Can Enterotoxigenic Escherichia coli (E. coli) cause persistently elevated calprotectin levels 10 months after the infection has been cleared?

Enteraggregative E. coli and Persistent Calprotectin Elevation

Enteraggregative E. coli (EAEC) infection should not cause persistently elevated calprotectin 10 months after clearance, as fecal calprotectin elevations from acute bacterial gastroenteritis typically normalize within weeks of infection resolution.

Understanding Calprotectin in Infectious Gastroenteritis

Fecal calprotectin is a neutrophil-derived protein that serves as a marker of intestinal inflammation 1, 2. During acute bacterial infections, including those caused by enteric E. coli pathogens, calprotectin levels become markedly elevated:

• Bacterial gastroenteritis causes significant calprotectin elevation during the acute phase, with median levels reaching 1610-1870 mg/L in children with bacterial infections 3, 4
• Bacterial infections produce higher calprotectin than viral gastroenteritis (median 689-765 μg/g for Salmonella/Campylobacter vs 87-95 μg/g for rotavirus/norovirus) 3
• Calprotectin correlates with disease severity during the acute infection phase and decreases as clinical symptoms resolve 3

Expected Timeline for Normalization

The critical point is that calprotectin elevation reflects active neutrophilic inflammation 1, 2. Once the infectious trigger is cleared and mucosal inflammation resolves, calprotectin levels should normalize. The evidence does not support persistent elevation 10 months post-infection from EAEC alone.

Alternative Explanations for Persistent Elevation

If calprotectin remains elevated 10 months after documented infection clearance, you must consider:

Inflammatory Bowel Disease (IBD)

• Persistently elevated calprotectin (>150 mg/g) in asymptomatic patients predicts disease relapse with a 4.4-fold increased risk in ulcerative colitis 5, 6
• The infection may have unmasked underlying IBD or triggered post-infectious IBD 5
• Calprotectin >150 mg/g warrants endoscopic evaluation to assess for chronic inflammatory conditions 5

Other Inflammatory Conditions

• Upper gastrointestinal inflammation (gastritis, peptic disease) 7
• Microscopic colitis or other chronic inflammatory conditions 1
• Colorectal neoplasia 1

False Positive Considerations

• In patients with normal colonoscopy, elevated calprotectin (>50 μg/g) was not associated with increased risk of significant GI disease over 3-year follow-up 7
• False positive rates are substantial: 18-26% in asymptomatic patients depending on cutoff used 5

Clinical Approach

For persistent calprotectin elevation 10 months post-infection:

1. Repeat calprotectin measurement to confirm persistent elevation (not transient) 5
2. If calprotectin >150 mg/g on repeat testing, proceed with endoscopic evaluation to assess for chronic inflammatory conditions 5
3. Consider upper endoscopy if colonoscopy is normal, as upper GI inflammation can elevate calprotectin 7
4. Rule out ongoing infection with stool cultures and microscopy, though this is unlikely 10 months out 3, 4

Key Caveat

Do not attribute persistent calprotectin elevation to a cleared infection from 10 months prior. The half-life of mucosal inflammation from acute bacterial gastroenteritis is measured in days to weeks, not months 3, 4. Persistent elevation indicates either ongoing inflammation from another cause or represents a false positive requiring endoscopic clarification 5, 7.