Risks of serious complications and death from smallpox vaccination: a systematic review of the United States experience, 1963-1968

BMC Public Health. 2003 Aug 11:3:26. doi: 10.1186/1471-2458-3-26.


Background: The United States (US) has re-instituted smallpox vaccinations to prepare for an intentional release of the smallpox virus into the civilian population. In an outbreak, people of all ages will be vaccinated. To prepare for the impact of large-scale ring and mass vaccinations, we conducted a systematic review of the complication and mortality risks of smallpox vaccination. We summarized these risks for post-vaccinial encephalitis, vaccinia necrosum (progressive vaccinia), eczema vaccinatum, generalized vaccinia, and accidental infection (inadvertant autoinoculation).

Methods: Using a MEDLINE search strategy, we identified 348 articles, of which seven studies met our inclusion criteria (the number of primary vaccinations and re-vaccinations were reported, sufficient data were provided to calculate complication or case-fatality risks, and comparable case definitions were used). For each complication, we estimated of the complication, death, and case-fatality risks.

Results: The life-threatening complications of post-vaccinial encephalitis and vaccinia necrosum were at least 3 and 1 per million primary vaccinations, respectively. Twenty-nine percent of vaccinees with post-vaccinial encephalitis died and 15% with vaccinia necrosum died. There were no deaths among vaccinees that developed eczema vaccinatum; however, 2.3% of non-vaccinated contacts with eczema vaccinatum died. Among re-vaccinees, the risk of post-vaccinial encephalitis was reduced 26-fold, the risk of generalized vaccinia was reduced 29-fold, and the risk of eczema vaccinatum was reduced 12-fold. However, the risk reductions of accidental infection and vaccinia necrosum were modest (3.8 and 1.5 fold respectively).

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Bioterrorism / prevention & control*
  • Encephalitis, Viral / chemically induced
  • Encephalitis, Viral / epidemiology
  • Encephalitis, Viral / mortality
  • Humans
  • Mass Vaccination*
  • Necrosis
  • Risk Assessment*
  • Smallpox / prevention & control*
  • Smallpox Vaccine / adverse effects*
  • Survival Analysis
  • Vaccinia / chemically induced
  • Vaccinia / epidemiology
  • Vaccinia / pathology


  • Smallpox Vaccine