Smallpox Fact Sheet
Information for Healthcare Facilities
This quick reference provides information for healthcare professionals on smallpox transmission, symptoms, precautions, treatment, and prophylaxis.
Last revised: August 2026
View or Download the Smallpox Fact Sheet (PDF)
Quick Information
Causative Agent:
Variola major virus, which is in the orthopoxvirus family.
Hospital Precautions:
In addition to standard precautions, both airborne precautions (requires N95) and contact precautions should be used.
Transmission:
Patient-to-patient transmission is likely from airborne and droplet exposure, and by contact with skin lesions or secretions. In general, close person-to-person proximity is required for transmission to reliably occur. Strict quarantine with respiratory isolation should be applied for 17 days to all persons in direct contact with the index case. Smallpox infected patients become infectious at the onset of the rash and remain infectious until their scabs separate (usually 3 weeks). Patients are considered more infectious if they are coughing. Indirect transmission from infected bedding or fomites is possible.
Decontamination
Patient decontamination after exposure to smallpox is not indicated.
Items potentially contaminated by infectious lesions should be handled using contact precautions.
Strict quarantine of asymptomatic contacts for 17 days after exposure is recommended.
Mechanism
Viral infection resulting in acute illness.
Routes
Inhalation of either small or large droplets, or contact with skin lesions or secretions. It is estimated that 35% of exposed individuals will contract the disease.
Symptoms / Onset
- Incubation period for smallpox is 7-19 days, with the average incubation period being 10 to 14 days. A prodromal phase of 2-4 days follows incubation period.
- Malaise, fever, rigors, vomiting, headache, and backache. Delirium is present in 15% of patients. Approximately 2-3 days after the onset of symptoms, lesions appear that quickly progress from macules to papules, and eventually to pustular lesions. Smallpox can be clinically distinguished from chickenpox: in chickenpox, macules, papules, and pustules/vesicles may be present simultaneously; in smallpox, all lesions are in the same stage at the same time.
Treatment
- No current recommended treatments have been tested in patients with smallpox. Symptomatic and supportive care.
- Tecovirimat (TPOXX) and brincidofovir (TEMBEXA) are FDA-approved treatment for smallpox and maintained in the strategic national stockpile (SNS). These agents can also be used via an EIND for Mpox.
- Cidofovir has been shown to stop the growth of the virus in animals but is not FDA approved for treatment of smallpox.
Prophylaxis
Three smallpox vaccines are available from the SNS to be administered to high-risk individuals such as healthcare workers or to personnel exposed within 3 days after the exposure.
- ACAM2000 (Imvamune) and JYNNEOS (Imvanex) are licensed.
- Aventis Pasteur Smallpox Vaccine (APSV) is available under an IND or EIND request.
If more than 3 days has elapsed since time of exposure, vaccinia immune-globulin (VIG) can also be administered and is available via an EIND request on a case-specific basis. Contact the CDC at (770) 488-7100.
Vaccines against smallpox do not confer life-long immunity. Previously vaccinated patients (those patients who have been vaccinated more than 10 years ago or patients who have been vaccinated more recently who do not have a take scar) should be considered susceptible to smallpox.
Adapted with permission from the Kansas Poison Control.
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