Immunity to Oral Rotavirus Vaccine, Immunity to Oral Polio Vaccine, Shedding of Oral Rotavirus Vaccine
Conditions
Keywords
rotavirus, polio, zinc supplement, probiotic supplement, rotavirus vaccine shedding
Brief summary
Background: Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function. This study enrolled infants 5 weeks old living in urban Vellore, India to assess the effects of daily zinc (5 mg), probiotic (1010 Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix,GlaxoSmithKline Biologicals) given at 6 and 10 weeks of age. Probiotics and zinc (or placebo) were provided for six weeks. A single dose of test product was administered daily one week prior to first study dose of rotavirus and polio vaccines through 1 week following second study dose of rotavirus and polio vaccines.
Detailed description
Co- Primary objectives: 1. To evaluate the serologic immune response to rotavirus vaccine (sero-conversion or four-fold rise in rotavirus immunoglobulin A (IgA) antibodies) among Indian infants receiving zinc supplementation given daily for a week prior to the administration of the first dose through a week following the second dose of oral rotavirus vaccine compared to those receiving a zinc placebo. 2. To evaluate the serologic immune response to rotavirus vaccine (sero-conversion or four-fold rise in rotavirus IgA antibodies) among Indian infants receiving probiotic supplementation given daily for a week prior to the administration of the first dose through a week following the second dose of oral rotavirus vaccine compared to those receiving a probiotic placebo.
Interventions
DIETARY_SUPPLEMENTProbiotic
A capsule that contains at least 1 x 10\^9 Lactobacillus rhamnosus GG organisms per capsule. The contents of this capsule were given once daily orally.
DIETARY_SUPPLEMENTZinc
Zinc sulphate syrup is zinc sulphate heptahydrate (concentration 1mg/ml). 5 ml of this suspension was given once daily orally.
DIETARY_SUPPLEMENTProbiotic placebo
The probiotic placebo was manufactured by the same company that manufactured the probiotic and contained inulin powder but no Lactobacillus rhamnosus GG. The contents of the capsule were given once daily orally.
DIETARY_SUPPLEMENTZinc placebo
The zinc placebo excluded the zinc sulphate but contained lactose and was diluted to match the taste. 5 ml of this suspension was given orally once daily.
BIOLOGICALRotavirus vaccine
1 ml Rotarix®, a lyophilized human rotavirus vaccine reconstituted with calcium carbonate buffer provided orally at 6 and 10 weeks.
BIOLOGICALOral polio vaccine
A liquid trivalent polio vaccine provided orally at 6 and 10 weeks.
Sponsors
Christian Medical College, Vellore, India
Ministry of Science and Technology, India
PATH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Weeks to 16 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Infants 35-41 days old * Live in area under surveillance * Current weight ≥3.2 kg * No syndromic evidence of immunocompromise as determined by medical doctor * No prior illness requiring hospitalization * No current medical condition as determined by medical doctor which precludes study involvement * Available for follow up for duration of study (through approximately 14 weeks of age) * Parents/guardians of infant are able to understand and follow study procedures and agree to participate in the study by providing signed informed consent
Exclusion criteria
* Child has history of atopic symptoms * Child has a known digestive system defect * Child has history of chronic diarrhea * Child has major congenital anomalies * Child has received a prior dose of rotavirus vaccine * Child has received a prior dose of polio vaccine (beyond the birth dose)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | from first dose of rotavirus vaccine to 4 weeks after last dose of vaccine | Defined as an increase in serum anti-rotavirus (RV) VP6 IgA antibodies consistent with seroconversion (detection of serum anti-RV VP6 immunoglobulin A (IgA) antibodies at a concentration ≥20 U/ml in a previously seronegative individual) or a fourfold rise in anti-RV VP6 IgA antibodies between baseline and 14 weeks of age. Pre-vaccination blood samples were taken when the subject received the first dose of rotavirus vaccine (when the subject was 6 weeks of age); post-vaccination blood samples were taken 4 weeks after the second dose of rotavirus vaccine was administered (14 weeks of age). |
| Geometric Mean Concentration of Rotavirus-specific IgA | from first dose of rotavirus vaccine to 4 weeks after last dose of vaccine | Pre-vaccination blood samples were taken when the subject received the first dose of rotavirus vaccine (when the subject was 6 weeks of age); post-vaccination blood samples were taken 4 weeks after the second dose of rotavirus was administered (14 weeks of age). Pre-vaccination blood samples were taken when the subject received the first dose of rotavirus vaccine (when the subject was 6 weeks of age); post-vaccination blood samples were taken 4 weeks after the second dose of rotavirus vaccine was administered (14 weeks of age). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | from first dose of OPV to 4 weeks after last dose of OPV | A serologic immune response to OPV is defined as a neutralizing antibody titer to polio virus subtype 3 greater than or equal to 1:8 at 14 weeks of age. This antigen will be used as a conservative estimate because it gives the lowest immune response of all three polio antigens. Pre-vaccination blood samples were taken when the subject received the first dose of OPV vaccine (when the subject was 6 weeks of age); post-vaccination blood samples were taken 4 weeks after the second dose of OPV was administered (14 weeks of age). |
| Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | 0, 4 and/or 7 day post dose 1 of rotavirus vaccine | Shedding of rotavirus following vaccination through detection of rotavirus antigen by ELISA and confirmed as vaccine type by Real-time polymerase chain reaction (RT-PCR). Stool samples were collected on Day 0 (i.e., day of vaccination or -1), Day 4 (±1) and Day 7 (-1 to +2) post vaccination. |
| Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | 0, 4 and/or 7 day post dose 2 of rotavirus vaccine | Shedding of rotavirus following vaccination through detection of rotavirus antigen by ELISA and confirmed as vaccine type by RT-PCR. Stool samples were collected on Day 0 (i.e., day of vaccination or -1), Day 4 (±1) and Day 7 (-1 to +2) post vaccination. |
| Serious Adverse Events (SAEs) | from first day of study to 4 weeks after last dose | Field workers documented information on SAEs through the duration of the study during home visits (twice weekly between study clinic visits) or SAEs were documented by study clinicians at the study clinic or hospital. All SAEs occurring at any time during the study were recorded on a SAE Form and were reviewed and evaluated by a study clinician and the local IRB. The relationship of the SAE to study vaccine was evaluated and recorded and reported to the local institutional review board (IRB). All SAEs were followed until satisfactory resolution. |
Countries
India
Participant flow
Recruitment details
Potential participants for this study lived in the area surrounding the Christian Medical College (CMC) in the town of Vellore, Tamil Nadu, India. Parents were contacted through the existing Demographic Surveillance System shortly after the child's birth. Procedures were conducted in the Chinallapuram Field Clinic.
Participants by arm
| Arm | Count |
|---|---|
| Zinc and Probiotic Received daily zinc and probiotic supplements, in addition to rotavirus vaccine and trivalent oral polio vaccines.
Probiotic: A capsule that contains at least 1 x 10\^9 Lactobacillus rhamnosus GG organisms per capsule. The contents of this capsule were given once daily orally.
Zinc: Zinc sulphate syrup is zinc sulphate heptahydrate (concentration 1mg/ml). 5 ml of this suspension was given once daily orally.
Rotavirus vaccine: 1 ml Rotarix®, a lyophilized human rotavirus vaccine reconstituted with calcium carbonate buffer provided orally at 6 and 10 weeks.
Oral polio vaccine: A liquid trivalent polio vaccine provided orally at 6 and 10 weeks. | 155 |
| Zinc Alone Received daily zinc and probiotic placebo supplement, in addition to rotavirus vaccine and trivalent oral polio vaccine.
Zinc: Zinc sulphate syrup is zinc sulphate heptahydrate (concentration 1mg/ml). 5 ml of this suspension was given once daily orally.
Probiotic placebo: The probiotic placebo was manufactured by the same company that manufactured the probiotic and contained inulin powder but no LGG. The contents of the capsule were given once daily orally.
Rotavirus vaccine: 1 ml Rotarix®, a lyophilized human rotavirus vaccine reconstituted with calcium carbonate buffer provided orally at 6 and 10 weeks.
Oral polio vaccine: A liquid trivalent polio vaccine provided orally at 6 and 10 weeks. | 155 |
| Probiotic Alone Received daily zinc placebo and probiotic supplement, in addition to rotavirus vaccine and trivalent oral polio vaccine.
Probiotic: A capsule that contains at least 1 x 10\^9 Lactobacillus rhamnosus GG organisms per capsule. The contents of this capsule were given once daily orally.
Zinc placebo: The zinc placebo excluded the zinc sulphate but contained lactose and was diluted to match the taste. 5 ml of this suspension was given orally once daily.
Rotavirus vaccine: 1 ml Rotarix®, a lyophilized human rotavirus vaccine reconstituted with calcium carbonate buffer provided orally at 6 and 10 weeks.
Oral polio vaccine: A liquid trivalent polio vaccine provided orally at 6 and 10 weeks. | 155 |
| Placebo Received daily zinc placebo and probiotic supplement, in addition to rotavirus vaccine and trivalent oral polio vaccine.
Probiotic placebo: The probiotic placebo was manufactured by the same company that manufactured the probiotic and contained inulin powder but no LGG. The contents of the capsule were given once daily orally.
Zinc placebo: The zinc placebo excluded the zinc sulphate but contained lactose and was diluted to match the taste. 5 ml of this suspension was given orally once daily.
Rotavirus vaccine: 1 ml Rotarix®, a lyophilized human rotavirus vaccine reconstituted with calcium carbonate buffer provided orally at 6 and 10 weeks.
Oral polio vaccine: A liquid trivalent polio vaccine provided orally at 6 and 10 weeks. | 155 |
| Total | 620 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Blood Analyzed for Immunogenicity | Protocol Violation | 4 | 2 | 6 | 1 |
| Evaluated for Safety | Physician Decision | 1 | 0 | 1 | 0 |
| Received Both Vaccines | Adverse Event | 2 | 0 | 0 | 0 |
| Received Both Vaccines | Lost to Follow-up | 4 | 3 | 4 | 4 |
| Received Both Vaccines | Withdrawal by Subject | 7 | 7 | 8 | 15 |
Baseline characteristics
| Characteristic | Zinc Alone | Zinc and Probiotic | Total | Placebo | Probiotic Alone |
|---|---|---|---|---|---|
| Age, Continuous | 5.1 weeks STANDARD_DEVIATION 0.3 | 5.1 weeks STANDARD_DEVIATION 0.3 | 5.1 weeks STANDARD_DEVIATION 0.3 | 5.2 weeks STANDARD_DEVIATION 0.3 | 5.1 weeks STANDARD_DEVIATION 0.3 |
| Region of Enrollment India | 155 participants | 155 participants | 620 participants | 155 participants | 155 participants |
| Religion Christian | 10 Participants | 5 Participants | 26 Participants | 6 Participants | 5 Participants |
| Religion Hindu | 96 Participants | 99 Participants | 415 Participants | 104 Participants | 116 Participants |
| Religion Muslim | 49 Participants | 51 Participants | 179 Participants | 45 Participants | 34 Participants |
| Sex: Female, Male Female | 87 Participants | 75 Participants | 326 Participants | 84 Participants | 80 Participants |
| Sex: Female, Male Male | 68 Participants | 80 Participants | 294 Participants | 71 Participants | 75 Participants |
| Type of house Mixed | 47 Participants | 59 Participants | 212 Participants | 54 Participants | 52 Participants |
| Type of house Permanent (pucca) | 92 Participants | 85 Participants | 360 Participants | 90 Participants | 93 Participants |
| Type of house Temporary | 16 Participants | 11 Participants | 48 Participants | 11 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 154 | 0 / 155 | 0 / 154 | 0 / 155 |
| other Total, other adverse events | 149 / 154 | 152 / 155 | 148 / 154 | 146 / 155 |
| serious Total, serious adverse events | 5 / 154 | 3 / 155 | 2 / 154 | 4 / 155 |
Outcome results
Primary
Geometric Mean Concentration of Rotavirus-specific IgA
Pre-vaccination blood samples were taken when the subject received the first dose of rotavirus vaccine (when the subject was 6 weeks of age); post-vaccination blood samples were taken 4 weeks after the second dose of rotavirus was administered (14 weeks of age). Pre-vaccination blood samples were taken when the subject received the first dose of rotavirus vaccine (when the subject was 6 weeks of age); post-vaccination blood samples were taken 4 weeks after the second dose of rotavirus vaccine was administered (14 weeks of age).
Time frame: from first dose of rotavirus vaccine to 4 weeks after last dose of vaccine
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Zinc and Probiotic | Geometric Mean Concentration of Rotavirus-specific IgA | Post-vaccination | 23.4 titer |
| Zinc and Probiotic | Geometric Mean Concentration of Rotavirus-specific IgA | Pre-vaccination | 9.3 titer |
| Zinc Alone | Geometric Mean Concentration of Rotavirus-specific IgA | Post-vaccination | 23.9 titer |
| Zinc Alone | Geometric Mean Concentration of Rotavirus-specific IgA | Pre-vaccination | 10.8 titer |
| Probiotic Alone | Geometric Mean Concentration of Rotavirus-specific IgA | Pre-vaccination | 11.3 titer |
| Probiotic Alone | Geometric Mean Concentration of Rotavirus-specific IgA | Post-vaccination | 25.4 titer |
| Placebo | Geometric Mean Concentration of Rotavirus-specific IgA | Pre-vaccination | 12.2 titer |
| Placebo | Geometric Mean Concentration of Rotavirus-specific IgA | Post-vaccination | 26.0 titer |
| Zinc | Geometric Mean Concentration of Rotavirus-specific IgA | Pre-vaccination | 10.0 titer |
| Zinc | Geometric Mean Concentration of Rotavirus-specific IgA | Post-vaccination | 23.7 titer |
| No Zinc | Geometric Mean Concentration of Rotavirus-specific IgA | Post-vaccination | 25.7 titer |
| No Zinc | Geometric Mean Concentration of Rotavirus-specific IgA | Pre-vaccination | 11.7 titer |
| Probiotic | Geometric Mean Concentration of Rotavirus-specific IgA | Pre-vaccination | 10.2 titer |
| Probiotic | Geometric Mean Concentration of Rotavirus-specific IgA | Post-vaccination | 24.4 titer |
| No Probiotic | Geometric Mean Concentration of Rotavirus-specific IgA | Post-vaccination | 24.9 titer |
| No Probiotic | Geometric Mean Concentration of Rotavirus-specific IgA | Pre-vaccination | 11.5 titer |
Primary
Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine
Defined as an increase in serum anti-rotavirus (RV) VP6 IgA antibodies consistent with seroconversion (detection of serum anti-RV VP6 immunoglobulin A (IgA) antibodies at a concentration ≥20 U/ml in a previously seronegative individual) or a fourfold rise in anti-RV VP6 IgA antibodies between baseline and 14 weeks of age. Pre-vaccination blood samples were taken when the subject received the first dose of rotavirus vaccine (when the subject was 6 weeks of age); post-vaccination blood samples were taken 4 weeks after the second dose of rotavirus vaccine was administered (14 weeks of age).
Time frame: from first dose of rotavirus vaccine to 4 weeks after last dose of vaccine
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zinc and Probiotic | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | No seroconversion | 83 Participants |
| Zinc and Probiotic | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | Seroconversion | 54 Participants |
| Zinc Alone | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | No seroconversion | 103 Participants |
| Zinc Alone | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | Seroconversion | 40 Participants |
| Probiotic Alone | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | Seroconversion | 42 Participants |
| Probiotic Alone | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | No seroconversion | 94 Participants |
| Placebo | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | No seroconversion | 98 Participants |
| Placebo | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | Seroconversion | 37 Participants |
| Zinc | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | No seroconversion | 186 Participants |
| Zinc | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | Seroconversion | 94 Participants |
| No Zinc | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | Seroconversion | 79 Participants |
| No Zinc | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | No seroconversion | 192 Participants |
| Probiotic | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | Seroconversion | 96 Participants |
| Probiotic | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | No seroconversion | 177 Participants |
| No Probiotic | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | No seroconversion | 201 Participants |
| No Probiotic | Number/Percentage of Subjects With Immune Response to Rotavirus Vaccine | Seroconversion | 77 Participants |
97.5% CI: [-4.4, 13.2]
95% CI: [-1.4, 16.2]
95% CI: [0.8, 22.8]
Secondary
Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1
Shedding of rotavirus following vaccination through detection of rotavirus antigen by ELISA and confirmed as vaccine type by Real-time polymerase chain reaction (RT-PCR). Stool samples were collected on Day 0 (i.e., day of vaccination or -1), Day 4 (±1) and Day 7 (-1 to +2) post vaccination.
Time frame: 0, 4 and/or 7 day post dose 1 of rotavirus vaccine
Population: Subjects who received the vaccination on schedule and had valid stool samples on the days of testing.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zinc and Probiotic | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | No shedding 4 or 7 days post-vaccination | 120 Participants |
| Zinc and Probiotic | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | Shedding 4 or 7 days post-vaccination | 1 Participants |
| Zinc Alone | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | Shedding 4 or 7 days post-vaccination | 1 Participants |
| Zinc Alone | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | No shedding 4 or 7 days post-vaccination | 118 Participants |
| Probiotic Alone | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | Shedding 4 or 7 days post-vaccination | 1 Participants |
| Probiotic Alone | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | No shedding 4 or 7 days post-vaccination | 113 Participants |
| Placebo | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | No shedding 4 or 7 days post-vaccination | 118 Participants |
| Placebo | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | Shedding 4 or 7 days post-vaccination | 2 Participants |
| Zinc | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | No shedding 4 or 7 days post-vaccination | 238 Participants |
| Zinc | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | Shedding 4 or 7 days post-vaccination | 2 Participants |
| No Zinc | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | Shedding 4 or 7 days post-vaccination | 3 Participants |
| No Zinc | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | No shedding 4 or 7 days post-vaccination | 231 Participants |
| Probiotic | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | Shedding 4 or 7 days post-vaccination | 2 Participants |
| Probiotic | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | No shedding 4 or 7 days post-vaccination | 233 Participants |
| No Probiotic | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | No shedding 4 or 7 days post-vaccination | 236 Participants |
| No Probiotic | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 1 | Shedding 4 or 7 days post-vaccination | 3 Participants |
Secondary
Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2
Shedding of rotavirus following vaccination through detection of rotavirus antigen by ELISA and confirmed as vaccine type by RT-PCR. Stool samples were collected on Day 0 (i.e., day of vaccination or -1), Day 4 (±1) and Day 7 (-1 to +2) post vaccination.
Time frame: 0, 4 and/or 7 day post dose 2 of rotavirus vaccine
Population: Subjects who received the vaccination on schedule and had valid stool samples on the days of testing.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zinc and Probiotic | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | No shedding 4 or 7 days post-vaccination | 118 Participants |
| Zinc and Probiotic | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | Shedding 4 or 7 days post-vaccination | 0 Participants |
| Zinc Alone | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | Shedding 4 or 7 days post-vaccination | 0 Participants |
| Zinc Alone | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | No shedding 4 or 7 days post-vaccination | 118 Participants |
| Probiotic Alone | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | Shedding 4 or 7 days post-vaccination | 0 Participants |
| Probiotic Alone | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | No shedding 4 or 7 days post-vaccination | 114 Participants |
| Placebo | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | No shedding 4 or 7 days post-vaccination | 118 Participants |
| Placebo | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | Shedding 4 or 7 days post-vaccination | 0 Participants |
| Zinc | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | No shedding 4 or 7 days post-vaccination | 136 Participants |
| Zinc | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | Shedding 4 or 7 days post-vaccination | 0 Participants |
| No Zinc | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | Shedding 4 or 7 days post-vaccination | 0 Participants |
| No Zinc | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | No shedding 4 or 7 days post-vaccination | 132 Participants |
| Probiotic | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | Shedding 4 or 7 days post-vaccination | 0 Participants |
| Probiotic | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | No shedding 4 or 7 days post-vaccination | 132 Participants |
| No Probiotic | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | No shedding 4 or 7 days post-vaccination | 136 Participants |
| No Probiotic | Number/Percentage of Subjects Exhibiting Rotavirus Shedding in Stool After Dose 2 | Shedding 4 or 7 days post-vaccination | 0 Participants |
Secondary
Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV)
A serologic immune response to OPV is defined as a neutralizing antibody titer to polio virus subtype 3 greater than or equal to 1:8 at 14 weeks of age. This antigen will be used as a conservative estimate because it gives the lowest immune response of all three polio antigens. Pre-vaccination blood samples were taken when the subject received the first dose of OPV vaccine (when the subject was 6 weeks of age); post-vaccination blood samples were taken 4 weeks after the second dose of OPV was administered (14 weeks of age).
Time frame: from first dose of OPV to 4 weeks after last dose of OPV
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zinc and Probiotic | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | No seroconversion | 17 Participants |
| Zinc and Probiotic | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | Seroconversion | 120 Participants |
| Zinc Alone | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | No seroconversion | 14 Participants |
| Zinc Alone | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | Seroconversion | 129 Participants |
| Probiotic Alone | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | Seroconversion | 117 Participants |
| Probiotic Alone | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | No seroconversion | 19 Participants |
| Placebo | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | No seroconversion | 14 Participants |
| Placebo | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | Seroconversion | 121 Participants |
| Zinc | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | No seroconversion | 31 Participants |
| Zinc | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | Seroconversion | 249 Participants |
| No Zinc | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | Seroconversion | 238 Participants |
| No Zinc | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | No seroconversion | 33 Participants |
| Probiotic | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | Seroconversion | 237 Participants |
| Probiotic | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | No seroconversion | 36 Participants |
| No Probiotic | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | No seroconversion | 28 Participants |
| No Probiotic | Number/Percentage of Subjects With Immune Response to Trivalent Oral Poliovirus Vaccine (OPV) | Seroconversion | 250 Participants |
95% CI: [-4.3, 6.6]
95% CI: [-8.6, 2.3]
95% CI: [-9.8, 5.7]
Secondary
Serious Adverse Events (SAEs)
Field workers documented information on SAEs through the duration of the study during home visits (twice weekly between study clinic visits) or SAEs were documented by study clinicians at the study clinic or hospital. All SAEs occurring at any time during the study were recorded on a SAE Form and were reviewed and evaluated by a study clinician and the local IRB. The relationship of the SAE to study vaccine was evaluated and recorded and reported to the local institutional review board (IRB). All SAEs were followed until satisfactory resolution.
Time frame: from first day of study to 4 weeks after last dose
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zinc and Probiotic | Serious Adverse Events (SAEs) | No SAEs | 149 Participants |
| Zinc and Probiotic | Serious Adverse Events (SAEs) | Related SAEs | 0 Participants |
| Zinc and Probiotic | Serious Adverse Events (SAEs) | Unrelated SAEs | 5 Participants |
| Zinc Alone | Serious Adverse Events (SAEs) | Related SAEs | 0 Participants |
| Zinc Alone | Serious Adverse Events (SAEs) | No SAEs | 152 Participants |
| Zinc Alone | Serious Adverse Events (SAEs) | Unrelated SAEs | 3 Participants |
| Probiotic Alone | Serious Adverse Events (SAEs) | Unrelated SAEs | 2 Participants |
| Probiotic Alone | Serious Adverse Events (SAEs) | Related SAEs | 0 Participants |
| Probiotic Alone | Serious Adverse Events (SAEs) | No SAEs | 152 Participants |
| Placebo | Serious Adverse Events (SAEs) | No SAEs | 151 Participants |
| Placebo | Serious Adverse Events (SAEs) | Unrelated SAEs | 4 Participants |
| Placebo | Serious Adverse Events (SAEs) | Related SAEs | 0 Participants |