Behavior-Modifying Compounds for Disease Vector Control

描述(由申请人提供)：一家主要的杀虫剂公司(巴斯夫)正在与一个调查网络合作，开发影响传染病节肢动物媒介行为的化学物质。其目标是识别改变节肢动物行为的化学物质，并评估它们通过防止人与媒介接触来降低疾病传播风险的有效性。该计划中确定的化合物将被转移到巴斯夫进行商业开发。贫穷国家迫切需要新的疾病控制工具；因此，这种化学品必须容易和廉价地制造。因此，已知的合成化合物将是拟议研究的主要重点。为了公众健康，理想的化学物质是一种在处理过的底物上持续存在，但在生命系统中迅速降解的化学物质。重点将放在探索性测试上，以比较针对不同媒介物种的各种测试方法，并使用优化的测试作为高通量方法来比较不同化学物质对病媒的驱避、刺激和毒害作用水平。第一个具体目标是优化一套标准化考试。测试将包括(1)局部驱避作用的体外测试(防止叮咬)，(2)接触刺激性行为的单一暴露和逃逸测试系统，(3)一套三个小室(由处理和未处理的小室组成的中央暴露小室)作为驱避作用的特殊测试，以及(4)接触毒性测试。将对最近定居的疟疾、登革热、利什曼病和巴尔通氏杆菌病的媒介进行测试。第二个具体目标是利用特定的驱避剂、刺激性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，这些化合物显示出强大的行为改变活性。现场测试将包括监测病媒进入和离开实验小屋的情况，以及对叮咬和24小时存活的观察，并将包括治疗和未治疗(对照)小屋之间的比较。随机模型和标准统计将被用来评估来自实验小屋的数据。我们认为，我们研究计划的成功将实现一种新的疾病控制试剂(S)和一种新的策略(S)。测试数据将提供给巴斯夫，作为决定是否继续进行进一步的毒理学评估和有前景的化合物的商业开发的基础。

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.