Accepted for/Published in: JMIR Research Protocols
Date Submitted: Dec 9, 2023
Date Accepted: Jan 30, 2024
Date Submitted to PubMed: Feb 8, 2024
Non-Specific Effects of BCG in Portuguese Children under 5 years of age: Protocol for a Population Based Historical Birth Cohort Study
ABSTRACT
Background:
In observational studies and randomized trials from low-income countries, the Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis has been associated with protection against non-TB infections. In other words, BCG has beneficial non-specific effects. The likely mechanism behind these effects is innate immune training. Until 2016, a single dose of BCG vaccine was administered to all new-borns in Portugal. In July 2016, a clinical guideline established that only children under 6 years belonging to high-risk groups should receive BCG which might have prevented non-vaccinated children from developing trained immunological responses as effectively as BCG vaccinated children.
Objective:
We aim to investigate whether there is variation observed in tuberculosis-related and all-cause mortality and severe, moderate, or mild morbidity in under-5 children between 2011-2021, and whether such variation might be explained by the BCG vaccination policy change that occurred in 2016.
Methods:
Population based historical (retrospective) birth cohort. Participants: under-5 children, born and registered in Portugal, between 1 July 2010 and 30 June 2021, except newborns with low-birth weight, premature or known or suspected HIV infection. Follow-up period until completion of 5 years of age or end of follow-up (30th June 2021). The study uses secondary data from: NHS users’ registry, information system of death certificates, vaccination registry, communicable diseases surveillance system, TB surveillance system, Diagnosis Related Groups information system for hospital admissions and emergency department visits and the primary health care information system; all linked into a single database through data linkage. Primary outcomes are person time incidence rate of death (all causes and TB), TB diagnosis, and all causes and some specific causes severe, moderate, and mild morbidity and incidence rate ratio of non-vaccinated to BCG vaccinated children. We compare the probability of surviving first and fifth year of life or of not having a severe, moderate or a mild morbidity episode during the follow-up period according to exposure (being or not vaccinate with BCG, number of doses and time from birth until 1st dose), using log rank test for differences in survival rates between exposed and non-exposed children and hazard ratios for quantifying the differences and proportional hazards regression analysis.
Results:
Ethical approval was obtained and the entity responsible for providing the data has been slowly sending the separate databases. Nevertheless, all contain a unique identifier which will enable linkage. The results will confirm or refute the hypothesis.
Conclusions:
The study will allow us to contribute to the growing evidence on the non-specific effects of vaccination with BCG and provide recent data from a high-income setting on the overall health impact of providing BCG shortly after birth, which may help authorities in establishing future vaccination guidelines. Clinical Trial: ClinicalTrials.gov NCT05471167; https://clinicaltrials.gov/study/NCT05471167
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