The efficacy and plasma profiles of abamectin plus levamisole combination anthelmintics administered as oral and pour-on formulations to cattle.

In phase I, faecal egg count reduction tests (FECRT) were conducted on six commercial cattle farms to compare the performance of two pour-on and one oral combination anthelmintic. Groups of 12-15 calves were sampled for faecal nematode egg count (FEC) before treatment with either abamectin oral, levamisole oral, an abamectin+levamisole oral combination or one of two abamectin+levamisole combination pour-ons. Samples were collected again 14days after treatment to calculate the percentage reduction in FEC. The proportions of infective stage larvae (L3) in faecal cultures were used to apportion egg counts to, and calculate efficacy against, the main parasite genera. Abamectin oral was effective against Ostertagia except on one farm where resistance was indicated, but had reduced efficacy against Cooperia on four farms. Levamisole oral was effective against Cooperia on all farms, but had variable efficacy against Ostertagia. The abamectin+levamisole oral was effective against both species on all farms. The abamectin+levamisole pour-ons were effective on some farms but not on others. In particular, pour-on 2 failed to achieve 95% efficacy in 45% of evaluations, 4/6 against Cooperia and 1/5 against Ostertagia. On some farms the combination pour-ons were less effective than their constituent actives administered alone as orals. In phase II, 8 groups of 6 calves, grazing parasite-free pasture, were infected with putatively ML-resistant isolates of Cooperia oncophora and Ostertagia ostertagi. Once infections were patent groups were treated with oral or pour-on formulations of abamectin alone, levamisole alone, abamectin+levamisole (two pour-ons) or remained untreated. Blood samples were collected for analysis and after 8days all calves were euthanized and abomasa and intestines recovered for worm counts. All treatments were effective against O. ostertagi and all treatments containing levamisole were effective against C. oncophora. Animals treated with the oral combination had higher Cmax and AUC values for abamectin in plasma than animals treated orally with abamectin alone. In contrast, animals treated with the combination pour-ons tended to have lower plasma levels for abamectin than those treated with abamectin alone as a pour-on, with differences in the Cmax and AUC values approaching statistical significance (p-values ≤0.07). There were no differences detected in plasma concentrations of levamisole. The inconsistent and sometimes poor efficacy of the combination pour-ons on-farm is likely due to reduced levels of abamectin in the plasma and hence less active reaching the target worms in the gut.

Managing anthelmintic resistance--use of a combination anthelmintic and leaving some lambs untreated to slow the development of resistance to ivermectin.

A field study was conducted to test the hypotheses that use of a combination anthelmintic and/or increasing the pool of unselected worms 'in refugia' by leaving a proportion of lambs untreated would slow the development of resistance to ivermectin. Twelve suites of four paddocks (farmlets) were seeded with a mixture of resistant and susceptible isolates of both Trichostrongylus colubriformis and Teladorsagia (Ostertagia) circumcincta calculated to yield a 95% reduction in faecal nematode egg count (FEC) after treatment with ivermectin. Each year for three years the farmlets were stocked in the spring with mobs of lambs which were treated five times at 28-day intervals with either ivermectin or an ivermectin+levamisole combination. In addition, in half the mobs the heaviest 10% of lambs remained untreated at each treatment occasion, resulting in a 2 × 2 factorial treatment structure (i.e. two drench types × two percentage treated) with three complete replicates. The development of resistance to ivermectin, and at the end to levamisole, was measured by larval development assays (LDA) and worm counts from treated and untreated tracer lambs. For T. colubriformis the development of resistance to ivermectin, as measured by tracer lamb worm burdens, was delayed by treatment with the combination and by leaving 10% of lambs untreated. In addition, the interaction between these factors approached significance (p=0.052). Similarly, results of the LDAs indicated a slower development of resistance when lambs were treated with the combination and when 10% of lambs were left untreated. For T. circumcincta, results were compromised by the rapid development of resistance, which appears to be the result of low viability in the field of the susceptible isolate used to contaminate the pastures. Although a small delay in the development of resistance to ivermectin was indicated, this was off-set by an increase in the level of resistance to levamisole. A post-study modelling experiment simulating the conditions of the field study and the starting efficacies for the two nematode species produced equivalent outputs to those measured in the field. Overall, results support the conclusions that use of combination anthelmintics and deliberately increasing 'refugia' of unselected genotypes will slow the development of anthelmintic resistance. However, as indicated in modelling studies, once resistance to all the constituent actives is well developed (efficacy<70%) the value of combinations for slowing the development of resistance is largely lost.

The production cost of anthelmintic resistance in lambs.

The economic impact of anthelmintic resistance was investigated in lambs by comparing productivity parameters in groups of animals treated either with a highly effective anthelmintic, or an anthelmintic to which three species of resistant worms were known to be present. Ten farmlets, each stocked with 30 lambs, were rotationally grazed for 5 months, with monthly treatments of either albendazole, to which resistance existed, or a new combination product containing derquantel and abamectin (DQL-ABA) to which there was no resistance. Stock on five farmlets were treated with each anthelmintic and productivity measures, including liveweights, body condition and faecal soiling were assessed throughout. In addition, fleece weights and information on carcass weight and quality was collected at the end of the trial. Anthelmintic efficacy was measured at the last two treatment dates by faecal egg count reduction test with larval cultures. Albendazole demonstrated efficacies of 48.4% and 40.9% for Trichostrongylus spp. and Teladorsagia circumcincta respectively. By contrast, the DQL-ABA treatments were >99% effective against all genera. The difference in live-weight gain was 9 kg in favour of the DQL-ABA treatments. This translated into a 4.7 kg increase in carcass weight with a 10.4% increase in carcass value. Significant differences in body condition scores, faecal breech soiling and fleece weights were also recorded, all in favour of the DQL-ABA treatments. The time required for 50% of the animals to reach a target live-weight of 38 kg was significantly shorter (by 17 days) in those animals treated with DQL-ABA. The results show that the production cost of subclinical parasitism as a result of using an anthelmintic product which is less than fully effective due to resistance can greatly exceed the cost of routine testing of anthelmintic efficacy and the adoption of new anthelmintic classes. There is a strong case for many farmers to re-evaluate their position on some of these issues in order to optimise financial performance.