Andreas Rieckmann 2018

Rieckmann, Andreas. 2018. Smallpox and BCG vaccinations and long-term non-specific effects on mortality, HIV-1 and cutaneous malignant melanoma.


Previous observations suggest that both smallpox and BCG vaccinations reduce non-specific mortality (i.e. mortality not related to smallpox and tuberculosis) and the risk of HIV-1 and cutaneous malignant melanoma (CMM) among adults. We tested these hypotheses in two very different settings, Denmark and Guinea-Bissau.


In Denmark, children born between 1965 and 1976 experienced smallpox and BCG vaccination being phased out. Information about vaccination status was available from school health records. We conducted two case-cohort studies and one case-base study, following this study population until midlife using Danish registers for all-cause mortality, HIV-1 and CMM. In Guinea-Bissau, we used smallpox and BCG vaccination scars as proxies for vaccination and estimated the association with HIV-1 in an urban population using a cross sectional study. A rural population of women was followed for all-cause mortality in a cohort study.


In Denmark, smallpox and/or BCG vaccination vs. none of the two vaccines was associated with a hazard ratio of 0.57 (95% confidence interval (CI) 0.40-0.81) for non-specific mortality due to natural causes between 5-45 years of age. There was no association with the control outcomes accidents, murders or suicides. In Guinea-Bissau, smallpox and/or BCG vaccination scars were associated with a hazard ratio of 0.89 (95% CI 0.72-1.09) for mortality compared with no scars among women between 32-70 years. The combined association of smallpox and/or BCG vaccination among study populations from Denmark and Guinea-Bissau was an odds ratio of 0.66 (CI 0.46-0.96) for HIV-1 compared with individuals who did not have the two vaccines. In Denmark, smallpox and/or BCG vaccination compared with none of the two vaccines was associated with a hazards ratio of 1.29 (95% CI 0.72-2.31) for CMM.


The findings suggest that smallpox and BCG vaccination may reduce mortality in early adult life or few decades after vaccination. Our understanding of effects into late adult life is still limited. In the context of previous epidemiological and immunological evidence, our findings indicate a protective effect of the smallpox vaccine against HIV-1 infection, while for CMM we now have less support for BCG and smallpox vaccination being effective prophylaxes. These findings should be interpreted with caution due to limited power and few baseline variables in some of the studies.