Green banana-supplemented diet in the home management of acute and prolonged diarrhoea in children: a community-based trial in rural Bangladesh.

SUMMARY OBJECTIVE: To determine the effectiveness of green banana in the home management of acute (<7 days) or prolonged (≥ 7 days) diarrhoea at the community level. METHODS: A cluster randomized field trial was conducted among 2968 Bangladeshi rural children 6-36 months old. Wards (villages) were randomly assigned to either a standard care group or a standard care plus green banana group where mothers were instructed to add cooked green banana to the diets of diarrhoeal children. Through a village-based surveillance system, diarrhoeal morbidity data (severity, duration, compliance) were collected for 14 days. Treatment effects were determined by analysing cumulative probability of cure by testing Cox proportional hazards models and relative risk (RR). RESULTS: The cumulative probability of cure was significantly (P < 0.001) different in children receiving GB for both acute [hazard ratio (HR) = 0.63 (95% CI: 0.56-0.67)] and prolonged diarrhoea [HR = 0.38 (95% CI: 0.26-0.59)]. The recovery rates of children with acute diarrhoea receiving GB (vs. control) were significantly more by day 3: 79.9%vs. 53.3% [(RR) = 0.47, 95% CI: 0.41-0.55], (P < 0.001) and day 7: 96.6%vs. 89.1% (RR = 0.32; 0.22-0.46), (P < 0.001). Children with prolonged diarrhoea receiving green banana had significantly higher recovery rates by day 10: 79.8%vs. 51.9% (RR = 0.42; 0.23-0.73), (P < 0.001) and day 14: 93.6%vs. 67.2% (RR = 0.22; 0.08-0.54), (P < 0.001). CONCLUSION: A green banana-supplemented diet hastened recovery of acute and prolonged childhood diarrhoea managed at home in rural Bangladesh.

Green banana and pectin improve small intestinal permeability and reduce fluid loss in Bangladeshi children with persistent diarrhea.

To evaluate the effects of green banana and pectin (nondigestible, dietary sources of colonic shortchain fatty acids [SCFA]) on intestinal permeability, 57 boys (5-12 months) with persistent diarrhea (> or = 14 days) were given a week's treatment with a rice-based diet containing either cooked green banana (n = 19), pectin (n = 17), or rice diet alone (n = 21). Intestinal permeability was assessed before and after treatment by giving a lactulose-mannitol (LM) drink and measuring urinary recovery after 5 hr. Treatment with banana significantly (P < 0.05) reduced lactulose recovery, increased mannitol recovery, and decreased the LM ratio, indicating improvement of permeability. Pectin produced similar results. Permeability changes were associated with a 50% reduction in stool weights which correlated strongly (green banana, r2 = 0.84, pectin, r2 = 0.86) with the LM ratio. Green banana-derived and SCFA-mediated stimulation of colonic as well as small bowel absorption is responsible for their antidiarrheal effects. The antidiarrheal effects of green banana and pectin are mediated by improvement of small intestinal permeability in addition to their known colonotrophic effects.

Arsenic concentrations in rice, vegetables, and fish in Bangladesh: a preliminary study.

Arsenic contaminating groundwater in Bangladesh is one of the largest environmental health hazards in the world. Because of the potential risk to human health through consumption of agricultural produce grown in fields irrigated with arsenic contaminated water, we have determined the level of contamination in 100 samples of crop, vegetables and fresh water fish collected from three different regions in Bangladesh. Arsenic concentrations were determined by hydride generation atomic absorption spectrophotometry. All 11 samples of water and 18 samples of soil exceeded the expected limits of arsenic. No samples of rice grain (Oryza sativa L.) had arsenic concentrations more than the recommended limit of 1.0 mg/kg. However, rice plants, especially the roots had a significantly higher concentration of arsenic (2.4 mg/kg) compared to stem (0.73 mg/kg) and rice grains (0.14 mg/kg). Arsenic contents of vegetables varied; those exceeding the food safety limits included Kachu sak (Colocasia antiquorum) (0.09-3.99 mg/kg, n=9), potatoes (Solanum tuberisum) (0.07-1.36 mg/kg, n=5), and Kalmi sak (Ipomoea reptoms) (0.1-1.53 mg/kg, n=6). Lata fish (Ophicephalus punctatus) did not contain unacceptable levels of arsenic. These results indicate that arsenic contaminates some food items in Bangladesh. Further studies with larger samples are needed to demonstrate the extent of arsenic contamination of food in Bangladesh.

Tetracycline in the treatment of severe cholera due to Vibrio cholerae O139 Bengal.

Vibrio cholerae O139 synonym Bengal, recognized in 1993, is the second member in the list of about 200 serogroups of V. cholerae with epidemic and pandemic potential. Although replacement of fluids and electrolytes remains the cornerstone in the management of cholera, antimicrobial therapy can significantly shorten the duration of diarrhoea, and reduce stool volume and requirements ofrehydration fluids. The role of antimicrobial therapy on the natural course of the disease caused by this relatively new pathogen has not been systematically assessed. A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the efficacy of tetracycline in the treatment of adults with severe cholera due to V. cholerae O139 Bengal. Forty-three adult males with severe cholera were randomly allocated to receive either 500 mg of tetracycline (n=21) or placebo (n=22) for three consecutive days. Demographic and clinical characteristics of these patients on admission were comparable. Tetracycline therapy was associated with significantly reduced total median (inter-quartile range) stool volume [216.48 (90.18-325.22) mL/kg vs 334.25 (215.12-537.64) mL/kg; p=0.001], higher rates of clinical cure (81% vs 27%; p<0.001), and shorter median (inter-quartile range) duration of diarrhoea [32 (24-48) hours vs 80 (48-104) hours; p<0.001]. The mean +/- (SD) requirement of intravenous fluid was not significantly different between the two groups [146.42 +/- 42.12 mL/kg vs 150.44 +/- 27.21 mL/kg; p=0.70]. The median (inter-quartile range) duration of faecal excretion of V. cholerae O139 was significantly shorter in the tetracycline group than the placebo group [1(1-2) day vs 5 (3-6) days; p<0.001]. The results of the study indicate that tetracycline therapy is clinically useful in the treatment of severe cholera due to V. cholerae O139 Bengal.

Clinical studies in persistent diarrhea: dietary management with green banana or pectin in Bangladeshi children.

BACKGROUND & AIMS: Because of the beneficial intestinal effects of dietary fibers, we have evaluated the therapeutic effects of green banana or pectin in children with persistent diarrhea. METHODS: In a double-blind trial, 62 boys, age 5-12 months, were randomly given a rice-based diet containing either 250 g/L of cooked green banana (n = 22) or 4 g/kg pectin (n = 19) or the rice-diet alone (control, n = 21), providing 54 kcal/dL daily for 7 days. Stool weight and consistency, frequency of vomiting and purging, and duration of illness were measured. RESULTS: Most children (60%) had no pathogens isolated from stools, 17% had rotavirus, 5% Vibrio cholerae, 4% Salmonella group B, and 11% had enterotoxigenic Escherichia coli infections. By day 3 posttreatment, significantly (P < 0.001) more children recovered from diarrhea receiving pectin or banana than controls (59%, 55%, and 15%, respectively). By day 4, these proportions correspondingly increased to 82%, 78%, and 23%, respectively, the study diet groups being significantly (P < 0.001) different than controls. Green banana and pectin significantly (P < 0.05) reduced amounts of stool, oral rehydration solution, intravenous fluid, and numbers of vomiting, and diarrheal duration. CONCLUSIONS: Green banana and pectin are useful in the dietary management of persistent diarrhea in hospitalized children and may also be useful to treat children at home.

Increased nitrite and nitrate concentrations in sera and urine of patients with cholera or shigellosis.

OBJECTIVES: Nitric oxide (NO) is an important regulator of cell function. In the intestine, NO regulates blood flow, peristalsis, secretion, and is associated with inflammation and tissue injury. The objectives of this study were to assess and compare the role of NO in cholera, a noninflammatory enteric infection, and in shigellosis, a bacterial inflammation of the colon. METHODS: We determined serum and urinary concentrations of nitrite and nitrate during acute illness and early convalescence in 45 hospitalized children: 24 with cholera and 21 with shigellosis; 18 healthy children served as controls. Nitrite and nitrate concentrations were determined spectrophotometrically using Greiss reaction-dependent enzyme assay. RESULTS: Serum nitrite and nitrate concentrations were significantly (p < 0.05) increased during acute illness compared to the early convalescence in both cholera and shigellosis. Urinary nitrite and nitrate excretions were significantly (p < 0.01) increased during acute disease in shigellosis, but not in cholera. Nitrite concentrations correlated with stool volume (r2 = 0.851) in cholera and with leukocytosis (r2 = 0.923) in shigellosis. CONCLUSIONS: Both cholera and shigellosis are associated with increased production of NO, suggesting its pathophysiologic roles in these diseases.

Vibrio cholerae O139 Bengal: a descriptive study.

A prospective study was conducted to determine the clinical and laboratory characteristics and the clinical course of cholera due to Vibrio cholerae O139 Bengal. The study subjects included 22 adult males with stool culture-proven V. cholerae O139. On enrollment, mean +/- SD concentrations (mmol/L) of serum sodium, potassium, chloride, and bicarbonate were 134 +/- 3, 4 +/- 1, 102 +/- 4, and 13 +/- 4 respectively, and stool sodium, potassium, chloride, and bicarbonate concentrations were 120 +/- 24, 18 +/- 6, 93 +/- 16, and 37 +/- 9 respectively. Seventeen patients (7.8%) had faecal leukocytes ranging from 11 to 50 per high-power field. All V. cholerae O139 isolates (100%) were susceptible to tetracycline, erythromycin, and ciprofloxacin, 92% to furazolidine, and only 5% to trimethoprim-sulphamethaxazole. The median (interquartile) volume of liquid stool during the first 24 hours was 9 (5-12) litre. The median (interquartile) volume of liquid stool and the amounts of intravenous and oral rehydration fluids required during the entire study period were 16 (9-24) litre, 9 (6-18) litre, and 14 (9-20) litre respectively. The median (interquartile) duration of diarrhoea was 80 (48-104) hours. The median (interquartile) duration of excretion of V. cholerae O139 in stool was 5 (3-6) days. Clinical and laboratory features, and case management of cholera due to V. cholerae O139 are very similar to conventional cholera due to V. cholerae O1.

Short-chain fatty acids inhibit fluid and electrolyte loss induced by cholera toxin in proximal colon of rabbit in vivo.

Short-chain fatty acids (SCFA), acetate, propionate, and butyrate, are produced by bacterial fermentation in the colon and stimulate Na+ and Cl- absorption. We have studied the effects of SCFA on fluid and electrolyte absorption during cholera toxin (CT) -induced colonic secretion in rabbit, using a steady-state perfusion technique with marker (PEG) dilution. Perfusion with SCFA significantly (P < 0.01) reduced colonic water secretion. Butyrate reduced water secretion the most (95%), followed by propionate (90%), and acetate (80%). Butyrate significantly (P < 0.001) reduced secretions of Na+ (95.5%), K+ (75.2%), and Cl-(80.7%) ions but not HCO3- ions. Propionate similarly reduced secretion of HCO3-(45.3%). Acetate significantly (P < 0.001) inhibited Na+ (76.4%) and Cl- (75.7%) secretion, but the inhibitions of K+ (23.6%) and HCO3 (28.8%) were not significantly different from the controls. We conclude that SCFA reduce CT-induced water and electrolyte secretion in the rabbit proximal colon, and its potential as an antidiarrheal agent should be further evaluated.

Mortality in severely malnourished children with diarrhoea and use of a standardised management protocol.

BACKGROUND: Severely malnourished children have high mortality rates. Death commonly occurs during the first 48 h after hospital admission, and has been attributed to faulty case-management. We developed a standardised protocol for acute-phase treatment of children with severe malnutrition and diarrhoea, with the aim of reducing mortality. METHODS: We compared severely malnourished children with diarrhoea aged 0-5 years managed by non-protocol conventional treatment, and those treated by our standardised protocol that included slow rehydration with an emphasis on oral rehydration. The standardised-protocol group included children admitted to the ICDDR,B Hospital, Dhaka between Jan 1, 1997, and June 30, 1997, while those admitted between Jan 1, 1996, and June 30, 1996, before the protocol was implemented, were the non-protocol group. FINDINGS: Characteristics on admission of children on standardised protocol (n=334) and non-protocol children (n=293) were similar except that more children on standardised protocol had oedema, acidosis, and Vibrio cholerae isolated from stools. 199 (59.9%) of children on standardised protocol were successfully rehydrated with oral rehydration solution, compared with 85 (29%) in the non-protocol group (p<0.0001). Use of expensive antibiotics was less frequent in children on standardised protocol than in the other group (p<0.0001). Children on standardised protocol had fewer episodes of hypoglycaemia than non-protocol children (15 vs 30, p=0.005). 49 (17%) of children on non-protocol treatment died, compared with 30 (9%) children on standardised protocol (odds ratio for mortality, 0.49, 95% CI 0.3-0.8, p=0.003). INTERPRETATION: Compared with non-protocol management, our standardised protocol resulted in fewer episodes of hypoglycaemia, less need for intravenous fluids, and a 47% reduction in mortality. This standardised protocol should be considered in all children with diarrhoea and severe malnutrition.

PIP: Severely malnourished children have high mortality rates, with death commonly occurring during the first 48 hours after hospital admission. Such mortality has been attributed to faulty case management. The authors therefore developed a standardized protocol for the acute-phase treatment of children with severe malnutrition and diarrhea, with the aim of reducing mortality. This paper compares severely malnourished children with diarrhea aged 0-5 years managed by nonprotocol conventional treatment to those treated by the authors' standardized protocol, which included slow rehydration with an emphasis upon oral rehydration. The characteristics on admission of the 334 children on the standardized protocol and the 293 nonprotocol children were similar, except that more children on the standardized protocol had edema, acidosis, and Vibrio cholerae isolated from stools. 59.9% of the children on the standardized protocol were successfully rehydrated with oral rehydration solution, compared with 29% of those in the nonprotocol group. The use of expensive antibiotics was less frequent in children on the standardized protocol than in the other group, and children on the standardized protocol had fewer episodes of hypoglycemia than nonprotocol children. 17% of nonprotocol and 9% of standardized protocol children died. These findings suggest that the standardized protocol should be considered for all children with diarrhea and severe malnutrition.

Short-chain fatty acids improve clinical, pathologic, and microbiologic features of experimental shigellosis.

Because of the metabolic and antibacterial actions of short-chain fatty acids (SCFA), their roles in modifying the clinicopathologic features of shigellosis were evaluated in a rabbit model of shigellosis. Acute colitis was induced in adult rabbits by intracolonic administration of Shigella flexneri 2a. After 24 h, rabbits were given 6-h colonic infusions of SCFA (acetate, propionate, n-butyrate; 60:30:40 mM) or SCFA-free solution (control); groups of rabbits were killed in batches of 2 or 3 animals at 24, 48, 72, and 96 h after treatment, for histologic and bacteriologic assessment. SCFA significantly reduced fecal blood and mucus and improved clinical symptoms. Histologically, SCFA significantly (P<.01) reduced mucosal congestion, cellular infiltration, and necrotic changes. SCFA also significantly (P<.05) reduced the number of shigellae in the colon. No such improvements occurred in the control group. SCFA may be useful agents in improving clinicopathologic features of shigellosis and should be clinically evaluated.

Food as a vehicle of transmission of cholera.

Cholera has been recognized as a killer disease since earliest time. Since 1817, six pandemics have swept over the world, and the seventh one is in progress. The disease is caused by infection of the small intestine by Vibrio cholerae O1 and O139 and is characterized by massive acute diarrhoea, vomiting, and dehydration: death occurs in severe, untreated cases. Cholera is a highly contagious disease, and is transmitted primarily by ingestion of faecally-contaminated water by susceptible persons. Besides water, foods have also been recognized as an important vehicle for transmission of cholera. Foods are likely to be faecally contaminated during preparation, particularly by infected food handlers in an unhygienic environment. The physicochemical characteristics of foods that support survival and growth of V. cholerae O1 and O139 include high-moisture content, neutral or an alkaline pH, low temperature, high-organic content, and absence of other competing bacteria. Seafoods, including fish, shellfish, crabs, oysters and clams, have all been incriminated in cholera outbreaks in many countries, including the United States and Australia. Contaminated rice, millet gruel, and vegetables have also been implicated in several outbreaks. Other foods, including fruits (except sour fruits), poultry, meat, and dairy products, have the potential of transmitting cholera. To reduce the risk of food-borne transmission of cholera, it is recommended that foods should be prepared, served, and eaten in an hygienic environment, free from faecal contamination. Proper cooking, storing, and re-heating of foods before eating, and hand-washing with safe water before eating and after defaecation are important safety measures for preventing food-borne transmission of cholera.

Gastric acid secretion and enteric infection in Bangladesh.

In developing countries many enteric infections are caused by acid-sensitive pathogens. Failure of the gastric acid barrier to infection has been reported in cholera but gastric acid secretion has been little studied in other enteric infections. We therefore studied basal and stimulated gastric acid in 185 Bangladeshi men admitted to hospital for the treatment of enteric infection. Patients with dysentery (amoebiasis, n = 24 and shigellosis, n = 19) and culture-negative diarrhoea (n = 69) had similar mean gastric acid levels (basal, 3-5 mmol/h; stimulated, 11-17 mmol/h), which remained stable in those patients studied throughout 12 weeks of convalescence. In contrast, patients with secretory diarrhoea caused by cholera or enterotoxigenic Escherichia coli (ETEC) had low gastric acid levels (P < 0.05 compared with other groups) (cholera, n = 34: basal mean 1.8 mmol/h [SD = 2.2], stimulated mean 7.9 mmol/h [SD = 6.4]; ETEC, n = 39: basal mean 2.7 mmol/h [SD = 2.8], stimulated mean 9.4 mmol/h [SD = 7.5]). Cholera patients' gastric acid level rose during convalescence to similar levels to the dysentery patients'. Low gastric acid level was associated with severe disease in patients with cholera (P < 0.02) or ETEC (P < 0.05). Gastric acid level fell with increasing age (P < 0.007) but this did not account for the differences between groups. Gastric acid levels were not associated with Giardia duodenalis or Strongyloides stercoralis co-infection, fever, use of tobacco, or chewing betel nut. Cholera and secretory diarrhoea caused by ETEC may, therefore, partly result from a reduction in gastric acid level which does not occur during dysentery. Factors which impair gastric acid secretion may predispose to diarrhoeal disease in developing countries.

Mechanism and treatment of diarrhoea due to Vibrio cholerae and Escherichia coli: roles of drugs and prostaglandins.

The primary objectives of these studies were to determine the clinical efficacy and safety of the potential antisecretory and antimicrobial drugs in the treatment of diarrhoea due to Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC). The drugs evaluated were chlorpromazine (CPZ), nicotinic acid, berberine, indomethacin, chloroquine, tetracycline, furazolidone, and bioflorin. Additionally, the role of prostaglandins (PGs) in the pathogenesis of cholera diarrhoea has been studied. The drug studies were carried out as placebo-controlled, randomized clinical trials in patients with active diarrhoea due to vibrio cholerae and ETEC. All patients received intravenous (i.v.) or oral rehydration solutions (ORS), but no other medications except the study drugs. Results indicate that CPZ (1 mg/kg or 4 mg/kg), berberine (200 mg), and nicotinic acid (2 g) all reduced stool volumes from 30% to more than 50% in diarrhoeal patients without significant side effects. It appeared that berberine was more effective in ETEC diarrhoea than in cholera. However, chloroquine, indomethacin, clonidine, and bioflorin had no clinically useful effects. Among the antimicrobial agents, a single dose of tetracycline was found to be effective in cholera, because the drug significantly (p < 0.05) reduced the total stool volume from 20.9 +/- 15.9 to 10.5 +/- 8.6 (liters in 6-days, mean +/- SD) compared to furazolidone. Drugs other than antimicrobial and antisecretory agents were also evaluated in the treatment of cholera. It has been shown that treatment with bioflorin, which is a bacterial preparation of lyophilized Streptococcus faecium, did not significantly (p > 0.05) reduce fluid-loss in cholera. Additional studies in animals indicated that treatment with short chain glucose polymers, alone or in combination with a chloride blocking agent, anthracene-9-carboxylic acid (A9C), significantly reduced intestinal secretion in a rat model of secretory diarrhoea. For the first time it was demonstrated that jejunal prostaglandin (PG) E2 concentrations were significantly increased during acute cholera and correlated with the volumes of stool and duration of diarrhoea. Furthermore, it was shown that treatment with indomethacin, a potent inhibitor of PG synthesis, significantly reduced jejunal PGE2 output in adults with acute cholera, in addition to net secretion of water and electrolytes. In summarizing the results, it is concluded that: (1) CPZ, berberine, and nicotinic acid are potential antidiarrhoeal agents, (2) PGs are involved in the pathogenesis of cholera, (3) tetracycline and furazolidone are effective antimicrobial agents in cholera, (4) and glucose short-chain polymers (used with the chloride blocking agent, anthracene-9-carboxylic acid) are better sources of carbohydrates in oral rehydration solutions.

Development of an improved animal model of shigellosis in the adult rabbit by colonic infection with Shigella flexneri 2a.

Rabbits are not usually susceptible to intestinal Shigella infection without extensive pretreatment, including starvation and administration of antimicrobial, antimotility, and toxic agents (carbon tetrachloride). Most animals infected this way die rapidly and do not always develop colonic lesions and signs of dysentery. We describe here a successful experimental infection in the adult rabbit which does not require preparatory treatment and which reproduced characteristic features of human shigellosis. Unstarved, untreated adult rabbits were infected by direct inoculation of virulent Shigella flexneri 2a (10 ml of 10(7) bacteria per ml) into the proximal colon after ligation of the distal cecum (cecal bypass). Within 24 h of infection, most inoculated animals consistently developed clinical dysentery, characterized by liquid stool mixed with mucus and blood, leukocytosis, anorexia, and weight loss. Histologically, there were edema, exudation, superficial ulceration, and polymorphonuclear infiltrations in the lamina propria; crypt abscess formation; focal hemorrhages; and the presence of immunohistochemically stained S. flexneri in the colonic mucosa. Successful bacterial colonization was indicated by the isolation of the challenge strain of S. flexneri 2a from the colonic contents. None of the control rabbits challenged with nonvirulent S. flexneri or without cecal bypass developed dysentery or colitis. We conclude that successful Shigella infection can be induced by direct colonic inoculation with virulent S. flexneri 2a in adult rabbits without starvation and pretreatment. The colitis is dependent on the virulence of the bacteria and on the cecal bypass. This model should be useful in studies of the immunopathogenesis of Shigella infection.

Indomethacin decreases jejunal fluid secretion in addition to luminal release of prostaglandin E2 in patients with acute cholera.

Human cholera is associated with an increased luminal release of prostaglandin E2 (PGE2), but whether inhibition of increased PGE2 synthesis will reduce or control intestinal secretion is uncertain. 'Steady state' perfusions (10 ml/minute) in 12 patients with acute cholera, and repeat perfusions in nine of these patients during the convalescent phase were therefore performed using the triple lumen technique. The proximal jejunum was perfused with isotonic saline containing sodium-sulphobromophthalein as a non-absorbable marker. After intravenous administration of indomethacin (1.0 mg/kg) the jejunal net transfer of fluid and the jejunal flow rate of PGE2 were determined in 30 minute periods for 120 minutes after a 120 minute control period. Indomethacin decreased net fluid secretion (2.1 (0.3-4.2) v 4.5 (2.5-8.4) ml/hour x cm; medians, Q50 ranges, p less than 0.01) and the jejunal flow rate of PGE2 (1.5 (1.2-2.7) v 2.2 (1.4-4.9) ng/minute, p less than 0.05). The results of similar perfusion studies in 22 patients with acute cholera, used to establish the spontaneous time related change in fluid secretion, showed no significant change in net fluid transfer (3.5 (2.2-6.2) to 3.5 (2.6-11.6) ml/hour x cm, p greater than 0.25) over 240 minutes. These data provide further evidence in favour of the hypothesis that prostaglandins have a role in the cholera toxin induced intestinal fluid secretion in man.