Reduced efficacy of moxidectin and abamectin in young red deer (Cervus elaphus) after 20 years of moxidectin pour-on use on a New Zealand deer farm.

A study was undertaken on weaned 4-5 month old farmed red deer to test the efficacy of moxidectin and abamectin anthelmintics, given by three different routes of administration, compared with an untreated control. Faecal samples were collected on days 0, 7 and 14 for a faecal egg count reduction test (FECRT), blood samples were collected on days 0, 0.5, 1, 2, 3, 5, 7, 10 and 14 for pharmacokinetics, and the deer were killed on days 14 or 15 for total nematode count. The control group averaged 1264 adult Ostertagia-type nematode parasite species and treatment efficacy was 77.4% for moxidectin injection, 26% for oral moxidectin and 27.6% for pour-on moxidectin, while the treatment efficacy was 72.4% for abamectin injection, 70.1% for oral abamectin (Hi-Mineral) and 34.1% for pour-on abamectin. Both moxidectin and abamectin injections were significantly more efficacious than their equivalent pour-ons. There was a significant difference in efficacy between oral abamectin (Hi-Mineral) and oral moxidectin (P<0.01). The control group averaged 2956 adult lungworm (Dictyocaulus eckerti) and 50 Oesophagostomum venulosum in the large intestine and treatment efficacy against these nematodes was 100% for all treatments. There were negligible numbers of other gastro-intestinal nematodes. At slaughter, there was a significant correlation (P=0.02) between FEC and Ostertagia-type nematodes in the untreated controls. Relatively few eggs were found in faeces from treated animals at 7 and 14 days post-treatment despite significant worm burdens in all six treatment groups, suggesting egg-laying suppression in resistant nematodes, and all three different FECRT calculations tended to overestimate the efficacy of the treatments compared with actual nematode counts. Peak plasma concentrations (Cmax) for both actives were measured 12h after treatment for injection and oral and at 5 days for pour-on. Cmax (ng/ml) for moxidectin injection, oral and pour-on were 71.8, 8.3 and 0.4, respectively, and for abamectin injection, oral and pour-on were 62.1, 30.3 and 10.0, respectively. Area under the curve (AUC) estimates for moxidectin injection, oral and pour-on were 106.6, 12.9 and 6.1, respectively, and for abamectin injection, oral and pour-on were 162.7, 57.5 and 74.3, respectively. The results demonstrate that significant anthelmintic resistance to moxidectin and abamectin is present on this deer farm. However, the injection was the most effective route of administration in young deer for both anthelmintics, although <80% efficacious. We conclude that the FECRT is unreliable in deer when anthelmintic resistance is present.

A large-scale clinical field study to evaluate the efficacy and safety of an oral formulation of the amino-acetonitrile derivative ( AAD ), monepantel , in sheep in New Zealand.

AIM: To evaluate the efficacy and safety of an oral formulation of the novel anthelmintic, monepantel (AAD 1566), in sheep, in comparison with some other anthelmintics currently registered in New Zealand. METHODS: A study was conducted on 18 farms located throughout the North and South Islands of New Zealand. On each farm, sheep naturally infected with the target nematodes were randomly assigned to groups, which were then treated with either monepantel, at a minimum dose rate of 2.5 mg/kg, or one of five other anthelmintics encompassing the range of single-entity and combination formulations that are commercially available in New Zealand, or left untreated as controls. Faecal samples were collected from all sheep pre-treatment (1-3 weeks before treatment), at the time of treatment, and approximately 1, 2 and 3 weeks after treatment (Days 7, 14 and 21). Faecal nematode egg counts (FEC) were measured in all samples, and the efficacy of treatments, as indicated by reductions in FEC, calculated. All sheep were inspected at least daily, to check for any adverse effects of treatment. RESULTS: On all 18 farms, on Days 7, 14 and 21 (54 test points), the efficacy of the monepantel solution was >95%. At Days 7 and 14 post-treatment, efficacies>99% were recorded in 15 flocks. At Day 21 post-treatment, efficacies>98% were recorded in 13 flocks. Monepantel was as effective, or more effective, than the registered anthelmintics with which it was compared. Moreover, it was effective against strains of nematodes resistant to one or more of the currently available broad-spectrum anthelmintics. The monepantel solution used in this study was well tolerated by the sheep, and no adverse events could be attributed to its use. CONCLUSIONS AND CLINICAL RELEVANCE: When administered as an oral formulation under field conditions, at a minimum dose rate of 2.5 mg/kg, monepantel appeared to be highly effective against all the major genera of gastrointestinal nematodes of sheep, including Haemonchus, Teladorsagia (=Ostertagia), Trichostrongylus, Cooperia, Nematodirus, Chabertia and Oesophagostomum. This included strains resistant to the currently available broad-spectrum anthelmintics. Monepantel is the first compound from the recently discovered amino-acetonitrile derivative (AAD) class of anthelmintics to be developed for use in sheep.

Dose confirmation studies for monepantel, an amino-acetonitrile derivative, against fourth stage gastro-intestinal nematode larvae infecting sheep.

Monepantel is the first compound from the recently discovered amino-acetonitrile derivative (AAD) class of anthelmintics to be developed for use in sheep. Nine dose confirmation studies were conducted in Australia, New Zealand and Switzerland to confirm the minimum therapeutic oral dose of monepantel to control fourth stage (L4) gastro-intestinal nematode larvae in sheep (target species were Haemonchus contortus, Teladorsagia (Ostertagia) circumcincta, Teladorsagia trifurcata, Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus vitrinus, Cooperia curticei, Cooperia oncophora, Nematodirusbattus, Nematodirusfilicollis, Nematodirus spathiger, Chabertia ovina and Oesophagostomum venulosum). In each study, sheep infected with a defined selection of the target nematodes were treated with 2.5mg monepantel/kg liveweight. Following euthanasia and worm counting, efficacy was calculated against worm counts from untreated control groups. The results demonstrate high (95<100%) efficacy of monepantel when administered orally to sheep at 2.5mg/kg for most species tested. Efficacy levels against N. spathiger and O. venulosum were variable and failed to meet the required regulatory standard (> or =90%) in some studies. Efficacy was demonstrated against L4 stages of nematodes known to be resistant to either benzimidazole and/or levamisole anthelmintics (macrocyclic lactone resistant isolates were not available for testing). The broad-spectrum activity of monepantel against L4 larvae of common gastro-intestinal nematodes in sheep and its favorable safety profile represents a significant advance in the treatment of parasitic gastro-enteritis in this animal species. No adverse effects related to treatment with monepantel were observed.

Field studies investigating anthelmintic resistance in young cattle on five farms in New Zealand.

AIM: To investigate the efficacy of pour-on anthelmintics against field strains of parasitic nematodes in young cattle on five farms in New Zealand. METHODS: Faecal nematode egg count (FEC) reduction (FECR) tests were carried out on five calf-rearing farms using pour-on formulations of levamisole, ivermectin, eprinomectin, and the simultaneous administration of levamisole and ivermectin. Faecal samples were collected per rectum before treatment and about 7, 14, 21 and 28 days after treatment, for FEC and faecal nematode larval culture. RESULTS: Resistance (i.e. <95% reduction in FEC) of Cooperia oncophora to ivermectin and eprinomectin was identified on all five farms. There was limited evidence of possible emerging resistance in Ostertagia spp to ivermectin but not eprinomectin, in short-tailed larvae of Cooperia spp to ivermectin and eprinomectin, and in Trichostrongylus spp to ivermectin, eprinomectin and levamisole used separately. Levamisole was effective against C. oncophora, but had variable efficacy against Ostertagia spp in the calves in this study. Simultaneous treatment with levamisole and ivermectin pour-on formulations were effective against all genera on all farms. CONCLUSIONS: To effectively manage roundworm parasites in their calves farmers need to be aware of the resistance status of the parasites on their farms. Levamisole is likely to be an effective anthelmintic on most farms at times of the year when the impact of Ostertagia spp is not high. Simultaneous administration of levamisole and ivermectin pour-on anthelmintics to cattle is likely to control both ML-resistant C. oncophora and stages of Ostertagia spp that are not controlled by levamisole alone.

Anomalous swelling in phospholipid bilayers is not coupled to the formation of a ripple phase.

Aligned stacks of monomethyl and dimethyl dimyristoyl phosphatidylethanolamine (DMPE) lipid bilayers, like the much studied dimyristoyl PC (DMPC) bilayers, swell anomalously in a critical fashion as the temperature is decreased within the fluid phase towards the main transition temperature, T(M). Unlike DMPC bilayers, both monomethyl and dimethyl DMPE undergo transitions into a gel phase rather than a rippled phase below T(M). Although it is not fully understood why there is anomalous swelling, our present results should facilitate theory by showing that the formation of the phase below T(M) is not related to critical phenomena above T(M).

Critical swelling in single phospholipid bilayers.

We approach the controversial anomalous swelling problem in membrane systems using small angle neutron scattering to measure relative changes in the bilayer thickness of unilamellar vesicles of dimyristoylphosphatidylcholine lipid bilayers in the vicinity of the main transition. These measurements conclusively demonstrate that at least half of the anomalous swelling previously observed in multilamellar vesicles of this system can be accounted for by the critical thickening of the bilayer itself, in contrast to conclusions drawn from several recent studies.

Clarification of the ripple phase of lecithin bilayers using fully hydrated, aligned samples.

Aligned samples of lipid bilayers have been fully hydrated from water vapor in a different type of x-ray chamber. Our use of aligned samples resolves issues concerning the ripple phase that were ambiguous from previous powder studies. In particular, our x-ray diffraction data conclusively demonstrate that, on cooling from the L alpha to the P beta' phase, both chiral and racemic samples of dipalmitoyl phosphatidylcholine (DPPC) exhibit phase coexistence of long and short ripples with a ripple wavelength ratio lambda L/lambda S approximately 1.8. Moreover, the long ripple always forms an orthorhombic unit cell (gamma L = 90 degrees), strongly supporting the possibility that these ripples are symmetric. In contrast, gamma S for short ripples was consistently different from 90 degrees, implying asymmetric ripples. We continue to find no evidence that chirality affects the structure of rippled bilayers. The relative thermodynamic stability of the two types of ripples was investigated and a qualitative free energy diagram is given in which the long ripple phase is metastable. Finally, we suggest a kinetic mechanism, involving loss of water, that promotes formation of the metastable long ripple phase for special thermal protocols.

A pilot study of the efficacy of topical ivermectin against lungworm in young red deer (Cervus elaphus).

Three groups of ten 4-month-old red deer (Cervus elaphus) calves naturally infected with lungworm (Dictyocaulus viviparus) were treated with either oral ivermectin (200 microg/kg), topical (pour-on) ivermectin (500 microg/kg) or oral oxfendazole (5 mg/kg). Faecal larval counts for lungworm were undetectable or very low for 14 days after treatment with oxfendazole, 28 days after treatment with oral ivermectin and for 49 days after treatment with topical ivermectin. This pilot study suggests that the topical formulation of ivermectin was very effective against lungworm and had a more persistent action than the oral ivermectin formulation in young red deer.

Effect of ivermectin and oxfendazole on shedding of larvae of the lungworm (Dictyocaulus viviparus) by red deer (Cervus elaphus).

Thirty eight newly weaned hinds were randomly allocated to one of two equal groups. One group received ivermectin, the other, oxfendazole at dose rates of 0.2 mg/kg and 4.5 mg/kg, respectively. All deer were drenched four times and were grazed on pasture. Both anthelmintics reduced D. viviparus faecal larval counts to low levels 20 days after dosing, but the mean larval output and the proportion of deer shedding D. viviparus larvae at 27 and 33 days after treatment, were significantly lower in the ivermectin treated group. There was no significant difference in weight gain between the two groups throughout the trial. This study suggests that ivermectin prevents reinfection with D. viviparus for approximately 14 days longer than oxfendazole.

Efficacy and pharmacokinetics of febantel and ivermectin in red deer (Cervus elaphus).

A trial was conducted to determine the efficacy and pharmacokinetics of fehantel and ivermectin in six month-old red deer calves (C. eluphus). Five calves received febantel by mouth at 7.5 mg/kg, five received a subcutaneous injection of ivermectin at 200 microg/kg and five were controls. All calves were killed seven days later and total lung and gastrointestinal worm counts carried out. Febantel was 85 and 99.8% efficient in removing immature and mature Dictyocaulus viviparus, respectively, and ivermectin was 100% efficient in both cases. There was no gastro-intestinal nematodes in any of the treated calves, compared to an average of 619 in the control calves. The metabolism of febantel resulted in plasma levels of fenbendazole, oxfendazole and sulphone for which the common curves fitted by compartmental model peaked at values (standard errors)-of 0.46 (0.03), 0.41 (0.02) and 1.73 (0.07) mg/l after approximately five, nine, and thirteen hours and were undetectable at 30,72 and 120 hours respectively. There was considerable variation among animals in response to ivermectin. The fitted common curve had a peak plasma level of 15.8 (0.08) microg/l at 20 hours after injection, which had dropped to 7.9 (1.1) microg/l seven days after injection. It was estimated that after 15 days plasma levels of ivermectin would not be detectable. It is concluded that the injectable form of ivermectin tested is a highly efficient anthelmintic in deer, and that plasma levels persist for over a week after subcutaneous injection. Fehantel is very efficient against mature D. viviparus in deer, but its reduced efficiency against immature D. viviparus may relate to the deer;s ability to metabolise and excrete benzimidazoles more quickly than sheep and cattle.

Equine hydatidosis: a new record for New Zealand.

Cysts found in the liver of a horse which had never been out of New Zealand were used to infect two dogs which were slaughtered 35 days after infection. Large numbers of Echinococcus granulosus were recovered. These cestodes were compared with mature dog-sheep cestodes, using light and scanning electron microscopy and identified as the dog-horse strain of E.granulosus.

Survey of internal parasitism and anthelmintic use in farmed deer.

Faecal samples and questionnaires from 115 and 130 farms respectively were used to survey the internal parasite status of the national deer herd and examine current drenching practices. The survey included farms with red deer and wapiti-red deer crosses (Cervus elaphus), and fallow deer (Dama dama). Gastrointestinal nematode eggs were recorded from 84% of all farms, Dictyocaulus viviparus larvae from 85% of all farms, and Elaphostrongylus cervi larvae from 35% of the farms with C. elaphus. Faecal egg and larval counts were generally low. There was a significant relationship between the presence of Elaphostrongylus and the introduction of deer from Southland/Fiordland. Fenbendazole, oxfendazole and albendazole were the most frequently used anthelmintics of the 14 reported. Drenching programmes were extremely varied.