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Duration of the persistent activity of moxidectin against Haemonchus contortus in sheep.

Weaned lambs were infected with Haemonchus contortus 35, 28, 21, 14 and 7 days after treatment with moxidectin at 0.2 mg/kg and 35 and 14 days after treatment with ivermectin at the same dose rate. Worm counts 14 days after infection showed that moxidectin prevented the establishment of over 99% of infective larvae for 28 days and reduced the establishment rate at 35 days by 96%, relative to ivermectin. There was no difference in the protective efficacy of ivermectin at 14 or 35 days. The persistence of moxidectin is likely to provide advantages in nematode control, particularly when used as a strategic early summer treatment or as a pre-lambing treatment to ewes. Implications of the persistent activity of moxidectin for the development of resistance during the decay phase are discussed.

Animals↗

Persistent efficacy of abamectin and doramectin against gastrointestinal nematodes of cattle.

OBJECTIVE: To assess the persistent activity of injectable formulations of abamectin and doramectin against gastrointestinal nematodes of cattle. DESIGN: Controlled slaughter study assessing residual efficacy. PROCEDURE: Nematode-free calves were treated with abamectin or doramectin (each at a dose of 200 micrograms/kg) and infections then induced with repeated doses of infective larvae of Trichostrongylus axei, Haemonchus placei, Ostertagia ostertagi and Cooperia species. The duration of challenge ranged from 14 to 28 days. The calves were slaughtered at either 38/39 or 45/46 days after the treatments and nematodes recovered from the gastro-intestinal tract. RESULTS: Significant reductions in numbers of O ostertagi occurred for both abamectin and doramectin treatments (> 93%) relative to counts in untreated calves, when challenge was administered up to 21 days after treatment. For T axei and Cooperia spp significant reductions occurred when the challenge occurred for 14 days after treatment (99%). Although differences from untreated animals were not significant, the results for H placei suggested high efficacy (> 85%) for up to 21 days for doramectin and up to 28 days for abamectin. CONCLUSIONS: There was no significant difference between abamectin and doramectin for any parasite at any challenge point, indicating that there is equivalent persistent activity of doramectin and abamectin against important gastrointestinal nematodes of cattle.

Animals↗

Reduced efficacy of ivermectin, abamectin and moxidectin against field isolates of Haemonchus contortus.

OBJECTIVES: To investigate the reduced efficacy of ivermectin, abamectin and moxidectin against two field isolates of Haemonchus contortus. These isolates were identified on separate properties in the New England region of New South Wales. PROCEDURE: Reduced efficacy of macrocyclic lactone anthelmintics against two field isolates of H contortus was suspected. These isolates were obtained from sheep on separate farms and pen trials were performed to investigate the efficacy of macrocyclic lactones. The percentage efficacy was calculated for moxidectin, ivermectin and closantel against the isolate from one farm (VHR23) and for moxidectin, ivermectin and abamectin against the isolate from the second (VHR29). The persistent activity of moxidectin against both isolates was investigated. RESULTS: Ivermectin and closantel were found to have efficacies below 80% against established populations of VHR23. Moxidectin was effective against an established population of VHR23 but the persistent activity was reduced to 7 days. Moxidectin was also found to be effective against established populations of VHR29, however, ivermectin and abamectin were found to have efficacies below 80%. There was no evidence of persistent activity of moxidectin against VHR29. CONCLUSION: A reduction in efficacy of abamectin and/or ivermectin against field isolates of H. contortus was identified from two farms in the New England region of New South Wales. The persistent effect of moxidectin was reduced against both isolates.

Animals↗

Effectiveness of copper oxide wire particles for Haemonchus contortus control in sheep.

OBJECTIVE: To assess the efficacy of copper oxide wire particles (COWP) for the control of H contortus infections in grazing sheep. PROCEDURE: In experiment 1, 40 worm-free Merino hoggets (11 to 12 months of age) were divided into four equal groups and allocated to separate 0.8 ha pasture plots. Two groups then received 2.5 g COWP whereas the other two groups were untreated. From 1 week after COWP treatment all lambs received a weekly infection of 2000 H contortus larvae. At week 8, six sheep from the untreated group were then allocated to two groups and treated with either 2.5 or 5.0 g of COWP to establish therapeutic efficacy of treatment. Experiment 2 followed a similar protocol but was conducted with 40 worm-free Merino lambs (3 to 4 months of age) and no assessment of therapeutic efficacy was made. RESULTS: In experiment 1 no significant difference in faecal worm egg counts was observed between treatments and faecal worm egg counts remained less than 3000 epg in all animals. Total worm counts were reduced by 37% by COWP treatment (P = 0.055). Both 2.5 g and 5.0 g doses of COWP at 8 weeks of infection reduced faecal worm egg counts by > 85% with the higher dose giving an earlier response to treatment. In experiment 2, faecal worm egg counts at 4 and 6 weeks were reduced by more than 90% in the COWP treated lambs and worm numbers were 54% lower after 6 weeks when all remaining untreated lambs had to be treated for haemonchosis. Mean faecal worm egg counts in the COWP lambs remained below 3500 epg and clinical disease did not develop in the majority of lambs before the end of the experiment at 10 weeks. CONCLUSION: Treatment with COWPs appears to have the potential to reduce establishment and worm fecundity of Haemonchus spp for an extended period and may offer livestock producers a supplementary means of reducing larval contamination of pasture particularly in areas where anthelmintic resistance is a problem and copper supplementation is likely to be beneficial.

Animal Husbandry↗

A field evaluation of benzimidazole and nonbenzimidazole drugs in a herd of dairy goats.

A study was conducted to investigate the efficacy of six anthelmintics in a herd of dairy goats. Pretreatment larval cultures indicated that the goats were infected with Haemonchus contortus and Trichostrongylus colubriformis. Three separate treatment regimens were administered. In each trial, mature nonlactating goats were allocated into two treatment groups and a control group. Treatment groups received thiabendazole (TBZ) or levamisole (LEV), mebendazole (MBZ) or fenbendazole (FBZ), and morantel tartrate (MOR) or ivermectin (IVR). LEV, MOR, and IVR reduced fecal strongyle egg counts by 99% to 100% of pretreatment values. The benzimidazole (BZD) drugs changed pretreatment fecal egg counts by +2% to -32%. Results of posttreatment larval culture demonstrated the presence of H contortus larvae following the administration of BZD drugs.

Animals↗

Interaction between fenbendazole and piperonyl butoxide: pharmacokinetic and pharmacodynamic implications.

The effect of the cytochrome P450 inhibitor, piperonyl butoxide on the pharmacokinetics and anthelmintic efficacy of the benzimidazole compound fenbendazole was studied in sheep and goats. Pretreatment of goats with the inhibitor caused a greater than three-fold increase in the relative bioavailability of fenbendazole and fenbendazole sulphoxide. A pharmacokinetic dose titration study was carried out in sheep with fenbendazole (5 mg kg-1) and piperonyl butoxide administered orally at 0, 15, 31, 63, 125 and 250 mg kg-1. The AUC of fenbendazole and the sulphoxide were significantly increased when fenbendazole was co-administered with piperonyl butoxide at dose rates equal to or higher than 31 mg kg-1. Peak plasma concentrations (Cmax) and mean residence time (MRT) were also significantly increased. The efficacy of the combination was assessed in sheep against two species of benzimidazole-resistant abomasal nematodes; Ostertagia circumcincta and Haemonchus contortus. The percentage reduction in the total number of O. circumcincta worms was 7.9% (fenbendazole) and 97.8% (fenbendazole-piperonyl butoxide). For H. contortus, the percentage reduction was 84.8% (fenbendazole) and 99.0% (fenbendazole-piperonyl butoxide). The in-vitro S-oxidation of fenbendazole and fenbendazole sulphoxide was studied using microsomal preparations from rat liver. Piperonyl butoxide inhibited significantly the sulphoxidation and sulphonation of fenbendazole. It was concluded that piperonyl butoxide inhibited the oxidative conversion of fenbendazole into inactive metabolites and this resulted in a potentiated anthelmintic action.

Animals↗

The localization of somatostatin-like immunoreactivity in the alimentary tract of the sheep with observations on the effect of an infection with the parasite Haemonchus contortus.

Cells containing somatostatin immunoreactivity were localized in the alimentary tract of parasite-free sheep by indirect immunocytochemistry, using an antiserum raised to ovine somatostatin. Nerve fibres showing somatostatin-like immunoreactivity were identified in the oesophagus, reticulum wall and groove, rumen pillar and wall, omasum sulcus and abomasum. Varicose fibres were found in the myenteric plexuses of the duodenum, jejunum, ileum and colon. The greatest distribution of endocrine cells (99 cells mm-2) was found in the antrum of the abomasum with 47, 29, 12 and 6 cells mm-2 respectively in the fundus, the first part of the duodenum, mid-jejunum and ileum. Some of the parasite-free sheep which had never experienced infection with larvae of the abomasal nematode, Haemonchus contortus, were paired with similar sheep in an experiment to investigate the effect of parasitism on nitrogen metabolism in the small intestine. The protocol of this experiment required observations before and after parasite infection, with final observations 2 weeks after removal of the infection by treatment with an anthelmintic drug. The sheep were then killed and tissues taken from each paired animal. Tissues from the recently parasitized sheep showed increases of D cells in the fundus and antrum of the abomasum. At present it is not clear if these increases were related to parasitism, per se, or were the post-treatment indicators of healing and recovery from infection with parasite larvae.

Animals↗

Protective immunity to a blood-feeding nematode (Haemonchus contortus) induced by parasite gut antigens.

To determine the ability of gut antigens to induce a protective immune response against blood-feeding nematodes, isolated gut antigens were used to immunize goats against Haemonchus contortus. Immunization-induced antibody responses recognized parasite gut antigens which were associated predominantly with the microvillous membrane region of the parasite gut. Antibody from immune serum also recognized seven predominant gut proteins on a Western blot (immunoblot). Several of these proteins appeared to be integral membrane proteins on the basis of their solubility in the detergent Triton X-114, indicating that the presentation protocol stimulated an antibody response to microvillous membrane antigens. Three different age groups of goats ranging from less than 6 months to greater than 1 year were immunized for challenge experiments. After infection with 10(4) larvae, an 87 to 95% reduction in fecal egg counts for all age groups of goats was achieved in the immunized compared with the control group. The reduction of worms in immunized goats ranged from 65% (kids) to 89% (yearlings) compared with controls. These results indicate that gut antigens can induce significant protection against blood-feeding nematodes. Antibody to H. contortus gut antigens also cross-reacted with microvilli of other blood-feeding nematodes including Ostertagia ostertagi and small strongyles of horses, which indicates that epitopes associated with the gut are phylogenetically conserved.

Animals↗

Identification of secreted cysteine proteases from the parasitic nematode Haemonchus contortus detected by biotinylated inhibitors.

Seven cathepsin B-like cysteine proteases (CBLs) were identified from the immunoprotective excretory-secretory products of Haemonchus contortus. Two-dimensional (2-D) zymography and biotinylated inhibitors were employed to localize active CBLs in 2-D protein gels. Mass spectrometry provided the identification of AC-4, HMCP1, HMCP2, and GCP7 as well as three novel CBLs encoded by clustered expressed sequence tags.

Amino Acid Sequence↗

The influence of breed on the susceptibility of sheep and goats to a single experimental infection with Haemonchus contortus.

Four breeds of sheep and three breeds of goats, maintained on both high and low planes of nutrition were given a single infection of 350 Haemonchus contortus larvae per kg. Although animals on a low protein diet had much higher faecal egg counts than those on the high protein diet the pattern of relative susceptibility was similar in both cases. It would appear that the nutritional status of the host influences its resistance to H contortus infection. Of the breeds studied the indigenous Red Masai was the most resistant breed of sheep while the exotic Saanen was more resistant than the the two indigenous breeds of goats.

Animals↗

Efficacy of febantel in sheep experimentally infected with five species of gastrointestinal nematodes.

The anthelmintic activity of the guanidine derivative febantel was tested in a total of 76 experimentally infected lambs in two control tests. Doses of 5.0 and 7.5 mg per kg body-weight were administered orally against fourth and pre-adult fifth or adult stages of Haemonchus contortus, Ostertagia circumcincta, Trichostrongylus colubriformis, B unostomum trigonocephalum and Oesophagostomum columbianum. The efficacy was between 98.5 and 100 per cent. The drug was well tolerated.

Acetanilides↗

Thiophanate as a low daily dosage anthelmintic in sheep.

Thiophanate administered daily at low dosages reduced nematode faecal egg output, egg hatchability and parasitic worm burdens in treated lambs and ewes. Six daily doses of 1 or 3 mg per kg thiophanate (approximately 1/25th to 1/75th of the median therapeutic dose), given to lambs experimently infected with Trichostrongylus colubriformis, were partially effective in suppressing faecal egg output and egg hatchability. Six doses of 5 mg per kg per day were effective in lambs infected with Haemonchus contortus and Nematodirus spathiger. Daily doses of thiophanate (50 or 200 mg per head) given over 14 weeks to lambs grazing contaminated pasture resulted in improved productivity (the higher dosage) and suppression of output of viable eggs and reduced worm burdens (both dosages). Reduced output of viable eggs was also obtained in housed, lactating ewes receiving 5 or 7 mg per kg thiophanate dispersed daily in the feed for 11 or nine weeks respectively after lambing.

Animals↗