Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans

Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.埃及伊蚊（Aedes aegypti）与白纹伊蚊（Ae. albopictus）均为5种重要虫媒病毒（arboviruses）的主要传播媒介，这5种病毒分别为基孔肯雅病毒、登革病毒、裂谷热病毒、黄热病毒以及寨卡病毒，因此这两类蚊子是全球传染病负担的重要影响因素。采用杀虫剂灭杀结合幼虫孳生地治理的媒介防控策略，对阻断上述病毒向人类的传播至关重要，但该策略正受到杀虫剂抗性出现的威胁。本研究综述了目前关于这两种主要媒介昆虫全球范围内杀虫剂抗性地理分布的现有证据，并针对4类主要神经毒性杀虫剂（氨基甲酸酯类、有机氯类、有机磷酸酯类、拟除虫菊酯类）的整理数据绘制了地理分布图谱。美洲、非洲与亚洲均已检测出对上述4类杀虫剂均产生抗性的现象。埃及伊蚊与白纹伊蚊的抗性已被证实与靶标位点突变及杀虫剂解毒能力增强相关，但仍需开展更多研究以进一步阐明其代谢机制，并开发可靠的诊断检测方法。本研究还提供了目前已被证实具有重要意义的抗性机制的地理分布情况。由于所用诊断工具缺乏标准化，且多个区域的抗性表型与基因型数据均存在缺失，导致对未采样区域的杀虫剂抗性进行评估存在困难。采用标准化方法加大采样力度，是解决威胁人类健康的杀虫剂抗性新兴问题的关键所在。具体而言，需针对用于防控埃及伊蚊与白纹伊蚊的全品类杀虫剂确定诊断剂量，并配备经过充分表征的敏感品系，以实现抗性表型检测的标准化；同时还需针对主要抗性机制开发经过校准的诊断检测方法。