Ecology of insecticide resistant vectors: consequences for the effectiveness of malaria control strategies

在蚊帐中浸渍杀虫剂是全世界控制和消除疟疾最普遍的策略。杀虫剂的作用是杀死可以传播疟疾的蚊子，并且在整个撒哈拉以南非洲地区非常成功地减少了疟疾病例。然而，蚊子对杀虫剂的抵抗力越来越强，威胁到它们的有效性。尽管这一迫在眉睫的威胁十分严重，但人们对杀虫剂抗药性的程度及其对公共卫生的影响仍然知之甚少。一个基本的假设是，除了对杀虫剂的反应外，抗性蚊子与易感蚊子在所有方面都是相同的。然而，有几个原因可以解释为什么情况并非如此。例如，众所周知，疟疾传播对蚊子长期生存和行为的变化比对蚊子总体数量的变化更为敏感。这些特征，以及蚊子的其他生活史特征，如繁殖成功，都可能在抗药性蚊子中发生改变。总之，这可能导致以杀虫剂为基础的控制方法即使在红外辐射水平高的地区也能保持比预期更高的有效性，这表明有可能开发控制方法来减轻抗药性的后果，即。“破坏抵抗策略”。因此，了解IR蚊子的生态和行为以及控制措施如何在短期和长期影响它们的生活史，对于预测耐药性后果至关重要。不幸的是，这些参数很难在自然现场条件下直接测量，并且在实验室生物测定中可能反映不佳。然而，生态建模的最新发展已经带来了突破，但尚未得到应用，从蚊子监测中常规收集的多种类型数据中获得这种隐藏（潜在）信息的方法。作者建议利用这些新方法研究高红外区疟疾蚊的种群动态和生态，并在野外操作条件下量化传统和新型控制方法对蚊子生活史的影响。我将重点关注布基纳法索的Banfora区，这是一个高IR地区，并将利用AvecNet项目合作者收集的蚊子监测数据，包括蚊子数量、传染性、IR状况和行为。这一数据收集是一项为期2年的90个村庄大规模干预试验的一部分，试验采用两种替代疟疾控制方法，实验室分析预测，这两种方法将通过两种不同途径减少蚊子数量：1)涂有杀虫剂拟除虫菊酯的传统蚊帐（LLIN），其作用是杀死成年雌蚊；2)新型Olyset DUO蚊帐涂有拟除虫菊酯，以减少成年蚊子的存活率，同时还涂有吡呋昔芬，这是一种影响繁殖力和寿命的昆虫幼年激素。然而，目前尚不清楚这些预期的人口影响在自然种群中应用时的可靠性。为了解决这些问题，我将运用新颖的分析工具，将广泛使用的监测技术产生的各种类型的数据与临床发病率数据相结合，以重建IR蚊子载体的隐藏种群动态和生活史特征，并利用它来确定IR蚊子的生态如何调节其疟疾传播潜力；2)量化当前和新型控制方法对这些蚊子的影响，3)设计未来在高IR地区干预方法的优化部署。

Insecticides impregnated into bednets is the most widespread strategy to control and eliminate malaria worldwide. Insecticides work by killing mosquitoes that can transmit malaria and have been extremely successful in reducing malaria cases throughout sub-Saharan Africa. However, mosquitos are increasingly resistant to insecticides, threatening to reduce their effectiveness. Despite the gravity of this impending threat, the extent of insecticide resistance (IR) and its consequences for public health remain poorly understood. A fundamental assumption is that resistant mosquitoes are identical to susceptible ones in all aspects other than their response to insecticides. However, there are several reasons why this may not be the case. For example, malaria transmission is known to be more sensitive to variation in the long-term survival and behaviour of mosquitoes than to their overall abundance. These features, in addition to other mosquito life-history traits such as their reproductive success, may be altered in resistant mosquitoes. Together this could result in insecticide-based control methods retaining a higher than expected degree of efficacy, even in areas where IR levels are high, which would suggest the possibility of developing control methods to mitigate the consequences of resistance i.e. "resistance busting strategies".Thus understanding the ecology and behaviour of IR mosquitoes and how their life history is affected in the short and long-term by control measures is crucial for prediction of the consequences of resistance. Unfortunately, these parameters are difficult to directly measure under natural field conditions, and may be poorly reflected in laboratory bioassays. However, recent developments in ecological modelling have delivered breakthrough, but as yet rarely applied, methods for deriving such hidden (latent) information from the multiple types of data that are routinely collected in mosquito surveillance. I propose to use these new methods to investigate the population dynamics and ecology of malaria mosquitoes in an area of high IR, and to quantify the impacts of both traditional and novel control methods on mosquito life history under field operational conditions. I will focus on the Banfora district of Burkina Faso, a region of high IR, and will make use of mosquito surveillance data, including mosquito abundance, infectiousness, IR status and behaviour, being collected by my collaborators in the AvecNet programme. This data collection is part of a 2-year 90-villages large-scale intervention trial of two alternative malaria control methods for which laboratory assays predict will reduce mosquito populations through two different routes: 1) traditional bednets (LLIN) that are coated with the insecticide pyrethroid, which works by killing adult female mosquitos; and 2) new Olyset DUO nets that are coated with a pyrethroid to reduce adult mosquito survival but also with pyriproxifen, an insect juvenile hormone that affects fecundity and longevity. However, it is unclear how reliably these expected demographic impacts occur when applied within natural populations. To address these issues I will apply novel analytical tools that integrate the various types of data generated from widely-used surveillance techniques with clinical incidence data, in order to reconstruct the hidden population dynamics and life history-traits of IR mosquito vectors, and use it to 1) determine how the ecology of IR mosquitoes modulates their malaria transmission potential, 2) quantify the impacts of current and novel control methods on these mosquitoes and 3) design optimal deployment of future intervention methods in areas of high IR.