Behavior-Modifying Compounds for Disease Vector Control

描述（由申请人提供）：一家大型杀虫剂公司（巴斯夫）正在与一个研究人员网络合作，开发影响传染病节肢动物媒介行为的化学品。目标是确定改变节肢动物行为的化学品，并评估其通过防止人与病媒接触减少疾病传播风险的功效。本计划中确定的化合物将转移至巴斯夫进行商业开发。贫穷国家对新的疾病控制工具的需求是迫切的，也是最大的;因此，这种化学品必须易于制造，成本低廉。因此，已知的合成化合物将是拟议研究的主要焦点。对于公共卫生来说，理想的化学品是一种持久存在于处理过的基质中或基质上，但在生命系统中迅速降解的化学品。重点将放在探索性测试上，以比较针对不同病媒物种的各种测试方法，并使用优化测试作为高通量方法，比较不同化学品对疾病病媒的驱避、刺激和毒性作用。第一个具体目标是优化一套标准化测试。试验将包括（1）局部驱避作用（防止叮咬）的体外试验，（2）接触刺激作用的单次暴露和逃逸试验系统，（3）一组三个室（中央暴露室，由处理和未处理室包围）作为驱避作用的特定试验，以及（4）接触毒性试验。将对最近定植的疟疾、登革热、利什曼病和巴尔通体病的病媒进行测试。第二个具体目标是使用特定的驱避剂、刺激剂或有毒化学品作为先导化合物，通过组合化学技术开发其他实验化学品。第三个具体目标是实地测试选定的化合物，证明有效的行为修改活动。实地测试将包括监测病媒进出实验小屋的移动情况，以及观察叮咬情况和24小时存活情况，并将包括对处理过的小屋和未处理过的小屋（对照）进行比较。一个随机模型和标准统计将被用来评估数据从实验小屋。我们建议，我们的研究计划的成功将实现一个新的代理（S）和一个新的战略（S）的疾病控制。测试数据将提供给巴斯夫，作为决定是否继续进行进一步毒理学评估和有前途的化合物商业开发的基础。

DESCRIPTION (provided by applicant): A major insecticide company (BASF) is working with a network of investigators to develop chemicals that influence behaviors of arthropod vectors of infectious diseases. The goals are to identify chemicals that alter arthropod behaviors and to evaluate their efficacy in reducing risks of disease transmission by preventing man-vector contact. Compounds identified in this program will be transferred to BASF for commercial development. The need for new disease control tools is urgent and greatest in poor countries; so the chemical must be easily and cheaply manufactured. Thus, known synthetic compounds will be the primary focus of proposed research. For public health, the ideal chemical is one that persists in or on treated substrates but rapidly degrades in living systems. Emphasis will be on exploratory testing to compare various test methods against different vector species, and to use optimized tests as a high throughput method to compare different chemicals for levels of repellent, irritant and toxicant actions against disease vectors. The First Specific Aim is to optimize a suite of standardized tests. Testing will consist of (1) an in vitro test for topical repellent action (prevent biting), (2) a single exposure and escape test system for contact irritant actions, (3) a set of three chambers (a central exposure chamber bracketed by treated and untreated chambers) as a specific test for repellent actions, and (4) a test for contact toxicity. Tests will be conducted with recently colonized vectors of malaria, dengue, leishmaniasis and bartonellosis. The Second Specific Aim is to use specific repellent, irritant or toxic chemicals as lead compounds for developing, through combinatorial chemistry technology, other experimental chemicals. The Third Specific Aim is to field test selected compounds that demonstrate potent behavior-modifying activity. Field testing will consist of monitoring the movement of disease vectors into and out of experimental huts, as well as observations on biting and 24-hour survival, and will consist of comparisons between treated and untreated (control) huts. A stochastic model and standard statistics will be used to evaluate data from experimental huts. We propose that success with our research plan will achieve both a novel agent(s) and a novel strategy(s) for disease control. Test data will be given to BASF as a basis for deciding whether to proceed with further toxicological evaluations and commercial development of promising compounds.