Environmental Health and Ecological Sciences, Ifakara Health Institute, Ifakara, Tanzania.
Barcelona Institute for Global Health (ISGlobal), Hospital Clinic, Barcelona, Spain.
PLoS One. 2021 Mar 18;16(3):e0248538. doi: 10.1371/journal.pone.0248538. eCollection 2021.
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.
Third-instar larvae of pyrethroid-resistant Anopheles arabiensis (both laboratory-reared and field-collected) were reared in different PPF concentrations, between 1×10-9 milligrams active ingredient per litre of water (mgAI/L) and 1×10-4 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.
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.
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 exacerbates 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.
吡丙醚（PPF）是一种昆虫生长激素模拟物，被广泛用作杀虫剂，并在一些第二代蚊帐中与拟除虫菊酯结合使用，以提高效果。它也被评估为通过成蚊自动传播来控制埃及伊蚊和按蚊属的候选药物。我们研究了在耐拟除虫菊酯的疟疾病媒幼虫栖息地添加 PPF 是否会调节新出现的成年蚊子中的抗药性水平。
用不同浓度的吡丙醚（1×10-9 毫克活性成分/升水（mgAI/L）至 1×10-4 mgAI/L）或根本不添加 PPF 处理三龄期耐拟除虫菊酯的埃及伊蚊（实验室饲养和野外采集）幼虫。从这些亚致死暴露中逃脱的成年蚊子用 WHO 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%丁硫克百威）和有机氯（4%滴滴涕）敏感性测定法进行测试。用 4% PBO 进行预暴露以研究吡丙醚抗性的生化基础。还测试了长效杀虫剂处理蚊帐 Olyset®和 PermaNet 2.0 对有或没有先前接触过 PPF 的水生环境的成年蚊子的生物效能。
在耐拟除虫菊酯的埃及伊蚊幼虫的幼虫栖息地添加亚致死剂量的 PPF，可显著降低接触拟除虫菊酯的成年蚊子的死亡率，但对氨基甲酸酯或滴滴涕无影响。在接触 PPF 水后，接触 Olyset®网的死亡率降低，但接触 PermaNet 2.0 网的死亡率未降低。与单独使用任何一种杀虫剂相比，用 PBO 预暴露后再用氯菊酯或溴氰菊酯处理，死亡率显著增加。
与没有这种预暴露的情况相比，接触亚致死水生浓度 PPF 的部分抗性蚊子可能对拟除虫菊酯的抗性增加。应进行研究以检查在野外种群中已经存在此类抗药性迹象的地区，通过幼虫处理或其他方式实际应用 PPF 是否会加剧拟除虫菊酯的抗药性。这些研究还应调查这种抗药性放大的机制，以及这可能如何影响在具有拟除虫菊酯抗性的地区使用基于 PPF 的干预措施的潜力。
