Recent dramatic declines in global malaria burden and mortality can be largely attributed to the large-scale deployment of insecticidal-based measures, namely long-lasting insecticidal nets (LLINs) and indoor residual spraying. However, the sustainability of these gains, and the feasibility of global malaria eradication by 2040, may be affected by increasing insecticide resistance among the Anopheles malaria vector. We employ a new differential-equations based mathematical model, which incorporates the full, weather-dependent mosquito lifecycle, to assess the population-level impact of the large-scale use of LLINs, under different levels of Anopheles pyrethroid insecticide resistance, on malaria transmission dynamics and control in a community. Moreover, we describe the bednet-mosquito interaction using parameters that can be estimated from the large experimental hut trial literature under varying levels of effective pyrethroid resistance. An expression for the basic reproduction number, [Formula: see text], as a function of population-level bednet coverage, is derived. It is shown, owing to the phenomenon of backward bifurcation, that [Formula: see text] must be pushed appreciably below 1 to eliminate malaria in endemic areas, potentially complicating eradication efforts. Numerical simulations of the model suggest that, when the baseline [Formula: see text] is high (corresponding roughly to holoendemic malaria), very high bednet coverage with highly effective nets is necessary to approach conditions for malaria elimination. Further, while >50% bednet coverage is likely sufficient to strongly control or eliminate malaria from areas with a mesoendemic malaria baseline, pyrethroid resistance could undermine control and elimination efforts even in this setting. Our simulations show that pyrethroid resistance in mosquitoes appreciably reduces bednet effectiveness across parameter space. This modeling study also suggests that increasing pre-bloodmeal deterrence of mosquitoes (deterring them from entry into protected homes) actually hampers elimination efforts, as it may focus mosquito biting onto a smaller unprotected host subpopulation. Finally, we observe that temperature affects malaria potential independently of bednet coverage and pyrethroid-resistance levels, with both climate change and pyrethroid resistance posing future threats to malaria control.

中文翻译：

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持久的杀虫网和对消灭疟疾的追求：一种数学建模方法。

全球疟疾负担和死亡率最近的急剧下降，在很大程度上可以归因于大规模采用基于杀虫剂的措施，即长效杀虫网（LLIN）和室内残留喷雾剂。然而，这些成果的可持续性以及到2040年全球消灭疟疾的可行性可能会受到按蚊疟疾媒介中杀虫剂抗药性增加的影响。我们采用了一个新的基于微分方程的数学模型，该模型结合了完整的，取决于天气的蚊子生命周期，以评估在不同水平的按蚊拟除虫菊酯类杀虫剂抗药性水平下大规模使用LLIN的人群水平对疟疾传播的影响社区中的动态和控制。此外，我们使用可从大型实验小屋试验文献中估算的不同拟除虫菊酯抗性水平下估计出的参数来描述蚊帐-蚊子的相互作用。推导了基本繁殖数的表达式[公式：见正文]，它是人口水平蚊帐覆盖率的函数。由于向后分叉的现象，表明[公式：见正文]必须被推到1以下，以消除流行地区的疟疾，这可能使消灭工作复杂​​化。该模型的数值模拟表明，当基线[公式：见正文]较高时（大致对应于全血统疟疾），为接近消除疟疾的条件，需要非常高的蚊帐和高效的蚊帐。此外，虽然> 50％的蚊帐覆盖可能足以从中等流行性疟疾基线的地区强烈控制或消除疟疾，即使在这种情况下，拟除虫菊酯的抗药性也会破坏控制和消除疟疾的努力。我们的仿真表明，蚊子中拟除虫菊酯的抗性会在整个参数空间内明显降低蚊帐的有效性。这项建模研究还表明，增加蚊子的血液前威慑力（阻止它们进入受保护的房屋）实际上会阻碍消除工作，因为这可能会将蚊子的叮咬集中在较小的未受保护的宿主亚群上。最后，我们观察到温度对疟疾潜势的影响独立于蚊帐的覆盖范围和拟除虫菊酯的抗药性水平，气候变化和拟除虫菊酯的抗药性都将对疟疾控制构成未来的威胁。