Cestode infections are insidious when from the larval stages of these parasites. They may cause serious liver, vascular or central nervous disease which can lead to death. In contrast, the adult stage tapeworm is often considered benign and ignored in areas of poor health care. This is often a result of the fact that the patients with the adult tapeworm living in the lumen of their intestines are unaware that they are infected. However, it is this stage of the infection that spreads the tapeworm eggs among family and community members causing the health threatening larval stage. Estimates suggest that 60 million persons are infected world wide and frequently it is women, as the family food preparer, who suffer a disproportionate number of central nervous system infections. Because of the insidiousness of the adult infection and potential impact of this stage on the spread of the disease, we are proposing to extend our examination of the interaction of adult tapeworm with its host and specifically the small intestine, in order to elucidate as yet undescribed effects on the host's intestinal physiology which may assist in diagnosis, lead to innovative prevention measures or more importantly, increase the motivation of the health community to eliminate the infection by demonstration that the adult tapeworm is not as benign as currently believed. We have shown that adult tapeworms modify gut behavior, transit of substance through the intestine, bacterial population of the enteric lumen, regional mast cell numbers and smooth muscle cell morphology. We have shown that mast cell are not involved in the altered motility occurring during infection and that the same altered contractile state of the small bowel will occur when homogenates of the tapeworm are introduced into an uninfected rat. These data suggest that the tapeworm controls intestinal physiology with secreted signal molecules. This proposal will identify the portions of the nervous system (central or enteric) which controls the tapeworm-induced altered motility by using a surgical bioassay developed by us and surgical transection and denervation techniques. In addition, we will identify specific afferent sensory neuron types responding to the tapeworm by using chemical ablation of those neuron classes known to be involved in sensory information transfer from and within the gut. We will assess the epithelial barrier function of infected intestine to determine if it is likely that parasite signal molecules can enter the intestinal wall and as a result, the likely location of receptors for signal molecules. Finally, we will test tapeworm fractions and classes of biochemical compounds for their ability to induce altered patterns of intestinal motility, in order to identify likely candidate molecules involved in tapeworm control of intestinal physiology.
