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by Maria Shaker
Helicobacter pylori is a spiral-shaped, Gram-negative, microaerophilic bacterium. The bacterial cells are equipped with multiple flagella located at one end and the bacterium uses this to burrow into the mucosal layer of the stomach. Optimal conditions for growth include oxygen levels between 5-15%, approximately 5% CO2, availability of specific amino acids, and a temperature range of 30-37degrees Celsius.
It was once thought that no microbe could survive the harsh living conditions of the stomach, and therefore microbial colonization of the stomach was not really considered a possibility. However, H. pylori produces a urease to convert urea from gastric juices as well as saliva into bicarbonate and ammonia—thus, the microenvironment directly surrounding the bacterium is neutralized and the pathogen escapes the corrosive effects of the gastric secretions.
The possibility of H. pylori as a zoonotic pathogen has been suggested, but there is no evidence to support this belief. No animal or environmental reservoirs harboring strains that infect humans have been reported, despite the isolation of H. pylori from other animals such as the cat. At this time, it seems that only the conditions of the human stomach are optimal for growth and viability of the pathogen.
Research is still being conducted to explain the routes of transmission. Many have been identified, but this is an area still poorly understood. Some evidence suggests that even the housefly has the potential to transmit H. pylori, but person-person contact is the most heavily favored route of transmission. Iatrogenic transmission can occur when an endoscope used to observe the gastric mucosa of one individual is used on another patient. Transmission has also occurred occupationally—either a gastroenterologist or endoscopist acquires the infection from a patient. Other heavily considered routes include fecal-oral as well as oral-oral contact. The latter route has been suggested as a result of PCR and culturable H. pylori from the oral cavity.
The pathogenesis of H. pylori infection varies between infected individuals as some may present with gastrointestinal symptoms while others remain asymptomatic, which is the case for most of the infected individuals. Most people who are infected with H. pylori can suffer from chronic active, chronic persistent, or atrophic gastritis. Gastritis can lead to ulceration of the stomach lining and duodenal ulcers because the integrity of the colonized mucosal layer is compromised and therefore the underlying epithelium is subjected to the acidic secretions of the stomach.
Symptoms of peptic ulcer disease include burning epigastrial pains, which usually occur when the stomach is empty. This pain is relieved upon eating or treatment with antacids. Nausea, vomiting, and a loss of appetite are other hallmarks of peptic ulcers. Chronic ulceration may lead to bleeding, and if bleeding persists, the blood loss can trigger the onset of other complications. These conditions have been identified as predisposing factors of stomach cancer since infected individuals have a 2- to 6- fold increased risk of developing gastric cancer and mucosal-associated-lymphoid-type lymphoma.
Chronic gastric inflammation results from the expression of two different virulence factors. H. pylori produces a protein, CagA which has been shown to enhance the inflammatory response. The components of the heightened immune response are unable to efficiently reach the pathogen due to the barrier of the stomach lining. Instead, as the white blood cells die, for example, they lyse and release their intracellular contents which provide the bacteria with nutrients, ultimately sustaining the infection. Another virulence factor, a cytotoxin encoded for by the vacA gene, is thought to induce vacuolation of the epithelial cells.
There are a number of different diagnostic techniques that can be used to confirm H. pylori infection. Diagnosis can be made based on non-invasive or invasive tests, at the discretion of the physician. A serology test can be performed from a simple finger prick to obtain a blood sample and test for the presence of circulating anti-H. pylori antibodies. The urea breath test is used to detect the presence of H. pylori for diagnostic purposes as well as to confirm the effectiveness of treatment. The patient consumes a urea solution containing radio-labeled carbon. As the microbes in the stomach metabolize the urea, bicarbonate and ammonia are released, travel through the bloodstream, and into the lungs where they are exhaled. The radioactive carbon can be detected from a breath sample obtained from the patient blowing into a balloon. This diagnostic technique is 96-98% accurate. A more invasive approach involves histological examination of a gastric biopsy, obtained by endoscopy. The tissue sample can also undergo a rapid urease test to confirm H. pylori infection.
A two-week course called the triple therapy has been shown to be the most effective treatment of chronic gastritis resulting from H. pylori infection. Triple therapy incorporates the administration of two antibiotics such as metronidazole and tetracycline, in addition to either an acid suppressor or stomach protector. This treatment reduces ulcer symptoms and kills the bacteria, which has been shown to reduce the recurrence of peptic ulcers in 90% of the affected individuals. Treatment is somewhat demanding since an individual may be required to take up to twenty pills per day however, the two-week period is required to completely eliminate H. pylori. In addition, Helicobacter resistance to antibiotics is on the rise throughout the world, and it is imperative for patients to continue treatment for the duration.
Serological tests have been used to conduct important epidemiological studies. This epidemiological research has shown that somewhere between one-half and two-thirds of the world’s population is colonized by the pathogen and infection with H. pylori is related to socioeconomic status (during childhood) rather than race. In the United States, individuals older than 50 years of age, minorities, and immigrants from developing countries have about a 50% or greater probability of being infected with H. pylori, and infection is less prevalent in affluent Caucasians. In the developing countries, the bacteria colonize 70-90% of the population, and colonization occurs before the age of ten. It is thought that poor sanitation and overcrowded living conditions contributes to the discrepancy of H. pylori infection between industrialized and developing countries.
Some other interesting statistics:
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© 2010, J.Graf. Site made by Maria Shaker, for comments please contact Joerg.Graf@uconn.edu