Viral infections of the gastrointestinal tract constitute major causes of morbidity and mortality in a variety of patient populations. Gastrointestinal infections with fastidious viruses such as rotaviruses, adenoviruses and coxsackie viruses are particularly serious in children with congenital immunodeficiency diseases and in patients rendered immunoincompetent on the basis of prematurity or immunosuppressive therapy. Conventional methods of providing protection, such as the parenteral administration of immunoglobulin preparations, have not proven to be highly successful for the prevention and treatment of gastrointestinal infections in these populations, probably due to the fact that these modalities do not provide sufficient immunoglobulin concentrations at the gastrointestinal site of viral replication. However, preliminary studies performed by us and by others indicate that immunocompromised patients might be provided mucosal antibody by the administration of immunoglobulin by the oral route. We thus propose to study the dose-response kinetics of orally administered immunoglobulins derived from serum and human breast milk in immunocompromised patients with severe viral gastroenteritis. In addition, we plan to examine the metabolic fate of administered immunoglobulins in an attempt to define the survival and binding capacity of different classes and subclasses of orally administered immunoglobulins in the gastrointestinal tract. We also will utilize a murine model of rotavirus infection in order to study the mechanisms of action of immunoglobulin subclasses as well as to evaluate the efficacy of oral immunoglobulin preparations which are not yet available for human administration. The results of these studies will be utilized to develop practical strategies for the prevention and treatment of viral diarrheal diseases in immunocompromised patients as well as in additional populations such as children in hospital wards and day care centers as well as adults residing in nursing homes. The successful application of these strategies might markedly decrease the current morbidity associated with viral gastrointestinal infections in these and other susceptible populations.
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