The Medscape Awards in Infectious Diseases: Bacterium

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.

References

1. Donati M. Demedica historia mirabilt. Mantuae per fr. Osanam, Lib. IV, Cap iii:1586;196.

2. Beaumont W. A case of wounded stomach. Med Record. 1825;8:14-9, 840.

3. Brinton W. On the Pathology, Symptoms, and Treatment of the Stomach. With an Appendix of Cases. London: Churchill Livingston; 1857.

4. Billroth CA. Offenes Schreiben an Herrn Dr. L. Wittelshöfer. Wien Med Wochenschr. 1881;31:161-165, 1427.

5. Krienitz U. Ueber das Auftreten von Spirochaeten verschiedener Form im Mageninhalt bei Carcinoma ventriculi. Dtsch Med Wochenschr. 1906;22:872.

6. Schwarz K. Ueber penetrierende Magen- und Jejunalgeschwure. Beitr Klin Chir. 1910;67:96-128.

7. Sippy BW. Gastric and duodenal ulcer. Medical cure by an efficient removal of gastric juice corrosion. JAMA. 1915;64:1625-1630.

8. Luck JM, Seth TN. The physiology of gastric unease. Biochem J. 1924;18:357-365.

9. Ash AS, Schild HO. Receptors mediating some actions of histamine. Br J Pharmacol Chemother 1966;27:427-439.

10. Black JW, Duncan WA, Durant CJ, Ganellin CR, Parsons EM. Definition and antagonism of histamine H2-receptors. Nature. 1972;236:385-390. Abstract

11. Ganser AL, Forte JG. K+-stimulated ATPase in purified microsomes of bullfrog oxyntic cells. Biochim Biophys Acta. 1973;307:169-180. Abstract

12. Lindberg P, Brändström A, Wallmark B, et al. Omeprazole: the first proton pump inhibitor. Med Res Rev. 1990;10:1-54. Abstract

13. Steer HW. Ultrastructure of cell migration through the gastric epithelium and its relationship to bacteria. J Clin Pathol. 1975;28:639-646. Abstract

14. Warren JR, Marshall BJ. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. 1983;1:1273-1275. Abstract

15. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;1:1311-1315. Abstract

16. Marshall BJ, Armstrong JA, McGechie DB, Glancy RJ. Attempt to fulfill Koch's postulates for pyloric Campylobacter. Med J Aust. 1985;142:436-439. Abstract

17. Rauws EA, Tytgat GN. Cure of duodenal ulcer associated with eradication of Helicobacter pylori. Lancet. 1990;335:1233-1235. Abstract

18. Coghlan JG, Gilligan D, Humphries H, et al. Campylobacter pylori and recurrence of duodenal ulcers -- a 12-month follow-up study. Lancet. 1987;2:109-111.

19. Bell GD, Weil J, Harrison G, et al. 14C-urea breath analysis; a non-invasive test for Campylobacter pylori in the stomach. Lancet. 1987;1:1367-1368.

20. Marshall BJ, Armstrong JA, Francis GJ, Nokes NT, Wee SH. Antibacterial action of bismuth in relation to Campylobacter pyloridis colonization and gastritis. Digestion. 1987;37 Suppl 2:16-30. Abstract

21. Luning G. Campylobacter pylori becomes Helicobacter pylori. Lancet 1989;2:1019-1020.

22. Goodwin CS, Armstrong JA, Chilvers T, et al. Transfer of Campylobacter pylori and Campylobacter mustelae to Helicobacter gen. nov. as Helicobacter pylori comb. nov., respectively. Int J Syst Bacteriol. 1989;39:397-405.

23. International Agency for Research on Cancer. Schistosomes, liver flukes and Helicobacter pylori. In: IARC Monographs on the Evaluation of Carcinogenic Risk to Humans. vol 6. Lyon: IARC; 1994.

24. Parsonnet J, Friedman GD, Vandersteen DT, et al. Helicobacter pylori infection and risk for gastric cancer. N Engl J Med. 1991;325:1127-1131. Abstract

25. Thamer M, Ray NF, Henderson SC, Rinehart CS, Sherman CR, Ferguson JH. Influence of the NIH Consensus Conference on Helicobacter pylori on physician prescribing among a Medicaid population. Med Care. 1998:36:646-660. Abstract

26. Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. European Helicobacter pylori Study Group. Gut. 1997;41:8-13. Abstract

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Cite this: The Medscape Awards in Infectious Diseases: Bacterium - Medscape - Jun 01, 2012.