A combined experimental-computational approach for spatial protection efficacy assessment of controlled release devices against mosquitoes (Anopheles)

This work describes the use of entomological studies combined with in silico models (computer simulations derived from numerical models) to assess the efficacy of a novel device for controlled release of spatial repellents. Controlled Release Devices (CRDs) were tested with different concentrations of metofluthrin and tested against An. quadrimaculatus mosquitoes using arm-in cage, semi-field, and outdoor studies. Arm-in-cage trials showed an approximate mean values for mosquito knockdown of 40% and mosquito bite reduction of 80% for the optimal metofluthrin formulation for a 15-minute trial. Semi-field outdoor studies showed a mean mortality of a 50% for 24 hour trial and 75% for a 48 hour trial for optimal concentrations. Outdoors studies showed an approximate mean mortality rate of 50% for a 24 hour trial for optimal concentrations. Numerical simulations based on Computational Fluid Dynamics (CFD) were performed in order to obtain spatial concentration profiles for 24 hour and 48 hour periods. Experimental results were correlated with simulation results in order to obtain a functional model that linked mosquito mortality with the estimated spatial concentration for a given period of time. Such correlation provides a powerful insight in predicting the effectiveness of the CRDs as a vector-control tool. While CRDs represent an alternative to current spatial repellent delivery methods, such as coils, candles, electric repellents, and passive emanators based on impregnated strips, the presented method can be applied to any spatial vector control treatment by correlating entomological endpoints, i.e. mortality, with in-silico simulations to predict overall efficacy. The presented work therefore presents a new methodology for improving design, development and deployment of vector-control tools to reduce transmission of vector-borne diseases, including malaria and dengue.Author summary: Spatial Repellents (SRs) represent another tool to fight vector-borne diseases, such as malaria and dengue. Newly developed active ingredients were designed to repel or kill vectors in space, creating a shield effect, unlike topical repellents, such as DEET, that rely on vectors to be near or in physical contact with protected target. Metofluthrin and transfluthrin are examples of active ingredients (AIs) designed as SRs against mosquitoes. The efficacy of SRs heavily depends on the delivery method. Currently, there is a lack of fundamental understanding of effectiveness of SR delivery methods. Current delivery modalities of SR do not rely on quantitative models to estimate targeted efficacy, making the end-user overshoot or undershoot the dosage required for protection. Optimizing the dosage over time is critical to obtain protection for a given space in a giving period of time, as well to prevent AI resistance in the long run. The key is therefore to deliver just enough dosage needed to repel or kill the vectors. The presented work provides a novel approach to predict performance of SRs based on an experimental-computational methodology to quantify effectiveness of controlled release devices as a function of AI physical properties (e.g. volatility), device design parameters combined with physical variables, and environmental conditions (e.g. temperature, wind velocity). This work therefore provides the groundwork for estimating quantitative effectiveness of SR delivery methods against mosquitoes.