An insect-tapeworm model as a proxy for anthelminthic effects in the mammalian host.

Abstract

Invertebrate models provide several important advantages over their vertebrate counterparts including fewer legislative stipulations and faster, more cost-effective experimental procedures. Furthermore, various similarities between insect and mammalian systems have been highlighted. To obtain maximum use of invertebrate models in pharmacology, their fidelity as analogues of vertebrate systems requires verification. We utilised a flour beetle (Tenebrio molitor)-tapeworm (Hymenolepis diminuta) model to evaluate the efficacy of known anthelmintic compounds, praziquantel, mebendazole and levamisole against H. diminuta cysticercoid larvae in vitro. Inhibition of cysticercoid activity during the excystation procedure was used as a proxy for worm removal. The effects of the three compounds mirrored their relative efficacy in treatment against adult worms in mammalian systems; however, further study is required to determine the fidelity of this model in relation to dose administered. The model precludes comparison of consecutive daily administration of pharmaceuticals in mammals due to cysticercoids not surviving outside of the host for multiple days. Treatment of beetles in vivo, followed by excystation of cysticercoids postdissection could potentially allow for such comparisons. Further model validation will include analysis of pharmaceutical efficacy in varying H. diminuta isolates and pharmaceutical dilution in solvents other than water. Notwithstanding, our results demonstrate that this model holds promise as a method to efficiently identify promising new cestocidal candidates.