Helicobacter pylori Dr. B. Boyle

Yüklə 457 b.
ölçüsü457 b.

Helicobacter pylori

  • Dr.B.Boyle

Contents/Aims of Lecture

  • History

  • Introduction

  • Microbiology

  • Epidemiology and Transmission

  • Pathogenesis

Helicobacter pylori

  • History

  • In 1982 following the Easter holidays in the Microbiology Dept of the Royal Perth Hospital a culture of a spiral-shaped bacterium from gastric biopsies of patients with gastritis was isolated

  • The discovery was by Dr.Robin Warren and Dr.Barry Marshall


  • This discovery have revolutionised the diagnosis, treatment and prognosis of upper gastrointestinal disease

  • H.pylori causes gastritis in over half of the world`s population and is the aetiological agent of 95% of duodental ulcers, 70-80% of gastric ulcers and has casual rate in probably up to 60-70% of Gastric Cancer

H.pylori -Microbiology

  • Small curved microaerophilic gram-negative rods 2-4ųm long

  • Selective medium required for isolation-10% sheep blood agar + selective antibiotic supplement

  • Incubated at 80-85% N2, 5-10% CO2, 5-10% H2 O @ 37ºC

  • Identified by urease, oxidase, catalase

Basis of Urease Test


  • Infection occurs worldwide

  • Prevalence will depend on the country and population groups

  • Overall prevalence strongly correlates with socio-economic conditions

  • In Middleaged adults in developing countries prevalence is 80%, in industralised countries 20-50% ( rate of acquistion decreasing)

  • Acquisition:Oral Ingestion of the bacterium

  • Transmission:Within families in early childhood, not isolated from water etc, e


  • H.pylori infection in adults is usually chronic without specific therapy: on the other hand , spontaneous elimination of the bacterium in childhood is probably relatively common

  • NEJM , Vol. 347, No. 15 Oct 10, 2002


  • H. pylori is found only on gastric epithelium where the organisms tend to cluster around the junctions between cells and virtually never penetrate the cells themselves.

  • H. pylori is able to survive in the gastric environment which is hostile to growth of most bacteria.


  • Factors permitting colonisation:

  • (i) Spiral shape and flagellate – for motility within this mucous layer.

  • (ii) Urease activity – which generate ammonium ions that buffer gastric activity

  • (iii) Micro-aerophilism – for survival within the mucous gel

  • (iv) Attachment to epithelial cells

  • (v) Evasion of Immune response



  • Hop proteins-enzymes which modify the antigenic structure of surface molecules, control entry of foreign DNA into bacteria and influence motility

  • VacA-95 kd protein, vaculoating cytotoxin inserts itself into the epithelial cell membrane and forms a hexameric anion-selective, voltage dependent channel, in through which nutrients like HCO3- and organic anions can be released and targets mitochondrial membrane inducing apoptosis

Host Response to H.pylori

  • H.pylori causes continuous gastric inflammination in virtually all infected persons

  • Host response triggered by attachment to gastric epithelium (Class II MHC-apotosis)

  • Initially neutrophils then T and B cells,plasma cells and macrophages

  • Role of cag-PAI(Stronger response IL8) and transolation of Cag A into gastric cells, Urease contributes

  • Infected gasric epithelium have increased levels of interleukin-1ß, interleukin-2,interleukin 6, interleukin-8 and TNFà.Interleukin 8 key role

Host Response to H.pylori

  • H.pylori induces a strong systemic and mucosal humoral response

  • This does not eradicate the pathogen but leads to further damage (useful in diagnosis)

  • For example : HP infected individuals may have an autoantibody response resulting in atrophy of the corpus due to antibodies against H+/K+ -ATPase of gastric pariental cells

Host Response to H.pylori

  • Although the pathogen is extracellular the T cell response of the gastric mucosa is Th1 , the resulting cytokines from Th1 response (Interleukin 2 and Interferon –ŷ) promote gastritis( whereas Th2 cytokines are protective)

  • The Th1 response may be due in part to antral production of Interleukin 18

  • The Th1 response and Fas mediated apoptosis may favour survival of the organism


Other Methods of Epithelial Damage

  • Activated netrophils release oxygens and nitrogens radicals

  • Chronic inflammination leads to epithelial cell turnover and apoptosis ( Fas mediated contact ILY and Th1)

Clinical Outcome

  • This is determine by Host and Pathogen factors

  • H.pylori is responsible for the majority of duodenal and gastric ulcers(50-80% of benign)

  • The lifetime risk of peptic ulcer is 3% in U.S. and 25% Japan-Treatment for HP lowers recurrence rate

  • 1994 H.pylori was classified as a type 1- definite carcinogen

  • Uemura et al 2001 1526, 2.9% of 1246 patients infected with H.pylori developed Gastric Cancer over 7.8 years as compared to none of 280 controls non-infected or 253 treated group

Clinical Outcome

  • H.pylori Infection increase risk of MALT lymphoma and 72-98% of pts with MALT lymphoma are infected

  • Therapy causes regression of MALT lymphoma in 70-80% cases

  • The role of H.pylori Infection in dyspepsia not associated with ulcers




Stool Antigen Test

  • Advantages : non-invasive , EIA format, easy to automate , results in hours, improving with Monoclonal design

  • Disadvantages: Not as good Negative predictive value as UBT, Kits vary


  • The Goal of therapy is eradication of the organism as if this is achieved reinfection rate are low and the benefit of treatment is longterm

  • 2 antimicrobials reduces the selection of resistance

  • Testing for Infection only required if treatment is intended

  • If test for H.pylori positive , use eradication therapy

Resistance to therapy

  • Geographical variation, depends on surveillance

  • Approx, 10% to clarithromycin

  • Approx. 30-50% to metronidazole in some studies

  • Treatment success correlates with compliance and active therapy



Yüklə 457 b.

Dostları ilə paylaş:

Verilənlər bazası müəlliflik hüququ ilə müdafiə olunur ©azkurs.org 2022
rəhbərliyinə müraciət

    Ana səhifə