The H pylori Story – Helicobacter pylori through the ages
Jin-Yong KangConsultant Gastroenterologist, St George’s
HospitalVisiting Professor
National University of Singapore
Helicobacter pylori
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
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
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?
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
Helicobacter pylori
Gastric ulcer
Gastric Cancer
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
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
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
Diagnosis of H pylori
• Serology • Urea breath tests – C13, C12• Stool Helicobacter antigen test• Biopsy tests: urease histology culture
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
Urea breath test
Biopsy Urease Test for H pylori
Helicobacter pylori
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
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
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
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, photosensitivityQuadruple therapy: add proton pump inhibitor • Standard ‘second line’ treatment• Complicated treatment – 17 tablets daily• Relatively high rate of side effects
Sequential Therapy
First described by Zullo Aliment Pharmacol Ther 2000;14:715
PPI 10 daysFirst 5 days Amoxycillin 1 g bdSecond 5 days Metronidazole 400 mg bd +
clarithromycin 500 mg bdMost studies give ITT eradication rates of >90%
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
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