Beyond redundant kill: A fundamental explanation of how insecticide mixtures work for resistance management.

The use of insecticide mixtures for resistance management has been a controversial topic for many decades. Here, we provide a reassessment of the fundamental theory of insecticide mixtures. First, we examine how mixtures differ from other strategies. We suggest that the fundamental strategy concept of a mixture is defined by the simultaneous use of insecticides and their overlapping exposure. Second, we provide a simple, illustrative model to show how mixtures affect resistance evolution. Following the existing literature, we identify a role for 'redundant kill' acting against resistant individuals, which we link to the overlapping exposure of insecticides. We also identify the occurrence of 'additional kill' acting against susceptible individuals, which is the immediate consequence of the simultaneous use of insecticides. Third, we take a basic approach to the comparison of mixtures and other strategies using a simple model. We find that a common comparison of the time to resistance alone leaves the effects of additional kill unaccounted for. Moreover, we demonstrate that different approaches to comparison can lead to different results because of biases that are introduced in the comparison setup. Fourth, still using the same model, we showcase a more sophisticated approach to comparison using optimised strategies. We find that optimised mixtures always perform better than other strategies due to the combination of redundant and additional kill. We suggest that the comparison of optimised strategies is unbiased because each strategy is performing the best that it can. On this basis, in theory (but not necessarily practice), we believe that mixtures are better than other strategies and, through the steps of our argument, we can tie this success back to the fundamental properties (of simultaneous use and overlapping exposure) that distinguish mixtures from other strategy concepts. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.