Graduating from Lincoln University in 1988, Dr Leathwick moved to the North Island of New Zealand as a post-doctoral fellow to study the development and management of anthelmintic resistance in nematode parasites of sheep. Twenty seven years later he is still there doing more or less the same thing, although he is now a principal scientist at AgResearch (a government research organisation) and has shifted focus away from parasites of sheep onto those infecting cattle and deer. His science has combined modelling with laboratory, indoor and small and large scale field studies to produce validated recommendations on the management of resistance.
Dave Leathwick PhD, Agresearch Grasslands, Palmerston North, New Zealand
Anthelmintic resistance in gastrointestinal nematodes is now a global phenomenon affecting most species of grazing animals (e.g. goats, sheep, cattle, deer and horses), and considerable scientific effort has been put into understanding how resistance develops and how it can be delayed or managed. However, the development and marketing of anthelmintic products has evolved more or less independently of any considerations for the development of resistance. This presentation will consider the hypothesis that the way in which anthelmintic products are formulated and delivered plays an important role in the rate at which resistance develops to the constituent actives. All anthelmintic products are registered as effective against a range of parasite species based on measured efficacy against populations which are susceptible to the active ingredient at the administered dose rate. However, the rate at which resistance develops is strongly influenced by efficacy against resistant genotypes, in particular the heterozygotes during the early phase of selection when resistance genes are still rare.
The way in which drugs are formulated and delivered can affect the dose, variability in dose and duration of exposure of the target worms to the drug, and all these factors can potentially influence the rate at which resistance develops in the treated population. Different routes of administration (e.g. pour-on, injection, oral) result in very large differences in plasma profiles, but, in fact these may be largely irrelevant as plasma levels may be a poor indicator of the concentration of drug reaching the target worms. Formulations and routes of administration which result in persistent activity influence the reproductive advantage afforded to resistant genotypes, especially when drug concentrations decline to suboptimal levels over time. Combining different actives with similar spectra of activity into a single product has been shown to have benefits in reducing the survival of resistant genotypes. However, use of combinations raises the potential of drug-drug interactions and formulation effects which may also be important.