Bovine Colostrum in the Treatment of Acute Diarrhea in Children: A Double-Blinded Randomized Controlled Trial.

OBJECTIVES: To evaluate the effect of bovine colostrum (BC) on the treatment of children with acute diarrhea attending the outpatient clinic. METHODS: This double-blind randomized controlled trial was conducted on 160 children with diarrhea; 80 cases were randomly treated with BC group and 80 cases randomly received placebo (placebo group). All cases were investigated for bacterial causes of diarrhea (Salmonella spp, Shigella spp, diarrheagenic E. coli (DEC), Campylobacter spp., and Vibrio cholerae) as well as for Rotavirus antigen in stool. RESULTS: After 48 h, the BC group had a significantly lower frequency of vomiting, diarrhea and Vesikari scoring compared with the placebo group (p = 0.000, p = 0.000, p = 0.000, respectively), whether it was due to Rotavirus or E. coli infection. CONCLUSIONS: BC is effective in the treatment of acute diarrhea and can be considered as adjuvant therapy in both viral and bacterial diarrhea to prevent diarrhea-related complications.

Oral zinc and common childhood infections--An update.

Zinc is an essential micronutrient important for growth and for normal function of the immune system. Many children in developing countries have inadequate zinc nutrition. Routine zinc supplementation reduces the risk of respiratory infections and diarrhea, the two leading causes of morbidity and mortality in young children worldwide. In childhood diarrhea oral zinc also reduces illness duration and risk of persistent episodes. Oral zinc is therefore recommended for the treatment of acute diarrhea in young children. The results from the studies that have measured the therapeutic effect of zinc on acute respiratory infections, however, are conflicting. Moreover, the results of therapeutic zinc for childhood malaria also are so far not promising.This paper gives a brief outline of the current evidence from clinical trials on therapeutic effect of oral zinc on childhood respiratory infections, pneumonia and malaria and also of new evidence of the effect on serious bacterial illness in young infants.

Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants.

BACKGROUND: In-home iron fortification for infants in developing countries is recommended for control of anaemia, but low absorption typically results in >80% of the iron passing into the colon. Iron is essential for growth and virulence of many pathogenic enterobacteria. We determined the effect of high and low dose in-home iron fortification on the infant gut microbiome and intestinal inflammation. METHODS: We performed two double-blind randomised controlled trials in 6-month-old Kenyan infants (n=115) consuming home-fortified maize porridge daily for 4 months. In the first, infants received a micronutrient powder (MNP) containing 2.5 mg iron as NaFeEDTA or the MNP without iron. In the second, they received a different MNP containing 12.5 mg iron as ferrous fumarate or the MNP without the iron. The primary outcome was gut microbiome composition analysed by 16S pyrosequencing and targeted real-time PCR (qPCR). Secondary outcomes included faecal calprotectin (marker of intestinal inflammation) and incidence of diarrhoea. We analysed the trials separately and combined. RESULTS: At baseline, 63% of the total microbial 16S rRNA could be assigned to Bifidobacteriaceae but there were high prevalences of pathogens, including Salmonella Clostridium difficile, Clostridium perfringens, and pathogenic Escherichia coli. Using pyrosequencing, +FeMNPs increased enterobacteria, particularly Escherichia/Shigella (p=0.048), the enterobacteria/bifidobacteria ratio (p=0.020), and Clostridium (p=0.030). Most of these effects were confirmed using qPCR; for example, +FeMNPs increased pathogenic E. coli strains (p=0.029). +FeMNPs also increased faecal calprotectin (p=0.002). During the trial, 27.3% of infants in +12.5 mgFeMNP required treatment for diarrhoea versus 8.3% in -12.5 mgFeMNP (p=0.092). There were no study-related serious adverse events in either group. CONCLUSIONS: In this setting, provision of iron-containing MNPs to weaning infants adversely affects the gut microbiome, increasing pathogen abundance and causing intestinal inflammation. TRIAL REGISTRATION NUMBER: NCT01111864.

Efficacy of high-dose Lactobacillus rhamnosus GG in controlling acute watery diarrhea in Indian children: a randomized controlled trial.

AIM: To evaluate the effective dose of Lactobacillus rhamnosus GG (LGG) as probiotic in acute watery diarrhea (AWD) in Indian children. SETTING: Hospital-based study. DESIGN: Randomized, controlled, blinded trial. METHODS: All patients of AWD admitted over 1 year were included in the study. They were randomized into 3 groups to receive either only oral rehydration solution (ORS) (group A/control), ORS+LGG powder containing 10(10) colony forming units (CFU) (group B), or ORS+LGG powder containing 10(12) CFU (group C) twice daily for a minimum period of 7 days or until diarrhea stopped along with correction of dehydration. None of them received any other drug such as antibiotic or antidiarrheal medication. The duration and frequency of diarrhea and vomiting were studied. Data were analyzed by SPSS-10 software. RESULTS: The study comprised of 559 patients, group A/controls (n=185), group B (n=188), and group C (n=186). All the groups were similar with respect to age, number of breastfed infants, presentation with dehydration, degree of protein energy malnutrition, and rotavirus infection. The frequency and duration of diarrhea, requirement for intravenous therapy, and hospital stay were significantly lower in both the intervention groups compared with the controls. There was no significant difference between the 2 intervention groups. No complication was observed from the doses of LGG used. CONCLUSIONS: Both the doses of LGG (10(10) and 10(12) CFU) were equally effective to decrease the frequency and duration of diarrhea and reduction in hospital stay in patients of AWD.

Bovine colostrum as a biologic in clinical medicine: a review--Part II: clinical studies.

The value of bovine colostrum as a biologic in medicine is documented in clinical trials and supported by relatively large databases containing case reports and anecdotal findings. The main actions include an antibacterial effect and modulation of the immune response. The ability of bovine colostrum concentrates (BCC are polyvalent bovine colostrum concentrates produced from the colostrums of several 100 cows) to neutralize lipopolysaccharides, i.e. endotoxins arising from Gram-negative bacterial pathogens and to inhibit enterogenic endotoxemia in animal models as shown in the last review to have its counterpart in patient therapy. Clinical trials with BCC provide evidence that oral application reduces the influx of LPS from the gut and this appears to be a major mechanism underlying its therapeutic effect in patients at risk for Gram-negative septic shock; data from two well-controlled clinical studies with a total of 100 surgical patients have shown that the inhibition of intestinal LPS absorption measured after the application of BCC not only reduced the LPS levels in the peripheral blood but also inflammatory parameters like IL-6 and CRP were found to be diminished. The usual daily dose of the commercially available BCC preparation, LactobinA (LC1) is 10 â 20 g daily, but higher doses can be used in the majority of patients because of the low incidence of intolerance problems. In chronic diarrhea involving severe forms of secondary immunodeficiencies, patients receiving LC1 were disease-free for about 4 weeks but the response may be lower in patients with AIDS. BCC is effective in infants with hemorrhagic diarrhea caused by infections with enterohemorrhagic E. coli and reduces the likelihood of the disease progressing to a hemolytic uremic syndrome. The safety of newer BCC products obtained from BSE-free regions seems now beyond contention. In the case of LC1, which was used as a commercial dietary foodstuff in Germany until 1992 and tested in three Phase 1 and 5 clinical studies (two trials in patients with secondary immunodeficiencies, one in surgical patients with gastrointestinal disorders, one in patients undergoing open heart surgery and one in pediatric patients with EHEC infections), there were no cases of BSE-associated disease such as the new variant of Creutzfeldt-Jakob disease. Side effects of clinical relevance are limited to possible intolerance to lactose and sensitivity to milk proteins as these are also present in many commonly used foodstuffs. Important synergistic actions with conventional drug therapies have been observed with BCC including a reduction in LPS plasma levels in patients with Gram-negative bacterial infections treated with bactericidal antibiotics. In healthy persons there are only small concentrations of LPS detectable in peripheral blood (normal values: 3 â 10 pg/ ml plasma, i.e. approximately 0.1 EU/ml). In contrast, elevated systemic levels with concentrations > 300 pg/ml are common in patients with severe Gram-negative sepsis and septic shock. Raised LPS levels occur mainly in patients with Gram-negative bacterial infections who have been treated with bacteriocidal antibiotics. The LPS-lowering effects of BCC are probably due to the numerous active components present in BCC which have their origin in the innate humoral and adaptive immune system of their biologic source, the cow.

[Oral rehydration with a plantain flour-based solution precooked with standardized electrolytes]. / Hidratación oral con una solución a base de harina de plátano precocida con electrolitos estandarizados.

BACKGROUND: The success of oral rehydration therapy in cases of severe diarrheas have led to a need for locally based therapy preparations. A preparation consisting of a precooked plantain flour-based solution and standard rehydration electrolytes was examined for its effectiveness in treating dehydration, as well as its anti-diarrhoeal properties. METHODS: A sample of 101 children, ranging in age from 1 to 48 months, was selected, which had presented diarrhea for less than one week from onset, with mild dehydration and no associated complications. Fifty-four children received the ORS/WHO standard treatment, and 47 received a solution with electrolytes similar to ORS/WHO, containing 50 g of precooked plantain flour instead of glucose (ORS/plantain). RESULTS: Successful rehydration was achieved in 94.4% of the children in the ORS/WHO group and 91.5% in the ORS/plantain group (p = 0.70). Required time for rehydration was 5.8 (SD +/- 3.0) hours in the ORS/WHO group and 6.2 (SD +/- 3.7) hours in the ORS/plantain group (p = 0.31). Stool output during rehydration was 7.5 g/kg body weight/hour (SD +/- 7.6) in the ORS/WHO group, and 7.05 g/kg/hour (SD +/- 9.4) in the ORS/plantain group (p = 0.78). No significant differences were noted in the concentrations of plasma sodium. The observation period was 22.3 hours (SD +/- 5.3) for the ORS/WHO group and 22.7 hours (SD +/- 4.7) for the ORS/plantain group. Stool output during the observation period was 5.7 g/kg/hour (SD +/- 4.7) in the ORS/WHO group and 6.3 g/kg/hour (SD +/- 7.9) in the ORS/plantain group (p = 0.67). The proportion of children requiring intravenous fluids during the first 24 hours was 11.1% in the ORS/WHO group and 8.5% in the ORS/plantain group (RR = 1.31; 95% CI 0.39-4.35). CONCLUSIONS: The plantain flour-based solution proved effective and safe in correcting dehydration; however the antidiarrhoeal properties of ORS/plaintain were not demonstrated.

[Total and specific IgA in colostrum and milk of mothers of Natal-Rio Grande do Norte, Brasil]. / IgA secretora total e específica no colostro e leite de mães da cidade do Natal-Rio Grande do Norte, Brasil.

PURPOSE: To determine the concentration of total secretory IgA and evaluate the repertoire of IgA antibodies to enteropathogenic Escherichia coli and Shigella flexneri antigens in colostrums and milk from mothers in Natal, RN. METHODS: The sample was constituted by 22 healthy clinically women whose babies were born at public hospital in Natal, RN. To determine total secretory IgA a radial immunedifusion tecnique (Mancini et al, 1965), was employed and to detect specific antibodies, immuneenzimatic assays, ELISA was used. RESULTS: The median values of total secretory IgA concentration presented individual variations with high levels in colostrums samples, decreasing during lactation, it was observed a p < 0.001 among the samples from the first day of lactation, to the thirtieth for total IgA concentration. All the donators present in colostrum and milk specific antibodies to Escherichia coli enteropathogenic (EPEC) and Shigella flexneri with titles higer in colostrum. There was parallel and directional pattern between total IgA and IgA anti-EPEC and Shegella flexneri, during period. CONCLUSION: The concentrations of total SIgA and specific antibodies to enteropathogenic Escherichia coli and Shigella flexneri in colostrums and milk in our study do not differ from others accomplished among populations with the same social and econimic features, stressing the importance of human milk as a protector agent against pathogens.

IgA secretora total e específica no colostro e leite de mães da cidade do Natal-Rio Grande do Norte, Brasil / Total and specific IgA in colostrum and milk of mothers of Natal-Rio Grande do Norte, Brasil

PURPOSE: To determine the concentration of total secretory IgA and evaluate the repertoire of IgA antibodies to enteropathogenic Escherichia coli and Shigella flexneri antigens in colostrums and milk from mothers in Natal, RN. METHODS: The sample was constituted by 22 healthy clinically women whose babies were born at public hospital in Natal, RN. To determine total secretory IgA a radial immunedifusion tecnique (Mancini et al, 1965), was employed and to detect specific antibodies, immuneenzimatic assays, ELISA was used. RESULTS: The median values of total secretory IgA concentration presented individual variations with high levels in colostrums samples, decreasing during lactation, it was observed a p < 0.001 among the samples from the first day of lactation, to the thirtieth for total IgA concentration. All the donators present in colostrum and milk specific antibodies to Escherichia coli enteropathogenic (EPEC) and Shigella flexneri with titles higer in colostrum. There was parallel and directional pattern between total IgA and IgA anti-EPEC and Shegella flexneri, during period. CONCLUSION: The concentrations of total SIgA and specific antibodies to enteropathogenic Escherichia coli and Shigella flexneri in colostrums and milk in our study do not differ from others accomplished among populations with the same social and econimic features, stressing the importance of human milk as a protector agent against pathogens.

The sialylated fraction of milk oligosaccharides is partially responsible for binding to enterotoxigenic and uropathogenic Escherichia coli human strains.

Milk oligosaccharides can act as soluble receptors that block bacterial adhesion to the different epithelia. Colonization factor antigens (CFA)/I- and CFA/II-expressing enterotoxigenic Escherichia coli (ETEC) strains constitute one of the main causes of diarrhea in infants. Here, the inhibition of hemagglutination mediated by these strains by milk oligosaccharides was tested. Human milk oligosaccharides showed a strong inhibitory capacity, which decreased when the oligosaccharides were desialylated. Because milk oligosaccharides also are present in the urine of neonates receiving mothers' milk, their ability to bind two uropathogenic Escherichia coli (UPEC) strains was also examined. UPEC strains expressing P (Pap) and P-like (Prs) fimbriae are responsible for infections of the urinary tract such as pyelonephritis and cystitis. The hemagglutination mediated by these strains was inhibited by human milk oligosaccharides. The sialylated fraction was partially responsible for this inhibition in the case of the UPEC expressing the P-like fimbria because differences were found after desialylation. Although bovine milk oligosaccharides were less efficient at inhibiting the hemagglutination of ETEC strains, they were still quite good inhibitors of UPEC strains.

Effect of bifidobacterium Bb12 with or without Streptococcus thermophilus supplemented formula on nutritional status.

Acute diarrhea is a common cause of infant morbidity and mortality. Probiotic supplemented infant formula is one of the effective methods for prevention of rotavirus diarrhea. Other benefits of the probiotics supplemented formula were evaluated by monitoring the growth of the children. A double-blind, placebo-controlled trial was done in 148 children aged 6-36 months. They were divided into 3 groups: the Bb12 group, 51 children received infant formula with Bifidobacteria Bb12 supplement; the Bb12+ST group, 54 children received infant formula with Bb12 and Streptococcus thermophilus supplement; and the control group, 43 children received infant formula without supplement. The mean weight Z-score according to WHO reference standard of the Bbl2 group was -1.8 +/- 0.12, the Bb12+ST group was -1.4 +/- 0.11 and the control group was -1.8 +/- 0.13 at entry. The mean weight Z-score of children after 6 month showed that the children in the Bbl2+ST group had the highest increase in weight which was increased from -1.4 +/- 0.11 to -0.9 +/- 0.12 compared to the Z-score of the Bb12 group which had increased from -1.8 +/- 0.12 to -1.2 +/- 0.13 and in the control group from -1.8 +/- 0.13 to -1.7 +/- 0.25. In terms of the mean height Z-score, the Bb12 group was -2.7 +/- 0.14 to -1.7 +/- 0.16 which was higher than the Bb12+ST group (- 2.2 +/- 0.13 to -1.7 +/- 0.13) but was not different from the control group. However, the mean weight/height Z-score of the Bbl2+ST group had approached the reference standard (Bb12 group -0.1 +/- 0.11 to -0.1 +/- 0.13, Bb12+ST group -0.1 +/- 0.10 to 0.3 +/- 0.17, control group -0.4 +/- 0.12 to -0.1 +/- 0.16). Data showed that children who received the probiotics supplement formula had better growth during the 6 month period.

Inhibition of enteropathogenic Escherichia coli (EPEC) adherence to HEp-2 cells by bovine colostrum and milk.

BACKGROUND: enteropathogenic Escherichia coli (EPEC) is the main etiological agent of infantile diarrhea in Brazil and other developing countries. Human milk IgA protects newborn intestinal mucosa by inhibiting bacterial adhesion to epithelial cells and this effect is shown by in vitro assays of EPEC adhesion to HEp-2 cultured cells. Bovine milk, if effective in promoting this protection, could be an useful tool in the absence of the natural breastfeeding, in high-risk nurseries or in hospital infections. METHODS: the effect of colostrum, milk, and serum from dairy cows on the adherence to EPEC to HEp-2 cells was investigated. Colostrum from immunized and control animals and industrialized milk formulas were fractionated through a membrane device with a molecular weight cut off 10 kDa. The high molecular weight fraction (HMWF) of bovine colostrum was depleted of IgG through an affinity column and absorbed with an EPEC adherent strain. Antibodies were searched by ELISA and immunoblotting (IB). RESULTS: colostrum and milk from EPEC-immunized animals showed and inhibitory activity on adherence similar to that of control non-immunized animals. The inhibitory effect on adhesion was related to the HMWF. IgG-depleted colostrum partially retained the inhibitory effect, whereas IgG-rich eluate lost this property. The EPEC-absorbed fraction retained the inhibitory property. Industrialized milk formulas and respective HMWF also inhibited bacterial adherence. In IB assays, colostrum and milk samples from immunized animals recognized proteins of 30-40 kDa and 94 kDa, a molecular weight consistent with the adhesin intimin, in EPEC extracts. CONCLUSIONS: the inhibitory effect of EPEC adherence may be mediated by HMWF components, and IgG was not the only component responsible for this phenomenon.

Homeopathic treatment of acute childhood diarrhea: results from a clinical trial in Nepal.

OBJECTIVE: To investigate whether the finding in a previous study that homeopathic medicines decrease the duration of acute diarrhea in children could be replicated in a different study population. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Private, charitable health clinic in Kathmandu, Nepal. SUBJECTS: A consecutive sample of 126 children, 6 months to 5 years of age, who presented during April through June, 1994, with more than three unformed stools in the previous 24 hours. INTERVENTION: Children received either an individualized homeopathic medicine or placebo, to be taken one dose after each unformed stool for 5 days. Parents recorded daily stools on diary cards, and health workers made home visits daily to monitor children. OUTCOME MEASURES: Predefined measures were based on the previous study: (1) duration of diarrhea, defined as the time until there were fewer than three unformed stools per day, for two consecutive days, and (2) Average number of stools per day for each group. RESULTS: Of the 126 children initially enrolled, 116 completed treatment. The mean number of stools per day over the entire 5-day treatment period was 3.2 for the treatment group and 4.5 for the placebo group (P = 0.023). A Kaplan-Meier survival analysis of the duration of diarrhea, which included data from all patient visits, showed an 18.4% greater probability that a child would be free of diarrhea by day 5 under homeopathic treatment (P = 0.036). CONCLUSIONS: These results are consistent with the finding from the previous study that individualized homeopathic treatment decreases the duration of diarrhea and number of stools in children with acute childhood diarrhea.

Bovine colostrum ameliorates diarrhea in infection with diarrheagenic Escherichia coli, shiga toxin-producing E. Coli, and E. coli expressing intimin and hemolysin.

BACKGROUND: Diarrheagenic Escherichia coli may cause serious extraintestinal complications, but there is no specific treatment. METHODS: Patients with diarrhea caused by diarrheagenic E. coli, specifically Shiga toxin-producing E. coli and E. coli-expressing intimin and enterohemorrhagic E. coli-hemolysin were treated by administration of pooled bovine colostrum, rich in antibodies to Shiga toxin and enterohemorrhagic E. coli-hemolysin, in a placebo-controlled, double-blind study. Symptom resolution and fecal excretion of infecting strains were assessed. RESULTS: No side effects were attributable to colostrum. Stool frequencies in the group treated with bovine colostrum were significantly reduced compared with those in the placebo group. No effect of therapy on the carriage of the pathogens or on complications of the infection could be demonstrated. CONCLUSIONS: Bovine colostrum is well tolerated and diminishes frequency of loose stools in children with E. coli-associated diarrhea. A prospective study should be conducted among a larger number of children with Shiga toxin-producing E. coli identified early in illness, to determine the effectiveness of colostrum therapy.

Inhibition of enteropathogenic Escherichia coli adhesion to HEp-2 cells by colostrum and milk from mothers delivering low-birth-weight neonates.

UNLABELLED: Breast milk samples from three groups of Brazilian women were evaluated for their inhibitory effect on enteropathogenic Escherichia coli (EPEC) adhesion to HEp-2 cells: G1, mothers delivering preterm babies of appropriate birth weight (n = 12); G2, mothers delivering term babies of low birth weight (n = 11); G3, the control group, mothers delivering term babies of appropriate birth weight (n = 39). Colostrum samples were obtained at 48-72 h and milk samples on the 7th, 30th and 60th days after delivery. All samples showed strong inhibitory activity (66%-100%), without significant differences among the three groups and four periods. Total IgA and anti-EPEC IgA concentrations were significantly higher in colostrum than in milk samples in the three groups studied. The levels of colostral IgA and anti-EPEC IgA observed in G1 and G2 were significantly higher compared to the control group. Western blotting assays showed that individual samples as well as pools of colostrum or milk samples contain IgA antibodies to many EPEC outer membrane proteins. A 94 kDa band with molecular weight consistent with the EPEC adhesin named intimin; was recognized by all samples analysed. Bands of different molecular weight were also recognized by some samples of colostrum and milk, such as a band of approximately 18.4 kDa, with molecular weight equivalent to bundle-forming pilus subunits. CONCLUSION: Our results suggest that colostrum and milk from mothers of premature and small-for-date term neonates are as effective in protecting the newborn against EPEC infections as those from mothers of term babies of appropriate birth weight.