Treatment Overview

Medical personnel must be able to recognize a vesicular exanthem and consider the etiology as potentially variola, and then quickly initiate appropriate countermeasures. Any confirmed case of smallpox should be considered an international emergency with immediate reporting to public health authorities. People who have been exposed to known cases of small pox should be monitored for a minimum of 17 days from exposure regardless of their vaccination status; such individuals should be immediately isolated using droplet and airborne precautions at the onset of fever. In a civilian setting, strict quarantine of asymptomatic contacts may prove to be impractical and impossible to enforce. A reasonable alternative would be to require contacts to remain at home and to check their temperatures daily. Any fever above 38°C (101°F) during the 17 days after exposure to a confirmed case would suggest the development of smallpox. The contact should then be isolated immediately, preferably at home, until smallpox is either confirmed or ruled out and remain in isolation until all scabs separate. Patients should be considered infectious until all scabs separate. Immediate vaccination or revaccination should also be undertaken for all personnel exposed to either weaponized variola virus or a clinical case of smallpox. Caregivers should be vaccinated and continue to wear appropriate PPE regardless of vaccination status. Weaponized smallpox strains encountered in the future may be genetically altered to render the current vaccine ineffective, a possibility demonstrated unequivocally in similar poxvirus animal models.

The potential for airborne spread to other than close contacts is controversial. In general, close person-to-person contact is required for transmission to reliably occur. Nevertheless, variola's potential for airborne spread in conditions of low relative humidity was alarming in two hospital outbreaks. Indirect transmission by contaminated bedding or by fomites was infrequent. Some close contacts harbored virus in their throats without developing disease and hence might have served as a means of secondary transmission.

Vaccination with a verified clinical "take" (vesicle with scar formation) within the past 3 years is considered to render a person immune to smallpox. However, given the difficulties and uncertainties under wartime conditions of verifying the adequacy of troops' prior vaccination, routine revaccination of all potentially exposed personnel would seem prudent if there existed a significant prospect of smallpox exposure.

Antivirals for use against smallpox are under investigation. Cidofovir has had significant in vitro and in vivo activity in animal studies. Whether it would offer benefit superior to immediate postexposure vaccination in humans has not been determined. While cidofovir is a licensed drug, its use for treating smallpox is "off-label" and thus it should be administered as an investigation new drug (IND). See Appendix L for guidelines on the administration of IND drugs. Topical antivirals such as trifluridine or idoxuridine may be useful for treating smallpox ocular disease.

Supportive care is imperative for successful management of smallpox victims; measures include maintenance of hydration and nutrition, pain control, and management of secondary infections.

Treatment for smallpox largely consisted of general supportive measures:

  • Adequate fluid intake (difficult because of the enanthem)
  • Alleviation of pain and fever
  • Keeping the skin lesions clean to prevent bacterial superinfection

No specific antiviral treatment of demonstrated effectiveness was available in the pre-eradication era.

  • In recent years, other compounds have been evaluated; cidofovir, adefovir dipivoxil, cyclic cidofovir, and ribavirin have shown significant in vitro activity against variola virus (Franz 1997). Recent studies, however, suggest that patients may require a higher dose of cidofovir than is currently licensed for humans and may also require probenecid to ameliorate the uptake of cidofovir by renal tubular epithelial cells (McSharry 2009).
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