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 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, 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 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%

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