Exploration of the Biologic Basis for Underperformance of Oral Polio and Rotavirus Vaccines in Bangladesh

Study Overview
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Brief Summary
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Oral polio and rotavirus vaccines are significantly less effective in children living in the developing world. Tropical enteropathy, which is associated with intestinal inflammation, decreased absorption and increased permeability, may contribute substantially to oral vaccine failure in developing country settings. Other possible causes of oral vaccine underperformance include malnutrition, interference with maternal or breastmilk antibodies, changes in gut microbiota, and genetic susceptibility. Primary Objective: to determine whether tropical enteropathy impairs the efficacy of oral polio and rotavirus vaccines in children in Bangladesh. Secondary Objectives: 1) to determine the impact of an inactivated polio vaccine (IPV) boost on the efficacy of oral polio vaccine and 2) to determine the efficacy of oral rotavirus vaccine to prevent rotavirus diarrhea The polio and rotavirus randomized clinical trials are embedded as secondary objectives within the exploratory study of tropical enteropathy. The primary and secondary outcome measures are relevant to the randomized clinical trials.

Official Title
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Exploration of the Biologic Basis for Underperformance of Oral Polio and Rotavirus Vaccines in Bangladesh

Conditions
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Rotavirus Diarrhea, Vaccine Virus Shedding, Tropical Enteropathy

Intervention / Treatment
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* Biological: IPV
* Biological: Rotarix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mother willing to sign informed consent form. Healthy infant aged 0 to 7 days old. No obvious congenital abnormalities or birth defects. No abnormal (frequency and consistency) stools since birth. Stable household with no plans to leave the area for the next one year. Exclusion Criteria: Parents are not willing to have child vaccinated at the field clinic. Parents are not willing to have child's blood drawn. Parents are planning to enroll child into another clinical study during the time period of this trial. Mother not willing to have blood drawn and breast milk extracted. Parents not willing to have field research assistant in home two times per week. History of seizures or other apparent neurologic disorders. Infant received any vaccines before start of study, except Bacillus Calmette-Guerin (BCG). Infant has any sibling currently or previously enrolled in this study, including a twin.

Ages Eligible for Study
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Maximum Age: 7 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rotarix + No IPV<br>Randomized to receive rotarix vaccine but no IPV boost | Biological: Rotarix<br>* Administered per protocol<br>|
| Experimental: Rotarix + with IPV boost<br>Randomized to receive both rotarix vaccine and IPV boost | Biological: IPV<br>* Administered per protocol<br>Biological: Rotarix<br>* Administered per protocol<br>|
| No Intervention: No Rotarix + No IPV<br>Randomized to receive neither rotarix vaccine nor IPV boost | |
| Experimental: No Rotarix + with IPV boost<br>Randomized to receive no rotarix vaccine but to receive IPV boost | Biological: IPV<br>* Administered per protocol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of fecal shedding of polio vaccine virus determined by culture (polio trial) |  | 25 days following week 52 visit | 
| One or more episodes of rotavirus-associated diarrhea (rotavirus trial) |  | Birth to one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of fecal shedding of polio vaccine virus (polio trial) |  | 25 days following week 52 visit | 
| Community fecal shedding of polio vaccine virus just prior to one year OPV dose (polio trial) |  | 52 weeks | 
| Presence and duration of fecal polio virus shedding within the three individual virus strains (polio trial) |  | 25 days following week 52 visit | 
| Serum neutralizing antibody response (polio trial) |  | 40 weeks and 53 weeks | 
| Total number of diarrheal episodes (rotavirus trial) |  | Birth to one year | 
| Total duration of rotavirus-associated diarrheal episodes (rotavirus trial) |  | Birth to one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral Vaccines, Vaccine Responsiveness, Tropical Enteropathy