The efficacy of eprinomectin extended-release injection against naturally acquired nematode parasites of cattle,with special regard to inhibited fourth-stage Ostertagia larvae

The efficacy of eprinomectin in an extended-release injection (ERI) formulation in the treatment of cattle harboring naturally acquired nematode populations (including inhibited nematodes) was evaluated. Five studies were conducted under a similar protocol in the USA, the UK, and in Germany. All study animals were infected by grazing naturally contaminated pastures. The adequacy of pasture infectivity was confirmed by examining tracer calves prior to allocation and treatment of the study animals. The cattle were of various breeds or crosses, weighing 79–491 kg, and aged approximately 6–15 months. In each study, 20 animals were infected by grazing, and then removed from pasture and housed in a manner to preclude further nematode infections for 8–16 days until treatment. Animals were blocked based on descending pre-treatment body weight and randomly allocated to one of two treatments: ERI vehicle (control) at 1 mL/50 kg body weight or eprinomectin 5% (w/v) ERI at 1 mL/50 kg body weight (1.0 mg eprinomectin/kg). Treatments were administered once on Day 0 by subcutaneous injection in front of the shoulder. For parasite recovery and count, all study animals were humanely euthanized 14/15 days after treatment. Cattle treated with eprinomectin ERI had significantly (p < 0.05) fewer of the following nematodes than the controls with overall reduction of parasite counts of ≥94%: adult Dictyocaulus viviparus, Capillaria spp., Cooperia oncophora, Cooperia pectinata, Cooperia punctata, Cooperia surnabada, Haemonchus placei, Nematodirus helvetianus, Oesophagostomum radiatum, Ostertagia lyrata, Ostertagia ostertagi, Trichostrongylus axei, Trichostrongylus colubriformis, Trichuris discolor, Trichuris skrjabini, and Trichuris spp.; developing fourth-stage larvae of Ostertagia spp. and Trichostrongylus spp.; and inhibited fourth-stage larvae of Cooperia spp., Haemonchus spp., Nematodirus spp., Oesophagostomum spp., Ostertagia spp., and Trichostrongylus spp.     

Nematode burdens of pastured cattle treated once at turnout with eprinomectin extended-release injection

The efficacy of eprinomectin in an extended-release injection (ERI) formulation was evaluated against infections with third-stage larvae or eggs of gastrointestinal and pulmonary nematodes in cattle under 120-day natural challenge conditions in a series of five studies conducted in the USA (three studies) and in Europe (two studies). For each study, 30 nematode-free (four studies) or 30 cattle harboring naturally acquired nematode infections (one study) were included. The cattle were of various breeds or crosses, weighed 107.5–273 kg prior to treatment and aged approximately 4–11 months. For each study, animals were blocked based on pre-treatment bodyweight and then randomly allocated to treatment: ERI vehicle (control) at 1 mL/50 kg bodyweight or Eprinomectin 5% (w/v) ERI at 1 mL/50 kg bodyweight (1.0 mg eprinomectin/kg) for a total of 15 and 15 animals in each group. Treatments were administered once on Day 0 by subcutaneous injection in front of the shoulder. In each study, all animals grazed one naturally contaminated pasture for 120 days. At regular intervals during the studies, fecal samples from all cattle were examined for nematode egg and larval counts. In four studies pairs of tracer cattle were used to monitor pasture infectivity at 28-day intervals before and/or during the grazing period. All calves were weighed before turnout onto pasture and at regular intervals until housing on Day 120. For parasite recovery, all study animals were humanely euthanized 27–30 days after removal from pasture.     

An eprinomectin extended-release injection formulation providing nematode control in cattle for up to 150 days

A series of 10 dose confirmation studies was conducted to evaluate the persistent activity of an extended-release injectable (ERI) formulation of eprinomectin against single point challenge infections of gastrointestinal and pulmonary nematodes of cattle. The formulation, selected based on the optimal combination of high nematode efficacy, appropriate plasma profile, and satisfactory tissue residue levels, includes 5% poly(d,l-lactide-co-glycolic)acid (PLGA) and is designed to deliver eprinomectin at a dose of 1.0 mg/kg bodyweight. Individual studies, included 16–30 cattle blocked based on pre-treatment bodyweight and randomly allocated to treatment with either ERI vehicle or saline (control), or the selected Eprinomectin ERI formulation. Treatments were administered once at a dose volume of 1 mL/50 kg bodyweight by subcutaneous injection in front of the shoulder. In each study, cattle were challenged with a combination of infective stages of gastrointestinal and/or pulmonary nematodes 100, 120 or 150 days after treatment and were processed for parasite recovery according to standard techniques 25–30 days after challenge. Based on parasite counts, Eprinomectin ERI (1 mg eprinomectin/kg bodyweight) provided >90% efficacy (p < 0.05) against challenge with Cooperia oncophora and Cooperia surnabada at 100 days after treatment; against challenge with Ostertagia ostertagi, Ostertagia lyrata, Ostertagia leptospicularis, Ostertagia circumcincta, Ostertagia trifurcata, Trichostrongylus axei, and Cooperia punctata at 120 days after treatment; and against challenge with Haemonchus contortus, Bunostomum phlebotomum, Oesophagostomum radiatum and Dictyocaulus viviparus at 150 days after treatment. Results of a study to evaluate eprinomectin plasma levels in cattle treated with the Eprinomectin ERI formulation reveal a characteristic second plasma concentration peak and a profile commensurate with the duration of efficacy. These results confirm that the Eprinomectin ERI formulation can provide high levels of parasite control against a range of nematodes of cattle for up to 5 months following a single treatment.     

LongRange™ (eprinomectin 5%) extended-release injection parasiticide and the utility of extended-activity antiparasitics in cattle

An extended-release injection, which is administered at a rate of 1 mg eprinomectin/kg body weight, has been developed to provide up to 150 days control of parasites of cattle. The product can facilitate the achievement of two of the fundamental aims of parasite control. The first is protection of the host against the negative impact of susceptible parasites in order to ensure control of disease and to enhance performance. The second is to reduce parasite transmission and hence the challenge to animals when grazing. In addition, farmers and veterinarians can benefit from high levels of convenience and hence compliance from a single administration, which also limits handling stress in the cattle. This introductory paper provides some perspective on the practical applications for this extended-release product under various husbandry systems and in different classes of cattle and discusses its role in sustainable parasite control.     

Persistent efficacy and production benefits following use of extended-release injectable eprinomectin in grazing beef cattle under field conditions

Seven studies were conducted in commercial grazing operations to confirm anthelmintic efficacy, assess acceptability, and measure the productivity response of cattle to treatment with eprinomectin in an extended-release injectable formulation (ERI) when exposed to nematode infected pastures for 120 days. The studies were conducted under one protocol in the USA in seven locations (Arkansas, Idaho, Louisiana, Minnesota, Missouri, Oregon, and Wisconsin). Each study had 67–68 naturally infected animals for a total of 475 (226 female, 249 male castrate) Angus or beef-cross cattle. The animals weighed 133–335 kg prior to treatment and were approximately 3–12 months of age. The studies were conducted under a randomized block design based on pre-treatment body weights to sequentially form 17 replicates of four animals each within sex in each study. Animals within a replicate were randomly assigned to treatments, one to Eprinomectin ERI vehicle (control) and three to Eprinomectin ERI (5%, w/v eprinomectin). Treatments were administered at 1 mL/50 kg body weight once subcutaneously anterior to the shoulder. All animals in each study grazed one pasture throughout the observation period of 120 days. Cattle were weighed and fecal samples collected pre-treatment and on 28, 56, 84, and 120 days after treatment for fecal egg and lungworm larval counts. Positive fecal samples generally were cultured en masse to determine the nematode genera attributable to the gastrointestinal helminth infection. Bunostomum, Cooperia, Haemonchus, Nematodirus, Oesophagostomum, Ostertagia, and Trichostrongylus, when present, were referred to as strongylids. At all post-treatment sampling intervals, Eprinomectin ERI-treated cattle had significantly (P < 0.05) lower strongylid egg counts than vehicle-treated controls, with ≥95% reduction after 120 days of grazing. Over this same period, Eprinomectin ERI-treated cattle gained more weight (43.9 lb/head) than vehicle-treated controls in all studies. This weight gain advantage was significant (P < 0.05) in six of the studies with the Eprinomectin ERI-treated cattle gaining an average of 42.8% and the control cattle gaining 33.1% of their initial weight. No adverse reactions were observed in the treated animals.     

The efficacy of eprinomectin extended-release injection against Hypoderma spp. (Diptera: Oestridae) in cattle

The efficacy of eprinomectin in an extended-release injection (ERI) formulation was determined in cattle harboring naturally acquired infestations of first- or second- and third-stage larvae of Hypoderma spp. in three studies conducted according to the same protocol in the USA (two studies) and Germany (one study). Thirty cattle sourced from herds with a history of Hypoderma infestation were included in each study. Cattle were formed into replicates of three animals each on the basis of pre-treatment anti-Hypoderma antibody titers. Within replicates each animal was randomly allocated to one of the following treatments: ERI vehicle (control) at 1 mL/50 kg bodyweight, administered once on Day 0; Eprinomectin 5% ERI at 1 mL/50 kg bodyweight (1.0 mg eprinomectin/kg), administered once on Day 0 (when larvae were expected to be first instars); or Eprinomectin 5% ERI at 1 mL/50 kg bodyweight (1.0 mg eprinomectin/kg), administered once when larvae were second or third instars (study dependent, Day 73, 119, or 140). Treatments were administered by subcutaneous injection in front of the shoulder. In all studies, emerging and/or expressed Hypoderma larvae were recovered, speciated, and counted and viability was determined. Eprinomectin LAI treatment was 100% (p < 0.05) efficacious against first- and second- or third-stage larvae of Hypoderma bovis (two studies) and Hypoderma lineatum (one study). All animals accepted the treatment well. No adverse reaction to treatments was observed in any animal in any study.     

The treatment of bovine sarcoptic mange (Sarcoptes scabiei var. bovis) using eprinomectin extended-release injection

The efficacy of eprinomectin in an extended-release injection (ERI) formulation was evaluated in cattle harbouring induced infestations of Sarcoptes scabiei var. bovis (sarcoptic mange) in three studies conducted in Germany (two studies) and Austria (one study). A total of 44 cattle were included in the studies, 12 in one study and 16 in each of the other two studies. Approximately eight weeks following initial induced infestation, cattle in each study were formed into replicates of two animals each on the basis of pre-treatment bodyweights. Within replicates the animals were randomly allocated to one of two treatments: ERI vehicle (control) or Eprinomectin 5% (w/v) ERI (1.0 mg eprinomectin/kg). Treatments were administered at 1 mL/50 kg bodyweight by subcutaneous injection in front of the shoulder once on day 0. The number of live mites in skin scrapings was determined prior to treatment and at weekly intervals for eight weeks after treatment. Severity of skin lesions was evaluated and scored when skin scrapings were taken. In all studies, animals were weighed before infestation and again prior to and at 56 days after treatment.     

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.     

Therapeutic and persistent efficacy of moxidectin 1% nonaqueous injectable formulation against natural and experimentally induced lung and gastrointestinal nematodes in cattle

Four controlled trials were conducted to evaluate the therapeutic and persistent efficacy of a new moxidectin formulation (moxidectin 1% nonaqueous injectable) against nematode parasites in cattle. This injectable moxidectin formulation, given as a single subcutaneous injection at a dose rate of 0.02 ml/kg BW to provide 0.2 mg moxidectin/kg BW, was highly efficacious (>90–100%) against larval and/or adult stages of many species of nematodes in cattle including, Dictyocaulus viviparus, Ostertagia spp., Trichostrongylus axei, Haemonchus placei, Trichostrongylus colubriformis, Cooperia spp., Nematodirus helvetianus, Strongyloides papillosus, Oesophagostomum radiatum and Trichuris spp. This formulation had persistent efficacy of >90% against D. viviparus for at least 6 weeks post-treatment, H. placei and Oe. radiatum for 5 weeks post-treatment, and Ostertagia spp. and T. axei for 2 weeks post-treatment.     

Efficacy of doramectin against naturally acquired adult and inhibited larval infections by some nematode parasites in cattle in New Zealand

A study was conducted to determine the therapeutic efficacy of 1% doramectin injected subcutaneously at 200 uglkg into cattle harbouring naturally acquired infections of inhibited Ostertagia ostertagi larvae. Sixteen yearling Friesian bulls, grazed without anthelmintic treatment throughout the autumn-winter, were selected on the basis of similar body weights and serum pepsinogen activities. After removal from pasture on day -23 they were weighed and randomly assigned to two treatment groups on the basis of this weight. On day 0, one group was given saline (1 ml/SO kg) while the second was treated with doramectin (200 𝛍g/kg). Both treatments were given by subcutaneous injection. All stock were slaughtered 14–1.5 days after treatment. Moderate to high levels of adult O. ostertagi and Trichostrongylus axei and early and late 4th larval stages of O. ostertagi were recovered from saline-treated calves at necropsy. Doramectin was highly effective in eliminating all stages of O. ostertagi (99.9%; p<0.0001) and T: axei (100%; p<0.0001). No evidence of lesions were detected at the injection sites at necropsy. These results confirm that doramectin is an extremely effective broad-spectrum avermectin anthelmintic with efficacy against inhibited as well as maturing larval and aduit forms of O. ostertagi.     

Efficacy of doramectin against naturally acquired adult and inhibited larval infections by some nematode parasites in cattle in New Zealand

A study was conducted to determine the therapeutic efficacy of 1% doramectin injected subcutaneously at 200 microg/kg into cattle harbouring naturally acquired infections of inhibited Ostertagia ostertagi larvae. Sixteen yearling Friesian bulls, grazed without anthelmintic treatment throughout the autumn-winter, were selected on the basis of similar body weights and serum pepsinogen activities. After removal from pasture on day -23 they were weighed and randomly assigned to two treatment groups on the basis of this weight. On day 0, one group was given saline (1 ml/50 kg) while the second was treated with doramectin (200 microg/kg). Both treatments were given by subcutaneous injection. All stock were slaughtered 14-15 days after treatment. Moderate to high levels of adult O. ostertagi and Trichostrongylus axei and early and late 4th larval stages of O. ostertagi were recovered from saline-treated calves at necropsy. Doramectin was highly effective in eliminating all stages of O. ostertagi (99.9%; p<0.0001) and T. axei (100%; p<0.0001). No evidence of lesions were detected at the injection sites at necropsy. These results confirm that doramectin is an extremely effective broad-spectrum avermectin anthelmintic with efficacy against inhibited as well as maturing larval and adult forms of O. ostertagi.     

The efficacy of triclabendazole (Fasinex) against immature and adult Fasciola hepatica in experimentally infected cattle

Eighteen Chinese cattle were experimentally infected with metacercariae of Fasciola hepatica and randomly assigned to 6 groups. Five groups of cattle were treated with a single oral dose of triclabendazole at a dose rate of 12 mg kg-1. At necropsy, the reduction in fluke burden compared with the untreated group was 85, 99.6, 99.8, 100 and 100% for cattle treated 2, 6, 8, 12 and 16 weeks after infection, respectively. Data are also presented on body weight changes during the experimental period and on serum gamma-GT activity in cattle from selected groups. Triclabendazole is considered to be safer and more efficacious than currently available fasciolicides in China.     

Evaluation of the persistent activity of moxidectin (10%) long-acting (LA) injectable formulation against Dictyocaulus viviparus, Haemonchus placei, Trichostrongylus axei and Oesophagostomum radiatum infections in cattle

Two controlled studies were conducted to evaluate the persistent efficacy of moxidectin (10%) long-acting (LA) injectable formulation against Dictyocaulus viviparus, Haemonchus placei, Trichostrongylus axei and Oesophagostomum radiatum in cattle. The moxidectin LA injectable formulation was administered as a single subcutaneous injection into the proximal third of the ear at a dose rate of 0.01 ml/kg BW to provide 1.0 mg moxidectin/kg BW. The product had persistent efficacy of >90% against D. viviparus, H. placei and Oe. radiatum for at least 150 days post-treatment and against T. axei for at least 90 days post-treatment.     

Evaluation of three formulations of fenbendazole (10% suspension, 0.5% pellets, and 20% premix) against nematode infections in cattle

Anthelmintic efficacies of 3 formulations of fenbendazole were evaluated in cattle naturally parasitized with nematodes: a 10% oral suspension, 0.5% pellets as a top dressing on feed, and a 20% premix. All formulations of fenbendazole were greater than 99% effective in removing adults of Haemonchus contortus, Ostertagia spp, Cooperia spp, and Oesophagostomum radiatum. Fenbendazole was greater than 96% effective in removing adults of Strongyloides papillosus and greater than 85% effective in the removal of Trichuris sp. Fenbendazole was greater than 96% effective against immature nematodes, which were thought to be primarily Cooperia spp. Adverse reactions were not observed in calves treated with the 3 formulations of fenbendazole.