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Helicobacter pylori
H pylori is a spiral-shaped, gram-negative rod. H pylori is associated with
antral gastritis, duodenal (peptic) ulcer disease, gastric ulcers, gastric
adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT)
lymphomas.
Morphology and Identification
Typical Organisms
H pylori has many characteristics in common with campylobacters. It has
multiple flagella at one pole and is actively motile.
Culture
Culture sensitivity can be limited by prior therapy, contamination with other
mucosal bacteria, and other factors. H pylori grows in 3–6 days when incubated at
37°C in a microaerophilic environment, as for C jejuni. 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). The colonies are translucent and 1–2
mm in diameter.
Growth Characteristics
H pylori is oxidase positive and catalase positive, has a characteristic
morphology, is motile, and is a strong producer of urease.
Pathogenesis and Pathology
H pylori grows optimally at a pH of 6.0–7.0 and would be killed or not grow at
the pH within the gastric lumen. Gastric mucus is relatively impermeable to acid
and has a strong buffering capacity. On the lumen side of the mucus, the pH is low
(1.0–2.0); on the epithelial side, the pH is about 7.4. H pylori is found deep in the
mucous layer near the epithelial surface where physiologic pH is present. H pylori
Microbiology
Medical bacteriology
Dr. Zainab D. Degaim
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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. H pylori overlies gastric-type but not
intestinal-type epithelial cells.
In human volunteers, ingestion of H pylori resulted in development of gastritis and
hypochlorhydria. There is a strong association between the presence of H pylori
infection and duodenal ulceration. Antimicrobial therapy results in clearing of H
pylori and improvement of gastritis and duodenal ulcer disease.
The mechanisms by which H pylori causes mucosal inflammation and damage are
not well defined but probably involve both bacterial and host factors. The bacteria
invade the epithelial cell surface to a limited degree. Toxins and
lipopolysaccharide 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.
Polymorphonuclear and mononuclear cell infiltrates are seen within the epithelium
and lamina propria. Vacuoles within cells are often pronounced. Destruction
of the epithelium is common, and glandular atrophy may occur. H pylori thus is a
major risk factor for gastric cancer.
Clinical Findings
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 and perhaps decades 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.
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Diagnostic Laboratory Tests
A. Specimens
Gastric biopsy specimens can be used for histologic examination or minced in
saline and used for culture. Blood is collected for determination of serum
antibodies. Stool samples may be collected for H pylori antigen detection.
B. Smears
The diagnosis of gastritis and H pylori infection can be made histologically. A
gastroscopy procedure with biopsy is required. Routine stains demonstrate
gastritis, and Giemsa or special silver stains can show the curved or spiral-shaped
organisms.
C. Culture
As above, culture is performed when patients are not responding to treatment, and
there is a need to assess susceptibility patterns.
D. 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.
E. Special Tests
Rapid tests to detect urease activity are widely used for presumptive 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 exhaled
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.
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Immunity
Patients infected with H pylori develop an IgM antibody response to the
infection. Subsequently, IgG and IgA are produced, and these persist, both
systemically and at the mucosa, in high titer in chronically infected persons. Early
antimicrobial treatment of H pylori infection blunts the antibody response; such
patients are thought to be subject to repeat infection.
Treatment
Triple therapy with metronidazole and either bismuth subsalicylate or bismuth
subcitrate plus either amoxicillin or tetracycline for 14 days eradicates H pylori
infection in 70–95% of patients. An acid-suppressing agent given for 4–6 weeks
enhances ulcer healing. Proton pump inhibitors (PPIs) directly inhibit H pylori and
appear to be potent urease inhibitors.
The preferred initial therapy is 7–10 days of a PPI plus amoxicillin and
clarithromycin or a quadruple regimen of a PPI metronidazole, tetracycline, and
bismuth for 10 days.