1. The H pylori Story – Helicobacter pylori through the ages
Jin-Yong Kang
Consultant Gastroenterologist, St George’s Hospital
Visiting Professor
National University of Singapore

2. Helicobacter pylori

3. Discovery of H pylori
Bizzozero 1893: Spiral bacteria in canine stomach
Krenitz 1906: Bacteria in human gastric cancer
Doenges 1938, Greedburg 1940: spiral bacteria in human stomach
These organisms cannot be grown
Stomach relatively sterile environment
Peptic ulcer thought to be due to excess gastric acid and/or impairment of mucosal defence

4. Discovery of Helicobacter pylori
Warren – Consultant Microbiologist – noted spiral bacteria associated with histological gastritis
Marshall – Medical Registrar – cultured Helicobacter pylori over Easter break
Completed Koch’s postulates by ingestion of Helicobacter pylori and becoming infected
H pylori cause of gastritis, peptic ulcer and gastric carcinoma
Nobel prize in Physiology and Medicine 2005

5. History of H pylori
Thought to have spread from East Africa, birthplace of modern humans
Strains used to map history of human migration
Gastric and duodenal ulcer disease became common only in the 20th century
Ulcer prevalence declined since 1980, parallel to decline of H pylori prevalence
Why did H pylori become pathogenic 100 years ago?

6. H pylori associations Histological gastritis Functional dyspepsia
Peptic ulcer (duodenal or gastric)
Gastric cancer
MALT lymphoma
CagA strains negatively associated with Barrett’s oesophagus and oesophageal adenocarcinoma (gastro-oesophageal reflux)
Non-GI – idiothrombocytopaenic purpura, rosacea

7. Helicobacter pylori

8. Gastric ulcer

9. Gastric Cancer

10. Epidemiology of H pylori
>50% of world population affected
Prevalence rates higher in developing countries
Infection occurs in infancy and childhood
In western countries older people more likely to be infected – association with socio-economic situation during childhood e.g. hot water, sharing of bedrooms
Re-infection in adult life said not to be common

11. Epidemiology of H pylori (2)
H pylori prevalence in UK higher in older individuals
Infection occurs during infancy and childhood
‘Cohort’ effect – older individuals acquire their infection at a young age, when socio-economic conditions sub-optimal
Younger individuals less likely to be infected
H pylori prevalence decreasing, due to improving socio-economic conditions
Peptic ulcer prevalence also decreasing

12. Natural history of H pylori infection
Most individuals with H pylori asymptomatic
All have histological gastritis
20 % get dyspepsia
10 % get peptic ulcer
< 1% get gastric cancer
Eradication of H pylori can cure some patients of dyspepsia, can cure or prevent peptic ulcer
Uncertain if treatment of H pylori in adult life affects cancer risk

13. Diagnosis of H pylori Serology Urea breath tests – C13, C12
Stool Helicobacter antigen test
Biopsy tests:
urease
histology
culture

14. H pylori: diagnosis
Serology (antibodies to H pylori) assesses previous exposure, does not differentiate between past and active infection
For all tests other than serology, proton pump inhibitors within 2 weeks or antibiotics within 4 weeks reduces sensitivity of the tests
Eradication can be confirmed by stool antigen test, urea breath test and biopsy tests

15. Urea breath test

16. Biopsy Urease Test for H pylori

17. Helicobacter pylori

18. H pylori infection is a ‘special’ infectious disease?
Even with in vivo sensitivity antibiotics, combination treatment is required, cure rates relatively low
Antibiotic sensitivity data not easy to obtain
Antibiotic sensitivity patterns vary with place and time. More than one strain of H pylori in the same patient.
Information on sensitivity patterns specific to the country or area often not readily available

19. H pylori infection is a ‘special’ infectious disease? (2)
Treatment outcome often not documented
Regimens may be complicated, with many side effects. Compliance often sub-optimal and can be a major determinant of success
Intention-to-treat eradication rates may be lower than per protocol rates

20. Treatment of H pylori (1)
Standard treatment since 1990s
Triple therapy – one week
twice daily proton pump inhibitor +
two of: amoxycillin, clarithromycin, metronidazole
Side effects: diarrhoea, nausea etc
Success rates latterly 70-80%, dependent on
clarithromycin and metronidazole resistance

21. Treatment of H pylori (2)
Classical bismuth-based therapy:
De-Nol (Bismuth subcitrate) 2 twice daily
Tetracycline 500 mg 4 x daily
Metronidazole 400 mg 3 x daily - all for 2 weeks
Bismuth overcomes resistance to antibiotics
Black stools, abdominal pain, photosensitivity
Quadruple therapy: add proton pump inhibitor
Standard ‘second line’ treatment
Complicated treatment – 17 tablets daily
Relatively high rate of side effects

22. Sequential Therapy First described by Zullo PPI 10 days
Aliment Pharmacol Ther 2000;14:715
PPI 10 days
First 5 days Amoxycillin 1 g bd
Second 5 days Metronidazole 400 mg bd + clarithromycin 500 mg bd
Most studies give ITT eradication rates of >90%

23. Advantages of Sequential Therapy
Amoxycillin with PPI eradicates 50% of infections and reduces bacterial load in others
Amoxycillin weakens the bacterial cell wall and prevents development of secondary clarithromycin resistance
Eradication rates (generally > 90%) often up to 80% even with clarithromycin or metronidazole resistance

24. H pylori: Summary Commonest infection in humans
Causes functional dyspepsia, peptic ulcer and gastric cancer
Can be diagnosed by serology, urea breath tests, stool antigen test and biopsy tests at gastroscopy
Antibiotic treatment can be given, but there is a significant failure rate. Successful eradication can be confirmed by non-invasive testing