A testing cascade to identify repurposed insecticides for next-generation vector control tools: screening a panel of chemistries with novel modes of action against a malaria vector.
A testing cascade to identify repurposed insecticides for next-generation vector control tools: screening a panel of chemistries with novel modes of action against a malaria vector.
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DOI：
10.12688/gatesopenres.12957.2
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发表时间：
2019-01-01
影响因子：
--
通讯作者：
Malone, David
中科院分区：
文献类型：
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作者：
Lees, Rosemary;Praulins, Giorgio;Malone, David
背景资料：随着疟疾病媒对杀虫剂的抗药性在地理范围和强度上的蔓延，需要具有新作用模式的化合物来维持迄今为止通过长效驱虫蚊帐和室内滞留喷剂取得的成功，作为杀虫剂抗药性管理战略的一部分。对现有注册农药（主要是为农业用途而开发的农药）进行筛选，与对新化合物进行筛选和化学合成方案相比，可以提供一种更快速、后勤挑战更小的途径来确定对公众健康有价值的活性成分。研究方法：对来自所有IRAC类别的杀虫剂和杀螨剂（包括具有未分类作用模式的杀虫剂和杀螨剂）进行了评估，以纳入针对冈比亚按蚊成虫的实验室生物测定测试级联。选择了一长串代表性候选化合物，排除了具有安全性问题、不合适的理化性质以及可能存在公共卫生用途注册障碍的化合物。使用局部应用的初始筛选消除了具有不足的内在活性的化合物，并且跗部接触测定鉴定了在适当浓度下具有活性的化合物。使用剂量反应测定和区分剂量计算，通过相对效价对目标化合物进行排序。结果如下：佐剂的包含增强了几种化合物的跗部功效，促进了具有巨大潜力的化学物质的促进，考虑到合适的制剂，其不会基于单独的化合物的活性而进展。测试级联中各阶段之间的数据比较表明，一种更精简的方法，即局部施用以测试内在活性并确定区别剂量以比较化合物的相对效力，可能足以确定具有用于长效杀虫蚊帐和室内残留喷洒产品的潜在价值的化合物。结论：确定了11种感兴趣的化合物作为病媒控制剂（按效力降序排列）：噻虫胺、乙基多杀菌素、氰氟虫腙、呋虫胺、茚虫威、阿维菌素、氟啶虫胺、恶唑磺酰、三氟唑嘧啶、唑螨酯和唑螨酮。
Background: With insecticide resistance in malaria vectors spreading in geographical range and intensity, there is a need for compounds with novel modes of action to maintain the successes achieved to date by long-lasting insecticidal nets and indoor residual sprays, used as part of an insecticide resistance management strategy. Screening existing registered pesticides, predominantly those developed for use in agriculture, may provide a more rapid and less logistically challenging route to identifying active ingredients of value to public health than screening and chemical synthesis programmes for novel compounds. Methods: Insecticides and acaricides from all IRAC classes, including those with unclassified modes of action, were assessed for inclusion in a laboratory bioassay testing cascade against adult female Anopheles gambiae mosquitoes. A longlist of representative candidate compounds was selected, excluding those with safety concerns, unsuitable physiochemical properties, and likely hurdles to registration for public health use. An initial screen using topical application eliminated compounds with insufficient intrinsic activity, and a tarsal contact assay identified those with activity at an appropriate concentration. Compounds of interest were ranked by relative potency using dose response assays and discriminating dose calculations. Results: Inclusion of an adjuvant enhanced the tarsal efficacy of several compounds, facilitating the promotion of chemistries with great potential, given suitable formulation, which would not progress based on activity of compound alone. Comparison of data between stages in the testing cascade suggest that a more streamlined approach, topical application to test for intrinsic activity and determining the discriminating dose to compare relative potency of compounds, may be sufficient to identify compounds with potential value for use in long lasting insecticidal nets and indoor residual spray products. Conclusions: Identified were 11 compounds of interest as vector control agents (in descending order of potency): clothianidin, spinetoram, metaflumizone, dinotefuran, indoxacarb, abamectin, sulfoxaflor, oxazosulfyl, triflumezopyrim, fenpyroximate, and tolfenpyrad.