Assessment of Community Transmission of Sabin Type 2 Virus in Bangladesh

Study Overview
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Brief Summary
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The Strategic Advisory Group of Experts on Immunization (SAGE) has set a plan to replace trivalent oral polio vaccine (tOPV) with bivalent OPV (bOPV) plus inactivated polio vaccine (IPV) in routine immunization globally, to be instituted in 2015-2016. At the community level, the impact of the change from tOPV + IPV to bOPV + IPV on Sabin virus fecal-oral transmission (duration of circulation, degree of genetic reversion) and the persistence of environmental contamination are unknown. Also unknown is the impact of the change from tOPV to bOPV on community circulation of Sabin 2 after a special immunization (SI) activity with monovalent oral poliovirus type 2 (mOPV2). Finally it is unknown at the level of an individual child if type 2 fecal shedding will be limited by cross-protection from oral vaccination with Sabin type 1 and 3. The investigators propose to measure at a community level transmission of Sabin 2 virus in Bangladesh, a low income country, where fecal-oral transmission and environmental exposures are high, comparing transmission in the setting of vaccination with tOPV+IPV vs. bOPV+IPV. The study will be conducted in 67 villages in Matlab, Bangladesh, using a cluster-randomized study design. Villages in Matlab will be randomly assigned to receive as part of routine immunization (RI) activities: (1) tOPV (6,10,14 weeks) plus IPV at 14 weeks; (2) bOPV (6,10, 14 weeks) plus IPV at 14 weeks; or (3) bOPV (6,10, 14 weeks) plus IPV at 14 and 18 weeks. Community and environmental surveillance for Sabin 2 virus will be conducted in each village over the 9 month period of these RI activities. In addition, a SI activity with mOPV2 will occur 9 months into the study to model an outbreak response. For the 6 months following the mOPV2 challenge, the impact of the different vaccination regimens on Sabin 2 transmission in the community will be determined, as well as individual level protection (as measured by fecal shedding from days 7-70 after mOPV2 challenge).

Official Title
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Assessment of Community Transmission of Sabin Type 2 Virus in Bangladesh

Conditions
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Vaccine Virus Shedding

Intervention / Treatment
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* Biological: tOPV
* Biological: bOPV
* Biological: IPV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female infant at least 6 weeks of age (42-48 days) at the time of enrollment For the Special Immunization Activity (SIA) only, being age 5 years or younger at the time of the SIA An infant whose parent or guardian's primary residence, at the time of first Expanded Program on Immunization (EPI) vaccinations, is a village selected to receive polio vaccine. Written informed consent obtained from the parent or guardian of the participant, prior to the participants's first study vaccination Exclusion Criteria: History of prior polio vaccination (in the 810 infants enrolled at 6 weeks of age only) Hypersensitivity to the active substance or any component in the vaccine Subjects with uncorrected congenital malformation Infants with known or suspected immunodeficiency

Ages Eligible for Study
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Minimum Age: 42 Days
Maximum Age: 48 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tOPV + IPV<br>tOPV (6, 10, and 14 weeks) + IPV (14 weeks) Randomized to receive tOPV plus IPV boost | Biological: tOPV<br>* administered per protocol<br>Biological: IPV<br>* administered per protocol<br>|
| Experimental: bOPV + IPV<br>bOPV (6, 10, and 14 weeks) + IPV (14 weeks) Randomized to receive bOPV plus 1 IPV boost | Biological: bOPV<br>* administered per protocol<br>Biological: IPV<br>* administered per protocol<br>|
| Experimental: bOPV + 2 IPV<br>bOPV (6, 10, and 14 weeks) + IPV (14 and 18 weeks) Randomized to receive bOPV plus 2 IPV boost | Biological: bOPV<br>* administered per protocol<br>Biological: IPV<br>* administered per protocol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fecal shedding of type 2 Sabin virus by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in 60% of infants that did not receive the mOPV2 challenge | The transmission rate of type 2 Sabin virus in the 60% of the enrolled infants that did not receive the mOPV2 challenge between Arm A vs Arm B, Arm A vs Arm C, and Arm B and Arm C. | 10 weeks following mOPV2 challenge at month 9 of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fecal shedding of type 2 Sabin virus by RT-qPCR in 40% of infants that received the mOPV2 challenge | Individual protection to type 2 poliovirus from different vaccination schedules | 10 weeks following mOPV2 challenge at month 9 of the study |