Failure of ivermectin and eprinomectin to control Amblyomma parvum in goats: characterization of acaricidal activity and drug pharmacokinetic disposition

The therapeutic efficacies of ivermectin (subcutaneous injection) and eprinomectin (topical treatment) given at two different dosage levels to goats naturally infested with Amblyomma parvum were assessed. Treatments included subcutaneous injection of ivermectin at 0.2 and 0.4mg/kg and extra-label pour-on administration of eprinomectin at 0.5 and 1mg/kgb.w. Ivermectin and eprinomectin failed to control Amblyomma parvum on goats. Treatment with ivermectin resulted in a low number of engorged female ticks in relation to untreated control goats and, at the highest dose rate (0.4mg/kg), the female engorgement weights were significantly lower and the pre-oviposition period significantly longer than those observed in ticks recovered from untreated control goats. The tick efficacy assessment was complemented in a separate group of tick-free goats with a pharmacokinetic characterization of eprinomectin (topically administered at 0.5, 1.0 and 1.5mg/kg) and ivermectin (subcutaneous treatment given at (0.2 and 0.4mg/kg) in goats. Heparinized blood samples were taken between 0 and 21 days post-treatment. Higher and more persistent drug plasma concentrations were recovered after the subcutaneous treatment with ivermectin compared to those obtained for eprinomectin topically administered. The understanding of the relationship among the pattern of drug absorption, the kinetic disposition and the resultant clinical efficacy is relevant to improve the poor performance observed for ivermectin and eprinomectin against A. parvum on goats.     

Duration of activity of topical eprinomectin against experimental infections with Teladorsagia circumcincta and Trichostrongylus colubriformis in goats

The immediate as well as the persistent anthelmintic efficacies of topically applied eprinomectin were evaluated in goats against induced infections with Teladorsagia circumcincta (2800 L3) and Trichostrongylus colubriformis (6000 L3). Twenty-three culled dairy goats were allocated to the following groups: control animals (group 1), animals treated 21 days prior to nematode infection (group 2), animals treated 7 days prior to nematode infection (group 3) and animals treated 21 days after nematode infection (group 4). Eprinomectin was applied at twice the cattle dose rate (1.0 mg/kg BW). According to the groups, necropsies were undertaken 28 days after nematode infection (groups 1-3) or 14 days after the anthelmintic treatment (group 4). Worm counts were determined for abomasum and small intestine. The curative anthelmintic efficacy of eprinomectin at 1.0 mg/kg BW on existing worm burdens was 100% against T. circumcincta and T. colubriformis. Quite similar worm burdens reductions were observed when eprinomectin was administered 7 days before infection whereas they were only 52.4 and 17.8% for T. circumcincta and T. colubriformis, respectively, for an administration of the drug 21 days prior to the nematode infection.     

Some Pharmacokinetic Parameters of Eprinomectin in Goats following Pour-on Administration

Some pharmacokinetic parameters of eprinomectin were determined in goats following topical application at a dose rate of 0.5 mg/kg. The plasma concentration versus time data for the drug were analysed using a one-compartment model. The maximum plasma concentration of 5.60±1.01 ng/ml occurred 2.55 days after administration. The area under the concentration–time curve (AUC) was 72.31±11.15 ng day/ml and the mean residence time (MRT) was 9.42±0.43 days. Thus, the systemic availability of eprinomectin to goats was significantly lower than that for cows. The low concentration of eprinomectin in the plasma of goats suggests that the pour-on dose of 0.5 mg/kg would be less effective in this species than in cows. Further relevant information about the optimal dosage and residues in the milk of dairy goats is needed before eprinomectin should be used in this species.     

Field trials in New Zealand confirming the efficacy of eprinomectin applied topically to cattle

The efficacy and acceptability of eprinomectin in a topical formulation against gastro-intestinal nematodes in cattle was assessed under field conditions. Seven similar commercial dairy farms in the North and South Islands of New Zealand were included in the studies, involving 247 Holstein-Friesian, Jersey or Jersey-cross cattle. Cattle were confirmed by positive faecal nematode egg counts to have natural infections of gastro-intestinal nematodes and were held in separate treatment groups. In each replicate, four animals received eprinomectin (500 microg/kg body weight) and one animal received vehicle solution, all applied topically at 1 ml/10 kg body weight. Faecal samples were collected before, and 14 days after treatment, for faecal trongylid egg counts. Animals treated with eprinomectin had significantly lower (p < 0.05) Day 14 faecal strongylid egg counts than the controls. There were no significant differences (p > 0.10) between treated and control groups for pretreatment strongylid egg counts. No formulation runoff or adverse reactions were observed. These studies showed eprinomectin to be effective against gastro-intestinal nematode infections and safe for use in dairy cattle under natural field conditions.     

Predicting milk-production responses after an autumn treatment of pastured dairy herds with eprinomectin

The objectives of this study were (1) to determine the effect of a treatment with eprinomectin in autumn of pastured dairy herds on the anti-Ostertagia ostertagi bulk-tank milk antibody level, (2) to determine the overall effect of this treatment on three milk-production parameters (milk yield, protein % and fat %) and (3) to investigate the value of the pre-treatment Ostertagia-specific bulk-tank milk antibody level to predict the production response after anthelmintic treatment. One hundred and nineteen herds in Flanders (Belgium) were randomly assigned to a treatment with eprinomectin or a placebo in October 2004. Bulk-tank milk samples were collected monthly from August 2004 until April 2005, and the antibody levels against O. ostertagi were determined as optical density ratios (ODRs) with an ELISA. The treatment effect over the 4 months following treatment on three production parameters (milk yield, milk-protein %, milk-fat %) was estimated by mixed models with herd as a random effect. The treatment effect on milk yield was also investigated within six categories of the pre-treatment ODR. The ODR values were lower in the eprinomectin group than in the control group at each time point after treatment. The overall effect on milk yield was estimated at 1.2 kg/cow/day, whereas no effect on the milk-protein % and milk-fat % was observed. Herds in the highest pre-treatment ODR category (>0.84) had a positive milk-yield response of 4.0 kg/cow/day (95%-confidence interval: 1.0; 7.0), while the 95%-confidence intervals of the milk-yield responses in the other categories all included zero. This study demonstrates that treatment with eprinomectin of pastured dairy cows in autumn will lower the Ostertagia-specific bulk-tank milk antibody level during the stabling period and can result in a consistent increase in milk yield. The results indicate that an O. ostertagi bulk-tank milk ELISA can be used to identify the herds where the greatest milk-yield response after an anthelmintic treatment is expected.     

Effect of eprinomectin treatment on milk yield and quality in dairy cows in South Tyrol, Italy

The effect of treatment with eprinomectin on milk yield, milk composition and somatic cell counts (SCCs) was studied in 105 dairy cows located on seven farms in South Tyrol, Italy. On each farm, half of the animals were treated with eprinomectin and the other half were used as an untreated control group. Three test day records per animal were obtained before treatment (days -117, -75 and -33) and another three test day records were obtained after treatment (days 22, 62 and 131). Test day records comprised milk yield, milk composition, SCC and days in milk. On the day of treatment, blood samples and faecal samples were taken for parasitological analysis. Cows with positive faecal egg counts yielded less milk. A significant effect of eprinomectin on milk yield was observed after treatment and was most pronounced on the second and the third test days after treatment (+1.90 kg [P=0.002] and +2.63 kg [P<0.001], respectively). Furthermore, a significant decrease in SCC was observed on the second test day after treatment.     

Eprinomectin pour-on for control of Boophilus microplus (Canestrini) ticks (Acari: Ixodidae) on cattle

The efficacy of a commercial pour-on formulation of eprinomectin, a macrocyclic lactone, against experimental infestations of Boophilus microplus (Canestrini) ticks was evaluated in two trials involving 27 Bos taurus calves. The first trial was designed to evaluate the effects of a single treatment at a dose of 0.5 mg/kg of body weight against standard size B. microplus females (4.5-8.0 mm long). A significant reduction in tick numbers (P<0.05, Wilcoxon test) was observed between treated calves as compared to untreated ones from Day 3 (44% efficacy) after treatment to the end of the trial on Day 28 (96.9%), with a peak efficacy of 97.1% on Day 21. In the second trial the effect of eprinomectin on standard size tick numbers, engorgement weight and fertility of female ticks from calves with a single treatment dose of 1 mg/kg on Day 0 and calves treated twice at a dose of 0.5 mg/kg on Days 0 and 4 was evaluated. An efficacy >93% was obtained from Day 2 to Day 28 after treatment in calves treated twice at 0.5 mg/kg, and to the end of the trial (Day 35) in calves treated once with 1 mg/kg. The 1mg/kg treatment provided >98% residual efficacy for at least 7 days. During the first part of the second trial the efficacy of eprinomectin resulted from a dramatic adverse effect on engorgement weight and fertility of female ticks, with 100% control on Day 5 (dosage of 1 mg/kg) and on Days 6 and 7 (two doses of 0.5 mg/kg). Following Day 7, most of the effect was due to reduction in the number of standard size female ticks.     

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.     

超排处理奶山羊获得可注射受精卵

通过对奶山羊在春秋两季分别进行同期发主超排处理发现，季节对奶山羊的超排效果影响不大，在注射ＬＨ后５０－５４ｈ是奶山羊原核注射的最佳时期。     

Field efficacy of minidosed eprinomectin against Hypoderma spp. in dairy cattle

A chemoprophylactic field trial was conducted to assess the efficacy of pour-on eprinomectin applied at the approximate dose of 50 mcg/kg to dairy cattle with naturally occurring hypodermosis. Two-hundred-eleven cattle, selected from two herds with a high prevalence of Hypoderma spp. infestation, were divided in three groups: Group A (N = 71) was treated with pour-on eprinomectin at the recommended dosage of 500 mcg/kg, Group B (N = 64) at the lower dose of 50 mcg/kg, a third group (Group C, N = 76) served as untreated control group. Treatments were performed in November-December 2002 and the animals were examined for the presence of warbles in the following April and June. No larvae emerged in the treated groups, whereas a variable number of warbles (ranging from 1 to 28) were found in control animals. Adverse reactions were not observed in any animal, and only minor side effects were observed. A larger field trial carried out in the following year (1064 treated and 131 untreated control cattle) confirmed the chemoprophylactic efficacy of minidosed eprinomectin against Hypoderma spp. Administration of eprinomectin minidoses in dairy cattle is interesting because of the low costs involved and no need for milk withdrawal.     

Eprinomectin treatment of psoroptic mange in hunter/jumper and dressage horses: a prospective, randomized, double-blinded, placebo-controlled clinical trial

The purpose of this prospective, double-blinded, placebo-controlled clinical trial was to investigate the efficacy of topical eprinomectin for the treatment of psoroptic mange infestation in horses. 24 privately owned hunter/jumper and dressage horses were diagnosed with psoroptic mange infestation based on physical findings and skin scraping results were enrolled and randomly assigned to either topical eprinomectin pour-on solution (at a dose of 500mug/kg body weight weekly once for four applications) treatment group or a placebo group (purified water). Clinical evaluations and skin scrapings were done by the same veterinary investigator at the beginning, during and at the end of the treatment. Both owners and veterinary investigator were blinded to the allocation to the groups. The efficacy of eprinomectin was assessed both clinically and parasitologically by the presence or absence of viable mites. Horses were scraped for psoroptic mites on days 7, 14, 21, 28 and 40 for follow-up. Fisher's exact test was used to assess differences between the eprinomectin treatment and placebo in the number of horses without mites (cure rates) on each assessment date. It was found that significantly fewer eprinomectin treated horses had P. equi mites detected on skin scrapings (p<0.01) than the placebo group. In conclusion, eprinomectin was effective and safe therapy against natural infestations of P. equi in the horses included in this study.     

Efficacy of eprinomectin pour-on against gastrointestinal nematode infections in sheep

Two field trials were conducted in two farms (farms A and B) in southern Italy, to assess the efficacy of eprinomectin applied topically at the dose rate of 500 micro g/kg to sheep with naturally occurring infections of gastrointestinal nematodes (GIN). The nematode population determined by necropsy consisted of Teladorsagia circumcincta, Haemonchus contortus, Trichostrongylus vitrinus, T. capricola, Nematodirus sp., and Chabertia ovina in sheep from farm A, and of T. circumcincta, T. vitrinus, T. capricola, T. colubriformis, and C. ovina in sheep from farm B. In each farm, 42 female sheep were assigned to a eprinomectin treated group (E-group) and a control untreated group (C-group) of 21 animals each. On farm A, the percentage reductions in strongyle faecal egg counts from E-group compared to C-group were 99.1% on day 10; 97.4% on day 30; and 67.0% on day 60. On farm B, on the same days, they were 95.4, 84.9, and 69.4%, respectively. In the course of the two trials, eprinomectin was well tolerated by all the animals with no adverse reactions following the topical treatment.     

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 ivermec- tin. 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 eprinomec- tin, 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.     

Genetic and environmental factors associated with nematode infection of dairy goats in northwestern France

The helminth parasitism (strongyles and Muellerius) of dairy goats was investigated in commercial farms of northwestern France. The study was undertaken in spring (n = 263 goats) and autumn (n = 165); the breed, age, polledness, absence or presence of wattles, and reproductive status were recorded for each goat. The faecal output of strongyle eggs was significantly related to breed, polledness, presence of wattles and age. The faecal output of first stage larvae of Muellerius was correlated with breed, age and pregnancy.     

Efficacy of eprinomectin pour-on against Dictyocaulus arnfieldi infection in donkeys (Equus asinus)

A trial to assess the efficacy of eprinomectin (EPM) against the lungworm Dictyocaulus arnfieldi was carried out on 15, naturally-infected donkeys. Ten animals were treated with a ‘pour-on’ EPM preparation (at a dose of 0.5 mg/kg bodyweight), and five animals acted as controls. Faecal larval counts were carried out two days before treatment, on day of treatment and 7, 14, 21 and 28 days post-treatment with the anthelmintic. EPM was 100% effective in eliminating faecal larvae from day 7, until the end of study at day 28. No adverse drug-reactions or side-effects were observed in any of the treated donkeys.     

Efficacy of eprinomectin pour-on against gastrointestinal nematodes and the nasal bot fly (Oestrus ovis) in sheep

The efficacy of the pour-on formulation of eprinomectin, at a dose rate of 0.5 mg/kg bodyweight, was assessed in sheep against three main species of gastrointestinal nematodes and against the nasal bot fly, Oestrus ovis, and some pharmacokinetic parameters were determined for 21 days after the treatment. By comparison with untreated control sheep, infected experimentally with Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis, eprinomectin was 100 per cent effective against the two abomasal species and 99.5 per cent effective against T. colubriformis. In ewes naturally infected with the nasal bot fly, the efficacy of the drug against O. ovis was 97.7 per cent. The mean (se) systemic area under the curve (AUC) was 56.0 (26.2) ng/day/ml and the mean residence time was 5.3 (1.0) days, but there were wide variations between individual sheep.     

The effect of season on reproduction in dairy cattle

A survey was carried out in North West Tasmania to compare the breeding performance of 2,068 cows in 27 dairy herds--15 herds calving in spring and 12 in autumn. The percentage of cows submitted to artificial insemination for the first time in the first 24 days of the mating period was 87% for the spring calving group and 75% for the autumn calving group. Figures for non-return-to-service rate over the subsequent 21 days were 72% and 55%, respectively. The difference in breeding performance associated with time of calving was not attributable to age, calving to mating interval or on cow condition or daily milk fat yield at 3 weeks (+/- 1 week) after the start of mating.     

Comparative study of the efficacy of eprinomectin versus ivermectin, and field efficacy of eprinomectin only, for the treatment of chorioptic mange in alpacas

The efficacy of eprinomectin versus ivermectin (Study 1: a single-centre, randomised, treatment-controlled, blinded field trial), and the field efficacy of eprinomectin (Study 2: a single-centre, open, un-controlled field trial) for the treatment of chorioptic infestation in naturally infested alpacas were assessed in two studies. Thirty alpacas, all positive for Chorioptes sp. mite, were randomly allocated to two treatment groups in Study 1. Group A received a single topical administration of a 0.5% formulation of eprinomectin at the dose rate of 500 μg/kg. Group B received three subcutaneous administrations at 14 days interval of a 1% formulation of ivermectin at the dose rate of 400 μg/kg. Response to treatment was assessed by periodic mite count, and skin lesions scored. In Study 2, one group of 19 alpacas received four administrations at weekly interval of topical eprinomectin at the dose rate of 500 μg/kg, and response to treatment was monitored by mite counts. No localised or systemic side effects were observed in either trial. There was a statistically significant decrease in mite counts on day 7 (P < 0.001) within treatment Groups A and B of Study 1, but mite counts increased again on day 14 and remained high for the duration of the trial in both treatment groups. On day 14 of Study 2, there was a statistically significant reduction in mite counts (P < 0.008) and the mite counts remained very low throughout the remainder of the study. The eprinomectin protocol employed in Study 2, consisting of four weekly topical administrations at the dose rate of 500 μg/kg of body weight, proved highly effective at reducing the Chorioptes mite burden in alpacas.     

The effect of eprinomectin treatment at calving on reproduction parameters in adult dairy cows in Canada

A clinical trial was carried out in two provinces of Canada to investigate the effect of treatment with eprinomectin at calving on production parameters in adult dairy cattle in 1999-2000. One of the objectives of this study was to evaluate the impact of treatment on reproductive performance as measured by: calving-to-conception interval, calving-to-first service interval and number of services per conception. The ability of an indirect ELISA using a crude adult Ostertagia ostertagi antigen to predict response to treatment also was evaluated. All lactating cows in 20 dairy herds were allocated randomly to receive either eprinomectin pour-on or placebo at calving. Information on reproductive parameters was obtained from computerised cow records. Survival models were used to evaluate the effect of treatment on the two intervals and a Poisson model was used to evaluate the number of services to conception. A total of 549 cows were included in these analyses. A marginally significant treatment effect on calving-to-conception interval was observed (hazard ratio=1.24, P=0.06) but not on calving-to-first service interval. A significant reduction in the number of breedings to conception for treated animals also was observed with a longer effect in cows with short interval to first service. Milk samples from a subset of 109 late-lactation cows were tested for antibodies against O. ostertagi. The ELISA optical-density ratio (ODR) values obtained between 120 days before calving and drying off were categorised as high ODR (>or=0.5) and low ODR (<0.5). Among untreated animals, the hazard of conception was lower (hazard ratio=0.38, 95% CI=[0.19,0.75]) for high-ODR cows compared to low ODR cows suggesting that higher parasite burdens had an adverse effect on reproductive performance. Treated high-ODR cows had a hazard of conception equivalent to the hazard for all cows in the low-ODR group (indicating that treatment prevented the negative effect associated with these higher parasite burdens).     

Field efficacy of minidosed pour-on ivermectin and eprinomectin against goat warble fly infestation by Przhevalskiana silenus

The efficacy of minidose of pour-on ivermectin and eprinomectin formulations against first instar larvae of Przhevalskiana silenus was observed in naturally infested goats in the Jammu region, North India. The study was performed in mid August 2011. A total of 280 goats were randomly divided in to 7 groups of 40 each. Goats of the first three groups were treated with pour-on ivermectin at dosage of 2, 5, and 200 μg/kg body weight, respectively, whereas animals of the fourth to sixth groups were treated with pour-on eprinomectin at 25, 50, and 500 μg/kg body weight, respectively. Group VII animals were kept as untreated control. The results indicated that no warbles were recorded between December 2011 and March 2012 on back of animals treated with pour-on preparations of ivermectin at dosage of 5 and 200 μg/kg body weight, respectively, and eprinomectin at dosage of 50 and 500 μg/kg body weight, respectively. Thus, it is concluded that administration of minidose of pour-on ivermectin (5 μg/kg body weight) and eprinomectin (50 μg/kg body weight) is cost effective and so can be used for warble fly control campaign in Jammu region.