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

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Abstract

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. We studied drug combination effects using the main standard anthelmintics, albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin in the < em > Trichuris muris < /em > model. Drug combinations were first tested < em > in vitro < /em > and additive and synergistic combinations investigated further < em > in vivo < /em > in female mice using ratios based on the ED < sub > 50 < /sub > of the respective drugs. < em > In vitro < /em > all 10 combinations of the standard anthelmintics tested against < em > T. muris < /em > revealed synergistic behavior. We identified three drug combinations < em > in vivo < /em > 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) < em > in vivo < /em > . Five combinations (albendazole-pyrantel pamoate, mebendazole-pyrantel pamoate, levamisole-pyrantel pamoate, levamisole-ivermectin and pyrantel pamoate-ivermectin) were antagonistic < em > in vivo. < /em > Conclusion Our results strengthen the evidence that combination chemotherapy might play a rolein the treatment of < em > Trichuris < /em > infections. Albendazole-mebendazole should be studied in greater detail in preclinical studies.

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Keiser, J., Tritten, L., Adelfio, R., & Vargas, M. (2012). Effect of combinations of marketed human anthelmintic drugs against Trichuris muris in vitro and in vivo. Parasites and Vectors, 5(1). https://doi.org/10.1186/1756-3305-5-292

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