Efficacy of ivermectin against benzimidazole-resistant nematodes of sheep

Two trials involving a total of 36 Dorset horn lambs were conducted to assess the anthelmintic efficacy of ivermectin against experimental infections of benzimidazole-resistant strains of Haemonchus contortus and Ostertagia circumcincta. Two resistant strains of each of the two species were used and in each trial the lambs were allocated to three groups. One group was given 200 micrograms ivermectin/kg bodyweight orally, the second group was given 5 mg oxfendazole/kg bodyweight orally and the third group remained untreated as controls. Fourteen days after treatment the lambs were necropsied. Ivermectin was found to be more than 99 per cent to 100 per cent effective against all four benzimidazole-resistant strains, whereas oxfendazole was 78.6 per cent and 83.8 per cent effective against the H contortus strains, and 25.6 per cent and 39.8 per cent effective against the O circumcincta strains.     

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.     

Efficacy of avermectin B1a for treatment of experimentally induced nematode infections in cattle

Two formulations of avermectin B1a, C-076 and MK-933, were examined for anthelmintic activity in two trials, each using 20 calves with experimentally produced nematode infections. In one trial, C-076 was given orally, and in the other trial, MK-933 was given by injection at dosages of 50, 100, and 200 micrograms/kg of body weight. Treated calves were held for 7 to 8 days and then, together with nontreated controls, were euthanatized and were examined for nematodes in their gastrointestinal tracts and lungs. Efficacy of C-076 approached 100% for Dictyocaulus viviparus, Ostertagia ostertagi, Trichostrongylus axei, T colubriformis, and Oesophagostomum radiatum at 50 micrograms/kg. A dosage level of 100 micrograms/kg was required to achieve 97% efficacy against Cooperia punctata. Efficacy of MK-933 at 50 micrograms/kg was variable, but at 100 micrograms/kg, it approached 100% for D viviparus, O ostertagi, Haemonchus placei, T axei, and T longispicularis. Activity against C oncophora was less, reaching 80% efficacy at 200 micrograms/kg.     

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.     

Activity of ivermectin against natural infections by abomasal nematodes in lambs in controlled tests: evaluation of equine and bovine injectable formulations administered intraorally

The efficacy of 2 injectable formulations of ivermectin, administered intraorally at the dosage of 200 micrograms/kg of body weight, was evaluated against naturally occurring infections by abomasal nematodes in lambs in 2 controlled tests. One test (A) included 17 lambs treated with the equine formulation and 16 nontreated lambs. For the other test (B), 14 lambs were treated with the bovine formulation, and 12 were nontreated. In controlled test A, only mature nematodes were recovered, and removals were 98% to 100% for Haemonchus contortus, Ostertagia circumcincta male, O trifurcata male, Ostertagia spp female, and Trichostrongylus axei. For controlled test B, removals were 99% to 100% for Haemonchus spp (immature), H contortus (mature), Ostertagia spp (immature), O circumcincta male (mature), O trifurcata male (mature), Ostertagia spp female (mature), Trichostrongylus spp (immature), and T axei (mature). Toxicosis was not evident in treated lambs.     

Efficacy of ivermectin against induced gastrointestinal nematode infections in goats

The efficacy of ivermectin (0.08 per cent w/v oral solution) at different dose levels was evaluated against induced infections of adult Haemonchus contortus (21 days old) and Trichostrongylus colubriformis (21 days old) and fourth stage larvae of Oesophagostomum columbianum (17 days old), Ostertagia circumcincta (five days old) and Strongyloides papillosus (five days old). Twenty-five Boergoats (mutton goats) were randomly allocated by bodyweight within each sex to an untreated control group and four ivermectin treatment groups; ivermectin was administered at either 25, 50, 100 or 200 micrograms/kg orally, once. The goats were killed and processed for worm recovery 25 to 27 days after treatment. At 25 micrograms/kg the efficacy of ivermectin varied from 43 per cent for adult T colubriformis to more than 99 per cent for fourth larval stage O columbianum. Ivermectin at 50 micrograms/kg or higher was 99 per cent or more effective against all induced parasite infections with the exception of ivermectin at 50 micrograms/kg against S papillosus (97 per cent). For all parasites there was a statistically significant (P less than 0.05) difference between the control group and the pooled treated groups. No adverse reactions to ivermectin treatment were observed in the 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.     

THE ANTHELMINTIC EFFICIENCY OF LAEVO-TETRAMISOLE HYDROCHLORIDE AGAINST NEMATODE PARASITES OF SHEEP AND CATTLE

Critical anthelmintic tests and controlled trials were used to assess the efficiency of laevo -tetramisole hydrochloride against nematode infections in sheep and cattle.
In sheep, oral dose rates of 5 mg/kg and above were 94 to 100% effective against adult Haemonchus contortus , intestinal Trichostrongylus spp, Nematodirus spp, Oesophagostomum columbianum, O. venulosum and Chabertia ovina . A dose rate of 7.5 mg/kg was required for consistently high activity against Ostertagia spp, but activity against Trichostrongylus axei remained variable at this dose level. Efficiency against Trichuris ovis ranged from 76 to 100% at a dose rate of 10 mg/kg. The drug was 94 to 100% effective against 7-day old and 14-day old H. contortus , intestinal Trichostrongylus spp and O. colun bianum infections, and 83 to 89% effective against 14-day old Ostertagia spp and T. axei , at a dose rate of 5 mg/kg. Seven-day old Ostertagia spp larvae were highly resistant at a dose rate of 10 mg/kg, while activity against T. axei infections of the same age appeared variable at 5 and 10 mg/kg.
In cattle, subcutaneous treatment at dose rates of 1.5 mg/kg and above, and oral treatment at 7.5 mg/kg, were 93 to 100% effective against adult Haemonchus placei , intestinal Trichostrongylus spp, Nematodirus helvetianus, Cooperia spp and Oesophagostomum radiatum , and 84 to 98% effective against Ostertagia ostertagi . Against Trichostrongylus axei , a rate of 5 mg/kg subcutaneously was 83% effective, and a rate of 7.5 mg/kg orally 97% effective, while these dose rates gave 88 to 100% clearance of adult Dictyocaulus viviparous .     

Activity of ivermectin against canine intestinal helminths

The anthelmintic activity of ivermectin was tested in 98 dogs against adult ascarids (Toxocara canis, Toxascaris leonina), hookworms (Ancylostoma caninum, A braziliense), and whipworms (Trichuris vulpis), and against experimentally induced infections (4th-stage larvae) of T canis and A caninum. Dosage levels tested were single subcutaneous injections of 50, 100, 200, or 400 micrograms/kg of body weight with appropriate vehicle-treated controls. A minimum of 4 (usually 5) dogs were tested with each parasite and dosage level. The lowest dosage level, 50 micrograms/kg, and all higher dosage levels expelled greater than 99% of the adult forms of both species of hookworms and intestinal larval forms of A caninum, as determined by worm counts at necropsy. A dosage level of 100 micrograms/kg was required to expel greater than 99% of whipworms and 200 micrograms/kg was necessary to expel adult (91%) and larval (97%) stages of T canis. Ivermectin was only marginally effective (34.2%, 46.2%, 69.2%, and 53.8%) against Toxascaris leonina at 50, 100, 200, and 400 micrograms/kg, respectively, and had no effect against occasional infections with the tapeworms, Dipylidium caninum (14 dogs) and Taenia spp (3 dogs).     

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.     

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.     

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.     

Anthelmintic efficacy of albendazole in cattle: comparison of critical and controlled tests.

Twelve calves were experimentally inoculated with 6 species of gastrointestinal nematodes and the liver fluke, Fasciola hepatica. Six calves were administered albendazole at 10 mg/kg of body weight, and the drug efficacy was determined by critical and controlled tests. Albendazole was only 74% effective against Haemonchus contortus (cambendazole-resistant strain), 99 to 100% effective against Ostertagia ostertagi, Trichostrongylus colubriformis, Cooperia oncophora, and Oesophagostomum radiatum, and 54% effective against the liver fluke. Except for H contortus, the critical test provided as accurate a measurement of drug activity against gastrointestinal nematodes as the controlled test provided.     

In vitro and in vivo characterization of p-amino-phenethyl-m-trifluoromethylphenyl piperazine (PAPP), a novel serotonergic agonist with anthelmintic activity against Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis

The neurotransmitter serotonin (5-hydroxy tryptamine or 5HT) regulates key physiological processes in nematodes such as locomotion and feeding. PAPP (p-amino-phenethyl-m-trifluoromethylphenyl piperazine) is a known agonist of the 5-HT(1Hc) receptor of the barber pole worm, Haemonchus contortus. In this study, PAPP was highly active against L3-stage larvae of H. contortus and Trichostrongylus colubriformis in an in vitro larval migration assay, with EC50 values of 9.36 and 11.8 microM, respectively, that were comparable to levamisole (10.2 microM) and superior to pyrantel (55.39 microM). When administered orally or subcutaneously to nematode infected gerbils, PAPP provided >99% efficacy against H. contortus and >98% efficacy against Teladorsagia circumcincta at 100 mg/kg, comparable to levamisole at 10 mg/kg. Drug titration revealed significant activity down to 50 mg/kg against these two species. Spectrum was limited, however, with somewhat lower efficacy (83%) in T. colubriformis infected gerbils at 100 mg/kg. Oral delivery of hydrochloride, acetate and phosphate salts of PAPP to nematode infected gerbils did not result in an increase in either potency or spectrum. The finding that PAPP exhibits significant anthelmintic activity suggests that the nematode-specific serotonergic system is a viable target for future anthelmintic discovery.     

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.     

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.     

Anthelmintic activity of the macrocyclic lactone F28249-alpha in sheep

The macrolytic lactone F28249-alpha was titrated in experimentally infected sheep and found to be highly effective against most of the common gastrointestinal nematodes as a single oral dose, given at a rate of 0.025, 0.05, or 0.1 mg/kg. Specifically, maximal activity was evident at even the lowest dosage against adult Haemonchus contortus, Ostertagia circumcinta, Trichostrongylus axei, and T colubriformis and L4 O circumcinta. Activity against Oesophagostomum columbianum was also high at all dosages, with a calculated ED95 of 0.029 mg/kg. Cooperia curticei was eliminated at 0.1 mg/kg, but control was erratic at the lower dosages. The greatest weakness of this compound was its activity against C oncophora. The activity against this parasite was weak (less than or equal to 85%) at all dosages, and the dosage-response curve was flat, suggesting dosages substantially higher than those given would be necessary for high-order control of this species.     

The effect of fenbendazole on nematode parasites in experimentally infected lambs.

Fenbendazole given orally to experimentally infected lambs at a dose rate of 5 mg per kg was found to be 100 per cent effective against three and 10-day larave and also against 20-day adults of H contortus, O circumcincta, N battus and T colubriformis. The same dose was also 100 per cent effective against 10-day, 17-day larvae and 27-day adult D filaria.     

Oxfendazole--anthelmintic activity in Egyptian goats artificially infected with gastrointestinal nematodes.

The recently developed benzimidazole anthelmintic, oxfendazole, was tested against artificial nematode infestations in Egyptian goats using oral dosing at 4.5 and 2.8 mg/kg. A 100% clearance of mature and immature Haemonchus contortus, Trichostrongylus axei, Ostertagia circumcincta, Coopera curticei, Bunostomum trigonocephalum and Chabertia ovina was obtained at the 4.5 mg/kg level. Very high levels of clearance against the mature worms were obtained at 2.8 mg/kg but the drug was less effective against immature worms at the lower dose rate. PCV, hemoglobin concentration and total erythrocyte counts declined after infection but became significantly (P less than 0.001) raised in treated animal.     

Effect of ivermectin on the control of ear mites (Psoroptes cuniculi) in naturally infested rabbits.

We examined the efficacy of ivermectin in the control of ear mites (Psoroptes cuniculi) in rabbits. The study involved 40 female and 35 male rabbits that were known to be naturally infested with ear mites. After a period of acclimation to the animal care facilities, the rabbits were ranked on the visual appearance of any ear lesion and the number of mites on glycerin-dipped ear swabs. The rabbits were then randomly assigned to 1 of 4 treatment groups; vehicle only (group 1), 50 micrograms of ivermectin/kg of body weight (group 2), 100 micrograms of ivermectin/kg (group 3) and 200 micrograms of ivermectin/kg (group 4). The rabbits were treated by SC injections on day 0 and day 14 of the trial; thus, the total dose of ivermectin given to groups 1 through 4, was 0, 100, 200, or 400 micrograms/kg, respectively. The study ended 2 weeks after the last treatment. Ear lesions of the treated rabbits improved significantly (P less than 0.001). By 28 days after the first treatment, the mean number of mites on the ear swabs (both ears) was 57.5 for untreated rabbits and 9.1, 0.5, and 2.5, respectively, for rabbits in groups 2, 3, and 4. The mean number of mites recovered from the ears of the untreated rabbits at necropsy was 24,297. For groups 2, 3, and 4, the mean number of mites recovered from the ears was 5,352, 96, and 96, respectively. The efficacy of treatment with a total dose of 100 micrograms/kg was 77.96%, with 200 micrograms/kg was 99.61%, and for 400 micrograms/kg was 99.61%.