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

University of Vermont700 enrolled

Overview

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 IPV (inactivated polio vaccine) boost on the efficacy of OPV (oral polio vaccine) and 2) to determine the efficacy of Rotarix 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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

SINGLE

Enrollment

700

Conditions

Rotavirus Diarrhea Vaccine Virus Shedding

Eligibility

Sex: ALLMax age: 7 DaysHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Mother willing to sign informed consent form. 2. Healthy infant aged 0 to 7 days old. 3. No obvious congenital abnormalities or birth defects. 4. No abnormal (frequency and consistency) stools since birth. 5. Stable household with no plans to leave the area for the next one year. Exclusion Criteria: 1. Parents are not willing to have child vaccinated at the field clinic. 2. Parents are not willing to have child's blood drawn. 3. Parents are planning to enroll child into another clinical study during the time period of this trial. 4. Mother not willing to have blood drawn and breast milk extracted. 5. Parents not willing to have field research assistant in home two times per week. 6. History of seizures or other apparent neurologic disorders. 7. Infant received any vaccines before start of study, except Bacillus Calmette-Guerin (BCG). 8. Infant has any sibling currently or previously enrolled in this study, including a twin.

Outcomes

Primary Outcomes

Presence of Fecal Shedding of Polio Vaccine Virus Determined by Culture (Polio Trial)

Any Sabin type poliovirus in any fecal samples at days 0, 4, 11, 18 or 25 following week 52 dose

Time frame: 25 days following week 52 visit

Number of Participants With One or More Episodes of Rotavirus-associated Diarrhea (Rotavirus Trial)

Diarrheal episode defined as presence of 3 or more abnormally loose stools in 24h period with \>=72 hours separating episodes. Rotavirus antigen detected by ELISA in diarrheal stool.

Time frame: Birth to one year

Secondary Outcomes

Duration of Fecal Shedding of Polio Vaccine Virus, Each Sabin Type (Polio Trial)

Shedding index, calculated as duration days multiplied by mean log (shedding amount) for Sabin types 1, 2, and 3. Outcome is conditioned on infants with at least one detection by quantitative PCR (qPCR) at day 4,11,18, or 25. If shedding data point was missing it was assumed that the infant was not shedding at that time. Lower shedding index is better outcome

Time frame: from day 4 to day 25 following the week 52 visit

Community Fecal Shedding of Polio Vaccine Virus Just Prior to Oral Polio Vaccine Dose at 52 Weeks (Polio Trial)

Only 8 infants were shedding at baseline so results are not presented for this outcome due to insufficient data

Time frame: post 52 weeks

Presence of Fecal Polio Virus Shedding Within the Three Sabin Strains (Polio Trial)

Frequency (%) of infants excreting poliovirus at any of the 5 time points (day 0, 4,11,18, 25) post week 52 oral polio vaccine dose. Presence of poliovirus is determined by polymerase chain reaction (PCR)

Time frame: 25 days following week 52 visit

Serum Neutralizing Antibody Response (Polio Trial)

Seropositive defined as antibodies present at ≥1:8 dilution, antibody titers \<1:8 were seronegative. Non-seroconversions are those who did not seroconvert between week 18 (post oral polio vaccine dose 2) and week 40, adjusted for residual maternal antibody

Time frame: 18-40 weeks

Total Number of Diarrheal Episodes (Rotavirus Trial)

A diarrheal episode is defined as the presence of 3 or more abnormally loose stools in a 24 hour period with at least 72 diarrhea-free hours separating distinct episodes

Time frame: Birth to one year

Total Duration of Rotavirus-associated Diarrheal Episodes (Rotavirus Trial)

A diarrheal episode is defined as the presence of 3 or more abnormally loose stools in a 24 hour period with at least 72 diarrhea-free hours separating distinct episodes. Rotavirus positive specimens were determined by ELISA Those with no rotavirus diarrheal episodes are counted as duration 0

Time frame: Birth to one year

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes