Farzana Afroze1, Steven Bloom2, Paul Bech2, Tahmeed Ahmed1, Shafiqul Alam Sarker1, John D Clemens1, Farhana Islam1, David Nalin3. 1. International Centre for Diarrheal Disease Research (icddr,b), Dhaka 1212, Bangladesh. 2. North West London Pathology Consortium, Hammersmith Hospital, Imperial College London, Du Cane Road, London W12 0NN, UK. 3. Department of Immunology and Microbial Diseases, Albany Medical College, Albany, NY 12208, USA.
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.
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 humancholera. 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 cholerapatients 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 humancholeragenesis, and inhibitors of intestinal VIP merit testing for potential therapeutic benefits.