Treatment of cowpox virus respiratory infections in mice with ribavirin asa single agent or followed sequentially by cidofovir

To better understand the potential of ribavirin in the treatment of orthopo xvirus infections (such as those acquired through bioterrorist activities), the efficacy of the drug was studied in a cowpox respiratory infection mod el in mice under varying disease severity. Mice did not survive a high intr anasal cowpox virus challenge [3x10(6) plaque forming units (pfu)/animal] t reated with subcutaneous ribavirin (100 mg/kg/day for 5 days), but lived 3. 9 days longer than placebos. In contrast, 100% of animals receiving the sam e dose of drug survived a 3x10(5) pfu challenge compared with 0% survival o f those that received placebo. Survival rates of 50 and 30% occurred with r ibavirin doses of 50 and 25 mg/kg/day, respectively. At the 100 mg/kg/day d ose, ribavirin reduced lung virus titres 40-fold on day 6 of the infection relative to titres in the placebo group. Weight loss resulting from illness and mean lung weights of mice treated with ribavirin were also significant ly reduced. Mice were infected intranasally with the high 3x10(6) pfu virus challenge dose and treated with 100 mg/kg/day ribavirin for 5 days, follow ed by single injections of 75 mg/kg cidofovir on day 6, 7, 8 or 9. Cidofovi r alone (without ribavirin) administered on day 6 had no beneficial effect on disease outcome. Ribavirin alone increased the mean time to death by 3.7 days. Ribavirin treatment for 5 days followed by cidofovir treatment on da ys 6 and 7 significantly increased the mean time to death beyond that achie ved with ribavirin alone by 8.2 and 4.4 days, respectively, with 30 and 40% of mice surviving the infection. These results suggest that many individua ls infected with an orthopoxvirus by aerosol route would benefit by a cours e of ribavirin therapy. Later, the fewer number of very sick individuals co uld be treated with intravenous cidofovir.