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Oral rehydration solution (ORS) was established as the cornerstone of therapy for dehydration secondary to acute infectious diarrhea approximately 40 years ago. The efficacy of ORS is based on the ability of glucose to stimulate Na and fluid absorption in the small intestine via a cyclic AMP-independent process. Despite the establishment that ORS is the primary reason for the substantial reduction in morbidity and mortality from diarrhea in children in developing countries, the use of ORS has lagged for many reasons. This review highlights efforts to establish a major reformulation of ORS following the demonstration that short-chain fatty acids (SCFA) stimulate colonic Na and fluid absorption by a cyclic AMP-independent mechanism. The addition of high-amylose maize starch (HAMS), a microbially-fermentable (or 'resistant') starch, to ORS results in delivery of non-absorbed carbohydrate to the colon where it is fermented to SCFA. To date, three randomized controlled trials with a HAMS-ORS in south India have demonstrated a substantial decrease in diarrhea duration in both adults and children hospitalized for acute diarrhea. Significant efforts are now underway to establish this dual-action, modified HAMS-hypoosmolar ORS solution as the standard ORS for the treatment of dehydration from acute diarrhea.

Background: Oral rehydration solution (ORS) for treatment of diarrhea relies on enhancement of small intestinal sodium and fluid absorption to correct dehydration. Amylase-resistant starch added to ORS significantly reduced the duration and severity of diarrhea in adults with cholera, presumably by generation of short-chain fatty acids in the colon and enhancement of colonic sodium and fluid absorption. The present study was initiated to determine whether addition of amylase-resistant starch to standard World Health Organization glucose-ORS (G-ORS) would reduce the duration of diarrhea and fecal fluid losses in children with acute diarrhea., Methods: One hundred eighty-three children (6 months to 3 years) with acute watery diarrhea were randomized to receive either standard treatment with G-ORS or G-ORS with additional amylase-resistant starch, HAMS (HAMS-ORS, 50g/L). Stool weight and consistency were monitored serially until development of formed stool or development of treatment failure defined as either the need for unscheduled intravenous fluid therapy or diarrhea longer than 72 hours., Results: Five of the subjects were lost to follow up. In 178 remaining children (87 HAMS-ORS and 91 G-ORS) with evaluable data, time from enrolment to last unformed stool was significantly less in children receiving HAMS-ORS (median, 6.75 hours; 95% confidence interval, 4.27-9.22) than in children treated with G-ORS (12.80 hours, 8.69-16.91) (P = 0.0292). Time to first formed stool was also significantly shorter in children receiving HAMS-ORS (median, 18.25 hours; 95% confidence interval, 13.09-23.41) compared with children receiving G-ORS (median, 21.50 hours; 95% confidence interval, 17.26-25.74) (P = 0.0440). The total amount of ORS consumed was similar in both groups. There was a trend toward lower mean stool weight in first 24 hours (P = 0.0752) as well as total diarrheal stool weight (P = 0.0926) in patients in the HAMS group compared with the G-ORS group., Conclusion: In children with acute diarrhea, the addition of amylase-resistant starch to glucose ORS significantly shortened duration of diarrhea compared with standard treatment.

Faecal lactoferrin, an iron-based glycoprotein found concentrated in secondary granules of neutrophils, may serve as a surrogate marker of inflammation in the intestine. We evaluated the usefulness of faecal lactoferrin as a predictor of infection with invasive enteropathogens in 262 children with diarrhoea. Lactoferrin at a dilution of 1:50 had the highest sensitivity for detection not only of conventionally cultured invasive enteropathogens but also of all other enteropathogens. Neither individual clinical symptoms nor the identification of faecal leucocytes by microscopy significantly predicted isolation of invasive enteropathogens from the faeces of children with diarrhoea. Faecal lactoferrin is a simple test which showed promise in predicting which children with diarrhoea are likely to be infected with invasive pathogens and can be incorporated as a screening test before faecal cultures are undertaken in this population.

Two epidemics of acute, watery diarrhoea in villages in North Arcot district, India, were investigated. The attack rates were 10.03 and 15.53 per 100 population, the median duration was 5 days and enteric pathogens were present in 56.8% and 60.3% of specimens from the two villages, but no predominant pathogen was identified. Examination of stools from a 20% age-stratified random sample of the population of one of the villages after the epidemic found 22.9% of asymptomatic subjects excreted bacterial enteric pathogens. Despite the high background of enteric pathogen carriage, the isolation rates for shigellae, enteropathogenic Escherichia coli and Shiga-toxin producing E. coli were significantly higher (P < 0.001, P < 0.02, P < 0.05) during the epidemic. The epidemics may have been caused by faecal contamination of well water following rain. Point-of-use techniques for water disinfection may be most effective for preventing such outbreaks, but further research into the development of appropriate technology is required.

Improvements in characteristics of solutions used for oral rehydration therapy, to provide significant reductions in amount and duration of diarrhea, are expected to contribute to wider use of these fluids. Recent studies suggest that these may come about from reducing the osmolality of the solution, and by providing short chain fatty acids for better fluid absorption from the colon. This article briefly reviews the physiology of intestinal and colonic absorption in diarrhea, and indicates the further studies that are needed to translate the above advances into universal practice for the treatment of diarrhea.

This study was undertaken to determine the carriage rate of various enteric pathogens in southern Indian patients with HIV infection, both with and without diarrhoea. Stool from 111 consecutive HIV-positive patients (50 without and 61 with diarrhoea) was examined by microscopy and culture. Jejunal biopsy and fluid examination were carried out if diarrhoea persisted, with negative stool examination. Enteric pathogens were detected from stool in 57.4 per cent of diarrhoeal patients compared to 40 per cent of those without diarrhoea (P > 0.05). Jejunal biopsy and fluid examination provided 11 additional diagnoses. Protozoa accounted for 71.8 per cent of all pathogens isolated. Isospora was significantly more common in patients with (11/61) than in those without (2/50) diarrhoea (P < 0.05). Bacterial pathogens were isolated more commonly from patients with diarrhoea (12/61 compared to 2/50, P < 0.05). Isolation rate of pathogens was higher from patients with diarrhoea for more than 2 wk, compared to those with less than 2 wk duration. Remission of diarrhoea either spontaneously or with symptomatic therapy was observed in 22 patients with acute diarrhoea. A high enteric carriage of a number of pathogens was noted in HIV patients without diarrhoea, but I. belli and bacterial enteropathogens were more likely to be associated with diarrhoea.

Background: Short-chain fatty acids (SCFA), produced in the normal colon by bacterial fermentation, are decreased in acute diarrhoea. This may have deleterious effects on epithelial function in the colon., Methods: The ability of several diarrhoeal pathogens to produce SCFA when incubated with starch in vitro was studied. Isolated pathogens were incubated for 24 h with either no added substrate, glucose, or starch under anaerobic conditions, and SCFA were quantitated by gas-liquid chromatography., Results: Unlike the normal colonic flora, the pathogens produced acetate but not propionate or butyrate. D-Lactate was also produced by all the pathogens studied. When the pathogens were incubated in anaerobic medium containing starch, significantly greater amounts of acetate and significantly lesser amounts of lactate were produced., Conclusions: The inability of enteric pathogens to produce butyrate may impair epithelial cell function, whereas production of D-lactate may enhance mucosal damage in diarrhoeal disease. The presence of luminal starch may be helpful in shifting the fermentation profile to a more favourable pattern.

A diarrhoeal epidemic in a village close to Vellore was investigated in January 1996. Faecal samples were obtained from 20 subjects with diarrhoea and from 11 individuals without diarrhoea (controls) and were examined for bacterial, viral and parasitic enteropathogens. Water samples from all sources in the village were analysed. The epidemic affected all age groups (overall attack rate 15%). The mean duration of diarrhoea was 11 days. Individuals who consumed water exclusively from a borewell had a lower relative risk (RR) of disease (0.14, 95% Cl 0.02-1.01) compared to users of two open wells (RR 6.93, Cl 0.99-48.66 and RR 7.81, Cl 1.02-59.79, respectively). No conventional bacterial enteropathogens were isolated from the stool samples. Enteroaggregative Escherichia coli (EAggEC) were identified in the stool of 11 of 20 subjects with diarrhoea, and in 1 of 11 control samples (P = 0.02). All the EAggEC isolates from the patients had identical antibiotic sensitivity patterns and produced a toxin in Ussing chamber studies. Serotyping indicated that all the EAggEC from individuals with diarrhoea belonged to one or other of two serotypes. All water samples had high coliform counts and E. coli were cultured from the two open wells but not from the borewell. The evidence suggests that EAggEC was responsible for this outbreak of diarrhoea. EAggEC should be considered as a possible pathogen in unexplained diarrhoeal outbreaks in developing countries.

The ability of the colonic epithelium to actively absorb sodium against electrochemical gradients confers on it the capacity to dehydrate the faeces. This capacity is of considerable importance in limiting fluid losses in acute diarrhoeal illnesses characterised primarily by small intestinal fluid secretion. Even in these illnesses, colonic absorptive capacity may be altered for various reasons. Loss of colonic absorptive capacity is also responsible for diarrhoea in those illness where the pathology is primarily epithelial cell damage in the large bowel. The present review analyses the information available on this subject from studies in patients with acute diarrhoea, and in experimental animals. It also outlines measures that might possibly restore optimal function of the colonic salvage mechanism in acute diarrhoeal disease.

Faecal concentrations and output of short chain fatty acids (SCFA) were assessed on successive days by gas-liquid chromatography in 24 patients with acute watery diarrhoea. Absorption of water and sodium from the rectum was also measured by a dialysis technique in 17 of these patients and in nine normal subjects in the presence and absence of luminal SCFA. Faecal SCFA concentrations were low on the first day of diarrhoea (mean (SEM) 9.9 (5.8) mmol/kg) and increased to 94.8 (16.4) mmol/kg by the fifth day. Faecal output of SCFA corresponded to these figures. Net water absorption, in the absence of luminal SCFA, was stopped in patients with acute diarrhoea (-59 (81) nl/cm2/min) compared with healthy controls (+322 (63) nl/cm2/min) (p < 0.01). Luminal SCFA restored net water absorption to +184 (67) nl/cm2/min in patients with acute diarrhoea (p < 0.01). Net absorption of sodium decreased in patients with acute diarrhoea in the absence of luminal SCFA, but returned to normal with luminal SCFA. Net secretion of potassium increased in acute diarrhoea, and did not change in the presence of SCFA. Defective absorption from the rectum in acute diarrhoea is reversed by luminal SCFA. The reduction of luminal SCFA in acute diarrhoea treated conventionally may be a factor contributing to colonic dysfunction.

The author discusses the small intestinal bacterial overgrowth identified by some patients with tropical sprue. He says that despite that this overgrowth is associated with an exaggerated ileal break, there is still a need to identify why only some of the patients have such exaggerated ileal hormone response to fat. He emphasizes that it can be presumed that a similar mechanism operates in other patients with fat malabsorption. He also stresses the significance of the study.