Although much is known about the role of H. pylori in gastrointestinal disease, many issues are still unresolved.

Further well-designed studies on the role of H. pylori eradication in the management of peptic ulcer disease are needed, particularly in populations not well studied to date, including children, patients with gastric ulcers, and patients with duodenal or gastric ulcers with complications. These studies should utilize standard definitions, be randomized, be analyzed on an intention-to-treat basis, have sample size adequate to detect clinically meaningful differences between treatment arms, and be double-blind whenever possible.

Fundamental questions remain concerning the initial evaluation of a patient who presents with dyspepsia. Should that patient be tested for H. pylori infection? Should that patient be treated empirically for H. pylori infection if it is present? The answers to these questions depend in part on whether antimicrobial therapy relieves symptoms in some or all symptomatic patients with H. pylori infection and gastritis but without ulcers. If the answer is yes, patients presenting to the physician with dyspepsia should be tested for H. pylori infection and, if the results are positive, be treated with antimicrobial therapy. However, if symptomatic H. pylori-infected patients without ulcers do not respond to antimicrobial therapy, it will continue to be imperative to confirm the diagnosis of peptic ulcer disease in order to identify the patients who will benefit from treatment of their infection. Under these circumstances, the question arises as to whether it is necessary, appropriate, and cost-effective to perform endoscopy in dyspeptic patients at initial presentation.

Another major question that remains to be answered is whether eradication of H. pylori infection prevents gastric cancer. Such a question cannot be answered directly without a long and costly study. Thus, an alternative approach might be to conduct studies looking at intermediate endpoints that are thought to predict the evolution of malignancy and their response to H. pylori eradication. Epidemiologic studies are also needed to define more precisely the subset of H. pylori-infected individuals who will develop gastric cancer.

A major opportunity for additional studies is in the area of mechanisms by which H. pylori infection leads to gastrointestinal disease. Virulence factors, bacterial genetics, mechanisms of immunity, animal models, antibiotic resistance, and modes of transmission are all issues that should be examined in future studies. Furthermore, the natural history of H. pylori infections and the nature of the host-organism interaction require further study. The pathogenic consequences of H. pylori infection in childhood and adolescence and the optimal management of infection are additional important questions. More information is needed on the value of testing to confirm eradication after antimicrobial therapy, and antimicrobial regimens need to be optimized to improve treatment efficacy. A comprehensive economic analysis should be conducted to examine the cost-effectiveness of treating H. pylori infection.