Optimization of long-lasting insecticidal bed nets for resistance management: a modelling study and user-friendly app
Authors: Madgwick Philip G. , Wubs Matthias , Kanitz Ricardo 
Published: September 2023

Abstract
Background
Up until the present, pyrethroid-treated bed nets have been a key tool for vector control in the fight against malaria. A global system that sets standards and facilitates procurement has successfully driven down the price of these bed nets to enable more of them to be distributed. As a result of their mass rollout, malaria cases have been significantly reduced, but pyrethroid resistance is now widespread. Going forward, new insecticides have been and continue to be developed for use on bed nets, but it is unclear how to best deploy them for maximum impact.

Methods
Here, an app for the optimization of bed nets based on their insecticide loading concentration and deployment lifespan is presented. Underlying the app are simple models that incorporate the chemical and physical properties of bed nets, and the genetic and ecological properties of resistance evolution in mosquitoes. Where possible, default parameter values are fitted from experimental data. The app numerically searches across a massive number of these simple models with variable loading and lifespan to find their optima under different criteria that constrain the options for vector control.

Results
The app is not intended to provide a definite answer about the best bed net design, but allows for the quantative exploration of trade-offs and constraints under different conditions. Here, results for the deployment of a new insecticide are explored under default parameter values across public health budgets for the purchase of bed nets. Optimization can lead to substantial gains in the average control of the mosquito population, and these gains are comparatively greater with lower budgets. Whilst optimizing a bed net within the constraints of the incentives of the existing system of standards and procurement leads to substantially greater control than not optimizing the bed net, optimizing the bed net without constraints leads to yet substantially greater control. The most important factor in this optimization is coverage, which depends on the price per bed net. With this in mind, it is unsurprising that the optimization for plausible budgets suggests that a pyrethroid would be the preferred partner for a new insecticide under current constraints because it is cost-effective in the balance of being less expensive than the new insecticide but also less effective due to pre-existing resistance. Surprisingly, a pyrethroid is shown to be an effective partner for a new insecticide in this model because of its contribution to resistance management in delaying the onset of resistance to the new insecticide.

Conclusions
This study highlights the importance of trade-offs in the design of bed nets for vector control. Further, it suggests that there are challenges in the roll-out of bed nets with new insecticides because of the constraints imposed by the global system of standards and procurement, which currently fails to adequately incentivize important considerations in bed net design like resistance management.