Existing malaria control insecticides - without the evolution of insecticide-resi

说明（由申请人提供）：杀虫剂是控制疟疾的最便宜、最有效和最有效的方法之一，但历史和当代经验表明，蚊子可以迅速产生抗药性。我们希望测试现有的公共卫生杀虫剂可以提供出色的疟疾控制，而不会仅仅通过使用较低浓度的活性成分来驱动抗药性蚊子的进化。这一假说与传统观点完全相反，它源于这样一种观察，即目前的杀虫剂范例不加区别地针对所有成年蚊子，因此对抗药性施加了巨大的选择，而疟疾实际上只由一小部分蚊子（年老的、受感染的个体）传播。如果杀虫剂只针对那些危险的蚊子，而避开所有其他蚊子，特别是那些对进化变化最负责任的年轻的繁殖活跃的蚊子，那么就有可能在不对杀虫剂抗性施加强大的“自然”选择的情况下实施强有力的疾病控制。我们的论点是，年老的、患病的蚊子将容易受到杀虫剂浓度太低而不能杀死年轻的、旺盛的蚊子的影响。因此，我们希望通过实验确定是否可以使用较低浓度的活性成分来选择性地切除危险的蚊子。如果这一横向想法是正确的，那么可以使用非常简单、易于实施的现有配方变化来确保我们现有的杀虫剂-这些杀虫剂在用于蚊帐或室内喷洒运动时可以提供出色的疟疾控制-在可预见的未来可以继续作为主要的疟疾控制工具。 公共卫生相关性：室内喷洒杀虫剂和蚊帐是全球疟疾控制工作的重要组成部分。目前使用的杀虫剂效果非常好，但只能通过创造破坏其未来的条件：它们赋予抗药性蚊子巨大的进化优势。我们试图测试一种想法，这种想法将延缓或完全防止杀虫剂耐药性的演变，同时仍然提供出色的疟疾控制。

DESCRIPTION (provided by applicant): Insecticides are among the cheapest, most effective and best proven methods of controlling malaria but as historical and contemporary experience shows, mosquitoes can rapidly evolve resistance. We wish to test the hypothesis that existing public health insecticides could be made to deliver excellent malaria control without driving the evolution of insecticide resistant mosquitoes simply by using their active ingredients at lower concentrations. This hypothesis, which is completely opposite to conventional wisdom, derives from the observation that current insecticide paradigms indiscriminately target all adult mosquitoes and thus impose immense selection for resistance, whereas malaria is actually transmitted by only a small faction of mosquitoes (old, infected individuals). If insecticides targeted only those dangerous mosquitoes, and avoided all the others, particularly the young reproductively-active mosquitoes most responsible for evolutionary change, then it would be possible to impose strong disease control without imposing strong 'natural' selection for insecticide resistance. It is our contention that old, diseased mosquitoes will be vulnerable to insecticide concentrations that are too low to kill young vigorous mosquitoes. We therefore want to experimentally determine whether lower concentrations of active ingredients can be used to selectively excise the dangerous mosquitoes. If this lateral idea is correct, then very simple, easy to implement changes in current formulations could be used to ensure that our existing insecticides - which demonstrably provide excellent malaria control when used on bed nets or in house spraying campaigns - can continue as leading malaria control tools for the foreseeable future. PUBLIC HEALTH RELEVANCE: Insecticides for house spraying and bed nets are vital components of global malaria control efforts. As currently used, existing insecticides work extremely well, but only by creating the conditions which undermine their future: they confer an immense evolutionary advantage on resistant mosquitoes. We seek to test an idea that would retard or completely prevent the evolution of insecticide resistance while still delivering excellent malaria control.