What is Shiga toxin-producing Escherichia coli (STEC) and how does it lead to Hemolytic Uremic Syndrome (HUS)?

Understanding STEC and the Pathogenesis of HUS

What is STEC?

Shiga toxin-producing Escherichia coli (STEC) are bacteria that produce toxins structurally and functionally similar to those made by Shigella dysenteriae type 1, causing approximately 100,000 illnesses, 3,000 hospitalizations, and 90 deaths annually in the United States. 1

Key STEC Characteristics

• E. coli O157:H7 is the most common serotype, accounting for an estimated 73,000 cases per year in the United States 1

• Six non-O157 serogroups (O26, O45, O103, O111, O121, and O145) account for the majority of non-O157 STEC infections 1, 2

• STEC produce two main toxin types: Shiga toxin 1 (Stx1), which is neutralized by antibodies against Shiga toxin, and Shiga toxin 2 (Stx2), which is not neutralized by antibodies against Shiga toxin but requires homologous antibodies 1

• The infectious dose is remarkably low, requiring less than 100 organisms for O157 and O111 strains to cause infection 1, 2

Transmission Routes

STEC spreads through multiple pathways 1:

• Consumption of undercooked ground beef
• Unpasteurized juice and raw milk
• Raw produce (lettuce, spinach, alfalfa sprouts)
• Contaminated water
• Direct contact with animals or their environment
• Person-to-person transmission, particularly in child-care settings

How HUS Develops from STEC Infection

Approximately 8% of persons diagnosed with O157 STEC infection develop hemolytic uremic syndrome (HUS), a life-threatening condition characterized by the triad of thrombocytopenia, hemolytic anemia, and renal failure. 1, 2

Pathophysiologic Mechanism

The progression from STEC infection to HUS follows this sequence:

1. Initial infection: STEC causes acute, often bloody diarrhea 1

2. Toxin production and absorption: The bacteria produce Shiga toxins that are absorbed from the gastrointestinal tract into the bloodstream 3

3. Endothelial damage: Shiga toxins bind to receptors on endothelial cells, particularly in the kidneys, causing direct cellular injury and triggering thrombotic microangiopathy 3, 4

4. Systemic manifestations: The resulting microangiopathic process leads to the classic HUS triad 1

Critical Virulence Factors

Whether illness progresses to HUS depends on both strain virulence and host factors. 1

• Stx2-producing strains are more often associated with HUS than strains producing only Stx1 or both Stx1 and Stx2 1, 2

• Non-O157 STEC strains can also lead to HUS, though the virulence varies by serotype 1

High-Risk Populations

Children under 5 years have the highest incidence of STEC infection and the greatest risk for HUS progression, with approximately 15.3% developing HUS compared to 6.3% overall. 2, 5

Additional risk factors include 5:

• Female sex (increased risk of HUS after STEC O157 infection)
• Young age (<5 years)
• Elderly age (≥60 years have highest mortality, though not highest HUS rate)

Clinical Outcomes and Mortality

Death occurs in 0.6% of all patients with STEC O157 infection but rises to 4.6% among those who develop HUS. 5

• Elderly patients (≥60 years) have the highest death rate: 3.1% overall, including 33.3% of those with HUS 5

• Young children with HUS have a 3.0% mortality rate 5

• Long-term sequelae affect 30% of survivors, including proteinuria (15-30%), hypertension (5-15%), chronic kidney disease (9-18%), and end-stage kidney disease (3%) 6

Critical Management Pitfall

Antibiotic therapy in patients with STEC infections might be associated with more severe disease and potentially increased HUS risk, making prompt diagnosis essential to avoid inappropriate treatment. 1, 7

Instead, management should focus on 1, 7:

• Aggressive parenteral volume expansion early in the course of infection to decrease renal damage
• Supportive care with careful fluid and electrolyte management
• Avoidance of antibiotics when STEC is suspected or confirmed

Extrarenal Manifestations

HUS can affect multiple organ systems beyond the kidneys 4:

• Neurological: altered mental status, seizures, stroke, coma
• Gastrointestinal: hemorrhagic colitis, bowel ischemia/necrosis, perforation
• Pancreatic: pancreatitis, acute and chronic insulin-dependent diabetes mellitus
• Cardiac: thrombotic microangiopathy in cardiac microvasculature, troponin elevation
• Musculoskeletal: rhabdomyolysis

Atypical HUS Consideration

STEC infection can also precipitate atypical HUS in patients with underlying complement dysregulation, representing a diagnostic challenge that requires genetic testing and may necessitate anti-complement therapy. 8