Helicobacter pylori
Introduction and History
Helicobacter pylori is a spiral-shaped bacterium
that infects over 3000 million people worldwide, making
it one of the most common bacterial infections. Between
1979-82, Australian pathologist, Robin Warren and Australian
gastroenterologist, Barry Marshall identified H. pylori
and suggested a link to the development of stomach ulcers.
Since this discovery, the World Health Organisation has
declared the bacteria to be a Class 1 carcinogen (meaning
the bacterium produces cancer). It invades the mucosal lining
of the stomach and is the cause of up to 95% of duodenal
and up to 75% gastric ulcers and has also been associated
with gastric cancer and lymphoma.
Despite intense investigation into the spread
of H. pylori, the precise mode of transmission remains
unclear. There is some evidence to suggest that H. pylori
is transmitted from person to person via the faecal-oral
route (in food or water contaminated with faeces) and/or
mouth-to-mouth (eg. kissing, shared drink bottles). Good
sanitation and hygiene are therefore important preventive
measures. Most infections occur during childhood. Crowded
living conditions, poor sanitation, poor personal hygiene
and a poor water supply correlate with higher rates of infection
(which can approach 80% of the population in the developing
world).
H. pylori infects both genders equally.
The presence of H. pylori in the stomach induces
a chronic, active, inflammation in almost everyone infected.
Majority of people with H. pylori however are asymptomatic.
Fewer than 10% of individuals colonised with H. pylori
develop peptic ulcer disease, gastric cancer or mucosa-associated-lymph-tissue
(MALT) lymphoma.
Symptoms
Symptoms experienced by infected patients
can include burning pain in the upper portion of the abdomen,
indigestion, nausea, vomiting, burping and loss of appetite.
Diagnosis  
There are many different tests used to diagnose
H. pylori infection. Tests for H. pylori can be divided
into two groups: a. invasive, which require upper gastrointestinal
endoscopy(gastroscopy) and are based on the analysis of
gastric biopsy specimens, and b. non-invasive.
-
Gastroscopy A Gastroenterologist may perform
a panendoscopy (also known as a gastroscopy). This examination
requires the patient to be sedated before an endoscope
equipped with miniature video equipment is inserted through
the mouth and down into the oesophagus. The Gastroenterologist
can then take a biopsy (sample of tissue) for pathological
testing to determine the presence of H. pylori infection.
Histologic diagnosis whereby this tissue sample is examined
under a microscope is probably the gold standard. As well
as confirming the presence of H. pylori, the pathological
state of the stomach lining can be determined and defined
as acute or chronic gastritis, atrophy, abnormal cells
(metaplasia or dysplasia - precancerous changes), Barrett's
oesophagus, or even lymphoma / malignancy. A rapid urease
test may also be used to prove infection. These tests
are known to achieve very high levels of accuracy. Culture
of H. pylori can be carried out on such a tissue biopsy
especially to determine sensitivity to particular antibiotics.
This is of most importance in those who had failed the
usual treatment and still carry the infection.
-
Urea Breath Tests Breath testing provides a rapid,
non-invasive way of detecting the presence of active infection
and is often used to check whether eradication has been
successful. This test uses a sample of exhaled breath
to determine infection. The principle of this exam relies
on the ability of the bacteria to convert a compound called
urea to carbon dioxide. When a specially labelled urea
is ingested, the exhaled breath can be tested for labelled
carbon dioxide. These tests are very accurate and easy
to perform.
-
Serology
Patients' blood may be screened for
the presence of antibodies to H. pylori indicating an
immune response to the bacteria. These tests are slightly
less accurate than other available tests and do not discriminate
between current infection and recent exposure.
-
Stool H.pylori Antigen Test This can be quite
an accurate test and is one which is becoming used more
frequently.
Complications
H. pylori has been strongly linked to the
development of gastric and duodenal ulcers. Eradication
of H. pylori can prevent ulcers forming. Indeed patients
presenting with ulcers should be tested for H. pylori and
treated because eradication of H. pylori in patients with
pre-existing ulcers cures the ulcer disease and can prevent
recurrences.
Gastric adenocarcinoma is the second leading
cause of cancer death worldwide. There is strong evidence
to suggest that H. pylori contributes to the development
of gastric cancer. Many factors are likely to combine to
cause cancer as only a tiny proportion of patients with
H. pylori go on to develop gastric cancer. Diet low in fruit/vegetables,
smoking, age and a high salt intake also increase the risk
of gastric cancer, independent of H. pylori infection. However,
of all these, it is H. pylori infection which is most closely
associated with stomach cancer. Hence, due to this known
association, all patients with H. pylori should be treated
with antibiotics to development of stomach cancer.
H. pylori infection can lead to the development
of a condition known as mucosa-associated-lymphoid-tissue
(MALT) in the stomach. Treatment and eradication of H. pylori
infection can result in regression of the malignancy in
up to 75% of cases.
Treatment
Treatment for H. pylori focuses on eradicating
the bacteria from the stomach using a combination of organism-specific
antibiotics with an acid suppressor and/or stomach protector.
The use of only one or two medications to treat H. pylori
is not recommended. Different countries have different approved
treatments for H. pylori. At this time, a proven and effective
treatment in Australia is a 7-day course of medication called
Triple Therapy comprising two antibiotics, amoxicillin and
clarithromycin, to kill the bacteria together with an acid
suppressor to enhance the antibiotic activity. This regimen
of triple therapy reduces ulcer symptoms, kills H. pylori
and prevents ulcer recurrence in more than 80% of patients.
Antibiotic regimens recommended for patients may soon differ
across regions of the world because different areas have
begun to show resistance to particular antibiotics.
Drugs that are used in different combinations
include:
| Antibiotics |
Proton Pump Inhibitors |
| Amoxicillin |
Omeprazole |
| Metronidazole |
Lansoprazole |
| Clarithromycin |
Pantoprazole |
| Tetracycline |
Rabeprazole |
| Rifabutin |
Ranitidine bismuth citrate |
With the use of antibiotics to treat many
infections it has become more difficult to treat H. pylori
due to prevalence of antibiotic resistant strains. As a
result, up to 20% of people fail their treatments.
At the Centre for Digestive Diseases following
failure of a treatment and at times on initial therapy,
the combination regime is designed on a patient-by-patient
basis, dependent upon the antibiotic sensitivity profile
of the infecting bacteria. With these tailored treatments
our Gastroenterologists have successfully eradicated H.
pylori from virtually all treated patients and in particular
in many patients who have failed standard therapies.
Patients with Resistant H. pylori
In those patients who have been treated for
H. pylori and the bacteria continue to be present eg as
determined by a Urea Breath Test, a further treatment using
the previous therapy should not be tried again. At the CDD
you will undergo a gastroscopy, have tissue samples collected
and sent to the Helicobacter Pylori Reference Laboratory.
Several weeks later, when the results become available (these
bacteria grow slowly,) your Gastroenterologist will construct
a 'custom' antibiotic combination to eliminate this infection.
From current results at the CDD even those with multiply
failed therapies previously can expect a 90% success rate
in curing this infection.
Research
At the Centre for Digestive Diseases, we
are especially interested in developing eradication treatment
alternatives effective in patients who have failed other
standard therapies. These 'salvage' or 'rescue' therapies
comprise varying combinations of three or more anti-H.
pylori drugs depending on antibiotic sensitivity results
of biopsies taken from such patients. Treatment components
which may be used include all those shown above as well
as pronase, gum mastic, and lactoferrin. Furthermore,
the immunity of the gastric lining may need to be 'stimulated'-
one of the current research projects in which it has been
shown that some patients have an immune deficiency which
contributes to eradication failure.
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