Hookworms, blood feeding intestinal parasites, remain a major health burden with approximately a billion people infected in tropical and subtropical regions of the world. In these geographical areas, they are a major contributor to iron-deficiency anemia, weight loss, stunted growth and malnutrition. Control strategies have relied on mass treatment with benzimidazole drugs. However, recent reports have described the resistance of hookworms and other soil-transmitted nematodes to these drugs. Consequently, there is an urgent need to develop alternative control tools such as vaccines and novel therapeutics. Our proposal aims at identifying and characterizing plant compounds with activity against the hookworm Ancylostoma ceylanicum, one of the species causing the human disease. Two plant candidate species tested during our preliminary studies, namely Dalea ornata and Oemlaria cerasiformis, showed anthelminthic activity (mortality and/or reduced motility) in crude extracts and enriched fractions. Associated worm mortality rates ranged from 25% at 24 hours to 100% at 120 hours, after incubating worms with the test compounds. Accordingly, the following hypotheses will be tested: 1) Plants represent a relatively untapped source of potentially effective anthelminthic molecules. 2) Plant extracts, enriched chromatographic fractions, and purified components are active ex vivo and in vivo against adult hookworms. The planned studies will isolate active component(s) of D. ornata and O. cerasiformis and assess their activity using both ex vivo and in vivo protocols developed in our lab. Evaluation of the effects of active component(s) on the hookworm infection will be evaluated using clinical, parasitological and immunological parameters such as weight gain, anemia, egg output, worm burden, immune cell proliferation indices, immune cell population sizes, and hookworm-specific antibody levels.
Hookworms are the leading cause of malnutrition and anemia in resource limited countries, where they infect about a billion people. The experiments described in this application are designed to purify, assess, and characterize natural plant compounds for activity against the hookworm Ancylostoma ceylanicum, with the hope of discovering new treatment options. Our goal is directly relevant to public health because of the increasing evidence of developing resistance of hookworm, and other soil-transmitted nematodes, to currently used drugs.
| Deardorff, Kaitlin; Ray, William; Winterstein, Eric et al. (2016) Phenolic Metabolites of Dalea ornata Affect Both Survival and Motility of the Human Pathogenic Hookworm Ancylostoma ceylanicum. J Nat Prod 79:2296-303 |
