The H pylori Story

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The H pylori Story Helicobacter pylori through
the ages

• Jin-Yong Kang
• Consultant Gastroenterologist, St Georges
  Hospital
• Visiting Professor
• National University of Singapore

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Helicobacter pylori
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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

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Discovery of Helicobacter pylori

• Warren Consultant Microbiologist noted spiral
  bacteria associated with histological gastritis
• Marshall Medical Registrar cultured
  Helicobacter pylori over Easter break
• Completed Kochs 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

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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?

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H pylori associations

• Histological gastritis
• Functional dyspepsia
• Peptic ulcer (duodenal or gastric)
• Gastric cancer
• MALT lymphoma
• CagA strains negatively associated with Barretts
  oesophagus and oesophageal adenocarcinoma
  (gastro-oesophageal reflux)
• Non-GI idiothrombocytopaenic purpura, rosacea

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Helicobacter pylori
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Gastric ulcer
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Gastric Cancer
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Epidemiology of H pylori

• gt50 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

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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

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Natural history of H pylori infection

• Most individuals with H pylori asymptomatic
• All have histological gastritis
• 20 get dyspepsia
• 10 get peptic ulcer
• lt 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

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Diagnosis of H pylori

• Serology
• Urea breath tests C13, C12
• Stool Helicobacter antigen test
• Biopsy tests
• urease
• histology
• culture

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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

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Urea breath test
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Biopsy Urease Test for H pylori
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Helicobacter pylori
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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

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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

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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

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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

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Sequential Therapy

• First described by Zullo
• Aliment Pharmacol Ther 200014715
• 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 gt90

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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 gt 90) often up to
  80 even with clarithromycin or metronidazole
  resistance

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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