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Detection of a vacuolating cytotoxin in stools from children with diarrhea
Abstract:
A cytotoxin inducing vacuolation in HEp-2 cells was detected in 19 (3.1%) of 618 stool specimens from children with diarrhea but in none of 135 from control children. Common enteric pathogens were found in only two (10.5%) of the 19 cytotoxin-positive stool specimens. The vacuoles induced by stool filtrates resembled those induced by the vacuolating toxin (VacA) of Helicobacter pylori. The vacuolating toxin was heat-labile and protease-sensitive, and it had an apparent molecular weight of > 100,000 but was not neutralized by an antiserum to H. pylori VacA. Although proper prospective case-control studies are needed to definitely assess the etiologic association between the new vacuolating cytotoxin and diarrhea, the present study suggests that microorganisms of the gastrointestinal tract produce a Helicobacter-like vacuolating toxin and may be responsible for cases of childhood diarrhea whose etiology is currently considered unknown.
Insights
A novel vacuolating cytotoxin was found in children with diarrhea, suggesting a new cause for unexplained childhood gastrointestinal illness. This discovery points to previously unrecognized gastrointestinal pathogens.
Area of Science:
- Microbiology
- Pediatric Gastroenterology
Background:
- Childhood diarrhea remains a significant health concern with many cases of unknown etiology.
- Enteric pathogens are well-established causes, but a portion of cases remain unexplained.
Purpose of the Study:
- To investigate the presence of a novel vacuolating cytotoxin in stool specimens from children with diarrhea.
- To explore the potential role of this cytotoxin in unexplained childhood diarrhea.
Main Methods:
- Detection of a cytotoxin inducing vacuolation in HEp-2 cells using stool filtrates from children with diarrhea and control groups.
- Characterization of the toxin's properties (heat-lability, protease sensitivity, molecular weight) and comparison to known toxins like Helicobacter pylori VacA.
Main Results:
- A vacuolating cytotoxin was detected in 3.1% of diarrhea cases but none of the controls.
- Common enteric pathogens were identified in only a small fraction of cytotoxin-positive cases.
- The induced vacuoles resembled those from H. pylori VacA, but the toxin was not neutralized by H. pylori VacA antiserum.
Conclusions:
- A novel, heat-labile, and protease-sensitive vacuolating cytotoxin is associated with childhood diarrhea.
- This toxin, distinct from H. pylori VacA, may be produced by gastrointestinal microorganisms and contribute to unexplained childhood diarrhea.
- Further case-control studies are warranted to confirm the etiological role of this newly identified cytotoxin.