Topical cidofovir shows promise in treating vaccinia-infected mice

Oct 11, 2004 (CIDRAP News) – The antiviral drug cidofovir is one of very few agents used to treat serious side effects of smallpox vaccination. In a recent study, a topical form of cidofovir worked better than an intravenous formulation to protect mice from the effects of vaccinia, the smallpox vaccine virus.

Donald F. Smee and colleagues at Utah State University in Logan treated several groups of mice with cyclophosphamide to cripple their immune systems and then applied vaccinia to scratches on the mice's skin. The study is reported in a recent issue of Journal of Infectious Diseases.

The mice were then treated with 1% cidofovir cream applied to the skin or with intravenous cidofovir. Control mice were treated with a placebo. The topical cidofovir was given twice daily for a week after virus exposure, while the IV treatments were given every 3 days for 21 days.

All the mice died of spreading vaccinia infections, but those treated with either formulation of cidofovir survived significantly longer than the control mice. The topical drug was much more effective than the parenteral form in limiting the size and number of skin lesions, a finding that was explained by markedly lower levels of virus (viral titers) in the lesions in mice treated with the cream.

The researchers also looked at whether the combination of topical and IV treatment works better than either treatment alone, with treatment starting 5 days after infection. Mice that received the combined treatment survived a mean of 28.3 days, compared with 19.8 days for the topical treatment alone and 21.4 days for the IV treatment alone.

"The 1% cidofovir formulation appeared to be well tolerated by the mice," the report states. "Topical treatment may not necessarily be safe for humans, because of potential to cause kidney damage and because the drug has been shown to be absorbed into the body by the topical route."

The authors add that using a topical antiviral drug may not be practical for treating actual smallpox infections, since the sores spread over the whole body. "However, topical treatment should definitely be considered for localized infections, particularly for those complications arising from smallpox vaccination."

According to the Centers for Disease Control and Prevention (CDC), cidofovir is a second-line treatment, after vaccinia immune globulin, for severe complications of smallpox vaccination. The drug can be used for that purpose under an investigational new drug protocol sponsored by the CDC. Currently it is available only in an IV formulation.

Smee DF, Bailey KW, Wong M, et al. Topical cidofovir is more effective than is parenteral therapy for treatment of progressive vaccinia in immunocompromised mice. J Infect Dis 2004 15 Sep;190(6):1132-39 [Abstract]

See also:

CIDRAP News article, "CDC offers clinicians guidance on smallpox vaccination reactions"

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