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INTRODUCTION: Rotavirus is one of the most common pathogens causing diarrhea in children

Rotavirus gastroenteritis affects all children. Studies indicate that by the age of 5 years, almost all children have developed rotavirus antibodies. It has been estimated that in Europe, approximately 6550 children each year die as a result of rotavirus infection. Most of this mortality does not affect children from identifiable risk groups, but previously healthy infants. There is no accountable evidence on increased severity of rotavirus infection in specific risk groups, including children previously born preterm or immunocompromised children. Universal immunization in areas that have successfully achieved large coverage has greatly improved the health of children, reducing infection rates, hospitalization, and costs. Vaccination of infants with presumed high risk may be beneficial for the vaccinated individuals, and such a strategy may also be cost-effective in certain settings. Identifying all high-risk infants within the first few weeks of life is rather difficult especially in countries without primary care pediatricians and goes along with additional costs. Conclusion: Rotavirus vaccines should be recommended as a universal approach for all children and not be restricted to subgroups with assumed increased risk. Targeted vaccination could be considered as an option in countries with limited financial resources.

Aim The Working Group on Acute Diarrhoea, part of The Consensus Group on Outcome Measures Made in Paediatric Enteral Nutrition Clinical Trials, previously developed a core outcome set for clinical trials on acute diarrhoea. This study aimed to create a core outcome measurement set to complement it. Methods The study had three phases. The first identified how the literature defined core outcome measures in clinical trials on acute diarrhoea and measured outcomes. The second phase used a questionnaire to seek the views of 109 leading researchers and clinicians in this specialist field. The third phase achieved a consensus on the core outcome measurement set. Results First, we identified 52 different measurement instruments or definitions. A questionnaire was then used to ask our experts what they thought were the most valid core outcome measurement instruments or definitions for each measure and 53 (49%) responded. Core outcome measurement instruments were then developed, including definitions of diarrhoea and acute gastroenteritis, diarrhoea duration, dehydration, the need for hospitalisation, discharge criteria and duration of hospitalisation. Conclusion The outcome measurement set can be used to evaluate therapeutic or preventive strategies and can be recommended for use in future acute diarrhoea trials.

Probiotics are increasingly used for prevention and treatment of diarrhea more in children than in adults. Given the broad spectrum of diarrhea, this review focuses on the main etiologies: acute gastroenteritis, antibiotic-associated diarrhea (AAD), and necrotizing enterocolitis (NEC). For each, we reviewed randomized controlled trials, meta-analyses, and guidelines. For acute gastroenteritis we found 12 guidelines: 5 recommended probiotics and 7 did not. However, the guidelines containing positive recommendations provided proof of evidence from clinical trials and meta-analyses. Lactobacillus rhamnosus GG (LGG) and Saccharomyces boulardii had the most compelling evidence of efficacy as they reduced the duration of the disease by 1 day. For AAD 4 meta-analyses were found, reporting variable efficacy of probiotics in preventing diarrhea, based on the setting, patient's age, and antibiotics. The most effective strains were LGG and S. boulardii. For NEC, we found 3 randomized controlled trials, 5 meta-analyses, and 4 position papers. Probiotics reduced the risk of NEC enterocolitis and mortality in preterm babies. Guidelines did not support a routine use of probiotics and asked for further data for such sensitive implications. In conclusion, there is strong and solid proof of efficacy of probiotics as active treatment of gastroenteritis in addition to rehydration. There is solid evidence that probiotics have some efficacy in prevention of AAD, but the number needed to treat is an issue. For both etiologies LGG and S. boulardii have the strongest evidence. In NEC the indications are more debated, yet on the basis of available data and their implications, probiotics should be carefully considered.

Antibiotic therapy is not necessary for acute diarrhea in children, as rehydration is the key treatment and symptoms resolve generally without specific therapy. Searching for the etiology of gastroenteritis is not usually needed; however, it may be necessary if antimicrobial treatment is considered. The latter is left to the physician evaluation in the absence of clear indications. Antimicrobial treatment should be considered in severely sick children, in those who have chronic conditions or specific risk factors or in specific settings. Traveler’s diarrhea, prolonged diarrhea, and antibiotic-associated diarrhea may also require antibiotic therapy. Depending on the severity of symptoms or based on risk of spreading, empiric therapy may be started while awaiting the results of microbiological investigations. The choice of antibiotic depends on suspected agents, host conditions, and local epidemiology. In most cases, empiric therapy should be started while awaiting such results. Empiric therapy may be started with oral co-trimoxazole or metronidazole, but in severe cases parenteral treatment with ceftriaxone or ciprofloxacin might be considered.

Intestinal permeability impairment is implicated in many gastrointestinal (GI) diseases. Chronic diarrhea, defined as the presence of diarrhea for more than 3 weeks in adults and 2 weeks in children, requires a different diagnostic and therapeutic work-up than acute diarrhea. Gelatin tannate, by reducing the clinical activity of acute colitis and the proinflammatory effects of lipopolysaccharide (LPS), is emerging as a mucosal barrier protector.New therapeutic strategies focusing on the physiological function of the intestinal barrier, may offer an innovative approach for the clinical improvement of highly debilitating chronic GI diseases. We review the available data on the role of gelatin tannate and tyndallized probiotics in the treatment of diarrhea.Gelatin tannate and tyndallized probiotics can be used to re-establish the physiological functions of the gut barrier, as well as for preventing dysbiosis. There is evidence that due to their particular properties, gelatin tannate and tyndallized probiotics are highly effective in the treatment of acute gastroenteritis and may be especially indicated in the management of moderate and prolonged diarrhea.Gelatin tannate and tyndallized probiotics may be effective in the management of chronic diarrhea. Further clinical trials are necessary to further explore their effects in clinical practice.

To the Editor: A Cochrane systematic review concluded that the use of specific probiotics along with rehydration therapy has beneficial effects in reducing the duration and stool frequency of acute infectious diarrhea. Cochrane experts acknowledged variability among studies and stated that research is needed to guide the use of particular probiotic regimens in specific patient groups. The results of the trial by Schnadower et al. and those of the trial by Freedman et al., which were published in the same issue of the Journal, should be interpreted with caution because of the late use of probiotic therapy and the unverified viability of strains in liquid suspension in both trials. Most children had mild gastroenteritis and were recruited after they had had diarrhea for 2 days. Guidelines recommend probiotic use within the first 24 to 48 hours after symptom onset in order to be effective. Infectious gastroenteritis in Western societies is typically mild and self-limiting, and the use of probiotics may not be critical. This is not the same in less developed areas. It would be advisable to perform a subanalysis focusing only on severe cases of diarrhea treated with reliable probiotic dosing within the first 48 hours after the onset of symptoms in order to properly assess the effectiveness of the intervention.

Gastroenteritis caused by single or multiple pathogens remains a major diagnostic challenge for the laboratory, as diagnosis is achieved using different techniques with variable sensitivity and specificity. The aim of this study was to evaluate the EasyScreen™ Enteric Protozoa Detection Kit, a multiplex PCR assay for the detection and identification of the 5 most common protozoan parasites in fecal samples. A total of 632 fecal samples, submitted for routine screening to 2 centers in north-eastern Italy, was included in the study. The results of the molecular assay were compared to those of the standard diagnostic procedures, represented by microscopy and immunoassays. Out of 32 samples testing positive by conventional tools, 31 were detected as concordantly positive using the EasyScreen Kit. Additionally, 91 out of 632 samples only tested positive by the molecular test, therefore increasing the positive detection rate by 275%. Finally, the EasyScreen assay detected 14 co-infections compared to 3 co-infections identified by conventional methods. The EasyScreen Kit provided a rapid and sensitive simultaneous identification of the most important diarrhea-causing protozoa that infect humans. Additionally, this molecular assay presents several advantages compared to conventional tools, such as the standardization and near-total automation of the process. Although critical issues related to the employment of molecular assays are still evident, the system is suitable for clinical parasitological diagnosis as long as it is used in association with conventional tools.

BACKGROUND AND OBJECTIVES: A 2007 meta-analysis showed probiotics, specifically Lactobacillus rhamnosus GG (LGG), shorten diarrhea from acute gastroenteritis (AGE) by 24 hours and decrease risk of progression beyond 7 days. In 2005, our institution published a guideline recommending consideration of probiotics for patients with AGE, but only 1% of inpatients with AGE were prescribed LGG. The objective of this study was to increase inpatient prescribing of LGG at admission to >90%, for children hospitalized with AGE, within 120 days. METHODS: This quality improvement study included patients aged 2 months to 18 years admitted to general pediatrics with AGE with diarrhea. Diarrhea was defined as looser or ≥3 stools in the preceding 24 hours. Patients with complex medical conditions or with presumed bacterial gastroenteritis were excluded. Admitting and supervising clinicians were educated on the evidence. We ensured LGG was adequately stocked in our pharmacies and updated an AGE-specific computerized order set to include a default LGG order. Failure identification and mitigation were conducted via daily electronic chart review and e-mail communication. Primary outcome was the percentage of included patients prescribed LGG within 18 hours of admission. Intervention impact was assessed with run charts tracking our primary outcome over time. RESULTS: The prescribing rate increased to 100% within 6 weeks and has been sustained for 7 months. CONCLUSIONS: Keys to success were pharmacy collaboration, use of an electronic medical record for a standardized order set, and rapid identification and mitigation of failures. Rapid implementation of evidence-based practices is possible using improvement science methods.

AIM: Implementing international guidelines guarantees high standards of clinical care. A group of experts developed an algorithm to drive the management of common gastrointestinal symptoms in infancyby paediatricians and general practitioners. METHODS: The algorithm started from the evidence-based recommendations of the European Society of Gastroenterology, Hepatology and Nutrition and the European Society of Pediatric Infectious Diseases and an updated review of the literature. We used the structured quantitative method of nominal group technique to reach a consensus. RESULTS: A practical algorithm for the management of infants with acute diarrhoea was designed based on theconsensus reached for each statement. The management of an infant with acute diarrhoeashould include a sequence of actions: 1) a semi-quantitative estimate of infant dehydration through validated clinical scores, 2) rehydration therapy and early re-feedingwith breast milk or regular formula and 3) effective agents to reduce the severity and duration of the diarrhoea. Finally, in children with prolonged diarrhoea, the search for aetiology should include persistent infections or reinfections, cows' milk protein allergy and celiac diseases. Lactose should always be withdrawn. CONCLUSION: This algorithm provides an evidence-based sequence of interventions to optimisethe management of infants with acute diarrhoea. This article is protected by copyright. All rights reserved.

The use of antiemetics for vomiting in acute gastroenteritis in children is still a matter of debate. We conducted a double-blind randomized trial to evaluate whether a single oral dose of ondansetron vs domperidone or placebo improves outcomes in children with gastroenteritis. After failure of initial oral rehydration administration, children aged 1-6 years admitted for gastroenteritis to the pediatric emergency departments of 15 hospitals in Italy were randomized to receive one oral dose of ondansetron (0.15 mg/kg) or domperidone (0.5 mg/kg) or placebo. The primary outcome was the percentage of children receiving nasogastric or intravenous rehydration. A p value of 0.014 was used to indicate statistical significance (and 98.6% CI were calculated) as a result of having carried out two interim analyses. 1,313 children were eligible for the first attempt with oral rehydration solution, which was successful for 832 (63.4%); 356 underwent randomization (the parents of 125 children did not give consent): 118 to placebo, 119 to domperidone, and 119 to ondansetron. Fourteen (11.8%) needed intravenous rehydration in the ondansetron group vs 30 (25.2%) and 34 (28.8%) in the domperidone and placebo groups, respectively. Ondansetron reduced the risk of intravenous rehydration by over 50%, both vs placebo (RR 0.41, 98.6% CI 0.20-0.83) and domperidone (RR 0.47, 98.6% CI 0.23-0.97). No differences for adverse events were seen among groups. In a context of emergency care, 6 out of 10 children aged 1-6 years with vomiting due to gastroenteritis and without severe dehydration can be managed effectively with administration of oral rehydration solution alone. In children who fail oral rehydration, a single oral dose of ondansetron reduces the need for intravenous rehydration and the percentage of children who continue to vomit, thereby facilitating the success of oral rehydration. Domperidone was not effective for the symptomatic treatment of vomiting during acute gastroenteritis.

Hospital-based surveillance of acute gastroenteritis caused by rotavirus has produced ample knowledge on the infection in children, whereas little is known on rotavirus infection among adults. The Italian surveillance program RotaNet- Italia collected 1,595 samples from patients admitted to hospital with gastroenteritis in 2012. All patients presented with vomiting, diarrhea, fever, and/or abdominal pain. Fortytwo samples obtained by the RotaNet-Italia (2.6%) were from adolescents or adults (10–89 years). The study compared the genotypes and gene sequences of the rotavirus strains identified in adults with strains obtained from children worldwide. All 42 Italian strains were genotyped by the EuroRotaNet RT-nested-PCR protocols, and 12 rotaviruses from patients >13-year-old were subjected to nucleotide sequencing of their VP7 and/or VP4 genes. All strains analyzed belonged to the common human genotypes G1P[8], G2P[4], G4P[8], and G9P[8], except an uncommon G3P[19] genotype detected in a single patient. Phylogenetic analysis of the 12 strains showed that within each genotype they clustered in RVA lineages reported worldwide. The amino acid sequences of the VP7 and the VP8 hypervariable regions were highly conserved between the RVA strains collected from adults and children, in each lineage. Genotyping, phylogenetic analysis, and the study of viral epitopes revealed that rotaviruses circulating in adults in Italy are closely similar to the strains circulating in children, with high nucleotide identity particularly with strains reported in Europe and Asia. The circulation of the same rotavirus strains in both children and adults suggests that adults may contribute to sustain the circulation of rotaviruses through the population.

BACKGROUND: Childhood gastroenteritis is associated with considerable health costs. The natural clay dioctahedral smectite increases intestinal barrier function and is effective against infectious diarrhea in children in developing countries. The purpose of this work was to investigate the efficacy of smectite in Italian children with acute diarrhea of mild to moderate severity. METHODS: A national, prospective, randomized, case-controlled study was performed in collaboration with primary care pediatricians. Children seen by pediatricians for acute gastroenteritis were treated with oral rehydration solution (ORS) alone or ORS with smectite. Parents returned a form in which total duration of diarrhea, incidence of vomiting and fever, persistence of diarrhea for more than 7 days and hospital admissions were recorded. RESULTS: Eight hundred four children with acute diarrhea were randomly assigned to treated or control groups. Administration of smectite was associated with significant reduction of the duration of diarrhea, as judged by stool frequency and consistency. The incidence and duration of vomiting and fever were not different. Diarrhea lasted more than 7 days in 10% of treated and in 18% of control children (P < 0.01). Hospital admission was necessary in seven treated and six control children. No side effects were observed. CONCLUSIONS: Smectite reduces the duration of diarrhea and prevents a prolonged course. It may therefore consistently reduce the costs of gastroenteritis.

Acute gastroenteritis (AGE) is a major cause of ED visits, hospitalizations, and prescription of investigations, drugs, and changes in diet. Several guidelines on management have been produced. RECENT FINDINGS: There is new information on different rehydration protocols, use of antiemetics, and antidiarrheal drugs that could reduce the burden of AGE. The need of intravenous (i.v.) rehydration is the main cause of hospital admission yet a standardized rehydration scheme is not available. Rehydration therapy through nasogastric tube is better than i.v. rehydration, in children with moderate-severe dehydration. Ultrarapid rehydration has been proposed by enteric or i.v. route to reduce the time in hospital and costs. However, reduced rehydration times are associated with high readmission rates and side effects. Antiemetics may reduce the need of i.v. rehydration because of vomiting and the number of hospital admissions. However, the main antiemetic, ondansetron, has been loaded with a warning for potentially severe side effects. Selected antidiarrheal drugs could reduce the length of stay, but data on their use in inpatients are still not conclusive. SUMMARY: Inappropriate medical interventions are still common in the hospital setting and have a high impact on costs. A validated management is still needed in inpatients.

OBJECTIVE. Gastric acidity (GA) inhibitors, including histamine-2 receptor antagonists (H2 blockers) and proton pump inhibitors (PPIs), are the mainstay of gastroesophageal reflux disease (GERD) treatment. A prolonged GA inhibitor–induced hypochlorhydria has been suggested as a risk factor for severe gastrointestinal infections. In addition, a number of papers and a meta-analysis have shown an increased risk of pneumonia in H2-blocker–treated intensive care patients. More recently, an increased risk of community-acquired pneumonia associated with GA inhibitor treatment has been reported in a large cohort of adult patients. These findings are particularly relevant to pediatricians today because so many children receive some sort of GA-blocking agent to treat GERD. To test the hypothesis that GA suppression could be associated with an increased risk of acute gastroenteritis and pneumonia in children treated with GA inhibitors, we conducted a multicenter, prospective study. METHODS. The study was performed by expert pediatric gastroenterologists from 4 pediatric gastroenterology centers. Children (aged 4–36 months) consecutively referred for common GERD-related symptoms (for example, regurgitation and vomiting, feeding problems, effortless vomiting, choking), from December 2003 to March 2004, were considered eligible for the study. Exclusion criteria were a history of GA inhibitors therapy in the previous 4 months, Helicobacter pylori infection, diabetes, chronic lung or heart diseases, cystic fibrosis, immunodeficiency, food allergy, congenital motility gastrointestinal disorders, neuromuscular diseases, or malnutrition. Control subjects were recruited from healthy children visiting the centers for routine examinations. The diagnosis of GERD was confirmed in all patients by standard criteria. GA inhibitors (10 mg/kg ranitidine per day in 50 children or 1 mg/kg omeprazole per day in 50 children) were prescribed by the physicians for 2 months. All enrolled children were evaluated during a 4-month follow-up. The end point was the number of patients presenting with acute gastroenteritis or community-acquired pneumonia during a 4-month follow-up study period. RESULTS. We obtained data in 186 subjects: 95 healthy controls and 91 GA-inhibitor users (47 on ranitidine and 44 on omeprazole). The 2 groups were comparable for age, gender, weight, length, and incidence of acute gastroenteritis and pneumonia in the 4 months before enrollment. Rate of subjects presenting with acute gastroenteritis and community-acquired pneumonia was significantly increased in patients treated with GA inhibitors compared with healthy controls during the 4-month follow-up period. In the GA inhibitor-treated group, the rate of subjects presenting with acute gastroenteritis and community-acquired pneumonia was increased when comparing the 4 months before and after enrollment. No differences were observed between H2 blocker and PPI users in acute gastroenteritis and pneumonia incidence in the previous 4 months and during the follow-up period. On the contrary, in healthy controls, the incidence of acute gastroenteritis and pneumonia remained stable. CONCLUSIONS. This is the first prospective study performed in pediatric patients showing that the use of GA inhibitors was associated with an increased risk of acute gastroenteritis and community-acquired pneumonia in GERD-affected children. It could be interesting to underline that we observed an increased incidence of intestinal and respiratory infection in otherwise healthy children taking GA inhibitors for GERD treatment. On the contrary, the majority of the previous data showed that the patients most at risk for pneumonia were those with significant comorbid illnesses such as diabetes or immunodeficiency, and this points to the importance of GA suppression as a major risk factor for infections. In addition, this effect seems to be sustained even after the end of therapy. The results of our study are attributable to many factors, including direct inhibitory effect of GA inhibitors on leukocyte functions and qualitative and quantitative gastrointestinal microflora modification. Additional studies are necessary to investigate the mechanisms of the increased risk of infections in children treated with GA inhibitors, and prophylactic measures could be considered in preventing them.

Background The severity of childhood gastroenteritis is generally believed to be age-related rather than aetiologyrelated. Rotavirus-induced gastroenteritis is more severe than gastroenteritis caused by other enteric pathogens and is also age-related. We thus addressed the question of whether the increased severity of rotavirus-induced gastroenteritis is related to age or to features intrinsic to the agent. Study design In this multicentre, hospital-based, prospective survey, we evaluated the severity of diarrhoea in rotavirus-positive and rotavirus-negative children up to 4 years of age. Severity was assessed with a score in four groups of age-matched children. Results Rotavirus was detected in 381 of 911 children. Disease severity was evaluated in 589 cases for which clinical data were complete. The rotavirus-positive and rotavirus-negative groups differed with regards to diarrhoea duration, hospital stay, degree of dehydration and the number of episodes of vomiting. Gastroenteritis was more severe in rotavirus-positive than in rotavirus-negative children. In contrast, none of the main severity parameters differed in the four age groups, irrespective of the presence of rotavirus. Conclusions These data provide the evidence that aetiology and not age determines diarrhoeal severity. The demonstration that diarrhoea was more severe in rotavirus-positive children supports the need for a rotavirus vaccine and for studies that address the duration of vaccine protection.

We report a significant high incidence of infection with G9P[8] rotavirus in Italian children during the winter epidemic season 1999-2000. The study was carried out on 439 children < 4 years hospitalized with acute diarrhea in Palermo. G9P[8] strains constituted 19% of all rotavirus identified and were not associated with more severe forms of gastroenteritis.