Helicobacter pylori is a gram negative, microaerophilic, curved bacillus. It is motile, has flagellae and has a special affinity for human gastric mucosa.
Since its initial discovery it has been implicated in the pathogenesis of a number of gastroduodenal disorders including acute and chronic gastritis, gastric and duodenal ulceration, gastric cancer and gastric MALT lymphoma.
Up to 50% of the population in developed countries such as Australia
will have evidence of H. pylori infection by the age of 50 years. The organism
is present in up to 92% of patients with active chronic gastritis, 88-100%
with duodenal ulceration, 58-100% with gastric ulceration and 46-94% with
gastric cancer. In duodenal ulcer disease eradication of the organism has
been shown to markedly reduce ulcer recurrence rates and possibly change
the natural history of the disease.
The organism is usually present in the gastric antrum and lives beneath the mucus layer. One of its special characteristics is its ability to produce urease, an enzyme that is not normally found in the human stomach.
Various methods have been developed for detecting H. pylori, including :
Histological examination is performed on endoscopic antral biopsy specimens. Numerous stains can be used including Haematoxylin & Eosin, Warthin-Starry, Giemsa. However, the results are not known immediately. Histological examination has the advantage of providing information on other mucosal abnormalities. This is particularly useful in the case of gastric ulceration, when the exclusion of malignancy is important.
The organism can be successfully cultured from antral biopsy specimens and grown in various media with enrichment at 37oC in a microaerobic atmosphere. The technique is very specific and permits strain typing of the organism. In addition to this antimicrobial susceptibility testing can be performed. The results however may take up to three days to be completed. At present H. pylori culture is mainly used in research and in assessing bacterial resistance after failed eradication therapy.
The polymerase chain reaction (PCR) has been used in identifying the organism accurately. This technique has a high specificity and again allows for detailed identification of the organism's strain. It is a complicated technique and no commercial kits are available, confining it to research. It has been used to distinguish treatment failure with recurrence of the same strain of organism from reinfection with a new strain.
This is the least expensive test that can be performed on endoscopic biopsy specimens. It is based on the ability of the H. pylori to produce urease which is not usually present in the stomach. The urease produced by the organism converts urea to ammonia resulting in a PH change detected by phenol red. The tests usually give a rapid result but typical sensitivity at 1 hour is 71% which increases to 96% at 6 hours. Some of this delay can be overcome by warming the specimen which speeds up the reaction.
With all the endoscopic biopsy tests there is some potential for sampling
error particularly following eradication therapy. Following treatment with
acid inhibiting drugs and antibiotics bacterial suppression in the antrum
can occur with inhibition of urease activity and redistribution of the
organism to the gastric fundus. Thus antral biopsy specimens alone may
not detect the organism. Further, as the organism usually resides beneath
the intact mucus layer, biopsies from areas of intestinal metaplasia and
gastric carcinoma may also result in low detection rates. If H. pylori eradication
is being assessed on endoscopic biopsies, in addition to performing antral biopsies
one should also take specimens from the gastric body.
The serological test offered by the IMVS is the pyloritest (Orion Diagnostica). This is a total antibody latex agglutination test for the detection of H. pylori antibodies. When compared to histology and rapid urease test and culture in 90 patients it was shown to have a sensitivity of 93% and specificity of 95%.
H. pylori serology is useful in screening the population but a small
proportion of elderly patients do not mount an IgG response and up to 31%
of patients with positive serology may not have active infection. Antibody
levels drop very slowly following eradication of the organism and up to
65% of patients may remain positive for 12 months post treatment. Serology
is thus not useful in assessing eradication.
The breath tests are performed by asking the patient to swallow carbon- labelled urea which is metabolised by H. pylori produced urease to produce labelled carbon dioxide. This is absorbed into the blood stream and then exhaled in the breath of infected individuals as illustrated.
Broadly, two forms of urea breath tests are available, using 13C urea which is a stable (non radioactive) isotope or 14C urea which is radioactive.
At the Royal Adelaide Hospital we offer the following techniques :
1. 13C urea breath test
The procedure is :
The RAPID-13 kit is a 13C urea breath test kit.
2. 14C urea breath test
The procedure is :
In assessing eradication the CUBT should be performed at least 4 weeks following cessation of antibiotics or antibacterials. The optimal length of cessation of H2 antagonists and proton pump inhibitors (PPI's) is not fully known and may range from 2 days to 2 weeks.
At present we follow the recommendation of ceasing H2 antagonists for 9 hours (during the fasting period) and PPI's for 7 days prior to CUBT, if possible. Other possible causes of false negative and positive CUBT's are shown below:
|Result type||Possible cause|
|False negative||Test performed too soon after antibiotics, acid suppression therapy
(should wait at least 1 month after eradication therapy)
|Rapid gastric emptying (post surgery)|
|False positive||Contamination with oral commensals (ie non-fasting)|
|Achlorhydria, gastric atrophy|
|Rapid urease test||
|13/14C Urea breath test||
The HIC will pay a rebate for 13/14C urea breath tests for the following indications
MBS Item 12533, 1 Nov. 2008
CARBON-LABELLED UREA BREATH TEST using oral C-13 or C-14 urea, performed by a specialist or consultant physician, including the measurement of exhaled 13CO2 or 14CO2, for either:-
Established reasons for H. pylori eradication are :
The 7 day treatment regimen available through the PBS for the treatment of H. pylori is:
Nexium Hp7 (Astra)
This consists of
- Omeprazole 20mg bd
- Amoxycillin 1000mg bd
- Clarithromycin 500mg bd
It is available on restricted PBS benefit for the eradication of H. pylori associated with peptic ulcer disease
This regime has superior eradication rates compared to the earlier regimens such as HELIDAC (Pharmacia & Upjohn) and LOSEC HELICOPAK (Astra)
In some countries, including Australia, high rates of metronidazole resistance have been found and studies have shown eradication rates greater than 90% with well tolerated 7 day regimens using clarithromycin.
Following treatment based on a PPI, a clarithromycin/metronidazole combination regimen could be repeated.
This is a test for fat malabsorption. Following an overnight fast the patient
is given a 40ml liquid meal comprising a mixed fat meal (Calogen) and 200 mg
13C-Triolein. The triolein is digested, absorbed and metabolized in the body
and 13CO2 produced that is exhaled and then measured in the breath.
In this test breath samples are collected hourly for 6 hours following the meal. The activity in the breath sample is measured in a mass spectrometer and the rate of fat absorption calculated. If there is fat malabsorption the amount of the ingested dose absorbed and 13CO2 exhaled is reduced. The test has a reported sensitivity of up to 100% and 96% specificity for fat malabsorption (Newcomer et al 1979). However diabetic gastroparesis, thyroid disease and severe respiratory insufficiency may affect the test.
This is a sensitive and specific test for bacterial overgrowth in the small
intestine. It depends on the ability of anaerobic bacteria to metabolize 14C-Xylose
resulting in the production in the body of 14CO2 that can be measured in the
breath. If there is bacterial overgrowth more 14CO2 is exhaled. For this test,
following an overnight fast the patient is given 370KBq oral 14C-Xylose. A
single breath sample is then taken at 30 minutes and analyzed. Bacterial overgrowth
is confirmed if >0.00014% of the ingested dose is exhaled in the breath
at 30 minutes.