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 injectable and pour-on formulations of moxidectin against lice on cattle

SUMMARY The efficacy of one administration of moxidectin against natural infestations of the 3 common species of cattle lice in Australia: Linognathus vitull, Damallnla bovls and Haematoplnus eurysternus, was determined. A high degree of control of L vituli (too long-nosed sucking louse) was achieved with both the cattle Injection (96.7% and 100%) at 0.2 mg/kg and the cattle pour-on formulation (94.6% and 100%) at 0.5 mg/kg on the 2 farms where this louse occurred. An Injection of moxidectin at 0.2 mg/kg did not eliminate D bovis. In these trials efficacy ranged from nll to 85.2%. In contrast the pour-on formulation at 0.5 mg/kg provided consistently high efficacy (83.6 to 100%) against D bovis on 3 farms. Infestations of H eurysternus (the short-nosed sucking louse) were low and no significant difference was recorded between treatment groups In a single trial, however, lice persisted on 3 to 7 cattle In the untreated group at each Inspection, whereas none were found on any animals in the 2 groups treated with moxidectin on Inspection after treatment.     

Efficacy of moxidectin 0.5% pour-on against swine nematodes

Forty pigs with induced infections of Ascaris suum, Trichuris suis, Metastrongylus spp., Oesophagostomum dentatum and O. quadrispinulatum were assigned to five-dose groups of moxidectin 0.5% pour-on with eight pigs per dose group. The doses were: moxidectin, 0 (vehicle control), 0.75, 1.00, 1.25, and 1.50 mg/kg(-1) body weight. Worm egg counts (EPG) were made from fecal samples collected on Day 2 pretreatment and on Day 14 or 15 post-treatment. Animals were ranked according to the descending order of A. suum egg counts made on Day 2 and blocked in groups of five. Pigs in blocked groups were assigned randomly to each of the five dose groups. Treatment doses were calculated on the basis of weights taken on Day 1 and were administered topically from the neck to the base of the tail. Pigs were housed by pairs in individual pens provided with self-feeders and automatic waterers. Necropsies were performed on equal numbers of pigs from each treatment group on days 14 and 15 post-treatment. Adult and larval worms were collected, identified and counted by standard parasitological techniques. All counts were transformed by Y=log10 (count+1) transformation prior to analysis. A two-way analysis of variance was conducted and treatment effect was tested for significance at the 5% level. Efficacies based on geometric means and optimal doses were as follows: Ascaris suum, 98.3% at 1.25; Metastrongylus spp., 100% at 0.75; Oesophagostomum quadrispinulatum, 100% at 1.50; and Trichuris suis, 93.5% at 0.75. Efficacy for O. dentatum was from 81.3% to 100%; however, the average number of O. dentatum (30) was too small for significance. Two species of lungworms were present, Metastrongylus apri and M. pudendotectus but they were not speciated at necropsy. As reported for several anthelmintics, the efficacy of moxidectin was variable for Trichuris. The highest efficacy was in the 0.75 dose group with six pigs harboring a few or no worms. The lowest efficacy was in the 1.25 group with only two pigs harboring a few or no worms.     

Field efficacy of injectable and pour-on moxidectin in cattle naturally infested with Psoroptes ovis (Acarina: Psoroptidae).

Field efficacy of moxidectin, a macrocyclic lactone endectocide, was evaluated in cattle naturally infested with Psoroptes ovis. Three groups of six animals were used based on parasitological and clinical status. Group 1 animals received one subcutaneous injection of injectable moxidectin at 0.2 mg kg-1 body weight; Group 2 animals received topically one dose of 0.5 mg kg-1 body weight of pour-on moxidectin; Group 3 individuals remained untreated as controls. Efficacy was assessed by (a) taking skin samples from each animal on Days -4, 14, 28, 42 and 56 post-treatment (PT) and observing numbers of viable mite stages and species and (b) clinical examination of animals on Days 14, 28, 42 and 56 with the percentage of affected body surface calculated for each animal on Days -4, 28 and 56. Both formulations gave 100% efficacy as no live mites were found in Groups 1 or 2, 14, 28 and 56 days after treatment. Clinical indices showed a sharp decrease in the affected body surface area from a mean of 5.48% and 6.1% on Day -4 in Groups 1 and 2, respectively, to 0% in both groups on Days 28 and 56 PT. All untreated animals remained positive until Day 28. The clinical condition of the controls worsened rapidly during the experiment (mean clinical index: 2.87% and 13.05% on Days -4 and 28, respectively) and they were given an emergency treatment on Day 28. No side-effects were observed with either formulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Osteochondrosis associated with copper deficiency in young farmed red deer and wapiti x red deer hybrids

Osteochondrosis is reported in association with copper deficiency in young red deer and wapiti X red deer hybrids on eight deer farms throughout New Zealand. On two farms, more than 30% of fawns were affected. Affected animals were lame, often had one or more swollen joints, and in some cases had an abnormal "bunny-hopping" gait or "cow-hocked" stance. Lesions were most common in the carpal, tarsal, stifle and hip joints, and were usually bilateral. Defects in articular cartilage ranged from loose flaps to complete separation with exposure of subchondral bone and the presence of cartilage fragments within the joint space. In advanced cases, the joints had features of degenerative arthropathy. Bilateral epiphyseolysis of the femoral head was observed in some severely lame deer. All deer with osteochondrosis had low serum and/or liver copper concentrations.     

Osteochondrosis associated with copper deficiency in young farmed red deer and wapiti x red deer hybrids

Osteochondrosis is reported in association with copper deficiency in young red deer and wapiti x red deer hybrids on eight deer farms throughout New Zealand. On two farms, more than 30% of fawns were affected. Affected animals were lame, often had one or more swollen joints, and in some cases had an abnormal “bunny-hopping” gait or “cow-hocked” stance. Lesions were most common in the carpal, tarsal, stifle and hip joints, and were usually bilateral. Defects in articular cartilage ranged from loose flaps to complete separation with exposure of subchondral bone and the presence of cartilage fragments within the joint space. In advanced cases, the joints had features of degenerative arthropathy. Bilateral epiphyseolysis of the femoral head was observed in some severely lame deer. All deer with osteochondrosis had low serum and/or liver copper concentrations.     

Observations of a long-acting formulation of oxytetracycline in red deer (Cervus elaphus)

Six nine-month-old red deer were injected intramuscularly with a long-acting injectable solution of oxytetracycline (Terramycin-LA, Pfizer Ltd) at a dose rate of 20 mg/kg. Four similar control deer were injected with saline. There was no significant pain response to injection, and only minor palpable swellings at the injection site were observed in three oxytetracycline-treated and one control animal. No statistically significant changes in white blood cell numbers, blood fibrinogen, creatine phosphokinase or glutamic oxaloacetic transaminase concentrations occurred as a result of oxytetracycline administration up to seven days after injection. Mean plasma oxytetracycline concentration reached a peak (4.68 mg/l) two hours after injection and declined to levels below assay sensitivity (0.3 mg/l) in five deer 72 hours after injection, and in all deer by 96 hours after injection. No gross lesions at the injection site were observed at slaughter 30 days after injection. There were traces of oxytetracycline at the injection site muscle of two deer after 30 days, but residues were not detected in injection site muscle from the other four deer, or in any of the liver, kidney or other muscle specimens.     

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

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

Breed differences on the plasma availability of moxidectin administered pour-on to calves

The pharmacokinetic profile of avermectin and milbemycin compounds is affected by different drug- and host-related factors. This work reports the influence of cattle breeds on the plasma kinetics of moxidectin (MXD) after topical (pour-on) administration. Parasite-free Aberdeen Angus and Holstein calves were treated with a commercial MXD pour-on formulation at 500 microg/kg. Blood samples were collected over a period of 35 days post-treatment and the recovered plasma was analysed by high performance liquid chromatography using fluorescence detection. MXD was detected in plasma from two hours up to 35 days post-treatment in animals from both breeds. A slow MXD absorption and delayed peak plasma concentration were observed in Aberdeen Angus compared to Holstein calves. Significant lower systemic availability (expressed as AUC) (P<0.01) and peak plasma concentration (C(max)) (P<0.05) were also observed in Aberdeen Angus calves, although the plasma mean residence time (MRT) and elimination half-lives (T(1/2el)) of MXD in both breeds were similar. The pharmacokinetic differences observed between cattle breeds contribute to explain the variability in the pattern of clinical efficacy for pour-on administered endectocide compounds reported in different field trials.     

Efficacy of moxidectin injectable and pour-on formulations in a pilot control program against bovine hypodermosis in Southern Italy

Bovine hypodermosis is a myiasis caused by Hypoderma bovis and Hypoderma lineatum (Diptera, Oestridae) larvae, which has a severe economic impact on the livestock industry. Though myiasis is widespread throughout Italy, no nationwide eradication program has ever been planned, unlike in other European Countries. With a view to setting up a national control program, a pilot study was carried out in Southern Italy on 9939 cattle bred in an area with a high prevalence of cattle hypodermosis, using moxidectin 0.5% pour-on (Cydectin, Fort Dodge) and 1% injectable (Cydectin, Fort Dodge) formulations. At the recommended dosage, moxidectin displayed efficacy levels of 99.9% in the pour-on and 100% in the injectable formulation, whereas the microdose (1 mg per head regardless of body weight) was less effective (65.7%). This trial contributed to a significant reduction in infestation rates in the study area and represented the first step through which a national program for eradicating warble fly infestation in Italy.     

Pharmacokinetics assessment of moxidectin long-acting formulation in cattle

The plasma kinetics disposition of moxidectin following a subcutaneous administration with a long-acting formulation (Cydectin) 10%, Fort Dodge Animal Health, France) at the recommended dose of 1 mg kg(-1) body weight was evaluated in Charolais cattle breed (five females weighing 425-450 kg) for 120 days. Furthermore, its concentration was measured in hair for the same period. After plasma extraction and derivatization, samples were analysed by HPLC with fluorescence detection. Moxidectin was first detected at 1 h after treatment for plasma (2.00+/-1.52 ng ml(-1)) and at 2 days for hair (446.44+/-193.26 ng g(-1)). The peak plasma concentration (C(max)) was 55.71+/-15.59 ng ml(-1) and 444.44+/-190.45 ng g(-1) for plasma and hair, respectively. The mean calculated time of peak occurrence (T(max)) was 3.40+/-3.36 and 2 days for plasma and hair, respectively. The mean residence time (MRT) was 28.93+/-2.87 and 13.32+/-2.48 days for plasma and hair cattle. The area under concentration-time curve (AUC) was 1278.95+/-228.92 ng day ml(-1) and 2663.82+/-1096.62 ng day g(-1) for plasma and hair, respectively. At the last sampling time (120 days), the concentration was 1.91+/-0.26 ng ml(-1) and 0.69+/-0.52 ng g(-1) for plasma and hair, respectively. The bioavailability of this long-acting formulation of moxidectin is similar to that registered after subcutaneous administration of moxidectin in cattle at 0.2 mg kg(-1) body weight. For the first time the moxidectin pharmacokinetics parameters in hair after a subcutaneous administration was described. The moxidectin profile concentrations in hair reflected that registered in plasma. The previous studies of efficacy have to be correlated to the extended period of absorption and distribution by the LA formulation due to the fivefold higher dose rate in comparison with the 1% injectable formulation (0.2 mg kg(-1) body weight).     

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.     

A pilot study of the efficacy of topical ivermectin against lungworm in young red deer (Cervus elaphus)

Three groups of ten 4-month-old red deer (Cervus elaphus) calves naturally infected with lungworm (Dictyocaulus viviparus) were treated with either oral ivermectin (200 microg/kg), topical (pour-on) ivermectin (500 microg/kg) or oral oxfendazole (5 mg/kg). Faecal larval counts for lungworm were undetectable or very low for 14 days after treatment with oxfendazole, 28 days after treatment with oral ivermectin and for 49 days after treatment with topical ivermectin. This pilot study suggests that the topical formulation of ivermectin was very effective against lungworm and had a more persistent action than the oral ivermectin formulation in young red deer.     

Selenium supplementation of young red deer (Cervus elaphus)

Abstract

Two selenium (Se) supplementation trials were conducted in successive years involving a total of 70 red deer calves 3–15 months of age grazing pasture containing 30–57 ppb of Se on a dry matter basis. The trials compared growth rate, whole blood Se and glutathione peroxidase (GSHpx) concentrations of calves which received periodic doses of oral Se or a single injection of barium selenate (equivalent to 50 mg Se) or no Se supplementation. There were no significant weight gain differences between treated and untreated groups in either trial. Whole blood GSHpx levels were strongly correlated with blood Se levels (r = 0.9278) and produced the following regression equation: GSHpx 0.0155 Se ? 2.292.

In both years the 3 month old calves had GSHpx levels of 6–9 kU/l which probably derived from maternal transfer of Se. The GSHpx levels in unsupplemented calves declined from these levels to a minimum in winter (group means ? 2.6) and then progressively rose the following spring and summer.

Periodical oral dosing with Se or a single injection of barium selenate significantly elevated blood Se and GSHpx levels throughout the trials.     

Selenium supplementation of young red deer (Cervus elaphus)

Two selenium (Se) supplementation trials were conducted in successive years involving a total of 70 red deer calves 3-15 months of age grazing pasture containing 30-57 ppb of Se on a dry matter basis. The trials compared growth rate, whole blood Se and glutathione peroxidase (GSHpx) concentrations of calves which received periodic doses of oral Se or a single injection of barium selenate (equivalent to 50 mg Se) or no Se supplementation. There were no significant weight gain differences between treated and untreated groups in either trial. Whole blood GSHpx levels were strongly correlated with blood Se levels (r = 0.9278) and produced the following regression equation: GSHpx = 0.0155 Se - 2.292. In both years the 3 month old calves had GSHpx levels of 6-9 kU/I which probably derived from maternal transfer of Se. The GSHpx levels in unsupplemented calves declined from these levels to a minimum in winter (group means approximately 2.6) and then progressively rose the following spring and summer. Periodical oral dosing with Se or a single injection of barium selenate significantly elevated blood Se and GSHpx levels throughout the trials.     

Dose confirmation of moxidectin pour-on against natural nematode infections in lactating dairy cows.

The nematocidal effectiveness of moxidectin, administered topically at the rate of 500 mcg/kg BW, was determined for lactating dairy cows. Naturally infected animals were given either topical vehicle or moxidectin (Cydectin Pour-On Fort Dodge Animal Health) at the rate of 1 ml/10 kg BW (10 animals per treatment group), and sacrificed 14-18 days post-treatment for nematode enumeration. 100% efficacies were recorded for Ostertagia lyrata males, Cooperia punctata males and Oesophagostomum radiatum L4, with treatment group differences in geometric means significant (P < 0.05) for all. Populations of Trichostrongylus L4 and adult O. radiatum were also reduced by 100%, but low prevalence rates in the control animals precluded meaningful statistical inference. Nematode populations for which efficacies ranged from 96.7 to 99.6% (based on geometric means) and for which treatment group differences were significant (P < 0.05) included Ostertagia spp. adult females, inhibited L4 and developing L4, O. ostertagi adult males, Trichostrongylus axei adults and Cooperia spp. adult females. For all nematodes combined, moxidectin was 98.9% efficacious. In addition to exhibiting excellent nematocidal effectiveness, topical moxidectin was demonstrated to be safe, with animal health and milk production unaffected during the study.     

A detailed assessment of the pattern of moxidectin tissue distribution after pour-on treatment in calves

The use of topical (pour-on) administration of endectocide drugs in cattle has reached world-wide acceptance. However, only limited information is available on the kinetic behaviour for topically administered moxidectin (MXD). To improve our understanding of the relationship between pharmacokinetics and efficacy for pour-on preparations, MXD concentration profiles were measured in tissues of endo- and ectoparasites location over 35 days postadministration. MXD distribution to the fluid content and mucosal tissue of the abomasum and different intestinal sections (duodenum, ileum, caecum and colon) was assessed. The comparative patterns of MXD distribution to skin and hypodermic tissue from different anatomical sites (backline, rib cage, thigh and face) were also investigated following the pour-on administration. Wide tissue distribution and long residence time characterized the kinetics of topically administered MXD. MXD was recovered between 1 and 35 days post-treatment in all the tissues investigated. The highest MXD availabilities were observed in the skin layers at the site of administration (backline) and in the fat tissue. The fluid contents of different intestinal sections showed MXD concentrations higher than those measured in their respective mucosal tissues, particularly at day 1 post-treatment. MXD concentrations in the skin (epidermis + dermis) were higher than those measured in the hypodermic tissue. Large differences in the availability of MXD in skin from different anatomical regions (backline > rib cage > thigh > face) were observed. The low plasma and the high skin availability indicate the formation of a skin depot of the drug, being released slowly to the plasma and reaching concentrations in systemic tissues (abomasal mucosa, lungs, etc.) similar to those measured after subcutaneous administration. These findings demonstrate that target parasites may be exposed to markedly different drug concentrations according to their location sites, which is particularly relevant for ectoparasites located in different anatomical regions. Knowledge of the tissue distribution of topically administered endectocides contributes to understand the differences observed in efficacy and/or persistence of activity and to optimize their use in cattle.