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

Abstract

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.

Insecticide resistance management strategies for public health control of mosquitoes exhibiting polygenic resistance: A comparison of sequences, rotations, and mixtures

“…One challenge with any study of different strategies/interventions/policies is defining how best to evaluate them (see discussions in Madgwick & Kanitz, 2022a ). For evaluating IRM we consider that there are three potential main outcomes of interest.…”

Insecticide resistance management strategies for public health control of mosquitoes exhibiting polygenic resistance: a comparison of sequences, rotations, and mixtures

“…One challenge with any study of different strategies/interventions/policies is defining how best to evaluate them (see discussions in Madgwick & Kanitz, 2022a). For evaluating IRM we consider that there are three potential main outcomes of interest.…”

What is the value of rotations to insecticide resistance management?

“…45 versus 21 ). Overall, the new theoretical models support that mixtures of two insecticides with different modes of action can outperform their rotation under many conditions, particularly when those insecticides are highly effective, which is expected to be the case for most insecticides, and when some fraction of the population escapes insecticide exposure (in particular, see 8,[44][45][46]48 ).…”

“…The discussion clearly outlined the logic of what became to be known as 'redundant kill', in which mixtures are understood to delay resistance evolution because an individual that is resistant to one insecticide would be killed by the other. 7,8 Around the same time, Coyne 9 proposed the use of rotations to delay the evolution of insecticide resistance through the periodic switching of insecticide use over time. Interestingly, Coyne does not clearly explain why a rotation would work, but rather he criticises the actions of some public health authorities and manufacturers who were already promoting the use of mixtures (for reasons other than resistance management), reasoning that it would lead to resistance to both insecticides at once (see also 10 ).…”

“…38 Although insecticides were the focus of more than half of the 29 theoretical models and 17 experimental studies that were analysed, the study missed many important insecticide studies (particularly field trials 1,4,39,40 ), downplayed life-history differences between taxa and ignored the institutional knowledge of organisations like the IRAC. 34,41,42 Regardless, in its wake, a series of new theoretical models brought methodological and computational advances to the modelling conducted in the 1980s, 8,[43][44][45][46][47][48][49] often struggling to reproduce results that were important to the critical perception of the resistance-management value of mixtures (e.g. 45 versus 21 ).…”