Development of novel resistance management strategies

开发新颖的阻力管理策略

• 批准号: 6806448
• 负责人: Janet Hemingway
• 金额: $ 54.06万
• 依托单位: TMLIVERPOOL SCHOOL OF TROPICAL MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6806448
• 关键词: Africa; Anopheles; animal population density; communicable disease transmission; cooperative study; cytochrome P450; disease vectors; drug interactions; field study; insecticide resistance; malaria; molecular biology; polymerase chain reaction; pyrethroid; toxin metabolism

DESCRIPTION (provided by applicant): Malaria affects at least a billion people worldwide, and over 1.5 million infected children less than 5 years old die each year. Insect vector control programs have historically been an effective strategy for reducing disease transmission, but many malaria vectors have developed resistance to available insecticides. In partnership with Bayer, Astrazeneca and the broader industrially funded IRAC group, we will take an innovative approach to evaluate novel resistance management programs against pyrethroid resistant Anopheles funestus in Southern Africa. The field part of the program will determine whether we can drive back the current pyrethroid resistance front in Mozambique, that extends down into South Africa, using an annual insecticide rotation strategy. Coincident with this, a laboratory program will identify the molecular basis of pyrethroid resistance in this major malaria vector. We will work with our industrial partners initially to optimize the current management strategy, and subsequently to engineer synergists to specifically block the developing pyrethroid resistance. Synergists will be designed against the regulators of pyrethroid resistance in An. funestus and An. gambiae. The program will benefit from partnerships already established within the group to investigate similar resistance mechanisms in Anopheles gambiae from East Africa. If identical resistance regulatory mechanisms are operating in the two species it is possible that the synergist development and commercialization phase could occur within the time frame of this project. These synergists should in the medium term feed into the field-based resistance management program to expand the range of available vector control tools and extend the useful life of the pyrethroids within both indoor and residual spraying and impregnated bednet-based malaria control programmes.

描述（由申请人提供）：疟疾在全球至少有10亿人，而每年不到5岁的受感染儿童死亡。从历史上看，昆虫载体控制程序一直是减少疾病传播的有效策略，但是许多疟疾媒介对可用杀虫剂产生了抗性。与拜耳，阿斯利康和更广泛的工业资助的IRAC集团合作，我们将采用一种创新的方法来评估南部非洲针对抗多灵甲性抗多灵的耐拟甲虫素耐药网的新型抗药性管理计划。 该计划的田地部分将确定我们是否可以使用年度杀虫剂旋转策略来延长莫桑比克目前的拟除虫菊酯抗性锋。与此相吻合，实验室计划将确定该主要疟疾载体中拟除虫菊酯抗性的分子基础。我们将最初与工业合作伙伴合作，以优化当前的管理策略，然后与工程师协同作用，以特别阻止发展中的拟除虫菊酯抗性。协同作用将针对An中的拟除虫菊酯耐药性调节器设计。 Funestus和An。冈比亚。 该计划将受益于该小组内已经建立的伙伴关系，以调查来自东非的Anopheles Gambiae类似的抵抗机制。如果在这两个物种中运行相同的阻力调节机制，则可能在该项目的时间范围内发生协同发展和商业化阶段。这些协同作用应在中期供应到基于现场的电阻管理计划中，以扩大可用的矢量控制工具的范围，并在室内和残留喷涂和基于卧网的疟疾控制计划中延长拟除虫菊酯的使用寿命。