HistoryThis section has been translated automatically.
In 1982 in Perth, Australia, the Australian scientists Barry Marshal and Robin Warren detected the bacterium for the first time from a stomach tissue sample of a patient with gastritis. In the end, this was only because the culture plates had been in the incubator longer than usual due to the Easter holidays, which gave the slow-growing bacteria the opportunity to multiply sufficiently. They were awarded the Nobel Prize in Medicine in 2005 for the discovery of the bacterium. H. pylori was declared the first carcinogenic bacterium by the WHO.
DefinitionThis section has been translated automatically.
Helicobacter pylori is a fastidious, spiral-shaped, Gram-negative, microaerophilic rod bacterium that only grows on special culture media at 5% oxygen atmosphere. Biochemically, the high activity of the enzyme urease is striking.
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ClassificationThis section has been translated automatically.
Major human pathogenic Helicobacter species:
- Helicobacter pylori
- Helicobacter cinaedi
- Helicobacter fennelliae
- Other species are known in animals.
PathophysiologyThis section has been translated automatically.
Pathogenicity factors of Helicobacter pylori: H. pylori has the ability to survive in the stomach and cause chronic infection of the gastric mucosa. A variety of pathogenicity factors are available to it for this purpose:
- Urease: One of the most characteristic properties of H. pylori is the production and release of urease. Urease converts urea found in the stomach into carbon dioxide and ammonia. Ammonia neutralizes gastric acid; the viscosity of mucus is reduced (transition from gel to sol). This allows H.pylori with its 4-5 unipolar flagella to reach the epithelial cells.
Flagella: H. pylori has so-called flagella, which give the germ a high mobility. This allows it to travel in the gastric mucus, reach the superficial gastric cells and attach there.
Adherence: In order to adhere to the stomach cells, H. pylori forms so-called adhesins (Bab A). These are special structures with which the pathogen can adhere to the cells like an anchor.
- Vacuolating cytotoxin (VaCA): The enterocytes damaged by VaCa form vesicle-like structures. VacA becomes active after contact with gastric acid and then exerts its damaging effect on gastric cells. In addition to cell destruction, VacA also impairs the healing and regeneration of the gastric mucosa.
- Lipopolysaccharide (LPS): On its surface, H. pylori carries molecules consisting of fatty acids and of sugars. These molecules are called lipopolysaccharide of the outer membrane (LPS). The LPS of H. pylori contains sugar building blocks that resemble the blood group system of humans. This may be a strategy of the germ to fool the human immune system and thus allow long-term survival in the stomach
- Cag pathogenicity island: The most important genetic difference in terms of the dangerousness of the different H. pylori strains is the presence of CagPAI. These are genes that code for a type of pump system. This pump, which works in the manner of a hypodermic needle, is used to introduce CagA into the cells.
- CagA: the CagA gene codes for a protein of the same name. After it has been introduced into the gastric cell, an enzyme modifies it by binding phosphorus to CagA. This leads to a change in the shape of the cell, including the formation of protuberances in the cell membrane of the host cell. These changes can lead to pronounced damage and possibly contribute to an increased risk of developing gastric cancer.
- Antibody production: The immune system is also stimulated. Class A and G antibodies are produced without achieving gastritis cure.
- Immune evasion: Immune evasion (high degree of antigen variability, molecular mimicry to human blood groups, suppression of T-cell mediated immune response) allows the bacterium to persist for a long time (possibly for life).
ManifestationThis section has been translated automatically.
The transmission of H. pylori occurs most frequently in infancy, namely from person to person. Like other infectious childhood diseases, infection is greatly promoted by unfavourable hygienic conditions, as well as by frequent diarrhoeal diseases and malnutrition. Food as a source of infection has not yet been identified. Poor drinking water quality is more likely to increase the number of diarrhoea attacks, which in turn promotes human-to-human transmission, as bacteria from the stomach pass more quickly through the intestinal tract during diarrhoea and are excreted in the faeces ready for infection.
The frequency of infection is extremely high in developing countries, while in industrialized countries it has been declining for years. However, the disease is still so common that it continues to be a health policy problem. The prevalence increases by 1% per age cohort, so that about half of the 50-year-olds have these bacteria in their stomachs without being manifestly ill.
Clinical pictureThis section has been translated automatically.
Infections can be asymptomatic for a long time or remain asymptomatic.
The following symptoms may indicate a Helicobacter pylori infection:
- Loss of appetite
- Bad breath
- Pain in the upper abdomen
In the case of favourable conditions due to reduced bleeding of the mucous membranes, development of chronic gastritis and possibly ulcerations of the gastric and intestinal mucosa (fasting pain).
An infection affecting mainly the antrum leads to increased gastrin production, probably via a local reduction in somatostatin release. The resulting hypersecretion of acid predisposes to the formation of prepyloric and duodenal ulcers.
Infections, predominantly in the corpus of the stomach, lead to gastric mucosal atrophy and decreased acid production, possibly via locally increased production of interleukin-1β. These patients are predisposed to the development of gastric ulcers and adenocarcinoma of the stomach.
DiagnosticsThis section has been translated automatically.
Breath test (urea-breath test): The patient ingests 13C-labelled urea in a drink containing citric acid. H. pylori has an enzyme, the so-called urease, which converts urea to ammonia and carbon dioxide. The carbon dioxide contains the 13C-labeled carbon atoms of the ingested urea. The 13C concentration of the exhaled air can be measured in a mass spectrometer. This in turn allows conclusions to be drawn about the amount of urea converted and thus about the Hp-related urease activity in the stomach. The simultaneous intake of acid-inhibiting drugs (proton pump inhibitors) can promote false negative results. Consumption of coffee should also be avoided before the test is performed for the same reasons.
Stool test: The patient provides a stool sample in which H. pylori components (Hp antigens) can be detected using a special procedure. In addition to diagnosing an H. pylori infection, the test can also be used to check the effectiveness of an antibiotic therapy (eradication therapy).
Serology: Serology is a very commonly used technique for detecting H. pylori infection (ELISA and immunoblot) for antibodies to H. pylori. The investigation of the antibody response to H. pylori is indicated in cases of pronounced atrophy of the gastric mucosa as well as in cases of gastric bleeding and under therapy with proton pump inhibitors. If antibodies are detectable, this indicates contact with the pathogen. Depending on the constellation of the findings, conclusions can be drawn about a currently existing infection or an infection that has been passed through. Since the antibodies can be detected for months after successful antimicrobial treatment, serological testing is not suitable for immediate monitoring of the success of the therapy.
The undoubtedly most reliable method for detecting a Helicobacter pylori infection is gastroscopy with biopsy. By means of a rapid test (Helicobacter Urease Test=HUT), H. pylori can be detected directly in the biopsy.
Laboratory: H. pylori is cultured from the biopsy specimen and its sensitivity to the antibiotics commonly used in treatment is determined. This allows targeted therapy against the pathogen using safely effective antibiotics. Bacteriological-cultural detection of the pathogen is considered the "gold standard", i.e. the most reliable, although not the most sensitive, diagnostic method. Colonies are small (0.5-1.0mm) smooth bordered, transparent and show discrete beta-haemolysis.
PCR: Detection of specific DNA sequences gives a reliable result in a very short time. Resistance to clarithromycin can also be identified in this way.
TherapyThis section has been translated automatically.
Indications for eradication (according to Maastricht consensus and S3 guideline):
- Ulcer disease (ulcus ventriculi or ulcus duodeni).
- MALT lymphoma of the stomach, stage I/II)
- Symptomatic H. pylori-associated gastritis.
- Giant fold gastritis (Ménétrier syndrome - rare clinical picture)
- Lymphocytic gastritis
- Gastric carcinoma prophylaxis (positive family history for gastric carcinoma)
- Condition after partial gastric resection
- After resection of an early gastric carcinoma
- ASA or NSAID long-term therapy
- Extragastric disease (e.g., unclear iron deficiency anemia)
- Functional dyspepsia after exclusion of other diseases
After detection of H. pylori, antibiotic therapy is initiated. The goal of this therapy is the complete elimination (eradication) of the H. pylori germ:
French triple regimen. Seven to 14 days
- 2 x 20 mg omeprazole (alternatively 2x 30 mg lansoprazole or 2 x 40 mg pantoprazole)
- 2 x 1000 mg amoxicillin
- 2 x 500 mg clarithromycin
Italian triple regimen. Seven to 14 days
- 2 x 20 mg omeprazole (alternatively 2x 30 mg lansoprazole or 2 x 40 mg pantoprazole).
- 2 x 400 to 500 mg metronidazole
- 2 x 250 to 500 mg clarithromycin
In case of quadruple resistance: If there is resistance to one of the antibiotics, resort to quadruple therapy, e.g. consisting of a proton pump inhibitor combined with tetracycline, metronidazole and a bismuth salt.
At the earliest four weeks after the last antibiotic intake, the success of the therapy should be checked by monitoring the H. pylori status. If the germ has survived, a new antibiotic therapy for complete eradication should be carried out by the treating physician. Therapy regimens with other antibiotics (e.g. PPI+amoxicillin+levofloxacin) or combinations with bismuth and tetracycline, among others, are used.
At the latest after the second unsuccessful eradication attempt, a culture of the germ should be prepared so that antibiotics can then be used in a targeted manner.
LiteratureThis section has been translated automatically.
- Burucoa C et al. (2017) Epidemiology of Helicobacter pylori infection. Helicobacter 22 Suppl 1. doi: 10.1111/hel.12403.
- Camilo V et al. (2017) Pathogenesis of Helicobacter pylori infection. Helicobacter 22 Suppl 1. doi: 10.1111/hel.12405.
- Hof H et al (2019) Helicobacter. In: Hof H, Schlüter D, Dörries R, eds Dual series medical microbiology. 7th, completely revised and expanded edition. Stuttgart: Thieme pp 451-454.
- Kamboj AK et al (2017) Helicobacter pylori: the past, present, and future in management. Mayo Clin Proc 92:599-604.
- Ménard A et al (2019) Review: Other Helicobacter species. Helicobacter 24 Suppl 1:e12645.