Combined albendazole-clorsulon treatment as strategy to control fasciola hepatica. Pharmacokinetic and efficacy evaluation in ovine

Abstract

Introduction: Fasciola hepatica causes fasciolosis, a growing zoonotic disease affecting livestock and humans worldwide. The WHO has recognized it as a significant emerging neglected disease. Anthelmintic treatments are the main strategy to control fasciolosis in livestock, based in drugs such as triclabendazole (TCBZ), albendazole (ABZ), clorsulon (CLOR), nitroxinil, closantel, and rafoxanide. Only TCBZ is available for human treatment. The intensive use of TCBZ in veterinary medicine has exerted significant selection pressure, leading to the development of resistant populations of F. hepatica. The combined use of drugs has been proposed as a strategy to preserve efficacy and delay the development of resistance. The goal of the work was to evaluate the potential pharmacokinetic interaction and efficacy of ABZ-CLOR co-administration in F. hepatica infected sheep. Methods: PK study: includes three groups of healthy sheep (n=6): Group ABZ, (7.5 mg/kg bw orally); Group CLOR (2 mg/kg bw subcutaneous); and Group ABZ+ CLOR, (same doses). Blood samples were taken previously and between 1 to 48 h post-treatment. Plasma was analyzed by HPLC. Efficacy controlled test: 16 sheep artificially infected with F. hepatica, were allocated into four (4) experimental groups: Control Group (without treatment) and treated groups, which received the same treatment mentioned in the PK study. Fifteen days after treatment animals were sacrificed and adult F. hepatica specimens were counted to evaluate the efficacy. Results: higher plasma availability was observed for ABZ-sulfoxide in the co-administered group compared to those in Group ABZ. CLOR PK behavior was not affected by co-administration with ABZ. The clinical efficacy was 85%, 92% and 100% for groups ABZ, CLOR and ABZ+CLOR, respectively. Conclusion: this study shows a PK interaction and improved efficacy after ABZ+CLOR co-administration, which can help to effectively control F. hepatica in sheep.