monepantel and Trichostrongyloidiasis

The effect of the route of administration (oral, intraruminal and intra-abomasal) on the efficacy and pharmacokinetics of the new anthelmintic monepantel in sheep was investigated. The target nematodes were fourth-stage Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus colubriformis and Cooperia curticei. A clear difference in efficacy was identified between the routes of administration, although the difference did not consistently reach statistical significance; oral treatment was most effective, followed by intraruminal and then intra-abomasal administration. The same pattern was observed in the pharmacokinetic analysis, with lambs treated orally having more favourable exposure to monepantel and its sulfone metabolite (albeit in all but one instance not significantly different) than the lambs treated by the other routes of administration, which were very similar for most parameters.

Topics: Abomasum; Administration, Oral; Aminoacetonitrile; Animals; Anthelmintics; Drug Administration Routes; Rumen; Sheep; Sheep Diseases; Trichostrongyloidea; Trichostrongyloidiasis

Recent reports of monepantel (MPTL) resistance in UK field isolates of Teladorsagia circumcincta has highlighted the need for a better understanding of the mechanism of MPTL-resistance in order to preserve its anthelmintic efficacy in this economically important species. Nine discrete populations of T. circumcincta were genotypically characterised; three MPTL-susceptible isolates, three experimentally selected MPTL-resistant strains and three field derived populations. Full-length Tci-mptl-1 gene sequences were generated and comparisons between the MPTL-susceptible isolates, MPTL-resistant strains and one field isolate, showed that different putative MPTL-resistance conferring mutations were present in different resistant isolates. Truncated forms of the Tci-mptl-1 gene were also observed. The genetic variability of individual larvae, within and between populations, was examined using microsatellite analyses at 10 'neutral' loci (presumed to be unaffected by MPTL). Results confirmed that there was little background genetic variation between the populations, global F

Topics: Aminoacetonitrile; Animals; Anthelmintics; DNA, Helminth; Drug Resistance; Genotype; High-Throughput Nucleotide Sequencing; Loss of Function Mutation; Male; Microsatellite Repeats; Scotland; Sequence Alignment; Sheep; Sheep Diseases; Trichostrongyloidea; Trichostrongyloidiasis; United Kingdom

The prevalence of anthelmintic resistance in Northern Ireland sheep flocks was evaluated between July and October 2011. Sampling kits were sent to 172 flock owners and returns were received from 91. Within this survey population, 27 flock owners used benzimidazole products, 10 used levamisole products, 15 used avermectin products, 26 used milbemycin products and 4 flock owners used the amino acetonitrile derivative, Monepantel. The remaining 9 flock owners used combination drenches (broad spectrum wormer plus fasciolicide). However, 15 sets of samples were ineligible for faecal egg count reduction testing due to either too low an egg count or insufficient faecal volume. Treatment efficacy below 95%, indicating significant resistance, was detected in 81% (n=24) of flocks tested for benzimidazole resistance; in 14% (n=1) of flocks tested for levamisole resistance; and in 50% (n=7) and 62% (n=13) of flocks tested for avermectin and milbemycin resistance, respectively. Monepantel resistance was absent in all (n=3) flocks tested. Combination products (broad spectrum nematocide plus flukicide) containing levamisole were entirely effective, while treatment efficacy below 95% was detected in 60% (n=3) of flocks where the nematocide in the combination product was a benzimidazole. Where parasite identification based on coproculture was completed, Trichostrongylus was the dominant genus detected in all cases post-treatment, indicating the occurrence of anthelmintic-resistant Trichostrongylus spp. populations. Benzimidazole efficacy was highest in treating Trichostrongylus spp. (51%) and lowest when treating Teladorsagia spp. Levamisole was 100% effective in treating Cooperia, but ineffective (0%) in treating Trichostrongylus spp. Avermectin efficacy was highest when treating Haemonchus contortus (100%) and Teladorsagia spp. (73%), with a marginally lower efficacy against Trichostrongylus spp. (71%). Moxidectin efficacy was 33% against Trichostrongylus spp., 68% against Teladorsagia spp., 97% against Cooperia spp. and 100% against Haemonchus contortus infections.

Topics: Aminoacetonitrile; Animals; Anthelmintics; Antinematodal Agents; Benzimidazoles; Drug Resistance; Feces; Gastrointestinal Diseases; Ivermectin; Levamisole; Macrolides; Northern Ireland; Parasite Egg Count; Prevalence; Sheep; Sheep Diseases; Sheep, Domestic; Treatment Outcome; Trichostrongyloidea; Trichostrongyloidiasis

Monepantel is the first molecule from the amino-acetonitrile derivatives to be developed for controlling gastro-intestinal nematodes in sheep. Two studies were undertaken to examine the drug's efficacy against inhibited fourth-stage larvae of Haemonchus contortus and Teladorsagia spp. in sheep when administered as an oral solution at 2.5mg/kg bodyweight. In study 1, efficacy was 99.7% against H. contortus (p<0.0001) and in study 2, 99.8% against Teladorsagia spp. (p<0.0001). This population consisted of 93% T. circumcincta and 7% T. trifurcata. In conclusion, monepantel is a highly effective treatment against inhibited fourth-stage larvae of H. contortus and Teladorsagia spp. and the studies reported here provide the first published evidence of efficacy of this new anthelmintic against these parasites.

Topics: Aminoacetonitrile; Animals; Anthelmintics; Australia; Female; Haemonchiasis; Haemonchus; Larva; Male; Sheep; Sheep Diseases; Treatment Outcome; Trichostrongyloidea; Trichostrongyloidiasis

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