Ribavirin therapy for Hantaan virus infection in suckling mice

We recently reported that ribavirin inhibited Hantaan virus (HV) replication in vitro. In the present study, we used the HV suckling mouse model to evaluate the efficacy of treatment with various doses of ribavirin. Beginning on day 10, untreated animals, infected with ten times the amount of HV (strain 76/118) required to kill 50% of the animals, lost weight; by days 15 to 18, they developed paralysis of both hind limbs, and they died between days 20 and 21. Treatment with 50 mg of ribavirin/kg per day begun on day 10-following onset of early clinical signs and demonstrable virus in serum and organs--saved 11 of 20 animals compared with 0 of 70 controls. Treated animals did not develop further signs of infection, and by day 22, survivors resumed normal weight gain. After ribavirin treatment, titers of virus decreased in serum, liver, and spleen by two days; in lung within six days; and in the kidney by eight days. By day 18, titers in organs of treated animals were 100-fold lower than in sham-treated animals, with the exception of the brain. Titers of virus in brain fell by day 20, when virus in untreated animals reached greater than 10(7) pfu/g. Treated survivors continued to have decreasing titers of virus in organs and were followed for 75 days with no sign of disease recurrence.