title: Effect of combinations of marketed human anthelmintic drugs against Trichuris muris in vitro and in vivo.
abstract: 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 ED50 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P.O. Box, CH-4002 Basel, Switzerland. jennifer.keiser@unibas.ch
authors.forename: Jennifer
authors.initials: J
authors.lastname: Keiser
authors.forename: Lucienne
authors.initials: L
authors.lastname: Tritten
authors.forename: Roberto
authors.initials: R
authors.lastname: Adelfio
authors.forename: Mireille
authors.initials: M
authors.lastname: Vargas
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage* / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005243:Feces / Q000469:parasitology; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D014257:Trichuriasis / Q000188:drug therapy* / Q000469:parasitology; D014258:Trichuris / Q000187:drug effects*
chemical_list: D000871:Anthelmintics