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Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. European Helicobacter Pylori Study Group.

There is considerable confusion over the management of Helicobacter pylori infection, particularly among primary care physicians, and numerous European countries lack national guidelines in this rapidly growing area of medicine. The European Helicobacter Pylori Study Group therefore organised a meeting in Maastricht of H pylori experts, primary care physicians and representatives of National Societies of Gastroenterology from Europe to establish consensus guidelines on the management of H pylori at the primary care and specialist levels, and to consider general health care issues associated with the infection. As in previous guidelines, eradication therapy was recommended in all H pylori positive patients with peptic ulcer disease. Additionally, at the primary care level in dyspeptic patients < 45 years old and with no alarm symptoms, diagnosis is recommended by non-invasive means (13C urea breath test, serology) and if H pylori positive the patient should be treated. Moreover, at the specialist level the indications for eradication of H pylori were also broadened to include H pylori positive patients with functional dyspepsia in whom no other possible causes of symptoms are identified by the specialist (after a full investigation including endoscopy, ultrasound and other necessary investigations), patients with low grade gastric mucosa associated lymphoid tissue (MALT) lymphoma (managed in specialised centres) and those with gastritis with severe macro- or microscopic abnormalities. There was consensus that treatment regimens should be simple, well tolerated and achieve an eradication rate of over 80% on an intention to treat basis. It was strongly recommended, therefore, that eradication treatment should be with proton pump inhibitor based triple therapy for seven days, using a proton pump inhibitor and two of the following: clarithromycin, a nitroimidazole (metronidazole or tinidazole) and amoxycillin.

Amoxicillin↗

Blood tests in the management of Helicobacter pylori infection. Italian Helicobacter pylori Study Group.

There are three main types of blood test available for the management of Helicobacter pylori infection: those that detect an antibody response; tests of the pathophysiological state of the stomach; and those that indicate an active infection. Enzyme linked immunosorbent assay (ELISA) based kits are the most numerous of the commercially available tests. Originally the kits used crude antigen preparations but many of the newer kits use a more purified antigen preparation giving increased specificity but a lower sensitivity. The sensitivity, specificity, and predictive values of the tests can also be affected by the population under test and coexistent disease in the patients. Near patient test kits are based on either latex agglutination or immunochromatography. Generally, they have low sensitivities compared with laboratory tests. Commercial western blotting kits have also been developed and are used to detect the presence of specific virulence markers. The exact role of serology in the management of Helicobacter infection has still to be defined, although there is evidence that, used as a screening procedure, it can reduce endoscopy cost and workload. Gastrin and pepsinogen blood concentrations may provide valuable information on the pathophysiological state of the stomach--for example, the presence of inflammation or gastric atrophy. A combination of serology and serum concentrations of gastrin and pepsinogen may be used effectively to detect serious gastroduodenal disease in patients.

Antibodies, Bacterial↗

Canadian Helicobacter pylori Consensus Conference update: infections in adults. Canadian Helicobacter Study Group.

The first Canadian Helicobacter pylori Consensus Conference took place in April 1997. The initial recommendations of the conference were published in early 1998. An update meeting was held in June 1998, and the present paper updates and complements the earlier recommendations. Key changes included the following: the recommendation for testing and treating H pylori infection in patients with known peptic ulcer disease was extended to testing and treating patients with ulcer-like dyspepsia; it was decided that the urea breath test (not serology) should be used for routine diagnosis of H pylori infection unless endoscopy is indicated for another reason; and recommended therapies were a twice daily, seven-day regimen of a proton pump inhibitor (omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg) or ranitidine bismuth citrate 400 mg, plus clarithromycin 500 mg and amoxicillin 1000 mg, or plus clarithromycin 500 or 250 mg and metronidazole 500 mg. The need was reiterated to have funding for readily accessible, accurate testing for H pylori infection with the urea breath test. It was strongly recommended that regional centres be established to monitor the prevalence of antibiotic-resistant H pylori infections. The initial consensus document referred to pediatric issues that were not addressed in this update but were the subject of a subsequent Canadian Helicobacter Study Group meeting, and will be published later in 1999.

Adult↗

Canadian Helicobacter Study Group Consensus Conference on the Approach to Helicobacter pylori Infection in Children and Adolescents.

Gastric infection with Helicobacter pylori is common in both children and adults, but children are considerably less susceptible to peptic ulcers and other pathological sequelae. As a result, the risk to benefit ratio of diagnostic studies and therapeutic regimens for H pylori in adults are likely different from those in pediatric populations. These guidelines for the management of pediatric H pylori infection, developed by the Canadian Helicobacter Study Group, are designed to identify when the diagnosis and treatment of H pylori may improve patient care. Given the low prevalence of this infection in Canada, it is important to recognize that indiscriminate testing and treatment programs in children are not recommended, and indeed may threaten the optimal care of children. Diagnostic tests should be employed judiciously and be reserved for children who are most likely to derive measurable benefit, such as those likely to have peptic ulcer disease. At this time a test and treat strategy in children cannot be considered prudent, evidence based or cost effective. It is appropriate to limit diagnosis and treatment to children and adolescents in whom H pylori has been identified during endoscopic investigation.

Adolescent↗

Canadian Helicobacter Study Group Consensus Conference: Update on the management of Helicobacter pylori--an evidence-based evaluation of six topics relevant to clinical outcomes in patients evaluated for H pylori infection.

As an update to previously published recommendations for the management of Helicobacter pylori infection, an evidence-based appraisal of six topics was undertaken in a consensus conference sponsored by the Canadian Helicobacter Study Group. The issues addressed and recommendations made were: bismuth-containing quadruple therapy is appropriate as an alternative first-line eradication strategy for H pylori infection; searching for and treating H pylori infection is warranted in patients considered to be at high risk for gastric cancer; H pylori infection should be eradicated before initiating long-term treatment with nonsteroidal anti-inflammatory drugs or acetylsalicylic acid; the stool antigen test has a limited role in the diagnosis of H pylori infection; the benefits of H pylori eradication in patients on long-term proton pump inhibitor therapy are not sufficient to warrant recommending a strategy of searching for and eradicating the infection among these patients; and a strategy of "test and eradicate" for H pylori infection in patients with uninvestigated dyspepsia is cost-effective in Canada relative to a trial of proton pump inhibitor therapy. The goal was to establish guidelines on the best evidence using the same structure to address and formulate recommendations for each issue. The degree of consensus for each issue is presented.

Antigens, Bacterial↗

Gastroduodenal Helicobacter pylori infection diagnosed by Helicobacter pylori stool antigen is related to atherosclerosis.

OBJECTIVE: The causative relation between Helicobacter pylori (H. pylori) and atherosclerosis has been determined as seropositivity or determination of H. pylori from atherome plaques by molecular methods. The site of entrance and the reservoir of the bacteria in the body is still a subject of discussion. In this study Helicobacter pylori stool antigen (HpSA) which shows gastrointestinal system colonization and infection with high specificity and sensitivity was determined in atherosclerotic, ectatic and angiographically normal groups. METHODS AND RESULTS: A total of 62 patients was categorized according to diagnostic coronary angiography as 12 had normal coronary arteries, eight had one, 18 had two, and 12 had three atherosclerotic coronary arteries. Twelve patients had ectatic vessels. There were 27 (44%) HpSA positive and 35 (56%) HpSA negative patients. There was a statistically significant relation between HpSA positivity and the degree of vessel involvement in coronary artery disease (CAD) patients, essentially between the group with three vessels (83%) obstructed and the normal group (25%). Ectatic vessel group had a higher incidence (50%) of HpSA positivity compared to the control group but not enough for statistical significance. CONCLUSIONS: The results indicate that gastrointestinal system H. pylori colonization increases the risk of atherosclerosis. We may speculate that the reservoir and spread of H. pylori is via gastrointestinal tract. Studies may be performed to detect whether gastrointestinal tract H. pylori infection treatment will decrease the risk of coronary artery damage caused by H. pylori.

Antigens, Bacterial↗

Remission of severe anemia persisting for over 20 years after eradication of Helicobacter pylori in cases of Ménètrier's disease and atrophic gastritis: Helicobacter pylori as a pathogenic factor in iron-deficiency anemia.

A man with a 20-year history of recurrent iron-deficiency anemia complicated by Helicobacter pylori-positive Ménètrier's disease was observed over a 10-year clinical course, during which time he was successfully treated for the anemia and a gastric Helicobacter pylori (H. pylori) infection through eradication. Considering the satisfactory therapeutic results in this case, we performed eradication therapy on another H. pylori-positive atrophic gastritis case with a 24-year history of iron-deficiency anemia of unknown etiology, and again, complete remission was obtained. The clinical evidence from these two cases suggests that the gastric H. pylori infection was deeply involved in the pathogeneses of the iron-deficiency anemia. We believe that these case reports will provide useful information on H. pylon-involved pathology in the fields of hematology and gastroenterology.

Adult↗

Helicobacter heilmannii gastritis: association with acid peptic diseases and comparison with Helicobacter pylori gastritis.

We analyzed 2 antral and 1 corpus full-thickness random endoscopic gastric mucosal samples obtained from 946 patients with duodenal ulcers (6077 biopsies) and from 281 patients with nonsteroidal anti-inflammatory drug-associated gastric ulcers (1794 biopsies). We stained tissue sections with hematoxylin and eosin and Warthin-Starry silver stain and immunostained them with polyclonal antibodies against Helicobacter pylori. Hematoxylin- and eosin-stained sections from 6 patients with Helicobacter heilmannii (18 biopsies) and 23 randomly selected patients with H. pylori (68 biopsies) were evaluated and semiquantitated for the presence of acute inflammation, chronic inflammation, glandular atrophy, intestinal metaplasia, H. pylori, H. heilmannii, lymphoid follicles, or vasodilatation. Additional specimens were obtained for H. pylori culture, a CLO test, and serologic examination. H. heilmannii was detected in 6 (0.49%) of 1227 patients (14 [0.18%] of 7871 biopsies). Of these, 4 (0.42%) of 946 were patients with duodenal ulcers (9 [0.15%] of 6077 biopsies), and 2 (0.71%) of 281 were patients with nonsteroidal anti-inflammatory drug-associated gastric ulcers (5 [0.28%] of 1794 biopsies). We found H. heilmannii with hematoxylin and eosin stain, Warthin-Starry stain, and immunoperoxidase stain for H. pylori. Culture for H. pylori was negative in the four patients with duodenal ulcers. The CLO and serologic tests were positive in three of five and five of five patients, respectively. Our results indicate that H. heilmannii, like H. pylori, is associated with peptic ulcer disease (both active and inactive gastritis) and that it preferentially colonizes the gastric antrum. The severity of the H. heilmannii-associated gastritis is less intense and lymphoid aggregates are less common than in H. pylori-associated gastritis. Morphologic detection seems to be the method of choice for detecting H. heilmanni. Immunoperoxidase stain specific for H. pylori also stains H. heilmannii, indicating cross-reacting antigenic epitopes between H. heilmannii and H. pylori.

Adult↗

[Particular features of the relationship of Helicobacter pylori and G cells in patients with duodenal ulcer, with special reference to the Helicobacter pylori strain].

Helicobacter pylori positive form of duodenal ulcer (CagA+ and CagA-) was studied in 120 patients with duodenal ulcer (DU). CagA+ was found in 78 patients (65%); CagA(-)--in 42 (35%). Diagnostic criteria of symbiosis between Helicobacter pylori and macroorganisms have been established. They describe normal mucous structure, absence of CagA+ and G-cell hyperplasia. It can be important for diagnosis and choice of a suitable mode of treatment to be employed in DU patients.

Antigens, Bacterial↗

Comparison of helicobacter pylori stool antigen test with CLO test in the diagnosis of helicobacter pylori associated dyspepsia in a Saudi population.

OBJECTIVE: To compare the diagnostic usefulness of Helicobacter pylori (H.pylori) stool antigen test (HpSA) enzyme immunoassay (EIA) with the Campylobacter-like organism (CLO) test in Saudi patients with H.pylori associated dyspepsia. METHODS: Sixty consecutive adult Saudi patients suspected of H.pylori infection with dyspepsia attending the Gastroenterology Unit of the King Khalid National Guard Hospital, Jeddah, were recruited into the study. The study was carried out between 1st January and 30th June 2003. There were 25 males and 35 females. Their ages ranged from 19-72 years. Mean age was 39.6 years. At endoscopy diagnosis was made by taking gastric antrum mucosal biopsy for histology (Giemsa stain) and the CLO test was performed on a biopsy sample. A stool sample from each patient was sent to the Microbiology Department for HpSA EIA test. Helicobacter pylori status was determined by the positivity of the CLO test, the histology, or both. RESULTS: Both tests were positive in 26 specimens and negative in 21 patients. Discordant results were obtained in 13 specimens. Discordant results were resolved using the histology biopsy results. The sensitivity of the HpSA test was 88.6% and specificity 93.5%. The positive predictive value (PPV) of the HpSA test was 93.9%, while the negative predictive value (NPV) was 87.8%. The sensitivity of the CLO test was 87.8%, and specificity 92.5%, while PPV of the CLO test was 93.5% and NPV was 86.2%. CONCLUSION: The HpSA test is a useful and reliable test for the diagnosis of H.pylori infection. It is non-invasive, relatively cheap and convenient for the patient. It can be performed in any laboratory performing the enzyme-linked immunoabsorbent assay test. It is particularly suitable for developing countries where facilities for endoscopy are not readily available.

Adult↗

[A systematic review of diagnosis of Helicobacter pylori infection by Helicobacter pylori stool antigen test].

OBJECTIVE: To evaluate the accuracy of Helicobacter pylori (Hp) stool antigen test for diagnosing Hp infection. METHODS: Articles related to diagnosis of Hp infection by Hp stool antigen test, published before March 2004, were retrieved in the databanks such as CBMdisc, CMCC, CNKI, and VIP. Related journals were searched manually. Meta-analysis was performed by SROC curve recommended by Diagnostic and Screening Group of the Cochrane Collaboration Web with the parameters such as sensitivity, specificity, accuracy, predictive values, and likelihood ratio. RESULTS: In total 19 studies including 3123 patients met the inclusion criteria. The sensitivity of Hp stool antigen for the diagnosis of Hp infection was 94% and its specificity was 93%. CONCLUSION: Helicobacter pylori stool antigen examination is a simple, noninvasive and highly accurate method in diagnosis of Hp infection.

Antigens, Bacterial↗

[Changes in serum anti-Helicobacter pylori IgG antibody, pepsinogen I, and pepsinogen II after eradication therapy of Helicobacter pylori].

To investigate the changes in serum anti-Helicobacter pylori IgG antibody (HP Ab), pepsinogen I (PG I), pepsinogen II (PG II), and pepsinogen I/II ratio (PG I/II) after eradication therapy of Helicobacter pylori (HP), we studied 78 patients with HP-positive peptic diseases. They received combination therapy (proton pump inhibitor + amoxicillin: n = 17, proton pump inhibitor + amoxicillin + clarithromycin: n = 61). In the 68 patients in whom HP was eradicated, HP Ab, PG I, and PG II decreased and PG I/II increased significantly after eradication. Especially, the decrease in PG II and the increase in PG I/II were rapid and remarkable, found 2 months after the beginning of eradication therapy, and then continued. On the other hand, in the patients in whom HP was not eradicated, HP Ab and PG I/II did not change significantly, while PG I and PG II temporarily increased at the end of administration of proton pump inhibitor. In conclusion, it seems that the measurement of PG II and PG I/II is useful for the early detection of HP eradication.

Amoxicillin↗

Absence of Helicobacter pylori in dental plaques in Helicobacter pylori positive dyspeptic patients.

To test the validity of reports on detection of Helicobacter pylori in the mouth, samples were obtained simultaneously from the gastric mucosa and dental plaques for culture in 94 patients examined consecutively by endoscopy. Histological examinations and serological tests were also performed. Helicobacter pylori was not found in the mouth of any of the patients including 52 who had culture-positive gastric biopsies. Thus earlier results could not be confirmed, however, other techniques such as the polymerase chain reaction might give different results.

Adult↗

Differentiation of clinical Helicobacter pullorum isolates from related Helicobacter and Campylobacter species.

BACKGROUND: Helicobacter pullorum, first detected in the liver and intestinal contents of poultry, was defined as a new species in 1994. This organism has since been isolated from humans with gastroenteritis. Phenotypic as well as genotypic methods have been used to identify H. pullorum associated with cases of human disease. MATERIALS AND METHODS: Clinical isolates were submitted for identification to the National Laboratory for Enteric Pathogens by Provincial Public Health Laboratories within Canada. Phenotypic characterization was conducted using a variety of growth and biochemical tests including oxidase, catalase, indoxyl acetate, H2S production in triple sugar iron (TSI) agar, antimicrobial susceptibility testing, and fatty acid analysis. Genotypic identification was performed using a polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis of a 1-kb fragment of the Helicobacter 16S rRNA gene. RESULTS: During the last 7 years (1993-1999) a total of 11 isolates of H. pullorum were detected from patients with gastroenteritis for inclusion in this study. Typically, these isolates were oxidase and catalase positive, produced optimal growth at 42 degrees C, and produced H2S in TSI. Of these 11 isolates, 1 showed DNase activity, while another did not produce H2S in TSI, and only 2 showed tolerance to 1% bile. Antimicrobial susceptibility assays indicated that 6 of the 11 strains were resistant to nalidixic acid. The fatty acid profiles of the isolates were similar to each other and provided a distinguishing profile from the other related species. Genetically identical and distinct species-specific restriction fragment-length polymorphism (RFLP) patterns were produced using the restriction enzymes Bsr I and Dde I. CONCLUSION: Phenotypic and genotypic procedures were used to identify H. pullorum. Interspecies phenotypic variability was apparent and supported the use of a polyphasic approach for identification. Similarities to the more prominent human pathogens Campylobacter coli and C. lari were also noted. The use of a combination of phenotypic and, in particular, genotypic markers for H. pullorum should prove valuable both for epidemiological investigations and for the diagnosis of disease related to this emerging human pathogen.

Campylobacter↗

Efficient and non-invasive method for investigating Helicobacter pylori in gravida with hyperemesis gravidarum: Helicobacter pylori stool antigen test.

AIM: To investigate the relationship between Helicobacter pylori infection and severe hyperemesis gravidarum (H. Gravidarum) by using Helicobacter pylori Stool Antigen (HpSA) and other serologic test results. METHODS: Twenty-seven pregnant women with H. Gravidarum and 97 asymptomatic pregnant women of matching gestational age without gastric problems were enrolled in a prospective study. Serum samples collected from cases were investigated in terms of specific antibodies for H. pylori (immunoglobulin-IgG, IgA) and feces samples were investigated for HpSA. Statistical analysis of the data obtained from the groups was made by appropriate chi2 tests. RESULTS: Rate of HpSA positivity in patients with H. Gravidarum was 40.7%, while the same rate was 12.4% in the control group. The difference between the two groups was significant (P = 0.001). Rates of positivity for specific IgG formed against H. pylori in gravida with H. Gravidarum and in the asymptomatic gravida were 85.2% and 73.2%, respectively, and the rates for IgA were 48.1% and 41.2%, respectively. There was no difference between groups in terms of specific Igs formed against H. pylori (P > 0.05). CONCLUSION: The HpSA scan showed a statistically significant relation between H. pylori infection and H. Gravidarum. HpSA test gives more efficient, reliable and realistic results than specific Igs formed against H. pylori in the identification of H. pylori positivity in gravida with H. Gravidarum.

Antigens, Bacterial↗

Properties of the P-type ATPases encoded by the copAP operons of Helicobacter pylori and Helicobacter felis.

The cop operons of Helicobacter pylori and Helicobacter felis were cloned by gene library screening. Both operons contain open reading frames for a P-type ion pump (CopA) with homology to Cd2+ and Cu2+ ATPases and a putative ion binding protein (CopP), the latter representing a CopZ homolog of the copYZAB operon of Enterococcus hirae. The predicted CopA ATPases contained an N-terminal GMXCXXC ion binding motif and a membrane-associated CPC sequence. A synthetic N-terminal peptide of the H. pylori CopA ATPase bound to Cu2+ specifically, and gene disruption mutagenesis of CopA resulted in an enhanced growth sensitivity of H. pylori to Cu2+ but not to other divalent cations. As determined experimentally, H. pylori CopA contains four pairs of transmembrane segments (H1 to H8), with the ATP binding and phosphorylation domains lying between H6 and H7, as found for another putative transition metal pump of H. pylori (K. Melchers, T. Weitzenegger, A. Buhmann, W. Steinhilber, G. Sachs, and K. P. Schäfer, J. Biol. Chem. 271:446-457, 1996). The corresponding transmembrane segments of the H. felis CopA pump were identified by hydrophobicity analysis and via sequence similarity. To define functional domains, similarly oriented regions of the two enzymes were examined for sequence identity. Regions with high degrees of identity included the N-terminal Cu2+ binding domain, the regions of ATP binding and phosphorylation in the energy transduction domain, and a transport domain consisting of the last six transmembrane segments with conserved cysteines in H4, H6, and H7. The data suggest that H. pylori and H. felis employ conserved mechanisms of ATPase-dependent copper resistance.

Adenosine Triphosphatases↗

Comparison of isolates of Helicobacter pylori and Helicobacter mustelae.

On the basis of analysis of protein profiles, isolates of Helicobacter pylori and Helicobacter mustelae were less than 40% similar. Cytotoxin produced by H. pylori was not detected in isolates of H. mustelae. Both bacterial species agglutinated human erythrocytes. These results substantiate a taxonomic difference between H. pylori and H. mustelae.

Bacterial Proteins↗

Attempts to isolate Helicobacter from cattle and survival of Helicobacter pylori in beef products.

This study focused on important factors related to the potential of cattle and beef products to transmit Helicobacter pylori to humans. Mucosal samples were collected from the rumen and abomasum of 105 cattle and were plated on a selective medium to isolate Helicobacter spp.; none of the samples examined contained these bacteria. Studies were also conducted to determine how long H. pylori survives in refrigerated or frozen ground beef; results indicated that the microorganism dies rapidly in ground beef, whether refrigerated or frozen. Packaging in vacuum or air had little effect on survival of the organism. The number of H. pylori decreased in refrigerated samples from 3.3 log10 CFU/g on day 0 to 1.4 log10 CFU/g on day 6. H. pylori died even more rapidly when frozen, decreasing from 3.3 log10 CFU/g on day 0 to 0.5 log10 CFU/g on day 6. Retail beef cuts (n = 20) were also examined for the presence of H. pylori by direct plating on a selective medium and by incubation in an enriched broth followed by plating on a selective medium. None of the retail samples contained H. pylori. This research suggests that transmission of H. pylori from beef and beef products is not a primary factor in the high prevalence of this bacterium in humans.

Animals↗