Efficacy and tolerability of racecadotril in the treatment of cholera in adults: a double blind,randomised, controlled clinical trial

BACKGROUND: The enkephalins, endogenous opiate substances, act as neurotransmitters along the entire digestive tract where they elicit intestinal antisecretory activity without affecting intestinal transit time or motility. Racecadotril, through inhibition of enkephalinase, reinforces the physiological activity of endogenous enkephalins and, therefore, shows intestinal antisecretory activity. AIM: We conducted the study to determine the role of racecadotril as an adjunct to the standard treatment of cholera in adults. METHODS: The study was a double blind, randomised, placebo controlled clinical trial involving 110 adult male cholera patients who received either racecadotril or placebo in addition to standard cholera treatment. The major outcome measures (stool output, oral rehydration solution (ORS) intake, requirements for unscheduled intravenous fluid infusion, and duration of diarrhoea) were compared between the groups. RESULTS: Of 110 patients enrolled, 54 received racecadotril and 56 received placebo. Admission clinical characteristics were comparable between the groups. There was no significant difference in (mean (SD)) total stool output (racecadotril v placebo 315 (228) v 280 (156) g/kg), total ORS intake (390 (264) v 369 (240) ml/kg), or duration of diarrhoea (35 (15) v 32 (13) hours) between the groups. Clinical success, defined as resolution of diarrhoea within 72 hours of initiation of study intervention, was similar in both groups (racecadotril v placebo 96% v 89%). The number of patients receiving unscheduled intravenous infusions was not significantly different between the groups (racecadotril v placebo 22% v 14%). No drug related adverse effect was noted. CONCLUSION: The study demonstrated that racecadotril therapy, although found to be safe, does not provide additional benefit in the treatment of severe cholera in adults.     

Continuous oral hydration or with fractionated doses in acute diarrhea-induced dehydration in children

OBJECTIVE: To evaluate the safety and effectiveness of two oral rehydration techniques. MATERIAL AND METHODS: A randomized clinical trial was conducted at the oral rehydration unit of Hospital Infantil de Mexico "Federico Gomez", between September 1998 and June 1999. Forty patients five-year old and younger children, dehydrated due to acute diarrhea, were given oral rehydration solution (ORS) ad libitum (AL group); another forty patients received ORS in fractionated doses (FD group). Clinical characteristics were similar in both groups. Results are presented as means, standard deviations and medians, according the distribution of simple and relative frequencies. RESULTS: The mean stool output in the AL group was 11.0 +/- 7.5 g/kg/h; as compared to 7.1 +/- 7.4 in the FD group (p = 0.03). ORS intake, rehydration time, and mean diuresis values were similar in both groups (p > 0.05). Six patients in the AL group and five in the FD group had high stool output (> 10 g/kg/h), that improved after administration of rice starch solution. One patient in the AL group and two in the FD group had persistent vomiting that improved with gastroclisis. No patient required intravenous rehydration. CONCLUSIONS: These results suggest that ORS administration ad libitum under supervision, is a technique as safe and effective as the fractionated doses technique, for the treatment of dehydrated children due to acute diarrhea.     

A controlled trial comparing the efficacy of rice-based and hypotonic glucose oral rehydration solutions in infants and young children with gastroenteritis

A prospective randomized trial was conducted to compare the efficacy of a rice-based oral rehydration solution (ORS) with glucose ORS in infants and children under 5 years of age with acute diarrhoea and mild to moderate dehydration (< 10%). One hundred children presenting to a large metropolitan teaching hospital were eligible for entry to the study and were randomized to receive rice ORS or glucose ORS. Outcome measures were stool output (SO), duration of illness (DD) and recovery time to introduction of other fluids (RTF) and diet (RTD). Significant differences were found for all outcome measures in favour of the rice ORS group. Mean SO was lower (160 vs 213 mL; P < 0.02), mean DD was reduced (17.3 vs 24.3 h; P = 0.03) and median RTF was decreased (12.7 vs 18.1 h; P < 0.001) in the rice ORS group compared with the glucose ORS group. The median time to introduction of diet and mean length of hospital stay showed similar significant reductions. Our study has shown rice ORS to be an acceptable alternative to glucose ORS in young children and have shown that it is significantly more effective in reducing the course of diarrhoeal illness and the time taken to return to normal drinking and eating habits.     

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

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 (P<.05) 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 means+/-SD] 32-48 h, 11.5+/-6.9 mL/kg vs. 18.8+/-16.0 mL/kg; 40-48 h, 6.7+/-4.4 mL/kg vs. 11.5+/-9.7 mL/kg; and 56-64 h, 6.3+/-5.8 mL/kg vs. 7.8+/-4.1 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, 82.5+/-44.4 mL/kg vs. 158.6+/-72.2 mL/kg [P<.01]; and 24-48 h, 41.6+/-40.4 mL/kg vs. 52.5+/-22.1 mL/kg [P>.05]). Administration of ORS with L-histidine also significantly reduced (P<.05) 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.     

Effects of rice powder salt solution and milk-rice mixture on acute watery diarrhea in young children

A randomized pilot study was carried out to compare the safety and effectiveness of rice powder salt solution (RPSS) in combination with milk-rice mixture (RPSS-MR group, n = 17) with other two regimens, glucose-based oral rehydration solution (ORS) combined with MR (ORS-MR group, n = 17) and ORS combined with formula milk (ORS-milk group, n = 14) in the treatment of acute watery diarrhea with mild to moderate dehydration in 48 boys younger than 2 years. Results showed that in the first 24 hours patients in the RPSS-MR group had significantly smaller amounts of stool weight (32.7 g/kg) than those in the ORS-MR group (67.5 g/kg) and ORS-milk group (59.2 g/kg) (p< 0.05 for both measurements). Patients in the RPSS-MR group also had significantly shorter duration of diarrhea (29.6 hours) than the other two groups (43.8 hours and 49.6 hours, respectively) (p < 0.05 for both measurements). The stool weight and duration of diarrhea between the ORS-MR group and the ORS-milk group were not significantly different. The positive effect of milk rice mixture was not demonstrated in the study due to the significantly more severe diarrhea in the ORS-MR group. The effectiveness of the RPSS-MR is therefore likely due to mainly RPSS.     

Effective treatment of diarrhoeal dehydration with an oral rehydration solution containing citrate

To compare the clinical efficacy of oral rehydration salts (ORS) from effervescent tablets containing citrate with the WHO recommended ORS for the treatment of dehydration due to acute diarrhoea, a randomized clinical trial was carried out in 57 adults and 58 children. These patients had mild or moderate degrees of dehydration and acidosis due to acute watery diarrhoea that was caused by enterotoxigenic Escherichia coli in 43-47% of the cases. Efficacies were compared by measuring oral fluid intake, stool output, gain in body weight, decrease in serum specific gravity and correction of acidosis during treatment. Successful rehydration and maintenance of hydration was achieved in 25 adults and 24 children treated with citrate containing ORS and 25 adults and 24 children treated with WHO ORS. The mean intake of ORS/kg body weight in children receiving WHO ORS was greater (p less than 0.05) and correction of acidosis was faster than the citrate group during the initial 24 h of therapy (p less than 0.05). By 48 h, however, both groups showed satisfactory and comparable intake of ORS and correction of acidosis. Thus ORS from effervescent tablets containing sodium citrate base is effective for management of diarrhoea in both adults and children and is a convenient stable form of ORS for use in the home and for travelers.     

Control study of oral rehydration solution (ORS)/ORS + dioctahedral smectite in hospitalized Thai infants with acute secretory diarrhea.

Dioctahedral smectite, a non systemic antidiarrheal agent, is mucoprotective and absorbs enterotoxins and rotavirus as demonstrated in animal models. Smectite has been successfully used in various countries in children and adults with acute diarrhea. This study was to assess the efficiency of smectite associated with rehydration in infants with acute secretory diarrhea. Sixty-two hospitalized Thai infants, aged 1-24 months, with acute secretory diarrhea were randomly divided into 2 groups receiving (1) oral rehydration solution (ORS) (30 cases), (2) ORS and Smectite (3.6 g/day) (32 cases). Both groups were comparable for age, weight, nutritional status and duration of symptoms before treatment. All 62 infants received lactose free formula and chicken rice soup as the standard diet. Stool frequency, weight change and duration of diarrhea were recorded. The mean duration of diarrhea was 84.7 +/- 48.5 hours in group 1, and 43.3 +/- 25.1 hours in group 2 (p = 0.005). The number of infants with diarrhea was significantly lower in group 2 on Day 1 (p < 0.01) and Day 3 (p = 0.001); furthermore 27% of infants in group 1 and 3% in group 2 had still diarrhea on Day 5. The stool frequency and weight changes were not statistically different in the two groups. No major side effects were observed except two cases of vomiting and hardened stools. It is concluded that (1) Smectite shortens the course of acute secretory diarrhea in Thai infants; (2) smectite may reduce the occurrence of prolonged diarrhea; furthermore (3) in our study dioctahedral smectite was found to be safe in children aged 1 to 24 months.     

Rice-flour-based oral rehydration solution for diarrhoeal diseases

Dehydration and electrolyte imbalance, the main causes of morbidity and mortality in diarrheal diseases, have been treated with glucose-based oral rehydration solutions. However, there have been difficulties due to unavailability, cost and unpalatable solutions. 300 children, from age 4 weeks to 12 years, in Jaffna, Sri Lanka, were treated with rice-flour based oral rehydration solution (ORS). This solution was made by boiling 50g. rice flour with 1 liter water and adding a prepackaged salt packet. 50 grams of rice flour is hydrolyzed to produce 35 grams glucose, 4.35 grams protein and 165 kilocalories. 3 children required hospitalization for intravenous therapy, but the rest responded well to the rice flour based ORS. Diarrhea resolved within 2 to 4 days. The rice flour and salt packet together cost Sri Lanka Rs 1.50 (US$0.06), which is significantly less than the glucose based ORS, which costs Sri Lanks Rs 5.00 (US$0.20). Rice-flour based ORS was found to be an inexpensive, palatable, easily available, and an effective alternative to glucose-based formulas.     

Does oral rehydration therapy alter food consumption and absorption of nutrients in children with cholera?

In order to estimate consumption of food and absorption of nutrients, a metabolic balance study was conducted in 47 children between 1 and 5 years old, suffering from acute cholera. Twenty-two of the children were treated by intravenous solution (IV) only and 25 others by oral rehydration along with intravenous solution (ORS/IV) when necessary. After initial rehydration a nonabsorbable charcoal marker was fed to the patients followed by a typical Bangladeshi home food of known composition offered ad libitum. Appearance of the first marker in the faeces was taken as zero hour (0 h); at 72 h a second marker was fed. Faeces, urine and vomitus were collected up to the appearance of the second marker. Intake of IV fluid, ORS and any other fluid or food were recorded accurately. Samples of faeces, urine and vomitus were analysed for energy, fat and nitrogen. Consumption of nutrients and absorption in both groups were calculated. There was no significant difference in the intake or absorption of energy or carbohydrate between the two groups. The consumption of fat and protein was slightly, but significantly, lower in the ORS/IV group during the acute stage of diarrhoea than in the IV group. Absorption of nitrogen was significantly lower in the ORS/IV group, but absorption of fat was not significantly impaired. Vomiting was significantly higher in the ORS/IV group. The differences in the consumption and absorption of nutrients between the two groups were transient and came to the same level within 2 weeks after recovery.     

Water and solute absorption from hypotonic glucose-electrolyte solutions in human jejunum.

While oral rehydration therapy with glucose-electrolyte solutions is highly effective, the optimal formulation has not yet been defined. Recent clinical studies suggest that stool volume, and thus water losses, may be reduced if glucose is replaced by a polymeric substrate which reduces osmolality. It is possible that the efficacy of glucose monomer based oral rehydration solutions (ORS) will also improve if osmolality is decreased. Using jejunal triple lumen perfusion in healthy adult volunteers net water and solute absorption were studied from three hypotonic solutions with different sodium concentrations (46, 60, 75 mmol/l) but identical glucose concentrations (90 mmol/l), thus allowing osmolality to rise (210, 240, and 270 mOsm/kg, respectively). Results from these solutions (ORS 45:210, ORS 60:240, and ORS 75:270) were compared with the World Health Organisation oral rehydration solution (WHO-ORS). Greatest water absorption was seen with ORS 60:240 (p less than 0.01). Sodium absorption from ORS 60:240 and WHO-ORS was similar and greater than sodium absorption from ORS 45:210 (p less than 0.05). Potassium and glucose absorption were greater from ORS 60:240 than from any of the other hypotonic solutions (p less than 0.05) and were equal to absorption from WHO-ORS). These results in a short segment of healthy human jejunum suggest that hypotonic ORS containing monomeric glucose may increase water absorption.     

Treatment of rotaviral gastroenteritis with Oiwei Baizhu powder

AIM To observe the effects of Qiwei Baizhu Powder ( QWBZP) on rotaviral gastroenteritis in children and in animal models.``METHODS Enrolled patients were divided into two groups, and one group was treated with oral rehydration solution(ORS) and the other treated with oral liquid of QWBZP. Neonate mice were orally infected with 50 μLrotavirus suspension (4 × l0s PFU/mL) and treated with ORS or oral liquid of QWBZP, respectively.``RESULTS Eighty-three cases of rotaviral gastroenteritis treated with QWBZP revealed a better efficacy than that treated with ORS (x2 - 10.8T, P<0.05). The contents of sodium and glucose as well as number of patients with positive human rotavirus antigen in stool in QWBZP group were all less than that in ORS group. In animal models,QWBZP was found effective in treating rotavirus gastroenteritis in neonate NIH mice, as compared with control groups. In QWBZP group, the mortality of infected mice was decreased by 73.3%, the body weight of infected mice was increased, the contents of sodium and glucose as well as number of mice with positive rotavirus antigen in feces were significantly reduced, and the pathological changes such as damage of small intestinal mucosa and villi were also obviously alleviated.``CONCLUSION QWBZP has effects on improving the absorptive function of small intestine, shortening the duration of diarrhea and rotavirus shedding from stool and alleviating the pathological changes of small intestine induced by rotavirus.``     

Treatment of rotaviral gastroenteritis with Qiwei Baizhu powder

AIM To observe the effects of Qiwei Baizhu Powder(QWBZP)on rotaviral gastroenteritis in children and inanimal models.METHODS Enrolled patients were divided into twogroups,and one group was treated with oral rehydrationsolution(ORS)and the other treated with oral liquid ofQWBZP.Neonate mice were orally infected with 50μLrotavirus suspension(4×10~8 PFU/mL)and treated withORS or oral liquid of QWBZP,respectively.RESULTS Eighty-three cases of rotaviral gastroenteritistreated with QWBZP revealed a better efficacy than thattreated with ORS(X~2=10.87,P<0.05).The contents ofsodium and glucose as well as number of patients withpositive human rotavirus antigen in stool in QWBZP groupwere all less than that in ORS group.In animal models,QWBZP was found effective in treating rotavirusgastroenteritis in neonate NIH mice,as compared withcontrol groups.In QWBZP group,the mortality of infectedmice was decreased by 73.3%,the body weight ofinfected mice was increased,the contents of sodium andglucose as well as number of mice with positive rotavirusantigen in feces were significantly reduced,and thepathological changes such as damage of small intestinalmucosa and villi were also obviously alleviated.CONCLUSION QWBZP has effects on improving theabsorptive function of small intestine,shortening theduration of diarrhea and rotavirus shedding from stool andalleviating the pathological changes of small intestineinduced by rotavirus.     

Rice-powder salt solution in the treatment of acute diarrhea in young children.

Dehydration is the most common cause of death in diarrheal patients. Early oral rehydration therapy (ORT) can prevent or reverse dehydration from diarrhea in almost almost all cases. Shortages of oral rehydration salt (ORS) packets in certain areas remain a major problem of the Diarrheal Diseases Control Program of Thailand. To find an effective solution that can be prepared locally, a randomized trial of oral rehydration solutions was conducted. A rice-powder salt solution containing rice-power 30 g/l and salt 3.5 g/l (RPSS) was evaluated in a group (n = 23) of infants and young children aged between 4 months and 5 years with mild or moderate dehydration from acute watery diarrhea, and the results were compared with those who received WHO recommended glucose electrolyte solution (WHO-ORS) (n = 21), and glycine supplemented WHO-ORS (G-ORS) (n = 20). The efficacies of WHO ORS and G-ORS were found to be similar. The RPSS was found to be more effective than WHO-ORS and G-ORS as shown by a significantly lower stool frequency, lower rate of stool output, a significantly shorter duration of diarrhea, and a smaller intake of rehydration fluid. Promotion of the effective rice-salt solution could increase early implementation of ORT in many rural communities.     

New developments in the understanding of cholera

Recent advances in prevention and treatment of cholera have occurred in the areas of vaccine testing, modifications of oral-rehydration solutions (ORS), and antimicrobial treatment. Oral vaccines consisting of killed whole bacterial cells (WC) with and without the B-subunit of cholera toxin (BS) were shown to be effective in large trials in Bangladesh, Peru, and Vietnam. However, the trials did not resolve whether two or three doses of vaccine are required and whether BS adds significantly to the immune protection of WC. Live, attenuated bacterial vaccines that are immunogenic and have been shown protective in human volunteer studies are candidates for future field trials. Rehydration of patients is a lifesaving effort. The best ORS contains rice powder in place of glucose, and solutions with reduced osmolarity (245 mOsm/L, sodium 75 mEq/L) are as effective as standard ORS. Ciprofloxacin in a single dose is effective in adults, and erythromycin or ampicillin in multiple doses is effective in children.     

Evidence of a dominant role for low osmolality in the efficacy of cereal based oral rehydration solutions: studies in a model of secretory diarrhoea.

Clinical trials suggest that including naturally occurring complex carbohydrate in oral rehydration solutions (ORS) in place of glucose increases water absorption and reduces stool volume during acute diarrhoea. The mechanisms for this greater clinical efficacy has not been established. This study examined the ability of two hypotonic rice based ORS, RS-ORS (137 mOsm/kg) and RP-ORS (143 mOsm/kg), and HYPO-ORS (240 mOsm/kg) a glucose equivalent ORS, to effect water absorption by in vivo perfusion of normal and secreting rat small intestine. The results were compared with those for two widely used conventional hypertonic ORS, WHO-ORS (331 mOsm/kg) and UK-ORS (310 mOsm/kg). In the normal intestine, water absorption was similar from WHO-ORS (87.4 (45.1-124.6) microliters/min/g; median and interquartile range) and UK-ORS (57.6 (41.5-87)) but less than from the hypotonic solutions (p < 0.02); water absorption from RS-ORS (181.8 (168.5-193.8)) and RP-ORS (195.7 (179.3-207.9)) was similar but less than from HYPO-ORS (241.3 (230.6-279.7); p < 0.005). In the secreting intestine, all ORS reversed net secretion of fluid to net absorption; the hypotonic solutions, HYPO-ORS (105.2 (95.2-111)), RS-ORS (127.7 (118.3-169.4)) and RP-ORS (133.7 (122.1-174.5)), produced more water absorption (p < 0.005) than the hypertonic solutions WHO-ORS (47.1 (29-75.9)) and UK-ORS (24.9 (18.4-29.4)). The rice based ions promoted most water absorption in secreting intestine (p < 0.007). These data indicate that low osmolality is of primary importance in mediating the increased water absorption from cereal based ORS.     

Gastric emptying of oral rehydration solutions in acute cholera

Gastric emptying of rice powder electrolyte solution and of glucose electrolyte solution was measured by a marker dilution double sampling technique in 14 and in 16 adult patients respectively after intravenous rehydration during an attack of acute cholera. Six patients who received rice powder electrolyte solution and seven who received glucose electrolyte solution re-attended for a repeat study with the same test meal 16 days later, when fully recovered from cholera. No differences in gastric emptying patterns of the two electrolyte solutions were observed, either in the acute or in the recovered patients. Similarly, gastric emptying of both solutions was rapid during acute cholera and comparable to that observed in recovered patients. This study indicates that gastric emptying is not impaired in acute cholera and that the rate of emptying of oral rehydration solutions is adequate to account for their observed clinical efficacy in fast purging patients with acute cholera.     

Single dose tetracycline in cholera.

A randomised clinical trial was carried out to explore the efficacy of single dose tetracycline therapy in cholera. One hundred and eighteen adult patients were assigned to receive either tetracycline in a single 1 g, or a single 2 g dose, or tetracycline 500 mg every six hours four times, or no antibiotics as controls. The means of total liquid stool volumes after treatment were lower in the single 1 g dose group (168.0 +/- 20.9 ml/kg), in single 2 g dose group (229.5 +/- 45.6 ml/kg), and multiple dose group (214 +/- 28.5 ml/kg), than in the control group (499.1 +/- 56.5 ml/kg) (p less than 0.05). Similarly, the means of durations of diarrhoea and intravenous fluid requirements were significantly lower in the single dose and multiple dose tetracycline groups, than in the controls (p less than 0.05). The mean durations of excretion of Vibrio cholerae were significantly shortened from 3.9 +/- 0.2 days in the control group to 1.9 +/- 0.2 days in single 1 g dose, to 2.2 +/- 0.4 days in single 2 g dose and 1.3 +/- 0.1 days in multiple dose groups, respectively (p less than 0.05). Three patients in the single 1 g dose group and two patients in single 2 g dose group had clinical relapses with excretion of V cholerae during the relapses, but this was not significantly more frequent than that in the multiple dose group (p greater than 0.05). These findings suggest that although multiple dose tetracycline therapy remains the best choice, a single dose of either 1 g or 2 g tetracycline appears to be a reasonable alternative for the treatment of cholera as an adjunct to rehydration therapy.     

Oral rehydration therapy: efficacy of sodium citrate equals to sodium bicarbonate for correction of acidosis in diarrhoea.

Forty patients with moderate degrees of dehydration and acidosis because of acute watery diarrhoea were successfully treated randomly with either WHO recommended oral rehydration solution containing 2.5 g sodium bicarbonate or an oral solution containing 2.94 g sodium citrate in place of sodium bicarbonate per litre of oral rehydration rehydration solution. Efficacies were compared by measuring oral fluid intake, stool and vomitus output, change in body weight, hydration status, and rate of correction of acidosis during a period of 48 hours. Seventy five per cent (21 cases) in the citrate group and 83% (19 cases) in the bicarbonate group were successfully rehydrated (p greater than 0.05). There were no significant differences in intake, output, gain in body weight, fall in haematocrit and plasma specific gravity, and correction of acidosis between the two groups of patients within 48 hours after initiation of therapy. The solution with sodium citrate base was as effective as WHO-oral rehydration solution for management of diarrhoea. This study shows the efficacy, safety, and acceptability of citrate containing oral rehydration solution for rehydration and correction of acidosis in diarrhoea.     

Rehydration and maintenance therapy of cholera patients in Jakarta: citrate-based versus bicarbonate-based oral rehydration salt solution

We compared the therapeutic efficacy of a World Health Organization standard bicarbonate-based oral rehydration salt solution (BBORS) with a citrate-based oral rehydration solution (CBORS) in a randomized, double-blind, controlled trial in 130 dehydrated patients with cholera aged three to 82 years. On admission the 70 patients who received CBORS and the 60 who received BBORS were similar except that the serum CO2 content (mmol/liter) was significantly lower in the CBORS group (10.8 +/- 3.6 vs. 12.5 +/- 5.3). The incidence of vomiting postadmission (41% vs. 62%, respectively), the stool output during the first 24 hr (4,252 +/- 3,900 ml vs. 6,025 +/- 4,389 ml, respectively), and the time until the patients' conditions were considered normal (38.9 +/- 14.5 hr vs. 46.3 +/- 22.7 hr, respectively) were all significantly less in the CBORS group. The serum CO2 content increased more rapidly during the first 48 hr in the CBORS group (87% +/- 74% vs. 61% +/- 68% for the BBORS group); 23% of the patients receiving CBORS and 35% of the patients receiving BBORS were considered oral-therapy treatment failures. The results indicate that CBORS was superior to BBORS for rehydration and maintenance therapy of hospitalized cholera patients in Jakarta.     

Treatment of enterotoxigenic and enteropathogenic Escherichia coli-induced diarrhoea in children with bovine immunoglobulin milk concentrate from hyperimmunized cows: a double-blind, placebo-controlled, clinical trial

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) and enteropathogenic Escherichia coli (EPEC) are important causes of diarrhoea in young children and are associated with significant mortality rates. Passive immunization with antibodies from immunized cows has previously been shown to be effective as prophylaxis against E. coli-induced diarrhoea and therapeutically against rotavirus and cryptosporidia-induced diarrhoea. METHODS: We tested the therapeutic efficacy of an oral bovine immunoglobulin milk concentrate (BIC) from cows hyperimmunized with ETEC and EPEC strains, in a randomized, placebo-controlled study in children with E. coli-induced diarrhoea. Eighty-six children between 4-24 months of age attending the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B) with E. coli-induced diarrhoea (63 EPEC/ETEC and 23 with other diarrhoeagenic E. coli) were randomly assigned to receive orally administered BIC (20 g) containing anti-ETEC/EPEC antibodies or a placebo preparation daily for 4 consecutive days. Daily stool output, intake of oral rehydration solution (ORS), stool frequency, and presence of diarrhoeagenic E. coli strains in the stool were monitored for 4 days. RESULTS: Children in the treatment group tolerated the BIC with no side effects. There were no significant differences between the two groups with regard to ORS intake, stool output, frequency of diarrhoea, or clearance of pathogen. Nor was there any significant alteration in the duration of diarrhoea. CONCLUSIONS: In contrast to the prophylactic efficacy of anti-E. coli BIC and the therapeutic efficacy of a similarly prepared anti-rotavirus BIC, antibodies from hyperimmunized cows appear to have no significant therapeutic benefit in the treatment of acute diarrhoea due to EPEC/ETEC.