title: Efficacy of the amino-acetonitrile derivative, monepantel, against experimental and natural adult stage gastro-intestinal nematode infections in sheep.
abstract: Multiple drug resistance by nematodes, against anthelmintics has become an important economic problem in sheep farming worldwide. Here we describe the efficacy of monepantel, a developmental molecule from the recently discovered anthelmintic class, the amino-acetonitrile derivatives (AADs). Efficacy was tested against adult stage gastro-intestinal nematodes (GINs) in experimentally and naturally infected sheep at a dose of 2.5mg/kg body weight when administered as an oral solution. Some of the isolates used in experimental infection studies were known to be resistant to the benzimidazoles or levamisole anthelmintics; strains resistant to the macrocyclic lactones were not available for these tests. Worm count-based efficacies of >98% were determined in these studies. As an exception, Oesophagostomum venulosum was only reduced by 88% in one study, albeit with a low worm burden in the untreated controls (geometric mean 15.4 worms). Similar efficacies for monepantel were also confirmed in naturally infected sheep. While the efficacy against most species was >99%, the least susceptible species was identified as Nematodirus spathiger, and although efficacy was 92.4% in one study it was generally >99%. Several animals were infected with Trichuris ovis, which was not eliminated after the treatment. Monepantel demonstrated high activity against a broad range of the important GINs of sheep, which makes this molecule an interesting candidate for use in this species, particularly in regions with problems of anthelmintic resistance. Monepantel was well tolerated by the treated sheep, with no treatment related adverse events documented.
authors.affiliation: Novartis Centre de Recherche Santé Animale SA, CH-1566 Saint-Aubin, Switzerland. heinz.sager@novartis.com
authors.forename: Heinz
authors.initials: H
authors.lastname: Sager
authors.forename: Barry
authors.initials: B
authors.lastname: Hosking
authors.forename: Béatrice
authors.initials: B
authors.lastname: Bapst
authors.forename: Philip
authors.initials: P
authors.lastname: Stein
authors.forename: Kathleen
authors.initials: K
authors.lastname: Vanhoff
authors.forename: Ronald
authors.initials: R
authors.lastname: Kaminsky
mesh_terms: D000607:Aminoacetonitrile / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000188:drug therapy / Q000662:veterinary*; D009348:Nematoda / Q000187:drug effects* / Q000302:isolation & purification; D009349:Nematode Infections / Q000188:drug therapy / Q000662:veterinary*; D010270:Parasite Egg Count / Q000662:veterinary; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy* / Q000469:parasitology
chemical_list: D000871:Anthelmintics; D000607:Aminoacetonitrile; C533978:monepantel