Vaccine Campaign Effects on General Hospital Admissions and Mortality Among Children

Phase 4

• Conditions: Oral Polio Vaccine; Non-specific/Heterologous Effects of Vaccines; Children; Measles Vaccination; Mortality; Morbidity
• Interventions: Biological: Measles vaccine; Biological: Oral polio vaccine

• Registration Number: NCT03460002
• Lead Sponsor: Bandim Health Project

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-11
• Study First Submitted: 2016-11-21
• Study First Submitted QC: 2018-03-04
• Study First Posted: 2018-03-09
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-28
• Last Update Posted: 2021-03-02
• Primary Completion: 2021-09
• Study Completion: 2022-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 28000

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Measles vaccine	Measles vaccine	In intervention villages children will be weighed and receive standard measles vaccine in one dose if they are between 9-59 months old.
Oral polio vaccine	Oral polio vaccine	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.

Primary Outcome Measures

Name	Time	Method
Composite outcome: mortality and hospital admission (measured as a rate)	Enrolment to end of study (longest follow-up 2 years)	Death (registered through follow-up visits, verified by verbal autopsies) or first admission (overnight stay at hospital registered by interview at follow up visits); Correction: Non-accidental death (registered through follow-up visits, verified by verbal autopsies) or first admission not caused by accident (overnight stay at hospital registered by interview at follow up visits) The outcomes were correctly specified in the protocol paper and analysis plan (doi: 10.1186/s12889-019-7813-y)

Secondary Outcome Measures

Name	Time	Method
Nutritional status	Enrolment to end of study (longest follow-up 2 years)	Mid-upper-arm-circumference registered with measurement tape as per UNICEF recommendations
Mortality	Enrolment to end of study (longest follow-up 2 years)	Death (registered through follow-up visits, verified by verbal autopsies); Corrections: Non-accidental death (registered through follow-up visits, verified by verbal autopsies) The outcome was correctly specified in the protocol paper and analysis plan (doi: 10.1186/s12889-019-7813-y)
Hospital admission	Enrolment to end of study (longest follow-up 2 years)	admission (overnight stay at hospital registered by interview at follow up visits); Correction: admission not caused by accident (overnight stay at hospital registered by interview at follow up visits) The outcome was correctly specified in the protocol paper and analysis plan (doi: 10.1186/s12889-019-7813-y)

Trial Locations

Locations (1)

Bandim Health Project; 🇬🇼 Bissau, Guinea-Bissau