Meta-analysis: Smectite in the treatment of acute infectious diarrhoea in children.

BACKGROUND: Although not currently recommended, dioctahedral smectite (smectite) is commonly used to treat acute infectious diarrhoea in many countries. AIM: To evaluate systematically the effectiveness of smectite in treating acute infectious diarrhoea in children. METHODS: Using medical subject headings and free-language terms, the following electronic databases were searched for studies relevant to acute infectious diarrhoea and smectite: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized-controlled trials were included. RESULTS: Nine randomized-controlled trials (1238 participants) met the inclusion criteria. Combined data from six randomized-controlled trials showed that smectite significantly reduced the duration of diarrhoea compared with placebo. The pooled weighted mean difference was (-22.7 h, 95% CI: -24.8 to -20.6) with a fixed model and remained significant in a random effect model (-24.4 h, 95% CI: -29.8 to -19.1). The chance of cure on intervention day 3 was significantly increased in the smectite vs. the control group (RR 1.64, 95% CI: 1.36-1.98; number needed to treat 4, 95% CI: 3-5). Adverse effects were similar in both groups. CONCLUSIONS: Smectite may be a useful adjunct to rehydration therapy in treating acute paediatric gastroenteritis. However, the results of this meta-analysis should be interpreted with caution as most of the included studies had important limitations. Cost-effectiveness analyses should be undertaken before routine pharmacological therapy with smectite is recommended.

Meta-analysis: non-pathogenic yeast Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea.

BACKGROUND: Antibiotic-associated diarrhoea occurs in up to 30% of patients who receive antibiotics but can be prevented with probiotics. AIM: To systematically evaluate the effectiveness of Saccharomyces boulardii in preventing antibiotic-associated diarrhoea in children and adults. METHODS: Using medical subject headings and free-language terms, the following electronic databases were searched for studies relevant to antibiotic-associated diarrhoea and S. boulardii: MEDLINE, EMBASE, CINAHL and The Cochrane Library. Additional sources were obtained from references in reviewed articles. Only randomized-controlled trials were considered for study inclusion. RESULTS: Of 16 potentially relevant clinical trials identified, five randomized-controlled trials (1076 participants) met the inclusion criteria for this systematic review. Treatment with S. boulardii compared with placebo reduced the risk of antibiotic-associated diarrhoea from 17.2% to 6.7% (RR: 0.43; 95% CI: 0.23-0.78; random effect model). The number needed to treat to prevent one case of antibiotic-associated diarrhoea was 10 (95% CI: 7-16). No side-effects were reported. CONCLUSIONS: A meta-analysis of data from five randomized-controlled trials showed that S. boulardii is moderately effective in preventing antibiotic-associated diarrhoea in children and adults treated with antibiotics for any reason (mainly respiratory tract infections). For every 10 patients receiving daily S. boulardii with antibiotics, one fewer will develop antibiotic-associated diarrhoea.

Epidemiology and impact of rotavirus diarrhoea in Poland.

Hospital and laboratory data were analysed in three hospitals to estimate rotavirus disease burden in 1994-96. Community acquired gastroenteritis was diagnosed in 757 children of whom 41% tested positive for rotavirus. A total of 196 children had rotavirus nosocomial infections (39% of all rotavirus community-acquired and nosocomial cases). Infants less than 24 months old and children less than 3 months old comprised 74% and 11.9% of admissions for rotavirus, respectively. Almost 94% of children with rotavirus infection had severe gastroenteritis (score > or =11). The annual rate of rotavirus associated hospitalization in Poland in 1996 was 3.1/1000 children under the age of 60 months and 5.2/1000 infants under 24 months of age. The mean hospital stay was 9.5 d (+/-9.8 d). We estimated that 8918 children under 60 months of age were hospitalized for rotavirus gastroenteritis in 1996; they accounted for 84899 inpatient days. We conclude that rotavirus is a leading aetiological agent of severe gastroenteritis in young children in Poland and that the burden of this infection is significant. Rotavirus vaccine could significantly decrease the hospitalization rate and the financial impact of rotavirus gastroenteritis in Poland.

[Mastoiditis--a forgotten disease?]. / Antritis--choroba zapomniana?

The symptoms and clinical course of latent mastoiditis in 18. children treated in Polish-American Children's Hospital in Cracow were presented. The ultimate diagnosis of mastoiditis was based on typical findings on antrotomy and the presence of granulation on histology of the tissue obtained during the operation. The main symptoms of latent mastoiditis were: a lack of appetite, chronic or recurrent fever and failure to thrive. 11 children (61%) had experienced more than 3 episodes of acute otitis media before the diagnosis of mastoiditis was established. Bacteria most commonly isolated from the middle ear were those of Staphylococcus, Streptococcus and Proteus species. Radiograms of mastoid processes were negative in up to 45% of those children. The mean duration of antibiotic therapy was 10.7 weeks. After antrotomy complete dissolution of symptoms were observed in 14 patients (78%). It is concluded, that in the presence of symptoms suggesting latent mastoiditis, the possibility of antrotomy, which may shorten the period of ineffective antibiotic therapy, should be considered earlier.

Probiotics in the treatment and prevention of acute infectious diarrhea in infants and children: a systematic review of published randomized, double-blind, placebo-controlled trials.

BACKGROUND: This review was designed to assess the evidence from randomized controlled trials on effects of probiotics in the treatment and prevention of acute infectious diarrhea in infants and children. METHODS: A systematic review of published, randomized, double-blind, placebo-controlled trials on probiotics in the treatment or prevention of acute diarrhea defined as >3 loose or watery stools per 24 hours in infants and children. RESULTS: The use of probiotics as compared with placebo was associated with a significantly reduced risk of diarrhea lasting >3 days. The pooled estimate risk was 0.43 (95% CI, 0.34-0.53) with a fixed-effect model, and remained significant in a random-effect model (0.40; 95% CI, 0.28-0.57). Only Lactobacillus GG showed a consistent effect. Probiotics significantly reduced the duration of diarrhea when compared with placebo, particularly in rotaviral gastroenteritis-the pooled, weighted, mean difference (WMD) assuming the random-effect model was -20.1 hours (95% CI, -26.1 to -14.2) and -24.8 (95% CI, -31.8 to -17.9) respectively. A meta-analysis of the prevention studies was not feasible because of significant clinical and statistical heterogeneity. CONCLUSIONS: There is evidence of a clinically significant benefit of probiotics in the treatment of acute infectious diarrhea in infants and children, particularly in rotaviral gastroenteritis. Lactobacillus GG showed the most consistent effect, although other probiotic strains may also be effective. Further research is needed. Clinical and statistical heterogeneity of the prophylactic interventions preclude drawing firm conclusions about the efficacy of probiotics in preventing acute gastroenteritis.

Extensively and partially hydrolysed preterm formulas in the prevention of allergic diseases in preterm infants: a randomized, double-blind trial.

AIM: A randomized, double-blind study was conducted to evaluate whether use of protein hydrolysate-based preterm formulas in infants with an atopic predisposition helps prevent the development of allergic diseases. METHODS: Preterm infants (n = 122) with at least one first-degree relative (parent or sibling) with allergic disease were randomly assigned to receive an extensively or partially hydrolysed preterm formula (intervention groups) or a standard preterm formula until 4 to 5 mo of age. Infants whose parents preferred that they be breastfed received their mothers' fortified breast milk. RESULTS: Intention-to-treat analysis showed that the overall incidence of allergic diseases did not significantly differ between groups at both 4-5 and 12 mo of age. However, by 12 mo, use of the extensively hydrolysed versus the standard preterm formula had significantly reduced the risk of atopic dermatitis. At 4-5 and 12 mo, there was a significantly increased risk of non-acceptance of the extensively hydrolysed formula compared with the other formulas. CONCLUSIONS: This study failed to show that extensively or partially hydrolysed preterm formulas in comparison with a standard preterm formula reduced the overall incidence of allergic diseases in infants at high risk for atopic disease. However, use of the extensively hydrolysed compared with a standard preterm formula significantly reduced the incidence of atopic dermatitis observed at 12 mo. Infants who received extensively hydrolysed formulas were at increased risk for intervention discontinuation for any reason, particularly non-acceptance of the formula. Because of the small number of patients eligible for this analysis, these results should be interpreted with caution.

Efficacy of Lactobacillus GG in prevention of nosocomial diarrhea in infants.

OBJECTIVE: Nosocomial diarrhea is a major problem in pediatric hospitals worldwide. We evaluated the efficacy of orally administered Lactobacillus GG (LGG) in the prevention of this disease in young children. STUDY DESIGN: Eighty-one children aged 1 to 36 months who were hospitalized for reasons other than diarrhea were enrolled in a double-blind trial and randomly assigned at admission to receive LGG (n = 45) at a dose of 6 x 10(9) colony-forming units or a comparable placebo (n = 36) twice daily orally for the duration of their hospital stay. RESULTS: LGG reduced the risk of nosocomial diarrhea (> or =3 loose or watery stools/24 h) in comparison with placebo (6.7% vs 33.3%; relative risk: 0.2; [95% CI: 0.06-0.6]; number needed to treat: 4 [95% CI: 2-10]). The prevalence of rotavirus infection was similar in LGG and placebo groups (20% vs 27.8%, respectively; relative risk: 0.72; 95% CI: 0.33-1.56). However, the use of LGG compared with placebo significantly reduced the risk of rotavirus gastroenteritis (1/45 [2.2%] vs 6/36 [16.7%], respectively; relative risk: 0.13; 95% CI: 0.02-0.79; number needed to treat: 7; 95% CI: 3-40). CONCLUSIONS: Prophylactic use of LGG significantly reduced the risk of nosocomial diarrhea in infants, particularly nosocomial rotavirus gastroenteritis.

Epidemiology of rotavirus in infants and protection against symptomatic illness afforded by primary infection and vaccination.

This study assessed the frequency of symptomatic and asymptomatic primary and secondary infections with rotavirus in children under 24 months and determined protection against symptomatic illness afforded by rhesus and human-rhesus rotavirus reassortant vaccines. Successive cohorts of children (n 236) were followed through five winter rotavirus seasons with cultures of each reported episode of diarrheal disease and serologic determination of rotavirus exposure on paired sera bracketing the winter. An average of 46% of children experienced rotavirus infection in each season with almost all infected by two years of age. The relative risk of rotavirus associated gastroenteritis in naive children versus naturally immune children was 2.4 (1.1, 5.3). The relative risk of rotavirus associated gastroenteritis in naive children versus vaccinees was 4.1 (1.6, 10.7). In a community with predominantly serotype G1 rotavirus rhesus rotavirus-based vaccines are as protective against rotavirus gastroenteritis as prior natural infection.

Viruses and cells with mutations affecting viral entry are selected during persistent rotavirus infections of MA104 cells.

To better understand mechanisms of persistent rotavirus infections of cultured cells, we established independent, persistently infected cultures of MA104 cells, using rotavirus strain SA11. The cultures were either passaged when the cells reached confluence or supplemented with fresh medium every 7 days. Viral titers in culture lysates varied from 10(4) to 10(7) PFU per ml during 350 days of culture maintenance. Trypan blue staining indicated that 72 to 100% of cells in the cultures were viable, and immunocytochemical staining using a monoclonal antibody directed against viral protein VP6 demonstrated that 38 to 63% of the cells contained rotavirus antigen. We tested the capacity of rotaviruses isolated from the persistently infected cultures (PI viruses) to infect cells cured of persistent infection. Although wild-type (wt) and PI viruses produced equivalent yields in parental MA104 cells, PI viruses produced greater yields than wt virus in cured cells, which indicates that viruses and cells coevolve during persistent rotavirus infections of MA104 cells. To determine whether mutations in viruses and cells selected during these persistent infections affect viral entry, we tested the effect of trypsin treatment of the viral inoculum on growth of wt and PI viruses. Trypsin pretreatment is required for postattachment penetration of rotavirus virions into cells. In contrast to the case with wt virus, PI viruses produced equivalent yields with and without trypsin pretreatment in parental MA104 cells. However, PI viruses required trypsin pretreatment for efficient growth in cured cells. These results indicate that mutant viruses and cells are selected during maintenance of persistent rotavirus infections of MA104 cells and suggest that mutations in each affect trypsin-dependent steps in rotavirus entry.

Safety and immunogenicity of live attenuated human-bovine (UK) reassortant rotavirus vaccines with VP7-specificity for serotypes 1, 2, 3 or 4 in adults, children and infants.

Live rotavirus vaccine candidates representing VP7 serotypes 1, 2, 3 or 4 derived by reassortment between bovine UK rotavirus and human rotavirus strains D, DS-1, P or ST3 were evaluated for safety and immunogenicity in adults, children and infants. Infection was defined by evidence of rotavirus shed in stools or a 4-fold or greater increase in serum rotavirus-specific IgA or IgG ELISA or plaque reduction neutralization antibody. A single oral dose (10(5.3) or 10(5.8) pfu) of reassortant virus was well tolerated and infected most infants: 10/20 (50%) by D x UK; 9/11 (82%) by DS-1 x UK; 8/10 (80%) by P x UK and 13/14 (93%) by ST3 x UK. All 14 infants given two doses of D x UK were infected. These findings demonstrating satisfactory levels of attenuation, safety, infectivity and immunogenicity of each reassortant in infants warrant additional studies of a candidate vaccine containing these four strains.