Abstract
BACKGROUND: The global prevalence of diseases transmitted by Aedes aegypti mosquitoes, such as dengue, Zika and Yellow Fever, is increasing, but development of promising new mosquito control technologies could reverse this trend. Target Product Profiles (TPPs) and Preferred Product Characteristics (PPCs) documents issued by the World Health Organization can guide the research and development pathways of new products and product combinations transitioning from proof of concept to operational use. METHODS: We used high resolution global maps of the case and economic burden of dengue to derive programmatic cost targets to support a TPP for Wolbachia replacement. A compartmental entomological model was used to explore how release size, spacing and timing affect replacement speed and acceptability. To support a PPC for a hybrid suppress-then-replace approach we tested whether Wolbachia replacement could be achieved faster, more acceptably or at a lower cost if preceded by a mosquito suppression programme. RESULTS: We show how models can reveal trade-offs, identify quantitative thresholds and prioritise areas and intervention strategies for further development. We estimate that for Wolbachia replacement to be deployable in enough areas to make major contributions to reducing global dengue burden by 25% (in line with 2030 WHO targets), it must have the potential for cost to be reduced to between $7.63 and $0.24 (USD) per person protected or less. Suppression can reduce the number of Wolbachia mosquitoes necessary to achieve replacement fixation by up to 80%. A hybrid approach can also achieve fixation faster and potentially improve acceptability, but may not justify their cost if they require major new investments in suppression technologies. CONCLUSIONS: Here we demonstrate the value dedicated modelling can provide for interdisciplinary groups of experts when developing TPPs and PPCs. These models could be used by product developers to prioritise and shape development decisions for new Wolbachia replacement products.