Clinical trial NCT01559636: 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
Overall status: COMPLETED
Phase: NA
Conditions: Seroimmunity
Diarrhea
Polio
Keywords: seroconversion
oral polio vaccine
OPV
poliomyelitis
diarrhea
seroimmunity
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
Collaborators: name: Tribhuvan University, Nepal
First posted: 2012-03-21
Enrollment: 699
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.


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

Primary outcomes:
measure: The proportion of infants who seroconvert or boost in antibody titers in the diarrhea arm compared to the non-diarrhea arm
timeFrame: 4 weeks after date of bOPV dose
Secondary outcomes:
measure: Frequencies of enteric infections isolated in stool among infants with diarrhea vs. infants without diarrhea
timeFrame: Date of enrollment
measure: Proportion of infants seropositive after receipt of 3 doses of any oral polio vaccine
timeFrame: 4 weeks after date of bOPV dose
measure: Proportion of infants with factors associated with poor bOPV seroconversion/boosting
timeFrame: 4 weeks after date of bOPV dose
Other outcomes:
Locations:
city: Kathmandu
country: Nepal
facility: Institute of Medicine
Study officials:
affiliation: Centers for Disease Control and Prevention
name: Cristina V Cardemil, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
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.