The effects of ivermectin and moxidectin on egg viability and larval development of ivermectin-resistant Haemonchus contortus

The in vivo effects of ivermectin and moxidectin on egg viability and larval development of ivermectin-resistant Haemonchus contortus were examined over time after anthelmintic treatment of sheep. Twenty merino sheep, (12 months old) were allocated to five treatment groups and infected with ivermectin-resistant H. contortus. Thirty one days later, the sheep were treated with intraruminal ivermectin capsules, oral ivermectin, oral moxidectin or injectable moxidectin at the manufacturer's recommended dosages, or left untreated. At various times up to 112 days after treatment, faecal egg counts (FEC) were determined and development rates of infective larvae (L3) cultured in faeces or on agar were measured. Eggs in faecal cultures from ivermectin capsule treated sheep showed reduced L3 development percentages in comparison to faecal cultures from untreated sheep. Eggs from ivermectin capsule treated sheep, isolated from faeces, and cultured on agar showed similar L3 development to eggs from control sheep. These results demonstrate an inhibitory effect of excreted ivermectin in faeces on larval development of ivermectin-resistant H. contortus. L3 development in faecal culture from animals receiving oral ivermectin were reduced for only 3 days after treatment. Faecal egg counts and development of L3 larvae in both culture systems from moxidectin treated sheep were low, due to the high efficacy of the drug. Egg counts in moxidectin treated sheep were reduced by approximately 90% 24h after treatment, before decreasing to almost 100% at 48h, suggesting that the current quarantine recommendation of holding sheep off pasture for 24h after treatment may still lead to some subsequent pasture contamination with worm eggs.     

Evidence for multiple anthelmintic resistance in sheep and goats reared under the same management in coastal Kenya

Four experiments, two with sheep and two with goats, were carried out to determine the efficacy of ivermectin, fenbendazole, levamisole, closantel and some of their combinations by faecal egg count reduction tests. In the first experiment, injectable ivermectin, oral ivermectin, fenbendazole and levamisole were tested in 6-month-old lambs, and their reduction percentages were 77%, 13%, 42% and 92%, respectively. In the second experiment, with yearling sheep, the reduction percentages were 35% for injectable ivermectin, 32% for fenbendazole, 99% for levamisole, 48% for closantel, 92% for injectable ivermectin combined with fenbendazole, 99% for injectable ivermectin combined with levamisole, and 100% for fenbendazole combined with levamisole. In the study with 18-month-old goats given the same dose rates as those recommended for sheep, the reduction percentages were 73% for injectable ivermectin, 25% for fenbendazole, and 78% for levamisole. Another group of 14-month-old goats was treated with dose rates 1.5 times those recommended for sheep and the reduction percentages were 93% for levamisole, 92% for injectable ivermectin, and 97% for a combination of levamisole and ivermectin. In all experiments with sheep and goats the gastrointestinal nematode parasites identified by larval cultures were Haemonchus contortus, Trichostrongylus spp. and Oesophagostomum spp. The gastrointestinal nematodes of both sheep and goats on this farm are resistant to ivermectin and fenbendazole, whereas levamisole is still effective in sheep, but not in goats. The results are discussed in relation to the farm as a source of breeding stock to smallholder farmers and its potential to spread anthelmintic resistance.     

Impact of dung from ivermectin-treated sheep on oogenesis and survival of adult Lucilia cuprina

Females of the Australian sheep blowfly, Lucilia cuprina, exploit sheep dung as a source of protein for egg development. Flies fed on dung collected from sheep 1 to 6 days after being drenched with the broad-spectrum antiparasitic drug ivermectin showed delayed reproductive development and reduced fecundity. Male and female survival was also reduced. Despite these effects, except where the recommended frequency of drenching (1 to 4 times per annum) is greatly exceeded, it is unlikely that ivermectin residues will affect any useful reduction in blowfly populations.     

Reduced efficacy of ivermectin, abamectin and moxidectin against field isolates of Haemonchus contortus

OBJECTIVES: To investigate the reduced efficacy of ivermectin, abamectin and moxidectin against two field isolates of Haemonchus contortus. These isolates were identified on separate properties in the New England region of New South Wales. PROCEDURE: Reduced efficacy of macrocyclic lactone anthelmintics against two field isolates of H contortus was suspected. These isolates were obtained from sheep on separate farms and pen trials were performed to investigate the efficacy of macrocyclic lactones. The percentage efficacy was calculated for moxidectin, ivermectin and closantel against the isolate from one farm (VHR23) and for moxidectin, ivermectin and abamectin against the isolate from the second (VHR29). The persistent activity of moxidectin against both isolates was investigated. RESULTS: Ivermectin and closantel were found to have efficacies below 80% against established populations of VHR23. Moxidectin was effective against an established population of VHR23 but the persistent activity was reduced to 7 days. Moxidectin was also found to be effective against established populations of VHR29, however, ivermectin and abamectin were found to have efficacies below 80%. There was no evidence of persistent activity of moxidectin against VHR29. CONCLUSION: A reduction in efficacy of abamectin and/or ivermectin against field isolates of H. contortus was identified from two farms in the New England region of New South Wales. The persistent effect of moxidectin was reduced against both isolates.     

Efficacy of ivermectin delivered via a controlled-release capsule against small lungworms (Protostrongylidae) in sheep

To evaluate the efficacy of an ivermectin controlled-release capsule (CRC), which delivers 1.6 mg ivermectin per day intraruminally for 100 days to sheep weighing 40-80 kg (IVOMEC Maximizer CR Capsule for adult sheep, Merial), against small lungworms two studies with 48 naturally infected adult female Merino Landrace sheep were conducted. The sheep were allocated by restricted randomization based on bodyweight to untreated controls or received an ivermectin CRC. Eight sheep per group were necropsied 35, 70 or 105 days post-treatment. Lungworms were recovered by dissection or peptic digestion of the lungs. Baermann/Wetzel technique was used for faecal lungworm larval counts at weekly intervals. The efficacy of treatment was 100% against Dictyocaulus filaria and Protostrongylus rufescens (P < 0.05) at each necropsy day. The efficacy against Protostrongylus brevispiculum, Cystocaulus ocreatus and Neostrongylus linearis increased from 35 to 105 days after administration of the CRC and was found to be 100% (P < 0.01), 96.6% (P < 0.01) or 99% (P < 0.01), respectively, at 105 days post-treatment. The reductions of Muellerius capillaris counts varied and were 96.2% (P < 0.05) at 70 days post-treatment and 44.6% (P > 0.1) at 105 days post-treatment. Faecal lungworm larvae disappeared nearly completely from at least 3 weeks after the ivermectin CRC administration for all protostrongylid species including M. capillaris so that pasture infectivity will be subsequently significantly reduced.     

Does closantel in therapeutic doses display thyroid hormone‐like activity in sheep?

The aim of this study was to define the thyroid hormone‐like activity of closantel in sheep by measuring some blood parameters that are known to be influenced by thyroid hormones triiodothyronine (T3) and thyroxine (T4). Our hypothesis was that, if closantel possesses thyroid hormone‐like activity, its use under in vivo conditions will result in changes similar to those in hyperthyroidism. The study was conducted in 20 Jezersko‐Solchava breed sheep. Blood sampling was performed before and 10 days after routine anthelmintic treatment with closantel. Complete blood count, plasma cholesterol, triglycerides, protein, and albumin levels, as well as those of serum T3 and T4, were compared before and 10 days after closantel administration. This routine anthelmintic treatment of sheep with closantel did not significantly influence hematological parameters, thyroid hormone levels, or most of the biochemical parameters. No evidence was found for thyroid hormone‐like activity of closantel in sheep. However, significantly (P < 0.01) elevated levels of plasma triglycerides were present 10 days after closantel administration.     

Efficacy of ivermectin jetting fluid against strike by some primary and secondary blowflies of sheep

SUMMARY Merino sheep, which were hand jetted with ivermectin jetting fluid, and untreated sheep were challenged with larval implants of Lucilia cuprina, Lucilia sericata, Calliphora noclva and Chrysomya ruflfacles at intervals of about 2 weeks from 6 to 16 weeks after treatment. Both Lucilia species produced strike rates of about 90% in untreated sheep; the respective rates were lower for Chr rufifacies (55%) and C nociva (60%). Strike rates for the treated group were about 17, 11, and 9% for L cuprina, L sericata, and Chr rufifacies, respectively. Only 1 implant site in the treated group was struck by C nociva. Treated sheep had significantly (P < 0.01) longer time to first strike than did untreated ones for each species of fly. L sericata, Chr rufifacies, and C nociva larvae implanted on treated animals had significantly (P < 0.05) longer time to first strike than did L cuprina larvae.     

The survival and fecundity of buffalo flies after treatment of cattle with three anthelmintics

Two anthelmintics with known insecticidal action (ivermectin and closantel) and one with no recorded effect on insects (levamisole) were tested to evaluate their effects on buffalo fly (Haematobia irritans exigua). Blood from animals given closantel or levamisole had no significant effect on mortality of buffalo flies in an in-vitro assay. In contrast, blood from animals given ivermectin showed a dose-dependent effect on the mortality of buffalo flies. At 24 h after one injection of the recommended dose of ivermectin, 98% of the flies applied to cattle in an in-vivo assay are killed. Blood from cattle injected with ivermectin killed 95% of flies 8 d after injection and still killed 15% of flies at 18 days after injection. Surviving flies laid almost no eggs and this effect on flies was significant up to 33 d after injection. The results indicate that ivermectin may be useful to control buffalo fly populations in the field.     

Field trials with closantel and Haemonchus contortus in sheep in Papua New Guinea

Sheep treated once with closantel at 7.5 or 15.0 mg/kg and grazing with untreated sheep remained free of Haemonchus contortus for at least 4 to 5 weeks and 6 to 7 weeks respectively after treatment. When the whole flock was treated with 15.0 mg/kg, H. contortus began to become re-established 7 to 8 weeks later. Maximum benefit of the residual anthelmintic effect of closantel against H.contortus was obtained only when all sheep in the flock were treated; it took 10 weeks longer for H.contortus to form 50% of larval cultures when the whole flock was treated than when only a part of the flock was treated.     

The negative effects of the residues of ivermectin in cattle dung using a sustained-release bolus on Aphodius constans (Duft.) (Coleoptera: Aphodiidae)

This paper reports the findings of two trials into the effects of the treatment of cattle with ivermectin slow-release (SR) bolus on the larval development of the dung beetle Aphodius constans Duft. Rectal faecal samples were collected prior to treatment and every 3 and 2 weeks in a first and second trial, respectively, and up to 156 days post-administration of the SR bolus. Faecal ivermectin concentration reached a peak at 63 days post-treatment (1427 ng g(-1)) and ivermectin was detected up to 147 days post-treatment in the first trial (7.2 ng g(-1)). First stage larvae of A. constans were reared with control or contaminated dung and adult beetles were counted after emergence. In the first trial, the comparison of pairwise samples showed that ivermectin prevented the development of larval A. constans until day 105, while at day 135 the rate of emergence was still significantly lower than the corresponding series of control (p < 0.05). In the second trial, the difference between control and treated series remained significant until 143 days post-treatment, with no emergence until 128 days post-administration of SR bolus to cattle. These results show the negative effect of ivermectin on the development of larval A. constans, even at a low concentration (38.4 ng g(-1)). The administration of ivermectin sustained-release bolus to cattle was highly effective in killing dung beetle larvae for approximately 143 days after treatment. The results were similar when dung was obtained from a single animal kept alone, or from a blending of faecal pats obtained from a group of animals kept in field conditions during the whole trial period.     

Efficacy of ivermectin jetting fluid for the curative treatment of blowfly strikes in sheep

SUMMARY A jetting fluid containing 7.5% w/v ivermectin, which was diluted to 0.03 mg/mL in water and applied using a standard hand jetting technique, was assessed for its efficacy in treating blowfly strikes on Merino sheep. Strikes were induced on sheep held under insectary conditions using laboratory-reared Lucilia cuprina. All struck sheep jetted at 28,48 or 72 hours after exposure to flies were successfully treated. All 1st, 2nd and early 3rd instar larvae were killed within 24 hours of treatment.     

Pharmacokinetics of a novel closantel/ivermectin injection in cattle

Two studies are described on the pharmacokinetics of a combination anthelmintic consisting of ivermectin and closantel for use in cattle. In the first, the pharmacokinetics of both active drugs in the combination were compared with the formulation with either ivermectin or closantel removed. No differences in the pharmacokinetics were observed, indicating that neither the absorption nor distribution of ivermectin or closantel in the combination were influenced by the presence of the other. In the second study the pharmacokinetics of ivermectin and closantel in the combination product were compared with control formulations of each. No difference was found between the closantel formulations. With ivermectin it was noted that absorption and excretion were more rapid and Cmax higher in the combination, although the AUC of both formulations were not significantly different.     

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.     

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 20 μg/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.     

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.     

MULTIPLE AND MULTIGENERIC ANTHELMINTIC RESISTANCE ON A SHEEP FARM IN KENYA

The anthelmintic efficacy of benzimidazoles (albendazole, fenbendazole and oxfendazole), levamisole, oral ivermectin and closantel was evaluated on a farm in Kenya using faecal egg count reduction test, larval cultures and a controlled slaughter trial. The results of this study indicated simultaneous resistance of Haemonchus contortus against benzimidazoles, levamisole and ivermectin, and of Trichostrongylus colubriformis and Oesophagostomum spp. against levamisole on the same farm. Ivermectin resistance developed to 47% within 15 months of first use. Closantel was effective against the benzimidazoles, levamisole and ivermectin resistant H. contortus.     

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.     

Effect of ivermectin and oxfendazole on shedding of larvae of the lungworm (Dictyocaulus viviparus) by red deer (Cervus elaphus)

Thirty eight newly weaned hinds were randomly allocated to one of two equal groups. One group received ivermectin, the other, oxfendazole at dose rates of 0.2 mg/kg and 4.5 mg/kg, respectively. All deer were drenched four times and were grazed on pasture. Both anthelmintics reduced D. viviparus faecal larval counts to low levels 20 days after dosing, but the mean larval output and the proportion of deer shedding D. viviparus larvae at 27 and 33 days after treatment, were significantly lower in the ivermectin treated group. There was no significant difference in weight gain between the two groups throughout the trial. This study suggests that ivermectin prevents reinfection with D. viviparus for approximately 14 days longer than oxfendazole.     

Activity of closantel in the prevention of Gasterophilus and Strongylus vulgaris larval infections in equine foals and yearlings

Two controlled tests were conducted in equine foals and yearlings to determine the optimal oral dosage and the duration of activity of closantel for the prevention of Gasterophilus spp larval infections. Additional data were collected on the activity of closantel against Strongylus vulgaris larval infections. In experiment 1, 12 foals and 12 yearlings were equally allocated to 4 experimental groups, and were given oral treatments with closantel at dosages of 0 (nontreated controls), 2, 5, or 8 mg/kg of body weight every 2 months during bot season. The foals and yearlings were allowed to graze on open pasture throughout the experiment to provide a natural source for bot and helminth infections. All animals were euthanatized and necropsied 6 weeks after the final treatment. Closantel was highly effective (98.6% to 100%) at all doses in preventing Gasterophilus spp larval infections in the foals, but only the 8 mg/kg dose had significant (P less than 0.05) activity (99.7%) in the yearlings. This dose also significantly reduced the numbers of 4th-stage and immature adult S vulgaris (86.0%) in the mesenteric arteries as compared with nontreated controls. In experiment 2, 9 foals and 9 yearlings received a single oral treatment of 8 mg of closantel/kg of body weight; 3 foals and 3 yearlings were kept as nontreated controls. Groups of 6 treated (3 foals, 3 yearlings) and 2 control (1 foal, 1 yearling) animals were euthanatized and necropsied 1, 2, and 3 months after treatment. Closantel remained effective for 2 months in preventing infections of G intestinalis larvae in these foals and yearlings. Clinical signs of toxicosis were not observed in the treated animals of either study.     

Anthelmintic resistance in sheep and goat farms on Peninsular Malaysia.

The faecal egg count reduction test (FECRT) was conducted on 39 sheep farms and 9 goat farms located in Peninsular Malaysia. The anthelmintic groups used in these tests were the benzimidazoles, levamisole, the benzimidazole/levamisole combination, macrocyclic lactones and closantel. Results indicated that the prevalence of resistance to the benzimidazole group was high, with approximately 50% of the sheep farms and 75% of the goat farms having resistant nematode parasite populations present. Resistance to levamisole, closantel and ivermectin was also detected. Differentiation of the infective larvae derived from faecal cultures indicated that by far the most predominant parasite species was Haemonchus contortus.