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 非洲疟疾病媒杀虫剂抗药性的生态学和遗传学 目前的一线病媒控制方法依赖于使用拟除虫菊酯的长效驱虫蚊帐， 室内滞留喷洒。选择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药性。杀虫剂耐药性的演变有可能扭转这种局面 全球疟疾防治成果1，2.由于撒哈拉以南非洲的杀虫剂抗药性不断增加，拟除虫菊酯- 最近在许多非洲国家采用了基于协同作用的下一代蚊帐， 杀虫剂抗药性的挑战。这些蚊帐含有三氧化二胡椒基丁醚（PBO）， 拟除虫菊酯解毒细胞色素P450酶的活性，通过与 酵素然而，关于非洲疟疾病媒如何在基因上对PBO暴露作出反应， 转录、生物化学和生物体水平。研究表明，在对腺苷酸敏感的果蝇中， PBO能够诱导P450和GST解毒基因家族的表达。增加的 通过PBO暴露产生P450和GST酶具有增加杀虫剂耐受性的潜力。如果 对于疟疾病媒来说，PBO对减轻杀虫剂抗药性的影响是有限的。中央 本延续申请的目的是更好地了解杀虫剂的生态学和遗传学 非洲主要疟疾病媒对拟除虫菊酯增效蚊帐的抗药性 肯尼亚西部，我们保持了选定的拟除虫菊酯抗性菌株，PBO蚊帐正在广泛使用， 分布在一些县。为了实现这一目标，制定了三个目标。在目标1中，我们将检查 下一代PBO蚊帐对病媒生物学和减少传播的影响。数据将 告知PBO蚊帐在先前存在高拟除虫菊酯的地区减少传播的有效性 阻力在目标2中，我们将确定PBO蚊帐引起的蚊子表型变异的遗传基础。 这一目标将提供信息的重要性，不同的机制，杀虫剂的抗药性，存在 这对制定PBO网部署战略至关重要。在目标3中，我们将确定 拟除虫菊酯抗性疟疾对PBO暴露在基因转录和生化水平上的反应 向量。这一目标的数据可以提供关于PBO遗传机制和风险的关键信息。 在具有高抗性的实地疟疾病媒种群中，总的来说，这三个目标将告知 PBO网络部署战略、对减少传播的影响以及无法缓解的潜在风险 阻力