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Background  Few effective drugs are available for soil-transmitted helminthiases and drug resistance is of concern. In the present work, we tested the efficacy of the veterinary drug monepantel, a potential drug development candidate compared to standard drugs  in vitro  and in parasite-rodent models of relevance to human soil-transmitted helminthiases.    Methodology  A motility assay was used to assess the efficacy of monepantel, albendazole, levamisole, and pyrantel pamoate  in vitro  on third-stage larvae (L3) and adult worms of  Ancylostoma ceylanicum ,  Necator americanus  and  Trichuris muris .  Ancylostoma ceylanicum - or  N. americanus- infected hamsters,  T. muris - or  Ascaris suum -infected mice, and  Strongyloides ratti -infected rats were treated with single oral doses of monepantel or with one of the reference drugs.    Principal Findings  Monepantel showed excellent activity on  A. ceylanicum  adults (IC 50  = 1.7 µg/ml), a moderate effect on  T. muris  L3 (IC 50  = 78.7 µg/ml), whereas no effect was observed on  A. ceylanicum  L3,  T. muris  adults, and both stages of  N. americanus . Of the standard drugs, levamisole showed the highest potency  in vitro  (IC 50  = 1.6 and 33.1 µg/ml on  A. ceylanicum  and  T. muris  L3, respectively). Complete elimination of worms was observed with monepantel (10 mg/kg) and albendazole (2.5 mg/kg) in  A. ceylanicum -infected hamsters. In the  N. americanus  hamster model single 10 mg/kg oral doses of monepantel and albendazole resulted in worm burden reductions of 58.3% and 100%, respectively.  Trichuris muris ,  S. ratti and A. suum  were not affected by treatment with monepantel  in vivo  (following doses of 600 mg/kg, 32 mg/kg and 600 mg/kg, respectively). In contrast, worm burden reductions of 95.9% and 76.6% were observed following treatment of  T. muris - and  A. suum  infected mice with levamisole (200 mg/kg) and albendazole (600 mg/kg), respectively.    Conclusions/Significance  Monepantel reveals low or no activities against  N. americanus ,  T. muris ,  S. ratti and A. suum in vivo , hence does not qualify as drug development candidate for human soil-transmitted helminthiases.

In Vitro and In Vivo Efficacy of Monepantel (AAD 1566) against Laboratory Models of Human Intestinal Nematode Infections