteria known as “gliding bacteria”.

Occurrence: Not uncommon in rats, rare in mice.

Significance: Important respiratory tract pathogen.

Epidemiology:
• Transmission is primarily by direct contact with respiratory tract secretions.
• Infection is persistent.

Clinical disease:
• Infection usually asymptomatic.
• Chronic respiratory disease in rats, manifested by hunched posture, lethary, rough coat and periocular porphyrin staining, commonly in association with Mycoplasma pulmonis.

Pathology:
• Severe bronchiolectasis, pulmonary abscesses and atelectasis of lung lobes.

Diagnosis:
• Serology
• Silver staining of histologic sections of lungs to detect argyrophilic bacilli adherent to the apical membranes of bronchial respiratory epithelium.
 

Mycoplasma pulmonis

Host species: Mice, rats

Type of agent: Pleomorphic, gram-negative bacterium.

Occurrence: Common in rats, rare in mice.

Significance: Important respiratory tract pathogen.

Epidemiology:
• Shed in secretions of the nares, eyes and genitalia.
• Transmission is by direct contact and aerosol.
• Transplacental transmission (in rats).
• Infection is persistent.
• Contaminant of fertilized eggs, hence may be transmitted during embryo transfer.
• May contaminate transplantable tumor lines.

Clinical disease:
• Infection in young animals usually asymptomatic.
• Acute bronchopneumonia occurs with other pneumotropic infections, e.g., Sendai virus, or extrinsic factors, e.g., high environmental ammonia levels.
• Sneezing, conjunctivitis and otitis media.
• Chronic respiratory disease manifested as “snuffling” in rats and “chattering” in mice; dyspnea, weigh loss, hunched posture, lethargy; and periocular and perinasal porphyrin staining in rats.
• Genital tract infections with reduction in fertility.

Pathology:
• Respiratory tract – damage of airway epithelial and alveolar epithelial cells, mucus secretion; in severe cases, suppurative bronchitis, bronchiectasis, emphysema and abscesses in the lungs.
• Genital tract – in females, resorbed fetuses, suppurative oophoritis and salpingitis or hydosalpingitis, and chronic suppurative endometritis or pyometra; in males, chronic inflammation of the epididymis, vas deferens and urethra.

Diagnosis:
• Serology
• Histopathology
 

References

Jacoby, R.O. and Lindsey, J.R. Health care for research animals is essential and affordable. FASEB Journal 11: 609-614, 1997.

Jacoby, R.O. and Lindsey, J.R. Risks of infection among laboratory rats and mice at major biomedical research institutions. ILAR Journal 39:266-271, 1998.

Society for Laboratory Animal Science. Laboratory Animal Health Monitoring. Laboratory Animals 33(Suppl. 1): S1:39-S1:87, 1999.

Jacoby, R.O., Fox, J.G. and Davisson, M. Biology and Diseases of Mice. In Laboratory Animal Medicine. 2nd Edition, Academic Press, New York. 35-120, 2002.

Kohn, D.F. and Clifford, C.B. Biology and Diseases of Rats. In Laboratory Animal Medicine. 2nd Edition, Academic Press, New York. 121-165, 2002.

Livingston, R.S. and Riley, L.K. Diagnostic testing of mouse and rat colonies for infectious agents. Lab Animal 32: 44-51, 2003.

Baker, D.G. Pathogens of rats and mice. In Natural Pathogens of Laboratory Animals. ASM Press, Washington, D.C. 19-107, 2003.