Impact of insecticide resistance on the behavior and fitness of malaria vectors

 描述(申请人提供)：疟疾仍然是非洲的一个主要公共卫生问题，尽管在该区域内不断部署干预措施。病媒控制是防治疟疾的重要战略之一。这些努力包括大规模分发长效浸渍蚊帐和室内滞留喷洒。虽然这些控制措施自21世纪初首次扩大疟疾发病率以来已成功地减少了疟疾发病率，但在过去几年中，疟疾发病率在包括肯尼亚在内的非洲大部分地区死灰复燃。导致疟疾死灰复燃的因素之一是杀虫剂抗药性。过去十年来，越来越多地使用以杀虫剂为基础的疟疾媒介控制工具，这给疟疾媒介种群带来了更大的选择压力，导致了更高的杀虫剂抗药性发生率，这可能会影响媒介控制的有效性。尽管加强了控制努力，但有证据表明，影响有限，临床疟疾在包括肯尼亚在内的撒哈拉以南非洲部分地区死灰复燃。也有证据表明病媒行为和物种组成发生了变化。迫切需要制定可行的抗药性管理战略。这些策略的前提是更好地了解杀虫剂耐药性对媒介行为和适合度的影响。这项应用的总体目标是确定抗药性对撒哈拉以南非洲主要疟疾媒介冈比亚按蚊行为和适合度的影响。Arabiens和An.以及它们对肯尼亚疟疾传播的影响。长期目标是确定在非洲最密集的疟疾干预计划期间疟疾媒介物种生态的变化。为实现这一目标，我设计了3个具体目标。这将是第一项将分析和量化非洲三大疟疾媒介物种使用不同杀虫剂的行为耐药性的研究。在目标1中，我们将确定媒介蚊子对杀虫剂耐药性的进化如何影响它们的取食和休息行为。杀虫剂抗药性可能会影响蚊子适应行为，因此由于使用基于室内的LLIN和IRS的压力，蚊子从室内取食转变为室外取食和室外休息。这些行为变化可能会影响媒介传播疟疾的可能性。目标2将测试媒介对杀虫剂的抗性如何影响它们的发育适宜性、存活率、繁殖潜力和传染性。需要研究适应度的实际成本，以了解抗性的发展如何影响这些载体的载体能力。目标3是预测和验证杀虫剂抗药性对疟疾传播的后果，这对于帮助政策制定者更好地将指导疟疾干预的模型参数化是很重要的。这项研究的结果将有助于了解疟疾在非洲卷土重来的机制，有助于制定更好的战略来管理疟疾媒介中的杀虫剂耐药性，并有助于提出疟疾媒介控制模型。

 DESCRIPTION (provided by applicant): Malaria is still a major public health problem in Africa despite the continuous deployment of interventions within the region. Vector control is one of the important strategies being used in the fight against malaria. These efforts include large-scale distribution of long-lasting impregnated nets (LLINs) and indoor residual spraying (IRS). Although these control measures have been successful in reducing malaria incidence since its initial scale-up in early 2000s, within the last few years there has been resurgence of malaria incidence in most parts of Africa, including Kenya. One of the factors that has been implicated in this malaria resurgence is insecticide resistance. The increased use of insecticide-based malaria vector control tools in the past decade have placed greater selection pressure on malaria vector populations resulting in higher rates of the incidence of insecticide resistance tha is likely to impact on the effectiveness of vector control. Despite increased control efforts, ther is evidence of limited impact and a resurgence of clinical malaria in parts of sub-Saharan Africa including Kenya. There is also evidence of shifts in vector behavior and species composition. There is pressing need to develop viable insecticide resistance management strategies. These strategies are predicated upon better understanding of the effects of insecticide resistance on vector behavior and fitness. The overall objective of this application is to determine the effect o insecticide resistance on the behavior and fitness of the main malaria vectors of Sub-Saharan Africa, Anopheles gambiae, An. arabiensis and An. funestus, and their impact on malaria transmission in Kenya. The long-term objective is to determine the changes in the ecology of malaria vector species during the period of most intensive malaria intervention programs in Africa. I have designed 3 specific aims to achieve this objectives. This will be the first study tht will analyze and quantify behavioral resistance in the three main major malaria vector species in Africa using different insecticides. In Aim 1, we will determine how evolution of insecticide resistance in vector mosquitoes affects their feeding and resting behavior. Insecticide resistance could affect mosquitoes to adapt behaviorally and therefore change from feeding indoors to outdoors and resting outdoors because of pressure from the use of LLINs and IRS, which are indoor based. These behavioral changes will likely affect vector potential to transmit malaria. Aim 2 will test how insecticide resistance in vectors affects their fitness for development, survivorship, reproductive potential and infectiousness. The actual cost of the fitness needs to be studied to understand how the development of resistance affects the vectorial capacity of these vectors. Aim 3 is to predict and validate the consequences of insecticide resistance on malaria transmission which is important in helping policy makers to better parameterize models that guide malaria interventions. Results from this study will help understand the mechanisms for malaria resurgence in Africa, help to come out with better strategies to manage insecticide resistance in malaria vectors and help in coming up with models for malaria vector control.