Antidiarrheal Effects of l‐Histidine–Supplemented Rice‐Based Oral Rehydration Solution in the Treatment of Male Adults with Severe Cholera in Bangladesh: A Double‐Blind, Randomized Trial
1Clinical Sciences Division, Centre for Health and Population Research, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh; 2Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Texas; 3Cytos Pharmaceuticals/CATO Research, Research Triangle Park, Durham, North Carolina
Background.
Because of the antisecretory potential of l‐histidine in the intestinal tract, its antidiarrheal effects were determined in cholera.
Methods.In a double‐blind trial of 126 adult male patients with cholera, l‐histidine (2.5 g/L) was mixed with a rice‐based oral rehydration solution (ORS) and administered to 62 patients; 64 patients received the same ORS without l‐histidine. All patients received ciprofloxacin at a dosage of 500 mg every 12 h for 72 h. Fluid output (of stool, urine, and vomit) and intake (of ORS, water, and intravenous fluid) were determined every 8 h for 72 h.
Results.Administration of ORS with l‐histidine significantly (
) reduced the frequency of stool output during 32–64 h after initiation of ORS treatment, compared with that in patients given ORS without l‐histidine ([all data are 
] 32–48 h, 
mL/kg vs. 
mL/kg; 40–48 h, 
mL/kg vs. 
mL/kg; and 56–64 h, 
mL/kg vs. 
mL/kg). An overall reduction of 22% in the volume of stool was observed in patients given ORS without l‐histidine. The amount of required unscheduled intravenous fluid was lower in patients given ORS with l‐histidine, compared with that in patients given ORS without l‐histidine (0–24 h, 
mL/kg vs. 
mL/kg [
]; and 24–48 h, 
mL/kg vs. 
mL/kg [
]). Administration of ORS with l‐histidine also significantly reduced (
) the intake of ORS and the duration of illness. No adverse effects were observed in these patients.
Conclusions.l‐histidine reduces the weight of stool and the frequency of stool output in cholera and could be a useful and safe adjunct treatment that will increase the success rate of ORS and antibiotic therapy in cholera.
Received 21 June 2004; accepted 21 October 2004; electronically published 18 March 2005.
Cited by
Online publication date: 1-Feb-2007.
CrossRef
Online publication date: 15-Jan-2006.
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Presented in part: Digestive Diseases Week, American Gastroenterology Association, San Francisco, 19–22 May 2002 (abstract 122:A117).
Financial support: Cytos Pharmaceuticals/CATO Research (grant to the International Centre for Diarrhoeal Disease Research, Bangladesh).