Recently, resistance to anthelmintics has emerged as the most important problem confronting the control of parasitic nematodes of ruminants. Resistance in parasites of other economically significant animals has also been reported and there can be little doubt that the incidence of resistance will increase and will also eventually appear in medically important parasites of man. The impact of resistance has been contained by the introduction of ivermectin, the most potent, and arguably the most efficacious, anthelmintic ever developed. However, recent reports suggest that development of resistance may soon reduce its value. Extensive investigations of ivermectin resistance in the model nematode Caenorhabditis elegans have generated a specific hypothesis regarding the likely form of ivermectin resistance in parasitic nematodes. The goals of Phase I are to test the hypothesis and to identify the genes responsible for ivermectin resistance in parasitic nematodes. During Phase II these genes will be cloned and diagnostic reagents capable of detecting ivermectin resistance in parasites will be developed. Diagnostic reagents will provide early warning of emerging resistance and an ability to monitor the efficacy of new methods designed to limit, and preferably reverse, the growth of ivermectin resistant populations.Awardee's statement of the potential commercial applications of the research:Our goal is to develop diagnostic reagents capable of detecting ivermectin resistance in significant parasites. These reagents will be used to test for nascent resistance in the field and to monitor progress toward the development of new anthelmintics with selective potency on ivermectin-resistant nematodes.National Institute of Allergy and Infectious Diseases (NIAID)