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

疟疾是一种寄生虫感染，通过传染性蚊子叮咬在人与人之间传播，每年造成约50万人死亡。因此，控制苔藓的干预措施至关重要，并已证明具有影响。据预测，2000年至2015年，大规模分发经杀虫剂处理的蚊帐在全球避免了超过4.5亿例疟疾临床病例。蚊子已经进化到可以在暴露于蚊帐上使用的一种关键杀虫剂后生存下来。这意味着驱虫蚊帐所提供的保护减少了。驱虫蚊帐和在人们家中的墙壁上喷洒杀虫剂的目的是杀死和阻止室内环境中的蚊子。蚊子也可以在户外叮咬，导致疟疾传播的户外叮咬估计每年在非洲造成超过1000万例疟疾病例，即使室内控制得到优化。“40年前归零”是对这场危机的回应，这场危机已经引起了世界领先的农用化学品公司的工业收购。Zero by 40旨在通过联合这些公司来消除疟疾，以便他们能够重新使用或开发新的室内和室外保护蚊虫控制工具。必须对这些工具进行适当评估，以了解其保护效益。影响将在不同的地点不同。这是因为蚊子和人都有不同的当地行为，这些行为改变了人们接受传染性叮咬的频率。需要新的实验方法来确保我们能够理解新工具的全部潜力。例如，如果人们花更多的时间在户外，室内蚊子控制干预措施可能会产生较小的影响，而干预措施无法防止叮咬。测试新的蚊虫控制工具的最佳方法是使用大规模的实地试验。这些试验比较了有或没有干预的社区之间随着时间的推移疟疾的临床病例。但此类审判的费用以及后续案件所需的时间（通常为2至3年）是一个重大挑战。数学模型可以重现疟疾在人与蚊子之间传播的基本机制，可以用来预测新的干预措施可能如何发挥作用。这些模型可以被定义为代表当地社区和蚊子种群，因此可以捕捉影响的地方差异。可以将数学模型的预测与田间试验的观察结果进行比较，以确认预测是有效的。我将使用这个模型来预测新的蚊子控制工具在哪里可能表现得最好。这些成果可确保病媒综合控制管理，并延缓今后抗药性的形成。这项工作对于支持农业化学公司做出投资决策至关重要。我将与布基纳法索的实地科学家密切合作，整理有关蚊子如何受到重新使用或新工具影响的数据。这些数据将有助于了解生物学，以便我可以使用传播模型预测新工具对公共卫生的影响。模型预测将支持两个网络工具。第一个网络工具将为工业合作伙伴提供一个平台，探索想象中的干预措施如何补充不同国家已经采用的干预措施。决定不同工具的最佳设置，以及如何让试图控制疟疾的国家负担得起，是我可以解决的关键问题，以使行业能够做出稳健的投资决策。第二个网络工具将为各国就如何在预算范围内实施干预措施做出具有挑战性的决定提供一个平台，以探索蚊子控制工具的不同组合，以便它们能够以最低的成本减少大多数病例。该网络工具可以支持额外预算的资金请求，以在一个国家内控制蚊子。这可以最大限度地发挥我们的全球努力，通过根据与蚊虫叮咬有关的当地特点制定干预措施，使干预措施最大限度地发挥公共卫生影响，并最大限度地减少财务成本。

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.