'Membrane Ion-channels in Helminth Parasites: Resistance and Sites of Action for Anthelmintics'The Neglected Tropical Diseases include the Soil-Transmitted Nematode (STN) parasites (ascariasis, hookworm, and trichuriasis), filariasis (river blindness and lymphatic filariasis) and schistosomiasis. These diseases are caused by Clade I, III and V parasitic nematodes and the trematodes S. mansoni, S. haematobium and S. japonicum. Ascariasis is caused by the large intestinal roundworm, Ascaris lumbricoides. Worldwide, it occurs in 1.4 billion people. Lymphatic filariasis (elephantiasis) threatens over a billion people in 83 countries and is caused by filarial nematodes like Wuchereria bancrofti and Brugia malayi. Schistosomiasis threatens over 1 billion people and infects some 300 million individuals. These infections are both caused by, and cause, poverty. Prophylaxis and treatment of these parasitic diseases relies on the use of anthelmintic drugs because no effective vaccines are available;but, there are real concerns that mass chemotherapy will lead to development of resistance. Single-dose Mass Drug Administration [MDA] is preferable for prevention and treatment, and is used by current control and elimination programs, but is not effective with most (all) anthelmintics. The emergence of resistance to any of the drugs currently used in MDA would deal a devastating blow to the control of these debilitating diseases. No current anthelmintic has optimal properties so there is an urgent need for new lead compounds, together with a better grounding of basic science to improve the use of existing drugs and new drug development. Ion-channels in helminths are major, validated, sites of action for existing and for potential novel anthelmintics. Our conference is planned as a Pre-meeting of the American Society of Tropical Medicine, in Philadelphia at the Downtown Marriot Hotel, Dec 1-3, 2011. The symposium is timely and will facilitate spread of knowledge and foster research interest in this important and expanding area of research by our program of speakers, interactions between delegates, discussions of strategic directions and publication of the meeting's papers. There will be an open registration to national and international attendees. Our current estimated number of attendees is 100. The field is expected to be of most interest to parasitologists and public health interests. The planning and location will allow accommodation for disabilities and actively seek input and contribution from minorities. The conference will include invited expert speakers from the field and to seek submissions from interested participants to present papers and/or posters. The intention of the conference is to encourage research and knowledge of ion-channel drug targets in helminths;to encourage collaborative research;to improve recognition and support for the field of research. The planned outcome is publication of papers in a special edition of the Journal Invertebrate Neuroscience. Each speaker will review their area of expertise and be invited to comment on how the community should organize itself to advance the field of study. An important aim is to invigorate the research area and to raise the level of interest in basic research for drug development of neglected tropical diseases. We have four aims at our conference: Aim #1: To review recent progress in understanding the actions of anthelmintics at ion channels, and how resistance to those drugs can emerge. Aim #2: To publish a special issue of a learned journal summarizing current knowledge in this area. Aim #3: To encourage the formation of new cross-disciplinary international collaborations that will recruit established workers in other fields to study parasitic helminths. Aim #4: To identify and pursue opportunities for increased funding for projects in this area. The overall impact will be a powerful influence on: Odispersion and expansion of the knowledge base of membrane and ligand gated ion-channels as helminth drug targets;Oan increase in the number of active scientists supporting the field;Oidentification of strategic directions for the development of the field;O within 24 months, two or more significant (R01 or similar) proposals and two or more collaborative projects between US and international researchers will be formed.

PUBLIC HEALTH RELEVANCE: Nematode parasites and flatworm parasites affect more than 1.5 billion people world- wide;these diseases are not a focus of interest in developed countries and part of a group of diseases known as the neglected tropical diseases. These helminth parasites reduce growth, health, cause lost work productivity and contribute to poverty. There are no effective vaccines and so in the absence of adequate sanitation, treatment and prophylaxis relies on anthelmintic drugs. There are concerns that Mass Drug Administration required for helminth control will produce resistance. To counter this real concern new drugs, new drug target sites and the necessary supporting basic research is required. Membrane and ligand-gated ion-channels are major, validated, anthelmintic drug target sites. The 2-day open symposium will bring together national and international experts in the field of membrane ion-channels of helminths as drug targets, will foster communication of the new knowledge base of the field, and identify strategic directions for the development of the field. It will also recruit new interest to this developing and important research topic.

R13AI096749

2011-08-15

2012-07-31