Insecticide Resistance Management to Preserve Pyrethroid Susceptibility in Aedes aegypti

项目摘要/摘要 埃及伊蚊是引起登革热和基孔肯雅热的主要城市传播媒介。 缺乏疫苗和有效的药物。美洲正在出现流行的登革热： 自2009年以来，墨西哥报告了75万例临床登革热病例。年报告了地方性基孔肯雅热 2013年首次出现在美洲，现在正蔓延到加勒比和墨西哥。唯一可用的 遏制登革热或基孔肯雅热暴发的战略是通过 杀虫剂的应用。然而，Ae.埃及伊蚊的抑制率最近在全国范围内迅速上升 拉丁美洲对拟除虫菊酯类杀虫剂的击倒抗性(Kdr)。广泛大量使用拟除虫菊酯 太空喷雾-由于其强大的人类安全概况-已经为 抵抗。这种抗性主要受电压门控钠通道基因(PARA)的控制。我们的 初步数据显示，高频率(&gt；80%)的kdr等位基因普遍出现在Ae。埃及伊蚊进入 墨西哥，而且用增效拟除虫菊酯处理的最先进的蚊帐有效地杀死了易感Ae。 埃及伊蚊，但对墨西哥Ae的杀灭率低得令人无法接受(~20%)。埃及伊蚊高频率菌株 携带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， 主要的原因是局部的杀虫剂压力，而不是携带kdr基因突变的蚊子的迁徙。 Ae的本地kdr配置文件的决定因素。埃及伊蚊；和b)高度致病突变的频率 在拟除虫菊酯压力下，抗性菌株在14代内从接近固定恢复到较低水平 已删除。这些调查结果提供了希望，即目前灾难性的kdr局势可以通过 恢复和保护无价拟除虫菊酯的抗药性管理(IRM)计划 Ae.的感病资源。埃及伊蚊。这项提案的目标是证明拟除虫菊酯 易感性在Ae中可以恢复和保护。Aegypti和Ae.白纹伊蚊通过杀虫剂轮换和 室内集中喷洒。我们还将确定除parA以外的其他基因赋予Ae对拟除虫菊酯的抗性。 埃及伊蚊通过RNAseq和外显子丰富文库的深度测序。我们的合作墨西哥机构是 Pública国家调查研究所-区域调查中心(INSP-CRISP) 塔帕丘拉。

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.