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JAC Advance Access published online on May 26, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh286
© 2004 by The British Society for Antimicrobial Chemotherapy
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Leading article

Antiviral prophylaxis of smallpox

Mike Bray 1* Chad J. Roy 2

1 Biodefense Clinical Research Branch, Office of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
2 Department of Aerobiology and Product Evaluation, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter St., Fort Detrick, Maryland 21702, USA

* To whom correspondence should be addressed. E-mail: mbray{at}niaid.nih.gov.


  Abstract

Proof-of-concept studies suggest that current defences against smallpox could be strengthened by supplementing vaccination with antiviral drug prophylaxis, based on aerosolized or orally available forms of the long-acting medication cidofovir. Delivery of aerosolized cidofovir to mice results in its prolonged retention in respiratory tissues and protection against lethal intranasal or aerosol poxviral challenge. Although cidofovir itself is not orally available, the addition of an alkoxyalkanol ether side-chain allows it to be absorbed from the gastrointestinal tract. This also markedly increases its antiviral activity and lengthens its intracellular half-life from roughly 3 to 8-10 days. Oral treatment also protected mice against lethal poxviral challenge. These results suggest that a single aerosol dose of cidofovir (or an alkoxyalkanol-ether derivative) could provide prolonged protection against initiation of smallpox infection, whereas oral treatment could prevent both initiation of infection and internal dissemination of virus. Both approaches may avoid the nephrotoxicity that occasionally results from intravenous cidofovir therapy.

Key Words: Keywords: monkeypox, airborne infections, antiviral therapy, aerosol therapy, cidofovir, vaccination, biodefence


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