Clinical Evaluation Tools for Smallpox Vaccine Adverse Reactions


The CDC and its partners in the Clinical Immunization Safety Assessment (CISA) network have developed Clinical Evaluation Tools to help health care providers manage patients with potential adverse reactions from smallpox vaccination in the absence of circulating smallpox virus (pre-event setting). These Clinical Evaluation Tools are based on studies conducted before routine childhood US smallpox vaccination was discontinued in 1972 and on expert opinion; they are not entirely evidence-based. The Tools may not apply to all patients with smallpox vaccine adverse reactions and are not intended to substitute for evaluation by a trained clinician. These tools are designed for use during face-to-face patient encounters and are not designed to be telephone triage tools, although they may useful as a companion to other telephone triage materials. Please direct feedback on these Tools to

Clinical Evaluation Tools

Frequently Asked Questions

How do I use the Clinical Evaluation Tools for Smallpox Vaccine Adverse Reactions?
The Clinical Evaluation Tools for Smallpox Vaccine Adverse Reactions are intended to be used by trained clinicians.

  1. Choose the appropriate Clinical Evaluation Tool using the title as a guide.
  2. Determine
    • the type of potential smallpox vaccine adverse reaction.
    • if the patient has a toxic or nontoxic appearance if applicable to the Tool (use both tools if toxicity is difficult to determine).
    • if the patient is a smallpox vaccine recipient (vaccinee) or a close contact of a smallpox vaccine recipient.
  3. Work through the boxes in the Clinical Evaluation Tool to determine if your patient fits one or more of the descriptions.
  4. Consider the differential diagnosis. The Clinical Evaluation Tools list clinical conditions not related to the smallpox vaccine that should be considered; this list is not exhaustive.
  5. After narrowing the diagnostic considerations, read about the conditions in more detail (see question on more information about smallpox vaccine adverse reactions).
  6. Review the diagnostic, treatment, and reporting information provided in the Clinical Evaluation Tool and contact your state/local health department and CDC as indicated.

What do the colors mean in the Clinical Evaluation Tools?
To assist clinicians triage and manage patients some of the Clinical Evaluation Tools are color coded. The morbidity and mortality risk legend is as follows:

Green – Low Risk
Clinical presentation/ diagnosis that is normal, mild, or self-limiting. Low risk of progression to a more severe condition. Provide routine/ symptomatic care and observe patient as indicated.

Yellow – Moderate Risk
Clinical presentation/ diagnosis that may require medical intervention, shares similar features to a more severe condition or has potential to progress to a severe condition. Observe patient closely and manage as clinically indicated.

Red – High Risk
Clinical presentation/diagnosis which carries a high risk of morbidity and may be life threatening. Initiate urgent clinical care and provide appropriate interventions. These patients usually require medical intervention and hospitalization.

What is the difference between a “toxic” and “nontoxic” appearance?
The terms “toxic” and “nontoxic” are clinical descriptors. They are determined based on the appearance of the patient to an experienced clinician. Toxicity does not refer to whether or not the etiology of the patient’s condition is infectious nor does it refer solely to the presence of systemic symptoms, such as fever. Although determining toxicity is subjective, certain signs and symptoms may be associated with toxicity. For example, toxic patients may have:

  • abnormal vitals signs (including high fever, tachycardia, and decreased blood pressure)
  • signs of poor perfusion (shock)
  • alterations in mental status
  • inability to maintain hydration without intravenous fluids

Where can I find more detailed information about smallpox vaccine adverse reactions?
The following links are suggested:

Where do I call to receive clinical consultation for a potential smallpox vaccine adverse reaction with or without a request for release of Vaccinia Immune Globulin (VIG) (first line agent) or Cidofovir (second line agent)?

  1. Civilian health care providers who need clinical consultation with or without release of Vaccinia Immune Globulin (VIG) (first line agent) or Cidofovir (second line agent)for potential smallpox vaccine adverse reactions should contact their state/ local health department or the CDC Emergency Operations Center at (770) 488-7100.
  2. Military health care providers (or civilian providers treating a DoD healthcare beneficiary) requesting clinical consultation should call (866) 210-6469, and if requesting VIG release should call (888) USA-RIID or (301) 619-2257.
  3. Health care providers should report smallpox vaccine adverse events to their state/ local health department and to the Vaccine Adverse Event Reporting System (VAERS) at icon or (800) 822-7967.
  4. Members of the general public with questions about smallpox vaccination should call 800-CDC-INFO (TTY 888-232-6348) or visit
  5. Persons experiencing urgent or life-threatening medical events should seek immediate medical assistance.

Where can I find the poster on evaluating patients for smallpox?

Do I have to report this to the Vaccine Adverse Events Reporting System (VAERS)?
Yes. All serious or unusual adverse events, including inadvertent inoculation (infection of self or another), should be reported to the Vaccine Adverse Events Reporting System (VAERS). Cases of inadvertent inoculation of a contact to a vaccinated person should be reported under the contact’s name. However, information on the vaccinee should be included in the notes section #7 about the person who infected them.

For more information on smallpox vaccination, please see the Smallpox Vaccination page.

Page last reviewed: February 7, 2007