Helicobacter pylori

Helicobacter pylori (H.ylori) is a spiral-shaped bacterium that infects well over 30% of the world’s population. In some

In some countries it infects more than 50% of the population. This is, therefore, one of the most common human bacterial infection.

CDD discovery

Following confirmation in the 1980s that H.pylori caused peptic ulcers, the Centre for Digestive Diseases Medical Director and Founder Professor Thomas Borody developed the first therapy to fight H.pylori and cure peptic ulcers. This went on to become the gold standard treatment globally.

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.

Transmission

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 yet the transmission mode remains unclear. Oral to oral or faecal to oral

Oral to oral or faecal to oral are the most likely routes at this stage. Most infections occur in 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 no symptoms at all, 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: invasive, which require upper gastrointestinal endoscopy (gastroscopy) and are based on the analysis of gastric biopsy specimens, and non-invasive using test strips and breadth tests.

  • 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. Histological 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. A 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. In those patients sensitivity of H. pylori organism is tested for appropriate treatment to be commenced.
  • 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 test relies on the ability of the bacteria to convert a compound called urea to carbon dioxide. A specially labelled urea is given by tablet form orally and the exhaled breath is 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. In those patients where the gastric lining has changed to the precancerous form of intestinal metaplasia, neither biopsy nor urea breath tests are able to be used as there are very few bacteria present. However serial serology from antibody concentrations can be used as follow-up post treatment of H. pylori infection.
  • Stool H. pylori Antigen Test – This can be quite an accurate test and is being used more frequently.

Complications

H.ylori has been strongly linked to the development of gastric and duodenal ulcers. Eradication of H. pylori can prevent ulcers forming. Patients presenting with ulcers should be tested for H. pylori and treated because eradication of H. pylori in patients with pre-existing ulcers cures ulcer disease and can prevent most recurrences.

There is strong evidence 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 its known association, all patients with H. pylori should be treated with antibiotics to prevent the development of stomach cancer.

H.pylori infection can also lead to the development of a condition known as mucosa-associated-lymphoid-tissue (MALT) Lymphoma, a type of cancer of the stomach. Treatment and eradication of H. pylori infection can result in regression of the malignancy in up to 75% of cases.

First Line Therapy

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 around 70% of patients but its efficacy is slowly falling.

With the use of antibiotics to treat so many patients with various conditions it has become more difficult to treat H. pylori due to increasing occurrence of antibiotic resistant strains. As a result, up to 35% of patients fail the first line therapy.

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, often 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.

Second line & subsequent therapies for resistant H. pylori

In those patients who have been treated for H. pylori and the bacteria continues to be present, for example as determined by a urea breath test, a further treatment using the previous therapy should not be tried again. At the Centre for Digestive Diseases patients undergo a gastroscopy, have tissue samples collected and sent for culture. The gastroenterologist will then proceed to construct a “custom” antibiotic combination to eliminate this infection. From current results at the Centre for Digestive Diseases even those with multiple failed therapies previously can expect around 90% success rate even with resistant 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. Treatment components which may be used may include Amoxicillin, proton pump inhibitors, furazolidone, bismuth, nitazoxanide, levofloxacin, as well as 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.