In vitro and in vivo changes observed in Trypanosoma brucei brucei-infected rats treated with artesunate and/or diminazene aceturate

Abstract

This study evaluated in vitro and in vivo antitrypanosomal effect of artesunate and/or diminazene aceturate in Wistar rats experimentally  infected with Trypanosoma brucei brucei. In vitro screening was carried out in triplicates using 50 μl of 0.2, 2 and 20 μg/μl of artesunate as test drug; diminazene aceturate, normal saline and trypanosome-infected blood served as controls in a 96-well microtitre plate, incubated at 37˚C for 5 minutes. Efficacy was observed over a period of 60 minutes for reduced or complete trypanosomal immobilization. Results showed concentration-dependent cessation of trypanosomal motility was significantly (p < 0.001) induced by artesunate when compared to the controls. Seventy Wistar rats of both sexes weighing between 190 and 210 g were randomly divided into 7 groups (5 males and 5 females) are used for in vivo study. Groups I and II served as normal control and model control respectively. Groups III to VII were infected with Trypanosoma brucei brucei (106 trypanosomes/ml) intraperitoneally. At peak parasitaemia (8 days post-infection), group III was treated with diminazene aceturate (3.5 mg/kg) intramuscularly once while groups IV, V, VI were treated with artesunate (200, 100, 50) mg/kg orally for 5 consecutive days and group VII was treated with combination of artesunate (50 mg/kg) orally and diminazene aceturate (1.75 mg/kg) intramuscularly for 5 days. Results indicated pre-patent period of 4 days and increase in levels of parasitaemia post-inoculation. PCV, Hb concentration, RBC count, MCV, MCHC and total leucocyte count decreased significantly (p < 0.05) between days 0
and 8 in groups II to VII. Following treatment, significant increases (p < 0.05) were recorded except for groups II, IV, V and VI where the rats died. Thus, combination of artesunate (50 mg/kg) and half the standard dose of diminazene aceturate was able to reduce parasitaemia and ameliorate the anaemia elicited by the trypanosomes.

Keywords: Artesunate, Diminazene Aceturate, Haematology, Trypanosoma brucei brucei, Wistar rats