Negative cross resistance mediated by co-treated bed nets: a potential means of restoring pyrethroid-susceptibility to malaria vectors

Insecticide-treated nets and indoor residual spray programs for malaria control are entirely dependent on pyrethroid insecticides. The ubiquitous exposure of Anopheles mosquitoes to this chemistry has selected for resistance in a number of populations. This threatens the sustainability of our most effective interventions but no operationally practicable way of resolving the problem currently exists. One innovative solution involves the co-application of a powerful chemosterilant (pyriproxyfen or PPF) to bed nets that are usually treated only with pyrethroids. Resistant mosquitoes that are unaffected by the pyrethroid component of a PPF/pyrethroid co-treatment remain vulnerable to PPF. There is a differential impact of PPF on pyrethroid-resistant and susceptible mosquitoes that is modulated by the mosquito’s behavioural response at co-treated surfaces. This imposes a specific fitness cost on pyrethroid-resistant phenotypes and can reverse selection. The concept is demonstrated using a mathematical model.