In vivo efficacy of the anthelmintic tribendimidine against the cestode Hymenolepis microstoma in a controlled laboratory trial

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 100 mg/kg body weight deacylated amidantel and 10, 25, 50, and 100 mg/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 (100 mg/kg levamisole plus 10 and 25 mg/kg tribendimidine, respectively) and alone (50 and 100 mg/kg) to investigate any possible interactions of the partner compounds against cestodes. Tribendimidine showed a very high efficacy at dosages of 50 mg/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.

Effects of drugs on the worm burden. Box plot shows the median numbers and quartiles of recovered adult Hymenolepis microstoma with wiskers representing 10% and 90% quantiles. +, arithmetic mean; **p < 0.01 vs. control; DAMD, deacylated amidantel; LEV, levamisole; TBD, tribendimidine. Dosages shown in square brackets are given in mg/kg body weight.Figure optionsDownload as PowerPoint slideHighlights
► Tribendimidine showed complete efficacy at 50 mg/kg against Hymenolepis microstoma.
► Deacylated amidantel led to no reduction of the worm burden.
► Multiple tribendimidine doses might be considered for treatment of helminthiases.