Liverpool School of Tropical Medicine (LSTM), Liverpool, UK.
Bill & Melinda Gates Foundation, Seattle, USA.
Malar J. 2020 Nov 10;19(1):398. doi: 10.1186/s12936-020-03466-4.
There is an urgent need for insecticides with novel modes of action against mosquito vectors. Broflanilide is a meta-diamide, discovered and named Tenebenal™ by Mitsui Chemicals Agro, Inc., which has been identified as a candidate insecticide for use in public health products.
To evaluate its potential for use in public health, Tenebenal™ was screened using an array of methodologies against Anopheles and Aedes strains. Initially it was assessed for intrinsic efficacy by topical application. Tarsal contact bioassays were then conducted to further investigate its efficacy, as well as its potency and speed of action. The potential of the compound for use in indoor residual spray (IRS) applications was investigated by testing the residual efficacy of a prototype IRS formulation on a range of typical house building substrates, and its potential for use in long-lasting insecticidal nets (LLIN) was tested using dipped net samples. Finally, bioassays using well-characterized insecticide-resistant mosquito strains and an in silico screen for mutations in the insecticide's target site were performed to assess the risk of cross-resistance to Tenebenal™.
Tenebenal™ was effective as a tarsal contact insecticide against both Aedes and Anopheles mosquitoes, with no apparent cross-resistance caused by mechanisms that have evolved to insecticides currently used in vector control. Topical application showed potent intrinsic activity against a Kisumu reference strain and an insecticide-resistant strain of Anopheles gambiae. Applied to filter paper in a WHO tube bioassay, Tenebenal™ was effective in killing 100% of susceptible and resistant strains of An. gambiae and Aedes aegypti at a concentration of 0.01%. The discriminating concentration of 11.91 µg/bottle shows it to be very potent relative to chemistries previously identified as having potential for vector control. Mortality occurs within 24 h of exposure, 80% of this mortality occurring within the first 10 h, a speed of kill somewhat slower than seen with pyrethroids due to the mode of action. The potential of Tenebenal™ for development in LLIN and IRS products was demonstrated. At least 12 months residual efficacy of a prototype IRS formulation applied at concentrations up to 200 mg of AI/sq m was demonstrated on a range of representative wall substrates, and up to 18 months on more inert substrates. A dipped net with an application rate of around 2 g/sq m Tenebenal™ killed 100% of exposed mosquitoes within a 3-min exposure in a WHO cone test.
Tenebenal™ is a potent insecticide against adult Aedes and Anopheles mosquitoes, including strains resistant to classes of insecticide currently used in vector control. The compound has shown great potential in laboratory assessment and warrants further investigation into development for the control of pyrethroid-resistant mosquitoes.
新型杀虫剂对于防治蚊虫媒介具有迫切需求。溴氟虫酰胺是一种新型邻苯二甲酰胺类杀虫剂，由三井化学农业株式会社研发并命名为特苯氟菊酯，已被认为是一种候选的公共卫生产品用杀虫剂。
为评估其在公共卫生领域的应用潜力，采用一系列方法对溴氟虫酰胺进行了筛选，涉及到按蚊和伊蚊种群。首先通过体表接触法进行了内在效力评估。然后进行了跗节接触生物测定，以进一步研究其效力，以及其效价和作用速度。通过测试一系列典型房屋建筑基底上原型滞留喷洒制剂的残留效力，研究了该化合物在室内滞留喷洒（IRS）制剂中的应用潜力；通过浸渍网样本测试，研究了其在长效杀虫剂网（LLIN）中的应用潜力。最后，利用经过良好特征描述的抗药性蚊虫品系进行生物测定，并进行杀虫剂靶标位点突变的计算机筛选，以评估对溴氟虫酰胺产生交叉抗性的风险。
溴氟虫酰胺作为一种跗节接触杀虫剂，对伊蚊和按蚊均具有效性，且没有明显的交叉抗性，这些交叉抗性是由目前用于病媒控制的杀虫剂进化而来的机制引起的。体表接触应用显示出对基苏木参考株和抗杀虫剂的冈比亚按蚊的有效内在活性。溴氟虫酰胺在世界卫生组织管生物测定中，以 0.01%的浓度应用于滤纸，对敏感和抗性的冈比亚按蚊和埃及伊蚊 100%有效。11.91μg/瓶的区分浓度表明，与先前被确定具有病媒控制潜力的化学物质相比，它具有很强的效价。死亡率在接触后 24 小时内发生，80%的死亡率在最初的 10 小时内发生，由于作用方式的原因，其杀灭速度比拟除虫菊酯稍慢。溴氟虫酰胺在长效杀虫剂网和 IRS 产品中的开发潜力得到了证明。在一系列代表性的墙壁基底上，以高达 200mg AI/sq m 的浓度应用原型 IRS 制剂，至少可达到 12 个月的残留效力，在更惰性的基底上，可达到 18 个月。在世界卫生组织锥形试验中，以约 2g/sq m 的浸渍网应用率，在 3 分钟暴露时间内，溴氟虫酰胺杀死了 100%暴露的蚊子。
溴氟虫酰胺是一种针对成蚊的高效杀虫剂，包括对目前用于病媒控制的杀虫剂类别的抗性品系。该化合物在实验室评估中表现出巨大的潜力，值得进一步研究，以开发用于防治对拟除虫菊酯产生抗性的蚊子。
