Non-specific Effects of BCG in Under-five Children

NCT05471167 | Unknown

• 1 other identifier: EXPL/SAU-EPI/0067/2021
• Study Type: observational
• Target: 80,000
• Locations: 1 country
• Sites: 1

Brief Summary

Studies have demonstrated that the reduction in mortality and morbidity due to vaccination extends beyond the targeted infections. This seems to result from the non specific effects of vaccines. BCG, a live attenuated vaccine against TB disease, administered to new borns, is one of the vaccines known to have non specific effects. In Portugal, between 1965 and June 2016, BCG was administered to all new borns. In July 2016, a clinical guideline established that only children under 6 years of age from high-risk groups should be vaccinated. In 2021, the first cohort of children not vaccinated for BCG reached 5 years of age and evidence is needed on the impact of this strategy. Aim: to investigate the incidence of specific and non-specific effects of BCG by comparing the incidence of TB disease and infection, mild and severe morbidity, and mortality in the first 5 years of life of children born between 2010 and 2021 according to their BCG status. Methods: historical birth cohort study of children born between 1st July 2010 and 30th June 2021. The investigators will create a single database that links data from the birth registry, the vaccination registry, the information systems of death certificates, epidemiological surveillance and TB surveillance, Diagnosis Related Groups and of primary health care of children born in the study period to reconstruct chronological sequences of morbidity and mortality events from birth until completion of 5 years of life or 30th June 2021. Only children born in Portugal, live-births and births coded as normal new-born will be included. New borns with low-birth weight (\<2kg), premature (\<37 weeks) and known or suspected HIV infections will not be included in the study. The follow-up period will be until completion of 5 years of age or 30th June 2022. Data will be analysed to compare the incidence of all-cause mortality (including TB), TB disease and severe and mild morbidity among BCG vaccinated and non-vaccinated children born during the reference period in a total of 11 birth cohorts and will comprise computation of person-time incidence rates for primary outcomes and the probability of surviving (Kaplan Meier method) first and fifth year of life or of not having a hospitalization, emergency department visit or a mild morbidity episode during the follow-up period according to exposure. To explore the effects of several variables on the survival outcomes we will use proportional hazards regression analysis.

Conditions

Immunity, Heterologous

Keywords

BCG; Mortality; Morbidity; Under 5 children; Immunity, Heterologous

Outcome Measures

Primary Outcomes (5)

• All cause mortality

  Person time incidence rate of death (all causes)

  First 5 years of life or until 30 June 2022

• Mortality due to TB

  Person time incidence rate of death (TB)

  First 5 years of life or until 30 June 2022

• Mild morbidity

  Contacts with the medical doctor or nurse at a primary health center unit due to disease or ill-health during the follow-up, besides contacts related to recommended child-surveillance scheme or other reasons besides health

  First 5 years of life or until 30 June 2022

• Severe morbidity

  Hospitalization and/or visits to the emergency department

  First 5 years of life or until 30 June 2022

• TB

  Confirmed case of TB

  First 5 years of life or until 30 June 2022

Secondary Outcomes (4)

• Mortality profile of under-5 children between 2010 and 2022

  2010 to 2022

• Morbidity profile of under-5 children between 2010 and 2022

  2010 to 2022

• Profile of non-vaccinated children before and after 2016

  2010 to 2022

• NHS hospital and PHC utilization profile of under-5 children

  2010 to 2022

Study Arms (11)

Birth cohort 2010

Children born from 01/07/2010 followed up until 30/06/2016

Biological: BCG

Birth cohort 2011

Children born from 01/07/2011 followed up until 30/06/2017

Biological: BCG

Birth cohort 2012

Children born from 01/07/2012 followed up until 30/06/2018

Biological: BCG

Birth cohort 2013

Children born from 01/07/2013 followed up until 30/06/2019

Biological: BCG

Birth cohort 2014

Children born from 01/07/2014 followed up until 30/06/2020

Biological: BCG

Birth cohort 2015

Children born from 01/07/2015 followed up until 30/06/2021

Biological: BCG

Birth cohort 2016

Children born from 01/07/2016 followed up until 30/06/2022

Birth cohort 2017

Children born from 01/07/2017 followed up until 30/06/2022

Birth cohort 2018

Children born from 01/07/2018 followed up until 30/06/2022

Birth cohort 2019

Children born from 01/07/2019 followed up until 30/06/2022

Birth cohort 2020

Children born from 01/07/2020 followed up until 30/06/2022

Interventions

BCG BIOLOGICAL

Exposure is defined as having received the BCG vaccine during the first year of life.

Birth cohort 2010; Birth cohort 2011; Birth cohort 2012; Birth cohort 2013; Birth cohort 2014; Birth cohort 2015

Eligibility Criteria

• Age: 0 Years - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Under-5 children born and registered in Portugal between 1 July 2010 and 30 June 2021.

You may qualify if:

• children born in Portugal, live-births and births coded as DRG 795 (normal new-born)

You may not qualify if:

• new-borns with low-birth weight (\<2kg), premature (\<37 weeks) and known or suspected HIV infection

Sponsors & Collaborators

• Universidade Nova de Lisboa: lead
• Fundação para a Ciência e a Tecnologia: collaborator

Study Sites (1)

Instituto de Higiene e Medicina Tropical

Lisbon, 1349-008, Portugal

Location

Related Publications (1)

• Fronteira I, Pacheco M, Schaltz-Buchholzer F, Ferrinho P. Nonspecific Effects of the Bacillus Calmette-Guerin Vaccine in Portuguese Children Under 5 Years of Age: Protocol for a Population-Based Historical Birth Cohort Study. JMIR Res Protoc. 2024 Mar 14;13:e55332. doi: 10.2196/55332.

  PMID: 38328938 DERIVED

Study Officials

• Ines Fronteira, PhD

  Instituto de Higiene e Medicina Tropical - Universidade Nova de Lisboa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor

Study Record Dates

• First Submitted: July 15, 2022
• First Posted: July 22, 2022
• Study Start: January 1, 2022
• Primary Completion: December 31, 2022
• Study Completion: June 30, 2023
• Last Updated: July 22, 2022

Record last verified: 2022-07

Locations

PT (1)