WITHDRAWN: Rice-based oral rehydration solution for treating diarrhoea.

BACKGROUND: Oral rehydration therapy is used to treat dehydration caused by diarrhoea. However the rehydration solution does not reduce stool loss or length of illness. A solution able to do this may lessen the use of ineffective diarrhoea treatments as well as improve morbidity and mortality related to diarrhoea. OBJECTIVES: The objective of this review was to assess the effects of rice-based oral rehydration salts solution compared with glucose-based oral rehydration salts solution on reduction of stool output and duration of diarrhoea in patients with acute watery diarrhoea. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase, Lilacs and the reference lists of relevant articles. We also contacted researchers in the field. SELECTION CRITERIA: Randomized trials comparing standard World Health Organization oral rehydration solution with an experimental oral rehydration salts solution in which glucose (20 grams per litre) was replaced by 50-80 grams per litre of rice powder, with the electrolytes remaining unchanged. DATA COLLECTION AND ANALYSIS: Data were extracted independently by a statistician and a clinician. MAIN RESULTS: Twenty-two trials were included. Concealment of allocation was adequate in 15 of these trials. Irrespective of age, people with cholera who were given rice oral rehydration salts solution had substantially lower rates of stool loss than those given oral rehydration salts solution in the first 24 hours. Mean stool outputs in the first 24 hours were lower by 67 millilitres/kg of body weight (weighted mean difference -67.40, 95% confidence interval -94.26 to -41.53) in children, and by 51 millilitres/kg of body weight (weighted mean difference -51.07, 95% confidence interval -65.87 to -36.27) in adults. The rate of stool loss in infants and children with acute non-cholera diarrhoea was reduced by only four millilitres/kg of body weight (weighted mean difference -4.29, 95% confidence interval -9.36 to 0.78). AUTHORS' CONCLUSIONS: Rice-based oral rehydration appears to be effective in reducing stool output in people with cholera. This effect was not apparent in infants and children with non-cholera diarrhoea.

Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial.

BACKGROUND: Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children. METHODS: We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause admissions. Analyses were per protocol and intention to treat. FINDINGS: 529 children assigned vaccine and 568 allocated placebo were not included in the per-protocol analysis. Results of per-protocol and intention-to-treat analyses were similar. By per-protocol analysis, 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo. Pneumococcal vaccine efficacy was 37% (95% CI 27-45) against first episode of radiological pneumonia. First episodes of clinical pneumonia were reduced overall by 7% (95% CI 1-12). Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. We also found an efficacy of 16% (3-28) against mortality. 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo. INTERPRETATION: In this rural African setting, pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease, and can substantially reduce admissions and improve child survival. Pneumococcal conjugate vaccines should be made available to African infants.

Quality of hospital care for seriously ill children in less-developed countries.

BACKGROUND: Improving the quality of care for sick children referred to hospitals in less-developed countries may lead to better outcomes, including reduced mortality. Data are lacking, however, on the quality of priority screening (triage), emergency care, diagnosis, and inpatient treatment in these hospitals, and on aspects of these potential targets that would benefit most from interventions leading to improved health outcomes. METHODS: We did a qualitative study in 13 district hospitals and eight teaching hospitals in seven less-developed countries. Experienced paediatricians used a structured survey instrument to assess initial triage, emergency and inpatient care, staff knowledge and practices, and hospital support services. FINDINGS: Overall quality of care differed between countries and among hospitals and was generally better in teaching hospitals. 14 of 21 hospitals lacked an adequate system for triage. Initial patient assessment was often inadequate and treatment delayed. Most emergency treatment areas were poorly organised and lacked essential supplies; families were routinely required to buy emergency drugs before they could be given. Adverse factors in case management, including inadequate assessment, inappropriate treatment, and inadequate monitoring occurred in 76% of inpatient children. Most doctors in district hospitals, and nurses and medical assistants in teaching and district hospitals, had inadequate knowledge and reported practice for managing important childhood illnesses. INTERPRETATION: Strengthening care for sick children referred to hospital should focus on achievable objectives with the greatest potential benefit for health outcome. Possible targets for improvement include initial triage, emergency care, assessment, inpatient treatment, and monitoring. Priority targets for individual hospitals may be determined by assessing each hospital.

Rice-based oral rehydration solution for treating diarrhoea.

BACKGROUND: Oral rehydration therapy is used to treat dehydration caused by diarrhoea. However the rehydration solution does not reduce stool loss or length of illness. A solution able to do this may lessen the use of ineffective diarrhoea treatments as well as improve morbidity and mortality related to diarrhoea. OBJECTIVES: The objective of this review was to assess the effects of rice-based oral rehydration salts solution compared with glucose-based oral rehydration salts solution on reduction of stool output and duration of diarrhoea in patients with acute watery diarrhoea. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase, Lilacs and the reference lists of relevant articles. We also contacted researchers in the field. SELECTION CRITERIA: Randomized trials comparing standard World Health Organization oral rehydration solution with an experimental oral rehydration salts solution in which glucose (20 grams per litre) was replaced by 50-80 grams per litre of rice powder, with the electrolytes remaining unchanged. DATA COLLECTION AND ANALYSIS: Data were extracted independently by a statistician and a clinician. MAIN RESULTS: Twenty-two trials were included. Concealment of allocation was adequate in 15 of these trials. Irrespective of age, people with cholera who were given rice oral rehydration salts solution had substantially lower rates of stool loss than those given oral rehydration salts solution in the first 24 hours. Mean stool outputs in the first 24 hours were lower by 67 millilitres/kg of body weight (weighted mean difference -67.4, 95% confidence interval -94.3 to -41.0) in children, and by 51 millilitres/kg of body weight (weighted mean difference -51.1, 95% confidence interval -65.9 to -36.3) in adults. The rate of stool loss in infants and children with acute non-cholera diarrhoea was reduced by only four millilitres/kg of body weight (weighted mean difference -4.3, 95% confidence interval -9.3 to 0.8). REVIEWER'S CONCLUSIONS: Rice-based oral rehydration appears to be effective in reducing stool output in people with cholera. This effect was not apparent in infants and children with non-cholera diarrhoea.

Efficacy of standard glucose-based and reduced-osmolarity maltodextrin-based oral rehydration solutions: effect of sugar malabsorption.

Previously we reported that standard oral rehydration salts (ORS) solution is not as effective as a reduced-osmolarity glucose-based ORS for the treatment of children with acute noncholera diarrhoea: with standard ORS the diarrhoea lasts longer, stool output is greater, serum sodium is higher, and there is more need for supplemental intravenous infusion. We studied a reduced-osmolarity maltodextrin (MD)-based ORS to determine whether it had similar benefits, and also the effect of sugar malabsorption on the efficacy of standard and MD-based ORS. A total of 90 boys aged 3-24 months with acute noncholera diarrhoea and moderate dehydration were randomly assigned to either standard ORS (glucose 20 g/l, osmolarity 311 mmol/l) or MD-ORS (MD 50 g/l, osmolarity 227 mmol/l). There were no differences in treatment results. Some 46% of subjects had a high total stool output (> 300 g/kg), which was unrelated to the type of ORS given. High stool output was significantly associated with a longer duration of diarrhoea (33 vs. 15 hours; P < 0.001), a persistently elevated serum sodium (149 vs. 144 mmol/l at 24 h; P < 0.02), the need for intravenous infusion (11/41 vs. 0/48; P < 0.002), and an increase in faecal reducing substances (10.8 vs. 3.4 g/l at 24 h; P < 0.001). We conclude that some children given standard ORS develop osmotic diarrhoea owing to the combined effect of transient sugar malabsorption and slight hypertonicity of the ORS. Earlier studies show that this adverse outcome can largely be avoided when extra water is given in reduced-osmolarity glucose-based ORS. Reduced osmolarity has no benefit, however, when glucose is replaced by maltodextrin, probably because the sugars released by hydrolysis of MD, when malabsorbed, raise the intraluminal osmolarity to equal or exceed that of standard ORS. Thus, reduced-osmolarity glucose-based ORS is superior to both standard ORS and reduced-osmolarity solutions based on maltodextrin and probably other complex carbohydrates. Studies are in progress to define the optimal formulation of reduced-osmolarity glucose-based ORS.

PIP: At the Diarrhoeal Disease Research and Rehydration Centre of Bab El-Sha'reya Hospital in Cairo, Egypt, clinical researchers randomly assigned 90 fully weaned boys aged 3-24 months with non-cholera diarrhea and signs of moderate dehydration to either the treatment group receiving the standard glucose-based oral rehydration solution (ORS) or the group receiving a reduced-osmolarity ORS with minimally hydrolyzed maltodextrins (MD) (50 g/l) in place of glucose (20 g/l). They wanted to determine whether the reduced-osmolarity, MD-based ORS yielded similar benefits as the glucose-based ORS and to examine the effect of sugar malabsorption on the efficacy of both solutions. The osmolarity of the MD-based ORS was 227 mmol/l compared to 311 mmol/l for the standard ORS. There were no significant differences in the clinical outcomes (duration of diarrhea, stool output, ORS intake, serum sodium level, and weight gain at discharge) for each treatment group. High stool output had a significant positive association with longer duration of diarrhea (33 vs. 15 hours for low stool output; p 0.01), a persistently elevated serum sodium concentration (149 vs. 144 mmol/l for low stool output; p 0.02), the need for intravenous infusion (11/41 vs. 0/48 for low stool output; p 0.002), and an increase in substances that reduce feces (10.8 vs. 3.4 g/l for low stool output; p 0.001). Based on these findings, the researchers hypothesized that, like the standard ORS, the reduced osmolarity ORS, in which glucose is replaced with MD, also caused sugar malabsorption. The sugar malabsorption, in turn, increased the effective intraluminal osmolarity to equal or exceed that of the standard ORS. Both sugar malabsorption and intraluminal hypertonicity were responsible for a net flow of water from extracellular fluid into the gut, an increased serum sodium concentration, increased thirst leading to greater intake of ORS, ORS treatment failure, an increase in stool output, and an increase in duration of diarrhea. In conclusion, reduced-osmolarity, glucose-based ORS is superior to the standard glucose-based ORS and reduced-osmolarity, MD-based ORS.

Is a low-osmolarity ORS solution more efficacious than standard WHO ORS solution?

The clinical efficacy of a diluted oral rehydration salts (ORS) solution was compared in a pilot study with that of intravenous (i.v.) therapy and of standard World Health Organization (WHO)/United Nations Childrens Fund (UNICEF) ORS solution in children with acute diarrhea. Sixty-one boys aged 3 to 24 months, admitted to hospital with acute diarrhea and signs of dehydration, were randomly assigned to groups receiving standard ORS solution, diluted ORS solution, or i.v. therapy. In children treated with standard ORS solution and small amounts of plain water, the total fluid intake was 25-39% greater, the stool output was 58-77% greater (p < 0.01), and the duration of diarrhea was 30-55% greater than in the other treatment groups. Intake of plain water, taken separately or added to the ORS solution, was greater in children given diluted ORS solution (73 +/- 23 ml/kg) than in those given standard ORS solution (21 +/- 32 ml/kg) (p < 0.001). The mean serum sodium concentration increased by 2.2 mEq/L in children given standard ORS solution, whereas it decreased by 2.9 mEq/L in those given diluted ORS solution. This study shows that some children develop worsening diarrhea and increasing serum sodium concentrations when treated with standard ORS solution and given only small amounts of plain water. This is probably caused by the slight hypertonicity of standard ORS solution combined with transient partial glucose malabsorption. This can be avoided if water, breast milk, or another low-solute drink is given liberally during maintenance therapy with ORS solution, as recommended by the WHO.

Clinical trials of improved oral rehydration salt formulations: a review.

Reviewed are all the published clinical trials of glycine-based oral rehydration salts (ORS), L-alanine-based ORS, L-glutamine-based ORS, maltodextrin-based ORS, and rice-based ORS, as well as the results of several recently completed, but unpublished, studies of these formulations that were supported by WHO. All experimental ORS formulations contained the same concentrations of salts as citrate-based WHO-ORS; all trials were randomized comparisons with WHO-ORS, and all except those with rice-based ORS were double-blind studies. The rate of stool loss and, less frequently, the duration of diarrhoea were used as indicators of clinical performance to compare ORS formulations. The following conclusions were reached concerning the efficacy and use of modified ORS formulations. Rice-based ORS (50 g/l) is superior to WHO-ORS for patients with cholera, and for such patients it can be recommended in any situation where its preparation and use are practical. Rice-based (50 g/l) and WHO-ORS solutions are equally effective for treating children with acute non-cholera diarrhoea, when feeding is resumed promptly following initial rehydration, as has been consistently recommended by WHO. Since rice-based ORS is not superior to WHO-ORS for such children, there is no apparent reason to advise a change from glucose to pre-cooked rice in the recommended formulation for WHO-ORS. Maltodextrin-based ORS formulations (50 g/l) and WHO-ORS appear to be equally effective for treating children with acute non-cholera diarrhoea; there is no reason to advise a change from glucose to maltodextrin in the recommended formulation for WHO-ORS. Amino-acid-containing ORS formulations are not recommended for either non-cholera or cholera diarrhoea, since they are more costly and have no clinical advantage over WHO-ORS for children with acute non-cholera diarrhoea or over rice-based ORS for persons with cholera.

Management of acute diarrhea in children: lessons learned.

PIP: Each year diarrheal disease causes an estimated 3.2 million deaths worldwide in children under 5 years of age. Reported attack rates in developing countries range from 1 to 12 episodes per child per year, with a global average of 3 episodes per child per year. Diarrhea is associated with 1/4 of all deaths in children under 5 years in developing countries. Oral rehydration therapy (ORT) is the cornerstone of global efforts to reduce mortality from acute diarrhea. The World Health Organization (WHO)/UNICEF ORS formula contains glucose and sodium in a molar ratio of 1.2:1. Potassium chloride is added to replace potassium lost in the stool. Trisodium citrate dihydrate (or sodium bicarbonate) corrects metabolic acidosis caused by fecal loss of bicarbonate. The WHO case management strategy for children with diarrhea consists of: prevention of dehydration through early administration of appropriate fluids available in the home; treatment of dehydration with ORS solution; treatment of severe dehydration with an intravenous electrolyte solution; continued feeding during, and increased feeding after the diarrheal episode; and selective use of antibiotics and nonuse of antidiarrheal drugs. The WHO/UNICEF formula is also suitable as a maintenance fluid when given with equal amounts of water, breast milk, or low carbohydrate juice. Despite the unquestioned success of ORT in developing countries, physicians in the United States, the United Kingdom, and other industrialized countries have been slow to adopt ORT. Guidelines for case management call for patient assessment. The physician evaluating a child with diarrhea should inquire about clinical features including its duration and the presence of blood in the stool. Thus, a reliable treatment plan can be made without need of laboratory tests. Most diarrheal episodes are self-limited and do not benefit from antimicrobial therapy. Children with bloody diarrhea should be treated for suspected shigellosis with an oral antibiotic.^ieng

Impact of rice based oral rehydration solution on stool output and duration of diarrhoea: meta-analysis of 13 clinical trials.

OBJECTIVE: To define the benefit of rice oral rehydration salts solution in relation to the glucose based World Health Organisation oral rehydration salts solution for treating and preventing dehydration in patients with severe dehydrating diarrhoea. DESIGN: Meta-analysis using data from 13 available randomised trials that compared these two formulations. SUBJECTS: The studies compared 1367 patients with cholera, severe cholera-like diarrhoea, or acute non-cholera diarrhoea. 668 received the standard WHO solution and 699 the rice based solution. INTERVENTION: Each trial report was reviewed to determine patient eligibility, the number of patients who were randomised and the number of these excluded from analysis, details of the randomisation procedure, and the precise timing of the outcome measurements. MAIN OUTCOME MEASURES: Stool output during the first 24 hours; weighted estimates of the difference in mean stool output between treatments. RESULTS: The rice solution significantly reduced the rate of stool output during the first 24 hours by 36% (95% confidence interval 28 to 44%) in adults with cholera and by 32% (19 to 45%) in children with cholera. The rate of stool loss in infants and children with acute non-cholera diarrhoea was reduced by only 18% (6 to 30%). CONCLUSIONS: The benefit of rice oral rehydration salts solution for patients with cholera is sufficiently great to warrant its use in such patients. The benefit is considerably smaller for children with acute, noncholera diarrhoea and should be more precisely defined before its practical value can be judged.

PIP: This meta-analysis used data from 13 available randomized trials to compare 2 rehydration salts solutions. Specifically, it sought to define the benefit of rice oral rehydration salts in relation to the glucose-based WHO oral rehydration salts solution for treating and preventing dehydration in patients with severe dehydrating diarrhea. The studies compared 1367 patients with cholera, severe cholera-like diarrhea, or acute noncholera diarrhea; 668 received the standard WHO solution and 699 the rice based one. Each report was reviewed to determine patient eligibility, the number of patients who were randomized, and the number of these excluded from the analysis, details of the randomization procedure, and the precise timing of the outcome measurements. Stool output during the 1st 24 hours was measured and there were weighted estimates of the differences in mean stool output between treatments. The rice solution significantly reduced the rate of stool output during the 1st 24 hours by 36% (95% confidence interval 28-44%) in adults with cholera and by 32% (19-45%) in children with cholera. The rate of stool loss in infants and children with acute noncholera diarrhea was reduced by only 18% (6-30%). The benefit of rice oral rehydration salts solution for patients with cholera is sufficiently great to warrant its use in these patients. The benefit is considerably less for children with acute, noncholera diarrhea and should be more precisely defined before its practical value can be judge.

Cholera in Africa: lessons on transmission and control for Latin America.

In January, 1991, epidemic cholera emerged in Peru and spread to 7 other countries of Latin America. Cholera was introduced 20 years ago to Africa, where it spread rapidly to 30 of the 46 countries of the region and by 1990 accounted for 90% of all cases reported to the World Health Organisation. Many lessons from the cholera epidemic in Africa are relevant to efforts to control the disease in Latin America. Public health practices from the past--quarantine and cordon sanitaire to halt introduction of cholera by travellers, and vaccination and mass chemoprophylaxis to control epidemics--are ineffective in preventing spread of the disease. Cholera can be transmitted not only by contaminated water but also by food. Social phenomena such as mass migrations and burial practices may play a greater role than previously understood. While efforts to prevent the spread of cholera have been ineffective, cholera-associated mortality can be decreased with rehydration therapy. Since the current pandemic is unlikely to retreat soon, new strategies are urgently needed to control the spread of cholera through sanitary and behavioural interventions or improved vaccines.

PIP: Latin America had been free of cholera for 70 years until January 1991 when the 7th pandemic of El Tor cholera struck Peru. It killed 1500 people and affected 200,000 people within 6 months. It soon spread to at least 7 other Latin American countries. 20 years earlier the it reached Africa. Foci of infections in Africa included markets, fairs, funerals, and refugee camps. Scientists doubted that vaccination or quarantine would have prevented its introduction into Africa. Yet, in Latin America, public health officials should earnestly reconsider chemoprophylaxis (tetracycline) of family contacts in families with high rates of illness. Presently no such data exist in Latin America. In addition, health workers should test the new oral vaccine in Latin America since there is no preexisting immunity and the people are exposed to high levels of contamination. Little epidemic research was done in Africa to pinpoint modes of transmission so health workers could learn what types of intervention were warranted. It should be done in Latin America, however. As for quarantine, symptomatic and mild to moderate cholera cases can outnumber severe cases as much as 100 to 1, so confining cases would not prevent the spread of the disease. Latin America should broaden diarrheal disease control programs to include adults so they will accept oral rehydration therapy (ORT). It should be used in mild to moderate dehydration cases and intravenous rehydration therapy for severe cases. If the environmental factors are not known and understood and if feces contaminate water supplies, foods, and fisheries, cholera may become endemic in Latin America. In conclusion prompt disease reporting, surveillance, and implementation of control measures could prevent the endemicity of cholera in Latin America.