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Diarrhea and Bivalent Oral Polio Vaccine Immunity

This study has been completed.
Sponsor:
Collaborator:
Tribhuvan University, Nepal
Information provided by (Responsible Party):
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT01559636
First received: January 4, 2012
Last updated: October 13, 2015
Last verified: October 2015
  Purpose

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.


Condition Intervention
Seroimmunity
Diarrhea
Polio
Biological: bivalent oral polio vaccine

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Effect of Diarrheal Disease on Bivalent Oral Polio Vaccine (bOPV) Immune Response in Infants in Nepal

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • The proportion of infants who seroconvert or boost in antibody titers in the diarrhea arm compared to the non-diarrhea arm [ Time Frame: 4 weeks after date of bOPV dose ] [ Designated as safety issue: No ]

    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 [ Time Frame: Date of enrollment ] [ Designated as safety issue: No ]
    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 [ Time Frame: 4 weeks after date of bOPV dose ] [ Designated as safety issue: No ]
    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 [ Time Frame: 4 weeks after date of bOPV dose ] [ Designated as safety issue: No ]
    Multivariable modeling will be used to assess factors associated with poor bOPV seroconversion/boosting.


Enrollment: 699
Study Start Date: August 2012
Study Completion Date: October 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Diarrhea
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.
Biological: bivalent oral polio vaccine
vaccine given during immunization campaigns
Active Comparator: Non-diarrhea
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.
Biological: bivalent oral polio vaccine
vaccine given during immunization campaigns

  Eligibility

Ages Eligible for Study:   6 Weeks to 11 Months   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01559636

Locations
Nepal
Institute of Medicine
Kathmandu, Nepal
Sponsors and Collaborators
Centers for Disease Control and Prevention
Tribhuvan University, Nepal
Investigators
Principal Investigator: Cristina V Cardemil, MD, MPH Centers for Disease Control and Prevention
  More Information

Additional Information:
Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT01559636     History of Changes
Other Study ID Numbers: CDC-458-GID-037 
Study First Received: January 4, 2012
Last Updated: October 13, 2015
Health Authority: United States: Federal Government

Keywords provided by Centers for Disease Control and Prevention:
seroconversion
oral polio vaccine
OPV
poliomyelitis
diarrhea
seroimmunity

Additional relevant MeSH terms:
Poliomyelitis
Diarrhea
Signs and Symptoms, Digestive
Signs and Symptoms
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Myelitis
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Spinal Cord Diseases
Neuromuscular Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 08, 2016