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.

项目摘要 /摘要 蚊子埃及埃及是引起登革热和基孔肯雅热的病毒的主要城市媒介 缺乏疫苗和有效的药物。流行迷在美洲正在出现： 自2009年以来，墨西哥报告了> 750,000名临床迷。 美洲是2013年的第一次，现在正在加勒比海和墨西哥传播。唯一可用的 抑制登革热或基孔肯雅热暴发的策略是通过 杀虫剂的应用。但是，AE。通过最近在整个迅速上升的迅速上升，埃及抑制受到损害 拉丁美洲的抗抑制性（KDR）对拟除虫菊酯杀虫剂。宽度，大量使用拟甲虫素 太空喷雾剂（由于其强大的人体安全性）为 反抗。这种电阻主要在电压门控钠通道基因（PARA）的控制之下。我们的 初步数据表明，高频率（> 80％）的KDR会议等位基因通常发生在AE中。埃及在 墨西哥，以及通过协同拟除虫毒治疗的最先进的网络有效地杀死了易感的AE。 埃及，但墨西哥AE的杀戮效率低（约20％）。具有高频的埃及菌株 kdr限制等位基因。我们的初步研究还表明：a）即使没有基因流动障碍， 局部杀虫剂的压力，而不是用KDR限制突变的蚊子迁移，是主要的 AE的本地KDR轮廓的决定因素。埃及b）高度的KDR限制突变的频率 当拟除虫菊酯压力为14代的耐药性应变从近固定恢复到较低的水平 删除。这些发现提供了希望，当前灾难性的KDR情况可以通过 杀虫剂耐药性管理（IRM）方案以恢复和保护宝贵的拟除虫菊酯 AE中的敏感性资源。埃及。该建议的目标是证明拟除虫菊酯 可以在AE中恢复和保护敏感性。埃及和ae。通过杀虫剂旋转和 聚焦的室内喷涂。我们还将确定除para以外的其他基因，该基因会议在AE中会议拟甲虫素抗性。 通过RNASEQ和外显子富含库的深度测序。我们合作的墨西哥机构是 Instituto nacional de saludpública - Centro区域deRespenduciónEnSaludPública（Insp-Crisp） tapachula。