Helicobacter pylori infection in the pathogenesis of duodenal ulcer and gastric cancer: a model.

virus led to epidemiological studies that showed an inT verse relationship between the average age of infection he last 150 years have witnessed a remarkable change in the incidence of both peptic ulcer disease and standards of hygiene. Thus, although improvements and gastric cancer. Duodenal ulcer disease changed from in sanitation and hygiene resulted in a marked reduction being an uncommon to a prominent disease and then in the frequency of enteric diseases caused by bacterial began to wane in incidence. In contrast, the incidence pathogens, it allowed the emergence of hitherto unrecogof gastric cancer, one of the most common cancers in nized or rare diseases transmitted by the fecal-oral route: the U.S. population, began a progressive and sustained paralytic polio and hepatitis A. Duodenal ulcer apdecline. Why? How might these observations relate to peared as a new disease during this period, and, similar what we know about Helicobacter pylori infection? The to paralytic poliomyelitis or hepatitis A, the prevalence 100-year period from 1850 to 1950 saw remarkable of H. pylori infection is related to standards and practices changes in diet, food preparation and storage, standards of hygiene and socioeconomic conditions. We used of living, sanitation, and hygiene. Duodenal ulcer, parathis historical lesson to hypothesize that a delay in the lytic poliomyelitis, and infectious hepatitis (hepatitis A) onset of H. pylori infection led to a lower rate of developall made their appearance during this period as ‘‘new’’ ment of atrophic gastritis and was responsible for the diseases. When poliomyelitis appeared, it was suggested increase in incidence of duodenal ulcer occurring around that it was either a new disease or that a new strain of the turn of the century. The same hypothesis would virus was spreading through the population (e.g., the also explain the concomitant reduction in the incidence Swedish disease). Polio was a problem in countries of gastric carcinoma because a delay in the onset of infecwith better standards of living and was thought not to tion would theoretically delay the onset of multifocal exist in poor countries such as Egypt. atrophic gastritis, the precursor lesion to gastric cancer, Ultimately, paralytic poliomyelitis was found not to until late in life. We now extend and refine the be a new disease but was instead a hitherto unrecognized argument to explain why and how H. pylori infection may manifestation of a common enteric infection. In retrolead to different diseases (e.g., simple gastritis, duodenal spect, the typical presentation of poliomyelitis was that ulcer, or gastric cancer). The first step is to review what of a mild or subclinical disease in infants. Paralysis was was known in the pre–H. pylori era regarding both disone manifestation of the infection that occurred in older eases to provide additional clues about the nature of these children or adults. Because immunity is lifelong, infecphenomena. tion in infancy resulted in the majority of older children and adults being immune from the paralytic form of the Data From the Pre–H. pylori Era disease. The increase in the average age of acquisition of In the pre–H. pylori era both duodenal ulcer and the infection occurred when an increasingly large portion gastric cancer were known to be intimately associated of the population escaped exposure during infancy. An with gastritis. The pattern and severity of the gastriever-increasing population of susceptible individuals tis was also known to differ between the two diseases. thus became liable for development of the paralytic form Gastritis in duodenal ulcer disease was primarily antral of the disease, leading to annual epidemics as a conseand spared the gastric corpus, allowing continued high quence of the remarkable improvements in hygiene, sanilevels of acid secretion. Because H. pylori are found tation, housing, and education and the development of relatively uniformly throughout the stomach, the restricclean water supplies that occurred in the latter half of the 19th century. q 1997 by the American Gastroenterological Association 0016-5085/97/$3.00 Development of serological assays for antibody to polio