Controlled test of anthelmintic activity of a macrocyclic lactone (compound F28249-alpha) in lambs

A controlled blind test was performed in 1984 to evaluate the anthelmintic activity of experimental formulations of compound F28249-alpha against gastrointestinal parasites in lambs in Kentucky. Twenty-five lambs were allotted to 5 groups of 5 lambs/group. The drug was administered SC to 2 groups (A, 0.2 mg/kg of body weight; B, 0.3 mg/kg) and orally to 2 groups (C, 0.2 mg/kg; D, 0.3 mg/kg). Group E received a placebo subcutaneously. Lambs were euthanatized 7 days after treatment for necropsy and identification and enumeration of worm parasites in the gastrointestinal tract. Group-E lambs harbored 7 genera (including 10 species) of nematodes and 1 genus of tapeworms. Worm collection data for group-A lambs indicated 97% to 100% of the mature Haemonchus, Ostertagia, Trichostrongylus, and Trichuris, and immature Haemonchus were removed; and 23% to 73% of the mature Cooperia, Nematodirus, and Strongyloides, and immature Nematodirus were removed. In group-B lambs, 94% to 100% of the mature Haemonchus, Nematodirus, Ostertagia, Trichostrongylus, and Trichuris, and immature Haemonchus were removed as were 70% to 84% of mature Strongyloides and immature Nematodirus, respectively, and 0% for mature Cooperia. The percentage of all nematodes removed in group C and D was 100%, except for Cooperia (95%) in group C and immature Nematodirus (93% and 95%), respectively. Toxicosis was not apparent. Small fibrotic or blood streaked lesions were observed at necropsy in muscle at the injection site of 2 lambs in group B and 1 lamb in group E.     

Critical and controlled tests of activity of a macrocyclic lactone (compound F28249-alpha) against natural infections in internal parasites of equids

Thirteen critical tests (n = 11 horses and 2 ponies) and 4 controlled tests (n = 4 donkeys and 6 horses) were performed to evaluate the activity of the experimental macrocyclic lactone compound F28249-alpha against internal parasites of equids. In the critical tests, activity was determined mainly against the large parasites, but 1 critical test also included benzimidazole-resistant small strongyles. In the controlled tests, evaluation of drug activity included large parasites and stomach worms in all 4 tests, and lungworms in 2 tests. The period between treatment and euthanasia was 6 to 9 days for the critical tests and 14, 17, or 52 days for the controlled tests. The compound was administered by stomach tube at dose rates of 1, 2, 3, 3.5, or 4 mg/kg of body weight. In the critical tests, removal at all 5 dose rates was 100% for Gasterophilus nasalis (2nd and 3rd instars), Parascaris equorum (mature), Strongylus vulgaris, and Strongulus edentatus from the gastrointestinal tract. For Gasterophilus intestinalis in the stomach, mean removals of 2nd instars were 88% at the rate of 2 mg/kg and 93% to 100% at rates greater than or equal to 3 mg/kg. For 3rd instars, mean removals were 7% at 1 mg/kg, 77% at 2 mg/kg, 90% at 3 mg/kg, and 98% at 3.5 mg/kg. Discharge of G intestinalis in feces was typically a slow, prolonged process and probably higher removal values, especially at lower dose rates, would have attended a longer interval after treatment before necropsy examination.(ABSTRACT TRUNCATED AT 250 WORDS)     

Farm management practices associated with macrocyclic lactone resistance on sheep farms in New Zealand

AIM: To identify farm practices associated with the presence of resistance to a macrocyclic lactone (ML) anthelmintic on sheep farms in New Zealand.

METHODS: A cross-sectional study was conducted to test for associations between the presence of resistance to an ML anthelmintic (ivermectin) and management practices on sheep farms in New Zealand. Selection of farms was both random (n=80) and purposive (n=32; being farms with a history of suspected ML resistance). Resistance was inferred from faecal nematode egg count (FEC) reduction (FECR) tests (FECRTs) when there was <95% reduction in FEC 7–10 days after treatment with a half dose of ivermectin (0.1 mg/kg). A logistic regression model was built to identify farm-level factors that were associated with the presence or absence of ML resistance.

RESULTS: Of the 112 flock managers that were approached for interview, 103 (92%) returned useable questionnaires. The odds of ML resistance were increased: on farms that had used long-acting ML products in ewes as a pre-lambing treatment for ≥3 of the previous 5 years (odds ratio (OR) = 7.2; 95% confidence interval (CI) = 1.7–30.3); on farms where <70% of the total stock units mid-winter were from sheep (OR=6.5; 95% CI=1.6–25.6); on farms which over the year purchased ≥10% of the number of sheep present mid-winter (OR=7.1; 95% CI=1.5–34.7); and on farms where the average wool diameter of the main flock was <37 (OR=4.1; 95% CI=1.1–14.7) microns. The model provided a good fit to the data (pseudo R²=0.64; Hosmer-Lemeshow statistic = 0.38).

CONCLUSIONS: Explanatory factors identified as associated with the presence of ML (ivermectin) resistance on farms included the use of long-acting anthelmintic formulations in ewes pre-lambing, sources of refugia of unselected parasites on the farm, breed of sheep and their requirements for anthelmintic treatments, and the importing of resistant parasites with purchased stock. The study provides support for controls that aim to provide refugia of susceptible worms and that minimise the risk of introduction of resistance through effective quarantine-drenching.     

Farm management practices associated with macrocyclic lactone resistance on sheep farms in New Zealand

AIM: To identify farm practices associated with the presence of resistance to a macrocyclic lactone (ML) anthelmintic on sheep farms in New Zealand. METHODS: A cross-sectional study was conducted to test for associations between the presence of resistance to an ML anthelmintic (ivermectin) and management practices on sheep farms in New Zealand. Selection of farms was both random (n=80) and purposive (n=32; being farms with a history of suspected ML resistance). Resistance was inferred from faecal nematode egg count (FEC) reduction (FECR) tests (FECRTs) when there was <95% reduction in FEC 7-10 days after treatment with a half dose of ivermectin (0.1 mg/kg). A logistic regression model was built to identify farm-level factors that were associated with the presence or absence of ML resistance. RESULTS: Of the 112 flock managers that were approached for interview, 103 (92%) returned useable questionnaires. The odds of ML resistance were increased: on farms that had used long-acting ML products in ewes as a pre-lambing treatment for > or =3 of the previous 5 years (odds ratio (OR) = 7.2; 95% confidence interval (CI) = 1.7-30.3); on farms where <70% of the total stock units mid-winter were from sheep (OR=6.5; 95% CI=1.6-25.6); on farms which over the year purchased >10% of the number of sheep present mid-winter (OR=7.1; 95% CI=1.5-34.7); and on farms where the average wool diameter of the main flock was <37 (OR=4.1; 95% CI=1.1-14.7) microns. The model provided a good fit to the data (pseudo R2=0.64; Hosmer-Lemeshow statistic = 0.38). CONCLUSIONS: Explanatory factors identified as associated with the presence of ML (ivermectin) resistance on farms included the use of long-acting anthelmintic formulations in ewes pre-lambing, sources of refugia of unselected parasites on the farm, breed of sheep and their requirements for anthelmintic treatments, and the importing of resistant parasites with purchased stock. The study provides support for controls that aim to provide refugia of susceptible worms and that minimise the risk of introduction of resistance through effective quarantine drenching.     

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.     

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.     

Anthelmintic activity of continuous low doses of fenbendazole into the rumen of sheep

Fenbendazole (FBZ) was continuously infused for 30 days into the rumen of 103 lambs which had mature or developing benzimidazole-susceptible or thiabendazole-resistant Haemonchus contortus and susceptible Trichostrongylus colubriformis infections. Ovicidal, larvicidal and adulticidal activities were exhibited against benzimidazole-susceptible and benzimidazole-resistant H. contortus worms by FBZ at a dose level of greater than or equal to 0.2 mg kg-1 body weight day-1. Reasonably consistent high level efficacy against H. contortus was obtained with dose levels greater than 0.4 mg kg-1. Excellent control of susceptible T. colubriformis worms was achieved with the lowest dose tested of 0.4 mg kg-1 day-1. The intraruminal infusion critical study method is a tool to determine the feasibility of incorporating a candidate anthelmintic compound in a continuous sustained-release rumen device formulation. The anthelmintic profile of FBZ obtained by low-level intraruminal administration suggests that it would be a potential candidate.     

Ivermectin-resistant Ostertagia circumcincta from sheep in the lower North Island and their susceptibility to other macrocyclic lactone anthelmintics

AIM: To confirm the ivermectin resistance status of a strain of Ostertagia circumcincta which was isolated from a sheep farm in the lower North Island of New Zealand and to assess the susceptibility of this strain to other macrocycliclactone anthelmintics. METHODS: Twenty-five lambs housed indoors were each infected with 12,000 L3 larvae of the above parasite strain. Approximately 3 weeks after infection the lambs were allocated to 1 of 4 treatment groups (3 groups of 6, and 1 group of 7 lambs), one of which remained untreated while the others were drenched orally with ivermectin, moxidectin or abamectin at 0.2 mg/kg liveweight. Faecal egg counts (FECs) before and after treatment, and post-mortem worm burdens 10 days after treatment were examined to assess efficacies of each anthelmintic. RESULTS: Treatment with ivermectin reduced the mean FEC by only 18% and the mean worm burden by only 42%, whereas moxidectin and abamectin reduced FECs by 92% and worm burdens by 95%. CONCLUSION: These results, together with a similar case described recently from the South Island , confirm the emergence of ivermectin resistance in nematode parasites of sheep in New Zealand. The superior efficacy of moxidectin and abamectin in this case indicates that, following the emergence of resistance to ivermectin, some short-term practical use may still be made of these other anthelmintics. However, their continued use will undoubtedly result in increased levels of resistance and eventual therapeutic failure of these products also.     

Ivermectin-resistant Ostertagia circumcincta from sheep in the lower North Island and their susceptibility to other macrocyclic lactone anthelmintics

Aim: To confirm the ivermectin resistance status of a strain of Ostertagia circumcincta which was isolated from a sheep farm in the lower North Island of New Zealand and to assess the susceptibility of this strain to other macrocycliclactone anthelmintics.

Methods: Twenty-five lambs housed indoors were each infected with 12,000 L3 larvae of the above parasite strain. Approximately 3 weeks after infection the lambs were allocated to 1 of 4 treatment groups (3 groups of 6, and 1 group of 7 lambs), one of which remained untreated while the others were drenched orally with ivermectin, moxidectin or abamectin at 0.2 mg/kg liveweight. Faecal egg counts (FECs) before and after treatment, and post-mortem worm burdens 10 days after treatment were examined to assess efficacies of each anthelmintic.

Results: Treatment with ivermectin reduced the mean FEC by only 18% and the mean worm burden by only 42%, whereas moxidectin and abamectin reduced FECs by > 92% and worm burdens by >95%.

Conclusion: These results, together with a similar case described recently from the South Island, confirm the emergence of ivermectin resistance in nematode parasites of sheep in New Zealand. The superior efficacy of moxidectin and abamectin in this case indicates that, following the emergence of resistance to ivermectin, some short-term practical use may still be made of these other anthelmintics. However, their continued use will undoubtedly result in increased levels of resistance and eventual therapeutic failure of these products also.     

Anthelmintic activity of artesunate against Fasciola hepatica in naturally infected sheep

In light of rapidly spreading triclabendazole resistance alternative fasciocidal drugs are urgently needed. Following up on promising results obtained with artemether in Fasciola hepatica infected sheep, we here report the efficacy and safety of artesunate in sheep with a natural F. hepatica infection. Artesunate was administered intravenously and intramuscularly, adverse events were monitored and drug efficacy was elucidated by means of faecal egg and worm burden reductions. A single 40 mg/kg intravenous dose of artesunate induced an egg count reduction of 68.9% and a worm burden reduction of 77.4%. Intramuscular artesunate at 40 mg/kg reduced faecal egg count and worm burden by 97.6% and 91.9%, respectively; whereas at 60 mg/kg it caused 93.2% and 87.1% reduction in faecal egg count and worm burden, respectively. Three sheep died 24-72 h post-treatment with a double dose of 40 mg/kg intramuscular artesunate, showing lethargy, sialorrhoea, reduced rumination and tremors. Egg and worm burden reductions of 93.3% and 83.9%, respectively, were calculated in the three surviving sheep. In conclusion, the interesting fasciocidal properties of artesunate in sheep warrant further investigations with an emphasis on toxicity studies.     

Anthelmintic activity of Azadirachta indica A. Juss against sheep gastrointestinal nematodes

Gastrointestinal nematode control has been performed through use of anthelmintics. However, the development of resistant populations has required research into new alternatives. There are popular reports about anti-parasitic activity of Azadirachta indica in animals and plants. The aim of this study was to evaluate the anthelmintic activity of A. indica after feeding sheep with the dried leaves. In this experiment, 40 sheep were allotted into four treatment groups. Group I received a treatment of A. indica dry leaves mixed in a concentrate at a rate of 0.1 g/kg dose for 3 months. Group II was treated with double the dose of Group I. Group III was treated with closantel (Diantel) at the manufacturer-recommended dose once at the beginning of the study and Group IV was not treated. To compare treatment effects, the following parameters were evaluated: egg count per gram of feces (EPG), worm burden, weight gain and haematocrit. EPG and worm burden results were statistically evaluated using the Kruskal-Wallis test. Haematocrit and live weight gain were submitted to analysis of variance (ANOVA) and the means evaluated by Tukey's test with 95% probability. None of the evaluated parameters of the treatment groups were statistically different when compared to the control group, demonstrating that, with the protocol used, A. indica has no anthelmintic effect.     

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.