Does early childhood BCG vaccination improve survival into adulthood in a population with a low tuberculosis prevalence? Quasi-experimental evidence on non-specific effects from 39 Swedish birth cohorts

The Bacillus Calmette-Guerin (BCG) vaccine for tuberculosis (TB) is widely used globally. Many high-income countries discontinued nationwide vaccination policies as the TB prevalence decreased. However, there is continued interest in whether the general childhood immunity boost conferred by the BCG vaccination impacts adult health and mortality in low-TB contexts (known as non-specific effects) and whether BCG vaccination should be continued as a population policy. While recent studies found evidence of an association between BCG vaccination and later-life survival, it is unclear whether these associations are causal or driven by unobserved characteristics of those who chose to voluntarily vaccinate. We use the abrupt discontinuation of mandatory BCG vaccination in Sweden in 1975 as a natural experiment to estimate the causal non-specific effect of the BCG vaccine on long-term cohort survival. Applying two complementary study designs, we find no evidence that survival to age 30 was affected by the discontinuation of childhood BCG vaccination. The results are consistent in the male and female subpopulations and are robust to several sensitivity and falsification tests. Overall, despite interest and prior correlational studies suggesting large non-specific effects, we do not find any population-level evidence for a non-specific effect of the BCG vaccine discontinuation on long-term survival in Sweden.