Sheep-farm risk factors for ivermectin resistance in Ostertagia circumcincta in Western Australia

On-farm risk factors associated with ivermectin resistance on sheep farms in Western Australia were identified from data derived from a postal survey of 235 farmers who had conducted a fecal egg-count-reduction test in 1999, 2000, or both years. A response of 54% was achieved. We developed a logistic-regression model. Contributory main effects in the final model were selling 10% more sheep in 2000 than is the usual policy (OR=4.00), farm purchased since 1975 (OR=2.34), and number of winter flock anthelmintic treatments in the previous 5 years (OR=1.04). A secondary logistic-regression model assessed risk factors for farms selling 10% more sheep than usual in 2000; these farmers appeared less committed to their sheep enterprises than other farmers. These results are discussed in relation to current hypotheses of anthelmintic resistance. This is the first time that the farmer’s management of the flock has been implicated in the development of anthelmintic resistance.     

Resistance to ivermectin in a field strain of Ostertagia spp. in goats

The occurrence of a field strain of Ostertagia spp. showing a resistance to ivermectin in Angora goats is reported. In a controlled anthelmintic trial using naturally-infected goats, ivermectin at a dose rate of 0.2 mg/kg demonstrated an efficacy of 87% against this strain.     

Confirmation of resistance to ivermectin by Cooperia curticei in sheep

AIM: To investigate the occurrence of resistance to a full dose of oral ivermectin by Cooperia curticei in sheep.

METHODS: Twelve lambs on a sheep and cattle property in the North Island of New Zealand were randomly allocated to one of two equal-sized groups. One group was treated orally with a single dose of ivermectin at the manufacturer's recommended dose rate of 0.2 mg/kg, while the other remained as an untreated control. Worm counts were carried out post mortem on the abomasa and small intestines of all animals in both groups 7 days after treatment.

RESULTS: While treatment with ivermectin reduced the numbers of all other worm genera to almost zero, those of Ostertagia (= Telodorsagia) circumcincta and C. curticei were reduced by only 37% and 19%, respectively.

CONCLUSIONS: These results provide clear evidence of resistance to ivermectin by O. circumcincta and C. curticei. They also appear to represent the first record of macrocylic lactone (ML) resistance in C. curticei in sheep in New Zealand or elsewhere.     

Confirmation of resistance to ivermectin by Cooperia curticei in sheep

AIM: To investigate the occurrence of resistance to a full dose of oral ivermectin by Cooperia curticei in sheep. METHODS: Twelve lambs on a sheep and cattle property in the North Island of New Zealand were randomly allocated to one of two equal-sized groups. One group was treated orally with a single dose of ivermectin at the manufacturer's recommended dose rate of 0.2 mg/kg, while the other remained as an untreated control. Worm counts were carried out post mortem on the abomasa and small intestines of all animals in both groups 7 days after treatment. RESULTS: While treatment with ivermectin reduced the numbers of all other worm genera to almost zero, those of Ostertagia(= Telodorsagia) circumcincta and C. curticei were reduced by only 37% and 19%, respectively. CONCLUSIONS: These results provide clear evidence of resistance to ivermectin by O. circumcincta and C. curticei. They also appear to represent the first record of macrocylic lactone (ML) resistance in C. curticei in sheep in New Zealand or elsewhere.     

Resistance to benzimidazole anthelmintics in field strains of Ostertagia and Nematodirus in sheep

SUMMARY: Resistance to a range of benzimidazole anthelmintics was investigated in 2 strains of Ostertagia spp. One strain (SRBO) had been exposed to fenbendazole, oxfendazole and thiabendazole, the other strain (KR79) only to thiabendazole. Both strains showed a high degree of resistance to albendazole, fenbendazole, oxfendazole and thiabendazole, which had efficiencies of 11–38% and 0–60% against all developmental stages of SR80 and KR79, respectively. There was no significant reduction in the KR79 worm count by thiabendazole at 132 mg kg-1 given either as a single dose or divided into 12 equal portions, one administered every 6h. Nematodirus spp were also found to be resistant to all benzimidazoles tested. Levamisole at 7 mg kg^-1 and naphthalophos at 30 mg kg-1 had efficiences of 89 and 66%, respectively, against SR80 Ostertagia and 99 and 19% against Nematodirus, all but the last of these being significant reductions in worm burdens. The resistant SR80 Ostertagia occurred on a research station, but possibly originated from a property which 3 years earlier had supplied ewes to the station. The use of benzimidazole anthelmintics and subsequent grazing on worm-free pasture may have enhanced the level of resistance. A relationship was established between egg counts and adult worm counts 10 days post-treatment, which suggested that for Ostertagia the worm count could be predicted from the geometric mean egg count from about 10 animals. Thus, where an Ostertagia population is suspected of being resistant, an anthelmintic efficiency assay using pre-and post-treatment faecal egg counts should provide a satisfactory diagnostic procedure.     

Resistance to thiabendazole in a field population of Ostertagia circumcincta from sheep.

A population of Ostertagia circumcincta from sheep has been found which, in field and laboratory trials, showed a lack of response to the recommended dose (44 mg/kg) of thiabendazole, suggesting that a degree of resistance exists to this anthelmintic. Preliminary experiments indicated a less than expected response to levamisole. This was not confirmed in a laboratory trial and therefore resistance to this anthelmintic has not been shown conclusively.     

Haemonchus contortus resistance to ivermectin and netobimin in Brazilian sheep.

Suffolk, Texel, Hampshire Down and Ile de France sheep from the municipalities of Porto Amazonas, Piraquara and Araucaria in the State of Paraná, and Bagé in the State of Rio Grande do Sul were brought to Sobral, State of Ceará, to be used in a cross-breeding project. On arrival they had clinical signs of nematode parasitosis, and one Suffolk female died. The animals were treated orally with ivermectin (0.2 mg kg-1) and fifteen days later with netobimin (20.0 mg kg-1). Neither drug reduced the egg counts (measured in eggs per gram, EPG) significantly, and this suggested that the nematodes in the sheep were resistant to the anthelmintics used. Haemonchus contortus was the species involved. The egg counts were reduced after oral treatment with trichlorfon (100.0 mg kg-1). Haemonchus contortus larvae obtained from these animals before trichlorfon treatment and passaged through two nematode-free sheep were used in a further experiment. Twenty 6- to 9-month-old nematode-free lambs were infected with the H. contortus larvae (10,000 per animal) and after the infection was confirmed, were randomly divided into four groups of five animals. Group I was orally treated with ivermectin at 0.2 mg kg-1, Group II with oral netobimin at 20.0 mg kg-1, Group III with oral trichlorfon at 100.0 mg kg-1 and Group IV was a non-treated control. Egg counts and faecal cultures were taken before dosing on the day of treatment and seven days later when all animals were necropsied and the nematodes were collected from the abomasa and counted.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of ivermectin against inhibited larvae of Ostertagia ostertagi

The efficacy of ivermectin against inhibited early 4th-stage larvae of ostertagia ostertagi and other nematodes of the abomasum and intestinal tract was determined in naturally infected yearling beef cattle. The time when large numbers of inhibited larvae were acquired was determined by monthly slaughter of monitor cattle, beginning in January. In April, 12 animals were removed from pasture and maintained free of further helminth exposure until slaughter (21 days). At 9 days after the cattle were removed from pasture, ivermectin was administered to the principals by subcutaneous injection (200 micrograms/kg); the other 6 animals were given subcutaneous injections of the ivermectin vehicle. both groups were klled and necropsied at 12 days after treatment. Mean numbers of O ostertagi in the 6 controls were: adults, 41,906; developing 4th stage, 73,813; and early 4th stage, 334,965. The mean proportion of early 4th-stage larvae was 73.7%. In the 6 principals (treated with ivermectin), the following reductions were observed: O ostertagi adults, 100%; developing 4th stage, 99.8%; and early 4th stage, 99,9%. Small numbers of dead and degenerated O ostertagi of all developmental stages were recovered from abomasal washings before fixation; few viable worms were recovered.     

Evidence that moxidectin is a greater risk factor than ivermectin in the development of resistance to macrocyclic lactones by Ostertagia spp in sheep in south eastern Australia

AIM: To determine associations between resistance of Ostertagia (=Teladorsagia) spp to macrocyclic lactone (ML) anthelmintics and history of use of anthelmintics, by type, on commercial sheep farms in temperate regions of southern South Australia and Victoria, Australia. METHODS: Faecal egg count reduction tests (FECRTs) were conducted during a 2.5-year period (from August 2001 to January 2004) and records of the type of anthelmintic used in the 5 years preceding the FECRTs were collected from commercial sheep farms (n=103) in southern South Australia and Victoria, and data analysed retrospectively. ML resistance was defined as <95% reduction of Ostertagia spp 10-14 days after treatment with ivermectin (IVM), orally, at half the manufacturer's recommended dose rate. Use of anthelmintics in the preceding 5 and 10 years on each property was classified according to the nett number of years each of the following classes of drug had been used: IVM oral liquid (IVO), IVM controlled-release capsules (CRCs), abamectin (ABA), moxidectin (MOX) or a non-ML anthelmintic. The prevalence of ML resistance, by property, was analysed for associations with prior use of anthelmintics. RESULTS: Resistance by Ostertagia spp to ML anthelmintics was evident on 51/103 (49.5%) properties. The prevalence of resistance was lowest (23%) on properties on which MOX had not been used, and was significantly higher (64-77%) on properties on which MOX had been used for > or =2 of the preceding 5 years (p<0.001). In contrast, the prevalence of resistance was highest (70-74%) on the properties on which IVM, or IVM and/ or ABA, had not been used in the previous 5 years (on which the use of MOX was predominant), and was markedly lower (20- 42%) on properties that had used IVM or IVM and/or ABA for at least one of the preceding 5 years. Prevalence of resistance was higher for properties on which the only ML anthelmintic used was MOX (19/29=66%) than for those on which the only ML used was IVO (2/19=11%; p<0.001). Properties on which the only ML used was MOX were 2.72 times more likely to have resistance than properties on which the only ML used was IVO (95% confidence interval (CI) = 1.01-5.08). CONCLUSION: Use of MOX for > or =2 of the preceding 5 years was associated with a higher prevalence of resistance to ML by Ostertagia spp on sheep farms in south eastern Australia than the use of IVO.     

Evidence that moxidectin is a greater risk factor than ivermectin in the development of resistance to macrocyclic lactones by Ostertagia spp in sheep in south eastern Australia

AIM: To determine associations between resistance of Ostertagia (= Teladorsagia) spp to macrocyclic lactone (ML) anthelmintics and history of use of anthelmintics, by type, on commercial sheep farms in temperate regions of southern South Australia and Victoria, Australia.

METHODS: Faecal egg count reduction tests (FECRTs) were conducted during a 2.5-year period (from August 2001 to January 2004) and records of the type of anthelmintic used in the 5 years preceding the FECRTs were collected from commercial sheep farms (n=103) in southern South Australia and Victoria, and data analysed retrospectively. ML resistance was defined as <95% reduction of Ostertagia spp 10–14 days after treatment with ivermectin (IVM), orally, at half the manufacturer's recommended dose rate. Use of anthelmintics in the preceding 5 and 10 years on each property was classified according to the nett number of years each of the following classes of drug had been used: IVM oral liquid (IVO), IVM controlled-release capsules (CRCs), abamectin (ABA), moxidectin (MOX) or a non-ML an- thelmintic. The prevalence of ML resistance, by property, was analysed for associations with prior use of anthelmintics.

RESULTS: Resistance by Ostertagia spp to ML anthelmintics was evident on 51/103 (49.5%) properties. The prevalence of resistance was lowest (23%) on properties on which MOX had not been used, and was significantly higher (64–77%) on properties on which MOX had been used for ≥2 of the preceding 5 years (p<0.001). In contrast, the prevalence of resistance was highest (70–74%) on the properties on which IVM, or IVM and/ or ABA, had not been used in the previous 5 years (on which the use of MOX was predominant), and was markedly lower (20– 42%) on properties that had used IVM or IVM and/or ABA for at least one of the preceding 5 years. Prevalence of resistance was higher for properties on which the only ML anthelmintic used was MOX (19/29=66%) than for those on which the only ML used was IVO (2/19=11%; p<0.001). Properties on which the only ML used was MOX were 2.72 times more likely to have resistance than properties on which the only ML used was IVO (95% confidence interval (CI) = 1.01–5.08).

CONCLUSION: Use of MOX for ≥2 of the preceding 5 years was associated with a higher prevalence of resistance to ML by Ostertagia spp on sheep farms in south eastern Australia than the use of IVO.     

Anthelmintic resistance in nematode parasites of sheep in Denmark with special emphasis on levamisole resistance in Ostertagia circumcincta.

This study was undertaken to elucidate the presence of anthelmintic resistance in nematode parasites of sheep in Denmark. Twenty two flocks of sheep were selected for Faecal Egg Count Reduction (FECR) tests, based on a prior history of either the same anthelmintic, or anthelmintic class having been used 3 times or more over the previous 5 years. Evidence of anthelmintic resistance was detected in 7 flocks. Two flocks showed FECR of 88% and 94% after treatment with thiabendazole, FECR of another 2 were 90% and 94% following treatment with fenbendazole. Three flocks showed FECR of 73%, 89% and 94%, respectively following the use of levamisole. Ostertagia circumcincta was isolated from 1 of the latter flocks and subjected to an in vivo controlled slaughter assay. Following treatment with levamisole at the recommended dose rate of 7.5 mg/kg, FECR was 44.5% and worm counts were reduced by 67.7%. These results were further substantiated by an in vitro egg hatch paralysis assay and by measuring pepsinogen levels in treated and non-treated lambs. This is the first instance of anthelmintic resistance in sheep nematodes in Scandinavia.     

A small scale survey of ivermectin resistance in sheep nematodes using the faecal egg count reduction test on samples collected from Scottish sheep

Thirty-eight sheep flocks, predominantly from the south/central Scotland, were examined using a faecal egg count reduction test (FECRT) for the presence of ivermectin (IVM) resistant nematodes. Efficacies of less than 95%, 14-17 days post-treatment, were identified in 6 of 17 naturally grazing flocks where pre-treatment faecal egg counts were in excess of 150 eggs per gram. Efficacies on these IVM resistant farms ranged from 66 to 92%. One other suspected cases of IVM resistance was also identified in returned material. The larvae detected in post-treatment coprocultures from resistant flocks were from the genera Teladorsagia (4 from 6) and Trichostrongylus (2 from 6).     

Non-confirmation of anthelmintic resistance in Ostertagia spp

An investigation was undertaken to confirm the existence of a mebendazole-resistant strain of Ostertagia spp. on a ram-breeding property in Taihape. The results indicated that while a strain of Haemonchus contortus from this farm was highly resistant to mebendazole, an isolate of Ostertagia spp. was fully susceptible. Possible reasons for the discrepancy between previous and present findings are briefly discussed.     

The pharmacodynamics of ivermectin in sheep and cattle

The concentrations of ivermectin in the gastrointestinal tract of sheep and cattle were determined after subcutaneous administration of ivermectin. Ivermectin was not detected (limit of detection 1 ng/ml) in abomasal and ruminal fluids either after a normal therapeutic dose of 200 micrograms/kg or even at an increased dose of 2000 micrograms/kg. It was also not detected in abomasal and ruminal fluids of a sheep infected with the abomasal parasite Ostertagia circumcincta. However, ivermectin was detectable at similar concentrations in abomasal mucus and in small intestinal mucus. Excretion of ivermectin was high in bile but the concentrations in small intestinal mucus, distal and proximal to the bile duct opening, were similar. It is hypothesized that the low efficacy of ivermectin against small intestinal nematodes compared with abomasal nematodes is not due to differences in ivermectin concentrations in the predilection sites but is probably due to tachyphylaxis in the nematodes allowing the small intestinal nematodes to re-establish before they have left their predilection site. Ivermectin was excreted in the milk of ewes at concentrations similar to those in plasma. Lambs suckling ivermectin-treated ewes received about 4% of a normal therapeutic dose (200 micrograms/kg) via the milk.     

Pharmacokinetics of ivermectin in pregnant and nonpregnant sheep

The plasma kinetic profile of ivermectin during the last trimester of pregnancy was studied in ewes after a single subcutaneous administration of 0.2 mg/kg body weight (BW). Sheep were randomly distributed into two groups. Ewes in group 1 (control, n=6) were left unmated, whereas in group 2 (pregnant, n=6) ewes were estrus-synchronized and mated with rams. Both groups were housed under similar conditions of management and feeding. At 120 days of pregnancy, both groups were given a subcutaneous injection of 0.2 mg/kg BW of ivermectin. Blood samples were taken by jugular puncture according to a fixed protocol between 1 h and 40 days post-treatment. After plasma extraction and derivatization, samples were analyzed by high performance liquid chromatography with fluorescence detection. A computerized pharmacokinetic analysis was performed, and the data were compared by means of the Student t-test. The results showed that plasma concentrations of ivermectin remained longer in the pregnant than in the control group. The mean values of pharmacokinetic parameters C(max), t(max), and area under the concentration-time curve (AUC) were similar for both groups of sheep. The mean residence time (MRT) values for the pregnant group (8.8+/-1.4 days) were higher (P<0.05) than those observed in the control group (5.3+/-1.9 days). It can be concluded that pregnancy increases the residence time of ivermectin in the plasma of pregnant sheep when it is administered subcutaneously.