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 ( approximately 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.