Background: Pyriproxyfen (PPF), an insect growth hormone mimic is widely used as a larvicide and in some second-generation bed nets, where it is combined with pyrethroids to improve impact. It has also been evaluated as a candidate for auto-dissemination by adult mosquitoes to control Aedes and Anopheles species. We examined whether PPF added to larval habitats of pyrethroid-resistant malaria vectors can modulate levels of resistance among emergent adult mosquitoes. Methodology: Third-instar larvae of pyrethroid-resistant Anopheles arabiensis (both laboratory-reared and field-collected) were reared in different PPF concentrations, between 0.000000001milligrams active ingredient per litre of water (mgAI/L) and 0.0001 mgAI/L, or no PPF at all. Emergent adults escaping these sub-lethal exposures were tested using WHO-standard susceptibility assays on pyrethroids (0.75% permethrin and 0.05% deltamethrin), carbamates (0.1% bendiocarb) and organochlorides (4% DDT). Biochemical basis of pyrethroid resistance was investigated by pre-exposure to 4% PBO. Bio-efficacies of long-lasting insecticide-treated nets, Olyset and PermaNet 2.0 were also examined against adult mosquitoes with or without previous aquatic exposure to PPF. Results: Addition of sub-lethal doses of PPF to larval habitats of pyrethroid-resistant An. arabiensis, consistently resulted in significantly reduced mortalities of emergent adults when exposed to pyrethroids, but not to bendiocarb or DDT. Mortality rates after exposure to Olyset nets, but not PermaNet 2.0 were also reduced following aquatic exposures to PPF. Pre-exposure to PBO followed by permethrin or deltamethrin resulted in significant increases in mortality, compared to either insecticide alone. Conclusions: Partially-resistant mosquitoes exposed to sub-lethal aquatic concentrations of PPF may become more resistant to pyrethroids than they already are without such pre-exposures. Studies should be conducted to examine whether field applications of PPF, either by larviciding or other means actually excercebates pyrethroid-resistance in areas where signs of such resistance already exist in wild the vector populations. The studies should also investigate mechanisms underlying such magnification of resistance, and how this may impact the potential of PPF-based interventions in areas with pyrethroid resistance.

中文翻译：

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亚致死性水生剂量吡吡氧芬可能会增加疟疾蚊子对拟除虫菊酯的抗药性

背景：吡虫啉（PPF）是一种昆虫生长激素模拟物，被广泛用作杀幼虫剂，并在某些第二代蚊帐中与拟除虫菊酯结合使用，以提高抗药性。它也被评估为成年蚊子自动传播以控制伊蚊和按蚊物种的候选者。我们检查了添加到拟除虫菊酯抗性疟疾载体幼虫栖息地中的PPF是否可以调节新生蚊虫的抗药性水平。方法：以不同的PPF浓度饲养拟除虫菊酯抗性阿拉伯按蚊的三龄幼虫（实验室饲养和田间采集），有效成分为每升水0.000000001毫克（mgAI / L）至0.0001 mgAI / L，或完全没有PPF。使用世卫组织标准的拟除虫菊酯（0.75％氯菊酯和0.05％溴氰菊酯），氨基甲酸酯（0.1％苯达威克）和有机氯化物（4％滴滴涕）进行了易感性测试，测试了逃脱这些亚致死危险的成年人。通过预先暴露于4％PBO来研究拟除虫菊酯抗药性的生化基础。还检查了经杀虫剂处理的长效网（Olyset和PermaNet 2.0）对成年蚊子的生物有效性，该成蚊具有或不具有先前对PPF的水生暴露。结果：向拟除虫菊酯抗性An的幼虫栖息地中添加了亚致死剂量的PPF。当暴露于拟除虫菊酯而不是扑灭威或DDT时，阿拉伯半岛持续导致新生成年人的死亡率显着降低。暴露于PPF后，暴露于Olyset网但未降低PermaNet 2.0的死亡率也降低了。与单独使用任何一种杀虫剂相比，预先暴露于PBO之后再加上氯菊酯或溴氰菊酯会导致死亡率显着增加。结论：暴露于亚致死浓度的PPF水中的部分抗性蚊子对拟除虫菊酯的抗性可能比没有预先暴露的蚊子更强。应该进行研究以检查在幼虫媒介种群中已经存在这种抗药性迹象的地区，通过杀幼虫剂或其他方法在田间施用PPF是否实际上会加剧拟除虫菊酯抗性。研究还应研究耐药性放大的潜在机制，以及这如何影响拟除虫菊酯耐药性地区基于PPF的干预措施的潜力。