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.     

The anthelmintic efficacy of netobimin against naturally acquired gastrointestinal nematodes in sheep

The broad-spectrum anthelmintic efficacy of netobimin (SCH 32481, Schering Corporation) was evaluated using 30 cross-bred spring lambs with naturally acquired infections of gastrointestinal nematodes. Three groups of 10 animals each were allotted into either control (given a tap water drench as a placebo) or 7.5 and 20 mg kg-1 dosage groups (given the netobimin as an oral drench). Seven to fourteen days post-treatment, animals were necropsied and nematodes recovered by standard techniques. Examination of fecal samples taken on dates of necropsy showed median egg production was reduced in treated animals (61.98% with 7.5 mg kg-1 and 100% with 20 mg kg-1). The compound was highly effective in removal of adult nematodes representing a number of genera and species of trichostrongyloids at the 7.5 and 20 mg kg-1 dose levels (shown, respectively, below). These included Ostertagia spp., with O. circumcincta, O. trifurcata, O. ostertagi and Teladorsagia davtiani (96.20%; 100%), Trichostrongylus spp., with T. axei, T. vitrinus and T. colubriformis (100%; 98.72%), Nematodirus spp., with N. spathiger, N. filicollis and N. battus (100% both levels) and Haemonchus contortus (100% both levels). High efficacies against other species of nematodes (at both dose levels) were not statistically significant (Cooperia spp., Chabertia ovina and Oesophagostomum venulosum). At 20 mg kg-1, netobimin significantly reduced populations of early and late fourth stage larvae of Ostertagia spp. by 100%. The overall efficacy (all life stages included) was 90.16% at 7.5 mg kg-1 and 98.77% at 20 mg kg-1 dose levels. No adverse reactions or signs of toxicosis were observed.     

Efficacy of moxidectin against an ivermectin-resistant strain of Haemonchus contortus in sheep.

The efficacy of moxidectin was determined against ivermectin-susceptible and resistant strains of Haemonchus contortus. At the onset of the trial, 40 lambs were each infected with 5000 third stage larvae of one of two strains of Haemonchus contortus. The lambs were randomly sorted into eight treatment groups 28 days post-infection and were treated as follows: Group 1, susceptible strain with no treatment; Group 2, resistant strain with no treatment; Group 3, susceptible strain treated with 0.2 mg moxidectin kg-1 body weight; Group 4, resistant strain treated with 0.2 mg moxidectin kg-1; Group 5, resistant strain treated with 0.4 mg moxidectin kg-1; Group 6, susceptible strain treated with 0.2 mg ivermectin kg-1; Group 7, resistant strain treated with 0.4 mg ivermectin kg-1; Group 8, resistant strain treated with 0.8 mg ivermectin kg-1. The lambs were killed 1 week post-treatment. Comparisons were made among groups based on the number of eggs per gram of feces on the day of treatment and the numbers of worms recovered from each lamb. Both moxidectin and ivermectin were effective in removing susceptible Haemonchus with efficacies of 100% and 99.7%, respectively. The efficacy of moxidectin against the resistant strain was 99.9% and 100% at 0.2 mg kg-1 and 0.4 mg kg-1, respectively, whereas there were only 38.8% and 53.1% efficacies in the lambs treated with 0.4 mg ivermectin kg-1 and 0.8 mg kg-1 body weight, respectively.     

The efficacy of netobimin against a benzimidazole susceptible and a resistant strain of Haemonchus contortus in sheep in The Netherlands

Netobimin was tested for efficacy against Haemonchus contortus using 7 groups of 5 parasite-free lambs of six months age. The lambs in group 1 and 2 were infected with 10,000 larvae of a benzimidazole susceptible strain and those in groups 3-7 with the same dose of a resistant strain. The following treatment scheme was applied 21 days after infection: lambs in groups 2 and 4-7.5 mg kg-1 netobimin, in group 5-20 mg kg-1 netobimin, in group 6-5 mg kg-1 oxfendazole and in group 7--3.8 mg kg-1 albendazole. The lambs in groups 1 and 3 remained untreated. All lambs were slaughtered 28 days after infection. Egg counts decreased in all lambs after treatment, but increased again in lambs in groups 4, 6 and 7. There was a slight increase in lambs in group 5, while those in group 2 remained negative. Post-mortem worm counts showed a reduction of 99.8 per cent in lambs in group 2 compared to those in group 1. In lambs in group 4-7 the reduction of worm counts was respectively 40.9, 89.5, 24.7 and 40.7 per cent compared to those in group 3. Egg development assays carried out 20 days after infection showed an average LD50 of 0.46 mg ml-1 thiabendazole for the resistant strain. After treatment (day 27) the LD50 was 0.53, 0.48, 0.58, 0.56 and 0.47 in lambs in the groups 3-7. It is concluded that netobimin and other (pro)-benzimidazoles should not be used in cases of benzimidazole resistance and that levamisole, pyrantel tartrate or ivermectin are preferable.     

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.     

Efficacy of some anthelmintics on an ivermectin-resistant strain of Haemonchus contortus in sheep

Following evidence of reduced efficacy of ivermectin in a field population of Haemonchus contortus in Brazil, this strain of the parasite was submitted to a controlled anthelmintic test. Eighty worm-free lambs were randomly split into two groups of 40. Each lamb in the first group was infected with 5000 third stage larvae (L3) of the ivermectin-resistant strain; the remaining 40 lambs were each infected with 5000 L3 of a H. contortus strain of known susceptibility to the major groups of anthelmintic compounds used in sheep. On Day 28 post-infection, each group was subdivided according to egg counts and at random into four sub-groups of ten lambs, each of which was treated with albendazole (ABZ) at 3.8 mg kg-1, levamisole (LEV) at 7.5 mg kg-1 or ivermectin (IVM) at 0.2 mg kg-1, or was left as untreated control. At slaughter, 7 days later, all the anthelmintics reduced worm burdens in animals infected with the susceptible strain (ABZ 98.9%, LEV and IVM 100%). By contrast, in the lambs infected with the ivermectin-resistant strain, LEV was 99.8% effective, but ABZ reduced worm counts by only 14.7% and IVM by only 10.4%. Interestingly at necropsy on Day 7 post-treatment, the egg counts in the resistant strain treated with ABZ had been reduced by 92.5%, although worm counts were reduced by only 14.7%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of three broad-spectrum anthelmintics against gastrointestinal nematode infections of goats

Groups of 10 goats, harbouring both naturally acquired and experimental infections of gastrointestinal nematodes, were drenched with either levamisole (5 mg kg-1), albendazole (3.8 mg kg-1) or parbendazole (15 mg kg-1), or remained untreated. Haemonchus contortus was the numerically dominant infection, with Strongyloides papillosus, Trichostrongylus colubriformis and Oesophagostomum columbianum also present. At 5-6 days post-treatment, goats were killed and necropsied. Post-mortem worm counts showed that the reduction in mean total worm burdens was 57.4% in levamisole-treated animals, 71.1% in the albendazole group and 85.1% in the parbendazole group. Reductions for H. contortus were 80.2, 87.9 and 83.9% in the levamisole-, albendazole- and parbendazole-treated groups, respectively. These data indicate that the anthelmintics in question are not being applied at an adequate dose rate for goats, and/or resistance to anthelmintics is occurring in the field in Pernambuco State, northeast Brazil.     

Cryopreservation of some common nematodes of ruminants for up to 11,3 years

Infective larvae of selected batched of the following nematode species from sheep and cattle were examined for survival and infectivity (by injection into either the abomasum, the duodenum, or the jugular vein) after having been stored in liquid nitrogen for 103-136 months: Haemonchus contortus, Haemonchus placei, Ostertagia circumcincta, Ostertagia ostertagi, Marshallagia marshalli, Cooperia spp., Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus falculatus, Nematodirus spathiger, Nematodirus helvetianus, Oesophagostomum columbianum, Oesophagostomum radiatum, Chabertia ovina and Dictyocaulus filaria. Excluding D. filaria, a mean of 97.7% of the ovine and 96.0% of the bovine nematode larvae were alive when thawed. Compared with previous investigations in this series, little or no reduction occurred with time in either the survival or the viability of the nematodes from cattle, or in the survival of those from sheep. In contrast, the larvae developed poorly in sheep, possibly owing to parenteral treatment of the animals with ivermectin at a dosage of 0.4 mg kg-1, either 6 or 8 days before they were infected.     

Comparison of ivermectin and thiabendazole for treatment of naturally occurring nematode infections of goats in Kenya

The anthelmintic activity of thiabendazole (TBZ) at 88 mg kg-1 and ivermectin at 0.2 mg kg-1 was examined in goats with naturally-acquired nematode infections. In one experiment, a herd of 450 does was treated with TBZ or ivermectin at 4-week intervals for 9 months and efficacy was measured by reduction in faecal egg counts after each treatment. In a second experiment, 100 kids were treated with ivermectin and effectiveness measured at 2 and 4 weeks after treatment by comparison of their egg counts with those of nontreated controls. In a third experiment, efficacy of treatment with TBZ and ivermectin was determined by recovery of parasites at necropsy in a controlled test with 15 kids. The results indicated that TBZ generally did not reduce egg counts and only removed 19% of Haemonchus contortus in the controlled test. The efficacy of ivermectin approached 100% for reduction in egg counts and elimination of H. contortus. Species of Ostertagia, Trichostrongylus, Nematodirus and Oesophagostomum also were present in some subjects, but not in sufficient numbers to evaluate effectiveness of treatment.     

Efficacy of moxidectin, nemadectin and ivermectin against an ivermectin-resistant strain of Haemonchus contortus in sheep.

The efficacies of ivermectin, nemadectin and moxidectin were evaluated when administered orally to lambs infected with either a susceptible laboratory strain of Haemonchus contortus or a strain reported to be resistant to ivermectin. Groups of 24 Dorset cross Cheviot cross Suffolk lambs were infected with either the susceptible or resistant strain of H contortus and allocated to treatment groups according to their faecal egg counts 27 days after infection. One day later the lambs were dosed orally with one of the three anthelmintics at 0.2 mg/kg bodyweight, and they were killed and surviving worms were recovered 13 or 14 days after treatment. Against the ivermectin resistant strain, ivermectin did not significantly reduce the egg count or the numbers of adult H contortus; however, both nemadectin and moxidectin reduced the nematode egg counts and the numbers of H contortus by 99 and 100 per cent, respectively. Against the susceptible strain, all the anthelmintics reduced the egg counts by 100 per cent as early as four days after treatment and reduced the numbers of susceptible H contortus by 100 per cent. No adverse reactions to any of the drugs were observed.     

Anthelmintic efficacy of ivermectin against immature gastrointestinal pulmonary nematodes of calves

Anthelmintic efficacy of ivermectin (greater than or equal to 80% 22,23-dihydroavermectin B1a and less than or equal to 20% 22,23-dihydroavermectin B1b) was evaluated in a controlled experiment against immature nematodes. Twenty calves raised to about 8 weeks of age under nematode-free conditions were allocated into 4 groups. Infective larvae of Haemonchus contortus, Ostertagia ostertagi, Trichostrongylus axei, T colubriformis, Cooperia oncophora, C punctata, Oesophagostomum radiatum, and Dictyocaulus viviparus were given orally to each calf on a staggered schedule 6 to 14 days before treatments. The drug was given subcutaneously when the nematodes were in the early 4th stage of development, and the calves were killed 23 or 24 days later. Group 1 nonmedicated control calves had a geometric mean of 25,102 nematodes; groups 2, 3, and 4 calves given ivermectin at dose rates of 50, 100, or 200 micrograms/kg had reductions of 88.2%, 98.0%, and 99.8%, respectively.     

Multispecific resistance of trichostrongyles to benzimidazoles in a goat herd in Germany

Anthelmintic resistance of nematodes to benzimidazoles and ivermectin was suspected from field observations in an Angora goat herd in northern Hesse. Larvae of the caprine trichostrongyle isolate were used for artificial infections of helminth-naive sheep. Groups of the lambs were treated with albendazole (3.8 mg/kg p.o.) or ivermectin (0.2 mg/kg s.c.) four weeks after infection or remained untreated as controls and were necropsied one week later. Albendazole reduced the mean faecal egg counts by 82% and the mean worm counts of Haemonchus contortus by 22%, Ostertagia circumcincta by 10% and Trichostrongylus colubriformis by 41% as compared with the controls. Ivermectin was 100% effective. This is the first report from Germany of multispecific resistance to benzimidazoles in a trichostrongyle population of goats.     

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.     

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.     

Effect of ivermectin on feeding by Haemonchus contortus in vivo

While several in vitro studies have shown that the anthelmintic ivermectin inhibits feeding by parasites, the relevance of this putative site of action in vivo has not been demonstrated. For this study, techniques to measure feeding by Haemonchus contortus in vivo relied on the blood feeding characteristics of the worm, and utilised tritiated inulin administered to sheep intravenously and subsequently measured in worms recovered from abomasa. Nematodes recovered from sheep treated with ivermectin 4 h prior to the [3H]inulin administration showed equivalent feeding levels (over a 1 h period) to those recovered from sheep not treated with ivermectin. In addition, there was no difference in the radioactivity in nematodes of an ivermectin-susceptible and an ivermectin-resistant isolate recovered from individual sheep with concurrent infections after a dose with ivermectin. Ivermectin, therefore, had no effect on feeding by H. contortus in vivo under these experimental conditions. The results are discussed in relation to the dynamics of the expulsion of H. contortus from sheep following ivermectin treatment.     

Resistance to macrocyclic lactone anthelmintics by Haemonchus contortus and Ostertagia circumcincta in sheep in New Zealand

AIM: To establish the efficacy of oral formulations of ivermectin and moxidectin against naturally acquired abomasal nematode infections on a North Island sheep farm. METHODS: Two controlled slaughter trials were undertaken. In the first, 30 sheep on pasture were randomly allocated on the basis of faecal egg count to 1 of 3 groups, comprising an untreated control group and 2 treatment groups. One treatment group was given a single oral dose of ivermectin and the other a single oral dose of moxidectin, both at the manufacturer's recommended dose rates of 0.2 mg/kg liveweight. Six days after treatment, all animals were slaughtered and their abomasa recovered for worm counting. The second trial, which involved 47 animals, was essentially the same as the first except that, as well as involving the slaughter of 30 sheep from all 3 groups, 6 days after treatment, it also included a further 8 untreated control animals and 9 moxidectin treated animals which were slaughtered 27 days after treatment. RESULTS: At 6 days after treatment, moxidectin was highly effective against all 3 of the abomasal nematodes present. While ivermectin was similarly effective against Trichostrongylus axei 6 days after treatment, it was not effective against either Ostertagia circumcinta or Haemonchus contortus, against which average efficacies of only 63.6% and 61.6%, respectively, were recorded. At 27 days after treatment, moxidectin, was also highly effective against T. axei (97.3% reduction) but not against either H. contortus (71.4% reduction) or O. circumcinta (61.0% reduction). CONCLUSIONS: These results provide the first record of macrocyclic lactone resistance in H. contortus in sheep or in any other host in New Zealand, and the first case where such resistance has been exhibited in more than one parasite species at a time. Although the therapeutic efficacy of moxidectin was high against these resistant H. contortus and O. circumcincta strains, resistance to moxidectin was indicated by its diminished prophylactic activity against them. It is suggested that this reduction in the prophylactic activity of moxidectin is also likely to reduce its apparent current high therapeutic efficacy. CLINICAL RELEVANCE: As well as providing further evidence that it can no longer be automatically assumed that macrocylic lactone anthelmintics will be effective on sheep farms in this country, these findings also present a warning that increasingly complex parasite control options may have to be faced in the future.     

Selection of ivermectin-resistant Trichostrongylus colubriformis in lambs

A mixed population of Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis was passed for four generations through lambs. In successive passages and on Day 6 (D6), lambs were dosed subcutaneously with ivermectin at 100, 200, 250 and 225 micrograms kg-1 body weight, respectively. No larvae of H. contortus were recovered after the first passage and following the third drug exposure only T. colubriformis was present. Larvae of the selected strain of T. colubriformis developed to third stage, sheathed larvae in vitro in concentrations of ivermectin that inhibited development of larvae from the original strain of T. colubriformis. A definitive control test was then run with 45 lambs, to compare this selected strain to the original strain. The treatments were 150 micrograms kg-1 subcutaneous (SC) D6, 200 micrograms kg-1 SC D6, 200 micrograms kg-1 intraruminal (IR) D6 and 200 micrograms kg-1 SC D21; all treatments were compared to non-treated controls, selected or original strain as applicable. The D6 IR and D6 SC 150 micrograms kg-1 treatments were greater than 99% effective in both strains, although the D6 SC 200 micrograms kg-1 treatment was 85 and 48% effective in the original and selected strain, respectively. The D21 200 micrograms kg-1 was only 58% effective against the selected strain. There was significant (P less than 0.001) differences between the original and selected strains of T. colubriformis for both fecal egg output and worm counts. The exposure of four generations of immature T. colubriformis to ivermectin selected for partial resistance.     

Multiple Anthelmintic Resistance in Haemonchus Contortus on a Sheep Farm in Kenya

Multiple resistance to albendazole, thiophanate, levamisole and orally administered ivermectin was detected in an isolate of Haemonchus contortus in sheep on a farm where benzimidazole resistance had already been identified. Following a faecal egg count reduction test, this was confirmed by both critical and controlled anthelmintic tests. Different groups of sheep infected naturally or given an experimental infection with the benzimidazole-resistant isolate were treated with the recommended doses of various anthelmintics. Compared to the control group, the percentage reductions in the faecal egg counts of sheep treated with albendazole, thiophanate, levamisole and ivermectin varied between 38.2% and 79.1% and the residual worm counts between 27.3% and 57.5%. The results indicate the presence of multiple anthelmintic resistance in this isolate of H. contortus. Sheep treated with closantel showed 100% reductions in faecal egg and worm counts, indicating that this drug was very effective against the population of H. contortus on the farm.     

Anthelmintic resistance in Australian sheep nematode populations

SUMMARY The resistance status of gastro–intestinal nematodes to anthelmintics was evaluated on 881 sheep farms throughout Australia during 1991–92. Resistance was shown to be widespread. Overall, 85% of farms had sheep infected with nematodes resistant to benzimidazole, 65% to levamisole and 34% to combination (benzimidazole + levamisole) products. Resistance to ivermectin was not detcted. On only 9% of farms did all anthelmintic groups reduce egg counts by greater than or equal to 95%. The culture of faeces from untreated sheep showed Telodorsagia circumcincta, Trichostrongylus spp, Chabertia ovina and Haemonchus contortus to be the principal species. The nature and prevalence of resistance was not significantly correlated with stocking rate. However, resistance to combination products was almost twice as prevalent on farms in areas with an average annual rainfall of greater than 500 mm.