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Helicobacter pylori update

Helicobacter pylori update. Dr.T.V.Rao MD. 1890’s: Spirochetes in animal stomachs 1900’s: Spirochetes in human stomachs 1954: No bacteria in gastric biopsies of 1000 patients 1975: Gram negative bacteria in 80% of GU’s (Pseudomonas)

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Helicobacter pylori update

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  1. Helicobacter pyloriupdate Dr.T.V.Rao MD Dr.T.V.Rao MD

  2. 1890’s: Spirochetes in animal stomachs 1900’s: Spirochetes in human stomachs 1954: No bacteria in gastric biopsies of 1000 patients 1975: Gram negative bacteria in 80% of GU’s (Pseudomonas) 1983: Warren and Marshall characterize H. pylori 2005 Nobel prize in 2005 History of H. pylori

  3. Dr.T.V.Rao MD

  4. Campylobacter like organisms Spiral shaped colonizes Gastric mucosa Etiological agent in Gastritis and peptic ulcer Most important bacteria. Helicobacter pylori Colonizes 50 % of the Individuals Helicobacter( Warren and Marshal ) Dr.T.V.Rao MD

  5. Warren and Marshal wins Nobel prize Dr.T.V.Rao MD

  6. General Characteristics of Helicobacter • Helicobacter pylori is major human pathogen associated with gastric antral epithelium in patients with active chronic gastritis • Stomach of many animal species also colonized • Urease (gastric strains only), mucinase, and catalase positive highly motile microorganisms • Other Helicobacters: H. cinnaedi and H. fenneliae • Colonize human intestinal tract • Isolated from homosexual men with proctitis, proctocolitis, enteritis, and bacteremia and are often transmitted through sexual practices Dr.T.V.Rao MD

  7. A silver stain of H. pylori on gastric mucus-secreting epithelial cells (x1000). From Dr. Marshall's stomach biopsy taken 8 days after he drank a culture of H. pylori (1985). Dr.T.V.Rao MD

  8. Helicobacter pylori • Gram –ve spiral shaped , motile with unipolar tuft of lopotrichus flagella Dr.T.V.Rao MD

  9. Gram negative Spiral rod Unipolar flagella Microaerophilic Urease positive* *Most important character H. pylori Bacteria *Scanning microscopic view of H. pylori

  10. Morphology & Physiology of Helicobacter • Gram-negative; Helical (spiral or curved) (0.5-1.0 um X 2.5-5.0 um); Blunted/rounded ends in gastric biopsy specimens; Cells become rod-like and coccoid on prolonged culture • Produce urease, mucinase, and catalase • H. pylori tuft (lophotrichous) of 4-6 sheathed flagella (30um X 2.5nm) attached at one pole • Single polar flagellum on H. fennellae & H. cinaedi • Smooth cell wall with unusual fatty acids Dr.T.V.Rao MD

  11. H. pylori Infection transmission • Transmissible • Oral-oral and oral-fecal • Infects the human stomach • Produces inflammatory response • This brings up the point of the importance of “hand washing”

  12. Dynamics of H.pylori infection Dr.T.V.Rao MD

  13. Grows on chocolate agar, Campylobacter media Grows under Microaerophilic conditions With presence of 5 – 20% co2 Oxidase + Catalase – Urease strongly +++ H2S Culturing and Biochemical characters Dr.T.V.Rao MD

  14. Type IV secretions apparatus(1) (translocate cag A) Possible insertion by needle like organelle coated with a sheath (Cag 7 protein) [Rohde et al] Phosphorylated + binds to SHP-2 tyrosine Phosphates Cytokine Production Growth Factor IL- 8+ chemokines Like cellular response H. Pylori PathogenesisBacterial Virulence Factors(Cag- PAI)( 37000 B-P – 29 genes) • Odenbreit S, et al. Science 2000;287:1497-1500

  15. Ingestion Evasion + Entrance of Mucus 1 Layer (Motility + Urea I) 2 Binding 3 Insertion 4 Intra cellular pathway H. Pylori PathogenesisBacterial Virulence Factors

  16. Helicobacter pylori and peptic ulcer diseasehistopathology with special stains .

  17. Dr.T.V.Rao MD

  18. Alter secretion of mucus TNF–α IL–Iß, INF- 1Y ↑ Gastrin release Stimulate parietal cells ↑Acid secretion TNF–α↓ D cells number ↓ Somatostatin ↑ Acid secretion H. Pylori PathogenesisThe Role of Cytokines

  19. H.pylori colonizes gastric mucosa Spread by oral – oral contact Feco oral spread prominent Poverty and overcrowding predisposes Poor Hygiene Causes mild to acute gastritis Gastric antrum - causes gastric metaplasia Any part of the stomach can be involved Colonizes overlying mucosa but donot invade mucosa Pathology and pathogenesis Dr.T.V.Rao MD

  20. Major Location ofH.Pylori infections Dr.T.V.Rao MD

  21. Pathogenesis of Helicobacter Infections • Colonize mucosal lining of stomach & duodenum in man & animals • Adherent to gastric surface epithelium or pit epithelial cells deep within the mucosal crypts adjacent to gastric mucosal cells • Mucosa protects the stomach wall from its own gastric milleu of digestive enzymes and hydrochloric acid • Mucosaalso protectsHelicobacter from immune response • Most gastric adenocarcinomas and lymphomas are concurrent with or preceded by an infection with H. pylori

  22. H.pylori infecting Mucosal layer Dr.T.V.Rao MD

  23. Pathogenesis of H.pylori. Dr.T.V.Rao MD

  24. Virulence Factors of Helicobacter • Multiple polar, sheathed flagella • Corkscrew motility enables penetration into viscous environment (mucus) • Adhesins: Hemagglutinins; Sialic acid binding adhesin; Lewis blood group adhesin • Mucinase: Degrades gastric mucus; Localized tissue damage • Urease converts urea (abundant in saliva and gastric juices) into bicarbonate (to CO2) and ammonia • Neutralize the local acid environment • Localized tissue damage • Acid-inhibitory protein

  25. H. Pylori Specific T Cell and B Cell Responses

  26. Mechanism of H.pylori infection Dr.T.V.Rao MD

  27. Urea Hydrolysis Urease C=O(NH2)2 + H+ + 2H2O  HCO3- + 2 (NH4+) Urea Bicarbonate Ammonium ions And then…HCO3- CO2 + OH-

  28. Virulence Factors of Helicobacter) • Tissue damage: • Vacuolating cytotoxin: Epithelial cell damage • Invasin(s)(??): Poorly defined (e.g., hemolysins; phospholipases; alcohol dehydrogenase) • Protection from phagocytosis & intracellular killing: • Superoxide dismutase • Catalase

  29. H. Pylori Pathogenesis and Application of Cutting Edge Technologies Molecular biology Genetics Imaging Cell culture models

  30. Strongly Recommended Dyspepsia History of/active peptic ulcer disease Gastric MALT lymphoma Following gastric cancer resection Following peptic ulcer surgery First-degree relative with gastric cancer Long-term Non-steroidal anti-inflamatory drugs (NSAID) therapy Indications for Noninvasive Testing for H. pylori* * In the absence of alarm signs for gastric cancer or ulcer disease 1. Malfertheiner P, et al. Aliment Pharmacol Ther. 2002;16:167. 2. Talley NJ et al. Aliment Pharmacol Ther. 1999;12:1135.

  31. Endoscopy Rapid urease tests Histology Culture Serologic (antibody) Stool antigen tests 13C Urea blood test Urea breath tests 14C-urea 13C-urea Types of H. pylori Tests Malfertheiner P, et al. Aliment Pharmacol Ther. 2002;16:167.

  32. 13C Urea Breath Test • Detects active infection • Sensitive and specific • Non-radioactive • No special handling requirements • Easy to collect and handle sample • Not indicated in pediatric population 1. Graham DY et al. Am J Gastroenterol. 2001;96:1741. 2. Leodolter A et al. Am J Gastroenterol. 1999;94:2100.

  33. Diagnosed by Invasive and Non Invasive tests Invasive, Endoscopic Biopsy of Gastric mucosa Microscopy – Biopsy Culture Staining by special stains Gram staining Culture more sensitive 3 – 7 days Biopsy testing for urease detection in urea medium Laboratory Diagnosis Dr.T.V.Rao MD

  34. Laboratory Identification • Recovered from or detected in endoscopic antral gastric biopsy material; Multiple biopsies are taken • Many different transport media • Culture media containing whole or lysed blood • Microaerophilic • Grow well at 37oC, but not at 25 nor 42oC • Like Campylobacter, does not use carbohydrates, neither fermentatively nor oxidatively

  35. Diagnosis by Non invasive methods • Serology ELISA • Urea breath test patient swallows urea solution In this test patient drinks urea solutions labeled with an isotope carbon If H.pylori is present in the urea is converted to ammonia and co2 in the breath measured. Dr.T.V.Rao MD

  36. Suggested Guidelines forTreatment of Patients with GI or Ulcer Disease History & Physical Exam Undifferentiated dyspepsia Symptoms of GERD Use of NSAIDs or aspirin Peptic ulcer disease Test for H. pylori Positive Eradication therapy Confirmation of cure Malfertheiner P, et al. Aliment Pharmacol Ther. 2002;16:167.

  37. Suggested Guidelines forTreatment of Patients with GI or Ulcer Disease History & Physical Exam Undifferentiated dyspepsia Symptoms of GERD Use of NSAIDs or aspirin Peptic ulcer disease Test for H. pylori Positive Eradication therapy Confirmation of cure Negative Treat for PUD, Initiate PPI therapy, or discontinue NSAIDs Malfertheiner P, et al. Aliment Pharmacol Ther. 2002;16:167.

  38. Use of antibiotics, bismuth salts Ingestion of Bismuth subsalicylate Antibiotics Tetracycline's and metronidazole for two weeks Use of Omeprazole Clarithromycin Do not treat for Asymptomatic colonization Drug resistance is a growing problem Treatment Dr.T.V.Rao MD

  39. Emerging drug resistance in h.pylori • Antibiotic treatment does not always completely inhibit or kill H. pylori with potential for antibiotic resistance. Resistance to antibiotics is the single most important factor for declining H. pylori eradication rates. • In Japan, resistance to antibiotic drugs has increased 400% while in Taiwan, it is 500%. This means that those who are infected while in these countries may find the bacterium rather resistant to their antibiotic treatments. Dr.T.V.Rao MD

  40. Epidemiology of Helicobacter Infections • Developed Countries: • United States: 30% of total population infected • Of those, ~1% per year develop duodenal ulcer • ~1/3 eventually have peptic ulcer disease(PUD) • 70% gastric ulcer cases colonized with H. pylori • Low socioeconomic status predicts H. pylori infection • Developing Countries: • Hyperendemic • About 10% acquisition rate per year for children between 2 and 8 years of age • Most adults infected but no disease • Protective immunity from multiple childhood infections Dr.T.V.Rao MD

  41. H. pylori is a transmissible, infectious disease with potentially serious outcomes H. pylori infection may be asymptomatic or cause dyspepsia Eradication therapy can cure H. pylori infection and prevent morbidity and downstream events such as PUD and gastric cancer Patients with symptoms of upper-GI disease, and who use aspirin or NSAIDs should be tested for H. pylori infection H.pylori continues to be an important pathogen

  42. Programme Created by Dr.T.V.Rao MD for Medical and Health Care Workers in the Developing World • Email • doctortvrao@gmail.com Dr.T.V.Rao MD

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