Reduced growth of Lucilia cuprina larvae fed serum from sheep treated with anthelmintics

The effect of three commonly used anthelmintics, levamisole hydrochloride, ivermectin and closantel, on the development of the sheep blowfly, Lucilia cuprina, was determined. Sheep were treated with each anthelmintic using the manufacturers' recommended dose for helminth control. Both ivermectin and closantel significantly (p < 0.05) reduced the growth rate of larvae of L cuprina cultured in vitro on serum from these sheep. Levamisole hydrochloride had no effect. Ivermectin was effective for less than 6 days after treatment, whereas closantel significantly reduced larval growth 21 days after treatment. Dose-response experiments showed that lower concentrations of both ivermectin and closantel were not as effective in reducing larval growth.     

Evidence for multiple anthelmintic resistance in sheep and goats reared under the same management in coastal Kenya

Four experiments, two with sheep and two with goats, were carried out to determine the efficacy of ivermectin, fenbendazole, levamisole, closantel and some of their combinations by faecal egg count reduction tests. In the first experiment, injectable ivermectin, oral ivermectin, fenbendazole and levamisole were tested in 6-month-old lambs, and their reduction percentages were 77%, 13%, 42% and 92%, respectively. In the second experiment, with yearling sheep, the reduction percentages were 35% for injectable ivermectin, 32% for fenbendazole, 99% for levamisole, 48% for closantel, 92% for injectable ivermectin combined with fenbendazole, 99% for injectable ivermectin combined with levamisole, and 100% for fenbendazole combined with levamisole. In the study with 18-month-old goats given the same dose rates as those recommended for sheep, the reduction percentages were 73% for injectable ivermectin, 25% for fenbendazole, and 78% for levamisole. Another group of 14-month-old goats was treated with dose rates 1.5 times those recommended for sheep and the reduction percentages were 93% for levamisole, 92% for injectable ivermectin, and 97% for a combination of levamisole and ivermectin. In all experiments with sheep and goats the gastrointestinal nematode parasites identified by larval cultures were Haemonchus contortus, Trichostrongylus spp. and Oesophagostomum spp. The gastrointestinal nematodes of both sheep and goats on this farm are resistant to ivermectin and fenbendazole, whereas levamisole is still effective in sheep, but not in goats. The results are discussed in relation to the farm as a source of breeding stock to smallholder farmers and its potential to spread anthelmintic resistance.     

Comparison of the time required to administer three different fluke and worm combination products to commercial beef cattle at housing

Larger livestock units, a decline in the farm labor force, animal welfare concerns, and a trend toward more selective use of drugs have increased the focus on animal handling, time management, convenience, and compliance in administering veterinary therapeutics. This study was undertaken to quantify and compare the time needed to treat commercial beef cattle with three fluke and worm combination products with different administration profiles. Young beef cattle (n = 270) weighing approximately 400 kg were allocated to batches of five, which were randomly assigned to receive ivermectin + clorsulon injection, ivermectin + closantel injection, or levamisole + triclabendazole oral drench. The mean time needed to administer ivermectin + clorsulon (single injection) to five cattle was 31 seconds, which was significantly less than the 100 seconds needed for ivermectin + closantel (two injections) and the 126 seconds needed for levamisole + triclabendazole (P less than .001). Such quantitative data can allow for better planning and selection of parasiticide treatment approaches at the farm level.     

Comparative pharmacokinetic disposition of closantel in sheep and goats

The pharmacokinetic disposition of closantel was examined following intraruminal (i.r.) or intramuscular (i.m.) administration to adult Merino sheep and to adult and 3-month-old, suckling Angora goats. In adult goats the maximum concentration (C_max) and area under the plasma concentration with time curve ( AUC ) following 3.75, 7.5 and 15.0 mg closantel/kg given i.r. increased with dose however the time of C_max (r_max= 2.6d) in plasma was unaffected by dose rate. The elimination phase (K₁₀) of closantel was monoexponential with a half-life ( t _½) of 4.7d again unaffected by dose rate. Apart from a more rapid absorption phase and earlier T_max following 3.75 mg closantel/kg i.m., pharmacokinetic behaviour was similar to that following i.r. administration at 3.75 or 7.5 mg/kg. Although absorption rate was more rapid in kids after i.r. administration at 7.5 mg/kg, pharmacokinetic disposition of closantel was otherwise similar to that in adult goats. No closantel was detected in milk of treated does or in the plasma of their kids. I.R. closantel at 7.5 mg/kg was more slowly absorbed in goats than in sheep but C_max was similar in both species. However, K₁₀ t _½ was significantly shorter in goats (4d) than in sheep (14d). Faster elimination resulted in an almost three-fold lowering of AUC in goats and could dramatically reduce the sustained action of closantel in this species compared with sheep.     

The survival and fecundity of buffalo flies after treatment of cattle with three anthelmintics

Two anthelmintics with known insecticidal action (ivermectin and closantel) and one with no recorded effect on insects (levamisole) were tested to evaluate their effects on buffalo fly (Haematobia irritans exigua). Blood from animals given closantel or levamisole had no significant effect on mortality of buffalo flies in an in-vitro assay. In contrast, blood from animals given ivermectin showed a dose-dependent effect on the mortality of buffalo flies. At 24 h after one injection of the recommended dose of ivermectin, 98% of the flies applied to cattle in an in-vivo assay are killed. Blood from cattle injected with ivermectin killed 95% of flies 8 d after injection and still killed 15% of flies at 18 days after injection. Surviving flies laid almost no eggs and this effect on flies was significant up to 33 d after injection. The results indicate that ivermectin may be useful to control buffalo fly populations in the field.     

Anthelmintic resistance in sheep and goat farms on Peninsular Malaysia.

The faecal egg count reduction test (FECRT) was conducted on 39 sheep farms and 9 goat farms located in Peninsular Malaysia. The anthelmintic groups used in these tests were the benzimidazoles, levamisole, the benzimidazole/levamisole combination, macrocyclic lactones and closantel. Results indicated that the prevalence of resistance to the benzimidazole group was high, with approximately 50% of the sheep farms and 75% of the goat farms having resistant nematode parasite populations present. Resistance to levamisole, closantel and ivermectin was also detected. Differentiation of the infective larvae derived from faecal cultures indicated that by far the most predominant parasite species was Haemonchus contortus.     

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.     

Ivermectin缓控释制剂的研究进展

近年来 ,ivermectin(伊维菌素 ,IVM)缓、控释制剂广泛应用于动物寄生虫及多种疫病的防治 ,本文就其作用、制剂、优点、药物代谢动力学和可能带来的问题等方面进行了综述     

Ketoconazole increases the plasma levels of ivermectin in sheep

The parasiticide ivermectin and the antifungal drug ketoconazole are drugs that interact with P-glycoprotein. We have tested the ability of ketoconazole at a clinical dose to modify the pharmacokinetics of ivermectin in sheep. Lacaune lambs were administered with a single oral dose of ivermectin alone at 0.2mg/kg (n=5) or in combination with a daily oral dose of ketoconazole (10mg/kg) given for 3 days before and 2 days after the ivermectin (n=5). The plasma kinetics of ivermectin and its metabolite were followed over 15 days by HPLC analysis. Co-administration of ketoconazole induced higher plasma concentrations of ivermectin, leading to a substantial increase in the overall exposure of the animals to the drug. Ketoconazole did not reduce the production of the main ivermectin metabolite but it may rather act by inhibiting P-glycoprotein, and thus increasing the absorption of ivermectin. The use of a P-gp reversing agent such as ketoconazole could be useful tool to optimize antiparasitic therapy in the face of the worldwide development of anthelmintic resistance.     

Pharmacokinetics of a new ivermectin/praziquantel oil suspension after intramuscular administration in pigs

A new oil suspension containing 0.15% ivermectin and 15% praziquantel for intramuscular injection was developed, and corresponding pharmacokinetics studies were conducted in swine. The combination product is a white- to cream-colored oil suspension and its physical properties such as settling volume ratio, redispersibility, syringeability and flowability are well consistent with the Technical Standards by the Ministry of Agriculture of the People's Republic of China. The pharmacokinetic study consists of two parts. First, the experiments were carried out to compare the pharmacokinetic parameters of the combination product and those same products with praziquantel or ivermectin removed merely. The results showed that no significant change in the major pharmacokinetic parameters (t(1/2z), T(max), C(max), AUC(INF), TimeDur) was observed when either of the component was removed from the combination product, indicating that ivermectin and praziquantel do not interfere with each other when being used together. Second, the pharmacokinetics of the combination product were compared with those of their respective single product. The results showed that the C(max) (15.94 ng/mL) of ivermectin in combination product was 9.01 times higher than the single product, while the AUC(INF) (1925.61 ng h/mL) was 6.02 times higher. Meanwhile, the C(max) (1.48 μg/mL), AUC(INF) (17.08μgh/mL), t(1/2z) (20.25 h), TimeDur3 (42.01 h) and TimeDur4 (16.60 h) of praziquantel in combination product were improved with a factor of 5.48, 13.66, 8.58, 10.10 and 7.31 times when compared with the single product, respectively. Therefore, the efficacy of the combination product was significantly prolonged, especially for praziquantel, so that comprehensive efficacy of controlling parasites sensitive to ivermectin and praziquantel can be achieved with one-single use of it.     

Biovailability of ivermectin administered orally to dogs

The bioavailability of three formulations of ivermectin was determined following oral administration to dogs. The average peak plasma level (C _max) of ivermectin administered in the standard tablet formulation at 6 and 100 µg/kg of body weight was 2.97 and 44.31 ng/g, respectively. This suggest dose-dependent pharmacokinetics.C _max and total ivermectin bioavailability, as assessed from the area under the plasma curve (AUC), were similar between two tablet formulations of ivermectin administered at 100 µg/kg. Furthermore,C _max was similar following administration of radiolabelled ivermectin at 6 µg/kg in either a beef-based chewable formulation or in the standard tablet formulation.     

Efficacy of monepantel and anthelmintic combinations against multiple-resistant Haemonchus contortus in sheep, including characterisation of the nematode isolate

Three experiments defined the resistance profile of a population of Haemonchus contortus, which was shown to express multiple resistances to the benzimidazole, levamisole, macrocyclic lactone and salicylanilide anthelmintic classes when given as a registered combination. Study 1 was a faecal egg count reduction (FECR) test and the efficacies for the anthelmintics were monepantel, 100%; abamectin+levamisole+oxfendazole, 40.0%; and abamectin+levamisole+oxfendazole+naphthalophos, 100%. No larvae were recovered from the post-treatment cultures for monepantel or the 4-way treatment, and for the 3-way treatment the culture was 100% Haemonchus spp. Efficacies in Study 2 were calculated from mean post-mortem nematode burdens of H. contortus and were levamisole+oxfendazole, 3.1%; abamectin+levamisole+oxfendazole, 5.0%; ivermectin, 0.4%; moxidectin, 28.4% and closantel, 70.2%. Study 3 was also a FECR test that resulted in efficacies of 100% for monepantel and 83.0% for a formulated 4-way combination of abamectin+levamisole+albendazole+closantel. Larvae recovered from the post-treatment culture for the combination-treated sheep were all Haemonchus spp. Multi-resistant parasites such as examined in these studies are a continuing challenge to be managed by farmers and their advisors. Control programs must be planned and well-managed, and should include on-farm testing for anthelmintic resistance, monitoring of nematode burdens (by FEC and larval culture) to determine appropriate treatment times and the management of pastures to reduce the overall parasite challenge. This should be in balance with the generation, use and maintenance of drug-susceptible nematode populations in refugia.     

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.     

Efficacy of ivermectin in oral drench and paste formulation against migrating larvae of experimentally inoculated Parascaris equorum

Twenty-one mixed-breed pony foals, reared and maintained under parasite-free conditions, were used to test the efficacy of ivermectin in oral drench and paste formulations (200 micrograms/kg) against 11-day-old migrating larvae of Parascaris equorum. Three replicates of 4 foals and 3 replicates of 3 foals were formed on the basis of age. Foals in replicates of 4 were randomly allocated to be indicators, or to receive vehicle (control) or ivermectin paste or ivermectin liquid. Foals in replicates of 3 were randomly allocated to receive vehicle or ivermectin paste or ivermectin liquid. The recovery of larvae from the lungs, liver, and small intestines of the indicator foals showed that 99.9% of the larvae were in the lungs 11 days after inoculation (day 0 of treatment). The recoveries of larvae from lungs and small intestines of controls at 25 days after inoculation indicated that all larvae had migrated to the small intestine by this time. The mean length of larvae recovered from the lungs (11 days after inoculation) was 0.87 mm the mean length of those recovered from the small intestine (25 days after inoculation) was 3.65 mm. Using larvae recovered from small intestinal contents for calculations, ivermectin in both formulations was 100% effective against 11-day P equorum (P less than 0.01, compared with control group geometric mean of 1498.4).     

Efficacy of ivermectin chewable tablets and two new ivermectin tablet formulations against Dirofilaria immitis larvae in dogs.

One hundred four heartworm-free Beagles less than 1 year old were studied to determine the efficacy of ivermectin chewable tablets and of 2 other ivermectin tablet formulations against heartworm larvae. At 30 days after SC inoculation of dogs with infective Dirofilaria immitis larvae, all ivermectin formulations were given orally at dosage of 6 micrograms/kg of body weight. The ivermectin chewable tablets also were given orally at dosage of 2 and 6 micrograms/kg at 30 and 45 days, respectively, after injection of larvae. Replicates of 6 or 8 dogs in each study were formed on the basis of gender and body weight and, within replicates, were randomly allocated to treatment groups. At 30 days after injection of larvae, the additional dogs (in replicates of 8) were assigned to the control group and to the group given ivermectin chewable tablets at dosage of 6 micrograms/kg. All dogs were housed individually. Necropsy was performed approximately 5 or 6 months after larvae were administered. In both trials, all control dogs had heartworms at necropsy (University of Illinois--geometric mean, 35.0; Florida--geometric mean, 26.1). In both trials, the ivermectin chewable tablet (6 micrograms/kg) and both tablet formulations (6 micrograms/kg) given at 30 days after larval injection, and the chewable formulation (6 micrograms/kg) given at 45 days after larval injection were 100% effective (P less than 0.01) in preventing development of induced infection with D immitis.(ABSTRACT TRUNCATED AT 250 WORDS)     

The comparative serum disposition kinetics of subcutaneous administration of doramectin, ivermectin and moxidectin in the Australian Merino sheep

This study evaluates the comparative serum disposition kinetics of injectable formulations of doramectin (DRM), ivermectin (IVM) and moxidectin (MXD) in Australian Merino sheep. Thirty-six, 2-year-old sheep were allocated by weight into six groups of six animals. Animals in each group received 200 microg/kg of DRM, MXD, IVM or a combination of two of these drugs by subcutaneous (s.c.) injection. Blood was collected at designated intervals (between 1 h and 40 days after treatment) and the serum analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The results indicated that MXD administration produced a significantly higher maximum serum concentration and a more rapid absorption as compared with DRM and IVM. MXD and DRM had a significantly larger area under the concentration vs. time curve (AUC) than IVM, suggesting a more persistent effect for the former two products in sheep. The AUC for DRM was significantly higher when administered alone as compared with that observed when given in combination with MXD or IVM, suggesting preferential elimination of DRM compared with IVM and MXD from concurrent s.c. administration.     

Multiple Anthelmintic Resistance in Haemonchus Contortus on a Sheep Farm in Kenya

Multiple resistance to albendazole, thiophanate, levamisole and orally administered ivermectin was detected in an isolate of Haemonchus contortus in sheep on a farm where benzimidazole resistance had already been identified. Following a faecal egg count reduction test, this was confirmed by both critical and controlled anthelmintic tests. Different groups of sheep infected naturally or given an experimental infection with the benzimidazole-resistant isolate were treated with the recommended doses of various anthelmintics. Compared to the control group, the percentage reductions in the faecal egg counts of sheep treated with albendazole, thiophanate, levamisole and ivermectin varied between 38.2% and 79.1% and the residual worm counts between 27.3% and 57.5%. The results indicate the presence of multiple anthelmintic resistance in this isolate of H. contortus. Sheep treated with closantel showed 100% reductions in faecal egg and worm counts, indicating that this drug was very effective against the population of H. contortus on the farm.     

Does closantel in therapeutic doses display thyroid hormone‐like activity in sheep?

The aim of this study was to define the thyroid hormone‐like activity of closantel in sheep by measuring some blood parameters that are known to be influenced by thyroid hormones triiodothyronine (T3) and thyroxine (T4). Our hypothesis was that, if closantel possesses thyroid hormone‐like activity, its use under in vivo conditions will result in changes similar to those in hyperthyroidism. The study was conducted in 20 Jezersko‐Solchava breed sheep. Blood sampling was performed before and 10 days after routine anthelmintic treatment with closantel. Complete blood count, plasma cholesterol, triglycerides, protein, and albumin levels, as well as those of serum T3 and T4, were compared before and 10 days after closantel administration. This routine anthelmintic treatment of sheep with closantel did not significantly influence hematological parameters, thyroid hormone levels, or most of the biochemical parameters. No evidence was found for thyroid hormone‐like activity of closantel in sheep. However, significantly (P < 0.01) elevated levels of plasma triglycerides were present 10 days after closantel administration.     

Effectiveness of strategic anthelmintic dosing in controlling Haemonchus contortus infections in sheep in the United Kingdom

The strategic use of anthelmintics in the control of infections of Haemonchus contortus in ewes and lambs, was investigated in a series of paddock trials. The levels of infection and clinical signs associated with the presence of either benzimidazole-resistant or benzimidazole-susceptible strains of H contortus in lambs were controlled by regular drenching with levamisole or mebendazole, respectively, or by the strategic use of closantel in combination with mebendazole. In the latter case, control was achieved by dosing either the ewes in the early part of the grazing season, or the lambs from June onwards. It was concluded that worm control strategies based on closantel could provide effective control of both benzimidazole-susceptible and benzimidazole-resistant strains of H contortus on farms in the United Kingdom.     

Evaluation of the comparative efficacy of a moxidectin plus triclabendazole pour-on solution against adult and immature liver fluke, Fasciola hepatica, in cattle

The objective of this study was to evaluate the efficacy of a pour-on solution containing moxidectin plus triclabendazole (MOX plus TCBZ) against immature and adult stages of the liver fluke in cattle and compare the efficacy with other commercially available preparations. To this end, 104 male Holstein-Friesian calves aged between 3 and 4 months, were randomly allocated to 13 groups of eight animals each, and infected with approximately 500 Fasciola hepatica metacercariae. One group remained untreated, four groups were treated with MOX plus TCBZ at a dose rate of 0.1mL/kg, four other groups were treated with ivermectin (IVM) plus clorsulon injectable at a dose rate of 0.02mL/kg, and the remaining four groups were treated with IVM plus closantel pour-on at a dose rate of 0.1mL/kg. Each treatment was applied to one of the groups at 4 weeks, 6 weeks, 8 weeks and 12 weeks after the experimental infection. At necropsy (99-102 days after infection), all untreated animals were infected with a minimum of 30 flukes. The MOX plus TCBZ treated animals had significantly (P<0.0001) lower fluke counts compared to the untreated control animals at all time points after treatment. Efficacy against 8-week old and adult flukes was >99.5%. For 6-week old immature fluke, the efficacy was 98.0% and for 4-week old immature fluke the efficacy was 90.9%. The IVM plus closantel pour-on treated animals had significantly lower fluke counts compared to the untreated control animals for adult and 8-week old flukes (P<0.0001), and for 6-week old flukes (P=0.002). The efficacy was 26.8%, 68.2%, 90.6% and 99.3% against 4-week, 6-week and 8-week old immature flukes, and adult flukes respectively. The IVM plus clorsulon treated animals had significantly lower fluke counts compared to the untreated control animals for adult (P<0.0001) and 8-week old (P<0.05) flukes. The efficacy was 29.7%, 43.4%, 53.2% and 99.2% against 4-week, 6-week and 8-week old immature flukes, and adult flukes respectively. For treatments at 4, 6 and 8 weeks after infection, the fluke counts were significantly (P<0.0001) lower for the MOX plus TCBZ treatment than for IVM plus closantel or IVM plus clorsulon. The results confirm the high efficacy (>90%) of the MOX plus TCBZ pour-on combination against 4-week old to adult liver fluke in cattle. The IVM plus closantel pour-on combination was effective (>90%) against 8-week old and adult flukes, but had low efficacy against 4- and 6-week old fluke. The IVM plus clorsulon injectable combination was effective (>90%) against adult fluke only.