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United States Department of Agriculture

Agricultural Research Service

Research Project: MANIPULATION OF ARTHROPOD BEHAVIOR FOR PROTECTION OF HUMANS
2006 Annual Report


1.What major problem or issue is being resolved and how are you resolving it (summarize project aims and objectives)? How serious is the problem? Why does it matter?
New chemical tools are urgently needed for the protection of humans against existing and emerging diseases transmitted by blood-sucking insects and other arthropods. Chemicals detrimental to disease-vectoring arthropod behavior and/or physiology will be identified, providing a means to reduce risks of disease transmission to humans. Discovery of topical repellents active at lower levels of active ingredient than contained in current repellents will enable more acceptable repellent formulations to be developed, thereby increasing human usage. Emphasis will be on exploratory chemical testing of compounds obtained from existing chemical libraries, and from model synthetic compounds generated by rational chemical design. New fabric-bound chemicals will be explored for vector control. Compounds will be evaluated against vectors of malaria, dengue, and West Nile virus using optimized high through put assays to compare different chemicals for levels of repellent, irritant and pesticide activity. These assays will identify new compounds having behavioral and/or insecticidal modes of action. In addition, new chemical attractants will be sought for improved mosquito surveillance, and spatial repellent compounds will be sought to guard against biting arthropods entering areas of human habitation. In all of the research, there will be an underlying effort to understand the mechanisms and modes of action of new and existing chemicals. In part, the proposed research involves a consortium of military, government, academic, and private industry groups. The new medically important chemical tools will be introduced into existing pest management programs related to public health protection.

This program falls within the National Program 104 Mission to develop effective means to prevent or suppress insects and other arthropods that affect human well being and to enhance the safety and quality of life for the U.S. public. The research involves a multidisciplinary approach involving entomology, insect behavior, vector biology, and organic, analytical and computational chemistry. The project focuses on NP104 goals 2.2.1 (Develop species-specific traps and traps that will automatically register and transmit collection information), 2.2.3 (Identify and synthesize host specific attractants for use in traps), 3.2.2 (Characterize and isolate pheromones and other cues used by Diptera in mating and host finding), 3.2.3 (Develop measurements of electrophysiological activation for use in selecting vector repellents.), 4.1.1 (Develop and use computational models for rapidly screening and predicting efficacy of available compounds from configurational extrapolation), 4.1.2 (Develop and test novel means of applying pesticides and repellents that are more efficient, methods to bond agents to material, and area repellents), and 4.1.3 (Identify and test new classes of topical and area repellents for previously synthesized or natural volatiles. Develop carrier formulations).


2.List by year the currently approved milestones (indicators of research progress)
Year 1 (FY2005)

Insects rearing optimized using blood-membrane feeding.

Standardized high through put screening (HTS) assay system in place.

A Computational methodology for compound selection from BASF library in place.

Design and synthesis of 3 pyrethroids containing molecular spacers complete.

Design and synthesis of several polymers with functional groups suitable for attaching repellent units studied.

Candidate compounds bioassayed against a mosquito. Method for chemically attaching the modified pyrethroids to polymer studied.

Known repellent compounds studied using Culex quinquifaciatus odorant binding proteins (OBPs) affinity columns.

Preliminary single cell electrophysiological screening recording (SCR) experiments conducted on Culex pipiens.

Cloning of OBP from Anopheles stephensi and Aedes aegypti initiated.

Year 2 (FY2006)

HTS-evaluated 3,000 BASF library compounds and two new model compounds identified. Computational chemistry models optimized. EPA requirements for product registration determined.

Synthetic polymers containing chemically bonded pyrethroids obtained and bioassayed.

Most promising polymers are spun into fibers.

Affinity columns prepared using cloned Anopheles stephensi and Aedes aegypti OBPs and SCR started with the two species.

Year 3 (FY2007)

Synthetic methods for preparation of model compounds for field tests developed. Field tests experimental designs complete.

Fabric development studied.

Complete experimental designs for field tests.

Compound screening started using CquiOBP affinity columns.

Year 4 (FY2008)

Final evaluation studies of most promising compounds completed. New refined and efficient computational chemistry strategies identified and published.

New fabrics developed.

Complete SCR comparisons in three mosquito species.

Year 5 (FY2009)

EPA registration and technology transfer of new products in final stages. Finish field tests to test vector-control efficacy.

Finish Quantitative Structure Activity Relationship (QSAR) studies using synthetic model compounds having optimized OBP affinity.


4a.List the single most significant research accomplishment during FY 2006.
None


4b.List other significant research accomplishment(s), if any.
None


4c.List significant activities that support special target populations.
None


5.Describe the major accomplishments to date and their predicted or actual impact.
Screening program established to identify new mosquito repellents We have designed and established an extensive chemical screening program to identify new mosquito repellents and toxicants. Our customers include industry partners interested in developing and marketing new topical skin repellents, the U.S. public interested in protecting themselves from the insects and other arthropods that transmit Lyme disease and West Nile virus, and the U.S. military that require new topical skin repellents to protect deployed forces from disease-transmitting, blood-sucking arthropods. To date, we have published a series of articles on new screening procedures that will be used by the scientific community interested in developing new repellents. The potential impact is the availability of new, E.P.A.-registered repellents. This accomplishment aligns with Component 4 (Control Technology) of National Program 104 (Veterinary, Medical and Urban Entomology).


6.What science and/or technologies have been transferred and to whom? When is the science and/or technology likely to become available to the end-user (industry, farmer, other scientists)? What are the constraints, if known, to the adoption and durability of the technology products?
Techniques for using in vitro bioassays to test compounds for repellent activity have been transferred to the scientific community in publications. A CRADA has been developed as well as several cooperative agreements. Our customers are the U.S. Military, public health-care industries, and pest management industries, other scientists and the consumer public. Constraints include the ability to conduct human repellent testing and changing guidelines for repellent approval by the EPA.


7.List your most important publications in the popular press and presentations to organizations and articles written about your work. (NOTE: List your peer reviewed publications below).
Klun, J.A. 2006. “SS220-a new compound to fend off blood-feeding arthropods.” Presentation to 2006 Pesticide Recertification Program and Agriculture Trade Show, March 3, 2006, USDA-ARS, BARC-West, Beltsville, MD.

Klun, J.A. 2006. “A new compound for personal protection against blood-feeding arthropods.” Presentation to The 2006 Pesticide Safety Conference for Forest, Aquatic, and Right-of-Way Pest Control and Industrial Weed Control, March, 23, 2006. BWI Airport Marriot Hotel..

Cantrell, C. 2006. "Folk Remedy Yields Mosquito-thwarting Compound.” International Pest Control news article, May/June 2006, 48(3):153-154.

Krajick, K. 2006. “Keeping the bugs at bay”. Science. 313:36-38.

Klun, J.A. 2006. “Upwind flight and feeding engorgement of Aedes aegypti in a flight tunnel.” Presentation to the Armed Forces Pest Management Board, Repellents Committee, July 25, 2006, Forest Glenn, MD.


Review Publications
Natarajan, R., Basak, S., Balaban, A., Klun, J.A., Schmidt, W.F. 2005. Chirality index, molecurlar overlay and the activity of stereoisomeric topical mosquito repellents. Pesticide Management Science. 61:1193-1201.

Klun, J.A., Khrimian, A., Debboun, M. 2006. The repellent and deterrent effects of ss220, bayrepel and deet against aedes aegypti, anopheles stephensi and phlebotomus papatasi. Journal of Medical Entomology. 43: 34-39.

Debboun, M., Klun, J.A., Strickman, D.A. 2005. Repellents and the military: our first line of defense.. Journal of the Mosquito Control Association. 21:4-6.

Houpt, J.T., Debboun, M., Michie, M.W., Paulus, H.I., Thompson, M.I., Lee, R.B., Klun, J.A. 2005. The 90-day dermal toxicity of the repellent ss-220 in rats. U.S. Army Center for Health Promotion and Preventative Medicine. Toxicology Study No. 85-XC-3929-04.

Tran, K., Chauhan, K.R. 2006. Structural activity of bovidic acid and related compounds as feeding deterrents against aedes aegypti. American Mosquito Control Association. Addendum 07/27/06.

Last Modified: 9/10/2014
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