Insecticide Resistance Management to Preserve Pyrethroid Susceptibility in Aedes aegypti

杀虫剂抗性管理以保持埃及伊蚊对拟除虫菊酯的敏感性

• 批准号: 9301476
• 负责人: WILLIAM C. BLACK
• 金额: $ 33.4万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9301476
• 关键词: Aedes; Alleles; Americas; Caribbean region; Clinical; Culicidae; Data; Dengue; Disease; Disease Outbreaks; Dose; Epidemic; Evolution; Exons; Fever; Frequencies; Gene Frequency; Generations; Genes; Genetic Transcription; Goals; Human; Indoor environment; Insecticide Resistance; Insecticides; Institution; Latin America; Libraries; Malathion; Metabolic; Mexican; Mexico; Mutation; Natural Resources; Organophosphates; Pharmaceutical Preparations; Pharmacologic Substance; Population; Predisposition; Reporting; Resistance; Resistance profile; Resources; Rotation; Safety; Scheme; Sodium Channel; Textiles; Time; Vaccines; Virus; chikungunya; deep sequencing; field study; killings; knock-down; migration; pressure; pyrethroid; resistance allele; resistant strain; restoration; sample fixation; transcriptome sequencing; vector; vector mosquito; voltage

Project Summary / Abstract The mosquito Aedes aegypti is the primary urban vector of the viruses causing dengue and chikungunya fever for which vaccines and effective pharmaceuticals are lacking. Epidemic dengue is emerging in the Americas: Mexico has reported >750,000 clinical dengue cases since 2009. Endemic chikungunya fever was reported in the Americas for the first time in 2013 and is now spreading into the Caribbean and Mexico. The only available strategy to suppress dengue or chikungunya fever outbreaks is to reduce vector populations through insecticide applications. However, Ae. aegypti suppression is compromised through a recent rapid rise across Latin America of knockdown resistance (kdr) to pyrethroid insecticides. Widespread, heavy use of pyrethroid space sprays – due to their strong human safety profile – has created immense selection pressure for resistance. This resistance is primarily under the control of the voltage gated sodium channel gene (para). Our preliminary data show that high frequencies (>80%) of kdr-conferring alleles occur commonly in Ae. aegypti in Mexico, and that state-of-the-art netting treated with a synergized pyrethroid effectively kills susceptible Ae. aegypti but has unacceptably low (~20%) killing efficacy for Mexican Ae. aegypti strains with high frequencies of kdr-conferring alleles. Our preliminary studies also show that: a) even in the absence of gene flow barriers, local insecticide pressure, rather than migration of mosquitoes with kdr-conferring mutations, is the primary determinant of the local kdr profile for Ae. aegypti; and b) the frequency of kdr-conferring mutations in a highly resistant strain reverted from near fixation to lower levels within 14 generations when pyrethroid pressure was removed. These findings provide hope that the current, disastrous kdr situation can be reversed through insecticide resistance management (IRM) schemes to restore and protect the invaluable pyrethroid susceptibility resource in Ae. aegypti. The goals for this proposal are to demonstrate that pyrethroid susceptibility can be restored and protected in Ae. aegypti and Ae. albopictus through insecticide rotation and focused indoor spraying. We also will identify genes other than para that confer pyrethroid resistance in Ae. aegypti through RNAseq and deep sequencing of exon enriched libraries. Our partnering Mexican institution is Instituto Nacional de Salud Pública – Centro Regional de Investigación en Salud Pública (INSP-CRISP) in Tapachula.

项目总结/摘要 埃及伊蚊是引起登革热和基孔肯雅热病毒的主要城市传播媒介 缺乏疫苗和有效的药物。流行性登革热正在美洲出现： 自2009年以来，墨西哥报告了超过750，000例临床登革热病例。年报告了地方性基孔肯雅热， 2013年首次出现在美洲，现在正在向加勒比海和墨西哥蔓延。唯一可用的 控制登革热或基孔肯雅热暴发的战略是通过以下措施减少病媒种群 杀虫剂的应用。然而，阿。埃及的镇压由于最近在全国范围内的迅速上升而受到损害。 拉丁美洲拟除虫菊酯类杀虫剂的击倒抗性。广泛大量使用拟除虫菊酯 太空喷雾剂--由于其对人类的安全性很强--给人类带来了巨大的选择压力， 阻力这种抗性主要受电压门控钠通道基因（帕拉）控制。我们 初步数据显示，高频率（>80%）的kdr赋予等位基因普遍存在于Ae.埃及人 墨西哥，并与协同拟除虫菊酯处理的最先进的蚊帐有效地杀死敏感的Ae。 埃及伊蚊，但对墨西哥Ae的杀灭效率低得令人无法接受（~20%）。高频率埃及菌株 kdr基因的等位基因。我们的初步研究还表明：a）即使在没有基因流动障碍的情况下， 当地的杀虫剂压力，而不是带有kdr基因突变的蚊子的迁移，是主要的 Ae的局部kdr曲线的决定因素。B）在高表达的人中kdr赋予突变的频率， 抗性品系在14代内从接近固定恢复到较低水平， 删除.这些发现为目前灾难性的kdr形势提供了希望， 杀虫剂抗药性管理计划，以恢复和保护宝贵的拟除虫菊酯 感病性资源埃及人。本提案的目标是证明拟除虫菊酯 在Ae中，敏感性可以恢复和保护。埃及伊蚊和埃及伊蚊。通过杀虫剂轮换， 集中在室内喷洒。我们还将确定基因以外的对位赋予拟除虫菊酯抗性的Ae。 通过RNAseq和外显子富集文库的深度测序，我们的墨西哥合作机构是 Instituto Nacional de Salud Pública - Centro Regional de Investigación en Salud Pública（INSP-CRISP）in 塔帕丘拉