Anthelmintic activity of paraherquamide in sheep

Paraherquamide, an oxindole alkaloid metabolite of Penicillium paraherquei, was tested against the common gastrointestinal nematode species of sheep at 0.25, 0.5, 1.0, and 2.0 mg/kg, per os. It was highly efficacious (greater than or equal to 98% reduction) as a single oral treatment dosages greater than or equal to 0.5 mg/kg against adult Haemonchus contortus, Ostertagia circumcincta, Trichostrongylus axei, Trichostrongylus colubriformis and Cooperia curticei, and the L4 stage of Cooperia spp. Noteworthy is the fact the isolate of H. contortus used was ivermectin-resistant and the isolate of T. colubriformis used was ivermectin- and benzimidazole-resistant. This suggests a different mode of action for paraherquamide relative to ivermectin and the benzimidazoles. The adult stage of Oesophagostomum columbianum was the dosage-limiting parasite with 79% efficacy recorded at the highest treatment level (2.0 mg/kg). Extrapolation from the O. columbianum response curve suggests a dosage in excess of 4.0 mg/kg would be required to attain 95% efficacy.