Flubendazole and ivermectin in vitro combination therapy produces a marked effect on Echinococcus granulosus protoscoleces and metacestodes
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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 µg/mL FLBZ, 1 µg/mL FLBZ, 1 µg/mL IVM, 10 µg/mL FLBZ + 1 µg/mL IVM, and 1 µg/mL FLBZ + 1 µg/mL IVM. The maximum protoscolicidal effect was found with the combination 10 µg/mL FLBZ + 1 µg/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.
KeywordsHydatid Cyst Ivermectin Cystic Echinococcosis Echinococcus Granulosus Germinal Layer
The authors acknowledge Dr. Leo Van Leemput and Dr. Kathleen Vlaminck (Janssen Animal Health, Beerse, Belgium) and Dr. Gustavo Viana (Janssen, Buenos Aires, Argentina) for providing the FLBZ used in the present experimental work and for their critical review of this manuscript. The help of Dr. González and Sr. Chasma is gratefully appreciated. This work was supported by the PICT 02 No. 01-12535, BID 1201/OC-AR.
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