新型莫西菌素浇泼剂对羊蜱蝇和消化道线虫驱虫药效评价

试验旨在通过新型莫西菌素（moxidectin,MOX）浇泼剂对羊的驱虫试验,评价MOX浇泼剂对羊蜱蝇和消化道线虫的临床药效。将150只阿勒泰羊经产母羊随机分为6组,每组25只,分别为不用药对照组、螨净药浴组、MOX注射组和MOX低（0.05 mL/（kg·BW））、中（0.1 mL/（kg·BW））和高（0.2 mL/（kg·BW））剂量浇泼组,试验期为1周。试验第1天按前述分组中方法和剂量驱虫1次。观察受试动物临床表现,测定给药前1天和给药后第7天体温、脉搏和呼吸（TPR）,血液生理、生化和尿常规指标;测定羊蜱蝇减虫率、治愈率。采取粪样测定消化道线虫每克粪中虫卵个数（EPG）减少率及转阴率。结果显示,与不用药对照组相比,给药后第7天各驱虫组TPR、血液生理、生化及尿常规指标均无显著差异（P>0.05）。螨净药浴组羊蜱蝇减虫率为43.7%,而MOX注射组及MOX低、中、高剂量浇泼组均为100%。螨净药浴组治愈率为13.0%,而MOX注射组及MOX低、中、高剂量浇泼组均为100%;与不用药对照组相比,螨净药浴组消化道线虫卵减少率为0,而MOX注射组及MOX低、中、高剂量浇泼组分别为91.6%、93.1%、94.9%和97.8%。螨净药浴组虫卵转阴率为0,而MOX注射组及MOX低、中、高剂量浇泼组分别为77.0%、69.2%、69.2%和84.6%。本试验结果表明,新型MOX浇泼剂对体外寄生虫和消化道线虫均有显著疗效,且优于螨净药浴,与MOX注射剂等效。实践应用中最适MOX浇泼剂量推荐为0.05 mL/（kg·BW）（即0.25 mg/（kg·BW））。     

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.     

Field studies of the immunisation of lambs with drug-abbreviated infections of Trichostrongylus colubriformis and Ostertagia circumcincta

Fifty, 5–6 month-old lambs were randomly allocated to five equal groups. Three groups of lambs were immunised by three oxfendazole-abbreviated (artificial) infections of Trichostrongylus colubriformis and Ostertagia circutncincta. Group 1 was immunised with a high dose of larvae, Group 2 with a medium dose and Group 3 with a low dose. A fourth group was treated with oxfendazole only and a fifth group was not treated (control). All groups were grazed together on pasture naturally contaminated with nematode larvae. Immunisation significantly reduced the number of eggs per gram of faeces in all three groups, but the lowest faecal egg count was seen in Group 3 (immunised with the lowest number of larvae). Significantly better liveweight gains and wool weight were observed in Group 2 animals than in the control group. Of all anthelmintic-treated animals, only Group 1 lambs did not have a signscantly lower dag weight than controls.     

Resistance to a triple-combination anthelmintic in Trichostrongylus spp. on a commercial sheep farm in New Zealand

Abstract

AIM: To evaluate resistance to anthelmintics containing abamectin, levamisole, and oxfendazole (AB-LEV-OX), derquantal and abamectin (DEQ-AB), moxidectin, and monepantel in naturally acquired gastrointestinal nematodes present on a sheep farm.

METHODS: Faecal nematode egg count reduction tests (FECRT) were carried out on lambs that were approximately 7 months-old and infected with naturally acquired nematodes. Lambs were randomly allocated to one of five groups (n=15 per group): treatment with 2?mg/kg derquantel and 0.2?mg/kg abamectin; 0.2?mg/kg abamectin, 8?mg/kg levamisole HCl and 4.5?mg/kg oxfendazole; 2.5?mg/kg monepantel; 0.2?mg/kg moxidectin, or no treatment. Post-treatment samples were collected 12 days later. Abomasa and small intestines were collected from two slaughtered lambs from each of the DEQ-AB, AB-LEV-OX, moxidectin and control groups 15 days after treatment, for nematode counting.

RESULTS: The FECRT demonstrated that efficacy was 90.3 (95% CI=84.2–94.1)% for AB-LEV-OX, 54.5 (95% CI=28.4–71.1)% for moxidectin, 99.2 (95% CI=97.4–99.8)% for DEQ-AB and 100% for monepantel, across all genera. For Trichostrongylus spp. efficacy was 85.5% for AB-LEV-OX and 46.7% for moxidectin. Haemonchus spp. were fully susceptible to all treatments. Post-treatment nematode counts indicated that the resistant Trichostrongylus spp. were from the small intestine.

CONCLUSIONS: Anthelmintic resistance to both AB-LEV-OX and moxidectin was present in the Trichostrongylus genus on a commercial sheep farm. Monepantel and DEQ-AB were both effective against Trichostrongylus spp. based on FECRT results.

CLINICAL RELEVANCE: This finding of resistance to an AB-LEV-OX triple-combination anthelmintic in the Trichostrongylus genus in sheep in New Zealand further limits anthelmintic treatment options available, and calls into question whether this combination is suitable for use as a quarantine treatment.     

Transmission of Babesia spp by the cattle tick (Boophilus microplus) to cattle treated with injectable or pour-on formulations of ivermectin and moxidectin

OBJECTIVE: To assess the efficacy of ivermectin and moxidectin to prevent transmission of Babesia bovis and Babesia bigemina by Boophilus microplus to cattle under conditions of relatively intense experimental challenge. DESIGN: Naive Bos taurus calves were treated with either pour-on or injectable formulations of either ivermectin or moxidectin and then exposed to larvae of B microplus infected with B bovis or larvae or adults of B microplus infected with B bigemina. One calf was used for each combination of haemoparasite, B microplus life stage, drug and application route. PROCEDURE: Groups of calves were treated with the test drugs in either pour-on or injectable formulation and then infested with B microplus larvae infected with B bovis or B bigemina. B bigemina infected adult male ticks grown on an untreated calf were later transferred to a fourth group of animals. Infections were monitored via peripheral blood smears to determine haemoparasite transmission. RESULTS: Cattle treated with either pour-on or injectable formulations of ivermectin and moxidectin became infected with B bovis after infestation with infected larvae. Similarly, larvae infected with B bigemina survived to the nymphal stage to transmit the haemoparasite to animals treated with each drug preparation. Cattle treated with pour-on formulations of ivermectin and moxidectin then infested with adult male ticks infected with B bigemina did not become infected with B bigemina whereas those treated with the injectable formulations of ivermectin and moxidectin did show a parasitaemia. CONCLUSIONS: Injectable or pour-on formulations of ivermectin and moxidectin do not prevent transmission of Babesia to cattle by B microplus. Use of these drugs can therefore not be recommended as a primary means of protecting susceptible cattle from the risk of Babesia infection.     

Reversal Effects of Ivermectin and Moxidectin on Multidrug Resistance in C6/adr Cells in vitro

Multidrug resistance(MDR) is a serious obstacle encountered in cancer treatment. This study was performed to explore the reversal MDR activity of ivermectin(IVM) from avermectin family and moxidectin(MOX) belonging to milbemycin family. The two compounds(5 μmol · L~(-1)) showed strong potency to increase adriamycin cytotoxicity toward adriamycin-resistant rat glioma cells C6/adr with fold reversal(FR) of 31.02 and 13.40, respectively. In addition, the mechanisms of them on p-glycoprotein(P-gp)-mediated MDR demonstrated that the two compounds significantly increased the intracellular accumulations of adriamycin and Rh123 via inhibiting P-gp efflux. Based on the analysis of P-gp, MDR1 and MRP1 gene expressions by using immunofluorescence flow cytometry and RT-PCR, the results revealed that the two compounds could down regulate the expression of P-gp, and that MDR1 and MRP1 gene expressions were down regulated. These findings suggested that ivermectin and moxidectin probably represented potent agents for reversing MDR in cancer therapy, and especially ivermectin was a better modulator.     

Comparative pharmacokinetic and pharmacodynamic response of single and double intraruminal doses of ivermectin and moxidectin in nematode-infected lambs

Abstract

AIMS: To compare the pharmacokinetics, distribution and efficacy (pharmacodynamic response) of intraruminal ivermectin (IVM) and moxidectin (MXD) administered at 0.2 and 0.4?mg/kg to naturally nematode-infected lambs, and to determine the ex vivo accumulation of these anthelmintics by Haemonchus contortus.

METHODS: Romney Marsh lambs, naturally infected with IVM-resistant H. contortus, were allocated to treatment groups based on faecal nematode egg counts. They received 0.2 or 0.4?mg/kg IVM or MXD (n=10 per group), or no treatment (Control; n=6), on Day 0. Samples from four animals from each treatment group, including abomasal parasites, were obtained on Day 1. Plasma samples were also collected from Day 0 to 14, and a faecal egg count reduction test (FECRT) and a controlled efficacy trial were carried out on Day 14. Concentrations of IVM and MXD in plasma, in abomasal and intestinal tissues and in H. contortus were evaluated by high-performance liquid chromatography. Additionally, the ex vivo drug accumulation of IVM and MXD by H. contortus was determined.

RESULTS: Peak plasma concentrations and the area under the concentration vs. time curve for both IVM and MXD were higher for 0.4 than 0.2?mg/kg treatments (p<0.05), but there were no differences for other parameters. Concentrations of IVM and MXD in the gastrointestinal target tissues and in H. contortus were higher compared to those measured in plasma. Concentrations of both drugs in H. contortus were correlated with those observed in the abomasal content (r=0.86; p<0.0001). The exposure of H. contortus to IVM and MXD was related to the administered dose. Mean FECRT and efficacy for removal of adult H. contortus was 0% for IVM at 0.2 and 0.4?mg/kg. For MXD, FECRT were >95% for both treatments, and efficacy against H. contortus was 85.1% and 98.1% for 0.2 and 0.4?mg/kg, respectively. The ex vivo accumulation of IVM and MXD in H. contortus was directly related to the drug concentration present in the environment and was influenced by the duration of exposure.

CONCLUSION: Administration of IVM and MXD at 0.4 compared with 0.2?mg/kg accounted for enhanced drug exposure in the target tissues, as well as higher drug concentrations within resistant nematodes. The current work is a further contribution to the evaluation of the relationship between drug efficacy and basic pharmacological issues in the presence of resistant parasite populations.     

Production benefits from pre- and post-lambing anthelmintic treatment of ewes on commercial farms in the southern North Island of New Zealand

Abstract

AIMS: To measure the magnitude and variability in production responses to anthelmintic treatments administered to adult ewes around lambing.

METHODS: Ewes carrying twin lambs, from sheep and beef farms (eight in Year 1 and six in Year 2) in the Wairarapa region of New Zealand, were enrolled in 14 trials (part of an experiment carried out on one farm in one year). Experiment 1 compared ewes treated 2–4?weeks pre-lambing with a controlled release capsule (CRC) containing abamectin, albendazole, Se and Co, to ewes injected pre-lambing with a long-acting Se plus vitamin B₁₂ product, and to untreated ewes. Experiment 2 included these treatments, plus a CRC administered at pregnancy scanning. Experiment 3 included the same treatments as Experiment 1, plus administration of a CRC containing albendazole, Se and Co, injectable moxidectin or oral derquantel plus abamectin, all administered pre-lambing, or oral derquantel plus abamectin administered 4–6?weeks after lambing. Variables compared were ewe liveweight at weaning and pre-mating, lamb liveweight at weaning, total weight of lamb weaned per ewe and ewe dag score at weaning.

RESULTS: Ewes treated with a CRC pre-lambing were heavier than untreated ewes (mean 3.2?kg) at weaning in 12/14 trials, and pre-mating (mean 2.8?kg) in 9/14 trials (p<0.001). Compared with mineral-treated ewes the mean difference was 2.8?kg pre-lambing (9/14 trials) and 1.7?kg pre-weaning (6/14 trials). Lambs reared by treated ewes were heavier (mean 1.55?kg) at weaning in 6/14 trials (p<0.001), but there was no effect of CRC treatment on total weight of lambs weaned per ewe (p=0.507). Variation in weight of lamb weaned per ewe was largely explained by differences in lamb survival from birth to weaning (p<0.001), with no effect of CRC treatment (p>0.65).

Treatment of ewes with a CRC at pregnancy scanning was neither better nor worse than a pre-lambing treatment (p=0.065).

There was no difference in the response from treatment with either of the two CRC or moxidectin. Treatment with short-acting oral anthelmintics resulted in no consistent benefit.

CONCLUSIONS: Anthelmintic treatments administered to ewes around lambing resulted in variable responses between farms and years, which in some trials were negative for some variables, and some of the variability was due to the mineral component of the CRC. The widespread perception amongst farmers and veterinarians that anthelmintic treatment of ewes around lambing will always result in positive benefits is not supported.     

新一代驱虫抗生素--莫西菌素

本文综述了莫西菌素的理化特性、作用机制、药效学、药动学、制剂、毒性、残留及耐药性等，并与伊维菌素进行了对比。     

The application of moxidectin formulations for control of the cattle tick (Boophilus microplus) under Queensland field conditions

Objective To assess the control of the cattle tick (Boophilus microplus) and the performance of commercial cattle treated with the macrocylic lactone endectocide, moxidectin, formulated either as an injection or as a pour-on. Design Groups of 10–12 tick infested cattle were treated with moxidectin injection, moxidectin pour-on or remained untreated (28-day trials) or were treated with deltamethrinethion as a dip (140-day trials). The cattle were exposed to natural tick challenge under field conditions. Procedure Tick numbers on trial cattle were recorded in each trial before the initial treatment and in the 28-day trials at 7, 14, 21 and 28 days or in the 140-day trials, at 28-day intervals before each of the treatments and at the final inspection. Body weights of the cattle were also recorded prior to the initial treatment and at the termination of each trial. Cattle were observed on the day of each treatment and at each inspection for evidence of any reactions to treatment. Results 28-day trials: Significant reductions in tick counts were recorded in both treatment groups when compared with cattle in the untreated group. Weight advantage was recorded in the moxidectin treated groups. 140-day trials: All three treatments resulted in zero or low tick counts at each inspection with the exception of the pour-on treatment at week 8 in one trial and week 9 in the other trial. Additional weight gain was recorded for both the moxidectin treated groups, relative to the deltamethrin-ethion dip groups, but was significant only for the pour-on groups. There was no evidence of any local or systemic adverse reaction in any treated cattle in any trial. Conclusion Good to excellent control of the cattle tick (Boophilus microplus) was demonstrated with the moxidectin formulations in all trials, the injection being particularly effective. An improved performance was recorded in all trials in cattle treated with both moxidectin formulations when compared with the untreated cattle and with cattle treated with the deltamethrin-ethion dip. There was no evidence of any local or systemic adverse reaction to treatment with either moxidectin formulation.