Transcript The H pylori Story – Helicobacter pylori through the ages

The H pylori Story – Helicobacter
pylori through the ages
Jin-Yong Kang
Consultant Gastroenterologist, St George’s
Hospital
Visiting 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
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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 socioeconomic 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 socioeconomic 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
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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
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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
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, photosensitivity
Quadruple 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 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%
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