A. van der Ende

Effect of Helicobacter pylori eradication on gastritis in relation to cagA: A prospective 1-year follow-up study

BACKGROUND & AIMS Whether Helicobacter pylori eradication resolves intestinal metaplasia and atrophy and whether infection with cagA+ H. pylori is related to a specific clinical outcome are not known. The aim of this study was to investigate the role of H. pylori eradication on the course of intestinal metaplasia (IM) and atrophy in relation to cagA. METHODS In a large prospective study, the cagA status of H. pylori isolated from consecutive dyspeptic patients was related to clinical outcome before and 1 year after successful eradication of H. pylori. At pretreatment and 4-6 weeks and on average 1 year after eradication therapy, the degree of gastritis and the status of H. pylori were assessed by culture and histopathology. RESULTS Specimens of cagA+ H. pylori were recovered from 122 of 155 (79%) patients infected with H. pylori. Pretreatment degrees of gastritis activity, superficial epithelial damage, IM, and atrophy were significantly greater in patients infected with cagA+ H. pylori (P < 0.001). After successful eradication of H. pylori, a significant improvement of activity of gastritis and superficial epithelial damage occurred (P < 0.001), but the degree of IM and atrophy did not change, irrespective of the cagA status. CONCLUSIONS The usefulness of H. pylori eradication to revert precancerous lesions such as IM and atrophy after 1-year follow-up is questionable.

Evaluation of a novel monoclonal enzyme immunoassay for detection of Helicobacter pylori antigen in stool from children

Background: Reliable non-invasive methods for detection of Helicobacter pylori infection are required to investigate the incidence, transmission, and clearance of infection in childhood. Aim: To evaluate a new monoclonal enzyme immunoassay (EIA) (FemtoLab H pylori Cnx) for detection of H pylori antigen in stool in a large cohort of children compared with invasive diagnostic methods and the 13C urea breath test. Patients and methods: A total of 302 symptomatic previously untreated children (aged 0.5–18.7 years; 148 girls) were recruited at three centres. H pylori status was defined by results of culture, histology, the rapid urease test, and the 13C urea breath test. Stool samples were investigated locally by the EIA using two different production lots. According to the manufacturer’s recommendations, an optical density (OD) of 0.150 was used as a cut off value. Results: OD values clearly differentiated between the 92 H pylori infected and the 210 non-infected children (median (5th–95th percentiles) 2.729 (0.232–>4.000) v 0.021 (0.009–0.075)). Only two false positive and two false negative results occurred, giving a sensitivity, specificity, positive predictive value, and negative predictive value of 98%, 99%, 98%, and 99%, respectively. No significant relation was found between age and OD values in infected or non-infected children. Conclusions: The monoclonal stool antigen EIA was excellent in diagnosing H pylori infection in symptomatic children. Accuracy was independent of the laboratory, production lot used, or the child’s age. Because only 18/116 children <6 years of age were infected with H pylori, further validation of the test is needed in young infected children.

Prevalence of Vacuolating Cytotoxin Production and Distribution of Distinct vacA Alleles in Helicobacter pylori from China

Studies of Helicobacter pylori from the West have linked production of vacuolating cytotoxin and a particular signal sequence (s1a) allele of the underlying vacA gene to peptic ulcer disease (PUD). Among Chinese H. pylori, most isolates from both PUD and gastritis patients were toxigenic (35/46 and 29/35, respectively). Polymerase chain reaction and DNA sequencing showed that 95 of 96 isolates carried vacA s1a alleles. In the mid-region, 78 of 96 isolates carried m2; 14 were m1-like but only 87% identical (DNA-level) to classical m1 and were designated m1b; the other 4 were unusual hybrids (m1b-type proximal, m2-type distal). Isolates with m1b and m1b-m2 alleles produced higher levels of vacuolating activity than did isolates with m2 alleles (P < .01). There was no association between any vacA allele and disease. These results suggest that the composition of H. pylori gene pools varies geographically and that other as-yet-unknown polymorphic H. pylori genes are important in PUD.

Influence of metronidazole resistance on efficacy of quadruple therapy for Helicobacter pylori eradication

Background—Metronidazole-containing eradication therapies are less effective for metronidazole resistantHelicobacter pylori. Although early data suggested improvement of the efficacy of bismuth triple therapy after the addition of acid suppressives, these findings were based on studies with small numbers of patients, incomplete post-eradication follow up, or omission of pretreatment susceptibility testing. Aims—To study the efficacy of quadruple therapy in the Amsterdam area, where the efficacy of bismuth triple therapy has been proved to be affected by metronidazole resistance. Patients and methods—Eighty two consecutive dyspeptic H pylori positive patients with either metronidazole susceptible (group I) or metronidazole resistant H pylori strains (group II) received quadruple therapy for one week: omeprazole 20 mg twice daily; colloidal bismuth subcitrate 120 mg four times a day; tetracycline 500 mg four times a day; metronidazole 500 mg three times a day. Susceptibility to metronidazole was determined by the E-test. Results—Intention to treat analysis showed thatH pylori infection had been cured in 42/43 patients (98%) in group I and 32/39 patients (82%) in group II (p = 0.02). Conclusion—The efficacy of quadruple therapy is significantly impaired in patients infected with metronidazole resistant H pylori. Therefore a non-metronidazole-containing regimen should preferably be used in areas known to have a high prevalence of pretreatment metronidazole resistance.

Polymorphisms of Helicobacter pylori HP0638 Reflect Geographic Origin and Correlate with cagA Status

ABSTRACT Since the associations between Helicobacter pylori genotype and disease differ in Asia and the West, we investigated the correlation between HP0638, encoding an outer membrane protein, and potential markers of virulence (cagA, vacA, and iceA). For 109 strains from nine countries, the status of cagA, vacA, and iceA was determined by PCR and/or a line probe assay. We also studied 18 strains from 8 patients (parents and 6 daughters) from a Dutch family and paired strains collected on average 8 years apart from 11 patients. When the HP0638 signal sequences were amplified by PCR and DNA sequence determinations were performed, 89 (96%) of 93 cagA-positive strains had HP0638 in frame, versus none (0%) of 16 cagA-negative strains (P < 0.001). Among strains in which HP0638 was in frame, a six-CT dinucleotide repeat pattern was dominant in Western countries (23 of 33 strains [70%]), while a pattern of three CT repeats with another CT after four T’s (3 + 1-CT-repeat pattern) was dominant in East Asia (31 of 46 strains [67%]); however, specific CT repeat patterns did not correlate with clinical outcome. HP0638 phylogenetic trees also showed geographic characters. The HP0638 frame status and CT dinucleotide repeat patterns were identical for 9 of 11 pairs of strains obtained on average 8 years apart from individuals and the 15 strains obtained from the mother and all six daughters. Thus, HP0638 frame status and cagA status are strongly correlated. The CT dinucleotide repeat pattern in the putative HP0638 signal sequence has geographic characters and appears stable in particular patients and families over a period of years. Analysis of HP0638 CT polymorphisms may serve as a new typing system to discriminate H. pylori isolates for epidemiological purposes.

Interobserver variation in the histopathological scoring of Helicobacter pylori related gastritis.

AIM: To test the reproducibility between two histopathologists of features of Helicobacter pylori gastritis, using the updated Sydney classification. METHODS: 290 dyspeptic Dutch patients with biopsy proven H pylori infection were enrolled in the study. Gastric antral mucosal biopsy specimens were analysed before and after H pylori eradication treatment. The biopsies were scored semi-quantitatively by two histopathologists, according to the updated Sydney classification system. Variables analysed included the density of H pylori infection, the degree of chronic inflammation, inflammatory activity, atrophy, intestinal metaplasia, and surface epithelial damage. Before grading biopsy specimens, both pathologists reached a consensus on the scoring of gastritis through interactive sessions using a multiheaded microscope. Subsequently all biopsy specimens were graded. Interobserver variability was also analysed using weighted kappa scores. RESULTS: For interobserver agreement on scoring the various gastritis features a high degree of reproducibility was reached overall. Agreement on grading of atrophy was the lowest; however, moderate to good reproducibility was achieved, with weighted kappa values of 0.49 in the pretreatment biopsies and 0.52 in the post-treatment biopsies. Disagreement was most common in biopsy specimens with lesser degrees of atrophy. A high degree of agreement was obtained for intestinal metaplasia, with weighted kappa values of 0.72 in the pretreatment biopsies and 0.73 in the post-treatment biopsies. The best agreement was reached in the assessment of the density of H pylori both before and after H pylori eradication treatment, with excellent weighted kappa values of 0.76 and 0.95, respectively. The grade of reproducibility of inflammatory activity, superficial epithelial damage, and chronic inflammation was high, with weighted kappa values varying from 0.60 to 0.76 and 0.62 to 0.83 before and after eradication, respectively. CONCLUSIONS: Reproducibility of grading H pylori related gastritis is high using the updated Sydney system. Despite the novel criteria for scoring atrophy, there was imperfect agreement on this feature between two independent histopathologists.

The susceptibility of Mycobacterium tuberculosis to isoniazid and the Arg→Leu mutation at codon 463 of katG are not associated

ABSTRACT A mutation (CCG→CTG [Arg→Leu]) in codon 463 ofkatG (catalase peroxidase) of Mycobacterium tuberculosis has been found in isoniazid (INH)-resistant strains. A PCR restriction endonuclease analysis to detect this mutation was applied to 395 M. tuberculosis isolates from patients in The Netherlands. The proportion of isolates with a detectable mutation was 32% (32 out of 100) and 29% (85 out of 295) among INH-susceptible isolates and INH-resistant or -intermediate isolates, respectively. Sequencing of five INH-susceptible isolates with such mutations showed that all five had the Arg463Leu mutation. We conclude that the Arg463Leu mutation of katG of M. tuberculosisis not a reliable indicator of INH resistance.

Clarithromycin-Susceptible and -Resistant Helicobacter pylori Isolates with Identical Randomly Amplified Polymorphic DNA-PCR Genotypes Cultured from Single Gastric Biopsy Specimens Prior to Antibiotic Therapy

ABSTRACT Of the Helicobacter pylori populations from 976 patients, six contained clarithromycin-resistant as well as -susceptible colonies. In each heterogeneous H. pyloripopulation, resistant H. pylori colonies harbored identical 23S ribosomal DNA (rDNA) mutations associated with clarithromycin resistance, while the susceptible H. pylori colonies all had wild-type 23S rDNA. The resistant and susceptible colonies of each of the heterogeneous H. pylori populations had identical randomly amplified polymorphic DNA-PCR genotypes. In conclusion, evaluation of antimicrobial susceptibility can be misinterpreted if only a single colony from the primary H. pylori population is used to test for clarithromycin susceptibility.

Reinfection versus recrudescence in Helicobacter pylori infection

Antimicrobial treatment of Helicobacter pylori is the proper management strategy in patients with ulcers. A high rate of H. pylori reinfection after successful eradication therapy however, may give rise to ulcer recurrence. The risk of reinfection, depending on the prevalence and the rate of acquisition of H. pylori infection, varies with socioeconomic status, age and geographical location. The rate of reinfection may vary in a similar way. The available data in the literature reveal that reinfection by H. pylori is low or absent in developed countries and may be lower than the initial rate of acquisition. In addition, reported cases of H. pylori reinfection are often cases of recrudescent H. pylori infection. Acquisition rate in developing countries is high, so the reinfection rate is expected to be higher than in developed countries. However, studies discriminating reinfection from recrudescence are lacking and therefore more data from developing regions are needed to settle if ‘cured once, cured forever’ holds true.

Hearing loss in adults surviving pneumococcal meningitis is associated with otitis and pneumococcal serotype

We assessed the incidence of hearing loss and its relationship with clinical characteristics and pneumococcal serotypes in adults surviving pneumococcal meningitis. We analysed hearing loss in 531 adults surviving pneumococcal meningitis included in two prospective nationwide cohort studies performed from April 1998 through to October 2002 and March 2006 through to January 2009. Hearing loss was evaluated on admission and discharge for all patients. Severe hearing loss was assessed by pure tone average on audiology and corrected for age, or by the combination of hearing loss on discharge and a score on the Glasgow Outcome Scale below 5, which could not be explained by other neurological sequelae. A total of 531 episodes of pneumococcal meningitis with non-lethal outcome were included. Predisposing conditions for pneumococcal meningitis were present in the majority of patients (64%), most commonly otitis (36%). Hearing loss was present at discharge in 116 patients (22%) and was classified as mild in 53% and severe in 47%. Hearing loss was related to otitis (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.66-4.02; p < 0.001) and inversely related to serotype 23 F infection (OR, 0.36; 95% CI, 0.13-0.98; p = 0.025), but not with parameters of disease severity or indicators of cerebrospinal fluid inflammation severity. Meningitis due to pneumococcal serotype 3 was associated with the highest rate of hearing loss. Hearing loss frequently complicates pneumococcal meningitis. Risk factors for hearing loss were infection with pneumococcal serotype 23 F and otitis, but not disease severity. Otitis and resulting perilympathic inflammation contribute to meningitis-associated hearing loss.