The presence of C. pyloridis in the stomach has been associated with peptic ulcer disease, non-ulcer dyspepsia and gastritis. Detection of the organism by either bacterial culture or histologic examination has required invasive endoscopic procedures which have precluded large scale studies. We have developed and validated a reliable noninvasive breath test based on the high endogenous urease content of C. pyloridis. This test uses 13C-urea and detects the presence of C. pyloridis infection in the stomach by the appearance of 13CO2 in the breath. The test also measures the in vivo antibiotic sensitivity of C. pyloridis and its response to drug treatment. We propose to study the epidemiology, pathology, molecular biology, immunology, and microbiology of C. pyloridis. The breath test will facilitate rapid economical studies of the seroepidemiology of C. pyloridis infections. These studies include: 1) the prevalence of C. pyloridis infection in asymptomatic individuals; 2) the prevalence of C. pyloridis in patients with gastric ulcers, duodenal ulcers, non-ulcer dyspepsia and children with chronic recurrent abdominal pain; 3) the transmission of C. pyloridis among family members; 4) the relationship of the anatomical extent and severity of C. pyloridis infection in the stomach to gastritis; 5) the relationship of C. pyloridis to development of chronic atrophic gastritis; 6) the relationship between C. pyloridis levels and relapse of duodenal ulcer disease and 7) the development of therapeutic regimens that permanently eradicate C. pyloridis. Finally, we will evaluate the consequences of eradicating C. pyloridis on gastric histology,, on relapse of duodenal ulcers and on obtaining symptomatic relief in non-ulcer dyspepsia. The clinical studies will provide the opportunity to address the basic questions: are there individual C. pyloridis strains, serotypes, plasmids, or DNA hybridization groups associated with specific disease processes? We will also compare the nature of the isotype and idiotype antibody response to C. pyloridis infection. An ELISA assay will be developed to identify those immunodominant epitopes of C. pyloridis antigens arising from current or past infection by C. pyloridis. Finally, we will characterize the virulence factors and mechanisms of C. pyloridis pathogenesis.
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