C PARVUM--MUCOSAL RESPONSE IN HEALTH HOSTS AND HIV/AIDS

点击翻译按钮获取中文摘要

Cryptosporidium parvum is an enteric parasite that causes outbreaks of diarrhea in communities and day care centers and is a significant factor in mortality and mortality in HIV/AIDS. This parasite is now recognized as an important public health threat and is considered as one of the new "emerging diseases". To date no curative treatment has been identified, and palliative treatment is only partially effective. The longterm objectives of this work are two-fold: 1) to elucidate and understand the relative contributions of various immune mechanisms involved in the control and/or prevention of C. Parvum infection/disease, and 2) by identifying these mechanisms to lay the groundwork for a rational approach to the intervention and/or prevention of infection. To address these objectives, we propose to study a unique population of individuals experimentally-challenged with C. Parvum oocysts. These healthy, adult volunteers will be followed clinically for a minimum for 4 weeks post-challenge, and specimens will be collected at intervals during the study. This work is an extension of continuing studies with the human model of C. Parvum infection initiated three years ago. To our knowledge no other investigators have undertaken such studies in immunocompetent volunteers. Findings from these subjects will then be compared to responses in immunodeficient (HIV/AIDS) individuals with chronic C. parvum infection. Experiments will be designed to: 1) measure total and specific secretory lgA from mucosal surfaces (saliva, fecal) against C. parvum crude extracts and to compare these data to serum antibody (IgA, IgG, IgM) response and kinetics, 2) determine the specificity of secretory and serum antibody by employing recombinant C. Parvum antigens and other related protozoan parasites, 3) identify changes in cell populations in fut biopsies over the course of the infection and relate those findings to the expression of cytokines in the same biopsy tissues, and 4) compare the above results to clinical outcome, intensity of infection, onset and duration of oocyst excretion and other parasitological parameters. Understanding the specific features of the mucosal immune response and its regulation during C. Parvum infection is an important step in designing effective intervention and prevention strategies for treatment and/or control of this disease.