A gram negative bacterium found in the lumen surface of the gastric epithelium.
A spiral microacrophilic, gram-negative bacteria with flagella that have urease, catalase and oxidase activity.
A common bacterial infection of the human stomach that affects more than half of the world population.
Incidence may be decreasing.
H.pylori infection is a common, usually lifelong infection found worldwide.
Prevalence in the US varies regionally and according to ethnic group or socioeconomic status.
The number of infected people has persisted or even increased over the past three decades because of population growth and because of re-infection and recrudescence due to unsuccessful eradication.
Catalase activity enables H. Pylori to survive oxidative stress.
Inflammation in the gastric epithelial lining allows H pylori to flourish.
Flagella mediated motility allows for colonization of the stomach motility and facilitates infection.
The H. pylori bacterium is thought to spread through consumption of contaminated food or water and direct mouth-to-mouth contact.
The CDC estimates that approximately two-thirds of the world’s population harbors H. pylori, with infection rates much higher in developing countries than in developed nations.
In most populations, the bacterium is first acquired during childhood.
H. pylori infection predominantly affects the gastric corpus and is associated with hypochlorhydrea because of damage to parietal cells.
H. pylori induces degradation of p53, a tumor suppression protein, in gastric epithelial cells, and subsequently leads to the formation of gastric cancer.
CagA Protein derived from H. Pylori interacts with epithelial E cadherin, promoting cell proliferation with an increased possibility of cancerogenic transformation.
Infection in the gastric antrum is associated with duodenal ulceration.
The above characteristics are vital to this agent’s survival in the acidic gastric environment.
The gastric mucosa is the only niche of H.pylori in the human body.
H.pylori strains vary in their expression of virulence, which affects their ability to cause disease.
East Asian strains are almost all capable of assembling a type IV secretion system with the oncoprotein CagA translocating into gastric target cells.
H.pylori is tenacious, and is typically contracted in early childhood, and persists for decades, quite possibly for the lifetime of the host in the face of humoral and T cell driven immune response.
Urease helps to convert urea to ammonia, which aids neutralizing gastric acid and promoting bacterial proteins synthesis.
Gene urel encodes for a hydrogen ion-gated urea channel that promotes urea uptake urease secretion in response in a decrease in gastric pH.
Urease accounts for up to 10% of total protein content of H pylori.
H pylori infection increases a release of phagocytic cells that attempt to kill the organism by releasing oxygen metabolites.
One of the most common bacterial pathogens, affecting more than half of the population worldwide.
Associated with gastritis.
Associated with unexplained iron deficiency and immune thrombocytopenia.
The main driver of non-cardia gastric cancer.
Helicobacter pylori is classified as a group I carcinogen and is an environmental risk factor for gastric cancer.
H.pylori it causes DNA damage which promotes malignant transformation.
H.pylori promotes malignant transformation in the context of hereditary, homologous recombination deficiency, suggesting that a multihit carcinogenesis is required for cancer to occur.
Global incidence rate of cancer attributed to H pylori infection his highest in in east Asia at 17.6 cases per hundred thousand person-years.
H. pylori infection risk factor of gastric cancer is associated with germline pathogenic variants in homologous recombination genes.
Induces chronic inflammation of the underlying mucosa.
Clinical manifestations of the organism develop only in a minority of cases.
It is the most common cause of gastric and duodenal ulcers, especially when nonsteroidal anti-inflammatory drug use has been ruled out.
The majority of infected persons remain asymptomatic.
In patients infected with H pylori there’s a 10-20% lifetime risk of peptic ulcer disease and a 1 to 2% risk of gastric cancer.
It is classified by the WHO as a group 1 carcinogen leading to gastric carcinoma.
Colonizes the mucous layer covering the gastric mucosa, with little invasion of the gastric glands.
The prevalence of H Pylori in patients with duodenal and gastric ulcers is nearly 100% and 80-90%, respectively and eradication of H pylori in infected patients shown to decrease peptic ulcer disease recurrence rates to less than 10%.
Strong association with adenocarcinoma of the stomach.
Standard of care for patients with ulcer disease and associated H. Pylori infection is to treat with antibiotics.
Among patients with H. pylori infection who had a family history of gastric cancer in first-degree relatives, H. Pylori eradication treatment reduced the risk of gastric cancer.
Prevalence of infection generally increases with age.
A lower socioeconomic status is a risk factor, because it is associated with more crowding and that favors intrafamilial transmission.
It can be iatrogenically introduced by means of endoscopes.
The serroprevalence is approximately 30% for individuals younger than 30 years of age, and 63% for individuals age 55 to 65 years.
Ethnic prevalence varies from whites 26%, blacks 53% and Mexican-Americans 62%.
The infection is higher in blacks and Hispanics than whites.
Human beings appear to be the only significant reservoir for H pylori.
Infection usually contracted in the first few years of life, and persists unless treated.
Infection prevalence increases with age and with lower socioeconomic status in children.
Infection is chronic and does not appear to resolve spontaneously.
Majority of infected patients remain asymptomatic and never develops significant disease.
At least 50% of the world’s population has H. Pylori infection.
Mechanism by which this infection is transmitted from one individual to another remains unknown.
The most common route of transmission is person to person spread through fecal-oral and oral-oral exposures.
Transmission risk factors are related to living conditions that can promote close person to person contact.
Some individuals remain protected from colonization by this organism for unknown reasons.
About 50% of adults in the U.S. are colonized with H pylori but only 15% to 20% of infected individuals develop PUD.
Chronic infection eventually causes gastric atrophy and metaplasia and is associated with both intestinal-type gastric carcinoma and MALT lymphoma.
Eradication of H pylori in patients with the gastric mucosal associated lymphoid tissue lymphoma can lead to 60 to 80% regression of the lymphoma.
Patients infected with cytotoxin associated gene A H pylori strains are at higher risk of peptic ulcer disease and gastric cancer because of greater inflammation.
In developing countries infection is commonly seen in children and chronic infection continues into adulthood.
Infection rate in the developing world is rare in children in the develops more commonly in adult today.
Exposure to H pylori early in life is associated with gastric pathology, progressing from atrophic gastritis to gastric ulcers and carcinoma.
Late onset of infection most commonly presents with duodenal pathology.
Little evidence of association with subsequent development for myocardial infarction.
Infection causes histologic damage in the stomach.
With duodenal ulcers gastric mucosal inflammation is most pronounced in the non-acid-secreting antral region of the stomach and stimulates increase release of gastrin which stimulates excess acid secretion from the more proximal acid-secreting fundus mucosa: the increased acid load damages the duodenal mucosa resulting in ulceration and gastric metaplasia.
In duodenal damage and metaplasia that occurs may become colonized by H. pylori and contribute to the ulceration process.
Treatment of H. Pylori in patients with duodenal ulcers by eradicating the infection provides a long-term cure in more than 80% of patients whose ulcers are not associated with non-steroidal anti-inflammatory drugs (Hentschel E).
Randomized trials show that therapy design to eradicate H. Pylori reduces the incidence of duodenal ulcer, gastric ulceration, and gastric cancer.
Gastric ulcers result from mucosal damage by H. pylori and eradicating the infection usually cures the process, providing the gastric ulcer is not due to NSAIDs.
Screening and treatment for H. pylori infection in persons who are starting or taking long term NSAID therapy reduces the risk of peptic ulcer disease.
Early infection associated with dyspepsia than patients become asymptomatic with an asymptomatic latent infection.
Infection is usually acquired in childhood with a prolonged latent period with clinical manifestations occurring late in life.
A chronic gastritis associated with a lifetime risk of gastric cancer between 1-15%, and a lifetime risk of peptic ulcer disease of one in six persons.
Patients with latent infections are the reservoir for further infections in the community.
Testing for H. Pylori infection in the presence of a history of duodenal ulcer, gastric ulcer, gastric low-grade B-cell lymphoma, after finding a gastric cancer, the presence of gastritis, the presence of dyspepsia, long-term aspirin use, long-term NSAID use, first-degree relatives of patients with gastric cancer or peptic ulcer.
Non-invasive tests include serological analysis, urea breath test and stool antigen testing.
Serological testing for H. Pylori IgG is no longer recommended for the diagnosis of infection in areas in which the prevalence is 30% or less as the current prevalence in the US is estimated to be 30%.
Serological testing for H. Pylori IgG antibodies persist for several years and has a specificity of less than 80% for active H. Pylori infection, and repeat serum IgG testing is not useful for assessing eradication.
Non-invasive tests are recommended in patients for whom endoscopy is not indicated but who have conditions associated with the infection such as a history of peptic ulcer disease, unexplained iron deficiency, immune thrombocytopenia, or are considered to be an increased rosk of infection or complications of infections such as with long-term NSAIDs or aspirin.
Non-invasive test for active infection include the stool antigen test and urea breath test.
Stool antigen testing involves a mixture of monoantibodies against H. Pylori used for initial diagnosis and for confirming eradication of the infection.
The sensitivity and specificity of stool antigen tests typically exceed 92%.
Urea breath test involve the ingestion of either 14C-labeled or 13C-labeled urea: If H.Pylori is present, bacterial urease releases the label, which is measured in compared with a baseline value.
This test has a sensitivity and specificity exceeding 95%.
Diagnosis can be established by endoscopy with histological biopsy, culture or rapid urease
Antigen testing of stool for H. Pylori has a sensitivity and specificity of more than 90%
Direct histological testing of gastric mucosal biopsy samples is used for the diagnosis in patients with indications for endoscopy, such as epigastric pain, weight loss, iron deficiency, and dyspepsia or in patients 60 years of age or older.
If a patient is from a region with a greater incidence of infection and gastric cancer, histologic testing should be done at a younger age is guided by local recommendations.
Direct testing is recommended in patients with long-term use of aspirin or nonsteroidal anti-inflammatory drugs for whom endoscopy is indicated, ensuring management of NSAID induced peptic ulcer disease is not complicated by the infection.
Histologic detection of H. Pylori in gastric tissues has a sensitivity and specificity they can exceed 95%.
Endoscopy can be used to determine eradication of infection but is usually repeated only in the context of persistent ulcers, to confirm healing of a gastric ulcer, or after removal of early gastric cancer or MALToma.
Early stage MALToma can be effectively treated with antibiotics to eradicate H. Pylori infection, while advanced stages requires chemotherapy, radiation, surgery or a combination of treatments.
Meta-analysis has identified 2 genome-wide loci statistically significantly associated with H. pylori seroprevalence: The toll-like receptor locus (TLR) on 4p14 and the FCGR2A locus on 1q23.3.
Serum testing for IgG antibodies to H. Pylori microorganisms has a sensitivity and specificity of 85%.
Camplyobacter-like organism (CLO) test based on the inoculation of mucosal gastric biopsy into a medium containing urea and phenol red, a dye that turns pink in a pH of 6.0 or greater which occurs as Heilcobacter metabolizes urea to ammonia by way of its urease activity.
This agent can survive the acidic environment because its high urease activity.
Urease converts the urea present in gastric juice to alkaline ammonia and carbon dioxide.
The CLO test has a 98% sensitivity and 100% specificity for diagnosis of this entity.
CLO test is the invasive test of choice for diagnosis.
Association with Maltoma.
Eradication of this agent has been shown to prevent recurrent peptic ulcer disease, to cure some gastric MALTOmas, and prevents the development of NSAIDs-associated ulcers.
Infection is a cofactor in the development of duodenal and gastric ulcers (1-10%), gastric cancer (0.1-3%), and gastric mucosa associated lymphoid lymphoma (.01%).
A strong relationship exists between H. pylori infection and noncardia gastric cancers: those distal to the GE junction (Hansen S).
The main driver of non-cardia gastric cancer.
The risk of gastric cancer is highest among patients with H. pylori infection that causes inflammation in both the antrum and the fundus mucosa with mucosal atrophy and intestinal metaplasia (Uemura N).
It is not known if eradication of H.pylori infection can reduce the risk of gastric cancer (Malfertheimer P).
Eradication of H, pylori using amoxicillin and omperazole reduced gastric cancer incidence by 39% after 15 years of follow-up (Ma JL et al).).
The overwhelming majority of patients with H. Pylori infection will not have significant complications.
Does not invade the gastric mucosa, and its location in the gastric mucus provides protection from hosts immune mechanisms, and makes delivery of antibiotics to the organism difficult.
Clarithromycin is sensitive to degradation in an acidic environment and has a half life of less than 1 hour in the stomach if the pH levels is 2 or lower.
Gastric mucus layer is a mechanical barrier to the delivery of antibiotics.
Gastric emptying limits the retention of antibiotics in the stomach making treatments less successful.
Culture and sensitivity studies are not readily available and when used may nor provide clinical benefit.
A number of treatment protocols are acceptable as first-line treatments.
Resistance to clarithromycin present in 10-12% of cases reported in1999-2002, and resistance to metronidazole was 25.1% during the same period (Duck).
Susceptible to ampicillin in vitro and ineffective in vivo.
Amoxicillin is effective in vivo, and resistance to this agent rare.
Clarithromycin combined with amoxicillin and a PPI is among the first recommendations in patients with no history of antibiotic treatment.
A combination of bismuth, tetracycline, metronidazole, and a PPI is commonly used, and is commonly used with penicillin allergy, or previous exposure to a macrolide.
Sensitivity studies reliable for clarithromycin, but not for metronidazole.
Proton pump inhibitor triple therapy most widely used treatment: a 7-10 course of a PPI plus clarithromycin and amoxicillin.
Proton pump inhibitors have suppressive effects on H. Pylori and should be discontinued before testing for infection and before confirming H. Pylori eradication my means of any testing.
Proton pump inhibitors should be discontinued for 2 weeks -30 days before testing.
Eradication rate of treatment with 10 days of triple therapy is 78% (Vakil).
Increasing treatment duration does not result in increased benefits.
Quadruple therapy with bismuth plus metronidazole, tetracycline and a PPI is an alternative treatment.
Quadruple therapy is not significantly better than triple therapy.
Sequential treatment consists of 10 days of treatment with a PPI, plus amoxicillin for the first 5 days and a combination of clarithromycin and tinidazole for the second five days.