Roadmap for the development of control strategies for liver fluke

What are we trying to achieve and why? What is the problem we are trying to solve?

• What is the prevalence of anthelmintic resistance in liver fluke populations to different actives, and how is this distributed?
• Can the implementation of best-practice management reverse the anthelmintic resistance status on a farm?
  Are refugia-based strategies for liver fluke control appropriate biologically and in terms of farmer willingness?
• How large must the refugia be and how long should it persist in order to minimize selection for AR? Is there a fitness cost to refugia?
• What is the proportion of animals that should be left untreated? How can we improve the timing of treatment?
• To what extent can alternative control methods, including grazing / pasture management, reduce the need for treatment and hence alleviate selection for resistance?

What are the scientific and technological challenges (knowledge gaps needing to be addressed)?

To date, there are >20 peer‐reviewed reports of TCBZ‐R on sheep farms within Europe, plus a number of anecdotal reports of resistance, which raises the question how prevalent is TCBZ‐R in Europe. Occurrence outside Europe is less well documented. It is not clear if reports of drug failure are effectively recorded through veterinary medicine
surveillance schemes in different countries and if so, if these data are available in the public domain. This information is needed to provide evidence for the widely held belief that resistance is widespread across northern Europe and to give a clear picture of the TCBZ‐R status at an individual farm level, to ensure the most effective control measures are
employed.
Better tests are needed to detect resistance. FECRT to detect resistance to TCBZ is validated for use in sheep but not cattle. Risk that farmers switch to other actives, leading to heavy use of e.g. closantel with risk of resistance emerging. Need for surveillance of resistance to closantel as well as TCBZ.

What approaches could/should be taken to address the research question?

• Quick and reliable test to detect AR in the field. Approaches to refine FECRT (e.g. faecal pooling) and use of other diagnostic tools (e.g. copro-antigen reduction) should be further investigated.
• Field surveillance data on progression of AR and the impact of alternative strategies to slow it.

What else needs to be done before we can solve this need?

• Development of new therapeutics, especially to cover immature flukes and acute disease.
• Development of molecular diagnostics for AR in liver fluke.
• Field studies of the integration of therapeutics in disease management strategies.

Existing knowledge including successes and failures

Recently, it was found that if the use of multiple active anthelmintics is combined with “best practice parasite
management,” based on avoiding overuse of anthelmintics, minimizing nematode challenge to susceptible animals, and maintaining a nematode population in refugia, resistant populations may even be reversed towards susceptibility. This concept, and the use of refugia-based strategies in general, remain unexplored for liver fluke. However, refugia-based and community replacement approaches trialled for nematodes might not be appropriate for liver fluke because of the high pathogenicity of the parasite and its capacity for rapid population increase through asexual reproduction in the snail host. This requires further research before recommendations are prematurely made. The use of multi-active or combination anthelmintic approaches, which are increasingly advocated for nematodes, also have not been assessed for liver fluke.