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Antimicrobial Agents and Chemotherapy, June 2004, p. 2267-2273, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2267-2273.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Efficacy of Cidofovir in a Murine Model of Disseminated Progressive Vaccinia

Johan Neyts,1* Pieter Leyssen,1 Erik Verbeken,2 and Erik De Clercq1

Rega Institute for Medical Research,1 Division of Histopathology, University Hospitals, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium2

Received 13 October 2003/ Returned for modification 20 January 2004/ Accepted 20 February 2004

An animal model that mimics progressive disseminated vaccinia was elaborated. To this end nude (athymic) mice were inoculated intracutaneously with vaccinia virus in the lumbosacral area. Viral replication (DNA) in the skin was detected as early as day 2 postinfection (p.i.). Mice developed typical vaccinia lesions at the site of inoculation by day 4 to 6 p.i. By about 2 weeks p.i., the infection had spread all over the body, a situation reminiscent of disseminated vaccinia in humans. The infection resulted in viremia and spread of the virus to visceral organs, as well as to the brain. Topical treatment with cidofovir, initiated at the day of infection or at day 1 p.i., completely protected against virus-induced cutaneous lesions and against associated mortality. When treatment was initiated at a later time (day 2 to 5 p.i.), a partial but marked protective effect was noted, which can be explained by the fact that by that time, the virus had spread from the skin to the visceral organs. Next, infected animals were left untreated until the time (~2 weeks p.i.) at which disseminated vaccinia had developed. When systemic treatment with cidofovir was initiated at that time, it caused lesions to heal and regress. In most of these animals, lesions had completely (or almost completely) disappeared by day 10 to 15 after the start of therapy. The observation that cidofovir is able to cause healing of disseminated vaccinia lesions in animals should have implications for the therapy of complications of vaccination against smallpox.

* Corresponding author. Mailing address: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Phone: 32-16-33-73-53. Fax: 32-16-33-73-40. E-mail: johan.neyts{at}rega.kuleuven.ac.be.

Antimicrobial Agents and Chemotherapy, June 2004, p. 2267-2273, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2267-2273.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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