Flubendazole and ivermectin in vitro combination therapy produces a marked effect on Echinococcus granulosus protoscoleces and metacestodes

The aim of the present work was to evaluate the in vitro efficacy of the flubendazole (FLBZ) and ivermectin (IVM) combination against Echinococcus granulosus protoscoleces and metacestodes. Protoscoleces and groups of ten peritoneal cysts obtained from BALB/c mice were incubated with the two drugs, either separately or in combination, at the following final concentrations: 10 A mu g/mL FLBZ, 1 A mu g/mL FLBZ, 1 A mu g/mL IVM, 10 A mu g/mL FLBZ + 1 A mu g/mL IVM, and 1 A mu g/mL FLBZ + 1 A mu g/mL IVM. The maximum protoscolicidal effect was found with the combination 10 A mu g/mL FLBZ + 1 A mu g/mL IMV. After 1 day of incubation, the presence of numerous blebs in the tegument of protoscoleces was observed. Ultrastructural studies revealed that the primary site of damage was the tegument of the parasite. The effect of the two drugs on hydatid cysts obtained from mice was more rapidly detected in cysts treated with the combination of FLBZ + IVM than when drugs were used separately. Ultrastructural studies revealed that the germinal layer of treated cysts lost the multicellular structure feature and underwent considerable degenerative changes after in vitro treatment. The outcomes obtained demonstrated the favorable effect of the combination of FLBZ and IVM against E. granulosus.