Nonspecific Effects of the Bacillus Calmette-Guérin Vaccine in Portuguese Children Under 5 Years of Age: Protocol for a Population-Based Historical Birth Cohort Study
Bibliographic record
Abstract
BACKGROUND: The Bacillus Calmette-Guérin vaccine (BCG) against tuberculosis (TB) shows beneficial nonspecific effects, which are likely related to innate immune training. Until 2016, a single BCG dose was administered to all newborns in Portugal. In July 2016, a clinical guideline established that only children under 6 years belonging to high-risk groups should receive BCG. This might have prevented nonvaccinated children from developing trained immunological responses as effectively as BCG-vaccinated children. OBJECTIVE: This study aims to investigate if there is variation in TB-related and all-cause mortality, and severe, moderate, or mild morbidity in children under 5 years of age, and whether such variation might be explained by the BCG vaccination policy change in 2016. METHODS: This population-based historical birth cohort study includes children under 5 years of age born in Portugal between July 1, 2010, and June 30, 2021. Newborns with low birth weight, premature status, or known or suspected HIV infection are excluded. The follow-up period is until the completion of 5 years of age or the end of follow-up (June 30, 2021). The study will use secondary data from the National Health Service user registry, death certificate database, vaccination registry, communicable diseases surveillance system, TB surveillance system, diagnosis-related group information system for hospital admissions and emergency department visits, and primary health care information system. The data will be linked. Primary outcomes include person-time incidence rates of death (all causes and TB), TB diagnosis, and all causes and some specific causes of severe, moderate, or mild morbidity, and the incidence rate ratio of nonvaccinated to BCG-vaccinated children. We will compare the probability of surviving the first and fifth years of life or of not having severe, moderate, or mild morbidity during the follow-up period according to exposure (BCG vaccinated or nonvaccinated, number of doses, and time from birth until the first dose), using the log-rank test for assessing differences in survival rates between exposed and nonexposed children and hazard ratios for quantifying the differences. Moreover, we will perform a proportional hazards regression analysis. RESULTS: Ethics approval has been obtained. In March 2022, database owners were contacted to present the project and discuss the request for data. A unique identifier will be used. In July 2023, a process of redefinition of the variables per database was initiated. Data were received in October and November 2023. In November 2023, further work was conducted. By April 2024, we expect to start analyzing the full data set. CONCLUSIONS: The results will contribute to the accumulating body of knowledge and might have relevance to guide global BCG vaccination policy. Data linkage can contribute to a swifter mechanism to use available health data to conduct population-based studies and inform policy decision-making. TRIAL REGISTRATION: ClinicalTrials.gov NCT05471167; https://clinicaltrials.gov/study/NCT05471167. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55332.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.016 | 0.012 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.003 | 0.003 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.003 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.019 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".