The comparative efficacy of four broad spectrum anthelmintics against some experimentally induced trichostrongylid infections in sheep and goats

A controlled slaughter trial was undertaken to compare the efficacies of oxfendazole (5 mg/kg), morantel citrate (10 mg/kg), levamisole (8 mg/kg) and ivermectin (0.2 mg/kg) against experimentally induced infections of adult Haemonchus contortus, Ostertagia spp., Trichostrongylus colubriformis and Cooperiacurticei in sheep and goats. Ivermectin and oxfendazole achieved similar levels of efficacy in both hosts against all four worm genera as did levamisole and mortantel against H. contortus and C. curticei. Against Ostertagia spp. and T. colubriformis, however, the latter two drugs were less effective in goats than sheep. Neither the numbers of Ostertagia spp. removed from goats by levamisole (81% reduction) nor the numbers of T. colubriformis removed from goats by morantel (56% reduction) were statistically significant (P>0.05).     

Efficacy of levamisole against immature and mature nematodes in goats with induced infections

Anthelmintic efficacy of levamisole against induced infections with 7- and 21-day-old Haemonchus contortus, Ostertagia circumcincta, Trichostrongylus axei, and T colubriformis was evaluated as an oral drench in goats. Group 1 (n = 8) was not treated, group 2 (n = 8) was given 3.96 mg of levamisole/kg of body weight, group 3 (n = 8) was given 7.92 mg of levamisole/kg, and group 3 (n = 7) was given 11.88 mg of levamisole/kg. Efficacy against all worms was low in goats given 3.96 mg of levamisole/kg, but was high against adult H contortus (99%) and adult T colubriformis (99.7%) in goats given 7.92 mg of levamisole/kg. Although efficacy against adults of all species was high in goats given 11.88 mg of levamisole/kg, some immature worms of all species remained in the abomasa of goats.     

THE ANTHELMINTIC EFFICACY OF NON-BENZIMIDAZOLE ANTHELMINTICS AGAINST BENZIMIDAZOLE RESISTANT STRAINS OF HAEMONCHUS CONTORTUS AND TRICHOSTRONGYLUS COLUBRIFORMIS IN SHEEP

The anthelmintic efficacy of 6 non-benzimidazole compounds and thiabendazole against standardised, benzimidazole resistant strains of H. contortus and T. colubriformis in sheep was determined using a controlled test. All compounds were administered intraruminally at their recommended therapeutic dose rates and 4 of the compounds were also assessed at half their recommended therapeutic dose rates. Levimisole at a dose of 6.4 mg/kg body weight, morantel at 4.4 mg/kg and 8.8 mg/kg, naphthalophos at 6.25 mg/kg and 12.5 mg/kg, rafoxanide at 7.5 mg/kg and phenothiazine at 530 mg/kg were 98% or more effective in removing adult infections of benzimidazole resistant H. contortus. Rafoxanide at 3.75 mg/kg, phenothiazine at 265 mg/kg and carbon tetrachloride at 0.05ml/kg were less effective, removing 80%, 73% and 72% respectively of the benzimidazole resistant H. contortus worm burdens. Against the benzimidazole resistant T. colubriformis levamisole at 6.4 mg/kg, and morantel at 4.4 mg/kg and 8.8 mg/kg removed 99%, 68% and 86% respectively of the adult infections. All other anthelmintics had little or no efficacy at the dose rates tested. Thiabendazole at 44 mg/kg had no significant effect against these strains of H. contortus and T. colubriformis. Several non-benzimidazole anthelmintics have shown high efficacy in this experiment and should be suitable for treating infections with benzimidazole resistant H. contortus. Of the anthelmintics tested, only levamisole and morantel show high efficacy against benzimidazole resistant T. colubriformis.     

Efficacy of levamisole and netobimin against Haemonchus contortus in lambs in Louisiana

Efficacy of levamisole was evaluated in a suspected levamisole-resistant population of Haemonchus contortus in the Louisiana State University sheep flock. The efficacy of netobimin also was evaluated against this population of Haemonchus. In trial 1, 5 lambs naturally infected with H contortus were given 8 mg of levamisole/kg of body weight as a drench, and 5 lambs were not treated (controls). Nematode recovery after slaughter indicated 0% efficacy against H contortus. In trial 2, 30 nematode-free lambs were each given 8,300 F1 generation infective larvae of H contortus, which were derived from parent H contortus that survived 2 levamisole treatments in lambs being maintained in a nematode-free environment. Ten lambs were treated with 8 mg of levamisole/kg as a drench, 10 were treated with 20 mg of netobimin/kg as a drench, and 10 were not treated (control). Nematode recovery after slaughter revealed 62.3% and 99.8% efficacy for levamisole and netobimin, respectively, against H contortus.     

Characterization of moxidectin resistant Trichostrongylus colubriformis and Haemonchus contortus

The development of moxidectin resistance (MOX-R) in sheep parasitic gastrointestinal nematodes already carrying multiple resistances to other anthelmintic groups has made control of these strains very difficult. The anthelmintic resistance patterns of MOX-R strains of Trichostrongylus colubriformis and Haemonchus contortus were characterized to provide an insight into the remaining role of anthelmintics in the control of such strains. Homozygous MOX-R individuals of both genera were unaffected by moxidectin. For MOX-R heterozygotes a dose rate of 200 microg/kg abamectin (ABA) given orally removed 25% of H. contortus while 200 microg/kg MOX given orally achieved a 72% reduction. Doubling the dose rate of ABA improved the mean efficacy to 37%. Consequently, in H. contortus, the degree of dominance differs markedly between the two anthelmintics. A dose rate of 8 mg/kg levamisole and 185 mg/kg napthalophos achieved >95% reduction in worm count of the MOX-R homozygous H. contortus but only 85 and 7%, respectively against the MOX-R homozygous T. colubriformis.     

An evaluation of an oral formulation of moxidectin against selected anthelmintic-resistant and -susceptible strains of nematodes in lambs

The efficacy of an oral formulation of the newly developed parasiticide, moxidectin, was tested against benzimidazole-resistant Haemonchus contortus, Trichostrongylus colubriformis, and Nematodirus spathiger, levamisole-resistant Ostertagia circumcincta, and susceptible Cooperia curticei infections in weaned lambs. Thirty-two lambs were experimentally infected with mixed doses of the above strains of nematodes. They were allocated into four treatment groups by stratified randomisation using liveweights and faecal egg counts 28 days later. One group received moxidectin at 0.2 mg/kg liveweight, one group oxfendazole at 4.5 mg/kg liveweight, one group levamisole at 7.5 mg/kg liveweight and the last group remained untreated as the control. Worm burdens in the lambs at slaughter 10 days after oral treatment confirmed the resistance status of the nematode strains used, and showed that moxidectin had a greater than 99.9% efficacy (p<0.01) against all of them. No adverse effects due to treatment with moxidectin were observed in any of the animals.     

The anthelmintic efficacy of albendazole against Fasciola hepatica and benzimidazole resistant strains of Haemonchus contortus and Trichostrongylus colubriformis in sheep.

The anthelmintic efficacy of albendazole (methyl [5-(propylthio) - 1H - benzimidazole -2 -yl] carbamate) against immature and adult Fasciola hepatica and against standardised strains of benzimidazole resistant Haemonchus contortus and Trichostrongylus colubriformis was evaluated in experimentally infected sheep. A single intrarumenal treatment of dose rates of 3.8 and 7.6 mg/kg was ineffective against immature (six weeks old) F hepatica. Dose rates of 5.7 and 7.6 mg/kg reduced the number of mature (12 weeks old) F hepatica by 70 and 91 per cent respectively. Dose rates of 5.7 and 7.6 mg/kg removed 92 and 99 per cent of four-week-old, benzimidazole resistant H contortus and 89 and 99 per cent of four-week-old, benzimidazole resistant T colubriformis.     

The effect of single and divided dose administration on the efficacy of fenbendazole against adult stages of benzimidazole resistant sheep trichostrongylids.

Sheep infected with benzimidazole resistant strains of Haemonchus contortus and Trichostrongylus colubriformis were used to compare the anthelmintic efficacy of fenbendazole given as a single dose or administered in a divided dose regime over five days. Statistical analysis showed no significant difference between the two methods of administration for H contortus. On the other hand, divided dose fenbendazole was significantly less effective than single doses against adult T colubriformis at dose rates of 5 and 7.5 mg/kg. In the case of H contortus a highly significant correlation coefficient between post treatment egg counts and worm counts (r = 0.789) was obtained. This suggests that reduction in faecal egg output following drug treatment would provide a useful field indication of anthelmintic performance of fenbendazole (and possibly related compounds) against benzimidazole resistant strains of this parasite.     

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.     

Anthelmintic activity of ivermectin against immature gastrointestinal nematodes of sheep

Twenty-four lambs of mixed breeding with mixed experimental infections of Haemonchus contortus, Ostertagia circumcincta, Trichostrongylus axei, and T colubriformis were allotted to 4 groups. One group (control) was given the vehicle propylene glycol, and the others were given 100, 200, or 300 micrograms of ivermectin/kg of body weight by mouth. Twelve days after treatment, the sheep were necropsied. The compound was greater than 99% effective against immature stages of 4 nematode species at all dosages, except at the 100 micrograms/kg dosage, where efficacy was 96% against H contortus.     

Laboratory investigations in sheep with a new anthelmintic.

The efficacy of fenbendazole against the following gastrointestinal nematodes was tested in experimentally infected lambs: O circumcincta, H contortus, T colubriformis and N filicollis. As low a dose as 0.5 mg per kg reduced the egg output of a patent infection with H contortus and T colubriformis by 85 per cent to 100 per cent. A dose of 3.5 mg per kg has a 100 per cent effect on three or 10-day-old stages of H contortus and one of more than 99 per cent or 100 per cent T colubriformis. The same dose reduces seven-day-old stages of O circumcincta and N filicollis by more than 94 per cent or 100 per cent, while 10 mg per kg produces a 100 per cent elimination of seven-day-old stages of O circumcincta. In field trials and efficacy of more than 99 per cent was determined after oral dosage with 5.0 mg per kg against Ostertagia, Haemonchus, Trichostrongylus, Cooperia, Nematodirus and Chabertia. Fenbendazole has a wide therapeutic-toxic dose ratio. Discoloration of the wool does not occur. Fenbendazole can be administered as a drench or with the feed.     

The effect of route of administration on the anthelmintic efficacy of benzimidazole anthelmintics in sheep infected with strains of Haemonchus contortus and Trichostrongylus colubriformis resistant or susceptible to thiabendazole

Observations of erratic anthelmintic activity of fenbendazole against known standardised thiabendazole-resistant strains of Haemonchus contortus and Trichostrongylus colubriformis in sheep were investigated. Fenbendazole at a dose rate of 10 mg/kg body weight was administered by oral, intra-ruminal or intra-abomasal routes, and was most effective against both resistant strains following intra-ruminal administration. In addition thiabendazole, oxibendazole, fenbendazole, parbendazole and mebendazole plus two unrelated compounds, levamisole and morantel tartrate, were used at one and a half times their suggested or recommended therapeutic dose rate against thiabendazole-resistant strains of H contortus and T colubriformis in sheep; each drug being administered by the intra-ruminal or intra-abomasal routes. Fenbendazole was more effective against both strains following intra-ruminal administration. Parbendazole was more effective against the resistant strain of T colubriformis following intra-ruminal administration. At the dose rate chosen for the other benzimidazoles used against these resistant strains, there was no difference in anthelmintic efficacy due to route of administration. Levamisole was highly effective against both resistant strains, irrespective of the route of administration. In the groups treated with morantel tartrate, the results obtained were difficult to interpret due to mortalities and a highly variable response in the surviving sheep. Fenbendazole, thiabendazole and mebendazole when used at their suggested or recommended therapeutic dose rate in sheep, were highly effective against known thiabendazole-susceptible strains of H contortus and T colubriformis following both intra-ruminal or intra-abomasal administration.     

Resistance of Teladorsagia circumcincta in goats to ivermectin in the Netherlands

Resistance of Teladorsagia circumcincta in goats to ivermectin In 2005, suspected ivermectin resistance of gastrointestinal nematodes was investigated in 17 goats on a farm in the Netherlands, using a faecal egg count reduction test combined with faecal larval cultures. Eight goats were treated orally with 0.2 mg/ kg ivermectin on 1 August 2005 and the other nine goats served as untreated controls. Faeces were collected from all goats on 1 August and on 12 August. Faecal egg counts were reduced by 80.6% in goats receiving ivermectin. On the basis of faecal larval cultures and the egg counts, ivermectin was found to be 100% effective against Haemonchus contortus, 15.0% effective against Teladorsagia circumcincta, and 93.3% effective against Trichostrongylus spp. The effect of levamisole and oxfendazole on gastrointestinal nematodes was also evaluated. Nine goats were treated subcutaneously with 5 mg/kg levamisole and seven goats orally with 4.5 mg/kg oxfendazole on 12 September On the basis of faecal egg counts performed on 12 and 22 September, levamisole reduced the total egg count by 95.4% and oxfendazole reduced the egg count by 85.8%. Differentiation of pooled faecal larval cultures revealed that levamisole was 99.9% effective against H. contortus, 81.9% effective against T. circumcincta, and 99.5% against Trichostrongylus spp. Oxfendazole was 75.5% effective against H. contortus, 33.2% effective against T. circumcincta, and 100% effective against Trichostrongylus spp. On 28 October the nine goats that were still present on the farm were orally treated with 0.4 mg/kg ivermectin. Faecal egg counts and differentiation of pooled larval cultures of faecal samples collected on 28 October and 9 November, respectively, revealed that total egg counts were reduced by 93.1%. Ivermectin was 49.1% effective against T. circumcincta but 100% effective against H. contortus and Trichostrongylus spp. Thus H. contortus appears to be resistant to oxfendazole and T. circumcinta appears to be resistant to oxfendazole and ivermectin. This is the first documented case of ivermectin resistance of a gastrointestinal nematode of small ruminants in the Netherlands.     

The efficacy of fenbendazole and albendazole against immature and adult stages of benzimidazole-resistant sheep trichostrongylids

The efficacy of two recently introduced benzimidazole anthelmintics, albendazole and fenbendazole, was determined for six-day, 10-day and adult stages of resistant strains of Haemonchus contortus and Trichostrongylus colubriformis. Albendazole, at 3.8 mg/kg reduced H contortus worm counts by 92.4, 70.8 and 67.1 per cent while fenbendazole, at 5.0 mg/kg, reduced worm burdens by 51.7, 95.5 and 93.4 per cent against six-, 10- and 25-day-old parasites respectively. For T colubriformis, the corresponding reductions with albendazole were 97.7, 95.8 and 64.9 per cent and for fenbendazole 29.0, 66.3 and 33.4 per cent. Compared with susceptible strains of H contortus and T colubriformis, for which therapeutic doses of benzimidazole anthelmintics are generally highly active against all stages of development, the present results show that these drugs do not have a uniform level of activity against all developmental stages of resistant strains.     

The efficacy of levamisole and ivermectin against a morantel-resistant strain of Trichostrongylus colubriformis

A controlled slaughter trial was undertaken to evaluate the efficacy of ivermectin (0.2 mg/kg) and levamisole (8 mg/kg) against a morantel-resistant field strain of Trichostrongylus colubriformis in sheep. Mean worm count reductions of greater than 99% were recorded with both anthelmintics. The apparent contradiction between the high efficacy of levamisole and the common belief that resistance to levamisole and morantel is co-inherited, is discussed.     

Multiple species of nematodes resistant to ivermectin and a benzimidazole-levamisole combination on a sheep farm in New Zealand

AIM: To confirm the presence of multiple anthelmintic resistance on a sheep farm in New Zealand. METHODS: Three groups of 10 weaned Romney-cross lambs were treated either with an oral dose of ivermectin (0.2 mg/kg), or a benzimidazole/levamisole (BZ/LEV) combination (4.75 albendazole and 7.5 mg/kg levamisole), or were left untreated. Ten days later, animals were necropsied, and adult worms recovered and identified from the abomasa and small intestines. Pre- and post-treatment faecal nematode egg counts (FEC) were recorded, and larval cultures were performed. RESULTS: In a faecal egg count reduction test (FECRT), adjusted to reflect pre- and post-treatment larval culture results, ivermectin resistance was detected in Teladorsagia (Ostertagia), Trichostrongylus and Haemonchus spp, while BZ/LEV combination- resistant Teladorsagia and Trichostrongylus spp were also present. Adult worm counts confirmed these results, and identified the species involved as Teladorsagia circumcincta, Trichostrongylus colubriformis and H. contortus. CONCLUSION: Multiple, multi-generic anthelmintic resistance was confirmed on a sheep property in New Zealand. This included the first confirmed case of ivermectin resistance in T. colubriformis from sheep in New Zealand.     

The efficacy of levamisole, and a mixture of oxfendazole and levamisole, against the arrested stages of benzimidazole-resistant Haemonchus contortus and Ostertagia circumcincta in sheep

Sheep were allowed to graze pasture that had been seeded with benzimidazole-resistant Haemonchus contortus and Ostertagia circumcincta in order to acquire a burden of arrested larvae. Following housing, sheep were dosed orally with either oxfendazole at a dose rate of 4.7 mg/kg (to confirm the benzimidazole-resistant status of the species of nematode), levamisole at a dose rate of 7.5 mg/kg, or an oxfendazole/levamisole mixture at a dose rate of 4.6 mg/kg oxfendazole and 8.1 mg/kg levamisole. The efficacies of the treatments were assessed by estimation of the arrested larval burden in the abomasum of each sheep, either at 10 or 11 days (oxfendazole and oxfendazole/levamisole mixture), or 12 or 13 days (levamisole), after treatment. Compared to the untreated controls, the protection afforded by a single dose of either levamisole or the oxfendazole/levamisole mixture was >99% against the arrested stages of both Haemonchus contortus and Ostertagia circumcincta. Treatment with oxfendazole confirmed the benzimidazole-resistance status of the two species.     

Anthelmintics for the control of nematode infections in the brushtail possum (Trichosurus vulpecula)

AIMS: To determine the efficacy of eprinomectin, doramectin and a combination of albendazole and levamisole in suppressing or eliminating nematode infections or faecal egg counts (FEC) in possums naturally or experimentally infected with Parastrongyloides trichosuri, Paraustrostrongylus trichosuri and Trichostrongylus colubriformis. METHODS: To establish an effective dose of eprinomectin, groups of naturally infected possums were treated with 0, 0.5, 2.5, 5.0 or 7.5 mg/kg liveweight (LW) eprinomectin pour-on (n=6 possums/group) and changes in FEC and nematode worm counts at necropsy determined, 18 days later. Efficacy of the 7.5 mg/kg dose was re-examined in a second group of naturally infected possums (n=12) by monitoring FEC weekly for 28 days post-treatment. Persistence of the anthelmintic effect of doramectin injection was tested using nematode-free possums treated with 0, 0.2, 0.4, 0.6 or 0.8 mg/kg LW (n=3 possums/ group), which were experimentally infected 14 days later with T. colubriformis, Paraustrostrongylus trichosuri and Parastrongyloides trichosuri infective larvae. Response to treatment was assessed by FEC and nematode worm counts at necropsy, 42 days posttreatment. Efficacy of a 1.0 mg/kg dose of doramectin was subsequently examined using naturally infected possums (n=11) by monitoring FEC weekly for 28 days post-treatment. To determine the efficacy of a levamisole-albendazole combination drench, possums with naturally acquired nematode infections (n=6) were treated orally with 37.5 mg/kg LW levamisole plus 23.75 mg/kg LW albendazole on 2 occasions, 7 days apart, and response to treatment was assessed by monitoring FEC for 57 days. RESULTS: Eprinomectin 7.5 mg/kg LW reduced Paraustrostrongylus trichosuri worm counts by 98 % (p<0.05). Doramectin 0.6 mg/kg LW reduced Parastrongyloides trichosuri and Trichostrongylus spp worm counts by 99% (p<0.05) and 0.8 mg/kg LW reduced Paraustrostrongylus trichosuri by 100% (p<0.05), in possums challenged with larvae 14 days after treatment. Treating possums with a levamisole-albendazole combination orally, twice, 7-days apart, reduced FEC by 99%. CONCLUSIONS: The doses of anthelmintics required to effectively control nematodes in possums were higher than those recommended for animals for which they are currently registered. Possums tolerate the high dose rates of anthelmintics used in this study without apparent adverse effects.     

Haemonchus contortus and Trichostrongylus colubriformis in pen-trials with Javanese thin tail sheep and Kacang cross Etawah goats

Weight gain costs due to infection were higher in sheep than goats, 28 and 17.5%, respectively, for Trichostrongylus colubriformis and 48.7 and 32.2%, respectively, for Haemonchus contortus. The extent of bodyweight cost attributed to anorexia in sheep infected with H. contortus was higher (13.5 g/day) than in sheep infected with T. colubriformis (2.3 g/day). On the other hand, bodyweight cost due to the other pathogenic effects in sheep infected with T. colubriformis were higher (35.6 g/day) compared to sheep infected with H. contortus (10.9 g/day). A strong relationship between faecal egg count and worm count (r=0.79, P=0.006) was shown only in sheep infected with T. colubriformis. About half of the infected sheep and goats had low or zero faecal egg counts throughout the study. In about 40% the egg count rose initially but became low by weeks 10-16, whereas in about 10% counts increased progressively throughout the period of observation and these animals also had the highest numbers of worms at slaughter. Packed cell volume was reduced in sheep and goats infected with H. contortus but serum protein and haemoglobin levels were unaffected. Sheep infected with T. colubriformis had a higher level of eosinophilia after 8 weeks (18.4%) than sheep infected with H. contortus (11.4%), whereas this pattern was reversed in goats and levels were also lower (4.1 and 8.9%, respectively). There was no apparent relationship between eosinophilia and resistance to infection with H. contortus or T. colubriformis.     

Efficacy of eprinomectin pour-on against gastrointestinal nematodes and the nasal bot fly (Oestrus ovis) in sheep

The efficacy of the pour-on formulation of eprinomectin, at a dose rate of 0.5 mg/kg bodyweight, was assessed in sheep against three main species of gastrointestinal nematodes and against the nasal bot fly, Oestrus ovis, and some pharmacokinetic parameters were determined for 21 days after the treatment. By comparison with untreated control sheep, infected experimentally with Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis, eprinomectin was 100 per cent effective against the two abomasal species and 99.5 per cent effective against T. colubriformis. In ewes naturally infected with the nasal bot fly, the efficacy of the drug against O. ovis was 97.7 per cent. The mean (se) systemic area under the curve (AUC) was 56.0 (26.2) ng/day/ml and the mean residence time was 5.3 (1.0) days, but there were wide variations between individual sheep.