Vaccines against tuberculosis and smallpox may reduce overall mortality

What if we affected health negatively when we phased out the two vaccines against smallpox and tuberculosis in the 1970s and 1980s in Denmark? Studies on non-specific effects of vaccines indicate that such live attenuated vaccines may reduce morbidity and mortality – not related to the vaccine-targeted diseases - through epigenetic changes of the innate immune system.

To better answer the above question, we examined whether the vaccines against tuberculosis and smallpox administrated in childhood were associated with long-term mortality reductions in a high-income population in Copenhagen, Denmark. Among all Danes attending school in Copenhagen and born 1965 to 1976 (47,622), we obtained information on vaccination status and potential determinants of vaccination from school health examination records for those individuals who had died before 2010 and a 13% sample. This study population experienced the phase-out of the vaccines against tuberculosis and smallpox. We followed the study population up to 2010 and we adjusted for potential confounders - sex, eczema, and family social class - and stratified by birth year.

Compared with individuals who had not received the vaccines against tuberculosis and smallpox, those who had received both vaccines had an adjusted hazard ratio of 0.57 (95% confidence interval: 0.40-0.81) for mortality due to natural causes of death. Having either one or both of the vaccines were not associated with any protection against deaths by accidents, suicide or murder, the combined adjusted hazard ratio being 0.94 (95% confidence interval: 0.62-1.42). For infectious diseases, cardiovascular diseases, neurological diseases, major autoimmune diseases, and other diseases, the adjusted hazard ratio was approximately 0.5 for individuals having received either one or both of the vaccines vs. having received none of the vaccines while the adjusted hazard ratio was approximately one for cancers.

The vaccines against tuberculosis and smallpox were associated with better long-term survival, which was not explained by specific protection against tuberculosis and smallpox.

Image: A demonstration by medical personnel on use of a bifurcated needle to deliver the smallpox vaccine, 2002. Photo Credit: James Gathany, CDC.


Rieckmann A, Villumsen M, Sørup S, Haugaard LK, Ravn H, Roth A, Baker JL, Benn CS, Aaby P. Vaccinations against smallpox and tuberculosis are associated with better long-term survival: A Danish case-cohort study 1971- 2010. Int. J. Epidemiol. 2016

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