title: In vivo efficacy of the anthelmintic tribendimidine against the cestode Hymenolepis microstoma in a controlled laboratory trial.
abstract: Tribendimidine has been registered for the treatment of human soil transmitted helminthiases in China. In the model nematode Caenorhabditis elegans it is an agonist of L-subtype nicotinic acetylcholine receptors and therefore shares its mode of action with levamisole and pyrantel. Besides its broad spectrum of nematicidal efficacy, tribendimidine is efficacious against several trematodes and has been attributed to have anti-cestodal effects. However, there are few published data available for the latter. The efficacy of tribendimidine and its nematicidal metabolite deacylated amidantel against Hymenolepis microstoma were examined for their anti-cestodal potential. Doses of 50 and 100mg/kg body weight deacylated amidantel and 10, 25, 50, and 100mg/kg tribendimidine were administered orally on three consecutive days to mice experimentally infected with eight cysticercoids. Necropsy was performed and the worm burdens were determined one day after the last treatment. Furthermore, levamisole was used in combination with tribendimidine (100mg/kg levamisole plus 10 and 25mg/kg tribendimidine, respectively) and alone (50 and 100mg/kg) to investigate any possible interactions of the partner compounds against cestodes. Tribendimidine showed a very high efficacy at dosages of 50mg/kg or higher. Surprisingly, deacylated amidantel led to no reduction of the worm burden in any of the treatments. Combinations of levamisole with tribendimidine did not augment the effects of tribendimidine alone and as expected levamisole alone also showed no anti-cestodal activity. To our knowledge, this study shows for the first time activity of tribendimidine against a cestode in a controlled laboratory study. Due to the excellent cure rates observed here, multiple tribendimidine treatments might be considered as useful scheme for treatments of cestode, nematode and trematode infections although this would significantly increase both costs and management efforts. Moreover, the differences between tribendimidine and deacylated amidantel indicate at least a strong difference in sensitivity of H. microstoma or a strong difference in drug availability.
authors.affiliation: Institute of Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Königsweg 67, 14163 Berlin, Germany. daniel.kulke@fu-berlin.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Kulke
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krücken
authors.forename: Claudia
authors.initials: C
authors.lastname: Welz
authors.forename: Georg
authors.initials: G
authors.lastname: von Samson-Himmelstjerna
authors.forename: Achim
authors.initials: A
authors.lastname: Harder
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006925:Hymenolepiasis / Q000188:drug therapy* / Q000469:parasitology; D006926:Hymenolepis / Q000145:classification / Q000187:drug effects*; D051379:Mice; D010655:Phenylenediamines / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000871:Anthelmintics; D010655:Phenylenediamines; C056017:tribendimidine; C019144:amidantel