To better understand the potential of
ribavirin in the treatment of
orthopoxvirus infections (such as those acquired through bioterrorist activities), the efficacy of the
drug was studied in a
cowpox respiratory
infection model in mice under varying disease severity. Mice did not survive a high intranasal cowpox virus challenge [3 x 10(6) plaque forming units (pfu)/animal] treated 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 same dose of
drug survived a 3 x 10(5) pfu challenge compared with 0% survival of those that received placebo. Survival rates of 50 and 30% occurred with
ribavirin doses of 50 and 25 mg/kg/day, respectively. At the 100 mg/kg/day dose,
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 significantly reduced. Mice were infected intranasally with the high 3 x 10(6) pfu virus challenge dose and treated with 100 mg/kg/day
ribavirin for 5 days, followed by single
injections of 75 mg/kg
cidofovir on day 6, 7, 8 or 9.
Cidofovir 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 days 6 and 7 significantly increased the mean time to death beyond that achieved 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 individuals infected with an orthopoxvirus by
aerosol route would benefit by a course of
ribavirin therapy. Later, the fewer number of very sick individuals could be treated with intravenous
cidofovir.