Efficacy of albendazole against experimental infections of coenurus cerebralis in goats. Humoral and molecular characterization of coenurus cerebralis

Resumen

In Mozambique, goats are an important protein source and a major form of income for rural families. Goats are seriously affected by parasitic infections which are a major cause of morbidity and mortality and are considered to be an important constraint to goat production. One of these parasitic diseases is coenurosis, caused by Coenurus cerebralis, the larval stage of Taenia multiceps. Coenurosis is a common disease of the central nervous system of ruminants, rarely found in humans. There are no reports on the molecular characterization of T. multiceps from Africa. The use of albendazole (ABZ) could be an alternative for C. cerebralis treatment. Understanding the factors related to the pharmacokinetic behaviour of albendazole in goats is very important to maximize the broad-spectrum anthelmintic activity. In this context, the study focused on the parasite and albendazole in goats. Regarding Taenia multiceps, aspects related to its occurrence in natural conditions and the morphological and molecular characteristics in goats were studied. Moreover, the pharmacokinetics of albendazole in simple and multiple doses in goats that were healthy and infected with T. multiceps were described and the efficacy of albendazole in those experimental infections was assessed. A high prevalence of different parasites was found in goats slaughtered at Tete Municipal Abattoir. Prevalence, infection rates, cyst localization and size at natural and experimental infection of Coenurus cerebralis in goats were described. The molecular characterization showed sequences of Taenia multiceps and no genetic differences were found between cysts with cerebral and non-cerebral localization. The immunochemical results of this study on antibody and antigens corroborate the suggestions from previous reports on the difficulty of developing immunoassays of practical use based on crude or sodium dodecyl sulphate polyacrylamide gel electrophoresis fractioned antigens. The plasma kinetic profile of ABZ and its metabolites after single or multiple oral administration of ABZ in healthy goats of different ages and sex and T. multiceps-infected adult males were analyzed, compared and discussed. Additionally, infected animals were treated with a single oral dose of 10 mg/kg ABZ. Twelve hours after drug administration, muscles, brain and cyst fluid were collected. Plasma, muscles, brain and cyst fluid were analysed using HPLC method. In healthy goats, age differences in the plasma profiles of ABZ metabolites were observed but no gender related differences were observed. The pharmacokinetic parameters of ABZ metabolites, albendazole sulphoxide (ABZSO) and albendazole sulphona (ABZSO2), obtained from infected and healthy goats treated with 10 or 20 mg/kg of ABZ, showed statistically significant differences in concentration (Cmax), time of peak plasma concentration (Tmax), area under the curve (AUC) and mean residence time (MRT). Lower Cmax and AUC for both metabolites were observed in infected goats when compared with healthy goats treated with the same dose, (10 mg/kg of ABZ). This suggests that T. multiceps cysts cause pathophysiological changes that alter the kinetics of ABZ and its metabolites. In a multiple ABZ dose (3x10mg/kg), ABZSO appeared earlier and in higher concentrations than ABZSO2 in the first 24 h, but after 48 hours, the plasma concentrations of ABZSO2 were greater than ABZSO. This suggest that ABZ can induce the ABZSO metabolism to ABZSO2 In a controlled trial with experimental T. multiceps-infected goats, two months after infection, the efficacy of ABZ was 90.3%, 72.7% and 73.9% for 10mg/kg/3 days, single 10mg/kg and 20mg/kg doses, respectively. No differences were observed in cyst viability between treated and control groups for cysts, 5 months after infection. The results of this study indicate that ABZ is effective, in goats, against cysts of T. multiceps located in tissues outside the brain two months after infection.