Risk factors for macrocyclic lactone anthelmintic resistance on New Zealand sheep farms

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Slide 1 : Risk factors for macrocyclic lactone anthelmintic resistance on New Zealand sheep farms Lawrence, K.1, Jackson, R.2 and Heuer, C.2 1Farm Services, Massey University; 2Epicentre, Massey University.
Slide 2 : Study background Between December 2004 and June 2005 a cross- sectional survey was undertaken to estimate the prevalence of anthelmintic resistance on sheep farms throughout New Zealand Brunsdon (1988) estimated that without effective drenches sheep production in New Zealand would fall by up to 33%
Slide 3 : Aim of study To identify farm practices that are associated with macrocyclic lactone (ML) resistance on New Zealand sheep farms.
Slide 4 : Farm selection The target population was sheep farms throughout New Zealand The study population was sheep farms listed in AgriBase (AgriQuality) and farms with suspected ML resistance referred by veterinarians The sample population was a random selection from AgriBase and most ML resistant farms offered by vets.
Slide 5 : Inclusion/Exclusion criteria Size: Over 1000 breeding ewes wintered Breeds: No Merinos (physiology different) Willingness to participate in study No South Island High Country Farms (management different) Farm not purchased annually > 25% of home bred lamb numbers
Slide 6 : Approach Use faecal egg count reduction test (FECRT) to assess drench efficacy on each tested farm Use an interview based questionnaire to survey farm and parasite management practices on tested farms Combine results in a case control study
Slide 7 : Sample size 80% of target 435 farmers were contacted and screened 154 met the criteria and agreed to participate
Slide 8 : Location of selected farms 112 farms 45 practices
Slide 9 : Location of selected farms Potential bias
Slide 10 : FECRT protocol Pre-sample - 700 epg 10 lambs per treatment group Sample/tag/weigh (dose calculation) Syringe administration Resample 7-10 days post treatment Questionnaire completion
Slide 11 : Calculation of drench efficacy Presidente formula (arithmetic mean) used: Efficacy% = 100*(1-[T2/T1][C1/C2] ) T1 = Pre treatment mean faecal egg count T2 = Post treatment mean faecal egg count C1 = Pre treatment control faecal egg count C2 = Post treatment control faecal egg count
Slide 12 : Random selected farms’ results
Slide 13 : Purposively selected farms’ results
Slide 14 : Confounding effect of date of test and farm selection method
Slide 15 : Confounding variables ‘Season of test’ If farm tested before 20th March - Summer if tested after - Autumn ‘Purposively sampled’ Yes if referred otherwise No
Slide 16 : Model The outcome variable was farm ivermectin resistance defined as <95% efficacy for the half dose ivermectin treatment group Variables were first screened using chi-square, p<0.20, continuous variables were first categorised as quantiles The base model included the two confounders ‘Season of test’ and ‘Purposively sampled’
Slide 17 : Model Built by forwards stepwise inclusion, retention at p=0.05 based on Wald statistic (missing data). Model fit assessed on Hosmer-Lemeshow (HL) statistic and pseudo R-square Influential covariate patterns identified using standardised Pearson residual and delta-beta values Predictive accuracy examined by ROC curve and area under the curve (AUC)
Slide 18 : Results Hosmer-Lemeshow statistic p = 0.38, pseudo R-square = 0.64
Slide 19 : Model outcomes The model output indicated that the odds of ivermectin resistance were increased: on farms tested in the summer; on purposively sampled farms; on farms where long acting macrocyclic lactone products had been used as pre-lambing treatments for at least 3 of the previous 5 years; on farms where less than 70% of the total winter stock units were from sheep; on farms which purchased more than 10% of their winter flock numbers over the year , and on farms where the wool diameter of the main flock was less than 37 micron
Slide 20 : ROC curve AUC = 0.91
Slide 21 : Interpretation of model outcomes The associations outlined above should be considered in general terms rather than absolute values Great care should be taken before attributing causality to any of these associations Reverse causality bias can be a problem in any cross-sectional study
Slide 22 : Interpretation of model outcomes Long acting ML products – ‘head/tail’ selection, resistant worms have greater reproductive advantage at pre-lambing because refugia is low Keeping sheep stock units > 70% of total farm stock units is protective – possibly through refugia concept Purchase of large numbers of stock – makes intuitive sense Wool thickness < 37 micron – could be a proxy variable for sheep breed
Slide 23 : Summary The first reported case of ivermectin resistance was in 1999, 19 years after registration Macrocyclic lactone resistance is now widespread in New Zealand, possibly even more common than levamisole resistance A combination of within-farm selection and between-farm transmission are probably responsible. Industry complacency has also played a big part
Slide 24 : Acknowledgements Sustainable Farming Fund and Meat and Wool New Zealand. Schering-Plough Animal Health for funding. Wrightson and Allflex for sponsorship. Schering-Plough, Ancare and Merial. Veterinarians and veterinary practices throughout New Zealand for undertaking the field work. The sheep farmers who participated, completing the questionnaire and made a real effort in handling and managing stock. AgriQuality for providing data from AgriBase. The staff at AgResearch, Palmerston North, who created, managed and received all the kits and samples, and who with staff from Massey University undertook sample analysis. Tony Rhodes.

 


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