Epizootic Diarrhea of Infant Mice (EDIM) – NAVLE Study Guide

Overview and Clinical Importance

Epizootic Diarrhea of Infant Mice (EDIM) is a highly contagious viral infection of neonatal and suckling mice caused by murine rotavirus (Group A rotavirus). The disease primarily affects mice between 0-14 days of age, with peak susceptibility at 4-14 days. Adult mice are asymptomatic carriers that shed virus to susceptible offspring.

While clinical disease is often subclinical in modern SPF colonies, EDIM can cause diarrhea, stunted growth, and mortality in affected litters. Understanding EDIM is important for the NAVLE as it represents a common research animal pathogen and illustrates rotavirus biology.

Etiology and Viral Characteristics

Viral Classification

• Family: Reoviridae
• Genus: Rotavirus (Group A)
• Genome: Double-stranded RNA, segmented (11 segments)
• Morphology: Wheel-shaped virion (Latin: rota = wheel), 70 nm diameter, non-enveloped
• Strains: Multiple strains identified with variable virulence

Environmental Stability

• Highly stable in environment; persists in feces, bedding, and fomites
• Resistant to many disinfectants; susceptible to bleach, formaldehyde, phenolics
• Survives at room temperature for extended periods

Epidemiology and Transmission

Age-Related Susceptibility

Susceptibility to EDIM is HIGHLY age-dependent:

Transmission

• Fecal-Oral Route (Primary): Virus shed in feces; ingested by susceptible neonates
• Direct Contact: Dam to offspring during nursing
• Aerosol: Airborne transmission via contaminated dust particles
• Fomites: Contaminated bedding, cages, equipment, personnel hands
• Vertical Transmission: Asymptomatic adult carriers continuously shed virus to each new litter

Pathogenesis

Step 1: Viral Entry

Virus is ingested via fecal-oral route. It survives gastric acid and reaches the small intestine.

Step 2: Enterocyte Infection

Rotavirus infects and replicates in mature enterocytes at the villous tips of the small intestine (duodenum, jejunum, ileum).

Step 3: Enterocyte Destruction

Infected enterocytes undergo vacuolar degeneration and necrosis. Villous tips blunt and atrophy. Loss of absorptive surface area impairs nutrient and fluid absorption.

Step 4: Malabsorptive Diarrhea

Destruction of enterocytes leads to lactase deficiency and osmotic diarrhea. Undigested lactose and nutrients remain in intestinal lumen, drawing water into the gut. Result: watery, yellow (mustard-colored) diarrhea.

Step 5: Clinical Manifestation

Diarrhea leads to dehydration, electrolyte imbalance, and malnutrition. Pups may develop perianal fecal matting causing constipation and obstruction. Surviving pups exhibit stunted growth due to malabsorption.

Clinical Signs and Presentation

Clinical Presentation

IMPORTANT: Many EDIM infections are SUBCLINICAL, especially in modern SPF facilities. When clinical disease occurs, it typically affects 4-14 day old pups.

Common Clinical Signs:

• Watery Yellow Diarrhea: Mustard-colored, profuse liquid stool
• Perianal Matting: Dried feces around anus and tail base ("megacolon appearance")
• Abdominal Distention: Bloated abdomen from fluid accumulation and gas
• Lethargy: Decreased activity, weakness
• Dehydration: Sunken eyes, poor skin turgor
• Stunted Growth: Survivors are smaller than unaffected littermates ("runts")
• Mortality: Variable; can be high in severe outbreaks, especially if perianal obstruction occurs

Adult Mice:

• NO clinical signs; asymptomatic carriers
• Continuously shed virus in feces
• Transmit infection to each new litter

Pathologic Findings

Gross Pathology

• Intestines: Contain scant, yellow, gaseous (frothy) contents
• Perianal Region: Dried fecal plug causing intestinal distention proximal to obstruction
• Abdomen: Fluid accumulation, distended bowel loops
• Body Condition: Poor body condition, small size compared to age-matched controls

Histopathology

Characteristic Lesions:

• Villous Atrophy: Blunting and shortening of intestinal villi
• Vacuolar Degeneration: Enterocytes at villous tips show cytoplasmic vacuolation (pathognomonic finding)
• Enterocyte Loss: Sloughing of necrotic enterocytes into intestinal lumen
• Crypt Hyperplasia: Compensatory increase in crypt epithelial proliferation
• Minimal Inflammation: Little to no inflammatory infiltrate (unlike bacterial enteritis)

Diagnosis

Diagnostic Approach

Differential Diagnoses

• Mouse Hepatitis Virus (MHV): Can cause diarrhea but typically with respiratory or hepatic signs; histology differs
• Bacterial Enteritis: E. coli, Salmonella cause inflammation and neutrophilic infiltrates (not seen in EDIM)
• Clostridium piliforme (Tyzzer Disease): Affects older mice; hepatic necrosis predominates
• Parasites (Giardia, Coccidia): Identified on fecal examination

Treatment and Management

Treatment

There is NO specific antiviral treatment for EDIM. Management is supportive and focuses on maintaining hydration and nutrition.

Supportive Care:

• Hydration: SC fluids (warmed saline or LRS) for dehydrated pups
• Nutritional Support: Ensure dam is nursing; supplement with hand-feeding if needed
• Perianal Cleaning: Gently remove dried fecal material with warm water to prevent obstruction
• Environmental Warmth: Maintain warm nest temperature (thermoneutral zone)
• Antibiotics: NOT indicated unless secondary bacterial infection suspected

Management in Research Colonies

Test and Remove Strategy:

• Serologic testing to identify seropositive (infected) animals
• Cull seropositive adults (carriers)
• Retain seronegative breeders or repopulate with SPF mice
• Thorough environmental decontamination

Alternatively: Depopulation and Restocking

Complete elimination of all mice followed by facility decontamination and restocking with SPF animals.

Prevention

• Source SPF Mice: Purchase from reputable specific pathogen-free facilities
• Quarantine: Isolate new arrivals for 30 days with serologic testing
• Barrier Housing: HEPA-filtered cages, dedicated equipment, strict PPE protocols
• Sentinel Monitoring: Regular serologic surveillance every 3-6 months
• Sanitation: Frequent cage changes, proper disinfection with bleach or phenolics
• Personnel Training: Hand hygiene, proper handling techniques

Prognosis and Public Health

Prognosis

• Mild Cases: Good; most pups survive with supportive care but may be runted
• Severe Cases: Guarded; mortality can be high if dehydration or obstruction occurs
• Survivors: Develop immunity; no long-term health issues beyond growth stunting

Public Health Considerations

Murine rotavirus (EDIM) is species-specific and does NOT infect humans. No zoonotic risk. However, personnel should maintain good hygiene as a general laboratory practice.