Escherichia coli Diarrhea

1. Introduction

Escherichia coli (E. coli) is a Gram-negative, facultative anaerobic bacillus belonging to the family Enterobacteriaceae. While most strains are commensals of the human gut, specific pathogenic strains have acquired virulence factors (via plasmids, bacteriophages, or pathogenicity islands) that allow them to cause diarrheal disease. These are collectively termed Diarrheagenic E. coli (DEC). They are a major cause of childhood morbidity and mortality worldwide, particularly in developing countries.

2. Classification

Diarrheagenic E. coli are classified into six major pathotypes based on their specific virulence properties, mechanisms of pathogenicity, and clinical syndromes:

1. Enterotoxigenic E. coli (ETEC): Major cause of traveler's diarrhea and infant diarrhea in developing nations.
2. Enteropathogenic E. coli (EPEC): Associated with acute and persistent diarrhea in infants (<2 years).
3. Shiga toxin-producing E. coli (STEC): Also known as Enterohemorrhagic E. coli (EHEC). Associated with hemorrhagic colitis and Hemolytic Uremic Syndrome (HUS).
4. Enteroinvasive E. coli (EIEC): Closely resembles Shigella; causes dysentery.
5. Enteroaggregative E. coli (EAEC): Associated with persistent diarrhea and growth retardation.
6. Diffusely Adherent E. coli (DAEC): Associated with prolonged watery diarrhea in young children.

3. Pathogenesis

The mechanism of disease varies by pathotype, generally involving colonization, adherence, and toxin production or invasion.

A. Enterotoxigenic E. coli (ETEC)

• Adherence: Colonization occurs via colonization factor antigens (CFAs) or fimbriae that adhere to small intestinal epithelium.
• Toxins: ETEC secretes plasmid-encoded enterotoxins: Heat-labile toxin (LT) (similar to cholera toxin) and/or Heat-stable toxin (ST).
• Mechanism: These toxins increase intracellular cyclic AMP (cAMP) or cyclic GMP (cGMP), leading to active secretion of fluids and electrolytes into the lumen and inhibition of absorption, resulting in secretory diarrhea without mucosal damage.

B. Enteropathogenic E. coli (EPEC)

• Attaching and Effacing (A/E) Lesion: EPEC adheres to enterocytes and destroys microvilli (effacement). This is mediated by the Locus of Enterocyte Effacement (LEE) pathogenicity island.
• Mechanism: EPEC uses a Type III secretion system to inject effector proteins (e.g., Tir) into the host cell. Intimin (a bacterial outer membrane protein) binds to Tir, triggering cytoskeletal rearrangement (actin polymerization) and pedestal formation. This leads to malabsorption and diarrhea.

C. Shiga toxin-producing E. coli (STEC/EHEC)

• Adherence: Like EPEC, STEC produces A/E lesions via intimin and Tir.
• Toxins: The distinguishing feature is the production of Shiga toxins (Stx1 and Stx2).
• Systemic Effects: Stx inhibits protein synthesis in endothelial cells. Stx2 is particularly associated with vascular endothelial injury leading to thrombotic microangiopathy, resulting in Hemolytic Uremic Syndrome (HUS),.

D. Enteroinvasive E. coli (EIEC)

• Invasion: Pathogenesis mimics Shigella. EIEC invades colonic epithelial cells, multiplies intracellularly, and spreads to adjacent cells causing cell death and mucosal ulceration. This process is mediated by a large virulence plasmid (pInv) sharing genes with Shigella.

E. Enteroaggregative E. coli (EAEC)

• Biofilm: Bacteria adhere to the mucosa in a characteristic "stacked-brick" aggregative pattern mediated by Aggregative Adherence Fimbriae (AAF).
• Toxins: Produces toxins like EAST1 and Pet, causing mucosal inflammation and secretory diarrhea,.

4. Clinical Features

The incubation period and clinical presentation vary by pathotype (Table 1).

Table 1: Clinical Syndromes of Diarrheagenic E. coli

5. Diagnosis

Routine stool cultures do not distinguish DEC pathotypes from normal flora. Specific methods are required.

1. Stool Culture:
   • MacConkey Agar: Most E. coli ferment lactose.
   • Sorbitol-MacConkey (SMAC) Agar: Specific for STEC O157:H7, which does not ferment sorbitol (appears colorless), unlike other E. coli.
2. Molecular Testing (PCR): This is the current standard for identification. Multiplex PCR panels can detect specific virulence genes:
   • st/lt (ETEC)
   • stx1/stx2 (STEC)
   • eae (EPEC/STEC)
   • ipaH (EIEC)
   • aggR (EAEC).
3. Toxin Detection: Enzyme Immunoassays (EIA) for Shiga toxins or Rotavirus-like assays.
4. Serotyping: Determination of O and H antigens (e.g., O157:H7). Useful for outbreak investigation but not routine diagnosis.
5. Microscopy: Fecal leukocytes are present in EIEC and occasionally STEC, but absent in ETEC/EPEC.

6. Management

A. Fluid and Electrolyte Therapy

The cornerstone of management is rehydration.

• Assessment: Rapidly assess dehydration status.
• Oral Rehydration Solution (ORS): WHO-ORS is the treatment of choice for mild to moderate dehydration.
• Intravenous Fluids: Ringer's lactate or Normal Saline is indicated for severe dehydration or shock.
• Nutrition: Early refeeding (breastfeeding, formula, solids) prevents malnutrition. Zinc supplementation (20 mg/day for 14 days; 10 mg if <6 months) is recommended.

B. Antimicrobial Therapy

Routine antibiotics are not recommended for uncomplicated E. coli gastroenteritis as most are self-limiting.

• Indications for Antibiotics:
  • Dysenteric presentation (presumed Shigellosis/EIEC).
  • Severe traveler's diarrhea (ETEC).
  • Immunocompromised hosts.
  • Persistent diarrhea (EAEC).
• Choice of Agents: Depends on local resistance patterns. Azithromycin is often the first line for children. Ciprofloxacin or Rifaximin are alternatives for traveler's diarrhea in appropriate age groups,. High resistance exists to Ampicillin and TMP-SMX.

C. Specific Management of STEC (EHEC)

• Antibiotics are CONTRAINDICATED: Antibiotic treatment of STEC infection may induce toxin release from bacteria and increase the risk of developing HUS.
• Antimotility Agents: Agents like loperamide are contraindicated as they may increase systemic toxin absorption and severity of disease.
• Monitoring: Patients with bloody diarrhea should be monitored for signs of HUS (pallor, oliguria, petechiae).

D. Prevention

• Hygiene: Handwashing, proper sewage disposal.
• Food Safety: Thorough cooking of meat (prevention of STEC from hamburger), pasteurization of milk.
• Breastfeeding: Protective against EPEC and other pathogens,.