Distribution of insecticide resistance and mechanisms involved in the arbovirus vector Aedes aegypti in Laos and implication for vector control

Distribution of insecticide resistance and mechanisms involved in the arbovirus vector Aedes aegypti in Laos and implication for vector control
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DOI:
10.1371/journal.pntd.0007852
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发表时间:
2019-12-01
影响因子:
3.8
通讯作者:
Brey, Paul T.
Brey, Paul T.
中科院分区:
医学2区
文献类型:
--
作者:
Marcombe, Sebastien;Fustec, Benedicte;Brey, Paul T.

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埃及伊蚊是登革热、黄热病、寨卡和基孔肯雅病毒的主要传播媒介。世界范围内的病媒控制主要基于杀虫剂处理,但不幸的是,由于蚊子对常用杀虫剂产生抗药性,病媒控制计划面临着操作挑战。在东南亚,抗Ae。埃及伊蚊对化学杀虫剂的抗药性在几个国家已有记录,但老挝没有关于杀虫剂抗药性的数据报告。为了填补这一空白,我们评估了11个Ae的杀虫剂抗性。埃及人口对该国公共卫生行动中使用的杀幼虫剂和杀成虫剂的反应。我们还调查了潜在的分子机制与电阻,包括靶位点突变和解毒酶puestrine参与代谢resistance.Methods和结果生物测定收集在五个省的成人和幼虫揭示了不同程度的抗性有机磷(马拉硫磷和temephos),有机氯(DDT)和拟除虫菊酯(氯菊酯和溴氰菊酯)。增效剂生物测定表明,暴露于解毒酶抑制剂后,蚊子对杀虫剂的敏感性显着增加。生化分析证实了这些结果,显示显着升高的活动细胞色素P450单加氧酶(P450),谷胱甘肽S-转移酶(GST)和羧酸酯酶(CCE)在成人。在所有受试人群中,通过qPCR分别以低频率和高频率检测到两种kdr突变V1016 G和F1534 C。检测到两个kdr突变之间的显著负相关。kdr基因1534 C和1016 G突变频率与DDT和氯菊酯的存活率无显著相关性(P > 0.05)。检测特定解毒酶的基因拷贝数变异(CNV)。在人口水平上,CNV影响羧酸酯酶CCEAE 3A和两个细胞色素P450 CYP 6 BB 2和CYP 6P 12的存在显着相关的杀虫剂resistance.ConclusionsThese结果表明,这两个kdr突变和代谢抗性机制是存在于老挝,但其对表型抗性的影响可能不同的比例在人口或个人水平。分子分析表明,CNV影响CCEAE 3A以前与temephos抗性也与马拉硫磷抗性,而CNV影响CYP 6 BB 2和CYP 6P 12与拟除虫菊酯和可能的DDT抗性。老挝的主要虫媒病毒对杀虫剂的抗药性水平很高,这令人担忧,可能对该国的登革热病媒控制产生重要影响。
BackgroundThe yellow fever mosquito Aedes aegypti is the major vector of dengue, yellow fever, Zika, and Chikungunya viruses. Worldwide vector control is largely based on insecticide treatments but, unfortunately, vector control programs are facing operational challenges due to mosquitoes becoming resistant to commonly used insecticides. In Southeast Asia, resistance of Ae. aegypti to chemical insecticides has been documented in several countries but no data regarding insecticide resistance has been reported in Laos. To fill this gap, we assessed the insecticide resistance of 11 Ae. aegypti populations to larvicides and adulticides used in public health operations in the country. We also investigated the underlying molecular mechanisms associated with resistance, including target site mutations and detoxification enzymes putatively involved in metabolic resistance.Methods and results Bioassays on adults and larvae collected in five provinces revealed various levels of resistance to organophosphates (malathion and temephos), organochlorine (DDT) and pyrethroids (permethrin and deltamethrin). Synergist bioassays showed a significant increased susceptibility of mosquitoes to insecticides after exposure to detoxification enzyme inhibitors. Biochemical assays confirmed these results by showing significant elevated activities of cytochrome P450 monooxygenases (P450), glutathione S-transferases (GST) and carboxylesterases (CCE) in adults. Two kdr mutations, V1016G and F1534C, were detected by qPCR at low and high frequency, respectively, in all populations tested. A significant negative association between the two kdr mutations was detected. No significant association between kdr mutations frequency (for both 1534C and 1016G) and survival rate to DDT or permethrin (P > 0.05) was detected. Gene Copy Number Variations (CNV) were detected for particular detoxification enzymes. At the population level, the presence of CNV affecting the carboxylesterase CCEAE3A and the two cytochrome P450 CYP6BB2 and CYP6P12 were significantly correlated to insecticide resistance.ConclusionsThese results suggest that both kdr mutations and metabolic resistance mechanisms are present in Laos but their impact on phenotypic resistance may differ in proportion at the population or individual level. Molecular analyses suggest that CNV affecting CCEAE3A previously associated with temephos resistance is also associated with malathion resistance while CNV affecting CYP6BB2 and CYP6P12 are associated with pyrethroid and possibly DDT resistance. The presence of high levels of insecticide resistance in the main arbovirus vector in Laos is worrying and may have important implications for dengue vector control in the country.