Evaluation of emodepside in laboratory models of human intestinal nematode and schistosome infections

Helminthiases are very prevalent worldwide, yet their treatment and control rely on a handful of drugs. Emodepside, a marketed broad-spectrum veterinary anthelminthic with a unique mechanism of action, undergoing development for onchocerciasis is an interesting anthelmintic drug candidate. We tested the in vitro and in vivo activity of emodepside on nematode species that serve as models for human soil-transmitted helminth infection as well as on schistosomes. In vitro viability assays were performed over a time course of 72 hours for Trichuris muris, Necator americanus, Ancylostoma ceylanicum, Heligmosomoides polygyrus, Strongyloides ratti, Schistosoma mansoni and Schistosoma haematobium. The drug effect was determined by the survival rate for the larvae and by phenotypical scores for the adult worms. Additionally, mice infected with T. muris and hamsters harboring hookworm infection (N. americanus or A. ceylanicum) were administered orally with emodepside at doses ranging from 1.25 to 75 mg/kg. Expelled worms in the feces were counted until 3 days post-drug intake and worms residing in the intestines were collected and counted after dissection. After 24 hours, emodepside was very active in vitro against both larval and adult stages of the nematodes T. muris, A. ceylanicum, N. americanus, H. polygyrus and S. ratti (IC