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Treatment of Helicobacter pylori: an overview.

Helicobacter pylori is recognized to be a serious pathogen, but there is still controversy as to who should be treated. There is consensus for treatment of Helicobacter-positive peptic ulcer and B-cell lymphoma. Lymphocytic gastritis and giant-fold gastritis (Ménétrièr's disease) may also respond to treatment. Patients with func-tional dyspepsia have a 20% placebo response with a 5-10% 'eradication' response, results not dissimilar from empirical treatment with a proton pump inhibitor. A 'test and treat' policy for patients with uninvesti-gated dyspepsia remains controversial. Some have suggested that eradication may increase the risk of GERD, or predispose to adenocarcinoma at the gastro-oesophageal junction. However, PPI treatment without Helicobacter eradication induces greater inflammation in the gastric corpus, the phenotype associated with non-cardia gastric cancer. A minority believe that Helicobacter should be eradicated in all individuals. When choosing treatment it is logical to start with a combination of antibiotics that, in the event of failure, will allow a second combination to be used without overlap.

Helicobacter Infections↗

Review article: Helicobacter pylori vaccines-the current status.

In this review, we take a look at the current status in the development of a vaccine against the human pathogenic bacterium, Helicobacter pylori, a major aetiological factor in peptic ulcer disease and gastric adenocarcinoma. Various animal models are now in use from mice infected with H. pylori, through gnotobiotic pigs and primates to ferrets naturally infected with their own Helicobacter, H. mustelae. A significant problem remains the requirement for a suitable mucosal adjuvant. Detoxification or the use of low doses of adjuvants already available may provide a solution and new immune stimulating compounds have been tested with some success. New approaches include the delivery of Helicobacter antigens by DNA immunization, microparticles or live vectors such as attenuated salmonella and the examination of alternative routes of vaccine administration. The phenomenon of post-immunization gastritis and improvements in vaccine efficacy are also discussed. A major area of interest is the mechanism by which immunization actually influences Helicobacter colonization. This remains a mystery: antibodies appear to be unimportant whereas CD4+ T-cells essential. Finally, a viewpoint is given on whom should be immunized when a final vaccine becomes available.

Animals↗

Helicobacter pylori infection among Japanese children.

BACKGROUND: In Japan, there are few reports describing Helicobacter pylori infection among young children. The aim of the present study was to identify risk factors associated with H. pylori in school-aged children. METHODS: Subjects were first-grade students of three elementary schools (n = 310) and second-grade students of a junior high school (n = 300). Personal information, such as student's medical history, parent's history, family size, sibshipsize and household pets, was collected from guardians using a questionnaire. Saliva samples and personal information were collected twice (1995 and 1996). By using the saliva samples, H. pylori IgG antibody was measured using a commercial kit. To analyze the risk factors for H. pylori infection, sex- and age-adjusted odds ratios (OR) were calculated using a multiple logistic model. RESULTS: Among the children, factors related to Helicobacter antibody in saliva included spending a longer period of time in a nursery school or kindergarten (OR = 4.0) and a maternal history of stomach disease (OR = 2.8). Birth order (OR = 2.2), sleeping situation (OR = 2.3) and sibshipsize (OR = 1.6) were not factors that were significantly related to Helicobacter antibody in the saliva. Chewing food for the infant, family size, rooms in the household, sharing a bedroom during childhood, pets, a past history and a paternal history were not related to positivity. CONCLUSIONS: The results indicate that transmission is person-to-person, mainly through close contact with other children and intrafamilial infection. Helicobacter pylori infection seems to occur frequently early in life, probably before 6 years of age.

Adolescent↗

Guidelines in the management of Helicobacter pylori infection in Japan.

BACKGROUND: In preparation of the approval of Helicobacter pylori therapy by the Japanese national health system, the board of directors of the Japanese Society for Helicobacter Research decided to prepare guidelines on the diagnosis and treatment of H. pylori infection for physicians in routine medical practice. METHODS: A guidelines preparation committee was formed and six meetings were held. Then, in December 1999, a consensus meeting was held in Kobe to obtain the opinions of general practitioners as well as experts from Europe, North America, and Asia. RESULTS: Helicobacter pylori eradication therapy is recommended in gastric or duodenal ulcer patients. Helicobacter pylori eradication therapy is recommended or gastric mucosa associated lymphoid tissue (MALT) lymphoma but it should be done at specialist institutions. The significance of H. pylori eradication therapy is still under evaluation in patients with hyperplastic polyps, chronic atrophic gastritis, non-ulcer dyspepsia and in patients after endoscopic mucosal resection of gastric cancer and after gastrectomy for gastric cancer. When diagnosing H. pylori infection, at least one of the tests requiring endoscopic biopsy (e.g. rapid urease test, histology, or culture) and tests not requiring biopsy (e.g. measurement of H. pylori antibody or urea breath test) should be used. Multiple tests are recommended to increase the accuracy. The drugs of first choice currently covered by the national health insurance system in Japan are: lansoprazole (30 mg) 1 capsule twice daily, amoxicillin (250 mg) 3 capsules twice daily, and clarithromycin (200 mg) 1-2 tablets twice daily. These three drugs should be administered after breakfast and dinner for 1 week. CONCLUSION: These guidelines are intended for utilization in routine medical practice after the Japanese national health system begins to cover the management of H. pylori infection.

Amoxicillin↗

High anti-Helicobacter pylori antibody seropositivity associated with the combination of IL-8-251TT and IL-10-819TT genotypes.

BACKGROUND: Helicobacter pylori induces inflammation of gastric mucosa regulated by several interleukins. This study examined associations between anti-Helicobacter pylori immunoglobulin G antibody seropositivity and functional polymorphisms of interleukin-8 T-251 A and interleukin-10 T-819C. MATERIALS AND METHODS: The subjects were 454 health check-up examinees (126 males and 328 females) without a history of cancer, aged 35-85 years, residing in Nagoya, Japan. After written informed consent was obtained individually, residual blood was anonymously applied for anti-Helicobacter pylori immunoglobulin G antibody testing and genotyping by the polymerase chain reaction with confronting two-pair primers. RESULTS: The genotype frequency of interleukin-8 T-251 A was 52.2% for TT, 39.5% for TA, and 8.3% for AA, and that of interleukin-10 T-819C was 49.5% for TT, 39.9% for TC and 10.6% for CC. Although the differences in the positive rates among the genotypes were not marked, 115 individuals with interleukin-8-251TT (low expression genotype) and interleukin-10-819TT (high expression genotype) had a higher rate (63.5%) than the others (52.0%). Relative to the combination of interleukin-8-251TT and interleukin-10-819TT, the sex-age-adjusted odds ratio for those with the other combinations was 0.62 (95% confidence interval, 0.39-0.98). The adjusted odds ratio among 65 current smokers was 0.13 (0.03-0.61). CONCLUSIONS: The observed association suggests that individuals with interleukin-8-251TT and interleukin-10-819TT, a combination presumably causing mild inflammation, have a higher probability of the continuing Helicobacter pylori infection, especially among current smokers.

Adult↗

[Predictive value of latex agglutination on Helicobacter pylori in children with recurrent abdominal pain].

In a prospective investigation, a rapid latex test for Helicobacter pylori in the serum (Pyloriset) was carried out in 39 patients with recurrent abdominal pain aged from six to 15 years. The test was positive in 19 patients. All of these children were subjected to gastroduodenoscopy. Seven cases showed a Helicobacter-associated chronic active antrum gastritis, whereas in the remaining 12 children gastritis not induced by Helicobacter or normal mucosa was found. Of the 20 Pyloriset-negative patients, only five could be biopsied. One of these showed a Helicobacter pylori-induced antrum gastritis. The latex test investigated had a positive predictive value which was too low (37%) to make it helpful in deciding for or against gastroduodenoscopy and the general anesthesia mostly associated with this.

Abdominal Pain↗

[The modified 13C-urea breath test in the diagnosis of Helicobacter pylori colonization of the gastric mucosa].

The value of a modified 13C-urea breath test for the detection of Helicobacter pylori was analysed in a prospective study of 50 consecutive patients (28 women, 22 men, aged 20-90 years) with unknown Helicobacter pylori status about to undergo upper intestinal endoscopy. Four biopsies each were obtained in each patient from the antrum and the body of the stomach and examined for Helicobacter pylori infection of the gastric mucosa histologically (haematoxylin-eosin and Giemsa stain), with the rapid urease test and by culture. The patients then underwent a modified 13C-urea breath test. Results were positive histologically and(or) by culture in 29 patients, while the breath test was positive in 28 (sensitivity 96.3%). The breath test was falsely positive in two (specificity 91.3%). The biopsy urease test had a sensitivity of 96.3% with a 100% specificity. These results demonstrate that the modified 13C-urea breath test is a simple and accurate way of demonstrating Helicobacter pylori infection, equal in diagnostic value to the biopsy urease test.

Adult↗

The GroES homolog of Helicobacter pylori confers protective immunity against mucosal infection in mice.

Helicobacter pylori is an important etiologic agent of gastroduodenal disease. In common with other organisms, H. pylori bacteria express heat shock proteins that share homologies with the GroES-GroEL class of proteins from Escherichia coli. We have assessed the heat shock proteins of H. pylori as potential protective antigens in a murine model of gastric Helicobacter infection. Orogastric immunization of mice with recombinant H. pylori GroES- and GroEL-like proteins protected 80% (n = 20) and 70% (n = 10) of animals, respectively, from a challenge dose of 10(4) Helicobacter felis bacteria (compared to control mice, P = 0.0042 and P = 0.0904, respectively). All mice (n = 19) that were immunized with a dual antigen preparation, consisting of H. pylori GroES-like protein and the B subunit of H. pylori urease, were protected against infection. This represented a level of protection equivalent to that provided by a sonicated Helicobacter extract (P = 0.955). Antibodies directed against the recombinant H. pylori antigens were predominantly of the IgG1 class, suggesting that a type 2 T-helper cell response was involved in protection. This work reports a protein belonging to the GroES class of heat shock proteins that was shown to induce protective immunity. In conclusion, GroES-like and urease B-subunit proteins have been identified as potential components of a future H. pylori subunit vaccine.

Animals↗

Helicobacter pylori in ectopic gastric mucosa in Meckel's diverticulum.

We report a case of a 25-year-old man who presented with a large rectal bleed and positive Meckel's scan followed by surgical excision of a Meckel's diverticulum. The diverticulum was lined by gastric body type mucosa showing evidence of active chronic gastritis associated with the presence of Helicobacter pylori organisms, these being identified immunohistochemically with a specific polyclonal antibody. We have reviewed another 21 cases of Meckel's diverticula removed at St Vincent's Hospital between 1984 and 1997: in nine of these cases the diverticulum was lined by ectopic gastric body type mucosa and in one of these there was an active chronic gastritis associated with Helicobacter pylori. There has been considerable controversy regarding both the presence and significance of Helicobacter organisms in Meckel's diverticula. This is the first study to use immunohistochemistry specifically to identify Helicobacter pylori within two cases of Meckel's diverticula. Both cases demonstrated an active chronic gastritis present within the gastric body type mucosa, thus suggesting that the organisms play a pathogenic role.

Adult↗

Helicobacter pylori-associated gastritis and the ascorbic acid concentration in gastric juice.

Patients infected with Helicobacter pylori have abnormally low ascorbic acid concentration in gastric juice. Low vitamin C intake and Helicobacter pylori infection have been related to an increased risk of gastric carcinoma. This report examines the association between ascorbic acid and Helicobacter pylori in patients referred for upper gastrointestinal endoscopy. Elevated gastric pH and the damage to the gastric surface epithelium were inversely associated with the ascorbic acid concentration in gastric juice. We postulate that these two factors mediate the ascorbic acid-decreasing effect of Helicobacter pylori. Patients with nonpremalignant conditions (normal gastric histology, diffuse antral gastritis, or duodenal ulcer) had lower gastric pH, less damage to the gastric epithelium, and higher levels of ascorbic acid in gastric juice than patients with atrophic gastritis, intestinal metaplasia, or dysplasia.

Adolescent↗

Severe inflammation and reduced bacteria load in murine helicobacter infection caused by lack of phagocyte oxidase activity.

The vaccine-induced immune mechanisms that protect against Helicobacter pylori infection in the mouse model have not been identified. This study investigated the contribution of reactive oxygen and nitrogen intermediates to Helicobacter pathogenesis and immunity. Mice deficient in nicotinamide-adenine dinucleotide phosphate oxidase activity (gp91(phox-/-)), nitric oxide synthase activity (NOS2(-/-)), or both (gp91(phox-/-)/NOS2(-/-)) were infected with Helicobacter organisms and evaluated for inflammation and bacteria load. Infection of all 3 transgenic strains resulted in significantly more inflammation than found in infected C57BL/6 wild-type mice. However, only gp91(phox-/-) and gp91(phox-/-)/NOS2(-/-) mice had significantly reduced numbers of infected gastric glands. Intranasal immunization of NOS2(-/-) or gp91(phox-/-)/NOS2(-/-) mice against H. pylori resulted in protective immunity comparable to that seen in C57BL/6 control mice. Therefore, reactive oxygen species may play a role in limiting the inflammatory response associated with H. pylori infection of the gastric mucosa but may also limit the host's ability to eradicate Helicobacter organisms.

Animals↗

Gastric colonization of the ferret with Helicobacter species: natural and experimental infections.

Helicobacter mustelae, isolated from the stomachs of adult ferrets, appears to have a world-wide distribution. Ferrets are colonized with H. mustelae at a young age, usually 5-6 weeks; in our experience 100% of adult ferrets are colonized in both the antrum and the fundus. Gastric infection correlates with elevation of serum IgG antibodies to H. mustelae. In the oxyntic mucosa the presence of superficial gastritis coincides closely with the presence of H. mustelae. In the distal antrum the organism is associated with chronic inflammation occupying the full thickness of the mucosa. In addition to lesions seen in the distal antrum, focal glandular atrophy and regeneration are noted in the proximal antrum and transitional mucosa. Antibiotics used to eradicate Helicobacter pylori in humans are also effective in eliminating H. mustelae from ferrets. H. mustelae-free ferrets do not become colonized with H. pylori when challenged orally; however, sparse colonization follows oral inoculation with a related gastric organism, "Helicobacter felis." Controlled studies of the pathophysiology of gastroduodenal disease induced by Helicobacter species can be performed in H. mustelae-infected ferrets and their H. mustelae-negative counterparts.

Age Factors↗

Relation of adult lifestyle and socioeconomic factors to the prevalence of Helicobacter pylori infection.

INTRODUCTION: The influence of adult socioeconomic status, co-habitation, gender, smoking, coffee and alcohol intake on risk of Helicobacter pylori infection is uncertain. METHODS: Subjects between aged 40-49 years were randomly invited to attend their local primary care centre. Participants were interviewed by a researcher on smoking, coffee and alcohol intake, history of living with a partner, present and childhood socioeconomic conditions. Helicobacter pylori status was determined by 13C-urea breath test. RESULTS: In all, 32 929 subjects were invited, 8429 (26%) were eligible and 2327 (27.6%) were H. pylori positive. Helicobacter pylori infection was more common in men and this association remained after controlling for childhood and adult risk factors in a logistic regression model (odds ratio [OR] = 1.15; 95% CI: 1.03-1.29). Living with a partner was also an independent risk factor for infection (OR = 1.30; 95% CI: 1.01-1.67), particularly in partners of lower social class (social class IV and V-OR = 1.47; 95% CI: 1.19-1.81, compared with social class I and II). Helicobacter pylori infection was more common in lower social class groups (I and II-22% infected, III-29% infected, IV and V-38% infected) and there was a significant increase in risk of infection in manual workers compared with non-manual workers after controlling for other risk factors (OR = 1.18; 95% CI: 1.03-1.34). Alcohol and coffee intake were not independent risk factors for infection and smoking was only a risk factor in those smoking >35 cigarettes a day. CONCLUSIONS: Male gender, living with a partner and poor adult socioeconomic conditions are associated with increased risk of H. pylori infection.

Adult↗

Alcohol dehydrogenase activities in the human gastric mucosa: effects of Helicobacter pylori infection, sex, age, and the part of the stomach.

BACKGROUND: Human gastric mucosa contains three alcohol dehydrogenase (ADH) isozymes (classes I, III, and IV). Various factors such as Helicobacter pylori infection, sex, age, and the part of the stomach involved have been suggested to affect alcohol dehydrogenase activities, although these views are controversial. In this study, these unsettled issues were reexamined. METHODS: Activities of class I and IV ADHs were evaluated in the cytosolic fraction of human gastric mucosa samples by reduction of their preferred substrates, namely acetaldehyde and m-nitrobenzaldehyde, and activities of class III were evaluated by oxidation of its preferred substrate, formaldehyde. Then, effects of Helicobacter pylori infection, sex, age, and the part of the stomach involved were examined. RESULTS: Class I, III, and IV ADH activities were 17.5 +/- 8.4, 4.2 +/- 2.5, and 8.9 +/- 3.9 nmol of nicotinamide adenine dinucleotide oxidation per minute per milligram of protein, respectively, for the entire population. Helicobacter pylori infection significantly reduced class I and IV ADH activities but did not affect activity of class III. In the samples without Helicobacter pylori infection and severe gastritis, sex did not affect class I, III, or IV ADH activities. In the same series, class IV ADH activity significantly decreased with age (p = 0.006), whereas no correlation was found between age and ADH activity of class I and III ADHs. The level of class IV ADH activity was significantly higher in the upper body than in the lower regions, whereas no such heterogeneity was observed in class I and III ADH. CONCLUSIONS: Various factors affect human gastric ADH activities, such that careful interpretation of their significance is necessary.

Adult↗

Helicobacter pylori prevalence in patients with diabetes and its relationship to dyspeptic symptoms.

As available data on Helicobacter pylori infection in patients with diabetes are scattered and discordant, we evaluated the prevalence of H. pylori and its relationship to dyspeptic symptoms in adult patients with diabetes and subjects with dyspepsia. H. pylori infection (evaluated using the 13C urea breath test) and dyspeptic symptoms (nausea, bloating, and epigastric distress) were investigated in 71 consecutive diabetic outpatients; the presence of gross lesions, histologic gastritis, and Helicobacter was verified in the patients with a positive urea test who agreed to undergo upper gastrointestinal tract endoscopy. Seventy-one age- and gender-matched subjects with dyspepsia were used as controls. Helicobacter pylori infection was detected in 49 (69%) patients with diabetes and in 33 (46%) subject with dyspepsia (p = 0.007). Helicobacter pylori was present in 27 (77%) of 35 patients with diabetes with dyspeptic symptoms and in 22 (61%) of 36 patients without dyspeptic symptoms. Endoscopy revealed peptic ulcers in 13 of 23 patients; H. pylori infection was histologically confirmed in the gastric antrum of all patients with diabetes, and in the body of the stomach in 74%. The significantly higher prevalence of H. pylori infection in the patients with diabetes may partially explain their dyspeptic symptoms. The high prevalence of H. pylori infection, esophagitis, and peptic ulcers found in our patients with diabetes (with or without dyspepsia) suggests that this population should be considered "at risk" for H. pylori infection and suitable candidates for treatment.

Diabetes Complications↗

Persisting Helicobacter antibodies in Finnish children and adolescents between two and twenty years of age.

BACKGROUND: Helicobacter pylori is an important gastric pathogen usually acquired in childhood. The presumed lifelong progression of H. pylori infection has recently been called into question in some longitudinal studies on children. In this follow-up study the prevalence and persistence of H. pylori antibodies in Finnish children and adolescents from three communities was determined. METHODS: We measured H. pylori antibodies in follow-up serum samples of 337 Finnish children who participated in a measles-mumps-rubella vaccine study started in 1982. All available samples collected in 1983, 1987 and 1995 were studied first; additional serum samples collected yearly were studied from children who became seropositive during the follow-up period. RESULTS: The overall prevalence of H. pylori antibodies was 5.6%. About two-thirds of the Helicobacter infections were acquired before the age of 7 years; of the remaining one-third the time of seroconversion varied between 7 and 19 years. No seroreverters were found. There were no statistically significant differences in the seroprevalence of H. pylori antibodies in the three communities studied. CONCLUSIONS: The prevalence of H. pylori antibodies in Finnish children studied was low. Although the majority of new infections were found in children younger than 7 years of age, new Helicobacter infections were acquired throughout childhood and adolescence. Once acquired H. pylori infection, as verified by Helicobacter antibodies, persisted.

Adolescent↗

Possible role of Helicobacter pylori in the etiopathogenesis of chronic otitis media.

OBJECTIVE: To investigate a possible contribution from Helicobacter pylori to the etiopathogenesis of chronic otitis media. STUDY DESIGN: Prospective clinical trial. METHODS: Tympanomastoidectomy, radical mastoidectomy, and modified radical mastoidectomy procedures were performed according to the pathology of ear disease. Biopsy specimens were taken from middle ear, mastoid antrum, and tympanic orifice of eustachian tube. Helicobacter pylori DNA was extracted from these biopsy specimens by using nested polymerase chain reaction. RESULTS: Helicobacter pylori DNA was detected in 3 (7.9%) of 38 chronic otitis media patients. CONCLUSION: Even though it is possible to detect Helicobacter pylori in middle ear cleft in chronic otitis media, its role in the etiopathogenesis of the issue is controversial.

Adolescent↗

Profiling of bacterial flora in gastric biopsies from patients with Helicobacter pylori-associated gastritis and histologically normal control individuals by temperature gradient gel electrophoresis and 16S rDNA sequence analysis.

The aim of this study was to establish bacterial profiles in gastric biopsy specimens from patients with Helicobacter pylori-associated gastritis by means of temporal temperature gradient gel electrophoresis (TTGE) of PCR-amplified 16S rDNA fragments. Specimens from eight patients with asymptomatic gastritis and five histologically normal controls revealed a Helicobacter-specific band in the TTGE profile with increased amounts of Helicobacter-specific DNA in the biopsies from most of the gastritis patients. DNA from other genera including Enterococcus, Pseudomonas, Streptococcus, Staphylococcus and Stomatococcus was also found in the stomach. In the absence of gastric inflammation, Helicobacter spp. appeared to be part of a complex, presumably indigenous microbial flora found in the biopsy specimens from the stomach.

Biopsy↗