Efficacy of Repeat and Combination Treatment with Diminazene aceturate and Isometamedium chloride Against Drug Resistant Trypanosoma congolense

Abstract

Mice infected with Trypanosoma congolense “ADRI” previously shown to be resistant to diminazene aceturate (70 mg/kg) and isometamedium chloride (20 mg/kg), were treated at four days post - infection with either drug at doses 21mg/kg or 42mg/kg and 10mg/kg or 20mg/kg intraperitoneally, respectively and   treatment repeated at 48 hours  interval with    the same   drug  or the alternative  drug. Similarly, infected mice were treated with single doses of diminazene aceturate (56-75mg/kg) and isometamidium chloride (10 - 22 mg/kg). For each repeat and combination treatment there was a corresponding treatment of uninfected mice to check on suspected toxicity of short - interval trypanocidal drug treatment. Single dose treatment with diminazene aceturate (56-70mg/kg) resulted in only two   out

of    31   mice (6.5% )  being cured while  treatment  with  isometamidium chloride  (10-22 mg/kg)  at  a single dose resulted  in 10 out of  38 animals (26%) being cured.  In contrast, eight out of 10 animals (80%) which received two dosea of diminazene aceturate (21 or 42 mg/kg) were cured while  all  five  mice  (100%)  which  received two doses of isometamidium chloride 10 mg/kg were cured. In coabination drug treatments involving diminazene aceturate 42mg/kg or 21mg/kg and isometamidium chloride 20mg/kg or 10 mg/kg, 23 out or 24 animals (96%) were cured. The efficacy of diminazene aceturate and isometamedium chloride given in two repeat doses compared to single dose treatment were significantly geater  (P < 0 . 001). Similarly the greater efficacy of combination treatment as compared to single dose treatment was highly significant (P < 0 .00 1) . There was no evidence of  toxicity  following repeat or combination treatment. Single doses of diminazene aceturate greater than 70mg/kg were highly toxic to mice. At a dose of 75mg/kg, three out of five mice died within two hours of treatment. These results demonstrated that a two dose treatment at 48 hours interval or drug combination is highly efficacious against trypanosome infection resistant to therapeutic single dose of diminazene aceturate and isometamedium chloride.