monepantel and Disease-Models--Animal

Drug resistance in gastrointestinal nematodes is a severe problem for sheep farmers. With the recent introduction of monepantel (Zolvix®) and of derquantel plus abamectin (Startect®) in New Zealand, two new anthelmintic classes will be available to control gastrointestinal nematodes. While monepantel covers a broad spectrum of nematodes, the efficacy of derquantel is mid-spectrum and limited to a smaller number of species and stages. The combination of derquantel and abamectin allows to enlarge the spectrum and to cover most parasitic nematodes in sheep. However, the question remained open, if the efficacy of the new anthelmintics can be maintained in the presence of severe anthelmintic resistance. The present study investigated the efficacy against adult stages of a multi-resistant Haemonchus contortus isolate. While monepantel resulted in 100 % elimination, derquantel in combination with abamectin resulted in efficacies <95 % (faecal egg counts and worm counts).

Topics: Aminoacetonitrile; Animals; Anthelmintics; Disease Models, Animal; Feces; Haemonchiasis; Haemonchus; Indoles; Ivermectin; Oxepins; Parasite Egg Count; Sheep; Treatment Outcome

Few effective drugs are available for soil-transmitted helminthiases and drug resistance is of concern. In the present work, we tested the efficacy of the veterinary drug monepantel, a potential drug development candidate compared to standard drugs in vitro and in parasite-rodent models of relevance to human soil-transmitted helminthiases.. A motility assay was used to assess the efficacy of monepantel, albendazole, levamisole, and pyrantel pamoate in vitro on third-stage larvae (L3) and adult worms of Ancylostoma ceylanicum, Necator americanus and Trichuris muris. Ancylostoma ceylanicum- or N. americanus-infected hamsters, T. muris- or Ascaris suum-infected mice, and Strongyloides ratti-infected rats were treated with single oral doses of monepantel or with one of the reference drugs.. Monepantel showed excellent activity on A. ceylanicum adults (IC(50) = 1.7 µg/ml), a moderate effect on T. muris L3 (IC(50) = 78.7 µg/ml), whereas no effect was observed on A. ceylanicum L3, T. muris adults, and both stages of N. americanus. Of the standard drugs, levamisole showed the highest potency in vitro (IC(50) = 1.6 and 33.1 µg/ml on A. ceylanicum and T. muris L3, respectively). Complete elimination of worms was observed with monepantel (10 mg/kg) and albendazole (2.5 mg/kg) in A. ceylanicum-infected hamsters. In the N. americanus hamster model single 10 mg/kg oral doses of monepantel and albendazole resulted in worm burden reductions of 58.3% and 100%, respectively. Trichuris muris, S. ratti and A. suum were not affected by treatment with monepantel in vivo (following doses of 600 mg/kg, 32 mg/kg and 600 mg/kg, respectively). In contrast, worm burden reductions of 95.9% and 76.6% were observed following treatment of T. muris- and A. suum infected mice with levamisole (200 mg/kg) and albendazole (600 mg/kg), respectively.. Monepantel reveals low or no activities against N. americanus, T. muris, S. ratti and A. suum in vivo, hence does not qualify as drug development candidate for human soil-transmitted helminthiases.

Topics: Administration, Oral; Aminoacetonitrile; Animals; Anthelmintics; Cricetinae; Disease Models, Animal; Female; Inhibitory Concentration 50; Locomotion; Male; Mesocricetus; Mice; Mice, Inbred C57BL; Nematoda; Nematode Infections; Rats; Treatment Outcome

Eighteen, six- to seven-month-old lambs were infected experimentally with larvae of Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus axei, Trichostrongylus colubriformis, Cooperia curticei and Nematodirus spathiger, and allocated to three equal groups. The infections were timed to ensure that fourth-stage larvae were present when groups 1 and 2 were treated orally with monepantel. Group 1 was not fed for 24 hours before the treatment, group 2 was fed two hours before the treatment and group 3 was fed at the same time as group 2 but not treated with monepantel. All the sheep had access to water. Worm burdens were determined 15 days after the treatments. Fasting or feeding had no statistically significant effects on the efficacy of the monepantel solution against the nematodes, and the period of fasting had no adverse effects.

Topics: Aminoacetonitrile; Animals; Antinematodal Agents; Disease Models, Animal; Euthanasia, Animal; Fasting; Larva; Parasitic Sensitivity Tests; Sheep; Sheep Diseases; Trichostrongyloidea; Trichostrongyloidiasis