Manejo de la gastroenteritis aguda en menores de 5 años: un enfoque basado en la evidencia / An evidence based Iberic-Latin American guideline for acute gastroenteritis management in infants and prescholars

La morbi-mortalidad en menores de 5 años por gastroenteritis aguda (GEA) en países en desarrollo sigue siendo elevada. Los autores han elaborado un documento que ayude a tomar decisiones en el tratamiento del menor de 5 años con GEA en el contexto Ibero-latinoamericano. Se realizó una revisión sistemática de la literatura (mayo 2008). La gradación de la evidencia se realizó siguiendo las guías Oxford y expertos latinoamericanos opinaron respecto a las recomendaciones. La rehidratación oral representa la piedra angular del tratamiento de la GEA en niños, asociándose a menos efectos adversos que la rehidratación intravenosa. La GEA no es contraindicación para la alimentación normal. Racecadotrilo, zinc y esmectita pueden coadyuvar al tratamiento, así como Lactobacillus GG y Saccharomyces boulardii. No se recomiendan otros fármacos. En el tratamiento de niños con GEA se recomienda la rehidratación oral junto con racecadotrilo, zinc o esmectita, y algunos probióticos (AU)

Acute gastroenteritis (AG) morbidity and mortality rates in infants and prescholars continue to be high in developing countries. Authors want to develop an evidence-based document that supports decision making regarding AG therapy in infants and children younger than 5 y/o. A systematic review of the literature was performed (May, 2008). Evidence grading was established according to Oxford guidelines and Latin American experts submitted their opinions on the recommendations generated. Oral rehydration solutions are the threatment's keystone for children with AG, showing lesser complications due to therapy than IV fluids. AG is no contraindication of a normal diet. Racecadotril, zinc and smectite can contribute to AG treatment, as well as Lactobacillus GG and Saccharomycces boulardii. No other drugs are recommended. It is recommended to treat children presenting AG with oral rehydration solutions among racecadotril, zinc or smectite as well as some probiotics (AU)

[An evidence based Iberic-Latin American guideline for acute gastroenteritis management in infants and prescholars]. / Manejo de la gastroenteritis aguda en menores de 5 años: un enfoque basado en la evidencia Guía de práctica clínica Ibero-Latinoamericana.

Acute gastroenteritis (AG) morbidity and mortality rates in infants and prescholars continue to be high in developing countries. Authors want to develop an evidence-based document that supports decision making regarding AG therapy in infants and children younger than 5 y/o. A systematic review of the literature was performed (May, 2008). Evidence grading was established according to Oxford guidelines and Latin American experts submitted their opinions on the recommendations generated. Oral rehydration solutions are the threatment's keystone for children with AG, showing lesser complications due to therapy than IV fluids. AG is no contraindication of a normal diet. Racecadotril, zinc and smectite can contribute to AG treatment, as well as Lactobacillus GG and Saccharomycces boulardii. No other drugs are recommended. It is recommended to treat children presenting AG with oral rehydration solutions among racecadotril, zinc or smectite as well as some probiotics.

Drug resistance trends among previously treated tuberculosis patients in a national registry in Peru, 1994-2001.

SETTING: National mycobacteriology reference laboratory in Peru conducting routine testing of susceptibility to isoniazid, rifampin, ethambutol, pyrazinamide, and streptomycin, in Mycobacterium tuberculosis isolates from previously treated patients. OBJECTIVE: To determine the percentage of isolates resistant to each of five anti-tuberculosis agents and to ascertain in these data the presence of trends of clinical relevance. DESIGN: Retrospective study of a national registry of M. tuberculosis isolates from patients referred for drug susceptibility testing between 1994 and 2001. RESULTS: Among 14,736 isolates tested, 10,837 (73.5%, 95%CI 72.8-74.3) demonstrated anti-tuberculosis resistance, and 8455 (57.4%, 95%CI 56.6-58.2) demonstrated resistance to at least both isoniazid and rifampin, by convention defined as multidrug-resistant tuberculosis (MDR-TB). A significant increasing trend could be discerned for resistance to each of the drugs tested and in isolates classified as MDR-TB (P < 0.001 for trend). Additional clinically relevant trends were found in polyresistance and multidrug resistance percentages. CONCLUSIONS: Data from a national reference laboratory can be used to inform the design of retreatment regimens.

Rotavirus diarrhea disease burden in Peru: the need for a rotavirus vaccine and its potential cost savings.

OBJECTIVE: To assess the disease burden of rotavirus diarrhea in Peru as well the need for and the potential cost savings with a rotavirus vaccine in that country. METHODS: To assess the burden of rotavirus diarrhea in Peru, we reviewed published and unpublished reports where rotavirus was sought as the etiologic agent of diarrhea in children. Rotavirus detection rates obtained from these studies were combined with diarrhea incidence rates from a number of national surveys in order to estimate both the burden of rotavirus diarrhea in the country and its associated medical costs. RESULTS: Rotavirus is a significant cause of morbidity and mortality in Peruvian children. In their first 5 years of life, an estimated 1 in 1.6 children will experience an episode of rotavirus diarrhea, 1 in 9.4 will seek medical care, 1 in 19.7 will require hospitalization, and 1 in 375 will die of the disease. Per year, this represents approximately 384,000 cases, 64,000 clinic visits, 30,000 hospitalizations, and 1,600 deaths. The annual cost of medical care alone for these children is approximately US$ 2.6 million--and that does not take into account the indirect or societal costs of the illness and the deaths. CONCLUSIONS: Rotavirus immunization provides the prospect of decreasing the morbidity and mortality from diarrhea in Peru, but a vaccine regimen would have to be relatively inexpensive, a few dollars or less per child. Future cost-effectiveness analyses should explore the total costs (medical as well as indirect or societal) associated with rotavirus diarrhea. Newly licensed vaccines should be tested according to both their ability to avert deaths and their efficacy with fewer than three doses. All three of these factors could increase the cost savings associated with a rotavirus vaccine.

Racecadotril in the treatment of acute watery diarrhea in children.

BACKGROUND: Racecadotril (acetorphan), an enkephalinase inhibitor with antisecretory and antidiarrheal actions, is an effective and safe treatment for acute diarrhea in adults and children. Whether treatment with racecadotril and oral rehydration therapy is more effective than treatment with oral rehydration alone in hospitalized children with acute watery diarrhea is not known. METHODS: We treated 135 boys 3 to 35 months of age who had watery diarrhea of five days' duration or less with racecadotril (1.5 mg per kilogram of body weight orally every eight hours) or placebo, in addition to oral rehydration solution. The primary end point was the 48-hour stool output (measured in grams); the total stool output, duration of diarrhea, and total intake of oral rehydration solution were also measured. RESULTS: The mean (+/-SE) 48-hour stool output was 92+/-12 g per kilogram in the racecadotril group and 170+/-15 g per kilogram in the placebo group (P<0.001), a 46 percent reduction with racecadotril. The results were similar among the 73 boys with rotavirus infections. The total stool output was 157+/-27 g per kilogram in the racecadotril group and 331+/-39 g per kilogram in the placebo group (P<0.001). The median duration of diarrhea was significantly less (P<0.001) in the racecadotril group (28 hours regardless of rotavirus status) than in the placebo group (72 and 52 hours, respectively, for rotavirus-positive and rotavirus-negative patients). The intake of oral rehydration solution was significantly lower in the racecadotril group than in the placebo group (P<0.001). Racecadotril was well tolerated; only seven patients taking racecadotril had adverse effects, which were all mild and transient. CONCLUSIONS: In young boys with acute watery diarrhea, racecadotril is an effective and safe treatment.

Differentiation of osmotic and secretory diarrhoea by stool carbohydrate and osmolar gap measurements.

Clinical features and laboratory tests that determine carbohydrate in faeces were evaluated to determine which was best able to distinguish between osmotic and secretory diarrhoea in infants and children. For this purpose 80 boys aged 3 to 24 months, with acute watery diarrhoea, were studied prospectively. The faecal osmolar gap (FOG) was calculated as: serum osmolarity-[2 x (faecal sodium + potassium concentration)]. Fifty eight patients were classified as having predominantly osmotic diarrhoea (FOG > 100 mosmol/l), and 22 as having predominantly secretory diarrhoea (FOG < or = 100 mosmol/l). The two groups were comparable in their clinical features on admission, in the results of blood and urine tests, and in the evolution of their diarrhoeal illness. Evidence of steatorrhoea (by positive Sudan III test) and of acid faecal pH on admission were significantly more frequent in patients with osmotic diarrhoea. Mean (SD) faecal osmolarity was not significantly different between the two groups (319 (80) mosmol/l in secretory diarrhoea v 361 (123) mosmol/l in osmotic diarrhoea). Tests for reducing substances in faeces such as Benedict's test--with and without hydrolysis--and glucose strip, all showed a positive and significant association with osmotic diarrhoea (p < 0.05, < 0.025, < 0.05, respectively). The presence of excess reducing substances (Benedict's test with hydrolysis > 2+) on admission was the most sensitive and specific test with the best predictive value for differentiating between the two types of watery diarrhoea.

Urinary excretion of retinol in children with acute diarrhea.

Acute infections of childhood are associated with an increased of xerophthalmia, apparently due to depletion of vitamin A stores. The mechanism responsible for this is not known. Recently, it has been reported that severe infections in adult patients (ie, sepsis and pneumonia) result in excretion of large quantities of retinol in the urine. In 44 children hospitalized for treatment of acute diarrhea we found mean urinary excretions of 1.44 mumol retinol/24 h on day 1 of hospitalization, 0.62 mumol retinol/24 h on day 2, and 0.23 mumol/24 h on day 3. Healthy control subjects matched for age did not excrete measurable amounts of retinol in the urine. Retinol excretion was associated strongly with rotavirus diarrhea and presence of fever. Furthermore, serum retinol concentration was negatively associated with duration of diarrhea before hospitalization, suggesting that urinary excretion of retinol may be an important contributor to vitamin A depletion.

[The development of a clinical scale for the diagnosis of cholera in infants with acute watery diarrhea]. / Desarrollo de una escala clínica para el diagnóstico de cólera en lactantes con diarrea aguda acuosa.

The diagnosis of cholera in infants based on clinical grounds is often difficult because other enteropathogens such as rotavirus or enterotoxigenic Escherichia coli (ETEC) can produced a very similar clinical picture. We studied 147 infants admitted consecutively to the Rehydration Unit of Cayetano Heredia Hospital in Lima, Perú, trying to identified those characteristics significantly associated with the isolation of Vibrio cholerae 01 on the admission stool culture. After a univariate comparison of cases and controls were selected those characteristics that showed a significantly different distribution. These were entered in a logistic regression model to analyze their interactions. After this analysis four variables remain significantly associated to cases: no history of fever, dehydration greater than 7%, fecal pH greater than 7 and no glucose in feces. Were developed a diagnostic score with these variables, which had a sensitivity of 77.6% and a specificity of 73.6%. It is important to prospectively validate the utility of this score.

Evaluation of alkaline phosphatase-labelled ipaH probe for diagnosis of Shigella infections.

The presence of many enteropathogens which are not easily detectable by routine stool culture has led to the development of alternative diagnostic methods. One of these techniques, nucleic acid probe hybridization, has been used to identify Shigella spp. and enteroinvasive Escherichia coli (EIEC) in stool specimens through the detection of genetic material encoded by a specific large approximately 200-kbp virulence-related plasmid. In the present study, an alkaline phosphatase-labelled oligonucleotide probe developed to detect the gene for ipaH, a repetitive genetic sequence thought to be present on both the virulence-related plasmid and the chromosomes of all strains of Shigella and EIEC, was tested in a developing-country setting through a prospective clinical trial. In a group of 219 Peruvian adults and children with acute gastroenteritis, the ipaH probe detected 85% of cases of shigellosis and demonstrated a specificity of 95% when compared with simultaneous detection by several stool culture techniques. Additionally, three cases of EIEC infection which could not be diagnosed by culture methods alone were detected with the ipaH probe and were confirmed by plasmid analysis and Sereny testing. These preliminary results suggest that, with further research, the ipaH probe should prove to be a useful and rapid adjunct in the diagnosis of acute gastroenteritis in developing countries.

Association of diarrhea and low serum retinol in Peruvian children.

To examine the relationship between acute diarrhea and vitamin A status, a study was conducted in 137 children (72 with diarrhea and 65 illness-free control subjects) in the city of Lima, Peru. Serum retinol was measured spectrophotometrically in samples collected in 1987 and kept frozen until they were analyzed simultaneously in 1989. Serum retinol was significantly lower in the children with diarrhea (mean +/- SD: 0.51 +/- 0.48 mumol/L) than in those without diarrhea (1.00 +/- 0.32 mumol/L; 1 mumol/L retinol = 28.6 micrograms/dL). The multivariate estimate of the effect of diarrhea (-0.464 mumol/L) in a model that incorporated age, sex, and acute malnutrition (ie, weight-for-height) as confounding variables was essentially the same as the unadjusted difference (-0.492 mumol/L). Thus, this model showed that the retinol concentration in the serum depends greatly on the presence of diarrhea. These findings suggest that diarrhea, as has been shown for other infections, may lead to lower circulating retinol concentrations and perhaps to its depletion.

A controlled trial of bismuth subsalicylate in infants with acute watery diarrheal disease.

BACKGROUND: Bismuth subsalicylate is a common constituent of over-the-counter medications for diarrhea. However, it is uncertain whether bismuth offers any more benefit than standard oral rehydration therapy with early feeding. METHODS: We conducted a placebo-controlled, randomized trial to evaluate the effect of bismuth subsalicylate (100 or 150 mg per kilogram of body weight per day for up to 5 days) on the duration and volume of acute watery diarrhea in 275 male infants and young boys (mean age, 13.5 months). Serum salicylate and bismuth levels were monitored throughout the study and were also measured two weeks after discharge. All the patients received fluid replacement by the oral route and early feeding of easily digestible foods with high caloric density. RESULTS: Diarrhea stopped within 120 hours of admission in 74 percent of the patients given placebo, 89 percent of those given 100 mg of bismuth per kilogram (P = 0.009 vs. the placebo group), and 88 percent of those given 150 mg of bismuth per kilogram (P = 0.019 vs. the placebo group). As compared with the patients given placebo, those given bismuth had significant reductions in their total stool output (P = 0.015), total intake of oral rehydration solution (P = 0.013), and duration of hospitalization (P = 0.005); there was no significant difference between the two groups given bismuth in these clinical outcomes. All measurements of bismuth and salicylate concentrations in blood were well below concentrations considered toxic. No adverse reactions were seen. CONCLUSIONS: Treatment with bismuth subsalicylate decreases the duration of diarrhea and is a safe and effective adjunct to oral rehydration therapy for infants and young children with acute watery diarrhea.

Handwashing practices and resistance and density of bacterial hand flora on two pediatric units in Lima, Peru.

The handwashing practices and bacterial hand flora of 62 pediatric staff members of a teaching hospital in Lima, Peru, were studied. Handwashing followed patient contact 29.3% of the time (204/697 contacts). Mean duration was 14.5 seconds, and significant differences in practices were found by unit (rehydration or neonatal intensive care), type of staff member (nurses or physicians), and type and duration of patient contact. Mean count of colony-forming units was log10 5.87 +/- 0.41, with significant differences in density of flora found between patient care and kitchen staffs. There was no significant effect of handwashing on counts of colony-forming units. Significant differences were also found by unit and by staff position with regard to species isolated and antimicrobial resistance of isolates. A more efficacious and cost-effective form of hand hygiene and a more prudent use of antimicrobial agents are indicated.

Evaluation of clinical management training programme for diarrhoea.

We report the evaluation of a training programme on clinical management of infantile diarrhoea. The training programme was delivered through a series of on-site clinical courses offered to a selected group of physicians and nurses from 16 health units in Peru and a series of local workshops conducted in their own health units. The outcome of this training programme was assessed by pre- and post-tests, knowledge, attitude, and practice (KAP) questionnaires, and observational surveys. A significant improvement in medical knowledge about diarrhoea, in particular about the use of ORT and drug therapy, was observed. Although the observational surveys showed significant improvement in the use of ORT at health facilities (2.9% to 23.6%, p = 0.007) the rate observed was still low compared to the high level of knowledge on ORT that was demonstrated by the KAP questionnaires. A reduction of antibiotic prescription for inpatients with diarrhoea (85.7% to 64.8%, p = 0.025) was observed. The training programme was also effective in promoting the establishment of Oral Rehydration Units in the participants' health facilities.

PIP: Physicians designed a training program on clinical management of diarrhea which consisted of 11 clinical training courses at the Cayetano Heredia University Hospital in Lima, Peru for 37 physicians and 37 nurses from 16 hospitals in 20 various cities in Peru; a number of local workshops on overall features of clinical management of diarrhea cases; and supervisory pre- and posttraining visits to the hospitals. Health workers treated only 2.9% of dehydration cases and 25.7% of inpatient diarrhea cases before dehydration set in and 7.7% of similar outpatients with oral rehydration therapy (ORT) during the pretraining observational survey. After the training, these corresponding figures increased to 23.6% (p=.007), 57.6% (p=.002), and 88.9% (p.0001). The 23.6% rate was still low compared with the high level of knowledge about diarrhea treatment, however. Before training, they prescribed antibiotics to 85.7% of inpatients and 50% of outpatients. After the training, health workers still prescribed antibiotics to 50% of outpatients even though 95% knew correct drug prescription practices. On the other hand, they prescribed antibiotics to a lower percentage of inpatients (64.8%; p=.025). Before the course, they recommended breast feeding and weaning foods in 25.7% and 28.6% of inpatients, respectively, and in 47.1% and 41.2% of outpatients, respectively. Following the course, health workers were more likely to advise breast feeding and weaning foods for outpatients (p=.015 and p=.001, respectively), but tended not do so for inpatients. They were less likely to recommend breast feeding (25.7% vs. 19.4%). This evaluation helped promote creation of rehydration units in 12 of the participating hospitals. The results showed a need for continuous medical education for the health workers in the new units.

Prospective study of systemic and mucosal immune responses in dysenteric patients to specific Shigella invasion plasmid antigens and lipopolysaccharides.

Shigellosis is a major cause of infant morbidity and mortality in developing countries. To find immunological correlates of specific protection against shigellosis, we examined chronological samples of sera, stool extracts, duodenal aspirates, and saliva samples from 39 adults and 22 children with shigellosis from Peru for the presence of specific antibody to invasion plasmid antigens (Ipa) common to all virulent Shigella strains, by using both a whole-organism enzyme-linked immunosorbent assay (ELISA) and a Western blot (immunoblot) assay. Antibody responses to lipopolysaccharide (LPS) from Shigella serotypes both homologous and heterologous to the infecting strain were also determined by ELISA. ELISAs showed that the highest serum immunoglobulin G (IgG) antibody titers to Shigella whole organisms both with and without surface Ipa were found in adults and malnourished children, the two groups with the shortest and longest durations of disease, respectively. Mucosal IgA antibody titers to Shigella strains decreased over time to a much greater extent than serum IgG titers, and IgA to Ipa in mucosal secretions was found in adults and well-nourished children but not in malnourished children. The presence of mucosal antibody to Ipa may limit the spread and severity of the infection, as indicated by the prolonged illness observed in malnourished children who have no significant mucosal antibody to Shigella Ipa. Serum antibody titers to the Ipa antigens were high relative to anti-Shigella LPS antibody titers, especially in pediatric patients. In contrast to the anti-Ipa responses observed, no differences in antibody responses to LPS in children compared by nutritional status were found. High levels of serum and mucosal cross-reacting antibody to heterologous serotype LPS were found between Shigella flexneri serotypes 1a and 2a. Different patterns of immune response to Ipa proteins and LPS that may aid in the definition of Shigella antigens important in host protection were observed in adults, well-nourished children, and malnourished children.

Measles-associated diarrhea in hospitalized children in Lima, Peru: pathogenic agents and impact on growth.

Because the causes of measles-associated diarrhea are not well known, 0- to 5-year-old children presenting to the hospital with measles-associated diarrhea (cases, n = 77) or acute diarrhea only (controls, n = 77) were compared. Growth and diarrheal morbidity were evaluated for 1 month after acute illness. Campylobacter jejuni was more frequently isolated from cases (31%) than controls (16%; P = .03). Rotavirus was absent in all cases versus 28% of controls (P less than .001). Incidence density for new episodes of diarrhea was significantly greater in cases (6.5 vs. 4.1; odds ratio, 1.6; confidence intervals, 1.09-2.34; P = .01), as was duration of episodes (3 vs. 2 days, P = .02). Both groups showed similar positive cumulative percentage weight gains throughout follow-up. These data support the theory of measles as a risk factor for developing diarrhea. The bacteriologic and virologic findings may reflect the immunologic response of the host to measles infection.

Case-control study of Cryptosporidium parvum infection in Peruvian children hospitalized for diarrhea: possible association with malnutrition and nosocomial infection.

A retrospective, hospital-based case-control study was used to investigate whether there were any clinical characteristics that could distinguish Cryptosporidium parvum-infected children with diarrhea from other non-C. parvum-infected children with diarrhea. Ten percent (24 of 248) of children admitted to a rehydration ward at Cayetano Heredia University Hospital, Lima, Peru, were infected with C. parvum. The 24 patients infected with C. parvum (cases) were matched to an equal number of noninfected patients (controls). C. parvum-infected patients were more likely to be malnourished than were children without this infection (P less than 0.05). Also nosocomial infection caused by C. parvum occurred in three severely malnourished patients, two of whom died. No other clinical or laboratory characteristics were found that would distinguish children with diarrhea caused by C. parvum from other children with diarrhea. In children hospitalized for diarrhea C. parvum infection occurs most frequently in malnourished children.

Early treatment with erythromycin of Campylobacter jejuni-associated dysentery in children.

To evaluate the efficacy of early treatment with erythromycin on the duration of fecal excretion and of diarrhea associated with Campylobacter jejuni, 170 patients, age 3 to 60 months, were randomly assigned in a double-blind fashion to receive either erythromycin ethyl succinate or placebo immediately after being seen at Cayetano Heredia Hospital because of acute dysentery. The groups' pretreatment characteristics were comparable. Of the 30 patients with stools positive for C. jejuni, 12 were in the placebo group and 16 in the treatment group. After 2 days of treatment, none of the patients in the placebo group and 36% of those in the erythromycin group had normal stools (P less than 0.05). After 5 days of treatment, 50% of the patients in the placebo group and 93% of those in the erythromycin group had normal stools (P less than 0.02). Fecal excretion of the organism continued significantly longer in the placebo group (P less than 0.01). There were no treatment failures in the treatment group compared with five (42%) in the placebo group (P less than 0.01). Thus, early administration of erythromycin significantly reduced the duration of both diarrhea and fecal excretion of the organism in infants and children with acute dysentery associated with C. jejuni.