Multiple-active anthelmintic formulations: Friend or foe in sustainable parasite control?

Multiple-active anthelmintic formulations (combinations of anthelmintics with a similar spectrum of activity and different mechanisms of action and resistance) are widely available in several regions of the world for the control of sheep nematodes. There are two main justifications for the use of such combinations: (i) to enable the effective control of nematodes in the presence of single or multiple drug resistance and (ii) to slow development of resistance to the component anthelmintic classes. Computer model simulations of sheep nematode populations indicate that the ability of combinations to slow development of resistance is maximised if certain prerequisite criteria are met, the most important of which appear to concern the opportunity for survival of susceptible nematodes in refugia and the pre-existing levels of resistance to each of the anthelmintics in the combination. The question then becomes whether these criteria are likely to be fulfilled under field conditions. Concerns include the potential to select for resistance to multiple anthelmintic classes concurrently if there are insufficient parasites in refugia, the potential for shared mechanisms of resistance between chemical classes of anthelmintics, the need for further empirical validation of computer simulations, the pre-existing frequency of resistance alleles which may be too high on some farms to warrant introduction of certain combinations and the potential encouragement of farmers to prepare their own mixtures and/or neglect other management principles for sustainable parasite control. In conclusion, multiple-active formulations can play an important role in resistance management. However, they are not a panacea and should always be used in accordance with contemporary principles for sustainable anthelmintic use.