Clinical field study to evaluate the efficacy and safety of the amino-acetonitrile derivative, monepantel, compared with registered anthelmintics against gastrointestinal nematodes of sheep in Australia

Objective   To determine the efficacy of monepantel, a developmental compound from the amino-acetonitrile derivative class of anthelmintics, against field infections of gastrointestinal nematodes in sheep.
Procedures   Comparisons of efficacy (using standard faecal worm egg count reduction tests) and safety (on the basis of visual observations) were made in a large-scale field study in Australia, between groups of sheep treated with either an oral solution of monepantel or a registered anthelmintic. The sheep were naturally infected with the major gastrointestinal nematode genera present in Australia.
Results   The post-treatment efficacy results for monepantel were: at 7 days (±1 day) efficacy was >98%; at 14 days (±1 day) it was generally close to or >99%; and at 21 days (±1 day) efficacy was consistently >99%. A high proportion of the targeted nematode populations were confirmed as being resistant to one or more of the currently available anthelmintic classes.
Conclusions   Monepantel when used under field conditions at a minimum dose rate of 2.5 mg/kg was highly effective against mixed-genus natural field infections of the major gastrointestinal nematode genera including Haemonchus , Teladorsagia ( Ostertagia ), Trichostrongylus , Nematodirus , Chabertia and Oesophagostomum . This result included efficacy against some populations resistant to the currently available broad-spectrum anthelmintics. Few Cooperia spp. were present to allow confirmation of efficacy against this genus. On no occasion after treatment did any commercial anthelmintic-treated groups have significantly lower faecal egg counts than the monepantel-treated groups. Monepantel was safe for the target animals and human operators when used in a field situation.     

宁夏羊胃肠道线虫对现行驱虫药的抗药性调查

采用粪便虫卵减少试验对宁夏地区所属灵武、贺兰、盐池、吴忠、中宁、中卫、永宁和银川市郊8个县（市）的12个绵羊场、6个山羊场进行了丙硫苯咪唑和阿维菌素抗药性的随机调查。结果表明：在用丙硫苯咪唑调查的10个绵羊场和6个山羊场中，虫卵减少率在95％以下和95％的置信域下限在90％以下的有山羊场2个、绵羊场2个，证明对丙硫苯咪唑有抗药性；1个绵羊场和1个山羊场的虫卵减少率是96．3％、95．9％，但95％置信域的下限在90％以下，具有抗药性可疑；山羊群中丙硫苯咪唑的抗药性为33．3％，绵羊群为20．0％。用同样的方法调查了1个山羊场和5个绵羊场（其中有4个羊场曾执行了丙硫苯咪唑的试验），查出1个山羊场和1个绵羊场对阿维菌素具有抗药性可疑，其虫卵减少率分别为97．3％和95．5％，置信域下限在90％以下。揭示了宁夏地区羊消化道线虫对现行驱虫药的抗药状态，为今后防治提供了依据。     

The efficacy of an albendazole-medicated block in controlling sheep nematodes in Xinjiang Province,north-west China

Medicated feed-blocks containing 2 mg/kg albendazole were fed for 12 days to ewe-lambs naturally infected with nematode worms in north-west China. The cumulative total average intake of albendazole was 15 mg/kg body weight. This treatment was compared with a single oral drench of 15 mg/kg albendazole and with no treatment. Both albendazole treatments were 99% effective in reducing the total strongyle egg counts. The medicated block was 100% effective in reducing the total trichostrongylid worm count, although only 86.4% of the sheep consumed an adequate amount. The single drench was 97% effective. Under the management conditions available to sheep herders in the northern provinces of China, albendazole-medicated feed-blocks used at strategic times could effectively control trichostrongylid nematodes.     

The Effects of a Controlled-Release Albendazole Capsule (Proftril-Captec) on Parasitism in Grazing Corriedale Ewes in the Nyandarua District of Kenya

Munyua, W.K., Githigia, S.M., Mwangi, D.M., Kimoro, C.O. and Ayuya, J.M., 1997. The effects of a controlled-release albendazole capsule (Profitril-Captec) on parasitism in grazing Corriedale ewes in the Nyandarua district of Kenya. Veterinary Research Communications, 21 (2), 85-99The effects of intraruminal sustained-release capsules (IRSRCs) on parasitism in grazing Corriedale ewes were investigated over a period of 119 days (4 June-30 September 1993) using 40 ewes aged approximately 2 years and randomly divided into two groups of 20 ewes each. Each of the ewes in the treatment group received an IRSRC while the controls were left untreated. The groups were placed on adjacent 2.5-acre paddocks obtained by subdividing a 5.0-acre permanent pasture which had previously been grazed by young untreated sheep, so exposing both groups of ewes to a similar challenge from a contaminated paddock. The faecal egg counts, herbage larval counts and worm burdens of the major gastrointestinal parasites of sheep were significantly reduced by the use of the IRSRC. These parasitological effects were reflected in the increased live weight gains and heavier fleeces of the IRSRC-treated ewes. The control ewes required occasional salvage treatments during the trial period and the herbage on their paddock was heavily contaminated with infected larvae, reflected in the high worm burdens in the control ewes necropsied at the end of the trial and in tracer sheep introduced into the paddocks during the initial (day 30), interim (day 58) and final (day 89) stages of the experiment. Most capsules were exhausted within 95 days of administration, leading to a rise in the count of eggs per gram in the faeces in the treated group towards the end of the study.     

Evidence that moxidectin is a greater risk factor than ivermectin in the development of resistance to macrocyclic lactones by Ostertagia spp in sheep in south eastern Australia

AIM: To determine associations between resistance of Ostertagia (= Teladorsagia) spp to macrocyclic lactone (ML) anthelmintics and history of use of anthelmintics, by type, on commercial sheep farms in temperate regions of southern South Australia and Victoria, Australia.

METHODS: Faecal egg count reduction tests (FECRTs) were conducted during a 2.5-year period (from August 2001 to January 2004) and records of the type of anthelmintic used in the 5 years preceding the FECRTs were collected from commercial sheep farms (n=103) in southern South Australia and Victoria, and data analysed retrospectively. ML resistance was defined as <95% reduction of Ostertagia spp 10–14 days after treatment with ivermectin (IVM), orally, at half the manufacturer's recommended dose rate. Use of anthelmintics in the preceding 5 and 10 years on each property was classified according to the nett number of years each of the following classes of drug had been used: IVM oral liquid (IVO), IVM controlled-release capsules (CRCs), abamectin (ABA), moxidectin (MOX) or a non-ML an- thelmintic. The prevalence of ML resistance, by property, was analysed for associations with prior use of anthelmintics.

RESULTS: Resistance by Ostertagia spp to ML anthelmintics was evident on 51/103 (49.5%) properties. The prevalence of resistance was lowest (23%) on properties on which MOX had not been used, and was significantly higher (64–77%) on properties on which MOX had been used for ≥2 of the preceding 5 years (p<0.001). In contrast, the prevalence of resistance was highest (70–74%) on the properties on which IVM, or IVM and/ or ABA, had not been used in the previous 5 years (on which the use of MOX was predominant), and was markedly lower (20– 42%) on properties that had used IVM or IVM and/or ABA for at least one of the preceding 5 years. Prevalence of resistance was higher for properties on which the only ML anthelmintic used was MOX (19/29=66%) than for those on which the only ML used was IVO (2/19=11%; p<0.001). Properties on which the only ML used was MOX were 2.72 times more likely to have resistance than properties on which the only ML used was IVO (95% confidence interval (CI) = 1.01–5.08).

CONCLUSION: Use of MOX for ≥2 of the preceding 5 years was associated with a higher prevalence of resistance to ML by Ostertagia spp on sheep farms in south eastern Australia than the use of IVO.     

The Effect of Strategic Anthelmintic Treatment on Internal Parasites in Communally Grazed Sheep in a Semi-Arid Area as Reflected in the Faecal Nematode Egg Count

Communally grazed sheep were dosed at 4-, 12-, 24- or 48-week intervals for 1 year. Dosing every 4 weeks proved to be the most effective (p<0.05), as reflected in a lower worm egg count compared to the 12-, 24- or 48-week intervals. Since most nematode life cycles lie between 3 and 6 weeks, the treatment has to be given during this critical period if maximum economic advantage is to be gained from deworming. However, treating communally grazed sheep every 12 weeks was found to keep worm egg numbers relatively low and may be advantageous in providing seasonal control, especially in semi-arid environments. Dosing communally grazed sheep once or twice a year under the same conditions is not recommended because reinfection appeared to result in similar faecal egg counts to those from the untreated animals (p>0.05).     

A survey of the prevalence of emerging macrocyclic lactone resistance and of benzimidazole resistance in sheep nematodes in the lower North Island of New Zealand

AIM: To investigate the occurrence of emerging macrocyclic lactone (ML) resistance and of resistance to benzimidazole anthelmintics on a number of sheep farms in the North Island of New Zealand.

METHODS: On commercial sheep farms (n=30) in the Taihape district in the North Island of New Zealand, 30 animals were randomly allocated to one of two equal-sized groups and treated with either half of the recommended dose rate of ivermectin (half of 0.2 mg/kg), or with the full recommended dose rate of oxfendazole (4.5 mg/kg). The ivermectin treatment only was used on a further six properties. Faecal egg counts, accompanied by pooled larval cultures, were conducted on all samples at the time of treatment and 7–10 days later.

RESULTS: Resistance, as indicated by a <95% faecal egg count reduction (FECR) in both instances, was found to oxfendazole on 13/30 (43%) farms and to a half dose of ivermectin on 12/36 (33%) properties. For oxfendazole, such resistance was found to involve all six nematode genera whereas for ivermectin it was almost entirely restricted to Ostertagia and Cooperia infections.

CONCLUSIONS: These results indicate that emerging ML resistance may be more common on sheep farms in New Zealand than is generally realised. They also suggest that the half-dose ivermectin faecal egg count reduction test (FECRT) may offer some very practical benefits for parasite control by providing early warning of developing resistance to ML drenches and by signalling the possible imminent failure of these at their therapeutic dose rates. The sensitivity and reliability of this procedure may be further enhanced by the inclusion of larval cultures.     

Resistance to moxidectin and abamectin in naturally acquired Ostertagia circumcincta infections in sheep

AIM: To investigate the occurrence of resistance to macrocylic lactone (ML) anthelmintics by Ostertagia circumcincta in lambs on a sheep and cattle property in the North Island of New Zea- land.

METHODS: Thirty lambs were randomly allocated to one of five equal-sized groups, consisting of an untreated control and four treatment groups. The treatments, which were administered at the manufacturer's recommended dose rates, included oral moxidectin, oral abamectin (both at 0.2 mg/kg), an albendazole-levamisole combination, and an albendazole-levamisole-ivermectin combination. Post mortem worm counts were undertaken 7 days after treatment to determine the efficacy of each anthelmintic.

RESULTS: The albendazole-levamisole and albendazole-levam-isole-ivermectin combinations both reduced O. circumcincta burdens to zero whereas for moxidectin and abamectin efficacies of only 72% and 29%, respectively, were recorded.

CONCLUSIONS: These results clearly demonstrated the occurrence of resistance to MLs by O. circumcincta. Although this is not the first occasion where resistance to this anthelmintic family has been detected in this parasite in sheep in New Zealand, it is the first instance that resistance to either moxidectin or abamectin has been reported.     

A comparison of plasma metabolite levels in goats and sheep during continuous low-level administration of fenbendazole

Plasma levels of fenbendazole (FBZ) and its sulphoxide (OFZ) and sulphone (FBZ.SO₂) metabolites were measured in goats and sheep during low-level administration of FBZ given by intraruminal infusion or formulated into a urea-molasses feed supplement block (UMB). In experiment 1, 6 goats and 6 sheep were offered UMB containing 0.5 g FBZ/kg (MUMB) and individual block consumption was measured daily for 18 days. In experiment 2, some of the same animals (n=4 for each species) received FBZ by intraruminal infusion at 1, 1.5 and 3 mg/kg liveweight per day for 7 days at each dosage. FBZ, OFZ and FBZ.SO levels were determined in plasma collected every 3 days in experiment 1 and on days 4, 5 and²6 of each infusion period in experiment 2. In both experiments, higher equilibrium levels were observed for the three metabolites in sheep than in goats. Significant linear relationships were observed between the daily FBZ dosages and the plasma levels of the three metabolites in both species. The regression coefficients were significantly higher in sheep than in goats for FBZ and OFZ but not for FBZ.SO₂, and they were also significantly higher during MUMB administration than during infusion for all three metabolites in both species. FBZ is a suitable anthelmintic for incorporation into a MUMB formulation for use in livestock production systems where responses to molasses urea supplementation have been demonstrated and gastrointestinal parasitism impairs productivity. The results indicate that target dose rates for goats should be 0.75 mg/kg per day compared with 0.5 mg/kg per day for sheep.Abbreviations ANOVA analysis of variance - FBZ fenbendazole - FBZ.SO₂ fenbendazole sulphone - HPLC high-performance liquid chromatography - MUMB urea-molasses feed supplement block containing 0.5 g fenbendazole/kg - OFZ fenbendazole sulphoxide - UMB urea-molasses feed supplment block     

捻转血矛线虫Hc38基因DNA疫苗对绵羊免疫保护性效果评价

为了研究基因疫苗对绵羊的免疫保护效果,本研究构建了捻转血矛线虫(H.contortus)Hc38基因DNA疫苗.将H.contortus Hc38基因保守结构域克隆到真核表达载体pcDNA3.1中,免疫鼠8d后用RT-PCR检测到该疫苗在鼠肌肉组织中进行了转录.将纯化的DNA疫苗免疫绵羊后,用western blot和ELISA方法检测疫苗在绵羊体内的翻译和诱导IgG的产生.二免后2周用10 000条H.contortus第3期幼虫攻击实验动物,检测绵羊粪便虫卵排出、成虫数量等免疫保护性指标.该H.contortus Hc38 DNA疫苗与对照组比较,免疫组绵羊排出虫卵减少66.6%、成虫减少33.1%.特别值得注意的是免疫组的静脉注射方式产生抗体最高,相应羊的虫卵数和成虫数低.本实验证明Hc38基因DNA疫苗对绵羊虫卵及成虫发育具有明显的抑制作用.     

黑龙江省松花江地区绵羊胃肠道线虫虫卵排出与成虫寄生的季节动态

采用粪便检查法、幼虫培养法和蠕虫学剖检法对黑龙江省松花江地区羊胃肠道线虫虫卵排出与成虫寄生的季节动态进行了研究。结果表明，成年羊胃肠道线虫的虫卵排出量和成虫寄生量于5月出现一次明显的春季高潮，8月又出现一次较小的高峰，而一年的其他时期，虫卵排出量和成虫寄生量很低。羊胃肠道线虫的优势虫种是捻转血矛线虫、哥伦比亚食道口线虫、羊仰口线虫、毛圆线虫和毛首线虫。羔羊粪便中最早检获虫卵的时间是6月下旬，一年内虫卵排出量只在7月下旬出现一次高峰。研究结果对控制黑龙江省羊消化道线虫病有十分重要的意义。     

Confirmation of resistance to ivermectin by Cooperia curticei in sheep

AIM: To investigate the occurrence of resistance to a full dose of oral ivermectin by Cooperia curticei in sheep.

METHODS: Twelve lambs on a sheep and cattle property in the North Island of New Zealand were randomly allocated to one of two equal-sized groups. One group was treated orally with a single dose of ivermectin at the manufacturer's recommended dose rate of 0.2 mg/kg, while the other remained as an untreated control. Worm counts were carried out post mortem on the abomasa and small intestines of all animals in both groups 7 days after treatment.

RESULTS: While treatment with ivermectin reduced the numbers of all other worm genera to almost zero, those of Ostertagia (= Telodorsagia) circumcincta and C. curticei were reduced by only 37% and 19%, respectively.

CONCLUSIONS: These results provide clear evidence of resistance to ivermectin by O. circumcincta and C. curticei. They also appear to represent the first record of macrocylic lactone (ML) resistance in C. curticei in sheep in New Zealand or elsewhere.     

Use of a formulation containing imidacloprid and moxidectin in the treatment of lice infestation in guinea pigs

Guinea pigs are susceptible to lice infestations. Ten guinea pigs infested with Gliricola porcelli were free of adult lice and eggs, and of adverse reactions, 30 days after treatment, with a single application of 0.05 mL of a solution containing 10% (w/v) imidacloprid and 1% (w/v) moxidectin indicating that this procedure is an effective treatment for lice infestations in guinea pigs.     

用丙硫苯咪唑检测羊线虫抗药性的体外虫卵孵化试验

为探讨用丙硫苯咪唑进行体外虫卵孵化试验检测羊线虫对苯并咪唑类药物的抗药性,对23个羊场的25份田间样品用丙硫苯咪唑和噻苯咪唑进行了虫卵孵化试验并与先前减卵试验（faecal egg count re-duction test,FECRT）的结果比较。结果表明,25份样品中,丙硫苯咪唑和噻苯咪唑对受检虫卵的半数致死量（LD50）均值分别为0.050 1和0.054 0μg/mL,差异不显著。FECRT检测有抗药性的4个羊场,75%的样品对丙硫苯咪唑和噻苯咪唑的LD50均值均在0.1μg/mL以上,只有1个羊场的的LD50值分别为0.068 9μg/mL（丙硫苯咪唑）和0.071 2μg/mL（噻苯咪唑）。检测为可疑的2个羊场,其样品的LD50值为0.04～0.07μg/mL;FECRT检测敏感的蠕虫群体的LD50均在0.04μg/mL以下。此外,丙硫苯咪唑用纯的二甲基亚砜溶解和稀释后于4℃保存7 d,LD50值变化不大,提示药效无明显下降,而保存14 d后药效有下降趋势。     

Anthelmintic Activity of Extracts of Spondias mombin Against Gastrointestinal Nematodes of Sheep: Studies In Vitro and In Vivo

This study was carried out to validate the efficacy of Spondias mombin, used locally as an anthelmintic, and to standardize the effective dose of the plant extract required for worm control in livestock. In vitro and in vivo studies were conducted to determine the direct anthelmintic effect of ethanolic and aqueous extracts of S. mombin towards different ovine gastrointestinal nematodes. A larval development assay (LDA) was used to investigate the in vitro effect of extracts on strongyle larvae. Another study was conducted in vivo to evaluate the therapeutic efficacy of the extracts administered orally at dose rates of 125, 250, 500 mg/kg to sheep naturally infected with gastrointestinal nematodes. Twenty sheep were selected on the basis of positive faecal egg counts (750 epg). The sheep were allocated randomly to a non-medicated control group (A) or to groups given 125 mg/kg (B), 250 mg/kg (C) or 500 mg/kg (D) of extract, respectively. Sheep in groups B-D were given extracts orally on two days. Individual faecal egg counts were performed on days 0, 3, 6, 9 and 12. The presence of S. mombin extracts in in vitro cultures of larvae decreased the survival of L3 larvae. The LC50 of the aqueous extract of S. mombin was 0.907 mg/ml, while the LC50 of the ethanolic extract was 0.456 mg/ml. This difference in LC50 was statistically significant (p > 0.05). The mean percentage faecal egg reduction of sheep drenched with 500 mg/kg S. mombin extracts was 15.0%, 27.5%, 65.0%, 65.0%, 100.0% against Haenmonchus spp., Trichostrongylus spp., Oesophagostomunm spp., Strongyloides spp. and Trichuris spp. respectively, on day 12. Extracts of S. mombin could find application in the control of helminths in livestock.     

Efficacy of a moxidectin/triclabendazole oral formulation against mixed infections of Fasciola hepatica and gastrointestinal nematodes in sheep

We have evaluated the efficacy in sheep of a combination drench formulation at the recommended dose rate of 0.2 mg moxidectin/kg bodyweight and 10 mg triclabendazole/kg bodyweight against an experimental infection with Fasciola hepatica and a natural infection with gastrointestinal nematodes. We confirmed that the efficacy of reducing fecal egg output was 98.3% for trichostrongyle eggs and 100% for F. hepatica eggs. Based on adult worm and fluke recovery, the efficacy varied according to the target species. A reduction was found in the number of Teladorsagia circumcincta, Trichostrongylus spp., Nematodirus spp., and Trichuris spp. greater than 95%, but the efficacy for Oesophagostomum spp. varied, with values below 90%. The reduction in F. hepatica was higher than 95% for all stages. The effectiveness of the formulation was also confirmed by an increase in total proteins and albumin following treatment.     

Minimising the development of anthelmintic resistance, and optimising the use of the novel anthelmintic monepantel, for the sustainable control of nematode parasites in Australian sheep grazing systems

Objective To compare the risk of different treatment scenarios on selecting for anthelmintic resistance on Australian sheep farms. Design A computer simulation model predicted populations of Trichostrongylus colubriformis, Haemonchus contortus or Teladorsagia (Ostertagia) circumcincta, and the frequency of anthelmintic resistance genes. Method Nematode populations and the progression of drug resistance for a variety of treatment options and management practices in sheep‐rearing areas of Western Australia (WA), Victoria (VIC) and New South Wales (NSW) were simulated. A scoring system was devised to measure the success of each option in delaying resistance to each anthelmintic and in controlling nematode populations. Results The best option at all sites was combining the new anthelmintic (monepantel) with a triple mixture of benzimidazole, levamisole and abamectin (COM). The next best option was: in NSW, rotation at each treatment between monepantel, moxidectin and COM; in VIC, rotation at each treatment between monepantel and COM; and in WA, rotation at each treatment between monepantel (used in winter) and COM or moxidectin (used in summer–autumn). In WA, rapid selection for resistance occurred as a consequence of summer–autumn treatments; however, if a small percentage of adult stock were left untreated then this selection could be greatly reduced. Despite purposely assuming relatively high resistance to benzimidazole and levamisole, COM was still effective in controlling worms and delaying resistance. Conclusions Because of cost constraints, it may not be feasible or profitable for producers to always use the combination of all drugs. However, the second‐ and third‐best options still considerably slowed the development of anthelmintic resistance.     

Evaluation of a regional nerve block with an experimental formulation of encapsulated lidocaine in sheep

ObjectiveTo compare the duration of nociceptive and proprioceptive blockade from an experimental encapsulated lidocaine preparation with that of conventional lidocaine.Study designProspective, blinded, randomly assigned, crossover study.AnimalsA total of six adult Dorset ewes, American Society of Anesthesiologists physical status I or II, weighing 60.4 ± 18.0 kg (mean ± standard deviation).MethodsUnder general anesthesia and guided by electrolocation, the common peroneal nerve was blocked unilaterally with encapsulated lidocaine (0.1 mL kg^–1, 200 mg mL^–1) or conventional lidocaine hydrochloride (0.1 mL kg^–1, 20 mg mL^–1). Each sheep was administered both treatments with an interval of 2 weeks between treatments. Nociception and proprioception were scored (scales of 0–3) before anesthesia, at 0.5, 1, 2, 4, 8, 12, 16, 20 and 24 hours after completion of local anesthetic injection, and every 12 hours thereafter for 9 days. Nociceptive and proprioceptive blockade ended the first time each score reached ‘0’; maximum blockade duration was considered and recorded to be the time point immediately prior to this end point. Significance of differences between treatments for duration of blockade was tested with the Wilcoxon rank-sum test. Effects of time and treatment on nociceptive and proprioceptive blockade were evaluated with mixed-effect models. Significance was set at p < 0.05.ResultsCompared with conventional lidocaine, nociceptive blockade lasted 88 hours longer with encapsulated lidocaine (p = 0.008), and proprioceptive blockade lasted 6 hours longer (p = 0.03). Significant effects of time (p < 0.0001), treatment (p = 0.0435) and treatment1time (p < 0.0001) were observed for nociception. Significant effects of time (p < 0.0001) and treatment1time (p = 0.0058) were observed for proprioception.ConclusionEncapsulated lidocaine produced nociceptive blockade with a duration substantially longer than conventional lidocaine.Clinical relevanceSustained-release encapsulated lidocaine alleviates pain and may minimize systemic analgesic use.