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.
