Helicobacter pylori

بسم الله الرحمن الرحيم

Helicobacter pylori
H pylori is a spiral-shaped, gram-negative rod, *gastritis, *duodenal (peptic) ulcer disease,
*gastric ulcers, *gastric adenocarcinoma, and *
gastric mucosa-associated lymphoid tissue (MALT) lymphomas.
In the past named Campylobacter pylori,
H pylori has many characteristics in common with campylobacters.
It has multiple flagella at one pole and is actively motile.

Nobel Prize

The Nobel Prize in Physiology or Medicine for 2005
jointly to Barry J. Marshall and J. Robin Warren for their discovery of
"the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease"

Morphology & identification

Culture:
1-H.pylori grows in 3-6 days when incubated at 37C° in a Microaerophilic environments.
• 2-The media for primary isolation include Skirrow’s medium with vancomycin, polymyxin B, and trimethoprim, chocolate medium, and other selective media with antibiotics (eg, vancomycin, nalidixic acid, amphotericin).
• 3-The colonies are translucent and 1–2 mm in diameter.

H. pylori

Growth Characteristics

H pylori is oxidase positive
catalase positive,
is motile,
and is a strong producer of urease.

Pathogenicity

H pylori grows optimally at a pH of 6.0–7.0 and killed or not grow at the pH within the gastric lumen.
Gastric mucus is impermeable to acid and has a strong buffering capacity.
On the lumen side of the mucus, the pH is low (1–2); on the epithelial side, the pH is about 7.4. H pylori is found deep in the mucous layer near the epithelial surface where pH is present.
H pylori also produces a protease that modifies the gastric mucus and further reduces the ability of acid to diffuse through the mucus.
H pylori produces potent urease activity, which yields production of ammonia and further buffering of acid.
H pylori is quite motile, even in mucus, and is able to find its way to the epithelial surface.
• Secretion the secretory enzyme like lipase.

Virulence factors

The bacteria invade the epithelial cell surface to a limited degree. Toxins and LPS may damage the mucosal cells, and the ammonia produced by the urease activity may also directly damage the cells.
Histologically, gastritis is characterized by acute and chronic inflammation. Neutrophile and Macrophage infiltrates within the epithelium and lamina propria.
Destruction of the epithelium is common, and glandular atrophy may occur.
H pylori thus is a major risk factor for gastric cancer.

Clinical finding

• Acute infection can yield an upper gastrointestinal illness with nausea and pain; vomiting and fever may also be present.
• The acute symptoms may last for less than 1 week or as long as 2 weeks.
• After colonization, the H pylori infection persists for years, decades and or even a lifetime.
• About 90% of patients with duodenal ulcers and
• 50–80% of those with gastric ulcers have H pylori infection.
• Recent studies confirm that H pylori also is a risk factor for gastric carcinoma and lymphoma.

Diagnosis

• 1- specimens: gastric biopsy specimens can be used for histologic examination or mixing with saline for bacterial culture.
• Blood is collected for determination of serum antibodies.
• Stool samples may be collected for H pylori antigen detection
• 3- culture on choclate and skirrows media.
• 4- antibodies: detection the serum antibodies against H.pylori
• 5- biochemical reaction specially the urease test

Antibodies

Several assays have been developed to detect serum antibodies specific for H pylori. The serum antibodies persist even if the H pylori infection is eradicated, and the role of antibody tests in diagnosing active infection or after therapy is therefore limited.

• Special Tests

• Rapid tests to detect urease activity are widely used for identification of H pylori in specimens. Gastric biopsy material can be placed onto a urea-containing medium with a color indicator. If H pylori is present, the urease rapidly splits the urea (1–2 hours), and the resulting shift in pH yields a color change in the medium.
• In vivo tests for urease activity can be done also. In urea breath tests, 13C- or 14C-labeled urea is ingested by the patient. If H pylori is present, the urease activity generates labeled CO2 that can be detected in the patient’s breath.
• Detection of H pylori antigen in stool specimens is appropriate as a test of cure for patients with known H pylori infection who have been treated.

Diagnostic Test Comparison

Testing Characteristics
Serology1
urea breath test
stool antigen test
Biopsy1
Sensitivity / Specificity§
85% / 79%
95% / 96%
96% / 97%
95% / 99%
Detects previous infection
Yes
No
No
No


Treatment
• 1- Triple therapy
• metronidazole and bismuth subcitrate + either amoxicillin or tetracycline for 14 days eradicates H.pylori in 70-95% of patients.
• 2- Proton pump inhibitors directly inhibit H.pylori, than inhibition of urease activity.
• 3- Acid-suppressing agent given for 4–6 weeks enhances ulcer healing

ANTIBIOTIC

MOA1-3
Metronidazole (MTZ)
DNA synthesis
Tetracycline (TCN)
RNA synthesis
Clarithromycin (CLAR)
RNA synthesis
Amoxicillin (AMOX)
Cell wall
Antibiotic Pharmacodynamics
Susceptibility testing of H. pylori for MTZ has not been standardized. No interprative criteria have been established for testing metronidazole against H. Pylori

Bismuth

• Considered a topical agent
antiseptic agent1
prevents bacterial adhesion
inhibits urease, phospholipase, and proteolytic activity and is synergistic with antibiotics1,2
lyse H. pylori near the gastric surface3
1 Megraud et al. Aliment Pharmacol Ther 2003;17:1333-43
2deBoer WA. Expert Opin Investig Drugs 2001:10;8,1559-1566
3 Klotz U. Clin Pharmacokinet 2000;38:243-70