Next-generation vector control for malaria: product profiling to implementation

Malaria is a parasitic infection passed between people by infectious mosquito bites that kills about half a million people annually. Mosquito control interventions are therefore crucial and have proven impact. Mass-distributed insecticide-treated bed nets (ITNs) are predicted to have averted > 450 million clinical cases of malaria globally from 2000 to 2015. Mosquitoes have evolved to survive exposure to a key insecticide that is used on nets. This means the protection afforded by ITNs is diminished. ITNs and the spraying of insecticides on the walls of peoples' homes are designed to kill and deter mosquitoes from indoor environments. Mosquitoes can also bite outdoors, and outdoor biting, that leads to malaria transmission, is estimated to cause > 10 million malaria cases annually in Africa, even were indoor control optimised.
'Zero by 40' is a response to this crisis that has generated industrial buy-in from the world's leading agrichemical companies. Zero by 40 aims to eradicate malaria by uniting these companies so that they can re-purpose or develop new mosquito control tools for both indoor and outdoor protection. These tools must be appropriately assessed to understand their protective benefit. Impact will be distinct in different locations. This is because both mosquitoes and people have distinct local behaviours that change how often people receive infectious bites. New experimental methods are needed to make sure we can understand the full potential of new tools. For example, indoor mosquito control interventions may have less impact if people spend more time outdoors where the intervention cannot prevent bites. The best approach to test new mosquito control tools is to use large-scale field trials. These trials compare clinical cases of malaria over time between communities with or without the intervention. But the expense of such trials, and the length of time needed for following cases (usually 2 to 3 years), is a major challenge. Mathematical models, that can recreate the underlying mechanisms that enable malaria to pass between people and mosquitoes, can be used to predict how new interventions might perform. These models can be defined to represent local communities and mosquito populations, so may capture local differences in impact. The predictions from mathematical models can be compared to observations from field trials to confirm predictions are valid. I will use the model to make predictions on where new tools for mosquito control are likely to perform best. The outcomes can ensure integrated vector control management and delay development of future resistance. This work will be crucial to support agrichemical companies making investment decisions.
I will work closely with field scientists in Burkina Faso to collate data on how mosquitoes are affected by re-purposed or new tools. These data will help understand the biology so that I can predict public health impacts of new tools using a transmission model. The model predictions will underpin two webtools. The first webtool will provide a platform to industrial partners to explore how imagined interventions might complement those already employed in different countries. Deciding the best settings for different tools, and what makes them affordable to countries trying to control malaria, are crucial questions I can address to enable industries to make robust investment decisions. The second webtool will provide countries making challenging decisions on how to implement interventions within a budget, with a platform to explore different combinations of mosquito control tools so that they can reduce the most cases for the lowest cost. The webtool can support funding requests for additional budget to enable mosquito control within a country. This can maximise our global effort to eliminate by specifying interventions based on local characteristics related to mosquito bites so that interventions maximise public health impact and minimise financial costs.

We have a unique opportunity to change the global burden of malaria given buy-in from industry via Zero by 40. However, the direction of effort can and must be informed by a strong evidence-base, one which I can lead through the proposed work. The two webtools that I will build can be crucial for the malaria elimination effort. Current decisions on whether to replace standard pyrethroid-only bed nets with next-generation piperonyl-butoxide (PBO) nets are principally based on the susceptibility bioassay test. This test exposes local mosquitoes to pyrethroid insecticides at a standardised dose and observes the percentage that are killed after exposure. However, there are well-documented challenges with the susceptibility bioassay and multiple other factors contribute to the potential protection afforded by nets. Consideration of the use of historic interventions alters the trajectory of the potential impact of new strategies because of underlying differences in malaria endemicity. The local behaviour of mosquitoes is equally crucial because this determines the window of time when interventions targeting specific mosquito behaviours - e.g. mosquitoes' blood-feeding indoors - can be effective. An advantage of the transmission model is that it provides a platform to explore the combined, non-linear interactions between local characteristics in a mechanistic way, building on meta-analyses of key data, and laying out the intuition and assumptions explicitly.

I am uniquely placed to change the global burden of malaria given buy-in from industry via Zero by 40. This proposal directly benefits UK based and international businesses including BASF, Bayer, Sumitomo Chemical, and UK charity, IVCC, through evidence-based guidance to help target investment toward the development of products that will be most cost-effective. An ambitious pathway to eradication has been laid out for malaria that identifies key challenges including potentially reduced political support and the decline in funding associated with country level control efforts once regions move to prevention of imported cases. I can lead efforts to positively influence vector control policy and investment in innovation for UK and International branches of world-leading agrichemical companies which aligns with the UK's commitment to invest to benefit developing nations. The webtools I propose in this FLF can help converge thinking on how new technologies can support the global effort to eliminate malaria.

I will optimise vector control strategy in a cost-effective manner and within the country-specified budget across management zones using a web interface with the flexibility to contextualise malaria-endemic settings in Africa. This alone should save lives and maximise the performance of vector control across the African continent so benefiting the wider public. This will also benefit policy-makers working in malaria-endemic settings, principally National Malaria Control Programs and the World Health Organization (WHO). The development of both webtools will be necessarily iterative, to ensure evidence on product impacts are driven by relevant up-to-date data and to include new products as they develop and gain WHO approval.

Collaborations with the CNRFP in Burkina Faso will be invaluable to understand fundamental mosquito behaviours that influence vector control efficacy at a fine scale. These will benefit the NMCP specifically in Burkina Faso. The data analysis will inform the wider research community focused on mosquito ecology, vector borne disease and malaria transmission through an understanding of transmission risk differences across villages. In summary, this timely proposal can influence vector control policy and investment in innovation so benefiting: i) UK and international branches of global agrichemical companies; ii) policy-makers working internationally and within malaria-endemic countries, and; iii) the wider public.