The Medscape Awards in Infectious Diseases: Bacterium


John G. Bartlett, MD


June 01, 2012

In This Article

Timeline: Historical Highlights -- Gastric Ulcer as a Chronic Bacterial Infection Caused by Helicobacter pylori Infection

1586: First report of gastric ulceration.1

1825: Classic description of gastric function based on observations in a patient with a war wound that resulted in a gastric-cutaneous fistula.2

1857: Symptoms of peptic ulcer disease reported in detail.3

1881: Billroth provides the first report of upper gastrointestinal endoscopy.4

1906: Spirochetes reported in gastric biopsy specimens.5

1910: Peptic ulcer was attributed to gastric acid,6 and antacids became standard treatment.

1915: The "Sippy diet" is reported, using milk and cream throughout the day and much of the night.7 This became a favored therapy for the next 6 decades.

1924: Urease activity reported in human stomachs.8 This was thought to be generated from gastric mucosal cells because the stomach was thought to be sterile.

1966: Report of the gastric histamine receptor,9 and the first report of H2-receptor therapy followed quickly.10

1973: The proton pump was described11; this was immediately followed by proton pump inhibitor treatment.12

1975: Spirochetes and chronic gastritis are shown on gastroscopy in 80% of patients with gastric ulcers.13

1979: Robin Warren detected bacteria growing in gastric biopsy specimens, but the findings were apparently uninteresting to fellow pathologists. Two years later he met Barry Marshall, a young gastroenterologist, and the men spent the next 7 years studying what is now known as H pylori.

1983: Warren and Marshall report on bacteria associated with gastritis and peptic ulcer disease from their initial collaboration.14

1984: The seminal report15 from the Warren/Marshall collaboration showed the association of curved bacteria in the lesions of patients with chronic antral gastritis and ulcers.

Some of the observations in the seminal report are interesting, convincing, and even compelling, because the investigators found typical spiral or curved bacteria in antral specimens from 58 of 100 patients who underwent endoscopy with gastric biopsy.

We found a close association between pyloric campylobacter and antral gastritis. When polymorphonucleocytes (PMNs) infiltrated the mucosa, the bacteria were almost always present (38/40). In the absence of inflammation they were rare (2/31), suggesting they are not commensals. We know of no other disease state where, in the absence of complicating factors such as ulceration, bacteria and PMNs are so intimately related without the bacteria being pathogenic.

Conventional wisdom at the time was that the stomach is normally sterile owing to the acid environment, but the investigators opined that the bacteria were not in gastric fluid but rather on gastric cells.

1985: Self-inoculation experiment by Dr. Marshall was reported.16 This was a failed attempt to satisfy the Koch postulates because the result was gastritis, but he never developed a gastric ulcer.

1987: Eradication of H pylori shown to be associated with long-term cure of duodenal ulcer.17,18

1987: Report of the urea breath test.19

1987: The antibacterial activity of bismuth against H pylori is reported.20

1989: Campylobacter pylori is renamed Helicobacter pylori. 21,22

1994: H pylori is named a grade 1 ("definite") carcinogen.23

1994: H pylori is implicated as the cause of gastric non-Hodgkin lymphoma.24

1994: A National Institutes of Health consensus report endorses antibacterial therapy for peptic ulcer disease.25

1997: Management guidelines for peptic ulcer disease recommend antibacterial treatment for the first time.26

2005: The Nobel Prize is awarded to Drs. Barry Marshal and Robin Warren.


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