Equine proliferative enteropathy (EPE) is an emerging enteric disease caused by the obligate intracellular bacterium Lawsonia intracellularis.
Overview and Clinical Importance
Equine proliferative enteropathy (EPE) is an emerging enteric disease caused by the obligate intracellular bacterium Lawsonia intracellularis. This condition primarily affects weanling foals (4-7 months of age) and represents an important cause of protein-losing enteropathy, weight loss, and peripheral edema in young horses. The disease has a characteristic seasonal distribution in North America, with most cases occurring between August and January. EPE is highly board-relevant due to its distinctive clinical presentation and the critical importance of early recognition and treatment for successful outcomes.
| Characteristic |
Description |
| Gram Stain |
Gram-negative |
| Morphology |
Curved, rod-shaped bacillus (1.25-1.75 μm length, 0.25-0.43 μm width) |
| Growth Requirements |
Obligate intracellular; requires dividing cells and microaerophilic atmosphere for in vitro culture |
| Motility |
Single polar flagellum (darting motility when extracellular) |
| Intracellular Location |
Resides freely in the apical cytoplasm of infected enterocytes (not membrane-bound) |
| Environmental Survival |
Survives 1-2 weeks in environment at 5-15°C |
| Culture |
Cannot be cultured on standard media; requires permissive cell lines |
Etiology
The Organism
Lawsonia intracellularis is the sole species in the genus Lawsonia, classified within the Desulfovibrionaceae family based on 16S rDNA phylogenetic analysis.
Organism Characteristics
High-YieldL. intracellularis is an OBLIGATE INTRACELLULAR pathogen - this is critical for understanding why antimicrobials with good intracellular penetration (macrolides, tetracyclines, chloramphenicol) are required for treatment, and why standard culture methods fail.
| Factor |
Details |
| Age Affected |
Primarily weanling foals 4-7 months; range 3-18 months; occasionally young adults |
| Seasonality (North America) |
August through January (peak: November-December) |
| Geographic Distribution |
Worldwide: USA, Canada, Europe, South Africa, Australia, Brazil, Japan |
| Transmission |
Fecal-oral route; ingestion of contaminated feces from infected animals |
| Reservoir Hosts |
Rabbits (cottontail), rodents (mice, rats), dogs, cats, opossums, skunks, deer, pigs |
| Attack Rate |
Approximately 5% clinical disease; additional 5% subclinical infection |
| Incubation Period |
7-14 days |
| Fecal Shedding Duration |
17-27 days (begins 5-17 days before clinical signs develop) |
Epidemiology
NAVLE TipThe classic NAVLE stem for EPE: 'A 6-month-old weanling foal in November with weight loss, diarrhea, and ventral edema.' The combination of AGE (weanling) + SEASON (fall/early winter) + CLINICAL SIGNS (protein-losing enteropathy) should immediately trigger EPE in your differential list.
| Common Signs |
Less Common Signs |
Severe/Complicated Cases |
| Lethargy, depression
Anorexia
Fever (greater than 38.5°C)
Rapid weight loss
Peripheral edema
Diarrhea (variable: soft to watery)
Rough hair coat |
Colic (mild)
Decreased borborygmi
Subclinical disease
Failure to thrive
Normal fecal character |
Necrotizing enteritis
Endotoxemia
Bacteremia
DIC
Rapid deterioration
Pulmonary edema |
Pathogenesis
The unique pathogenesis of EPE involves enterocyte invasion and proliferation rather than typical inflammatory destruction. Understanding this mechanism explains both the clinical presentation and treatment approach.
Mechanism of Infection
- Entry: L. intracellularis enters host enterocytes via receptor-mediated endocytosis; bacteria enter cells individually
- Vacuolar Escape: Bacteria escape the entry vacuole and reside freely in the apical cytoplasm
- Proliferation Induction: Infection inhibits enterocyte differentiation, causing infected crypt cells to continue dividing
- Hyperplasia: Marked adenomatous proliferation of immature crypt epithelial cells lacking microvilli
- Malabsorption: Immature enterocytes lack absorptive capacity, leading to malabsorption and protein loss
- Resolution: Disappearance of intracellular organisms correlates with lesion resolution
Anatomic Distribution of Lesions
- Primary: Ileum (especially near ileal-cecal junction)
- Secondary: Distal jejunum
- Occasional: Cecum and colon
High-YieldINFLAMMATION IS NOT A HALLMARK OF EPE! Unlike most bacterial enteritides, EPE is characterized by enterocyte PROLIFERATION and HYPERPLASIA, not inflammatory infiltrates. This explains why the classic finding is protein-losing enteropathy without marked leukocytosis or inflammatory changes on peritoneal fluid analysis.
| Parameter |
Finding in EPE |
Clinical Significance |
| Total Protein |
Less than 5.0 g/dL (50 g/L) |
MOST CONSISTENT finding; present in virtually all clinical cases |
| Albumin |
Less than 2.0-3.0 g/dL (normal 2.7-4.2 g/dL) |
Hypoalbuminemia causes peripheral edema |
| CBC |
Variable: leukocytosis common; neutropenia in severe cases |
Non-specific; neutropenia suggests necrotizing form |
| Fibrinogen |
Often elevated (hyperfibrinogenemia) |
Indicates inflammation/infection |
| Electrolytes |
Hypocalcemia, hypochloremia, hyponatremia possible |
Related to GI losses |
| Peritoneal Fluid |
Non-inflammatory transudate (if increased) |
Helps rule out peritonitis |
Clinical Signs
Peripheral Edema Distribution
Due to hypoalbuminemia, dependent edema develops in characteristic locations: ventral abdomen, sheath/prepuce, distal limbs, throatlatch region, and head.
| Test |
Advantages |
Limitations |
| Fecal PCR |
High specificity; real-time PCR most sensitive; confirms active shedding |
False negatives if: prior antimicrobials, advanced disease (shedding ceased), improper sample |
| Serology (IPMA) |
Most specific serologic test; detects exposure; useful for herd screening |
False negatives early in disease; cannot distinguish exposed vs. infected; positive titer ≥60 |
| Serology (IFAT/ELISA) |
More readily available than IPMA |
Less specific than IPMA for equine samples |
| Histopathology |
Definitive diagnosis; Warthin-Starry silver stain or IHC visualizes organisms |
Requires biopsy or necropsy; limited sensitivity in autolyzed tissue |
Diagnosis
Diagnosis of EPE is based on clinical presentation, clinicopathological findings, imaging, and confirmatory laboratory testing. A presumptive diagnosis can often be made based on the characteristic presentation.
Clinicopathological Findings
Abdominal Ultrasonography
Key Finding: Thickened small intestinal wall (greater than 5 mm; normal is 3 mm or less)
- Segments of thickened small intestine, particularly ileum
- Increased peritoneal fluid may be present
- NOTE: Normal ultrasound does NOT rule out EPE (sensitivity is variable)
Confirmatory Testing
High-YieldCOMBINE SEROLOGY AND PCR for best diagnostic accuracy! A negative PCR can occur if the animal has stopped shedding or received antimicrobials, while a negative serology can occur early before antibody development. The gold standard histology finding is intracellular curved bacteria in the apical cytoplasm of hyperplastic crypt enterocytes on Warthin-Starry silver stain.
| Differential |
Distinguishing Features |
| Salmonellosis |
More acute, severe diarrhea; leukopenia common; fever; positive fecal culture; affects all ages |
| Rhodococcus equi (enteric) |
Often concurrent pneumonia; abdominal abscesses; 1-4 months age; positive serology/culture |
| Clostridial enterocolitis |
Acute hemorrhagic diarrhea (Type C); younger foals; toxin detection; rapid deterioration |
| Potomac Horse Fever |
Summer/fall near water; adults more common; laminitis risk; PCR/serology positive |
| Intestinal parasitism |
Fecal egg count elevated; responds to deworming; may be concurrent with EPE |
| Rotavirus/Coronavirus |
Younger foals; self-limiting; electron microscopy or PCR positive |
| Gastric ulcers |
May be concurrent; bruxism, salivation; gastroscopy diagnostic |
Differential Diagnosis
| Drug Class |
Drug/Dose |
Duration |
Notes |
| Tetracyclines |
Oxytetracycline: 6.6 mg/kg IV q12h
Doxycycline: 10 mg/kg PO q12h |
OTC 3-7 days IV, then doxy 14-21 days PO |
First-line; excellent intracellular penetration; monitor renal function |
| Macrolides |
Erythromycin: 25 mg/kg PO q6-8h
Clarithromycin: 7.5 mg/kg PO q12h
Azithromycin: 10 mg/kg PO q24h |
3-4 weeks |
Often combined with rifampin; risk of diarrhea and hyperthermia |
| Chloramphenicol |
50 mg/kg PO q6-8h |
2-3 weeks |
Alternative; human health precautions required |
Treatment
Treatment of EPE involves antimicrobial therapy targeting the intracellular organism combined with supportive care. Early treatment is associated with better outcomes.
Antimicrobial Therapy
Supportive Care
- IV Fluid Therapy: Crystalloids for hydration and electrolyte correction
- Plasma Transfusion: For severely hypoproteinemic foals; helps maintain oncotic pressure
- Parenteral Nutrition: May be needed in anorectic foals
- Gastroprotectants: Omeprazole for concurrent/stress ulcers
- Anti-inflammatories: Flunixin meglumine for fever and discomfort (use cautiously)
NAVLE TipThe key to antimicrobial selection is INTRACELLULAR PENETRATION. L. intracellularis lives INSIDE enterocytes, so you need drugs that concentrate within host cells. This is why tetracyclines (lipophilic) and macrolides (concentrate in cells) work, while beta-lactams (which stay extracellular) do NOT.
| Factor |
Outcome Data |
| Survival Rate (treated) |
81-93% with appropriate treatment; up to 97.5% in some studies |
| Time to Clinical Improvement |
Rapid improvement expected with treatment; protein normalization takes weeks |
| Long-term Prognosis |
Excellent; no long-term effects on body condition or blood values |
| Athletic Performance |
Racing earnings not significantly different from unaffected horses |
| Negative Prognostic Indicators |
Necrotizing enteritis, severe leukopenia, DIC, pulmonary edema, delayed treatment |
Prognosis
Prevention and Control
Monitoring Strategies for Endemic Farms
- Daily physical examination of all foals, including rectal temperature
- Bimonthly measurement of total protein/albumin (refractometry or chemistry)
- Regular weight monitoring and calculation of daily weight gain
- Begin monitoring 4 weeks before historical first case detection
- Serological surveillance of herdmates when index case identified
Biosecurity Measures
- Isolate clinically affected or suspected foals
- Rodent and rabbit control programs
- Prevent wildlife access to feed storage and feeding areas
- Proper manure management and pasture hygiene
- Avoid spreading pig manure on horse pastures
Vaccination
A modified-live L. intracellularis vaccine (Enterisol Ileitis) labeled for pigs has been used extra-label in horses via intrarectal administration. Studies show the vaccine induces humoral and cellular immune responses and reduces clinical disease. Protocol: 30 mL intrarectally, two doses 30 days apart. Timing should be synchronized with historical disease occurrence on the farm. NOTE: This is off-label use; check state regulations.
L = Low protein (hypoalbuminemia - HALLMARK finding)
A = Age 4-7 months (weanlings)
W = Weight loss (rapid)
S = Seasonal (August-January, peak Nov-Dec)
O = Obligate intracellular (need special antibiotics)
N = No inflammation (proliferative, not inflammatory)
I = Ileum primarily affected
A = A good prognosis with treatment (greater than 90% survival)