CBRNE - Smallpox Treatment & Management

Updated: Jul 21, 2021
  • Author: Christopher J Hogan, MD; Chief Editor: Duane C Caneva, MD, MSc  more...
  • Print

Prehospital Care

No prehospital care is indicated except to stabilize the patient. Strict blood, body fluid, and droplet protection are required for all personnel involved with treating or transporting patients with known or suspected smallpox. All EMS personnel exposed to the patient require quarantine and vaccination.


Emergency Department Care

In the emergency department (ED), containment of the disease is the single most important intervention in patients in whom variola infection is suggested. ED considerations are as follows:

  • Immediate contact and droplet isolation of the patient is required.

  • The patient and any individual who came into contact with the patient up to 17 days prior to the illness (including the treating physician and nursing staff) should remain in isolation until a definite diagnosis is made. Presently, this requires sending a viral culture to the Centers for Disease Control and Prevention (CDC) in Atlanta, Ga.

  • Notify the local health authorities immediately.

  • The most likely scenario of a variola outbreak is from a terrorist attack. [9] Given the highly infective nature of the organism (not taking into account a genetically altered virus), researchers estimate that one infected patient can subsequently infect 20 new contacts during the infectious stage of the illness.

  • The presentation of a clinically apparent case implies that a larger population has probably been infected.

  • Because of the medicolegal and social implications of quarantine and isolation for a minimum of 17 days, coordinated involvement on the federal, state, and local levels is mandatory. In practicality, a strict quarantine of a large segment of the population is probably not possible.





Consult the infectious disease service early since it may help determine the diagnosis. As mentioned previously, contact the state, federal, and local public health authorities.


Medical Care

Vaccination can prevent or lessen the severity of smallpox if it is given within 2 to 3 days after the initial exposure, and may decrease symptoms if given within the first week of exposure. 

In July 2018, the US Food & Drug Administration approved tecovirimat (TPOXX), the first drug indicated for treatment of smallpox, should smallpox ever be used as a bioweapon. Tecovirimat is an antiviral that inhibits the activity of the orthopoxvirus VP37 protein. The effectiveness of tecovirimat against smallpox was established by studies in animals infected with viruses closely related to variola virus, which demonstrated higher survival rates compared with placebo. The safety of tecovirimat was demonstrated in 359 healthy human volunteers, in whom the most frequently reported adverse effects were headache, nausea, and abdominal pain. [10, 11]  

The FDA approved a second antiviral according to the animal rule, brincidofovir, for treatment of smallpox in June 2021. Brincidofovir is a prodrug of cidofovir. Brincidofovir effectively penetrates cells via its lipid conjugate, releasing the nucleotide analog cidofovir, which then acts to inhibit viral replication. Cidofovir diphosphate selectively inhibits orthopoxvirus DNA polymerase-mediated viral DNA synthesis by incorporation of cidofovir into the growing viral DNA chain. This results in reductions in the rate of viral DNA synthesis. It is indicated for treatment of smallpox caused by variola virus in adult and pediatric patients, including neonates. [12]

Tecovirimat and brincidofovir are available through the US government’s Strategic National Stockpile (SNS). To obtain, clinicians should contact the Centers for Disease Control and Prevention (CDC) Emergency Operations Center at 770-488-7100, which will coordinate shipment with the SNS. [13]