Risk Factors for Gastric Disease in Pediatric Helicobacter Pylori (H. Pylori)

Helicobacter pylori (Hp) is a major cause of chronic-active gastritis and primary duodenal ulcers, and is strongly linked to gastric cancer. Most Hp infections worldwide are acquired in childhood. Why some individuals develop symptomatic disease is unclear and, until recently, no studies critically evaluated the role of pediatric Hp strains and/or host factors in disease outcomes. Over the past 5 years of National Institutes of Health (NIH) funding, 486 children from Atlanta, Cleveland, and Miami were enrolled; 184 (38%) were Hp-infected. Race (African American) and younger age, in conjunction with Hp strains expressing cagA and vacAs1B, were shown to be risk factors for both esophageal and gastric disease, suggesting a different disease paradigm from Hp-infected adults. Using the updated Sydney system, the investigators demonstrated a histopathologic spectrum in children, which included novel observations of atrophic gastritis with intestinal metaplasia. Overall hypothesis for competitive renewal: disease manifestations in Hp-infected children are influenced by specific host factors (i.e., race, immune phenotype), environmental exposures, and specific virulence factors of infecting Hp strains. Specific aims:

1. 1.Using well defined cases and controls, further characterize specific host factors and environmental exposures contributing to symptomatic childhood infection emphasizing targeted enrollment in specific age, gender and demographic strata to facilitate detection of significant differences not attained previously and follow-up of 2 established specific cohorts to ascertain immune response natural history.
2. 2.Utilize gene-array technology for the whole Hp genome assessment and bacterial gene expression of specific virulence determinants associated with pediatric Hp strains.
3. 3.Further characterize the host immunologic and mucosal response in Hp-infected children.