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H Rautelin

Publications and source records attributed to H Rautelin.

At least 19 recordsLinked to original sources

Effects of anti-Helicobacter pylori treatment and probiotic supplementation on intestinal microbiota.

The aims of this study were (i) to evaluate the effect of recommended antimicrobial treatment of Helicobacter pylori infection, consisting of clarithromycin, amoxicillin and lansoprazole, on intestinal microbiota and (ii) to determine the ability of a probiotic combination containing Lactobacillus rhamnosus GG, L. rhamnosus LC705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99 to prevent treatment-induced alterations in the intestinal microbiota. Faecal samples were obtained from 39 H. pylori-infected patients randomised into two treatment groups. In addition, 19 H. pylori-negative volunteers were included in the study as a control group. Samples were collected before, during and after treatment and microbiota were analysed by fluorescence in situ hybridisation and culture. The quantities of the predominant bacterial groups were altered significantly in both groups and disturbances were seen even 9 weeks after treatment was complete. Probiotics slightly counteracted the effects of anti-H. pylori treatment, seen as significantly less alterations in the total numbers of aerobes and lactobacilli/enterococci. At baseline, the composition of the microbiota between H. pylori-positive versus H. pylori-negative control individuals differed with regard to clostridia and the total number of anaerobes. The recommended treatment for H. pylori infection induces long-term disturbances in the intestinal microbiota. The probiotic combination appeared to result in only minor changes in the microbiota.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Lactobacillus bacteremia, species identification, and antimicrobial susceptibility of 85 blood isolates.

BACKGROUND: Data regarding antimicrobial susceptibility of clinical Lactobacillus isolates are scarce, and appropriate interpretation criteria for susceptibility tests are not available. METHODS: We examined 85 cases of Lactobacillus bacteremia, of which 47 cases have been included in our previous studies. Overall, 14 antimicrobial agents were evaluated by the E-test method, and these results were compared with disk diffusion test findings. The clinical outcomes of the patients and their antimicrobial treatments were registered. RESULTS: The antimicrobial susceptibility of Lactobacillus strains was species dependent. The considerable number of Lactobacillus rhamnosus (n=46), Lactobacillus fermentum (n=12), and Lactobacillus casei (n=12) strains available for testing made it possible to compare the susceptibilities within 1 species, as well. Of the 46 L. rhamnosus isolates, 22 were identified as L. rhamnosus GG type by pulsed-field gel electrophoresis. All Lactobacillus isolates demonstrated low minimum inhibitory concentrations (MICs) of imipenem, piperacillin-tazobactam, erythromycin, and clindamycin. MICs of vancomycin were high (>256 microg/mL) for all other species except Lactobacillus gasseri and Lactobacillus jensenii. Disk diffusion and E-test results were concordant. The MICs of cephalosporins varied; cefuroxime demonstrated a higher level of activity than did ceftriaxone. Benzylpenicillin and ampicillin MICs had variable ranges between different species. Combination therapy was given to 83% of the patients, but, in 54% of them, therapy included only 1 microbiologically active agent, according to results of the susceptibility tests. Mortality at 1 week was 12% among patients who presumably were receiving adequate treatment and 27% among patients who were receiving inadequate treatment (P=.131, by E-test). CONCLUSION: Most clinical Lactobacillus blood isolates demonstrated low MICs of imipenem, piperacillin-tazobactam, erythromycin, and clindamycin, but they had variable susceptibility to penicillin and cephalosporins.

Anti-Bacterial Agents↗

IgA antibodies in persisting Helicobacter pylori infection in Finnish adults.

Most individuals infected with Helicobacter pylori have elevated levels of specific IgG antibodies, but only in about two-thirds of cases does the IgA titre exceed the cut-off level. The aim of this study was to determine whether H. pylori-infected subjects with elevated IgG levels would subsequently produce IgA antibodies, and whether elevated IgA levels increased during infection. Paired sera were available from 336 adults who took part in a large population-based health survey in 1977-1980 and a follow-up study on asthma and atopic diseases in 1997-1998 (series A). Data on paired sera from 224 adults who participated in a population-based health survey in Vammala, Finland in 1973 and who gave a follow-up blood sample in 1994 (series B) were also re-analysed. H. pylori IgG and IgA levels were determined with commercially available (series A) and in-house (series B) enzyme immunoassays. Twenty-one (35%) of the 60 subjects who initially had elevated levels of IgG antibodies only were found to be IgA-positive at follow-up. In those subjects whose baseline and follow-up samples were IgG- and IgA-positive, the median IgA levels increased by 48% and 22% in series A and B (p < 0.0001 and p 0.0241), respectively, whereas the median IgG levels did not change significantly in either series. During H. pylori infection, an increase in specific IgA was reflected by the increase in the number of responders and by the rise in titres.

Adolescent↗

Strain and host characteristics of Campylobacter jejuni infections in Finland.

The relative importance of different risk-factors for Campylobacter infections and the role of bacterial strain and host characteristics are uncertain. Swimming in natural sources of water was recently described as a novel independent risk-factor for domestically-acquired Campylobacter infections. The present study investigated exposure factors and demographical characteristics (collected in a questionnaire), and determined whether Campylobacter jejuni serotypes could be linked to each other or to the severity of the disease in domestically-acquired sporadic C. jejuni infections during a seasonal peak in Finland. Swimming was associated positively with an age of <or= 5 years, and C. jejuni serotype Pen 6,7 was found significantly more frequently among patients who reported swimming. The geographical distribution among serotypes differed, in that 54% of the isolates belonging to the Pen 4 complex serotype were identified in the Helsinki area, and 74% of the Pen 21 isolates were from the Kuopio area. Pen 57 was associated with a disease of shorter duration, but no serotype could be linked to hospitalisation or antimicrobial therapy. However, advanced age was associated with hospitalisation and a longer period of hospitalisation. Risk-factors and sources of infection for C. jejuni infection may not be identical for all individuals. This study supports the concept that individuals belonging to different age groups and living in different geographical areas may acquire C. jejuni infections from different sources.

Adolescent↗

Genetic and environmental factors in the immunopathogenesis of atopy: interaction of Helicobacter pylori infection and IL4 genetics.

BACKGROUND: Both genetic and environmental factors, e.g. early childhood infections, have a role in the pathogenesis of atopic diseases. OBJECTIVE: To examine simultaneously the strength and possible interactions of two known such factors, IL4 genetics and Helicobacter pylori infection, on the risk of atopy and asthma. METHODS: Gene polymorphism analyses and skin prick tests (SPT) were determined in 245 adult asthmatics and 405 nonasthmatic controls of population-based case-control study. SPTs were used as an indicator of atopy. H. pylori infection was verified by detecting anti-H. pylori IgG antibodies in sera. RESULTS: A significant negative association was seen between the presence H. pylori antibodies and SPT positivity (> or =1 positive reactions) in both asthmatics and controls (p = 0.002 and p = 0.025, respectively) but the effect of IL-4 polymorphism (SNP -590C/T) was nonsignificant in both groups (p = 0.071 and p = 0.072, respectively). However, IL4 genetics had an effect on susceptibility to H. pylori: asthmatics carrying the IL4 -590 allele T had a diminished risk to be H. pylori infected (OR 0.485 95%CI 0.287-0.819). This effect was not seen in controls. Logistic regression analysis indicated that H. pylori and IL4 effects on atopy risk are not interdependent. CONCLUSIONS: This study showed that the effect of H. pylori infection on atopy risk is stronger than that of IL4 genetics. There is no interaction between these factors on the pathogenesis of atopy suggesting that these factors have distinct immunopathogenetic mechanisms. However, the genetic effect may modify the role of infective agents by effecting on susceptibility to disease.

Aged↗

Probiotic supplementation improves tolerance to Helicobacter pylori eradication therapy--a placebo-controlled, double-blind randomized pilot study.

BACKGROUND: H. pylori is the major cause of chronic gastritis, and a risk factor for peptic ulcer and gastric cancer. AIM: To investigate the effect of probiotic supplementation on the tolerance and efficacy of H. pylori eradication treatment in a randomized, double-blind, placebo-controlled trial. METHODS: A total of 338 volunteers were screened for H. pylori infection. The eligibility criteria were met by 47 subjects whose H. pylori infection was verified at the outset and re-evaluated after the treatment by the 13C-urea breath test and by enzyme immunoassay serology. The subjects were randomized to receive probiotic therapy (Lactobacillus rhamnosus GG, L. rhamnosusLC705, Bifidobacterium breve Bb99 and Propionibacterium freudenreichii ssp. shermanii JS) or a placebo during H. pylori eradication and for 3 weeks following the treatment, and recorded their daily symptoms in a standardized diary. RESULTS: When the frequencies of new or aggravated symptoms were evaluated, no significant differences were found between the two groups for individual symptoms. However, the probiotic group showed less treatment-related symptoms as measured by the total symptom score change (P = 0.038) throughout the H. pylori eradication therapy in contrast to the placebo group. The H. pylori eradication rate was non-significantly higher in the group receiving probiotic therapy (91% vs. 79%, P = 0.42). In this group the recovery of probiotic bacteria in the faeces increased significantly (P < 0.001). CONCLUSIONS: In this pilot study, probiotic supplementation did not diminish significantly the frequency of new or aggravated symptoms during H. pylori eradication. However, our data suggest an improved tolerance to the eradication treatment when total symptom severity was taken into account. Furthermore, the results show that probiotic bacteria are able to survive in the gastrointestinal tract despite the intensive antimicrobial therapy.

Adult↗

Three cases of cardiac complications associated with Campylobacter jejuni infection and review of the literature.

Presented here are three cases of acute cardiac disease (myocarditis, myopericarditis, and acute atrial fibrillation) associated with Campylobacter jejuni infection, followed by a review of the corresponding literature. Since Campylobacter jejuni is the most common cause of human bacterial enteritis in developed countries, these cases emphasize the importance of keeping cardiac complications in mind when treating patients with acute gastroenteritis due to this pathogen.

Adult↗

Inflammation and cytokeratin 7/20 staining of cardiac mucosa in young patients with and without Helicobacter pylori infection.

BACKGROUND: Both Helicobacter pylori and gastro-oesophageal reflux disease (GORD) may cause inflammation in cardiac mucosa. Intestinal metaplasia (IM) is found more often in GORD associated inflammation than in inflammation caused by H pylori, especially in young individuals. AIM: To examine morphological differences in chronic inflammation in these two conditions by immunohistochemistry. PATIENTS/METHODS: Tissue blocks from cardiac mucosa of patients <45 years were available as follows: 10 patients with chronic inflammation of cardiac mucosa (carditis) and H pylori gastritis (group 1); 10 patients with (possibly GORD related) carditis, but normal antrum and corpus (group 2); and 10 patients with non-inflamed cardiac mucosa and normal antrum and corpus (group 3). Haematoxylin and eosin staining and immunohistochemical staining for various inflammatory cells were performed for patients in groups 1 and 2 as follows: CD20 (B cells), CD3 (T cells), CD4 (T helper cells), CD8 (T suppressor cells), CD163 (macrophages), CD138 (plasma cells), and CD117 (mast cells). For all patients, cytokeratin 7/20 (CK7/20) staining was performed. RESULTS: No clear differences were seen in the morphology of chronic inflammation between groups 1 and 2. In both, plasma cells were most abundant. CK7/20 staining showed no differences between these groups. CONCLUSION: Helicobacter pylori negative (possibly GORD associated) and H pylori related carditis cannot be distinguished on a morphological basis. The stronger tendency towards IM in the first entity cannot be explained by differences in the type of inflammation. Barrett-type CK7/20 staining seems typical for cardiac mucosa, irrespective of the type of inflammation or presence of IM.

Adult↗

Age-dependent accuracy of Helicobacter pylori antibody assays for adults, with special emphasis on atrophic gastritis.

The accuracy of Helicobacter pylori antibody assays for 561 consecutive adult outpatients who had undergone gastroscopy was studied. The sensitivity of an immunoglobulin G test was 99 to 100% for all age groups, but the specificity declined by age group, from 99% for those aged 15 to 49 years to 75% for those aged > or =65 years. The exclusion of false-positive results for patients with atrophic gastritis improved the specificity to 93 to 97% for the older age groups.

Adolescent↗

An outbreak of gastroenteritis from a non-chlorinated community water supply.

STUDY OBJECTIVE: To determine the source and the extent of a community wide outbreak of gastroenteritis. DESIGN: A matched case-control study with postal questionnaires. Subtyping of campylobacter strains by pulsed field gel electrophoresis (PFGE). SETTING: A rural municipality with a population of 8600 in southern Finland, August 2000. Two thirds of the population receive non-chlorinated ground water from the municipal water supply. PARTICIPANTS: Cases were randomly selected among residents of the municipality who contacted the municipal health centre because of gastroenteritis and had illness onset between 31 July and 20 August 2000. Community controls were identified from the population registry and matched according to sex, year of birth, and postal code. MAIN RESULTS: Four hundred and sixty three persons contacted the municipal health centre because of gastroenteritis. Campylobacter jejuni was isolated from stool samples of 24 persons. One hundred and thirty seven cases and 388 controls were enrolled in the case-control study. In multivariate analysis, drinking unboiled water from the municipal supply was significantly associated with illness (odds ratio 11.1, 95% confidence interval 1.4 to 90.2). C jejuni was isolated from one tap water sample. The water isolate and all but one of the patient isolates were indistinguishable by PFGE. CONCLUSIONS: Combining epidemiological investigation with molecular subtyping methods provided strong evidence that water was the source of the outbreak. Non-chlorinated small ground water systems may be susceptible to waterborne outbreaks and constitute a risk to rural populations.

Adolescent↗

The course of Helicobacter pylori infection in kidney transplantation patients.

BACKGROUND: Helicobacter pylori has been found to be only a minor risk factor for gastroduodenal complications in kidney transplantation patients. The aim of the study was to follow up the course of H. pylori infection in a group of immunosuppressed kidney transplantation patients. METHODS: After a median follow-up of 6.8 years, control serum samples were taken from 93 originally seropositive and 88 originally seronegative kidney transplant recipients. H. pylori antibodies of the IgG and IgA classes and serum pepsinogen I levels were measured from pretransplant and follow-up samples in parallel. In addition, CagA antibodies were measured from the baseline samples of the seropositive patients. RESULTS: 83 of the 93 seropositive patients were also cagA-positive. In addition to the 10 patients who received H. pylori eradication therapy, 27 (29%) of the 92 patients with originally elevated H. pylori IgG antibody titres showed IgG titres at normal level or levels decreased by more than 70% and below 2000 (regarded as seroreverters) after the follow-up. One of the originally seronegative patients seroconverted during the study period. After transplantation, the decrease of serum pepsinogen I values was in accordance with improved kidney function. Patients with lower serum pepsinogen I levels before the transplantation seroreverted more easily. CONCLUSIONS: A spontaneous H. pylori seroreversion occurred in 29% of the immunosuppressed kidney transplantation patients. After a successful kidney transplantation, serum pepsinogen I values declined significantly.

Adolescent↗

Detection and typing of Campylobacter jejuni and Campylobacter coli and analysis of indicator organisms in three waterborne outbreaks in Finland.

Waterborne outbreaks associated with contamination of drinking water by Campylobacter jejuni are rather common in the Nordic countries Sweden, Norway, and Finland, where in sparsely populated districts groundwater is commonly used without disinfection. Campylobacters, Escherichia coli, or other coliforms have rarely been detected in potential sources. We studied three waterborne outbreaks in Finland caused by C. jejuni and used sample volumes of 4,000 to 20,000 ml for analysis of campylobacters and sample volumes of 1 to 5,000 ml for analysis of coliforms and E. coli, depending on the sampling site. Multiple samples obtained from possible sources (water distribution systems and environmental water sources) and the use of large sample volumes (several liters) increased the chance of detecting the pathogen C. jejuni in water. Filtration of a large volume (1,000 to 2,000 ml) also increased the rate of detection of coliforms and E. coli. To confirm the association between drinking water contamination and illness, a combination of Penner serotyping and pulsed-field gel electrophoresis (digestion with SmaI and KpnI) was found to be useful. This combination reliably verified similarity or dissimilarity of C. jejuni isolates from patient samples, from drinking water, and from other environmental sources, thus confirming the likely reservoir of an outbreak.

Animals↗

Temporal and geographical distribution and overlap of Penner heat-stable serotypes and pulsed-field gel electrophoresis genotypes of Campylobacter jejuni isolates collected from humans and chickens in Finland during a seasonal peak.

The association of Penner heat-stable serotypes and pulsed-field gel electrophoresis genotypes of 208 human and 30 chicken Campylobacter jejuni isolates was studied. Overall, 46% of the human strains had overlapping sero- and genotype combinations with chicken strains. The percentage was reduced to 31% for strains that were considered temporally related. This suggests common environmental sources.

Animals↗

Inflammation and intestinal metaplasia at the squamocolumnar junction in young patients with or without Helicobacter pylori infection.

BACKGROUND: Intestinal metaplasia (IM) in the oesophagus is a known risk factor for adenocarcinoma of the oesophagus. The incidence of adenocarcinoma of the cardia and oesophagus has increased in Western countries simultaneously with a decrease in Helicobacter pylori prevalence. AIMS: To determine the association of H pylori infection with inflammation and IM at the squamocolumnar junction (SCJ) in young individuals. PATIENTS: A total of 168 (121 women; 72%) consecutive outpatients, </=45 years, undergoing gastroscopy, and with no prior H pylori eradication treatment. METHODS: Biopsy specimens taken from the antrum, corpus, SCJ, and oesophagus were assessed according to the updated Sydney system, and type of IM (complete or incomplete) was determined. Serum samples from H pylori positive patients were studied for CagA antibodies. RESULTS: In 86% of 37 patients with gastritis in the antrum and/or corpus (24 histologically H pylori positive) and in 23% of 125 patients with a healthy stomach, inflammation was present in the glandular mucosa at the SCJ. In the latter, cardiac mucosa more often than fundic mucosa at the SCJ was inflamed (p<0.001), the inflammation was usually milder in nature, and was associated with signs of reflux disease. IM (incomplete or complete) at the SCJ was evident in nine of those 24 with a healthy stomach and inflamed cardiac mucosa at the SCJ but in none of those with H pylori gastritis. CONCLUSIONS: IM at the SCJ can also appear in young individuals in whom it seems to be associated with reflux related isolated inflammation in cardiac mucosa at the SCJ but not with H pylori gastritis.

Adolescent↗

Intraluminal casein model of necrotizing enterocolitis for assessment of mucosal destruction, bacterial translocation, and the effects of allopurinol and N-acetylcysteine.

An intraluminal casein model (ICM) of necrotizing enterocolitis (NEC) is able to produce small-bowel changes reminiscent of human NEC in neonatal animals. We studied bacterial translocation (BT) in NEC induced by using the ICM in neonatal piglets. We also studied whether allopurinol (AL) and N-acetylcysteine (NAC) have an effect on BT and mucosal changes in the ICM of NEC. Twenty-eight neonatal piglets were randomized into four groups. NEC was induced in 21 by injecting casein-d-gluconate into a loop of terminal ileum: group Cas (n = 7) had no premedication, in group Cas/AL (n = 7) intravenous (i.v.) Al (100 mg/kg), and in group Cas/NAC (n = 7) i.v. NAC (200 mg/kg) was given. Group Sham (n = 7) had the ileum injected with 0.9% saline with no premedication. Immediately after the injection a mesenteric lymph node (MLN) adjacent to the loop was harvested for quantitative aerobic bacterial culture; 4 h after the injection another MLN and samples of spleen, liver, kidney, and lung were harvested and cultured. Comparison of the incidence of samples with positive bacterial cultures and the number of colony-forming units (CFU) in samples was made between groups. The severity of NEC in the ileum was graded from 0 to 3 according to macroscopic and histologic findings. NEC changes in the bowel were most severe in Cas piglets, less severe in Cas/NAC piglets ( P < 0.5), and sham piglets had the least severe changes ( P < 0.05). piglets with NEC changes in the ileum had a higher incidence of BT into the MLN than piglets without NEC changes ( P < 0.05), but the difference in CFU was not significant ( P > 0.05). In Cas and Cas/NAC piglets a high incidence of BT into the MLN was noted as early at -5 min after casein injection. The incidence of BT into the MLN was significantly higher in Cas and Cas/NAC piglets than in Sham piglets ( P < 0.05), the difference in CFU being not significant ( P > 0.05). BT in Cas/Al piglets was not significantly different from that of Cas piglets ( P > 0.05), but less than in Cas/NAC piglets ( P < 0.05). Four hours after casein injection into the ileum there was significant BT into the MLN. Premedication with NAC was associated with less severe NEC changes, but neither NAC nor AL significantly affected BT.

Acetylcysteine↗

The effect of Helicobacter pylori eradication on the natural course of atrophic gastritis with dysplasia.

BACKGROUND: There are few data on the natural course of Helicobacter pylori-related atrophic gastritis. AIM: To investigate the effect of H. pylori eradication on advanced atrophic gastritis in the corpus. METHODS: Twenty-two elderly men with H. pylori infection and moderate or severe atrophic corpus gastritis formed the study population. These men were under endoscopic surveillance because of the presence of indefinite or definite dysplastic gastric lesions in addition to atrophic corpus gastritis. The men were gastroscopically and bioptically examined four times before they received H. pylori eradication therapy (mean follow-up time, 7.5 years), and once again 2.5 years after eradication therapy. Serum levels of pepsinogen I and H. pylori antibodies were analysed at baseline, immediately before and 2.5 years after eradication therapy. RESULTS: During the 7.5-year period prior to eradication therapy, no significant changes were observed in the mean atrophy and intestinal metaplasia scores or in the mean serum level of pepsinogen I. However, a significant improvement occurred in the mean histological scores of inflammation (from 2.2 to 0.5), atrophy (from 2.2 to 1.2) and intestinal metaplasia (from 1.6 to 1.1) in the corpus mucosa after H. pylori eradication. In addition, the mean serum level of pepsinogen I increased from 16.3 to 25.7 microg/L (P=0.0071, Wilcoxon signed rank test) after eradication therapy. CONCLUSIONS: The results suggest that advanced atrophic corpus gastritis (and intestinal metaplasia) improves and may even heal after the eradication of H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Campylobacter-triggered reactive arthritis: a population-based study.

OBJECTIVE: To study the incidence and clinical picture of Campylobacter-associated reactive arthritis (ReA) and other reactive musculoskeletal symptoms in the population. METHODS: A questionnaire on enteric and extraintestinal, including specifically musculoskeletal, symptoms was sent to 870 consecutive patients with Campylobacter-positive stool culture and 1440 matched controls. Analysis of self-reported musculoskeletal symptoms with clinical examination was performed. RESULTS: Forty-five of the patients (7%) had ReA and eight (1%) had reactive tendinitis, enthesopathy or bursitis. No child had ReA. The arthritis was oligo- or polyarticular, and, in most cases, mild. HLA-B27 was positive in 14% of ReA patients. Of the 45 ReA patients, 37 had C. jejuni and 8 had C. coli infection. No controls had ReA. CONCLUSION: ReA is common following Campylobacter infection, with an annual incidence of 4.3 per 100000. At the population level, acute ReA is mild, more frequent in adults, and not associated with HLA-B27. Besides C. jejuni, C. coli can trigger ReA.

Adult↗

Evidence that cagA(+) Helicobacter pylori strains are disappearing more rapidly than cagA(-) strains.

BACKGROUND AND AIMS: The prevalence of Helicobacter pylori colonisation in populations in developed country has been declining, as shown by community based serological surveys of adults in Vammala, Finland in 1973 and 1994. In this study, we determined whether the proportion of subjects colonised by cagA(+) or cagA(-) H pylori strains has changed as the overall prevalence of H pylori(+) has declined. METHODS: We examined 911 sera from Vammala's study for antibodies to the CagA antigen of H pylori using a truncated CagA protein as the antigen in an ELISA and we examined the trend in acquisition and carriage of cagA(+) strains. RESULTS: As expected, the prevalence of carriage of both cagA(+) and cagA(-) strains fell between 1973 and 1994 (p<0.001). However, the prevalence of cagA(+) strains among those <45 years declined (34% to 8%) significantly (p<0.001) more than for cagA(-) strains (12% to 6%). Of 221 subjects with paired serum samples, 12 (5.4%) changed H pylori status; the estimated seroconversion and reversion rates were 0.4% and 0.13% per year, respectively. Except for the few individuals who changed serostatus, absolute antibody levels to H pylori antigens, including CagA, changed little over the 21 year period. CONCLUSIONS: The decline in CagA seroprevalence predominantly reflects declining acquisition of cag(+) strains in younger subjects. In addition, these data confirm that H pylori acquisition chiefly occurs during childhood but continues to occur during adulthood, albeit at low rates, in developed countries.

Adolescent↗