Heliobacter pylori is a gram-negative bacterium that causes gastritis. Although about half of the world's population is chronically infected with Heliobacter pylori, only a small part of these people will eventually develop gastric ulcers or cancer due to this microorganism.
Most H. pylori infections remain asymptomatic although signs of a chronic gastritis or duodenitis are revealed by histopathological analysis. People infected with H. pylori do therefore not consult their physicians until they develop symptoms of gastric or duodenal ulcers.
Generally, these ulcers are associated with pain in the upper abdomen, loss of appetite, nausea and even vomiting. Patients often report that they feel full and bloated after eating a small portion of food. In case of ulcer hemorrhage, stools may be of a very dark color and additional symptoms associated with anemia may be detected. Those principally comprise hematologic alterations and overall fatigue.
Although the probability of an H. pylori infection leading to cancer is low, there is still a considerable number of people affected by this severe complication because the overall prevalence of the bacterium is very high. Patients suffering from a gastric carcinoma usually present with the symptoms mentioned above, but may also exhibit severe weight loss and other clinical signs associated with the primary tumor and possible metastases.
Routine testing to identify patients infected with H. pylori is not necessary. Only if an ulcerative gastritis is suspected or confirmed, its causes should be evaluated and a screening for H. pylori should be part of this examination.
Serologic tests are the method of choice to corroborate the suspected presence of the bacterium. Their sensitivity and specificity are >85% and they are therefore well suited to give an initial indication. However, there are some limitations to serological screenings for antibodies against H. pylori. Antibody titers do not decrease significantly until up to one year after successful treatment and serologic tests may still be positive for up to three years after therapy. Thus, serologic tests are little conclusive in patients that did receive treatment against H. pylori recently; these tests are also not used to evaluate the success of a therapy.
To confirm an infection with H. pylori - and to verify its successful elimination - a urea breath test or a stool antigen assay is indicated. A urea breath test is carried out by oral administration of carbon-labeled urea that will be enzymatically decomposed to ammonia and carbon dioxide by H. pylori. The carbon dioxide exhaled by a patient infected with H. pylori is therefore also isotope-labeled while this is not the case in patients who do not carry H. pylori . Sensitivity and specificity of this test are >90%. False-negative results may be prompted by use of antibiotics or proton pump inhibitors, since only a strongly acidic environment inside the stomach causes H. pylori to release urease. Testing should therefore be delayed up to four weeks after antibiotic therapy and up to one week after proton pump inhibition. Stool antigen assays seem to be of similar sensitivity and specificity and are currently being updated towards a more user-friendly format .
These non-invasive tests are strongly preferred over invasive ones, if merely carried out to confirm an existing H. pylori infection. However, if tissue samples need to be taken for histopathological analysis, mucosal samples may be used to conduct a rapid urease test . Similar to the urea breath test, this test depends on the presence of urease released by H. pylori. Biopsy samples should be histologically analyzed in cases of negative test results after recent use of antibiotics or proton pump inhibitors and if a malignant transformation is assumed. Sensitivity and specificity of both the rapid urease test and histological analysis of the biopsy are >90%.
As long as the infection with H. pylori stays asymptomatic, treatment is not necessary. Due to the increased risk for malignant transformation, elimination of H. pylori may nevertheless be indicated, but this is still a controversial topic.
If complications such as an ulcerative gastritis or even gastric cancer arise, the bacterium should be eradicated. While gastric ulcers and lymphoma of the mucosa associated lymphoid tissue may be cured by an appropiate antibacterial therapy, gastric carcinoma will not.
In order to eliminate H. pylori, antimicrobials are usually combined with proton pump inhibitors. These antacids increase gastric pH and thus do not only suppress H. pylori growth and replication but also allow for a better accumulation and higher concentration of antibiotics in the stomach.
A possible treatment regimen would be 500 mg clarithromycin bid, plus 1000 mg amoxicillin bid, plus 20 mg omeprazole bid. Amoxicillin may be replaced by 500 mg metronidazole bid if the patient suffers from hypersensitivity to pencillin and related compounds. Omeprazole may be replaced by 30 mg lansoprazole bid if needed, or by 400 mg ranitidine bismuth citrate bid if proton pump inhibitors are to be avoided .
Tetracycline is also effective against H. pylori and may be administered bid in a dose of 500 mg. It may be complemented with metronidazole and a proton pump inhibitor as indicated above and with 525 mg bismuth subsalicylate or subcitrate bid . This quadruple therapy, however, is less well tolerated than the triple therapy involving clarithromycin and amoxicillin or metronidazole.
These regimens should be followed for 14 days and are expected to cure the vast majority of H. pylori infections. Acid suppression should be continued for another two weeks to allow healing of ulcers.
In the unlikely case that H. pylori cannot be completely eliminated, the treatment should be repeated. If the second therapy also fails, samples for sensitivity testing should be obtained endoscopically.
The prognosis is excellent, unless the patient develops a gastric carcinoma. This good prognosis also applies to cases complicated by the development of a lymphoma of mucosa associated lymphoid tissue.
The prognosis for patients diagnosed with gastric carcinoma is poor.
There is a chance for reinfection, but the rate is very low. The highest rate of reinfection has been observed in children and women and did not surpass 8%.
Although H. pylori is generally considered an extracellular pathogen that specifically adheres to gastric cells, recent reports provide evidence that it can also be classified as a faculative intracellular bacterium. It does directly influence intracellular pathways and metabolism, e.g by decreasing intracellular levels of glutathione and altering the cells' redox state. Recently, it has been proposed that H. pylori may even be able to adapt to gastric stem cells, to alter their biology and thereby contribute to tumorigenesis .
Even though H. pylori carries several pathogenicity factors, most infections remain asymptomatic. However, H. pylori does damage the protective mucus layer and thus leaves epithelial cells vulnerable to gastric acid. This eventually results in ulcerative gastritis. Chronic inflammation due to H. pylori infection may ultimately lead to gastric mucosa atrophy, a condition associated with an increased risk for gastric cancer. Also, a correlation between H. pylori infections and incidence of certain lymphomas has been proposed.
H. pylori prevalence depends on geographic location, sanitary and living conditions, socioeconomic status and age. Prevalence is significantly higher in developing than in industrialized countries and does increase with age. This fact results in a high prevalence among elder people in the Western world, where more than 50% of people older than 60 years carry H. pylori . However, in developing countries this trend can be observed when comparing H. pylori prevalence in young children and adults. Here, the prevalence among children younger than five years may already have reached 50% and an estimated 90% of the adults are infected . Particularly high prevalences have been reported for South America, Asia, the Middle East, North Africa and Eastern Europe .
Studies regarding the prevalence among patients presenting with gastrointestinal diseases show a clear correlation between those disorders and H. pylori infections .
H. pylori is presumably transmitted in a fecal to oral or oral to oral manner, a fact that explains why family members or people that otherwise maintain close contact are frequently infected concomitantly. A gastro-oral infection route has been discussed and would mean that health care givers are at risk.
H. pylori may cause a chronic gastritis histopathologically characterized by immune cell infiltration into the epithelial layer and the lamina propia of the gastric mucosa. Neutrophil granulocytes, lymphocytes, macrophages and mast cells can be detected. They are most likely attracted by chemotactic factors released by gastric epithelial and other types of cells upon contact with H. pylori, maybe even after infection with the bacterium. It is not yet clear whether H. pylori itself is able to reside intracellularly or merely uses the protective mucus layer in order to protect itself from the acidic environment of the stomach.
The former hypothesis may be corroborated by the fact that H. pylori does carry a highly immunogenic lipopolysaccharide (LPS) whose composition includes important virulent factors that enable the pathogen to adhere to the gastric cells. These virulence factors may trigger an immune response by stimulating the release of chemotactic factors to attract immune cells. Also, the CagA gene product does induce the release of chemotactic factors by host cells, but is only expressed by about 60% of H. pylori strains. CagA-positive and CagA-negative H. pylori strains do alter catalase, glutathione peroxidase and superoxide dismutase activity differently. Thus, the DNA may be more susceptible to damage induced by reactive oxygen species, which, in turn, may contribute to tumorigenesis.
Another important virulence factor of H. pylori is the expression of VacA, a gene whose product is a vacuolating cytotoxin. Epithelial cells exposed to this cytotoxin develop vacuoles that fill up with gastric acid until they burst and expose adjacent epithelial cells to their acidic content. Only about 40% of H. pylori strains express VacA . Persistence of H. pylori infection presumably depends on the expression of LPS antigens, CagA, VacA and further, as of yet only partially detected, virulence factors. They may enable the bacterium to modulate the host's immune response by affecting host cell gene expression and cell cycle. For instance, H. pylori is able to upregulate caspase expression and to induce apoptosis in epithelial cells.
The chronic inflammation caused by H. pylori may ultimately lead to gastric cancer and lymphoma. In this context, it has been proven that the LPS of H. pylori is able to stimulate tumor proliferation of enterochromaffin-like cells in the gastric wall. If a histopathological analysis is carried out at this stage of the disease, alterations corresponding to cancerous tissue changes may be found .
Because the fecal to oral route is likely the main way of infection, standard hygiene measures may help to avoid infection with H. pylori. These measures include regular and thorough hand washing, particularly after using the toilet, and an appropiate hygiene of food and drinking water.
Further preventive measures have not yet been recommended. Vaccines are currently being developed.
It has been estimated that more than 50% of the world's population carry Heliobacter pylori (H. pylori), a gram-negative obligate pathogen, in their stomachs. H. pylori may cause gastritis and duodenitis, but does not provoke any symptoms in the vast majority of carriers . Only about 10% of people infected with H. pylori eventually develop gastric ulcers that, however, render them predisposed to gastric cancer.
The ability of H. pylori to survive in the strongly acidic environment of the stomach made this ecological niche accessible for this bacterium. It has been reported that H. pylori avoids the gastric acid by settling below the protective mucus layer and by catalyzing the decomposition of urea into ammonia and carbon dioxide, thus increasing the pH in close proximity to the bacterium. Surprisingly, this neutralization of gastric acid reduces the incidence of acid reflux and subsequent diseases of the esophagus. The degree of adaptation to the acidic environment of the stomach may be recognized by the fact that the expression of the flagellin gene and thereby the motility of the germ is indeed acid-regulated .
The prevalence of H. pylori is particularly high in developing countries. However, a significant share of the population of Western world countries is also infected. It has been proposed that H. pylori is mainly transmitted in a fecal to oral pattern.
H. pylori is a bacterium that resides in the stomachs of approximately half of the world's population. Although it generally does not cause any discomfort or other symptoms, H. pylori may cause gastric inflammation and gastric ulcers.
H. pylori may spread from an infected person to someone still uninfected. The bacterium takes the fecal-oral or oral-oral route into the second person's stomach. Scientists do not yet fully understand why H. pylori causes gastric ulcers in some people while it does not in others.
As it has been mentioned above, the majority of people infected with H. pylori does not experience any symptoms. However, if gastric ulcers are developed, they are generally accompanied by pain in the upper abdomen, uneasiness until or after eating, a sensation of fullness, loss of appetite, nausea and vomiting. Furthermore, dark stools, bloody vomiting, overall fatigue and weight loss may be observed.
If the patient does present the abovementioned symptoms or the physician suspects H. pylori to be the cause of gastric problems, the physician will obtain the patient's medical history and carry out a clinical examination. Furthermore, blood and stool tests may be conducted. An infection with H. pylori may also be detected by analyzing the patient's breath. If neither of these tests provide conclusive results, an endoscopic examination may be indicated before deciding on the following steps.
If H. pylori is responsible for any gastric disorder and the bacterium needs to be eliminated, the therapy of choice consists of a combined pharmacological approach comprising antibiotics and drugs that inhibit gastric acid production.
Antibiotics that may be prescribed are clarithromycin, amoxicillin, metronidazole and tetracycline. Gastric acid production may be inhibited with compounds such as omeprazole or lansoprazole as well as with ranitidine or famotidine.
These drugs have to be taken for two weeks. While they may be discontinued after this time, acid inhibitors possibly need to be taken another two weeks. The final decision regarding the treatment regimen is taken by the physician. He or she will also decide whether additional drugs may be necessary.