Vaccine Campaign Effects on General Hospital Admissions and Mortality Among Children

Study Overview
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Brief Summary
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The world is set on eradicating measles and polio infections in the coming decade. Once both infections are under control, campaigns with measles and oral polio vaccines will be phased out. This might do more harm than good for child survival in low-income countries. Studies from the Bandim Health Project in Guinea-Bissau, and elsewhere, have revealed, that the live measles and oral polio vaccines have beneficial non-specific effects, i.e. effects on child morbidity and mortality unrelated to prevention of the targeted diseases. The campaigns are presumed to be most beneficial for children not reached by routine vaccination programs, as they are not already protected. However, studies show that prior routine or campaign vaccination may boost resistance against unrelated infections. If we phase out measles and oral polio campaigns after eradicating their target infections without considering the impact on child survival, the drastic decline in child mortality since 1990 could change direction. We will conduct the first cluster randomized controlled trial to evaluate the effect of measles and oral polio campaigns on general child morbidity and mortality via the Bandim Health Project. Bandim Health Project runs a Health and Demographic Surveillance System in Guinea-Bissau since 1978 and assesses child health interventions' real-life effects, via continuous registration of all interventions given to all children, and follow-up of individuals. We will conduct the trials in rural Guinea-Bissau monitoring all nine health regions. The hypotheses are: RECAMP-MV: Measles vaccination campaign in Guinea-Bissau reduce morbidity and mortality among children between 9 and 59 months of age by 80% during the subsequent 18 months in a context of limited measles infection. RECAMP-OPV: Oral polio vaccination campaigns in Guinea-Bissau reduce morbidity and mortality among children between 0 and 8 months of age by 25% during the subsequent 12 months in a context with no polio infection. Originally, the trials were meant to be implemented in 182 clusters, enrolling 21000 children. Following revised sample size calculations and discussions with the Data Safety and Monitoring Board, the number of clusters were increased to 222 and the planned number of enrolments increased from 21,000 to 28,000 (RECAMP-MV: 18000, RECAMP-OPV: 10000). To explore the hypothesis that at least part of the beneficial non-specific effects of OPV is driven by changes in the gut and/or respiratory microbiome, we will collect microbiome samples in a sub-group: A nasal swab and a rectal swab will be collected from 50 infants allocated to the intervention group, and 50 infants allocated to the control group. Two sample will be collected for each infant one when recruited for RECAMP-OPV and a second two months later.

Official Title
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A Cluster Randomized Controlled Trial on the Campaign Effect of Measles Vaccine and Oral Polio Vaccine on General Hospital Admissions and Mortality Among Children

Conditions
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Measles Vaccination, Oral Polio Vaccine, Non-specific/Heterologous Effects of Vaccines, Mortality, Morbidity, Children

Intervention / Treatment
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* Biological: Measles vaccine
* Biological: Oral polio vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged 0-59 months living with families registered in the rural Bandim Health Project Health and Demographic Surveillance Site are included, provided a parent/guardian consent. Exclusion Criteria: the child has temperature > 39.0◦C or a severe acute illness as defined by the examining nurse OR the child has as a mid upper arm circumference < 110 mm and is older than 6 months (most feasible local indicator of AIDS and chronic immunosuppressive disease) OR the child has experienced a severe allergic reaction after previous vaccination, drug or food. OR the child is enrolled in an ongoing study of Bacillus Calmette Guerin vaccine and is < 2 months old OR For the RECAMP-MV trial: the child is enrolled in RECAMP-OPV

Ages Eligible for Study
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Minimum Age: 0 Months
Maximum Age: 59 Months

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
Interventional Model Description: The RECAMP trials test two separate hypotheses relating to the potential beneficial non-specific effects of providing live vaccines in general vaccination campaigns. The RECAMP-MV trial tests the effect of a Measles Vaccination campaign among children aged 9-59 months The RECAMP-OPV trial tests the effect of an Oral Polio Vaccination campaign in children aged 0-8 months
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Measles vaccine<br>In intervention villages children will be weighed and receive standard measles vaccine in one dose if they are between 9-59 months old. | Biological: Measles vaccine<br>* A measles vaccine prequalified from the World Health Organization will be administered in one dose by deep subcutaneous injection into the left subscapular region by a local nurse.<br>|
| Experimental: Oral polio vaccine<br>In intervention villages children will be weighed and receive standard oral polio vaccine in one or two doses if they are between 0-8 months old. | Biological: Oral polio vaccine<br>* A bivalent oral polio vaccine prequalified by the World Health Organization will be administered in one or two doses directly into the mouth of the vaccinee with two drops per dose by a local nurse.<br>|
| No Intervention: Weighing-MV<br>In control villages children aged 9-59 months acting as controls to the MV-intervention arm will be weighed only. | |
| No Intervention: Weighing-OPV<br>In control villages children aged 0-8 months acting as controls to the OPV-intervention arm will be weighed only. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite outcome: mortality and hospital admission (measured as a rate) | Death (registered through follow-up visits, verified by verbal autopsies) or first admission (overnight stay at hospital registered by interview at follow up visits) | Enrolment to end of study (longest follow-up 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Death (registered through follow-up visits, verified by verbal autopsies) | Enrolment to end of study (longest follow-up 2 years) | 
| Hospital admission | admission (overnight stay at hospital registered by interview at follow up visits) | Enrolment to end of study (longest follow-up 2 years) | 
| Nutritional status | Mid-upper-arm-circumference registered with measurement tape as per UNICEF recommendations | Enrolment to end of study (longest follow-up 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Measles vaccine, Oral polio vaccine, Campaign, Child mortality, Child morbidity, Non-specific effects