S. Sazawal

Enteroaggregative Escherichia coli and Salmonella associated with nondysenteric persistent diarrhea

A hospital-based case-control study including 92 children with diarrhea for longer than 14 days and 92 controls without gastrointestinal symptoms was performed to describe the association between the excretion of enteric pathogens and persistent diarrhea. In patients the most frequently isolated stool pathogens were enteroaggregative Escherichia coli (19.6%), nontyphoidal Salmonella spp. (17.4%), E. coli with diffuse adherence pattern (7.6%), G. lamblia (7.6%) and enterotoxigenic E. coli (5.4%). The excretion rates in patients were significantly greater than in controls only for nontyphoidal Salmonella spp. (P = 0.0006) and enteroaggregative E. coli (P = 0.016).

Impact of massive dose of vitamin A given to preschool children with acute diarrhoea on subsequent respiratory and diarrhoeal morbidity.

Abstract Objective: To assess the impact of vitamin A supplementation on morbidity from acute respiratory tract infections and diarrhoea. Design: Double blind randomised placebo controlled field trial. Setting: An urban slum area in New Delhi, India. Subjects—900 children aged 12-60 months attending a local health facility for acute diarrhoea of less than seven days duration randomly allocated to receive vitamin A 200000 IU or placebo. Main outcome measures: Incidence and prevalence of acute lower respiratory tract infections and diarrhoea during the 90 days after termination of the enrolment diarrhoeal episode measured by twice weekly household surveillance. Results: The incidence (relative risk 1.07; 95% confidence interval 0.92 to 1.26) and average number of days spent with acute lower respiratory tract infections were similar in the vitamin A supplementation and placebo groups. Among children aged 23 months or less there was a significant reduction in the incidence of measles (relative risk 0.06; 95% confidence interval 0.01 to 0.48). The incidence of diarrhoea was also similar (relative risk 0.95; 0.86 to 1.05) in the two groups. There was a 36% reduction in the mean daily prevalence of diarrhoea associated with fever in the vitamin A supplemented children older than 23 months. Conclusions: Results were consistent with a lack of impact on acute lower respiratory tract related mortality after vitamin A supplementation noted in other trials and a possible reduction in the severity of diarrhoea.

Mortality associated with acute watery diarrhea dysentery and persistent diarrhea in rural North India.

Mortality associated with diarrhea was investigated in a longitudinally followed cohort of children under six years of age in rural North India. During the follow‐up, 1663 episodes of diarrhea and 23 diarrhea related deaths were recorded in 1467 children followed up for 20 months. The case fatality rate was 0.56% for acute watery diarrhea, 4.27% for dysentery and 11.94% for non‐dysenteric persistent diarrhea. Most of the episodes lasted less than a week; 5.2% became persistent (duration > 14 days). The case fatality rate was similar in episodes of one and two weeks’duration (0.64% and 0.8%) and increased to 13.95% for persistent episodes. Of the total 86 persistent episodes, 22.1% were dysenteric; the case fatality rate for such dysenteric persistent episodes was 21.1% and for watery persistent diarrhea 11.4%. Diarrheal attack rates were similar among different nutritional groups, but diarrheal case fatality rates progressively increased with increasing severity of malnutrition, these were 24 times higher in children with severe malnutrition (7.48%) compared to those normally nourished (0.31%). With availability and use of oral rehydration therapy, dysentery and persistent diarrhea emerge as major causes of diarrhea related mortality, with underlying malnutrition as a key associated factor.

Association of antecedent malnutrition with persistent diarrhoea: a case-control study.

To determine the effect of nutritional state on persistent diarrhoea a case-control study was carried out on 756 children followed up prospectively for 18 months. Children who developed persistent diarrhoea were compared with population controls and controls with acute diarrhoea. The mean weight for age in the children with persistent diarrhoea (69.9%) was significantly lower than that in the population controls (77.0%) and the diarrhoeal controls (76.2%). Weight for age of less than or equal to 70% was associated with persistent diarrhoea in both case-control analyses (population controls, matched odds ratio 3.25; diarrhoeal controls, matched odds ratio 2.46). The corrected odds (multiple logistic regression) in the two analyses were 3.2 (95% confidence interval 1.3 to 8.1) and 3.4 (1.2 to 9.1). Weight for age of less than or equal to 70% increases the risk of persistent diarrhoea. In an underweight child there is a higher risk of diarrhoea becoming persistent. Prevention of malnutrition and intensive management of acute diarrhoea in malnourished children should help reduce the risk of the diarrhoea persisting.

Efficacy of milk versus yogurt offered as part of a mixed diet in acute noncholera diarrhea among malnourished children

We compared the clinical outcome of acute diarrhea in 96 malnourished boys (aged 4 to 47 months) receiving full-strength milk compared with yogurt offered as part of a mixed diet. All had weight for height less than or equal to 80% of the National Centre for Health Statistics median. They were randomly assigned to receive milk formula (MF; 67 cal/100 ml) or yogurt formula (YF; prepared from the same milk formula) at the rate of 120 ml/kg body weight in seven divided feedings. Stool-reducing substances (> 1%) were detected more frequently in the MF group, and the differences were significant for day 3 of the study (p = 0.04). However, the geometric mean (95% confidence interval) of the total stool weights (gm/kg) during 0 to 72 hours (MF 128.8 [103, 161.4]; YF 110.9 [87, 142.2]) was comparable (p = 0.37) as was the median (range) duration of diarrhea (hours) (MF 45 [4, 183]; YF 52 [7, 173] p = 0.94). The treatment failure rates in the MF (8.2%) and YF (6.3%) groups were also similar (p = 0.67). The children consuming milk had higher median percent weight gain at the end of 72 hours of the study (p = 0.04) and at recovery (p = 0.02). Routine substitution of yogurt as small frequent feedings as an addition for semisolid food to malnourished children with acute diarrhea does not achieve any significant clinical benefit versus milk.

Comparison of a lactose-free cereal-based formula and cow's milk in infants and children with acute gastroenteritis.

Sixty children less than 2 years of age suffering from mild acute gastroenteritis with less than 5% dehydration were randomly assigned to two different isocaloric feeding regimens, viz., a locally prepared milk-free formulation (group A) of rice, lentil, sugar, and coconut oil and a spray dried commercial cows milk formula (group B). There were two treatment failures in group A and one in group B. The postintervention duration of diarrhea (days) in group A (11.0 +/- 10.0) was higher than in group B (7.6 +/- 10.8), but these differences were not significant (p greater than 0.05). The energy intake (kcal/kg/24 h) on postintervention day 4 was 78.7 +/- 31.7 in group A and 101.3 +/- 41.1 in group B (p greater than 0.05). The corresponding values for day 7 were 74.2 +/- 29.1 and 110.0 +/- 41.1, respectively (p less than 0.05). The mean weight gain (g/kg/24 h) between admission and the day of recovery in group A (2.0 +/- 4.2) was significantly lower (p less than 0.05) than in group B (5.8 +/- 7.8). Similar trends in weight gain were observed at days 4 and 7. These findings suggest that a cows milk-based formula is well tolerated by majority of the infants with mild acute gastroenteritis after initial rehydration with ORS. The infants who were fed the milk-free cereal-based diet showed significantly less energy intake and gained weight less rapidly than those who were fed the cows milk-based formula.

Type of milk feeding during acute diarrhoea and the risk of persistent diarrhoea: A case control study

The role of feeding breast milk, unmodified bovine milk or adapted infant formula during acute diarrhoea in protecting against or causing persistence of the episodes was investigated in a population‐based case control study in an urban area of north India. After adjustment for confounding variables, exclusive breast‐feeding was associated with an odds ratio of 0.06 (95% CI 0.002‐2.1), a 16.5 times lower odds in favour of developing persistence of an episode. Infants fed unmodified bovine milk in addition to breast milk had an odds of 2.5 times (95% CI 1.0‐9.9) in favour of developing persistence of acute diarrhoea (p= 0.04). In infants receiving unmodified bovine milk and no breast milk, this odds ratio was 11.1 (95% CI 1.0‐228.8) (p= 0.05). This study indicates that promoting exclusive breastfeeding may reduce the persistence of diarrhoea over and above its effect in decreasing the incidence of acute diarrhoea. In urban areas of the developing countries where working mothers often use milk supplementation beyond the age of three months, our findings suggest that use of adapted spray dried formula may be safer than unmodified bovine milk with respect to the risk of developing persistent diarrhoea.

Quantitation and properties of fecal and upper small intestinal aerobic microflora in infants and young children with persistent diarrhea.

The duodenal juice and fecal aerobic microflora was investigated in 54 patients with persistent diarrhea (age less than or equal to 2 years). The duodenal aspirates yielded increased aerobic bacteria (greater than 10(5) organisms/ml) in 28 (51.9%) of the patients. Established enteric pathogens were isolated from the duodenal aspirates of 12 (22.2%) of the 54 patients, viz., enteroadherent Escherichia coli (EAEC) (5), enterotoxigenic E. coli (ETEC) (3), enteropathogenic E. coli (EPEC) (1), nontyphoidal Salmonella (1), and Giardia lamblia (2). The total aerobic bacterial count was greater than 10(5) in all 12 patients positive for specific pathogens apart from one case in whom E. coli showing diffuse adherence to HEp-2 cells were identified. Among the remaining 42 specific pathogen-negative patients, 19 (45.2%) also had greater than 10(5) aerobic organisms/ml in the small bowel. Eight strains of Klebsiella from four of the patients were negative for enterotoxin production in a rabbit ileal loop assay and for adherence to HEp-2 cells. In contrast, 28/54 (51.9%) of the same patients had known enteric pathogens in their stools, viz., nontyphoidal Salmonella (8 or 14.8%), Shigella (2 or 3.7%), Campylobacter (1 or 1.9%), ETEC (4 or 7.4%), EPEC (2 or 3.7%), EAEC (7 or 13.0%), and G. lamblia and Entameba histolytica (3 or 5.6%). Further search for potential virulence factors among aerobic bacteria colonizing the upper small intestine in persistent diarrhea is warranted.

Efficacy of Massive Dose Oral Gentamicin Therapy in Nonbloody Persistent Diarrhea with Associated Malnutrition

Summary Overgrowth of aerobic and anaerobic bacteria in the upper small intestine is a common finding in persistent diarrhea. We hypothesized that a large dose of broad spectrum, nonabsorbable oral antibiotic would hasten recovery from persistent diarrhea by eradicating aerobic bacterial overgrowth. Sixty-eight patients were randomly assigned to treatment with either oral gentamicin (n = 33) or placebo (n = 35) for a period of 6 days. The two groups were comparable in their clinical features, stool weights, duodenal and fecal microflora, during an initial 24 h observation period before randomization. The proportion of patients recovering within 6 days post-treatment was similar in the antibiotic (45.2%) and placebo (50%) groups. The stool weights in the two groups during 24–72, 72–120, and 120–168 h of the study did not differ significantly. The percent mean weight gain (g) at 168 h post-treatment in the antibiotic (1.0± 5.1) and placebo (1.4± 5.3) groups also did not differ significantly (p = 0.8). A similar proportion of antibiotic- (61.3%) and placebo- (60.7%) treated patients had started to gain weight by the last day of the study. We conclude that oral gentamicin was no more effective than placebo in reducing purge rates, in achieving earlier recovery from diarrhea, and in promoting the earlier onset of weight gain in this study.

Glycine, Glycyl–Glycine and Maltodextrin Based Oral Rehydration Solution Assessment of Efficacy and Safety in Comparison to Standard ORS

ABSTRACT. We evaluated the efficacy and safety of an oral rehydration solution containing glycyl‐glycine, glycine, and maltodextrin (GGG‐ORS), in comparison to the glucose based ORS (standard ORS). The osmolality of the GGG‐ORS (305 mOsm/1) and standard ORS (311 mOsm/1) was similar. Ninety‐two children presenting with acute gastroenteritis and moderate dehydration, aged 3 months to 3 years, were randomly assigned to receive standard ORS or GGG‐ORS. All the patients were successfully rehydrated orally. The two groups were comparable for baseline characteristics including the microbial etiology. Rotavirus (49%, 36%), ETEC (11%, 18%) or a combination of rotavirus and ETEC (15%, 9%) were the main stool pathogens isolated. There was no significant difference in the mean stool output or duration of diarrhoea between the two groups. Patients in the GGG‐ORS group had higher urine output (p<0.01) and weight gain (p<0.05) in the initial 6 hours when feeding was withheld, but no such differences were observed beyond this period. Hypernatremia did not develop in any patient during the study. We conclude that glycine and glycyl‐glycine supplemented oral rehydration solution does not have any therapeutic advantage in the treatment of acute gastroenteritis with moderate dehydration caused predominantly by rotavirus.