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
Introduction
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
Epidemiology
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)
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
Pathogenesis
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.
Pathogenesis
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
Pathogenesis
Pathogenesis
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
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
Gastrin/Somatostatin
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
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
Diagnosis
Diagnosis
Diagnosis
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
Therapy
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
