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