The long term objective of the proposed research is the development of an animal model to elucidate the host-parasite interactions that control the relationship between the intestinal nematode, Strongyloides stercoralis, and its hosts (man, primates and dogs). In these interactions, the host usually prevails, resulting in a well-tolerated, self-limiting infection. Sometimes, however, neither host nor parasite prevails and a highly persistent, chronic infection is established. Occasionally, the controls on parasite abundance and distribution fail, resulting in massive hyperinfection, sometimes with invasive, often fatal, disseminated infection.
The specific aims of the proposal involve the population dynamics of the parasite's larval stages within the tissues and the intestines. These include: 1) quantitative characterization of routes of larval migration so that autohyper-, and, in particular, disseminated infection can be rigorously described and measured. 2) investigations of interrupted tissue migration to (a) identify way-stations where larvae interrupt migration, (b) determine the proportion of larvae that interrupt migration, as well as the duration of such interrupted migration, and (c) assess the importance of sites of interrupted migration for (i) long-term larval persistence in chronic infections, (ii) larval destruction in immunologically sensitized hosts, or (iii) extra-intestinal development in disseminated infections. 3) elucidation of the course, rates and rate controls of intestinal larval development that usually result in limited internal autoinfection in normal hosts, but sometimes result in uncontrolled autoinfection leading to hyper- and even disseminated infection, especially in immunocompromised hosts. Larval population dynamics will be investigated using culture-derived, raiolabeled S. Stercoralis larvae and commercially reared, specific-pathogen-free dogs. To obtain larval populations differing in early developmental history with respect to the host's immunological status, unlabeled larvae will be taken directly from hosts exhibiting differing levels of resistance to infection.
Showing the most recent 10 out of 88 publications
