BCG Vaccination Policy, Natural Boosting and Pediatric Brain and CNS Tumor Incidences

Bacille Calmette-Guérin (BCG) vaccination supposedly imparts and augments “trained immunity” that cross-protects against multiple unrelated pathogens and enhances general immune surveillance. Gradual reductions in tuberculosis burden over the last 3-5 decades have resulted in the withdrawal of BCG vaccination mandates from developed industrialized countries while reducing to a single neonatal shot in the rest. Concurrently, a steady increase in early childhood Brain and CNS (BCNS) tumors has occurred. Though immunological causes of pediatric BCNS cancer are suspected, the identification of a causal protective variable with an intervention potential has remained elusive. An examination of the countries with contrasting vaccination policies indicates significantly lower BCNS cancer incidence (per hundred-thousand) in countries following neonatal BCG inoculations (n=146) vs . non-BCG countries (n=33) [Mean: 1.26 vs . 2.64; Median: 0.985 vs . 2.8; IQR: 0.31–2.0 vs . 2.4–3.2; P =<0.0001(two-tailed)]. Remarkably, natural Mycobacterium spp. exposure likelihood is negatively correlated with pediatric BCNS cancer incidences in all affected countries [ r (154): —0.6085, P =<0.0001]. Seemingly, neonatal BCG vaccination and natural “boosting” are associated with a 15-20-fold lower BCNS cancer incidence. We attempt to synthesize existing evidence implying the immunological basis of early childhood BCNS cancer incidences and briefly indicate possible causes that could have precluded objective analysis of the existing data in the past. A comprehensive evaluation of immune training as a potential protective variable through well-designed controlled clinical trials or registry-based studies as feasible may be warranted for its potential applications in reducing childhood BCNS cancer incidences. Statement of Significance Potential causal protective variable for childhood Brain and other CNS (BCNS) tumors has eluded discovery. Neonatal BCG vaccination and boosting by Mycobacterium tuberculosis complex exposure seem associated with over 15-20 times lower BCNS cancer incidences. Data suggests neonatal BCG vaccination followed by “boosting” may be preventive for early childhood BCNS cancer incidences.