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Smallpox - Vaccine Safety
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Rare but Serious Side Effects After Vaccination

  1. What are the rare but serious side effects after smallpox vaccination?

    Smallpox vaccination is generally a safe and effective means of preventing smallpox. However, in a number of individuals, smallpox vaccination can result in untoward effects and adverse reactions. Most are totally benign, but may be alarming in appearance. Some are serious, but treatable. A few, which rarely occur, are serious, life threatening and can be fatal. Severe adverse reactions are more common in persons receiving primary vaccination compared to those being revaccinated.

    Local Reactions

    • Progressive vaccina. Progressive vaccinia is one of the most severe complications of smallpox vaccination. It is almost always life threatening (primary vaccination site fails to heal dies and turns black. This necrosis then spreads to surrounding tissue, often affecting major portions of the body).

    Systemic Reactions

    • Generalized Vaccinia (systemic spread of the vaccinia virus from the vaccination site)
    • Erythema Multiforme ( a hypersensitivity/allergic reaction to vaccination resulting in lesions erupting in multiple areas of the body)
    • Progressive Vaccinia (primary vaccination site fails to heal dies and turns black. This necrosis then spreads to surrounding tissue, often affecting major portions of the body).
    • Eczema Vaccinatum (extensive vaccinial lesions developing either through direct inoculation of the virus onto diseased skin or possibly viremic spread if they were recently vaccinated)
    • Occular Vaccinia (eye infection resulting from transfer of the vaccinia virus to the eye)
    • Fetal Vaccinia (vaccinia virus infects the unborn baby, usually resulting in stillbirth)
    • Post Vaccinial Encephalitis(inflammation of the brain occurring shortly after vaccination), Ecephalopathy (infection of the brain), Encephalomyelitis (inflammation of the brain and spinal cord)
    • Myocarditis (inflammation of the heart muscle)
    • Pericarditis (inflammation of the sac surrounding the heart)
    In the past, about 1,000 people for every 1,000,000 vaccinated people experienced reactions that were serious, but not life-threatening. Most involved the spread of virus elsewhere on the body.


    In the past, between 14 and 52 people out of 1,000,000 vaccinated for the first time experienced potentially life-threatening reactions. These reactions included serious skin reactions and inflammation of the brain (encephalitis).

    From past experience, one or two people per 1 million who received smallpox vaccine died as a result of vaccination side effects. Serious side effects generally are rarer after revaccination, compared to first time vaccinations. Careful screening of potential vaccine recipients is essential to ensure that those at increased risk for serious side effects do not receive the vaccine.

    These side effect rates are based on data collected in the United States during the 1960s, when about 300,000 adults got their first smallpox vaccination and over 4,000,000 adults got repeat smallpox vaccinations (revaccinations).

    A few heart attacks, some fatal, have been reported after smallpox vaccination. After reviewing these cases, the rate of heart attacks in smallpox vaccinated and unvaccinated people is the same and there is no evidence of a cause-and-effect link between smallpox vaccine and heart attacks. Even so, DoD medically exempts people with heart conditions.

    We try to reduce the risk of side effects by exempting people who should not receive this vaccine.

    For more information about side effects of the smallpox vaccine please visit