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

描述（由申请人提供）：杀虫剂是控制疟疾最便宜、最有效和最可靠的方法之一，但历史和当代经验表明，蚊子可以迅速进化出抗药性。我们希望验证这样一种假设，即只要使用较低浓度的有效成分，就可以使现有的公共卫生杀虫剂在不推动抗药性蚊子进化的情况下，提供出色的疟疾控制。这一假设与传统观点完全相反，它源于这样一种观察，即目前的杀虫剂模式不分青红皂白地针对所有成年蚊子，从而对抗性产生了巨大的选择，而疟疾实际上仅由一小部分蚊子（年老的受感染个体）传播。如果杀虫剂只针对那些危险的蚊子，而避开所有其他的蚊子，特别是那些对进化变化负有最大责任的繁殖活跃的年轻蚊子，那么就有可能实施强有力的疾病控制，而不强加对杀虫剂抗性的强烈“自然”选择。我们的观点是，如果杀虫剂浓度过低，不足以杀死活力旺盛的年轻蚊子，那么年老的患病蚊子就会很脆弱。因此，我们想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消灭危险的蚊子。如果这种横向的想法是正确的，那么就可以利用对当前配方进行非常简单、易于实施的改变，以确保我们现有的杀虫剂——在蚊帐或室内喷洒运动中使用时证明提供了出色的疟疾控制——在可预见的未来继续作为主要的疟疾控制工具。

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.