Insecticide Resistance in Anopheles minimus Mosquitoes

描述(申请人提供)：疟疾是中国的主要公共卫生问题。拟除虫菊酯浸泡蚊帐和室内喷洒拟除虫菊酯是疟疾媒介控制的主要工具。然而，拟除虫菊酯的广泛使用导致了蚊子种群中抗药性的出现和传播。杀虫剂抗药性已严重阻碍了中国和世界范围内的疟疾防治工作。这一应用将集中在南方中国重要的疟疾媒介微小按蚊C的抗性机制上。中心假说是击倒抗性(Kdr)和代谢解毒作用都使人对拟除虫菊酯产生抗性。因此，蚊子对拟除虫菊酯的抗性水平取决于kdr基因的突变和单加氧酶的活性。将测定自然种群中kdr基因的多态性，并研究kdr突变、单加氧酶活性与拟除虫菊酯抗性表型的相关性。这项研究将为中国和东南亚这一重要疟疾媒介物种开发基于分子或生物化学的抗药性诊断工具奠定重要基础。拟议中的研究将通过培训一名博士生和一名博士后研究员，帮助建设中国的研究能力，并加强南京医科大学的分子昆虫学实验室。这项研究将作为NIH资助R01 AI050243-07的延伸进行。 公共卫生相关性：本应用重点研究了南方中国地区最重要的疟疾媒介微小按蚊的耐药机制，了解其耐药机制将为开发新的耐药诊断工具奠定重要基础。此外，本研究将通过为1名博士生和1名博士后提供研究培训，为中国医学昆虫学研究能力建设做出贡献，并加强南京医科大学分子昆虫学实验室的建设。

DESCRIPTION (provided by applicant): Malaria is a major public health problem in China. Pyrethroid-impregnated bed nets and indoor spray with pyrethroids are the main malaria vector control tools. However, the wide use of pyrethroids has resulted in the emergence and spread of resistance in mosquito populations. Insecticide resistance has significantly hindered the efforts of malaria control in China and worldwide. This application will focus on resistance mechanisms in an important malaria vector in Southern China, Anopheles minimus C. The central hypothesis is that both knockdown resistance (kdr) and metabolic detoxification confer resistance to pyrethroids in An. minimus, and consequently, the resistance level of a mosquito to pyrethroids is contingent on mutations in kdr gene and monooxygenase activity. The kdr gene polymorphism in natural populations will be determined, and correlations between the kdr mutations, monooxygenase activity with pyrethroid resistance phenotype will be examined. This research will play an important foundation for the development of molecular- or biochemically-based resistance diagnosis tools in this important malaria vector species in China and Southeast Asia. The proposed research will contribute to building research capacity in China by training one Ph.D. student and one postdoc fellow and strengthen the molecular entomology laboratory at the Nanjing Medical University. This research will be conducted as an extension of NIH grant R01 AI050243-07. PUBLIC HEALTH RELEVANCE: This application focuses on resistance mechanisms in the most important malaria vector in Southern China, Anopheles minimus C. Understanding the resistance mechanisms will play an important foundation for the development of new resistance diagnosis tools. Further, this research will contribute to building research capacity in medical entomology in China by providing research training for one Ph.D. student and one postdoc fellow, and strengthen the molecular entomology laboratory in Nanjing Medical University.