Smallpox (Variola Virus)
BASICS
DESCRIPTION
- Smallpox is a life-threatening, acute, contagious, eruptive disease caused by variola virus.
- The disease is characterized by a febrile prodrome followed by the development of rash.
- Rash evolves in a stereotypical fashion: macules → papules → vesicles → pustules; scabs form and fall off, leaving scars called pockmarks.
- There are two clinical forms of smallpox:
- Variola minor is a less common and milder form of disease.
- Variola major is the more common and serious form of disease, of which there are five types:
- Ordinary smallpox
- Modified smallpox
- Flat (malignant) smallpox
- Hemorrhagic smallpox
- Variola sine eruption
EPIDEMIOLOGY
- The last documented case of endemic smallpox was in Somalia in 1977.
- The last case in the United States was in the late 1940s.
- Smallpox was declared eradicated by the World Health Organization in 1979.
- Historically, in unvaccinated individuals, ordinary smallpox accounted for 90% of cases, flat smallpox for 7% of cases, and hemorrhagic and modified smallpox making up the remainder. Modified smallpox was rare in unvaccinated individuals but accounted for 25% of cases of disease in vaccinated individuals.
ETIOLOGY
- Variola virus is a member of the poxvirus family and Orthopoxvirus genus.
- Variola is a double-stranded DNA virus usually transmitted during face-to-face contact via respiratory aerosols or direct contact with infected skin lesions.
- Transmission of the virus via infected fomites is uncommon.
- Humans are the only vectors.
GENERAL PREVENTION
- Prior to 1971, smallpox vaccination was part of the routine childhood schedule in the United States.
- Vaccines are produced from the vaccinia virus, a closely related orthopoxvirus to variola.
- Due to concern for use of smallpox as an agent of bioterrorism, the U.S. Strategic National Stockpile still stores smallpox vaccine.
- Two vaccines are approved for use in patients with occupational exposure to orthopoxviruses: ACAM2000 and JYNNEOS.
- Currently, the Advisory Committee on Immunization Practices (ACIP) recommends smallpox vaccination for the following:
- Public health response teams responsible for investigating suspected smallpox cases
- Hospital-based health care teams responsible for assessing and caring for suspected smallpox cases
- Laboratory personnel who work with the virus that causes smallpox or other orthopoxviruses
- Prior to administration of vaccines, clinicians should review the current indications, contraindications, and known adverse events available at https://www.cdc.gov/smallpox/clinicians/vaccines.html
PATHOPHYSIOLOGY
- The virus infects the upper respiratory tract and replicates; rarely, primary infections can occur via skin, conjunctival, or placental routes.
- The virus enters the bloodstream (primary viremia) and is taken up by macrophages.
- Patient is asymptomatic during this time.
- Next, the virus enters the reticuloendothelial system where it continues to replicate.
- Secondary viremia occurs as the virus reenters the bloodstream and infects organs.
- Can cause epidermal necrosis and swelling
- Infections of the bone marrow, kidneys, liver, lymph nodes, spleen, and other organs result in coagulopathy and multiorgan system failure.
- Exact mechanisms of viral toxicity are not understood but may involve both viral cytopathic effects and inflammatory pathology.
There's more to see -- the rest of this topic is available only to subscribers.
Citation
Cabana, Michael D., editor. "Smallpox (Variola Virus)." 5-Minute Pediatric Consult, 9th ed., Wolters Kluwer, 2025. Pediatrics Central, peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617019/all/Smallpox__Variola_Virus_.
Smallpox (Variola Virus). In: Cabana MDM, ed. 5-Minute Pediatric Consult. Wolters Kluwer; 2025. https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617019/all/Smallpox__Variola_Virus_. Accessed July 14, 2026.
Smallpox (Variola Virus). (2025). In Cabana, M. D. (Ed.), 5-Minute Pediatric Consult (9th ed.). Wolters Kluwer. https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617019/all/Smallpox__Variola_Virus_
Smallpox (Variola Virus) [Internet]. In: Cabana MDM, ed. 5-Minute Pediatric Consult. Wolters Kluwer; 2025. [cited 2026 July 14]. Available from: https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617019/all/Smallpox__Variola_Virus_.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC
T1 - Smallpox (Variola Virus)
ID - 617019
ED - Cabana,Michael D,
BT - 5-Minute Pediatric Consult
UR - https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617019/all/Smallpox__Variola_Virus_
PB - Wolters Kluwer
ET - 9
DB - Pediatrics Central
DP - Unbound Medicine
ER -

5-Minute Pediatric Consult

