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

Karpstein, Tanja and Pasche, Valérian and Häberli, Cécile and Scandale, Ivan and Neodo, Anna and Keiser, Jennifer. (2019) Evaluation of emodepside in laboratory models of human intestinal nematode and schistosome infections. Parasites and Vectors, 12. p. 226.

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Abstract

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; 50; < 4 µM). The good in vitro activity was confirmed in vivo. Hamsters infected with the hookworms were cured when administered orally with 2.5 mg/kg of the drug. Emodepside was also highly active in vivo against T. muris (ED; 50; = 1.2 mg/kg). Emodepside was moderately active on schistosomula in vitro (IC; 50; < 8 µM) 24 h post-drug incubation and its activity on adult S. mansoni and S. haematobium was low (IC; 50; : 30-50 µM).; Emodepside is highly active against a broad range of nematode species both in vitro and in vivo. The development of emodepside for treating soil-transmitted helminth infections should be pursued.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Helminth Drug Development (Keiser)
UniBasel Contributors:Karpstein, Tanja and Pasche, Valérian and Häberli, Cécile and Keiser, Jennifer
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:BioMed Central
ISSN:1756-3305
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:23 May 2019 13:27
Deposited On:23 May 2019 13:27

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