febantel and Trichostrongylosis

Drug resistance in sheep gastrointestinal trichostrongyles is a cosmopolitan major constraint to small ruminant production. Despite reports that anthelmintic drug resistance has become common, there are limited information on the presence of drug resistance in Italy. The purpose of this study was to determine the effect of four anthelmintics to control infection in sheep in central Italy. Fifty sheep with fecal egg counts (FEC) > or =150 eggs per gram were selected on each of three farms (n = 150 total sheep) which were randomly allocated to one of five groups. Groups were treated with febantel, levamisole, ivermectin, or moxidectin while the fifth group acted as the control group. A FEC reduction test (FECRT) was conducted on each animal and the mean FEC of each treatment group was compared to that of the control group within farm. Resistance was declared when percentage reduction (R) <95% and the lower 95% confidence interval was <90%. Levamisole (mean R = 89%) resistance was found on all farms and ivermectin (mean R = 93%) resistance was found on two of the three farms. Posttreatment larval cultures showed the presence of Teladorsagia (Ostertagia) circumcincta and Trichostrongylus spp. larvae. Febantel (mean R = 96%) and moxidectin (mean R = 100%) remained effective. This study suggests that drug resistance in sheep gastrointestinal trichostrongyles is present in central Italy and a potential problem which would justify a broader nationwide geographical investigation.

Topics: Animals; Antinematodal Agents; Drug Resistance, Multiple; Feces; Guanidines; Italy; Ivermectin; Levamisole; Macrolides; Ostertagia; Ostertagiasis; Parasite Egg Count; Sheep; Sheep Diseases; Treatment Outcome; Trichostrongylosis; Trichostrongylus

Plasma concentrations of febantel and its major metabolites, fenbendazole, oxfendazole and fenbendazole sulphone, were determined after oral administration of 7.5 mg/kg febantel in lambs before and 28 days after infection with 100,000 L3 larvae of a benzimidazole (BZ)-sensitive or BZ-resistant strain of Ostertagia circumcincta or with 75,000 L3 larvae of a BZ-sensitive Trichostrongylus colubriformis strain. The febantel concentrations were always low, and in only a few samples were higher than the limit of detection. A mean decrease in the area under the curve (AUC) for the three metabolites of 10.2%, 16.4% and 4.9% in lambs infected, respectively, with BZ-sensitive O. circumcincta, BZ-resistant O. circumcincta and T. colubriformis was observed. The Cmax for all the metabolites was higher in the BZ-sensitive O. circumcincta group than in the naive sheep, while the Tmax occurred earlier. The Cmax and the Tmax values for all the metabolites were lower in the BZ-resistant O. circumcincta group than in their own naive controls. In the T. colubriformis group the Cmax values of the metabolites were lower and the Tmax occurred much later.

Topics: Administration, Oral; Animals; Anthelmintics; Benzimidazoles; Drug Resistance; Feces; Fenbendazole; Guanidines; Male; Ostertagia; Ostertagiasis; Parasite Egg Count; Pepsinogens; Sheep; Sheep Diseases; Trichostrongylosis; Trichostrongylus

Plasma concentrations of febantel and its major metabolites fenbendazole, oxfendazole and oxfendazole sulphone were determined after oral administration of 7.5 mg/kg febantel in lambs before and 28 days after infection with 50,000 L3 larvae of Ostertagia circumcincta or Trichostrongylus colubriformis. The febantel concentrations were always very low and only in a few samples higher than the detection limit. The mean decrease in AUC for the three metabolites for the infected sheep in comparison to the parasite naïve sheep was 13.9% +/- 4.1% (mean +/- SEM) and 23.7% +/- 5.3% in the O. circumcincta infected and the T. colubriformis infected lambs respectively. This reduction was only significant for the T. colubriformis infected group. In order to determine a more complete pharmacokinetic profile, febantel was injected intravenously at a dose of 2.5 mg/kg in a further study.

Topics: Administration, Oral; Animals; Anthelmintics; Benzimidazoles; Biological Availability; Chromatography, High Pressure Liquid; Feces; Fenbendazole; Guanidines; Injections, Intravenous; Male; Ostertagiasis; Parasite Egg Count; Sheep; Sheep Diseases; Trichostrongylosis