Pyrethroid Resistance in Malaria Mosquito Anopheles sinensis

描述（申请人提供）：疟疾是最重要的蚊媒疾病之一，中华按蚊是中国主要的疟疾媒介。驱虫蚊帐和室内滞留喷雾剂是最有效的病媒控制手段。蚊帐和室内残留喷雾剂的杀虫剂选择是拟除虫菊酯，因为它们效率高、杀灭速度快、对哺乳动物的毒性低。然而，据报道，拟除虫菊酯类杀虫剂抗药性。这极大地阻碍了最近在中国提出的消除疟疾计划的有效性。杀虫剂耐药性的早期发现和耐药性监测对抗药性管理和合理使用杀虫剂至关重要。本研究的长期目标是阐明拟除虫菊酯类抗性的分子机制。并利用这些知识开发适用于现场且具有成本效益的抗性检测方法。该应用程序将验证遗传作图、转录组测序和功能基因组学方法的结合将大大提高我们对An的分子机制的理解的中心假设。中华蚊对溴氰菊酯的抗性。具体目的有三个：1)鉴定安家蝇对溴氰菊酯的主要抗性位点。2)对溴氰菊酯敏感和抗性品种进行转录组分析。3)确定天然安蚊对溴氰菊酯有机抗性的关系。中华白蚁种群及其抗敲低基因和代谢解毒基因的分子多态性。遗传作图和转录组分析与野外医学昆虫学相结合，将使鉴定和全面评价不同机制对拟除虫菊酯抗性的贡献成为可能。本研究将有助于加深对拟除虫菊酯类杀虫剂抗性的认识。为开发新的耐药诊断方法奠定了重要基础。

DESCRIPTION (provided by applicant): Malaria is one of the most important mosquito-borne diseases, and Anopheles sinensis mosquito is the predominant malaria vector in China. Insecticide-impregnated bed nets and indoor-residual spray are the most effective means of mosquito vector control. The insecticides of choice for bed nets and indoor-residual spray are pyrethroids because of their high efficacy, rapid rate of knockdown, and low mammalian toxicity. However, pyrethroid resistance has been reported in An. sinensis populations throughout China in bioassays, and this has significantly hindered the effectiveness of the recently proposed malaria elimination program in China. Early detection of insecticide resistance and resistance surveillance are critical to resistance management and to the rational use of insecticides. The long-term goal of this research is to elucidate the molecular mechanisms of pyrethroid resistance in An. sinensis mosquitoes, and to use the knowledge to develop field-applicable and cost-effective resistance detection methods. This application will test central hypothesis that combination of genetic mapping, transcriptome sequencing and functional genomics approaches will greatly improve our understanding of molecular mechanisms of An. sinensis mosquito resistance to deltamethrin. The three specific aims are: 1) to identify the major loci for resistance to deltamethrin in An. sinensis using quantitative trait loci mapping technique, 2) to conduct transcriptome analysis between deltamethrin-susceptible and resistant An. sinensis populations, and 3) to determine the association between organismal deltamethrin resistance in natural An. sinensis populations and molecular polymorphisms in knockdown resistance (kdr) gene and metabolic detoxification genes. Combination of genetic mapping and transcriptome analysis and field medical entomology will allow identification and a comprehensive evaluation of the contribution of different mechanisms to pyrethroid resistance. This research will significantly enhance the understanding of resistance to pyrethroid insecticides in An. sinensis mosquitoes, and lays an important foundation for developing new resistance diagnostic methods for the most important malaria vector in China. PUBLIC HEALTH RELEVANCE: Insecticide resistance is the biggest obstacle to successful control of malaria vectors in China. This project will improve the understanding of the genetic mechanisms of resistance to pyrethroid insecticide in mosquitoes, and lay an important foundation for developing novel diagnosis methods.