1. Preserving new anthelmintics: a simple method for estimating faecal egg count reduction test (FECRT) confidence limits when efficacy and/or nematode aggregation is high.
- Author
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Dobson, R.J., Hosking, B.C., Jacobson, C.L., Cotter, J.L., Besier, R.B., Stein, P.A., Reid, S.A., Dobson, R.J., Hosking, B.C., Jacobson, C.L., Cotter, J.L., Besier, R.B., Stein, P.A., and Reid, S.A.
- Abstract
As it has been 30 years since a new anthelmintic class was released, it is appropriate to review management practices aimed at slowing the development of anthelmintic resistance to all drug classes. Recommendations to delay anthelmintic resistance and provide “refugia” are reviewed and a simulation model used to find optimum treatment strategies that maintain nematode control. Simulated Australian conditions indicated that a common successful low-risk treatment program was a rapid rotation between a “triple-combination” product (benzimidazole + levamisole + abamectin) and a new high-efficacy drug (monepantel). Where Haemonchus contortus was a threat, moxidectin was required at critical times because of its persistent activity against this parasite. Leaving up to 4% of adult sheep untreated provided sufficient “refugia” for non-selected worms to reduce the risk of selecting for anthelmintic resistance without compromising nematode control. For a new anthelmintic, efficacy estimated by faecal egg count reduction (FECR) is likely to be at or close to 100%, however using current methods the 95% confidence limits (CL) for 100% are incorrectly determined as 100%. The fewer eggs counted pre-treatment, the more likely an estimate of 100% will occur, particularly if the true efficacy is >90%. A novel way to determine the lower-CL (LCL) for 100% efficacy is to reframe FECR as a binomial proportion, i.e. define: n and x as the total number of eggs counted (rather than eggs per gram of faeces) for all pre-treatment and post-treatment animals, respectively; p the proportion of resistant eggs is p = x/n and percent efficacy is 100*(1-p) (assuming equal treatment group sizes and detection levels, pre- and post-treatment). The LCL is approximated from the cumulative inverse beta distribution by: 95%LCL = 100*(1-(BETAINV(0.975,x + 1,n-x + 1))). This method is simpler than the current method, independent of the number of animals tested, and demonstrates that for 100% efficacy at leas
- Published
- 2012