Ecology and genetics of insecticide resistance in African malaria vectors

非洲疟疾媒介的杀虫剂抗药性的生态学和遗传学

• 批准号: 10674140
• 负责人: YAW ASARE AFRANE
• 金额: $ 13.7万
• 依托单位: UNIVERSITY OF GHANA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10674140
• 关键词: Africa; Africa South of the Sahara; African; Age; Area; Beds; Behavior; Biochemical; Bite; Child; Complex; Country; County; Culicidae; Cytochrome P450; Data; Development; Dose; Drosophila genus; Drug Metabolic Detoxication; Ecology; Effectiveness; Enzyme Inhibition; Enzymes; Evolution; Exposure to; Feeding behaviors; Frequencies; Gene Family; Genetic; Genetic Transcription; Genotype; Goals; Heterogeneity; Human; Insecticide Resistance; Insecticides; Kenya; Malaria; Measures; Mediating; Metabolic; Methods; Mutation; Outcome; Pattern; Persons; Phenotype; Population; Production; Recording of previous events; Residual state; Resistance; Rest; Risk; Role; Sahara; Shapes; Site; Variant; Vector Ecology; density; genome-wide; next generation; prospective; public health relevance; pyrethroid; resistant strain; response; scale up; synergism; transcriptome sequencing; transcriptomics; transmission process; vector; vector control; vector transmission

Project summary Title: Ecology and genetics of insecticide resistance in African malaria vectors The current first-line vector control methods rely on pyrethroid-based long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). Insecticide-resistant vector genotypes are selected, leading to widespread of insecticide resistance in sub-Saharan Africa. The evolution of insecticide resistance is threatening to reverse the global gains in malaria control1,2. Due to the increasing insecticide resistance in sub-Saharan Africa, pyrethroid- based synergized next generation bednets were recently introduced in many African countries to overcome the challenge of insecticide resistance. These nets contain synergist piperonyl butoxide (PBO) which inhibits the activity of pyrethroid detoxifying cytochrome P450 enzymes by forming a metabolite-inhibitory complex with the enzyme. However, little is known about how African malaria vectors respond to PBO exposure at the gene transcription, biochemical and organismal level. It has been shown that in insecticide-sensitive Drosophila that PBO is capable of inducing the expression of the P450 and GST detoxification gene families. The increased production of P450 and GST enzymes by PBO exposure has the potential to increase insecticide tolerance. If this is true to malaria vectors, the impact of PBO on insecticide resistance mitigation is limited. The central objective of this continuation application is to better understand the ecology and genetics of insecticide resistance in the face of pyrethroid synergized nets introduction in the major African malaria vectors in western Kenya where we maintain selected pyrethroid resistant strains and PBO nets are being widely distributed in some counties. To achieve this goal three aims are developed. In aim 1, we will examine the impact of next-generation PBO bednets on vector bionomics and transmission reduction. Data from this will inform the effectiveness of PBO nets in transmission reduction in areas with pre-existing high pyrethroid resistance. In aim 2, we will determine the genetic basis of variations in mosquito phenotypes due to PBO nets. This aim will provide information on importance of the different mechanisms of insecticide resistance that exist in western Kenya which is critical to the development of PBO net deployment strategy. In aim 3, we will determine the response to PBO exposure at the gene transcription and biochemical level in pyrethroid resistant malaria vectors. Data from this aim can provide critical information on the genetic mechanisms and risks of PBO synergist in resistance mitigation in field malaria vector populations with high resistance. Overall, these 3 aims will inform PBO net deployment strategy, impact on transmission reduction and potential risks on its inability to mitigate resistance.

项目摘要 标题：非洲疟疾媒介中杀虫剂抗性的生态和遗传学 当前的一线矢量控制方法依赖于基于拟甲虫素的长期杀虫网（LLIN）和 室内残留喷涂（IRS）。选择了耐杀虫剂的载体基因型，导致广泛的 撒哈拉以南非洲的杀虫剂抗性。抗杀虫剂的演变威胁要逆转 疟疾控制的全球收益1,2。由于撒哈拉以南非洲的杀虫剂耐药性的增加，拟除虫菊酯 - 最近在许多非洲国家引入了基于基于的下一代床网，以克服 抗杀虫剂的挑战。这些网中包含协同的哌啶丁氧化物（PBO） 拟除虫菊酯排毒细胞色素P450酶的活性，通过与代谢物抑制性复合物与 酶。但是，关于非洲疟疾媒介如何应对基因的PBO暴露，知之甚少 转录，生化和生物水平。已经表明，在对杀虫剂敏感的果蝇中 PBO能够诱导P450和GST解毒基因家族的表达。增加 通过PBO暴露生产P450和GST酶有可能提高杀虫剂的耐受性。如果 疟疾载体确实如此，PBO对杀虫剂耐药性缓解的影响受到限制。中央 这种延续应用的目的是更好地了解杀虫剂的生态和遗传学 面对拟除虫菊酯的耐药性在主要非洲疟疾媒介中协同网络引入 肯尼亚西部我们维持选定的拟甲虫素抗性菌株和PBO网络广泛 分布在一些县。为了实现这一目标，开发了三个目标。在AIM 1中，我们将检查 下一代PBO床头对矢量bionomics和传输减少的影响。来自此的数据 告知PBO网中PBO网的有效性在降低高拟甲虫素的区域的传输降低区域 反抗。在AIM 2中，我们将确定由于PBO网络引起的蚊子表型变化的遗传基础。 此目标将提供有关存在的不同机制的重要性的信息 在肯尼亚西部，这对于制定PBO净部署战略至关重要。在AIM 3中，我们将确定 在拟甲虫素疟疾中对PBO暴露的反应 向量。该目标的数据可以提供有关PBO协同作用的遗传机制和风险的关键信息 在耐药性疟疾载体群体中的抗性中，具有较高的抗性。总体而言，这三个目标将告知 PBO净部署策略，对减少传输的影响以及无法减轻的潜在风险 反抗。