Abstract
Background: Cholera remains a major global health problem, causing high output diarrhea leading to severe dehydration and shock in developing countries. We aimed to determine whether vasoactive intestinal polypeptide (VIP), the mediator of pancreatic cholera syndrome, has a role in the pathophysiology of human cholera. Methods: We conducted a prospective observational study of cholera cases hospitalized with severe dehydration. Plasma and stool water levels of VIP were measured just after admission, after complete rehydration (3–4 h), at 24 h post-rehydration and at discharge after diarrhea ceased. Results: In total, 23 cholera patients were examined between January and August 2018. The geometric mean of stool VIP (sVIP) and plasma VIP (pVIP) on admission were 207.67 and 8.34 pmol/L, respectively. pVIP values were all within the normal range (</= 30 pcmol/L); however, sVIP levels were very high at all timepoints, though less so just after rehydration. In multivariable GEE models, after adjustment for covariates, sVIP levels were significantly associated with duration of hospitalization (p = 0.026), total stool volume (p = 0.023) as well as stool output in the first 24 h (p = 0.013). Conclusions: The data suggest that VIP, which is released by intestinal nerves, may play an important role in human choleragenesis, and inhibitors of intestinal VIP merit testing for potential therapeutic benefits.
Highlights
In 1976, pursuing a possible shared mechanism between cholera and pancreatic cholera syndrome [1,2,3], an abstract described persistent elevated stool vasoactive intestinal polypeptide levels in Bangladeshi cholera patients and in U.S volunteers contracting cholera or enterotoxigenic Escherichia coli diarrhea in vaccine development studies [4]
The geometric means (GM) of stool VIP (sVIP) and plasma VIP (pVIP) on admission were 207.67 and 8.34 pmol/L, respectively (Table 2). pVIP values were all within the normal range (
The findings suggest that human cholera diarrhea may be mediated by heightened intestinal neural production of vasoactive intestinal polypeptide (VIP) and luminal release of VIP, consistent with earlier in vitro and in vivo animal model studies suggesting participation of a neural/hormonal mechanism in pathogenesis
Summary
In 1976, pursuing a possible shared mechanism between cholera and pancreatic cholera syndrome [1,2,3], an abstract described persistent elevated stool vasoactive intestinal polypeptide (sVIP) levels in Bangladeshi cholera patients and in U.S volunteers contracting cholera or enterotoxigenic Escherichia coli diarrhea in vaccine development studies [4]. Cholera patients in shock had elevated plasma VIP (pVIP) levels. These declined to normal levels after correction of shock and dehydration. Intraluminal CT and intra-arterial VIP led to elevated cAMP levels associated with reduced salt and water absorption in villi, but not in crypts, where most secretion into the lumen is believed to originate [9]. This finding might be due to cAMP turnover being more important in crypt cells than cAMP concentration [10]. VIP has other effects possibly associated with intestinal fluid accumulation, such as raising aquaporin three levels after a 3 h delay [17], similar to the delay between CT exposure and onset of fluid accumulation [18]
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