Antibacterial Treatment Against Diarrhea in Oral Rehydration Solution
Antibacterial Treatment Against Diarrhea in Oral Rehydration Solution
This study hopes to demonstrate the potentials of a new form of therapy for childhood
 diarrhea, a major cause of morbidity and deaths in Bangladesh and other developing countries,
 and thus a priority for improving child health.
This randomized double-blind, placebo controlled trial (RCT) aims to evaluate the effect of
 oral administered E. coli phage in children aged 4-60 months of age with proven ETEC and EPEC
 diarrhea. Children will be screened to exclude V. cholerae infections by dark field
 microscopy, rotavirus by stool ELISA, and invasive diarrhoea clinically as well as by stool
 microscopy, to identify children with possible ETEC and EPEC diarrhoea. Enrolled children
 will be randomly assigned, in equal numbers, to receive either: (i) a new T4 phage cocktail
 or (ii) Russian anti-E. coli phage cocktail (Microgen) at the dose recommended by the
 manufacturer or (iii) only oral rehydration solution (placebo) for 5 days in addition to
 management of dehydration and continued feeding in accordance with WHO guidelines. Duration
 of diarrhea, daily and cumulative stool output, volume of oral rehydration solution intake,
 stool frequency, time to recovery and weight gain will be the main outcome measures. As the
 dose of phage we intend to use in this therapeutic trial is higher than the dose administered
 to young children in earlier safety trial, we plan to initially conduct a safety study with
 these three study products in 45 children with non cholera, non rotavirus and non invasive
 diarrhea, to randomize equally in the three intervention groups, as for the final study
 mentioned above. The outcome measures in this safety part will include assessment of
 laboratory parameters including renal and liver function tests, haematological indices, and
 microbiological efficacy of phage by measuring phage and E. coli titre in daily stool
 samples. If the higher dose is found safe, tolerable, and not associated with any significant
 adverse event, we will proceed to the clinical efficacy trial.

 We believe if T4 coli phage is assessed to be effective in the overall diarrhea management,
 this might lead to development of an affordable and sustainable adjunct to the currently
 available case management of E. coli diarrhea, benefiting millions of children worldwide.
Inclusion Criteria:

 1. Sex: male

 2. Age: 6 - 24 months

 3. Better nourished (weight for age > 60 NCHS median)

 4. H/o. diarrhea of less than 48 hours

 5. Written informed consent from either parents/guardian (thumb impression for those who
 are not literate) for children

 6. Negative test results for dark field microscopy of Vibrio cholerae and ELISA test for
 rotavirus in initial stool samples

 Exclusion Criteria:

 1. Systemic infection requiring antibiotic treatment

 2. Severe malnutrition (W/A < 60%)

 3. Unwilling to comply with study procedures

 4. Currently participating or have participated in another clinical trial within the last
 4 weeks at screening

 5. Clinically significant abnormalities from medical history, physical examination, vital
 signs, haematology, clinical chemistry results, or other laboratory abnormalities

 6. Clinically suggestive of invasive diarrhea