Quantifying insecticide impact on malaria transmission: does resistance matter?

 描述(申请人提供)：大规模部署针对成虫蚊媒的杀虫剂干预措施，有助于近年来全球疟疾负担的显著下降。然而，许多受疟疾影响的国家现在报告出现了杀虫剂抗药性。如果不加以控制，抗药性蚊子的传播可能会破坏当代的疟疾控制。然而，令人惊讶的是，杀虫剂耐药性的流行病学意义仍然很不明确，证明耐药性与疟疾死灰复燃之间存在因果联系的例子很少。我们在当前提案中的总体目标是确定杀虫剂抗药性最终是否以及如何影响疟疾传播。具体地说，我们的目标是确定在考虑到一系列生态因素的影响时，如昆虫年龄、感染状况、环境条件、实际暴露模式和昆虫行为，按世卫组织的“行业标准”分析，名义上被定义为抗药性的蚊子在多大程度上仍具有功能性抗药性。为了补充这些传播相关的措施，我们将量化与杀虫剂抗药性相关的任何健康相关成本，再次捕捉现实环境应激源的影响。最后，我们将使用一套由新的经验数据参数化的建模方法来探索耐药性对疟疾传播的影响，并评估在不同的环境条件和可能的管理处方下耐药性可能如何传播。总而言之，这项研究将促进对抗药性流行病学意义的基本理解，并为适当制定抗药性管理策略提供证据基础。

 DESCRIPTION (provided by applicant): The wide scale deployment of insecticide-based interventions against adult mosquito vectors has contributed to significant declines in the global malaria burden in recent years. However, many malaria-affected countries are now reporting the emergence of insecticide resistance. If left unchecked, the spread of resistant mosquitoes could derail contemporary malaria control. Yet surprisingly, the epidemiological significance of insecticide resistance remains very poorly defined and examples demonstrating a causal link between resistance and malaria resurgence are few. Our overall objective in the current proposal is to determine whether and how insecticide resistance ultimately affects malaria transmission. Specifically we aim to determine the extent to which mosquitoes nominally defined as resistant using the `industry standard' WHO assays, remain functionally resistant when the influence of a suite of ecological factors such as insect age, infection status, environmental conditions, realistic exposure patterns and insect behavior are taken into account. To complement these transmission-related measures, we will quantify any fitness related costs associated with insecticide resistance, again capturing the effects of realistic environmental stressors. Finally, we will use a suite of modeling approaches parameterized from the novel empirical data to explore the implications of resistance for malaria transmission and to evaluate how resistance might spread under different environmental conditions and possible management prescriptions. Combined, the research will advance fundamental understanding of the epidemiological significance of insecticide resistance and provide an evidence base for appropriate development of insecticide resistance management strategies.