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.

项目概要/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媒介 美洲正在出现登革热流行病，目前缺乏疫苗和有效药物： 自 2009 年以来，墨西哥报告了超过 75 万例登革热临床病例。 2013 年首次登陆美洲，目前已扩展到加勒比海地区和墨西哥。 抑制登革热或基孔肯雅热爆发的策略是通过以下方式减少病媒种群： 然而，由于最近埃及伊蚊的快速增长，杀虫剂的应用受到了影响。 拉丁美洲对拟除虫菊酯杀虫剂的击倒抗性 (kdr) 广泛、大量使用拟除虫菊酯。 太空喷雾剂——由于其强大的人体安全特性——给人们带来了巨大的选择压力 这种抵抗主要受电压门控钠通道基因的控制（段落）。 初步数据显示，赋予 kdr 的等位基因频率较高（>80%），常见于埃及伊蚊。 墨西哥，最先进的蚊帐经过协同拟除虫菊酯处理，可有效杀死易感伊蚊。 埃及伊蚊，但对高频率墨西哥伊蚊菌株的杀灭效率低得令人无法接受（~20%）。 我们的初步研究还表明：a) 即使没有基因流动障碍， 当地的杀虫剂压力，而不是带有 kdr 突变的蚊子的迁移，是主要的影响因素。 埃及伊蚊局部 kdr 谱的决定因素；和 b) 高度突变的 kdr 突变频率。 当拟除虫菊酯压力降低时，抗性菌株在 14 代内从接近固定恢复到较低水平 这些发现为扭转当前灾难性的 kdr 局面带来了希望。 杀虫剂抗性管理 (IRM) 计划旨在恢复和保护宝贵的拟除虫菊酯 埃及伊蚊的敏感性资源 本提案的目标是证明拟除虫菊酯。 通过杀虫剂轮换可以恢复和保护埃及伊蚊和白纹伊蚊的敏感性。 我们还将鉴定除对位基因之外赋予白蚊拟除虫菊酯抗性的基因。 aegypti 通过 RNAseq 和外显子富集文库的深度测序来实现。 国家公共健康研究所 – 公共健康区域调查中心 (INSP-CRISP) 塔帕丘拉。