Peptic Ulcer and Helicobacter pylori Infection History: In 1983, Barry Marshall and Robin Warren, reported that H. pylori is associated with chronic gastritis and gastric ulcers, conditions that were not previously believed to have a microbial cause. They were awarded Noble Prize in Epidemiology: More than 50% of the world's population harbor H. pylori in their upper gastrointestinal tract (70% in developing countries and 35% in developed countries). However only 20% of theses are symptomatic patients. Microbiology: H. pylori is a curved rod, helix-shaped, Gram- negative bacilli. All species are pleomorphic; spiral, and coccoidal shape. All are motile by four to six lophotrichous flagella. Helicobacter pylori species are non-spore formers, and most strains have a glycocalyx. Pathogenesis and clinical picture: Transmission : Person to person: oral-oral or fecal-oral. Waterborne: inadequate sanitation, and poor hygiene. Iatrogenic transmission: mediated by contaminated endoscopy. H. pylori virulence factors and pathogenesis: To establish the infection H. pylori have to : Overcome the high acidity PH 1-2. Overcome stomach peristalsis. Overcome inflammatory response. Damage the gastric epithelia. To overcome stomach acidity: H. Pylori produces the enzyme urease which hydrolyses the urea into carbon dioxide and ammonia (neutralize the environment). To overcome stomach peristalsis: o Flagella & spiral shape confers hydrodynamic movement: motility; penetrate to the submucosa. o Outer membrane proteins: - Adhesin protein: adhesion to target host cells. To overcome inflammatory response: The lipopolysaccharide (LPS)-O antigen: mimics Lewis blood group antigen on the gastric epithelium (evade immune response; chronic infection). Virulence factors for gastric epithelia damage: o Secretory Enzymes: Urease: ammonia causes mucosal injury. Mucinase, protease: mucosal injury. o Exotoxins: Vacuolating (vac A) toxins: gastric mucosal injury. Cag A cytotoxin: cytotoxin associated with gene A: cause uncontrolled host cell growth and apoptosis inhibition (carcinoma). N Damage: Persistent mild inflammation chronic superficial gastritis in all infected individuals. End result of the chronic infection: o The majority remain asymptomatic. o 10% develop gastric or duodenal ulcer. o 1-3% develop atrophic gastritis and gastric adenocarcinoma ( Cag A protein production). o 0.1% develop MALT lymphoma. N Mechanism of ulcer development: H. pylori destruct the D cells in the antrum. low somatostatin production. increased gastrin production. increased acid production. gastric ulceration. Mechanism of adenocarcinoma development: H. pylori strains produce high levels of Cag A Epithelial continuous proliferation Disturbed acid homeostasis Atrophic gastritis Intestinal metaplasia Dysplasia Gastric adenocarcinoma. N Mechanism of MALToma and non-Hodgkin lymphoma development: H. Pylori induced gastritis T cell activation lead to uncontrolled B cell proliferation (host factor contribution). Eradication of H. pylori in the early stages cure the tumor. Clinical Presentations of H. pylori Infection Complications of chronic infection: Bleeding. Perforated ulcer. Adenocarcinoma of the stomach. MALToma of the stomach: Non-Hodgkins lymphoma of the stomach (B-cell Lymphoma). n Duodenal and gastric ulcer n n MALToma and gastric carcinoma Diagnosis Non-invasive tests: Urea breath test: carbon13 labelled urea is swallowed, exhaled 13-CO2 is then measured either in the clinic or sent to special labs. Fecal antigen test. Serology: detect IgG antibodies against H. pylori. Useful for diagnosis but not for follow-up. Detection of anti-Cag A antibodies. Invasive tests: Gastric biopsies are collected by endoscopes. Biopsy urease test: production of urease is tested in a biopsy collected by endoscopy. Histopathology: The biopsies can be stained by H& E, Giemsa, immunohistochemistry stain or silver stain. Culture: Isolation identification and antibiotics sensitivity testing. Biopsy urease test Giemsa stain H & E stain Warthin-Starrys silver stain Immunohistochemistry stain for H.pylori. Cultural characteristics: H. pylori is a fastidious microaerophilic bacteria. Selective enriched media: Columbia agar supplemented by horse blood, and specific antibiotics combination. Incubated at 37C in microaerophilic atmosphere (10% CO2, 5% O2, and 85% N2) and humidity > 95%. For 2-10 days. Identification: Colony morphology: small, round, translucent, non- hemolytic colonies. All Helicobacter pylori species are positive for oxidase, catalase and urease (++++) reactions. sensitive to cephalothin and resistant to nalidixic acid. Treatment: Triple eradication therapy: proton pump inhibitor + clarithromycin + amoxicillin or metronidazole. For days. Prevention: no vaccine is available yet. References: Schaechters Mechanism of Microbial Diseases. 5 th edition. Manual of Clinical Microbiology. 11 th edition. UpToDate. com