Günter Bode

The coccoid forms of Helicobacter pylori. Criteria for their viability.

The fact that Helicobacter pylori can revert to a coccoid form has stimulated speculation about its role in transmission and as a possible cause of reinfection in duodenal ulcer disease. Bismuth subcitrate (32 micrograms/ml), bismuth subsalicylate (64 micrograms/ml), amoxicillin (0.05 micrograms/ml) and erythromycin (4 micrograms/ml) inhibited the growth of H. pylori and stimulated the formation of basically respiring but non-culturable coccoid structures. The presence of polyphosphates as energy and phosphorus source permits a certain level of endogenous metabolism to preserve RNA and DNA, as well as structural components like cell wall, cell membrane and cytoplasma for at least 3 months. However, the applied standard laboratory methods were insufficient for regrowth of H. pylori out of the coccoid form.

Relation of smoking and alcohol and coffee consumption to active Helicobacter pylori infection: cross sectional study.

Abstract Objective: To assess the relation of smoking and alcohol and coffee consumption to active Helicobacter pylori infection. Design: Cross sectional study of patients attending a general practitioner. Active H pylori infection was measured by the 13C-urea breath test and detailed quantitative information on smoking and on alcohol and coffee consumption was obtained by a standardised self administered questionnaire. Setting: One general practice in Germany. Subjects: 447 patients aged 15–79 who had not had peptic ulcer disease or treatment for H pylori infection. Main outcome measures: Prevalence of H pylori infection according to smoking and alcohol and coffee consumption. Results: Overall prevalence of infection was 21% (94/447). There was no significant relation between smoking and active H pylori infection. Alcohol consumption showed a negative dose-response relation and coffee consumption a positive dose-response relation with active infection. After adjustment for potential confounders, the odds ratios for patients who drank ≥3 cups of coffee per day compared with those who did not drink coffee were 1.49 (0.71 to 3.12) and 2.49 (1.23 to 5.03), respectively (P value for trend 0.007). Conclusion: These results suggest a protective effect of alcohol consumption against active infection with H pylori and an opposite effect of coffee consumption. Key messages Although H pylori infection is commonly acquired during childhood, active infection may be acquired and eliminated throughout adulthood This study of patients in a general practice found no significant relation between smoking and active H pylori infection Drinking alcohol seemed to protect against active H pylori infection This protective effect was dose dependent and similar for beer and wine Drinking coffee was associated with an increased prevalence of active H pylori infection The protective effect of alcohol on active H pylori infection may be related to its antimicrobial effects

Pathogenetic Implications of Ultrastructural Findings in Campylobacter pylori Related Gastroduodenal Disease

There is now substantial evidence that Campylobacter pylori (Cp) is able to colonize the gastroduodenal mucosa and is responsible for active chronic gastritis, its role in duodenitis, gastric ulceration and duodenal ulceration is still under debate. Cp has a lot of characteristics which are prerequisites for a pathogen: the typical S-shape, the corkscrew-like movement and the powerful urease and protease enzymes. These features allow a rapid movement through the mucous layer to permit access to the apical membranes of the surface mucous cells. There they adhere directly to the membranes and induce several ultrastructural alterations: degeneration of microvilli, depletion of mucous granules and an increase in sialic-acid rich glycoproteins in the apical part of the cytoplasma. Cp weakens the tight-junction complex and is found between the cells and sometimes intracellularly. Cp is phagocytized by invading polymorphonuclear leukocytes and causes an intense inflammatory response. These observations clearly demonstrate pathological alterations which in the cellular level induced by Cp with the result of a disrupted mucosal barrier of the stomach and the duodenum.

Helicobacter pylori infection among offspring of patients with stomach cancer

BACKGROUND & AIMS A positive family history is associated with an increased risk of stomach cancer. We compared the prevalence of Helicobacter pylori infection, a known risk factor for stomach cancer, between subjects with and without parental history of stomach cancer to evaluate a potential role of H. pylori infection in familial aggregation of stomach cancer. METHODS A total of 1351 men and women aged 30-74 years who participated in the German Health and Nutrition Survey conducted in the western part of Germany in 1987-1988 were included in the study. Detailed information on sociodemographic factors, nutritional factors, and parental history of cancer was obtained by standardized interviews. Serum samples were analyzed for immunoglobulin G antibodies against H. pylori by enzyme-linked immunosorbent assay. RESULTS The prevalence of H. pylori infection was much higher (69%) among subjects with a parental history of stomach cancer than among other subjects (44%). This association persisted after control for potential confounders by multiple logistic regression (adjusted odds ratio, 2.7; 95% confidence interval, 1.3-5.9), and was particularly strong among subjects below age 55 (adjusted odds ratio, 5.1; 95% confidence interval, 1.6-16.1). CONCLUSIONS These results suggest that familial aggregation of stomach cancer may be explained at least partly by familial clustering of H. pylori infection.

Acquisition of Helicobacter pylori infection in a high-risk population occurs within the first 2 years of life

OBJECTIVE To elucidate age at acquisition of Helicobacter pylori infection, we conducted a study in a population of children known to be at high risk for H pylori infection. METHOD Children with no symptoms who were of Turkish nationality and living in the city of Ulm, Germany, and nearby communities and on whom routine health screening examinations were performed at age 1 year (56 children), 2 years (55 children), or 4 years (69 children) were included in this cross-sectional study. Stool samples were collected by the parents and sent by mail to the University of Ulm. An H pylori antigen enzyme immunoassay for the detection of H pylori in stool was used to define current infection status. Sensitivity was 84.6% (95% CI 63. 1% to 94.7%) and specificity 97.7% (95% CI 86.2% to 99.9%) in the 4-year-old children in whom the stool test was compared with the (13)C-urea breath test. RESULTS The prevalence of infection was 8. 9% (95% CI 3.0% to 19.6%) among the 1-year-old children, 36.4% (95% CI 23.8% to 50.4%) among the 2-year-old children, and 31.9% (95% CI 21.2% to 44.2%) among the 4-year-old children. CONCLUSION In this high-risk group of Turkish children living in Germany, H pylori acquisition seems to occur mainly between the first and the second years of life. Therefore preventive measures such as vaccination necessitate application early in infancy. Further studies are now required to ascertain the mechanisms for transmission in this age group.

Helicobacter pylori infection and serum ferritin: A population-based study among 1806 adults in Germany.

OBJECTIVE:Helicobacter pylori may possibly affect the iron metabolism by occult bleeding, impaired absorption of nonhem iron, and by scavenging hem iron or ferritin, as some studies have suggested. The aim of this study was to analyze the association between H. pylori infection and serum ferritin, a marker of the body iron stores. In this analysis, we paid particular attention to the role of dietary iron intake and CagA, an established virulence factor of the agent.METHODS:The analysis is based on a cross-sectional national health and nutrition survey among healthy people in Germany conducted in 1987/1988. The examination included a detailed questionnaire on medical history and lifestyle factors, a 7-day food record, and blood samples. Infection with H. pylori was measured serologically by ELISA and Westernblot.RESULTS:In total, 39.2% of 1806 persons aged 18 to 89 yr included in the study were H. pylori positive, of whom 57.6% had an infection with a CagA-positive H. pylori strain. Age- and sex-adjusted geometric mean of ferritin was 54.5 μg/dl among H. pylori-infected compared with 63.8 μg/dl among uninfected persons. A multiple linear regression model with log-transformed serum ferritin concentration as dependent variable and H. pylori infection and several potential confounding factors as independent variable was fitted. In this model, H. pylori infection was associated with a 17.0% decrease of the serum ferritin concentration (95% CI = 9.8–23.6). The association between H. pylori infection and serum ferritin levels did not vary by gender, age, and iron intake, and it was similar for CagA-positive and CagA-negative H. pylori infections.CONCLUSIONS:The decreased serum ferritin concentration among subjects infected with H. pylori might be induced by the uptake of ferritin in the stomach by H. pylori. Possible health implications of H. pylori-induced low ferritin levels warrant further investigation.

Recurrent abdominal pain in children Evidence from a population-based study that social and familial factors play a major role but not Helicobacter pylori infection

OBJECTIVE To analyze the relationship between social and familial factors, Helicobacter pylori infection and recurrent abdominal pain (RAP) in children in a population-based cross-sectional study among 1221 preschool children aged 5-8 years. METHODS H. pylori infection status was determined by 13C-urea breath test (13C-UBT) and information on medical history of the child and on RAP as well as on family demographics was obtained by a standardized questionnaire. RESULTS Overall, 129 children (11.3%) were infected with H. pylori and 29 children were identified as having RAP within the past 3 months (2.5%). Analysis by multiple logistic regression demonstrated a clear relationship of RAP with living in a single parent household [odds ratio (OR) 2.9, 95% confidence interval (95% CI) 1.2-6.7], with parental history of peptic ulcer (OR 3.7, 95% CI 1.3-10.4) and with parental history of nonulcer gastrointestinal disorders (OR 5.3, 95% CI 2.1-13.2). By contrast, there was a nonsignificant relation between H. pylori infection and occurrence of RAP (OR 1.6, 95% CI 0.5-5.5). CONCLUSION Social and familial factors play a major role but not H. pylori infection in RAP.

Inverse Relationship between Gastric Colonization of Helicobacter pylori and Diarrheal Illnesses in Children: Results of a Population-Based Cross-Sectional Study

It has been suggested that carriage of Helicobacter pylori may protect against infections by exogenous intestinal pathogens. An analysis was done of all children who were screened for school fitness during 1996-1998 in Ulm, Germany, to compare rates of diarrheal illnesses in H. pylori-positive and H. pylori-negative children. Of 2477 5-8-year-old children studied, 304 (12.3%) were H. pylori-positive by carbon 13-labeled urea breath test. For H. pylori-positive children, diarrhea within the prior 3 months was less often reported than for H. pylori-negative children (54.3% vs. 76.1%; P<.001, adjusted for nationality). Compared with H. pylori-negative children, the odds ratio (OR) for the occurrence of diarrhea within the prior 3 months was 0.37 (95% confidence interval [CI], 0.28-0.49) for H. pylori-positive children; after adjustment for covariates, the OR was 0.56 (95% CI, 0.42-0.76). These data support the hypothesis that H. pylori colonization may protect against diarrheagenic gastrointestinal infections.

Structural, functional and mutational analysis of the pfr gene encoding a ferritin from Helicobacter pylori

The function of the pfr gene encoding the ferritin from Helicobacter pylori was investigated using the Fur titration assay (FURTA) in Escherichia coli, and by characterization of a pfr-deficient mutant strain of H. pylori. Nucleotide sequence analysis revealed that the pfr region is conserved among strains (> 95% nucleotide identity). Two transcriptional start sites, at least one of them preceded by a sigma 70-dependent promoter, were identified. Provision of the H. pylori pfr gene on a multicopy plasmid resulted in reversal of the Fur-mediated repression of the fhuF gene in E. coli, thus enabling the use of the FURTA for cloning of the ferritin gene. Inactivation of the pfr gene, either by insertion of a resistance cassette or by deletion of the up- and downstream segments, abolished this function. Immunoblot analysis with a Pfr-specific antiserum detected the Pfr protein in H. pylori and in E. coli carrying the pfr gene on a plasmid. Pfr-deficient mutants of H. pylori were generated by marker-exchange mutagenesis. These were more susceptible than the parental strain to killing by various metal ions including irons, copper and manganese, whereas conditions of oxidative stress or iron deprivation were not discriminative. Analysis by element-specific electron microscopy revealed that growth of H. pylori in the presence of iron induces the formation of two kinds of cytoplasmic aggregates: large vacuole-like bodies and smaller granules containing iron in association with oxygen or phosphorus. Neither of these structures was detected in the pfr-deficient mutant strain. Furthermore, the ferritin accumulated under iron overload and the pfr-deficient mutant strains lacked expression of a 12 kDa protein which was negatively regulated by iron in the parental strain. The results indicate that the nonhaem-iron ferritin is involved in the formation of iron-containing subcellular structures and contributes to metal resistance of H. pylori. Further evidence for an interaction of ferritin with iron-dependent regulation mechanisms is provided.

Helicobacter pylori in dental plaque: a comparison of different PCR primer sets.

This study was designed to compare differentprimer sets for PCR analysis of H. pylori in the sameseries of 40 dental plaque samples. Three pairs ofprimers, HPU1/HPU2, HP1/HP2, and EHC-U/EHC-L, directed to the urease A gene, 16S rRNA gene, or 860-bpDNA of H. pylori, respectively, were used. Our resultsdemonstrate that EHC-L/EHC-U were moRespecific andsensitive for H. pylori added to saliva or dental plaque than HPU1/HPU2 and HP1/HP2. Thedetection rates for H. pylori DNA in dental plaquesamples from randomly selected adult patients from theDental Clinic of the University of Ulm were 26.5% (9/34) for HPU1/HPU2, 78.9% (30/38) for HP1/HP2, and100% (40/40) for EHC-U/EHC-L (P < 0.001). Nested PCRusing primers directed to the 860-bp DNA of H. pylorifurThe r confirmed the presence of H. pylori DNA (40/40) in all these samples. Our resultsindicate that primers EHC-U/EHC-L are to be recommendedfor PCR detection of H. pylori in the oralcavity.