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.     

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.     

Persistent anthelmintic activity of topically administered ivermectin in cattle

The persistent anthelmintic effect of ivermectin as a topical treatment at 500 µg/kg was evaluated against induced infections of Ostertagia ostertagi, Trichostrongylus axei and Dictyocaulus vivparus in calves. The results showed a highly significant (P<0.001) anthelmintic activity for at least 14 days against O. oslertagi and T: axei (>99 per cent efftcacies) and for at least 28 days (98 per cent efficacy) against D. viviparus.     

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.     

Persistent anthelmintic activity of topically administered ivermectin in red deer (Cervus elaphus L.) against lungworms (Dictyocaulus viviparus)

A controlled trial was conducted to evaluate the persistent anthelmintic effect of ivermectin as a topical treatment at 500 μg/kg against induced infection with lungworm (Dicryocaulus viviparus) in red deer (Cervus elaphus). The results showed a highly significant (p < 0.01) anthelmintic activity for at least 28 days against a newly acquired infection with Dictyocauus viviparus (> 99% efficacy).     

The difference in efficacy of ivermectin oral, moxidectin oral and moxidectin injectable formulations against an ivermectin-resistant strain of Trichostrongylus colubriformis in sheep

AIM: To evaluate the efficacy of ivermectin oral, moxidectin oral and moxidectin injectable formulations against an ivermectin-resistant strain of Trichostrongylus colubriformis in sheep. METHODS: Twenty-four mixed breed lambs were infected with 15,000 infective third-stage larvae of an ivermectin-resistant strain of T. colubriformis which had originally been isolated from a goat farm in Northland in 1997. Twenty-six days post infection, the lambs were divided into 3 treatment groups and a control group (n=6 lambs/group). Treatment consisted of either ivermectin oral formulation (0.2 mg/kg), moxidectin oral formulation (0.2 mg/kg), or moxidectin injectable formulation (0.2 mg/kg). Faecal egg counts (FECs) were determined at 0, 3, 5, 7 and 10 days after treatment. All animals were necropsied 12 days after treatment and worm counts were performed. Larval development assays were conducted 24 days post infection. A further 3 lambs were infected with 15,000 infective third-stage larvae of a fully susceptible strain of T. colubriformis for comparative purposes in the larval development assay. The efficacy of the moxidectin injectable formulation was also confirmed in these 3 lambs. RESULTS: The FEC reduction test at day 10 after treatment revealed 62%, 100% and 0% reductions in arithmetic-mean FECs for ivermectin oral, moxidectin oral and moxidectin injectable groups, respectively. The ivermectin oral, moxidectin oral and moxidectin injectable formulations achieved 62%, 98% and 4% reductions in arithmetic-mean worm burdens, respectively. Larval development assays showed resistance ratios for ivermectin of 4:1, avermectin B2 of 2.7:1, ivermectin aglycone of 37:1, moxidectin of 1.4:1, thiabendazole of 14.6:1 and levamisole of 1.8:1. CONCLUSIONS: The moxidectin oral formulation provided a high degree of control against ivermectin-resistant T. colubriformis whereas the moxidectin injectable formulation had very low efficacy. Ivermectin aglycone was the analogue of choice for diagnosis of ivermectin resistance in T. colubriformis in the larval development assay.     

Persistent efficacy of a long acting injectable formulation of moxidectin against natural infestations of the sheep nasal bot (Oestrus ovis) in Spain

Cydectin(?) 2% LA Solution for Injection for Sheep (Pfizer Animal Health) is a long-acting (LA) formulation of moxidectin for the treatment and prevention of mixed infections of gastro-intestinal nematodes, respiratory nematodes and certain arthropod parasites in sheep. To evaluate the duration of persistent efficacy against nasal bots (Oestrus ovis), a natural exposure study was conducted in Spain during the summer of 2011. One hundred and twenty nasal bot-free, Rasa Aragonesa sheep were randomly allocated to eight groups of 15 animals each. On Day 0, four groups were treated at the recommended dose rate of 1 mg moxidectin/kg bodyweight. Four groups remained untreated as negative controls. All animals were held in nasal bot-proof housing except for exposure to natural challenge when one group of treated sheep and one of group of control animals were transferred to a local pasture at either 0-20, 20-40, 40-60, or 60-80 days after treatment. Following challenge, sheep were scored for clinical signs of bot infestation, necropsied and the heads sectioned for larval recovery. Nasal bot larvae were retrieved from 7 to 11 control sheep following each exposure period indicating that adult bots were active throughout the study. In the first challenge up to 20 days after treatment, when sheep were slaughtered immediately after exposure, the majority of larvae were first instar (L1) and only 3 of the 15 control sheep were infested with second instars (L2). There was 100% efficacy against L2 and 38.1% reduction in the number of live L1 in the treated sheep but mean counts were not significantly different between treatment and control groups (P ≥ 0.05). For the subsequent exposure periods 20-80 days after treatment (necropsies 7-9 days after challenge), 6-10 sheep were infested with L1 and 9-11 control sheep were infested with L2 and third instars (L3). There was negligible efficacy against L1, but treatment with moxidectin resulted in 100% control of L2 and L3. These results are consistent with the biology of nasal bots and control with a systemic agent, as the slower growing L1 have limited feeding and are therefore less susceptible to systemic parasiticides. The study demonstrated that the persistent efficacy of this long-acting injectable formulation of moxidectin protects against the development of active O. ovis infestations for at least 80 days after treatment.     

Persistent activity of moxidectin long-acting injectable formulations against natural and experimentally enhanced populations of lice infesting cattle

A study was conducted under a common protocol in Wisconsin and Wyoming, USA, to evaluate therapeutic and persistent efficacy of two long-acting injectable formulations of moxidectin against lice populations infesting cattle. At each site, 30 beef calves were blocked into groups of three based on naturally acquired Linognathus vituli populations, then randomly assigned to treatments within blocks. Treatments, injected subcutaneously into the proximal third of the ear on Day 0, included saline, a long-acting oil-based formulation containing 10% moxidectin given at the rate of 1 mg moxidectin/kg body weight (M10/1.0), or a long-acting oil-based formulation containing 15% moxidectin given at the rate of 0.75 mg moxidectin/kg b.w. (M15/0.75). Species of sucking and chewing lice were quantified on nine predilection sites before treatment, then 28, 63, 98, 133 and 168 days after treatment. During intervals between lice counts after Day 28, study animals from the three treatment groups were commingled for 32 days with two lice-free sentinels plus four to six seeder calves with infestations of both sucking and chewing lice. Following each 32-day commingling interval, seeder and sentinel animals were removed, and principal animals were sorted into pens by treatment. Lice were quantified on sentinel animals on the day of removal, and lice were quantified on principal study animals 3 days after removal of sentinel and seeders. Moxidectin was generally not efficacious against Bovicola bovis in the injectable formulations tested, whereas Haematopinus eurysternus infestations were inadequate to judge product effectiveness. Based on geometric means, both M15/0.75 and M10/1.0 provided statistically significant therapeutic efficacy against existing infestations of L. vituli and Solenopotes capillatus (100% efficacy on Day 28), and provided persistent protection against reinfestation with L. vituli and S. capillatus (efficacy >97%) for at least 133 days following treatment.     

Persistent activity of moxidectin pour-on and injectable against sucking and biting louse infestations of cattle

To evaluate the persistent activity of pour-on and injectable moxidectin against natural challenge by sucking (predominantly Linognathus vituli) and chewing (Bovicola bovis) cattle lice, 96 mixed-breed calves that had been treated to remove all lice were blocked by body weight and randomly allocated to three treatments: untreated control, moxidectin at 500 microg/kg by topical application and moxidectin at 200 microg/kg by subcutaneous injection. Twelve pens were blocked into groups of four and randomly allocated to four challenge times: 14, 21, 28 and 35 days post-treatment. Treatment groups were assigned to challenge pens randomly. Two donor calves, with demonstrated infestations of both sucking and chewing lice, were introduced into each pen containing eight principal calves at the start of each challenge time. Donors remained in the challenge pen for 7 days. Principal calves were examined for lice, 7, 14, 21 and 28 days after donor removal using a standardized hair-parting technique. Moxidectin injectable prevented re-infestation with L. vituli for up to 42 days, but did not provide persistent activity against B. bovis longer than 35 days post-treatment. Moxidectin pour-on demonstrated persistent activity against both B. bovis and L. vituli for 42 days.     

Effects of subcutaneous injections of a long acting moxidectin formulation in grazing beef cattle on parasite fecal egg reduction and animal weight gain

Trials were conducted in Arkansas, Idaho, Illinois and Wisconsin using a common protocol to evaluate effectiveness and safety of a long acting (LA), oil-based injectable formulation of moxidectin in beef cattle grazing spring and/or summer pastures. At each site, 150 cattle (steers and/or heifers) were blocked based on pretreatment fecal strongyle egg counts (EPG) and then randomly assigned to treatments within blocks. Presence of naturally acquired parasitic infections, confirmed by presence of parasite eggs in feces, was a prerequisite for study enrollment. Within each block of three animals, two received moxidectin LA injectable on day 0 at a dosing rate of 1.0 mg moxidectin/kg b.w. into the dorsal aspect of the proximal third of the ear, and one received a placebo control treatment. Cattle were weighed before treatment and on day 55 or 56 (55/56) after treatment. Fecal samples were also collected from 10 randomly selected blocks of animals at each site on days 14, 28 and 55/56 for EPG quantification. Average daily gain (ADG) was computed over the posttreatment period. Data pertaining to ADG and EPG were combined across sites and analyzed by mixed model analysis of variance to assess the fixed effect of treatment and random effects of site, block within site and the treatment by site interaction. Compared to placebo-treated controls, the geometric means of fecal EPG counts from cattle treated with moxidectin LA injectable were reduced 99.8% 14 days after treatment, 99.1% 28 days after treatment and 96.7% 55/56 days after treatment. Rate of weight gain by cattle treated with moxidectin LA injectable was 0.59 kg/day, or 23% (0.11 kg/day) more than placebo-treated controls (P<0.05). None of the cattle treated with moxidectin LA injectable exhibited signs of macrocyclic lactone toxicosis. Summarized across all study sites, proportions of cattle that received concurrent therapeutic treatments were similar among treatment groups. Study results demonstrate that moxidectin cattle LA injectable administered at a dosing rate of 1.0 mg moxidectin/kg b.w. to grazing beef cattle was effective and safe.     

The anthelmintic efficacy of ivermectin in experimentally infected cattle

The 22,23-dihydro derivative (ivermectin) of the major B₁ components of the avermectins was evaluated, by oral and parenteral routes, for anthelmintic activity in cattle experimentally infected with 7 gastro-intestinal nematode species and lungworm. Treatment at three dosage levels was administered when the parasites were in the L₄ developmental stage or when adult. The dosage expected to remove 95% of the nematodes (ED₉₅) by each route of administration against the various developmental stages of each species of parasite was calculated by methods of linear regression to choose dose levels to be used in subsequent developmental field trials. Parenterally, efficacy against L₄ stages of Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, T. colubriformis, Cooperia oncophora, C. punctata, Oesophagostomum radiatum and Dictyocaulus viviparus exceeded 99% with treatment at 0.2 mg ivermectin/kg. Parenteral treatment of the adult parasites resulted in at least 98% reduction of worm burdens, except $\text{? 90\%}$ for T. colubriformis, with 0.2 mg/kg. Oral treatment of L₄ stages of development with 0.2 mg/kg resulted in at least a 95% reduction in worm burdens of each of the 8 species of parasite. Oral treatment of the adult worms with 0.1 mg ivermectin/kg produced at least a 98% decrease in each parasite species, except for T. colubriformis (90% reduction) for which dose-response calculations suggest 95% efficacy with oral treatment at 0.2 mg/kg.     

Assessing the efficacy of Duddingtonia flagrans chlamydospores per gram of faeces to control Haemonchus contortus larvae

The aims were (a) to quantify the number of Duddingtonia flagrans chlamydospores per gram of faeces (CPG) recovered from sheep administered with different oral doses and, (b) to describe the relationship between CPG and eggs per gram of faeces (EPG) on the efficacy to reduce Haemonchus contortus infective larvae. Three doses of chlamydospores per kg BW were orally administered during seven days: (T1) non treated control group, (T2) 1 × 10⁶, (T3) 2.5 × 10⁶ and (T4) 5 × 10⁶. Three lambs, infected with H. contortus, were used per group. Faeces were obtained from the rectum of each lamb during the fungal administration period (days 0–6) and for six days after that period. Four coproculture replicates were made from each animal in days 2, 4, 6, 8 and 10. A higher chlamydospore dose produced higher CPG in faeces (p < 0.05), but a clear dose dependent effect was not found either in the larvae reduction or in the CPG:EPG ratio. When ratios were re-analyzed, independently of the treatment groups of origin, a better efficacy was obtained with a ratio from 5 to 10 CPG:EPG and a higher ratio (>10 per egg) showed a lower reduction efficacy (p < 0.05). The binomial analysis showed that for each unit of increment in CPG:EPG ratio there was a reduction of larvae number until a point (between 5 and 10 CPG:EPG) where no further reduction was detected. The surface response test indicated that the number of larvae was reduced by CPG until possible saturation. The highest CPG:EPG ratios did not necessarily improve efficacy of D. flagrans.     

Efficacy of moxidectin 1% injectable and 0.2% oral drench against natural infection by Dictyocaulus filaria in sheep

Two separate trials (I and II) with 34 and 32 Churra ewes, respectively, and distributed into two groups, have been carried out to evaluate the efficacy of two different formulations of moxidectin at a dose rate of 0.2mg/kg body weight (b.w.) against natural infection by Dictyocaulus filaria in sheep. Trial I was designed to evaluate a 1% moxidectin injectable formulation, whereas in trial II a 0.2% moxidectin oral drench formulation was used. The efficacy was measured on the basis of the reduction of the faecal larval counts and of adult worm recoveries at slaughter.In each trial, a group of animals was treated on day 0 with moxidectin 1% injectable or moxidectin 0.2% oral drench and the other group acted as untreated control.When the faecal larval counts was compared within the treated groups, the efficacy was over 95% until day +13, and 100% at the remainder of the sampling dates after the application of injectable moxidectin, whereas in trial II, the larvae per gram (lpg) of faeces increased until the first sampling time post treatment (p.t.), day +6, and zero counts were recorded for all animals by the following days. On the basis of adult worm recoveries at necropsy, the efficacy of the treatment was 100% in both trials, however, adult worms were detected at slaughter for all control sheep. These results indicate that moxidectin 1% injectable and moxidectin 0.2% oral drench, administered at 0.2mg/kg b.w., were 100% effective against D. filaria infection in sheep. No adverse reactions to the treatments were observed in the animals.     

Dose determination of the persistent activity of moxidectin long-acting injectable formulations against various nematode species in cattle

The effectiveness, safety and production-enhancing benefit (improved weight gains) of moxidectin long-acting injection given subcutaneously in the ear at the rates of 0.75, 1.0 and 1.5mg/kg bw were evaluated in three studies under common protocol. The only adverse reaction to treatment was a mild (<2 tablespoons in volume), and for the most part transient (<28 days for the treatment rate of 1.0mg/kg bw) injection site swelling as noted in a minority of the animals (12.2% of the animals treated at the rate of 1.0mg/kg bw). Regardless of study site, post-treatment interval or dose rate, average daily gains were improved over control cattle by approximately 33%. Reductions in strongyle EPG counts relative to controls were > or = 90% for all dose rates of moxidectin for a post-treatment period of 42 days (Wisconsin), 84 days (Arkansas) and 140 days (Louisiana). In Arkansas and Louisiana, the majority (>80%) of post-treatment strongyle eggs, as determined by coproculture, were Cooperia spp. As determined by sequential necropsies, periods of continuous, post-treatment protection (> or = 90% efficacy in at least two out of three studies) for moxidectin long-acting injection given at the rate of 1.0 mg/kg bw were 90 days (adult Haemonchus spp.), 120 days (Dictyocaulus viviparus and adult Ostertagia and Oesophagostomum) and 150 days (Ostertagia spp. EL4).     

Effect of moxidectin against natural infestation of the cattle tick Boophilus microplus (Acarina: Ixodidae) in the Mexican tropics

The study was divided in to two trials and carried out in a ranch in eastern Yucatan state, Mexico. In the first trial, two groups of 15 BostaurusxBosindicus heifers, 6-12 month of age and naturally infested with Boophilus microplus ticks were used. Heifers in Group 1 were treated with a 1% injectable formulation of moxidectin at the dose of 0.20mg/kg body weight by subcutaneous injection. The other group remained as untreated controls. Number of immature and engorging female ticks were assessed on days 0, 7, 14, 21, 28 and 35 post-treatment (PT). The efficacy of moxidectin on adult ticks from day 7 to 28 PT was greater than 95%. The efficacy decreased to 74.9% by day 35. In the second trial, animals in Group 1 were treated with the moxidectin product as before, while cattle in Group 2 were treated according to the routine procedure for the control of ticks on that property (125 g/l amitraz as a dip). Treatment of all cattle was repeated four times at intervals of 28 days. The efficacy of the experimental moxidectin treatment was similar to that of the routine amitraz treatment, i.e., greater than 99%.     

Reduced efficacy of moxidectin and abamectin in young red deer (Cervus elaphus) after 20 years of moxidectin pour-on use on a New Zealand deer farm

A study was undertaken on weaned 4–5 month old farmed red deer to test the efficacy of moxidectin and abamectin anthelmintics, given by three different routes of administration, compared with an untreated control. Faecal samples were collected on days 0, 7 and 14 for a faecal egg count reduction test (FECRT), blood samples were collected on days 0, 0.5, 1, 2, 3, 5, 7, 10 and 14 for pharmacokinetics, and the deer were killed on days 14 or 15 for total nematode count.The control group averaged 1264 adult Ostertagia-type nematode parasite species and treatment efficacy was 77.4% for moxidectin injection, 26% for oral moxidectin and 27.6% for pour-on moxidectin, while the treatment efficacy was 72.4% for abamectin injection, 70.1% for oral abamectin (Hi-Mineral) and 34.1% for pour-on abamectin. Both moxidectin and abamectin injections were significantly more efficacious than their equivalent pour-ons. There was a significant difference in efficacy between oral abamectin (Hi-Mineral) and oral moxidectin (P < 0.01).The control group averaged 2956 adult lungworm (Dictyocaulus eckerti) and 50 Oesophagostomum venulosum in the large intestine and treatment efficacy against these nematodes was 100% for all treatments. There were negligible numbers of other gastro-intestinal nematodes.At slaughter, there was a significant correlation (P = 0.02) between FEC and Ostertagia-type nematodes in the untreated controls. Relatively few eggs were found in faeces from treated animals at 7 and 14 days post-treatment despite significant worm burdens in all six treatment groups, suggesting egg-laying suppression in resistant nematodes, and all three different FECRT calculations tended to overestimate the efficacy of the treatments compared with actual nematode counts.Peak plasma concentrations (C_max) for both actives were measured 12 h after treatment for injection and oral and at 5 days for pour-on. C_max (ng/ml) for moxidectin injection, oral and pour-on were 71.8, 8.3 and 0.4, respectively, and for abamectin injection, oral and pour-on were 62.1, 30.3 and 10.0, respectively. Area under the curve (AUC) estimates for moxidectin injection, oral and pour-on were 106.6, 12.9 and 6.1, respectively, and for abamectin injection, oral and pour-on were 162.7, 57.5 and 74.3, respectively.The results demonstrate that significant anthelmintic resistance to moxidectin and abamectin is present on this deer farm. However, the injection was the most effective route of administration in young deer for both anthelmintics, although <80% efficacious. We conclude that the FECRT is unreliable in deer when anthelmintic resistance is present.     

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.     

Use of a long acting injectable formulation of moxidectin to control the periparturient rise in faecal Teladorsagia circumcincta egg output of ewes

A field study was conducted in a sheep flock in the south east of Scotland with a history of ivermectin resistance in Teladorsagia circumcincta. The objective of the study was to compare the effects of single anthelmintic treatments in ewes before turn-out onto pasture that was contaminated with a moderate level of overwintered, ivermectin resistant, T. circumcincta infective larvae. The ewes were treated according to label directions with either a long acting injectable formulation of moxidectin (1mg/kg; affording up to 14weeks persistent action against macrocyclic lactone (ML)-susceptible T. circumcincta) or an oral formulation of moxidectin (0.2mg/kg; affording up to 5weeks persistent action against ML-susceptible T. circumcincta). The lambs were enrolled in the normal management of the farm, and received a total of three oral ivermectin treatments during the 16week study. The efficacy of both treatment strategies in controlling the periparturient rise in faecal nematode worm egg counts and subsequent pasture contamination was assessed from the faecal worm egg counts of the ewes and their lambs between lambing and weaning. Ewes that were treated with the oral formulation of moxidectin shed approximately 3.5 times more T. circumcincta eggs between lambing and weaning than ewes that were treated with the long acting formulation of moxidectin. This difference was reflected in the faecal worm egg counts of the lambs that were grazed alongside the different treatment groups of ewes. The results of the current study demonstrate persistent efficacy of the long acting formulation of moxidectin against an ivermectin resistant T. circumcincta population. The decreased pasture contamination after treatment could lead to improved lamb growth and a need for fewer anthelmintic treatments, thus potentially reducing one possible selection pressure for anthelmintic resistance. However, treatment with the long acting formulation of moxidectin would give rise to fewer susceptible nematodes being present in refugia, which could increase another possible selection pressure for anthelmintic resistance, depending on the subsequent grazing management of that pasture. The rationale for use of a persistent anthelmintic drug to control the periparturient rise in faecal ML-resistant T. circumcincta egg output of the ewes is discussed and potential differences in selection for macrocyclic lactone anthelmintic resistance using the different formulations of moxidectin are acknowledged.     

Dose confirmation studies of moxidectin 1% non-aqueous injectable and moxidectin 0.5% pour-on formulations against experimentally induced infections of larval and adult stage Oesophagostomum radiatum and Trichuris discolor in cattle

Separate controlled trials were conducted to evaluate the efficacy of two formulations of moxidectin (1% non-aqueous injectable solution and 0.5% pour-on (Cydectin) against larval or adult stages of Oesophagostomum radiatum and Trichuris discolor infecting cattle. Fifty-three strongylate-free dairy breed steer calves were obtained from commercial sources. After a brief acclimation period, calves were randomly divided into two pools to evaluate the efficacy of the moxidectin formulations against targeted larval (n = 27 calves) or adult (n = 26 calves) parasites. Calves in the larvacidal trial were inoculated on Day -16 relative to treatment with approximately 1000 embryonated Trichuris spp. eggs and approximately 640 infective Oesophagostomum spp. larvae. Calves were allocated by lottery to one of three treatment groups (n = 8 per group), which included: Group 1--moxidectin 0.5% pour-on (0.5 mg/kg body weight (BW)) applied topically; Group 2--moxidectin 1% non-aqueous injectable (0.2 mg/kg BW) administered subcutaneously; Group 3--untreated controls. Treatments were administered on Day 0 and calves were housed by group with no contact among animals of different treatments. Three sentinel calves were necropsied on Day 0 of the larvacidal trial to assess viability of larval inocula. On Days 14, 15 and 16 after treatment, calves were euthanatized (two or three from each group per day) and samples of gut contents were collected for determination of total worm counts. On Day -63 relative to treatment, calves in the adulticidal efficacy trial were inoculated with approximately 1000 embryonated Trichuris eggs and then on Day -35 with approximately 2500 infective Oesophagostomum spp. larvae. Fecal samples were collected on Day -7 and the 24 calves with the highest egg counts were assigned by lottery to the following three treatment groups (n = 8 per group): Group 4--moxidectin 0.5% pour-on; Group 5--moxidectin 1% injectable; Group 6--untreated controls. Details of experimental treatments, calf housing and necropsy scheduling were similar to the larvacidal trial. In both the larvacidal and adulticidal trials, inocula contained a variety of parasites in addition to the targeted species. Based on geometric means, both moxidectin 0.5% pour-on and moxidectin 1% non-aqueous injectable significantly reduced (P < 0.05) numbers of Oesophagostomum spp. and Trichuris spp. with anthelmintic efficacies of >99% when used against adult or larval stages of infection. In addition, both formulations of moxidectin demonstrated >95% efficacy (P < 0.05) against larval stages of Strongyloides papillosus. The pour-on formulation had >97% adulticidal and larvacidal efficacy against Cooperia spp. females, while the injectable product was effective against female Cooperia spp. larvae and Cooperia oncophora adult males.     

A comparison of the efficacy of subcutaneously administered ivermectin,doramectin, and moxidectin against naturally infected <Emphasis Type="Italic">Toxocara vitulorum</Emphasis> in calves

This study was conducted to investigate the efficacy of ivermectin (IVM), doramectin (DRM), and moxidectin (MXD) against Toxocara vitulorum in calves. In the study, 20 calves naturally infected with T. vitulorum were divided into four groups: three different treatment groups (n?=?5) and one positive control (n?=?5). The animals in each group received either IVM (Baymec®, Bayer), DRM (Dectomax®, Pfizer), or MXD (Cydectin®, Fort Dodge) by subcutaneous injection at a single dose of 0.2 mg/kg. Fecal egg counts were performed on all animals on days 0, 2, 4, 8, 12, and 16 post-treatment. In conclusion, IVM, DRM, and MXD significantly reduced the fecal egg counts on day 8 post-treatment (99.90%, 98.77%, and 99.57%, respectively). After the 12th day, IVM, DRM, and MXD were found to be 100% effective. There was no significant difference in efficacy between the three treatment groups at any of the sampling dates (P?>?0.05). No side effects associated with nervous, respiratory, and gastrointestinal systems were observed. This is the first study to evaluate the comparative efficacy of subcutaneous administration of ivermectin, doramectin, and moxidectin against naturally infected T. vitulorum in calves.