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Background  Soil-transmitted helminth (STH) infections are responsible for a huge public health burden, however treatment options are limited. The discovery and development of novel efficacious drugs or drug combinations for the treatment of STH infections therefore has a high research priority.    Methods  We studied drug combination effects using the main standard anthelmintics, albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin in the  Trichuris muris  model. Drug combinations were first tested  in vitro  and additive and synergistic combinations investigated further  in vivo  in female mice using ratios based on the ED 50  of the respective drugs.    Results   In vitro  all 10 combinations of the standard anthelmintics tested against  T. muris  revealed synergistic behavior. We identified three drug combinations  in vivo  as strongly synergistic, namely mebendazole-ivermectin (Combination index (CI)=0.16), mebendazole-levamisole (CI=0.17) and albendazole-mebendazole (CI=0.23). For albendazole-ivermectin, moderate synergism was observed (CI=0.81) and for albendazole-levamisole a nearly additive effect was documented (CI=0.93)  in vivo . Five combinations (albendazole-pyrantel pamoate, mebendazole-pyrantel pamoate, levamisole-pyrantel pamoate, levamisole-ivermectin and pyrantel pamoate-ivermectin) were antagonistic  in vivo.Conclusion  Our results strengthen the evidence that combination chemotherapy might play a role in the treatment of  Trichuris  infections. Albendazole-mebendazole should be studied in greater detail in preclinical studies.

Effect of combinations of marketed human anthelmintic drugs against Trichuris muris in vitro and in vivo