GM2 Gangliosidosis in Shiba Inu Dogs with an In-Frame Deletion in HEXB.

Consistent with a tentative diagnosis of neuronal ceroid lipofuscinosis (NCL), autofluorescent cytoplasmic storage bodies were found in neurons from the brains of 2 related Shiba Inu dogs with a young-adult onset, progressive neurodegenerative disease. Unexpectedly, no potentially causal NCL-related variants were identified in a whole-genome sequence generated with DNA from 1 of the affected dogs. Instead, the whole-genome sequence contained a homozygous 3 base pair (bp) deletion in a coding region of HEXB. The other affected dog also was homozygous for this 3-bp deletion. Mutations in the human HEXB ortholog cause Sandhoff disease, a type of GM2 gangliosidosis. Thin-layer chromatography confirmed that GM2 ganglioside had accumulated in an affected Shiba Inu brain. Enzymatic analysis confirmed that the GM2 gangliosidosis resulted from a deficiency in the HEXB encoded protein and not from a deficiency in products from HEXA or GM2A, which are known alternative causes of GM2 gangliosidosis. We conclude that the homozygous 3-bp deletion in HEXB is the likely cause of the Shiba Inu neurodegenerative disease and that whole-genome sequencing can lead to the early identification of potentially disease-causing DNA variants thereby refocusing subsequent diagnostic analyses toward confirming or refuting candidate variant causality.

Cervical vertebral malformation-malarticulation syndrome in the Bernese mountain dog: clinical and magnetic resonance imaging features.

OBJECTIVES: To describe the clinical and magnetic resonance imaging features of cervical vertebral malformation-malarticulation in Bernese mountain dogs. METHODS: Seven Bernese mountain dogs (four males and three females) were diagnosed with cervical vertebral malformation-malarticulation by magnetic resonance imaging. The following data were evaluated retrospectively: (1) abnormalities of the cervical vertebral column and spinal cord, (2) spinal cord compression, (3) intervertebral disc degeneration and herniation, (4) severity of clinical signs pretreatment and after treatment, (5) type of treatment and (6) outcome. RESULTS: Spin echo T1-weighted and T2-weighted images disclosed multi-level, extradural compressive spinal cord lesions (ventral, dorsolateral or both) spanning from intervertebral disc spaces C3-4 to C6-7. In all seven dogs, T2-weighted images disclosed one or more intramedullary hyperintensities associated with extradural spinal cord compression. Surgery was performed in five dogs. Two dogs were managed medically. The prognosis for surgical or conservative management in Bernese mountain dogs was similar to cervical vertebral malformation-malarticulation in other breeds. CLINICAL SIGNIFICANCE: Cervical vertebral malformation-malarticulation is an important differential diagnosis for young to middle-aged Bernese mountain dogs with a C1-5 or C6-T2 neuroanatomic localisation. Dorsolateral spinal cord compression associated with articular process hypertrophy was the most common feature of cervical vertebral malformation-malarticulation in the seven Bernese mountain dogs evaluated.

Comparative efficacy of maropitant and selected drugs in preventing emesis induced by centrally or peripherally acting emetogens in dogs.

Maropitant (Cerenia; a novel, selective neurokinin(1) receptor antagonist), chlorpromazine, metoclopramide and ondansetron were compared in two randomized, placebo-controlled studies for efficacy in preventing emesis induced by emetogens acting centrally (apomorphine; Study 1) or peripherally (syrup of ipecac; Study 2) in dogs. In each study, ten male and ten female beagles were treated in a five-treatment, five-period crossover design. The five treatments were 0.9% saline (0.1 mL/kg), maropitant (1 mg/kg), metoclopramide (0.5 mg/kg), or chlorpromazine (0.5 mg/kg) all administered subcutaneously, or ondansetron (0.5 mg/kg) administered intravenously. One hour posttreatment dogs were challenged with apomorphine at 0.1 mg/kg intravenously (Study 1) or syrup of ipecac at 0.5 mL/kg orally (Study 2). Following emetogen challenge, dogs were observed for 30 min (Study 1) or 1 h (Study 2) for emesis. No clinical signs, other than those related to emesis, were observed. Efficacy of maropitant in preventing emesis induced centrally by apomorphine was not different (P > 0.05) from metoclopramide or chlorpromazine but was superior (P < 0.0001) to ondansetron. Efficacy of maropitant in preventing emesis induced by syrup of ipecac was not different (P > 0.05) from ondansetron but was superior (P

Safety and efficacy of injectable and oral maropitant, a selective neurokinin 1 receptor antagonist, in a randomized clinical trial for treatment of vomiting in dogs.

Maropitant (Cerenia), a selective neurokinin(1) receptor antagonist, was evaluated for safety and efficacy in treatment and prevention of acute vomiting due to various etiologies in dogs in a randomized clinical trial. Two-hundred seventy-eight dogs were enrolled from 29 veterinary hospitals. Two-hundred fifty-two were evaluable for efficacy, while 275 were evaluable for safety. A randomized block design was utilized (three maropitant- and one placebo-treated dog per block). Initial treatment was maropitant at 1 mg/kg body weight (0.45 mg/lb) or an equivalent volume of saline (placebo) administered subcutaneously. On the subsequent 1 to 4 days, maropitant or placebo (dependent on allocation) was administered subcutaneously or orally at approximate 24-h intervals as needed. Oral doses were administered as maropitant tablets using unit dosing to deliver a minimum dose of 2 mg/kg body weight (0.9 mg/lb) or equivalent numbers of similar placebo tablets. Dogs and housing were observed twice daily for evidence of vomiting. Emesis was significantly (P

An evaluation of dirlotapide to reduce body weight of client-owned dogs in two placebo-controlled clinical studies in Europe.

The clinical efficacy for weight loss and safety of dirlotapide in dogs were evaluated in two multi-centre studies with parallel designs. Overweight, adult dogs (n = 245) of various breeds were randomized to treatment with dirlotapide or placebo in a 2:1 ratio. Dirlotapide was administered orally once daily to dogs at an initial dose of 0.05 mg/kg/day commencing on day 0 and doubled after 14 days. Every 28 days, dogs were examined, weighed, body condition scores (BCS) were recorded, and dose was adjusted to meet weight loss targets. Each study comprised three consecutive phases: weight-loss (up to day 196); weight-stabilization (84 days); and post-treatment (28 days). pre-treatment feeding and exercise regimens were continued during treatment. Dirlotapide-treated dogs showed mean weight loss of 15.9% (study A) and 14.0% (study B) by the end of weight loss phase (up to day 196). Percentage weekly weight losses for dirlotapide were significantly greater than for placebo (P < or = 0.0002). Emesis and diarrhoea were experienced in both treatments but were more frequent with dirlotapide; resolution was spontaneous. BCS improved for 75.7-82.5% of dogs on dirlotapide treatment compared with 15.4-41.4% for placebo. Mean dirlotapide dosage at end of weight-loss phase was 0.38 (study A) and 0.29 (study B) mg/kg initial body weight/day. Dirlotapide was found to be clinically safe and effective in the reduction of body weight in overweight dogs.

Efficacy and safety of dirlotapide in the management of obese dogs evaluated in two placebo-controlled, masked clinical studies in North America.

Dirlotapide was evaluated in the management of obesity in dogs in two multicenter, clinical studies in North America. A total of 335 obese dogs of various breeds were randomized to dirlotapide or placebo in a 2:1 ratio. Dirlotapide was administered orally once daily to dogs at an initial dose of 0.05 mg/kg, increased after 14 days to 0.1 (study B, label dose) or 0.2 mg/kg (study A) and then adjusted according to individual weight loss at 28-day intervals. Dogs were examined and weighed, and body condition scores (BCSs) were recorded every 28 days. Study A had three consecutive phases: weight loss (16 weeks, day 0-112); weight management (12 weeks); and post-treatment (8 weeks). Study B had a weight loss phase only. For dirlotapide-treated dogs, mean weight loss by day 112 was 11.8-14.0% compared with 3.0-3.9% for placebo (P = 0.0001). In study A, weight losses for dirlotapide were 19.3% after 12 weeks of weight management and 16.7% (regain of 3.4%) by 8 weeks after dirlotapide was discontinued. In both studies, dogs in both treatments had emesis, lethargy, anorexia, diarrhea, and mildly elevated hepatic transaminase activity, that resolved spontaneously with time. These were experienced more frequently with dirlotapide. Improved activity levels and BCS for >50% dogs were reported with dirlotapide. Dirlotapide was safe and effective in the reduction and management of body weight in obese dogs.

Efficacy of ivermectin in a controlled release formulation against Psoroptes ovis (Hering, 1838) gervais, 1841 (Acari: Psoroptidae) on sheep.

Three trials including 42 sheep were conducted in Brazil or Germany to evaluate the therapeutic (two trials) and prophylactic (one trial) efficacy of an ivermectin controlled release capsule (CRC) against Psoroptes ovis infestation. In one therapeutic trial naturally infested sheep were used while in the other trials infestations were experimentally induced. In each trial half of the animals were treated on Day 0 with one ivermectin controlled release capsule that delivers ivermectin at a rate of 1.6 mg/day for approximately 100 days, that is 20 mcg/kg/day to a 80 kg animal, while the other half remained untreated. In both therapeutic trials mites were counted in skin scrapings and their presence was recorded at predilection sites one day before treatment and at weekly intervals from Day 7 to Day 56. In the trial conducted to evaluate the prophylactic efficacy the sheep were experimentally infested with P. ovis 21 and 28 days post-treatment and mites were counted and recorded at predilection sites on Days 42, 49 and 56. The ivermectin controlled release capsule was completely effective in eliminating the P. ovis mites within 28 days of administration and it prevented the establishment of an infestation of P. ovis induced 21 and 28 days after administration.

Efficacy of ivermectin in a controlled-release capsule for the control of breech strike in sheep.

OBJECTIVE: To investigate the efficacy of ivermectin in an intraruminal controlled-release capsule (CRC) against blowfly strike. DESIGN: Pen and field trials with controls. ANIMALS: Pen studies: Two breech strike trials involving 60 Romney and 60 Merino sheep. One body strike trial using 100 Merino sheep. Field trials: Eight trials in New Zealand used 1000 Romney and Romney-cross sheep. Fifty Merino lambs in one trial in Australia. PROCEDURE: Pen studies: Sheep were allocated to two equal groups. One was not treated, the other sheep received a CRC that delivered ivermectin at > or = 20 micrograms/kg/day for 100 days. In the breech strike trials, each animal was given an oral laxative 2 days before exposure to adult Lucilia cuprina. In the body-strike trial, the sheep sheep were kept wet to increase susceptibility prior to the release of blowflies. Field trials: Fifty or 200 sheep allocated to equal groups of nontreated or treated with the CRC and grazed at pasture exposed to natural blowfly challenge. RESULTS: Pen studies: Breech strikes developed in 24 of 60 controls but in none of 60 CRC-treated sheep. There was a 35% reduction in the number of CRC-treated sheep struck on the body. Field trials: The average number of breech strikes in CRC-treated sheep was reduced by 86% (P < 0.001). The number of body strikes in the treated groups was a reduced by 27% (P < 0.05). CONCLUSION: The ivermectin CRC is a useful aid in controlling breech strike, but provides only moderate reduction in the incidence of body strike.

Efficacy of an ivermectin controlled-release capsule against nematode and arthropod endoparasites in sheep.

Five controlled trials were conducted in Germany or in the United Kingdom, using 74 female sheep of merino or Dorset horn breeds, to evaluate the efficacy of an ivermectin controlled-release capsule against naturally acquired or induced infections of gastrointestinal nematodes, lungworms and nasal bot larvae and against incoming infections with gastrointestinal and pulmonary nematodes. Half of the animals were treated with one ivermectin controlled-release capsule that delivered ivermectin at the rate of 1.6 mg per day for 100 days while the other half remained untreated. Parasites were counted 21, 28, 35 or 56 days after administration of the capsule. The treatment was highly effective (> or = 99 per cent) against established parasites of the following species: Haemonchus contortus (adults and fourth-stage larvae), Ostertagia circumcincta, O pinnata, O trifurcata, Ostertagia species fourth-stage larvae, Trichostrongylus axei, T colubriformis, T vitrinus, Cooperia curticei, Nematodirus battus, N filicollis, Strongyloides papillosus, Chabertia ovina, Oesophagostomum venulosum, Trichuris ovis, Tr skrjabini, Dictyocaulus filaria, Protostrongylus rufescens and Oestrus ovis (larvae). The treatment prevented the establishment of the gastrointestinal nematodes H contortus, O circumcincta, T axei, T colubriformis, C curticei, N battus, N filicollis, Ch ovina, Oe vennulosum and the establishment of the lungworm D filaria by > 99 per cent compared with untreated controls (P < or = 0.01).

Field trials evaluating ivermectin controlled-release capsules for weaner sheep and for breeding ewes.

OBJECTIVE: To confirm the efficacy of ivermectin released from a controlled-release capsule administered to young sheep and to breeding ewes under field conditions. DESIGN: Randomised field trials. PROCEDURE: In each of ten field trials 25 weaned lambs were treated with ivermectin controlled-release capsules and 25 remained untreated. Eight similar field trials were conducted using adult ewes. Efficacy against infections of gastrointestinal nematodes was assessed by faecal egg counts and faecal larval culture. Body weights were recorded and faecal soiling of the breech wool (dags) was assessed. RESULTS: Nematode faecal egg counts in the two groups were not different (P = 0.13) before treatment in the weaner trials or before treatment in the ewe trials (P = 0.49), but thereafter eggs in the untreated sheep persisted, whereas counts in sheep given capsules were negligible (P < or = 0.01). In the weaner trials, dag scores for the two groups were not different at the start of the trials (P = 0.18) but at the end, untreated sheep had significantly more dags (P = 0.04) than treated sheep. In the ewe trials, dag scores remained low in both groups. Weaners treated with the capsule gained 1.4 kg (95% CL: 0.7, 3.1) more weight over the 16 week trial period compared to untreated weaners (P = 0.01). Both groups of ewes lost weight as a result of parturition but the mean loss by week 16 was greater for untreated (3.7 kg) (95% CL: -5.1, -2.2) than for treated ewes (1.8 kg) (95% CL: -3.3, -0.4). The mean change in ewe body weight for the two groups was however not significant (P = 0.07). Differentiation of nematode larvae recovered from cultures of faeces from untreated animals indicated that the capsules were effective against the common parasites of sheep. CONCLUSION: The capsule was efficacious against gastrointestinal nematodes judging from faecal egg counts. It has the potential to significantly reduce contamination of pasture with nematode eggs. Treated weaners had less dags for 16 weeks and gained more weight than untreated weaners.

Efficacy of eprinomectin against Hypoderma spp in cattle.

OBJECTIVE: To determine the efficacy of a topical formulation of eprinomectin against natural infestations of first (L1)-stage, and second and third (L2/L3)-stage larvae of Hypoderma spp. ANIMALS: 140 approximately 6- to 18-month-old cattle of various breeds. PROCEDURE: Cattle, selected from herds with high prevalence of Hypoderma infestation, were treated in 4 experiments: within each replicate, 1 animal received eprinomectin at a dosage of 500 micrograms/kg of body weight against first-stage larvae (L1). The second animal received the same treatment against second or third-stage larvae (L2/L3). The third animal served as an untreated control. In a fifth experiment, visible warbles were treated on half of the cattle. Remaining cattle served as vehicle-treated controls. In 1 experiment, warbles were examined from time of treatment until all lesions were resolved. In 4 experiments, emerging Hypoderma larvae were recovered, speciated, and enumerated, and viability was determined. RESULTS: Eprinomectin (500 micrograms/kg) efficacy was complete against L1. Hypoderma L2/L3 eradication approached 100% efficacy (1 live larva was recorded). Warbles in treated cattle resolved in a significantly shorter time than did those in controls. Adverse reactions related to treatment were not observed in any of the trials. CONCLUSIONS: Eprinomectin (500 micrograms/kg) applied topically was safe and highly efficacious for treatment of all larval stages of Hypoderma spp in these trials. CLINICAL RELEVANCE: Attributes of eprinomectin besides antiparasite efficacy allow treatment of all classes of cattle with no need for meat or milk withdrawal.

Efficacy of eprinomectin against mange mites in cattle.

OBJECTIVE: To determine whether eprinomectin was effective against mange caused by Chorioptes bovis and Sarcoptes bovis in cattle. ANIMALS: 80 cows naturally infested with C bovis and 30 cattle experimentally infested with S bovis. PROCEDURE: 6 trials were performed to determine efficacy against C bovis, and 2 trials were performed to determine efficacy against S bovis. In each trial, a group of untreated animals or of animals treated with vehicle alone was compared with a group of animals treated with a 0.5% formulation of eprinomectin applied topically (500 micrograms/kg). Number of mites in skin scrapings was determined prior to treatment and at weekly intervals for 8 weeks after treatment. Severity of skin lesions was evaluated when skin scrapings were obtained. In 5 trials, animals were weighed before and 56 days after treatment. RESULTS: Mite counts for treated cattle were significantly less than counts for control cattle from day 14 onwards in trials to determine efficacy against C bovis and from day 7 onwards in trials to determine efficacy against S bovis. Mites were not detected in scrapings collected from treated cattle on day 56. Mean weight gain of treated cattle was not significantly different from mean weight gain of control cattle in trials evaluating efficacy against C bovis but was significantly greater in trials evaluating efficacy against S bovis. CONCLUSION AND CLINICAL RELEVANCE: Eprinomectin was highly effective against C bovis and S bovis. Because eprinomectin can be administered to lactating cows, it may be useful for controlling mange in cattle.

Demonstration of the sustained anthelmintic efficacy of a controlled-release capsule formulation of ivermectin in weaner lambs under field conditions in New Zealand.

Ten field trials were conducted in the North and South Islands of New Zealand to evaluate the anthelmintic efficacy and production responses attributable to treatment of weaner lambs with an intra-ruminal controlled-release capsule formulation of ivermectin. A total of 800 Coopworth, Perendale and Romney lambs weighing on average 20.8-34.8 kg were used. Lambs were either untreated or treated shortly after weaning with an ivermectin controlled-release capsule which delivers ivermectin at 0.8 mg per day for 100 days (minimum dose rate 20 microg/kg/day). Bodyweights, faecal nematode egg counts and dag scores (assessment of faecal soiling in the breech area) were determined before treatment and at about 4,8, 12, 14 and 16 weeks after treatment. Sheep treated with the Ivermectin capsule gained significantly more weight (11.6 kg) over the 16 weeks of the trials compared to untreated sheep (7.3 kg) (p < 0.01). Before treatment, faecal strongylid and Nematodirus spp. egg counts were equivalent (p > 0.10) but, at each time point thereafter, egg counts in ivermectin capsule-treated sheep were significantly lower (p < 0.01 or p < 0.05). Dag scores were not different at the start of the trial (p > 0.10), but at the end of the trial control sheep had significantly greater dags (p < 0.05) than sheep treated with the ivermectin capsule. These findings indicate that treated animals contributed significantly fewer nematode eggs to the contamination of pasture and therefore pasture contamination should be significantly reduced for at least 112 days. The productivity of the ivermectin capsule-treated sheep over the I6 weeks of the trials was also significantly increased compared to salvage-treated controls. Furthermore, the presence of dags, which predispose sheep to blowfly strike in the breech area and result in production losses due to the costs of dagging and downgrading of breech wool, were also significantly (p < 0.05) reduced in the ivermectin capsule-treated sheep.

Demonstration of the sustained anthelmintic activity of a controlled-release capsule formulation of ivermectin in ewes under field conditions in New Zealand.

Ten field trials were conducted in the North and South Islands of New Zealand to evaluate the anthelmintic efficacy of an intraruminal controlled-release capsule formulation of ivermectin. A total of 810 Coopworth, Perendale, Romney or Coopworth ' Romney ewes, weighing on average 42-70 kg, were used. Ewes were either untreated or treated shortly before lambing in late winter-early spring (eight trials) or in late spring (two trials) with an ivermectin controlled-release capsule which delivers ivermectin at 1.6 mg per day for 100 days (minimum dose rate 20microg/kg/day). Bodyweights, faecal nematode egg counts and dag scores were determined before treatment and at about 2 and/or 4, 6 or 8, 10 or 12, 14 and 16 weeks after treatment. Ewes treated with the ivermectin controlled-release capsule gained on average 1.1kg more than untreated sheep over the 16 weeks of the trials, but this difference was not significant (p > 0.10). Before treatment, faecal strongylid egg counts were equivalent (p > 0.10), but at each time point thereafter, egg counts in ivermectin controlled-release capsule treated sheep were significantly lower (p < 0.01; p < 0.05 at Week 2). Dag scores were not different at the start of the trial (p > 0.10), but at the end of the trial ivermectin controlled-release capsule treated ewes had significantly lower scores (p < 0.01) than untreated ewes. These findings indicated that treated animals shed significantly fewer nematode eggs and therefore pasture contamination with nematode eggs should be significantly reduced for at least 112 days. The control of dags should result in reduced direct losses due to the decreased value of dag wool, and indirect losses due to the cost of dagging sheep and the cost associated with the treatment and control of flystrike initiated by dags in the breech area.

Nematocidal efficacy of eprinomectin, delivered topically, in naturally infected cattle.

OBJECTIVE: To assess the nematocidal efficacy of eprinomectin in naturally infected cattle. ANIMALS: 62 (31 eprinomectin-treated and 31 control) beef mixed-breed or Holstein cattle, either 6 to 11 or 48 to 96 months old. PROCEDURE: Cattle were housed 21 to 27 days before treatment to allow parasites to reach maturity. Animals were grouped by sex, ranked by weight, and randomly assigned to treatment group. Fecal flotation was done to identify cattle with intestinal nematode infections. Treatment groups were: 1--eprinomectin topical vehicle (1 ml/10 kg) and 2--eprinomectin topical solution (1 ml/10 kg). Cattle were euthanatized by replicate on day 14 or 15, and standard procedures were used to recover of pulmonary, abomasal, small intestinal, and large intestinal nematodes. RESULTS: Eprinomectin efficacy across all trials was 100% against adult Trichostrongylus axei, Haemonchus placei, Oesophagostomum radiatum, and Dictyocaulus viviparus, as well a fourth-stage larval Oes radiatum, Ostertagia ostertagi, Nematodirus helvetianus, and Cooperia spp. Efficacy against adult O ostertagi, Cooperia oncophora, C punctata, C surnabada, C spatulata, N helvetianus, Trichuris sp, and Trichuris fourth-stage larvae was 99.9 and 99.8, 99.6, 98.9, 98.3, 99.7, 97.8, and 84.3%, respectively. All results were significant (P < 0.01) except those for C spatulata. Adverse reactions were not observed. CONCLUSION AND CLINICAL RELEVANCE: Eprinomectin is a safe and effective nematocide against naturally acquired nematode infections in cattle when administered at a dosage of 500 micrograms/kg. Milk and meat withholding is not necessary when using this product.

Effect of simulated rain, coat length and exposure to natural climatic conditions on the efficacy of a topical formulation of eprinomectin against endoparasites of cattle.

A series of five controlled studies involving 114 cattle were conducted in Australia, North America and the United Kingdom to examine the effect of simulated rain, coat length and exposure to natural climatic conditions, on the efficacy of a topical formulation of eprinomectin against nematode parasites of cattle. In all trials infections were induced with a range of bovine nematode species and treatment was applied when the majority of nematodes were mature. In one study, simulated rain was applied to cattle ending one hour before treatment or beginning one, three or six hours after treatment. In a second study cattle had short (1 cm) or long (3-6 cm) haircoats at the time of treatment. Three other studies were conducted using cattle housed indoors or exposed to various natural climatic conditions. Nematode counts were determined using standard techniques and the efficacy of treatment was assessed relative to vehicle-treated controls. Regardless of the timing of simulated rain relative to treatment, eprinomectin was at least 99.9% effective (P < 0.01) against Haemonchus placei, Ostertagia ostertagi. Trichostrongylus axei and Cooperia spp. There were also no differences (p > 0.10) in efficacy between treatment administered to dry or wet cattle, or treatment administered before or after simulated rainfall. Efficacies against O. ostertagi, T. axei, Cooperia ancophora and Dictyocaulus viviparus were > 99.5% (p < 0.01) regardless of the length of the haircoat at the application site. Exposure of treated cattle to sunshine and precipitation had no effect on anthelmintic efficacy (p > 0.10) with efficacies of greater than 99.5% being maintained against H. placei, O. ostertagi (adult and fourth-stage larvae), T. axei, Cooperia spp., Nematodirus helvetianus (adult and inhibited fourth-stage larvae) and Oesophagostomum radiatum. These findings indicate that eprinomectin (500 micrograms/kg) in a topical formulation is a safe and highly effective nematocide for cattle regardless of their coat length and this high level of efficacy is maintained in cattle exposed to a wide variety of climatic conditions.

Efficacy of a pour-on formulation of eprinomectin (MK-397) against nematode parasites of cattle, with emphasis on inhibited early fourth-stage larvae of Ostertagia spp.

OBJECTIVE: To evaluate efficacy of topically applied eprinomectin against inhibited early fourth-stage larvae (IL4) of Ostertagia spp in calves. ANIMALS: 4 groups (n = 6 [replicates]) for dose titration; 2 groups (n = 8 calves [replicates]) for dose confirmation. PROCEDURE: 2 dose titration studies-0, 125, 250, and 500 micrograms of eprinomectin/kg of body weight-Louisiana and Georgia- and 2 dose confirmation studies of selected therapeutic dosage (500 micrograms/kg) in Scotland and France. Monitor calves were used to determine inhibition percentage of Ostertagia IL4. Test calves were ranked by weight in replicates of 4 (titration trials) or 2 (confirmation trials) animals each, and within replicates, were randomly allocated to treatment groups. Drug treatments were done on day 0, and animals were euthanatized by replicate, with holding time between treatment and euthanasia varying among trials from 14 to 27 days. RESULTS: Observations indicated high efficacy (> 99%) of 500 micrograms of eprinomectin/kg in removal of Ostertagia IL4. Ostertagia and Cooperia were only genera common across sites, with efficacy of aforementioned dosage against adult and larval stages of both genera consistently high (> 99%). Results of 1 or both titration studies (500 micrograms/kg) indicated > 99 to 100% efficacy against adult Haemonchus placei, Trichostrongylus axei, T colubriformis, Bunostomum phlebotomum, Dictyocaulus viviparus, and Oesophagostomum radiatum. Lower efficacy values were observed at minimal (125 micrograms/kg) dosage. In France, 500 micrograms/kg was 85% effective against Trichostrongylus spp adults; however, numbers of control calves infected with Trichostrongylus spp and degree of infection were low. Adverse reactions were not evident. CONCLUSION: Eprinomectin given topically (500 micrograms) was highly effective against Ostertagia IL4 and other common nematodes of cattle.

Control of gastro-intestinal parasitism in sheep with ivermectin delivered via an intraruminal controlled-release capsule.

The efficacy of ivermectin delivered by an intraruminal controlled-release capsule against gastro-intestinal nematodes of sheep was evaluated under controlled conditions. In seven Australian studies involving 170 Merino or Merino x Border Leicester sheep, intraruminal capsules developed for 20-40 kg or 40-80 kg sheep, and delivering 0.8 or 1.6 mg of ivermectin/day respectively for 100 days (minimum dose 20 microg/kg/day), were evaluated. Studies were designed to test the therapeutic efficacy against naturally acquired and induced infections treated at the adult and fourth larval stage, and the prophylactic efficacy against naturally acquired and induced infections with third stage infective larvae. The predominant pathogenic nematodes of sheep were represented. Two studies included known benzimidazole- and levamisole-resistant nematode strains. Sheep were necropsied for total nematode counts 21-8.5 days after treatment. The efficacy of the ivermectin controlled-release capsule was generally >99% against all nematode species tested, including those confirmed to be benzimidazole- and levamisole-resistant. High therapeutic activity was demonstrated against existing adult and fourth larval stage nematode infections at the time of treatment, and high prophylactic efficacy was shown against incoming third stage larvae of all species and strains tested.

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.

Efficacy of a topical formulation of eprinomectin against endoparasites of cattle in New Zealand.

Two controlled studies involving 24 cattle were conducted in New Zealand to determine the efficacy of a topical, non-flammable formulation of eprinomectin against induced and naturally acquired nematode infections. In Trial 1, nematode infections were induced on Day -5 with third-stage larvae of Cooperia spp., Haemonchus contortus, Ostertagia ostertagi and Trichostrongvlus colubriformis so that the nematodes would be at the fourth larval stage when the cattle were treated. In Trial 2, cattle had naturally acquired nematode infections as determined by faecal nematode egg counts and larval cultures. The cattle were allocated on Day 0 (Trial 1) or Day 6 (Trial 2) on a stratified random basis according to bodyweight to one of two treatments: untreated control or eprinomectin (0.5% w/v) applied topically at 1 ml/10 kg bodyweight. Necropsies were undertaken on Days 14 and 15 and total nematode counts were done. In Trial 1, cattle treated with eprinomectin had significantly (p < 0.05) fewer Cooperia spp. and O. ostertagi than the controls. Larvae of H. contortus and T. colubriformis did not establish. In Trial 2, cattle treated with eprinomectin had significantly (p < 0.05) fewer of the following parasites than the controls: Haemonchus spp. (adult), Cooperia surnabada (adult), C. oncophora (adult), Cooperia spp. (L,), Ostertagia lyrata (adult), O. ostertagi (adult), Oesophagostomum spp. (adult), T. avei (adult and L1) and Trichuris spp. (adult). Reductions of 100% were observed for Capilfaria spp. (adult), D. viviparus (adult and L,), and Nematodirus helvetianus (adult), but these were not statistically significant (p > 0.05) because four or fewer control animals were infected with these parasites. In Trial 2, efficacies of greater than 99% were observed against all species for which moderate to high burdens occurred in the untreated controls. These findings indicate that eprinomectin in a topical formulation is a highly effective nematocide in cattle.