Treatment with suramin and 2-substituted 5-nitroimidazoles of chronic murine Trypanosoma brucei infections with central nervous system involvement

Abstract

Mice infected with either of two isolates of Trypanosoma brucei, GVR 23/1 or GVR 35/1, develop a chronic infection in which trypanosomes are localized in the central nervous system. These infected mice were used to evaluate the efficacy of a combination drug treatment comprising suramin and one of three 2-substituted 5-nitroimidazoles. None of the three 5-nitroimidazoles tested alone, cured mice when administered 21 days after infection. However, it was found that T. brucei GVR 23/1 infections could be cured by a single dose of 20 mg/kg suramin followed by a single dose of 80 mg/kg L611,744 [3a,4,5,6,7,8,9,9a-octahydro-3-(1-methyl-5-nitroimidazol-2yl)cycloocta(D) isoxazole].