Dataset Information

Oral Phage Therapy of Acute Bacterial Diarrhea With Two Coliphage Preparations: A Randomized Trial in Children From Bangladesh.

ABSTRACT: Antibiotic resistance is rising in important bacterial pathogens. Phage therapy (PT), the use of bacterial viruses infecting the pathogen in a species-specific way, is a potential alternative.T4-like coliphages or a commercial Russian coliphage product or placebo was orally given over 4 days to Bangladeshi children hospitalized with acute bacterial diarrhea. Safety of oral phage was assessed clinically and by functional tests; coliphage and Escherichia coli titers and enteropathogens were determined in stool and quantitative diarrhea parameters (stool output, stool frequency) were measured. Stool microbiota was studied by 16S rRNA gene sequencing; the genomes of four fecal Streptococcus isolates were sequenced.No adverse events attributable to oral phage application were observed (primary safety outcome). Fecal coliphage was increased in treated over control children, but the titers did not show substantial intestinal phage replication (secondary microbiology outcome). 60% of the children suffered from a microbiologically proven E. coli diarrhea; the most frequent diagnosis was ETEC infections. Bacterial co-pathogens were also detected. Half of the patients contained phage-susceptible E. coli colonies in the stool. E. coli represented less than 5% of fecal bacteria. Stool ETEC titers showed only a short-lived peak and were otherwise close to the replication threshold determined for T4 phage in vitro. An interim analysis after the enrollment of 120 patients showed no amelioration in quantitative diarrhea parameter by PT over standard care (tertiary clinical outcome). Stool microbiota was characterized by an overgrowth with Streptococcus belonging to the Streptococcus gallolyticus and Streptococcus salivarius species groups, their abundance correlated with quantitative diarrhea outcome, but genome sequencing did not identify virulence genes.Oral coliphages showed a safe gut transit in children, but failed to achieve intestinal amplification and to improve diarrhea outcome, possibly due to insufficient phage coverage and too low E. coli pathogen titers requiring higher oral phage doses. More knowledge is needed on in vivo phage-bacterium interaction and the role of E. coli in childhood diarrhea for successful PT.The study was supported by a grant from Nestlé Nutrition and Nestlé Health Science. The trial was registered with Identifier NCT00937274 at ClinicalTrials.gov.

SUBMITTER: Sarker SA

PROVIDER: S-EPMC4776075 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Oral Phage Therapy of Acute Bacterial Diarrhea With Two Coliphage Preparations: A Randomized Trial in Children From Bangladesh.

Sarker Shafiqul Alam SA Sultana Shamima S Reuteler Gloria G Moine Deborah D Descombes Patrick P Charton Florence F Bourdin Gilles G McCallin Shawna S Ngom-Bru Catherine C Neville Tara T Akter Mahmuda M Huq Sayeeda S Qadri Firdausi F Talukdar Kaisar K Kassam Mohamed M Delley Michèle M Loiseau Chloe C Deng Ying Y El Aidy Sahar S Berger Bernard B Brüssow Harald H

EBioMedicine 20160105

<h4>Background</h4>Antibiotic resistance is rising in important bacterial pathogens. Phage therapy (PT), the use of bacterial viruses infecting the pathogen in a species-specific way, is a potential alternative.<h4>Method</h4>T4-like coliphages or a commercial Russian coliphage product or placebo was orally given over 4 days to Bangladeshi children hospitalized with acute bacterial diarrhea. Safety of oral phage was assessed clinically and by functional tests; coliphage and Escherichia coli tite ...[more]

PMID: 26981577

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Project description:BACKGROUND:Diarrhea and acute respiratory infection (ARI) are major causes of child mortality. We aimed to identify risk factors associated with diarrhea and ARI among children under 2 years of age in rural northern Bangladesh. METHOD:We collected information on diarrhea and ARI in the previous 14 days and the previous 6 months at 6, 12, 18 and 24?months of age as part of a longitudinal, cluster randomized effectiveness trial, the Rang-Din Nutrition Study which enrolled 4011 pregnant women at ?20 gestational weeks. Women and their children were followed up until 2 years postpartum. Information on household socioeconomic status, type of toilet, garbage disposal system, food insecurity, number of under-five children in the household, type of family, maternal characteristics and child characteristics was collected at baseline and/or at 6, 12, 18 and 24?months postpartum. Data on newborn health and feeding behaviors were collected within 72?h of delivery. Associations between potential risk factors and morbidity prevalence outcomes were assessed using logistic regression controlling for potential confounders. RESULTS:Out of 3664 live born children, we collected information from ~?3350 children at 6, 12, 18 and 24?months of age. Diarrhea in the previous 14 days, and in the previous 6 months, was associated with maternal depression score and food insecurity; diarrhea in the previous 6 months was also associated with family type (nuclear vs. joint). ARI in the previous 14 days was associated with maternal depression score, type of toilet and garbage disposal, household food insecurity and sex. Cough or nasal discharge in the past 6 months was associated with maternal depression score, type of toilet and garbage disposal, household food insecurity, sex and perceived overall physical condition of the infant after birth. CONCLUSION:Maternal depression and food insecurity appear to be important risk factors for diarrhea and respiratory infection among children under 2 years of age in this setting. These findings suggest that policies and programs that include strategies to address maternal mental health and household food insecurity may contribute to improved child health. TRIAL REGISTRATION:The trial was registered with the US National Institutes of Health at ClinicalTrials.gov, # NCT01715038 , with registration completed October 26, 2012.

Project description:Zinc supplementation is an added intervention with oral rehydration solution (ORS) for treating childhood diarrhea as per World Health Organization recommendations. Our study aimed to determine the prevalence of zinc administration in addition to ORS for childhood diarrhea before hospitalization and the nutritional profile of those children admitted to the outpatient department of the largest diarrheal facility in Bangladesh. This study used a screening dataset of a clinical trial (www.clinicaltrials.gov; NCT04039828) on zinc supplementation at a Dhaka hospital (International Centre for Diarrhoeal Disease Research, Bangladesh) between September 2019 and March 2020. A total of 1,399 children aged 3-59 months were included in our study. Children were divided into two groups (one group received zinc and another did not) and were analyzed accordingly; 39.24% (n = 549) children received zinc along with ORS for the current diarrheal episode prior to hospitalization. Percentages of underweight (weight-for-age z-score < -2 SD), stunting (length/height-for-age z-score < -2 SD), wasting (weight-for-length/height z-score < -2 SD), and overweight (weight-for-age z-score > +2 SD) among these children were 13.87% (n = 194), 14.22% (n = 199), 12.08% (n = 169), and 3.43% (n = 48), respectively. In logistic regression after adjusting age, sex, and nutritional status (underweight, stunting, wasting, and overweight), association of dehydration (adjusted odds ratio [aOR]: 0.06; 95% CI: 0.03-0.11; P < 0.01), bloody diarrhea (aOR: 0.18; 95% CI: 0.11-0.92; P < 0.01), and fever (aOR: 0.27; 95% CI: 0.18-0.41; P < 0.01) were less with children who received zinc at home. Bangladesh is one of the leading zinc coverage areas globally but lags behind the target for zinc coverage in diarrheal illness among under-five children. Policymakers should scale up and formulate guidelines with sustainable strategies to encourage zinc supplementation in diarrheal episodes in Bangladesh and elsewhere.

Dataset Information

Oral Phage Therapy of Acute Bacterial Diarrhea With Two Coliphage Preparations: A Randomized Trial in Children From Bangladesh.

Publications

Oral Phage Therapy of Acute Bacterial Diarrhea With Two Coliphage Preparations: A Randomized Trial in Children From Bangladesh.

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