Efficacy of heteropolyanions against rabies virus infection in mice

Abstract

Summary A mouse model was established for the study of treatment of rabies using heteropolyanions. The 14 chemical compounds were administered by the i.c. route. Moreover, 8 of them, available in large amounts, were also used by the i.m., i.p. and i.v. routes. Treatments were given either early, starting one day post-infection when rabies virus as still at the inoculation site, or later, starting at the mid-incubation period, when rabies virus was already in the brain. Therapy was fully effective when administered early, intramuscularly, near the site of virus inoculation. Of the 8 available compounds (HPA-23, -32, -39, -46, -47, -52, -56 and -59), HPA-39 gave the best results, i.e. 100 % survival with 5 daily doses of 177 mg/kg, starting 24 h post-infection. By the i.p. route, treatments were less effective; only a few survivors were obtained. By the i.c. route, only 5 of the 14 compounds (HPA-23, -39, -46, -51 and -56) were effective. HPA-39 gave the best results, i. e. 20–65 % survival with 3 to 5 daily doses at 0.01 mg/mouse. Whatever the route of treatment, surviving mice had no sign of virus multiplication in the brain, i. e. there was an absence of infectious virus and an absence of accumulation of the major viral protein. Therapy starting at the mid-incubation period had no significant effect on survival whatever the route of administration: i.c., i.v., or i.m. or combined i.c. plus i.v. treatments. Use of HPA-39 as an alternative to post-exposure treatment in contaminated animals or man is discussed.