Efficacy of Isometamidium in Combination with Verapamil, Chlorpromazine or Sodium-ethylenediaminetetra-acetic Acid in Treatment of Experimental Diminazene Aceturate-resistant Strain of Trypanosoma brucei brucei Infection in Rats

Abstract

This study investigated the efficacy of different chemotherapeutic regimes in the treatment of rats experimentally infected with
diminazene aceturate-resistant strain Trypanosoma brucei brucei. Thirty Sprague Dawley male rats used for the study were
randomly assigned to six groups of five rats each as follows: group A-uninfected untreated (negative control), group Binfected and untreated (positive control), groups C-F were infected and treated with 1.0 mg/kg isometamidum chloride, administered  intramuscularly on day 11 post-infection. However, rats in groups D, E and F received further treatments with 700 mg/kg sodium-ethylenediamine tetra-acetic acid, 0.4 mg/kg verapamil and 3 mg/kg chlorpromazine, respectively, administered orally for four days. Clearance of parasite post-treatment (PT), mortality PT, relapse parasitaemia post-clearance, body weight change, rectal temperature, packed cell volume (PCV), haemoglobin (HB) concentration and red blood cell count (RBC) were determined during the experiment. Result showed parasite clearance PT of 100% in groups D and E, 80% in group F and 20% in group C by 24 hours PT. The infection relapsed on day 35 PT in 40% of rats in group C, on day 37 PT in 20% of rats in group F and lastly 20% of rats in groups D and E on day 39 PT. Rats that received drug combination showed marginal improvement in erythrocytic parameters analysed when compared with those treatment with isometamidium alone. Combination therapy showed faster clearance of parasite from the blood and also prolonged relapse post-clearance, thus had a better promising efficacy when compared to using isometamiduim chloride alone.

Keywords: Chlorpromazine, Diminazene aceturate-resistance; Isometamidium chloride; Sodium-EDTA salt; Trypanosoma brucei brucei; Verapermil