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Diarrhea and Bivalent Oral Polio Vaccine Immunity

Primary Purpose

Seroimmunity, Diarrhea, Polio

Status

Completed

Phase

Not Applicable

Locations

Nepal

Study Type

Interventional

Intervention

bivalent oral polio vaccine

About this trial

This is an interventional diagnostic trial for Seroimmunity focused on measuring seroconversion, oral polio vaccine, OPV, poliomyelitis, diarrhea, seroimmunity

Eligibility Criteria

6 Weeks - 11 Months (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

The investigators will be including Nepali infants aged at least 6 weeks and no more than 12 months, who have received <3 doses of OPV (cumulative from routine and SIA) and present to outpatient clinics in participating study sites. Whenever possible, the child's immunization status based on the caretaker's report will be cross-checked with available immunization cards.
Infants with diarrhea must also have:
Current diarrhea, defined as three loose stools per day in the past 24 hours. This may include children with acute or chronic diarrhea, low grade fever, and those with intermittent vomiting who are able to tolerate oral fluids and do not present with severe dehydration on the initial visit.
Non-diarrhea children also must:
Present with other, non-diarrheal minor acute complaints. This can include but is not limited to children presenting for non-severe illnesses such as skin problems (e.g., rash), conjunctivitis, and mild cough, congestion, or cold. These children should be diarrhea-free for at least two weeks prior to enrolment.

Exclusion Criteria:

Infants younger than 6 weeks or older than 12 months of age
Infants who have received 3 or more cumulative doses of OPV (including both routine and SIAs)
Infants who require hospitalization or are deemed too ill to participate by the study site clinician
Infants with blood in the stool (as this may represent more severe cases including dysentery, or non-infectious severe illnesses such as intussusception)
Infants who require IV medications for a severe illness (e.g., pneumonia); however, this does not include medications for mild or moderate illnesses, such as paracetamol, ORS, eye ointment, etc.
Infants who have a chronic underlying illness requiring long term medications
Infants who are unable to take any oral fluids by mouth, require IV hydration and therefore would be unable to tolerate oral medications in the study
Infants whose caregivers do not consent, or are not present to give consent, to the study
Infants who will not be able to return to the clinic to participate the full length of the study

Sites / Locations

Institute of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Diarrhea

Non-diarrhea

Arm Description

Infants with diarrhea will have blood and stool sample taken and receive zinc and ORS. They will then receive bivalent oral polio vaccine as the intervention. Four weeks later another blood sample will be drawn to measure seroconversion.

Infants without diarrhea will have blood and stool sample taken and receive multivitamins. They will then receive bivalent oral polio vaccine as the intervention. Four weeks later another blood sample will be drawn to measure seroconversion.

Outcomes

Primary Outcome Measures

The proportion of infants who seroconvert or boost in antibody titers in the diarrhea arm compared to the non-diarrhea arm

Seropositive: antibody titer of at least 1:8 for poliovirus type 1 or 3 Seronegative: antibody titer of less than 1:8 for poliovirus type 1 or 3 Seroconversion: proportion of children who change from seronegative to seropositive to types 1 or 3, four weeks after receipt of bOPV. Boost (increase in titer): seropositives at baseline who increase at least 4-fold in antibody titer four weeks after receipt of bOPV.

Secondary Outcome Measures

Frequencies of enteric infections isolated in stool among infants with diarrhea vs. infants without diarrhea

One stool sample will be collected from each infant the day of enrollment.

Proportion of infants seropositive after receipt of 3 doses of any oral polio vaccine

A subset of infants who received two doses of any OPV prior to study entry, and a third dose of bOPV as part of the study, will have their seroimmunity reported. This outcome is intended as a proxy measure for seroprevalence after 3 doses of OPV, which is how the vaccine is used in routine immunization.

Proportion of infants with factors associated with poor bOPV seroconversion/boosting

Multivariable modeling will be used to assess factors associated with poor bOPV seroconversion/boosting.

Full Information

NCT ID

NCT01559636

First Posted

January 4, 2012

Last Updated

October 13, 2015

Sponsor

Centers for Disease Control and Prevention

Collaborators

Tribhuvan University, Nepal

1. Study Identification

Unique Protocol Identification Number

NCT01559636

Brief Title

Diarrhea and Bivalent Oral Polio Vaccine Immunity

Official Title

Effect of Diarrheal Disease on Bivalent Oral Polio Vaccine (bOPV) Immune Response in Infants in Nepal

Study Type

Interventional

2. Study Status

Record Verification Date

October 2015

Overall Recruitment Status

Completed

Study Start Date

August 2012 (undefined)

Primary Completion Date

August 2013 (Actual)

Study Completion Date

October 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centers for Disease Control and Prevention

Collaborators

Tribhuvan University, Nepal

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Global eradication of poliomyelitis has proven to be elusive. Although 99% of cases have been eliminated since 1988, outbreaks continue to occur, and new tools are needed to accelerate eradication. One concern in this effort is that some populations have decreased immunogenicity to oral poliovirus vaccine (OPV). Past studies have shown decreased seroimmunity to trivalent OPV (tOPV) in children with diarrhea. In 2009, bivalent OPV (bOPV) was recommended for use in immunization campaigns, and will likely replace tOPV in routine immunization in 2016. However, the effect of diarrhea on seroconversion to bOPV has not been studied. This project evaluated the effect of diarrhea on seroconversion to bOPV among infants who reside in Nepal. The investigators conducted a prospective, interventional study that assessed immune response to bOPV among infants with and without diarrhea. Immune responses were compared among infants with and without diarrhea. This study will result in a better understanding of the factors that decrease the ability of some children to seroconvert to OPV and be protected from poliomyelitis infection.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Seroimmunity, Diarrhea, Polio

Keywords

seroconversion, oral polio vaccine, OPV, poliomyelitis, diarrhea, seroimmunity

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

699 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Diarrhea

Arm Type

Active Comparator

Arm Description

Arm Title

Non-diarrhea

Arm Type

Active Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

bivalent oral polio vaccine

Intervention Description

vaccine given during immunization campaigns

Primary Outcome Measure Information:

Title

The proportion of infants who seroconvert or boost in antibody titers in the diarrhea arm compared to the non-diarrhea arm

Description

Time Frame

4 weeks after date of bOPV dose

Secondary Outcome Measure Information:

Title

Frequencies of enteric infections isolated in stool among infants with diarrhea vs. infants without diarrhea

Description

One stool sample will be collected from each infant the day of enrollment.

Time Frame

Date of enrollment

Title

Proportion of infants seropositive after receipt of 3 doses of any oral polio vaccine

Description

Time Frame

4 weeks after date of bOPV dose

Title

Proportion of infants with factors associated with poor bOPV seroconversion/boosting

Description

Multivariable modeling will be used to assess factors associated with poor bOPV seroconversion/boosting.

Time Frame

4 weeks after date of bOPV dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Weeks

Maximum Age & Unit of Time

11 Months

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: The investigators will be including Nepali infants aged at least 6 weeks and no more than 12 months, who have received <3 doses of OPV (cumulative from routine and SIA) and present to outpatient clinics in participating study sites. Whenever possible, the child's immunization status based on the caretaker's report will be cross-checked with available immunization cards. Infants with diarrhea must also have: Current diarrhea, defined as three loose stools per day in the past 24 hours. This may include children with acute or chronic diarrhea, low grade fever, and those with intermittent vomiting who are able to tolerate oral fluids and do not present with severe dehydration on the initial visit. Non-diarrhea children also must: Present with other, non-diarrheal minor acute complaints. This can include but is not limited to children presenting for non-severe illnesses such as skin problems (e.g., rash), conjunctivitis, and mild cough, congestion, or cold. These children should be diarrhea-free for at least two weeks prior to enrolment. Exclusion Criteria: Infants younger than 6 weeks or older than 12 months of age Infants who have received 3 or more cumulative doses of OPV (including both routine and SIAs) Infants who require hospitalization or are deemed too ill to participate by the study site clinician Infants with blood in the stool (as this may represent more severe cases including dysentery, or non-infectious severe illnesses such as intussusception) Infants who require IV medications for a severe illness (e.g., pneumonia); however, this does not include medications for mild or moderate illnesses, such as paracetamol, ORS, eye ointment, etc. Infants who have a chronic underlying illness requiring long term medications Infants who are unable to take any oral fluids by mouth, require IV hydration and therefore would be unable to tolerate oral medications in the study Infants whose caregivers do not consent, or are not present to give consent, to the study Infants who will not be able to return to the clinic to participate the full length of the study

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Cristina V Cardemil, MD, MPH

Organizational Affiliation

Centers for Disease Control and Prevention

Official's Role

Principal Investigator

Facility Information:

Facility Name

Institute of Medicine

City

Kathmandu

Country

Nepal

12. IPD Sharing Statement

Citations:

PubMed Identifier

27085172

Citation

Cardemil CV, Estivariz C, Shrestha L, Sherchand JB, Sharma A, Gary HE Jr, Oberste MS, Weldon WC 3rd, Bowen MD, Vinje J, Schluter WW, Anand A, Mach O, Chu SY. The effect of diarrheal disease on bivalent oral polio vaccine (bOPV) immune response in infants in Nepal. Vaccine. 2016 May 11;34(22):2519-26. doi: 10.1016/j.vaccine.2016.03.027. Epub 2016 Apr 13.

Results Reference

derived

Links:

URL

http://www.polioeradication.org

Description

Global Polio Eradication Initiative

Learn more about this trial

Diarrhea and Bivalent Oral Polio Vaccine Immunity

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