The Japan Pediatric Helicobacter pylori Study Group published the first guidelines on childhood H. pylori infection in 1997. They were later revised by the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition (JSPGHAN). The H. pylori eradication rates, when employing triple therapy with amoxicillin and clarithromycin, currently recommended as the first-line therapy of H. pylori infection in Japan, have substantially decreased, creating an important clinical problem worldwide. In Japanese adults, the "test-and-treat" strategy for H. pylori infection is under consideration as an approach for gastric cancer prevention. However, the combined North American and European pediatric guidelines have rejected such a strategy for asymptomatic children. As risk for gastric cancer development is high in Japan, determining whether the "test-and-treat" strategy can be recommended in children has become an urgent matter. Accordingly, the JSPGHAN has produced a second revision of the H. pylori guidelines, which includes discussion about the issues mentioned above. They consist of 19 clinical questions and 34 statements. An H. pylori culture from gastric biopsies is recommended, not only as a diagnostic test for active infection but for antimicrobial susceptibility testing to optimize eradication therapy. Based upon antimicrobial susceptibility testing of H. pylori strains (especially involving clarithromycin), an eradication regimen including use of the antibiotics to which H. pylori is susceptible is recommended as the first-line therapy against H. pylori-associated diseases. The guidelines recommend against a "test-and-treat" strategy for H. pylori infection for asymptomatic children to protect against the development of gastric cancer because there has been no evidence supporting this strategy.

Helicobacter pylori is a human-specific pathogen, which leads to gastric pathologies including gastric cancer. It is a highly unique bacterium considered as a carcinogenic agent. H. pylori remains a major human health problem, responsible for ~90% of the gastric cancer cases. Approximately four billion individuals have been detected for H. pylori infection worldwide in 2015. At the turn of the twenty-first century, the prevalence of H. pylori has been declining in highly industrialized countries of the Western world, whereas prevalence has plateaued at a high level in developing and newly industrialized countries. However, the infection status remains high in immigrants coming from countries with high prevalence of H. pylori infection. H. pylori can be diagnosed both by invasive and non-invasive methods. Urea breath test and stool antigens detection are among the most commonly used non-invasive ones. Although the way H. pylori is transmitted remains still not fully clear, the level of contamination is strongly dependent on the familial and environmental context, with a drastic impact of living conditions with poor hygiene and sanitation. However, familial socioeconomic status is the main risk factor for H. pylori infection among children. In addition, food and water source have a high impact on the prevalence of H. pylori infection worldwide. This chapter highlights the latest knowledge in the epidemiology of H. pylori infection, its diagnosis and critical risk factors responsible for its high prevalence in some populations and geographic areas.

Serologic tests are commonly used for screening Helicobacter pylori infection because they not only provide quick results but also are inexpensive. A new latex agglutination serum antibody assay (LZ test) has been developed and it is expected to be as effective as conventional assays. This study aimed to calculate a reliable cutoff value for the LZ test and to estimate the sensitivity and specificity of the cutoff value in screening adolescents for H. pylori infection in Japan.

We screened junior high school students in Akita Prefecture, Japan, for H. pylori infection. We used the data of 213 such students who underwent H. pylori stool antigen (HpSA) tests in 2016. The students who had positive results with HpSA tests were diagnosed with H. pylori infection. Of the 213 students, 209 underwent the LZ test.

The prevalence rate of H. pylori infection was 3.8% (8/209). The area under the curve for the LZ test was 0.88. The cutoff value of the LZ test was determined to be 3.1 U/mL. At this value, the sensitivity and specificity were 87.5 and 91.5%, respectively.

The accuracy of the LZ test in adolescents was well balanced for sensitivity and specificity as well as for tolerable results.

Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori.

To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started.

We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively.

We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as 13C or 14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection.

Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities.

We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons.

In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions.

Helicobacter pylori culture on gastric biopsy was performed on 4964 subjects aged <18 years from 1988 to 2007 at a central laboratory in Brussels. The total number of biopsies increased markedly from 941 in 1988-1993 to 1608 in 2004-2007. Biopsies were repeated at least once for 922 subjects (603 initially negative and 319 initially positive for H. pylori). Persistence rate of H. pylori at 1 year after initial positive biopsy was greater in the 1998-2007 cohort than in the 1988-1997 cohort (72.7% vs. 45.8%, P = 0.002), suggesting a tailored selection of candidates for biopsy with non-invasive tests (13C urea breath test). Of 68 subjects initially positive and re-examined subsequently after a documented cure, re-infection/relapse rate was 48.6% within 5 years post-elimination of H. pylori. Acquisition rate over 10 years follow-up in the initially negative cohort (603 patients) was 38.7% (re-infection/relapse vs. acquisition: P < 0.001). Multivariate analysis showed a fourfold greater risk of H. pylori acquisition in children of non-European origin vs. European origin (P < 0.001). Clarithromycin and metronidazole susceptibility were determined in 226 and 223 paired positive cultures in cases of re-infection/relapse or persistence. An initial non-susceptibility profile was highly predictive of a subsequent non-susceptibility profile, and the non-susceptible proportion increased markedly from 13.3% to 21.2% for clarithromycin (P < 0.001) and from 27.3% to 35.0% for metronidazole (P = 0.014), with no difference regarding European or non-European origin.

The (13) C-urea breath test ((13) C-UBT) is a safe, noninvasive and reliable method for diagnosing H. pylori infection in adults. However, the test has shown variable accuracy in the pediatric population, especially in young children. We aimed to carry out a systematic review and meta-analysis to evaluate the performance of the (13) C-UBT diagnostic test for H. pylori infection in children.

We conducted a systematic review of the PubMed, Embase and Liliacs databases including studies from January 1998 to May 2009. Selection criteria included studies with at least 30 children and reporting the comparison of (13) C-UBT against a gold standard for H. pylori diagnosis. Thirty-one articles and 135 studies were included for analysis. Children were stratified in subgroups of <6 and ≥6 years of age, and we considered variables such as type of meal, cutoff value, tracer dose, and delta time for the analysis.

The (13) C-UBT performance meta-analyses showed 1, good accuracy in all ages combined (sensitivity 95.9%, specificity 95.7%, LR+ 17.4, LR- 0.06, diagnostic odds ratio (DOR) 424.9), 2, high accuracy in children >6 years (sensitivity 96.6%, specificity 97.7%, LR+ 42.6, LR- 0.04, DOR 1042.7), 3, greater variability in accuracy estimates and on average a few percentage points lower, particularly specificity, in children ≤6 years (sensitivity 95%, specificity 93.5%, LR+ 11.7, LR- 0.12, DOR 224.8). Therefore, the meta-analysis shows that the (13) C-UBT test is less accurate for the diagnosis of H. pylori infection in young children, but adjusting cutoff value, pretest meal, and urea dose, this accuracy can be improved.

As the clinical implications of Helicobacter pylori infection in children and adolescents continue to evolve, ESPGHAN and NASPGHAN jointly renewed clinical guidelines using a standardized evidence-based approach to develop updated recommendations for children and adolescents in North America and Europe.

An international panel of 11 pediatric gastroenterologists, 2 epidemiologists, 1 microbiologist, and 1 pathologist was selected by societies that developed evidence-based guidelines based on the Delphi process with anonymous voting in a final face-to-face meeting. A systematic literature search was performed on 8 databases of relevance including publications from January 2000 to December 2009. After excluding nonrelevant publications, tables of evidence were constructed for different focus areas according to the Oxford classification. Statements and recommendations were formulated in the following areas: whom to test, how to test, whom to treat, and how to treat. Grades of evidence were assigned to each recommendation based on the GRADE system.

A total of 2290 publications were identified, from which 738 were finally reviewed. A total of 21 recommendations were generated, and an algorithm was proposed by the joint committee providing evidence-based guidelines on the diagnostic workup and treatment of children with H pylori infection.

These clinical practice guidelines represent updated, best-available evidence and are meant for children and adolescents living in Europe and North America, but they may not apply to those living on other continents, particularly in developing countries with a high H pylori infection rate and limited health care resources.

We analyzed the rates of antimicrobial resistance of Helicobacter pylori strains isolated from patients from 1990 to 2009 and identified risk factors associated with resistance. Gastric biopsy specimens were collected from several digestive disease centers in Brussels, Belgium. We routinely performed antimicrobial susceptibility testing for clarithromycin (CLR), metronidazole, amoxicillin, tetracycline, and ciprofloxacin. Evaluable susceptibility testing was obtained for 9,430 strains isolated from patients who were not previously treated for Helicobacter pylori infection (1,527 isolates from children and 7,903 from adults) and 1,371 strains from patients who were previously treated (162 isolates from children and 1,209 from adults). No resistance to amoxicillin was observed, and tetracycline resistance was very rare (<0.01%). Primary metronidazole resistance remained stable over the years, with significantly lower rates for isolates from children (23.4%) than for isolates from adults (30.6%). Ciprofloxacin resistance remained rare in children, while it increased significantly over the last years in adults. Primary clarithromycin resistance increased significantly, reaching peaks in 2000 for children (16.9%) and in 2003 for adults (23.7%). A subsequent decrease of resistance rates down to 10% in both groups corresponded to a parallel decrease in macrolide consumption during the same period. Multivariate logistic regression revealed that female gender, age of the patient of 40 to 64 years, ethnic background, the number of previously unsuccessful eradication attempts, and the different time periods studied were independent risk factors of resistance to clarithromycin, metronidazole, and ciprofloxacin. Our study highlights the need to update local epidemiological data. Thus, the empirical CLR-based triple therapy proposed by the Maastricht III consensus report remains currently applicable to our population.

The urea breath test (UBT) is generally considered the gold standard for the diagnosis of Helicobacter pylori infections in adults.

To investigate the utility and accuracy of urea breath testing in children from the United States.

Children scheduled to undergo upper gastrointestinal endoscopy for various clinical symptoms underwent a 13C-UBT using the US standard protocol for adults. Results were compared with rapid urease testing (RUT), culture, and histology. H. pylori positivity was defined according to the FDA, Division of Anti-Infective Drug Products criteria, i.e. positive culture and/or positive RUT and histology. H. pylori negativity was defined as all tests negative. Results were evaluated by delta over baseline (DOB) and urea hydrolysis rate (UHR).

A total of 176 children from five centers were evaluated; 48 were infected. Compared to the defined standard, the results with the UBT based on delta over baseline (DOB) cut-off value (positive: > or = 2.4 per thousand) showed that the sensitivity and specificity of the UBT were 97.9% and 96.1%, respectively. Based on the UHR cut-off value (positive: > or = 10.0 microg/min), the sensitivity and specificity were 95.8% and 99.2%. In young children (2- to 5-year olds), sensitivity and specificity of UHR method were higher than the DOB method (100% and 100% vs 100% and 82.4%, respectively).

The US standard (13)C-UBT proved to be both simple and accurate for the diagnosis of H. pylori infections in children. The UHR method to calculate of (13)C-UBT result provided excellent results for children of all ages.

Endogenous CO(2) production may be a possible explanation for higher false-positive results reported for (13)C-urea breath test (UBT) in children below 6 years. In this study, we evaluated whether age affects the diagnostic accuracy of the (13)C-UBT even after the application of urea hydrolysis rate (UHR) in children.

A total of 612 (13)C-UBTs and endoscopic biopsies were performed on children divided into two groups; children under 6 years (n = 126) and children aged 6-18 years (n = 486). For (13)C-UBT, 75 mg (13)C-urea was ingested, and breath sample was collected 30 minutes later. Delta over baseline (DOB) was determined, and UHR was calculated to normalize the DOB values for endogenous CO(2) production.

There was significant difference between the DOB values of children under 6 years and those of children over 6 years in H. pylori-positive (p = .029) and -negative groups (p = .002). On applying the UHR, no significant difference was observed between the UHR values of children under 6 years and those of children over 6 years in H. pylori-positive (p = .877) and -negative groups (p = .427). In 12.6% children under 6 years, false-positive results were observed on applying the DOB, and in 9.0% on applying the UHR (p = .125).

The (13)C-UBT is a noninvasive method exhibiting high diagnostic accuracy with both UHR as well as DOB. However, high false-positive results for (13)C-UBT were noted in children below 6 years on applying both UHR as well as DOB. Thus, this may not only be due to the effects of endogenous CO(2) production but also due to other factors.

The rates of acquisition and spontaneous eradication of Helicobacter pylori infection in children has yet to be established. To determine these rates in children living in an urban region of Japan, the levels of urine H. pylori antibodies in children of three different age groups were measured.

A urine-based enzyme-linked immunosorbent assay (ELISA) was used to detect H. pylori antibodies twice within a 12 month interval over 2 years in 452 healthy children living in Tokyo. The subjects were divided into three groups: ages 4, 7, and 10 years.

The prevalence of H. pylori infection was not different among the groups, being between 4.0% and 6.7%. The rate of turn to positivity for H. pylori infection was 1.5% per year and the rate of turn to negativity was 1.1%, but in the 10 year age group the rates were markedly lower than in the younger children.

The prevalence of H. pylori infection in Tokyo was 4.0-6.7% and was not different among 4, 7, and 10 year age groups.

Attempts to understand determinants of anemia and iron deficiency have led researchers to examine the role of Helicobacter pylori infection. The current study assessed determinants of anemia and iron deficiency, including H. pylori, in Alaska Native children.

In 1999, a population-based survey was conducted among 86 children (67% response rate), mean age of 43.7 months (standard deviation = 16.8 months). Samples of breath, stool, and venous blood were obtained from children for measures of anemia, iron deficiency, H. pylori, fecal blood loss, and current inflammation. Standardized interviews with parents provided information on demographics, illness, and intake of dietary iron, iron-absorption inhibitors, and enhancers.

Of the 86 children studied, 17.4% were anemic and 38.6% were iron deficient. Forty-one percent of the cohort had H. pylori-specific IgG antibodies, 86% tested positive by the urea breath test (UBT), and 80% tested positive by the stool antigen test. Presence of H. pylori antibodies emerged as a significant risk factor for anemia and iron deficiency in adjusted analyses controlling for demographic factors, current inflammation, and antibiotic use. In contrast, children with positive UBT or stool antigen results were significantly less likely to have anemia or iron deficiency than those with negative results.

Results from different measures of H. pylori may reflect different stages of infection. Relationships between H. pylori and anemia/iron deficiency may depend on the phase of infection measured, with serologic tests reflecting established H. pylori infection associated with anemia/iron deficiency, and UBT and stool antigen results reflecting an earlier stage of infection.

The discovery of Helicobacter pylori in 1982 was the starting point of a revolution concerning the concepts and management of gastroduodenal diseases. It is now well accepted that the most common stomach disease, peptic ulcer disease, is an infectious disease, and all consensus conferences agree that the causative agent, H. pylori, must be treated with antibiotics. Furthermore, the concept emerged that this bacterium could be the trigger of various malignant diseases of the stomach, and it is now a model for chronic bacterial infections causing cancer. Most of the many different techniques involved in diagnosis of H. pylori infection are performed in clinical microbiology laboratories. The aim of this article is to review the current status of these methods and their application, highlighting the important progress which has been made in the past decade. Both invasive and noninvasive techniques will be reviewed.

Helicobacter pylori (Hp) is a chronic stomach infection common throughout the world. The pediatric diabetes literature on the relation between Hp and HbA1c is sparse and controversial. This study aimed to investigate this relation.

The study included 100 youth with type 1 diabetes and seropositive for Hp (European Caucasians: n=49; Moghrabin Caucasians: n=51). Mean socioeconomic status was lower among the latter. Hp infection was demonstrated by the (13)C-urea breath test and a gastric biopsy for antibiotic susceptibility testing. HbA1c levels were measured for a year (mean: 6 measurements; upper normal limit: 6.2%) before and after Hp eradication, which was proved by the (13)C-urea breath test.

Of 100 Hp-seropositive patients, 49 had active Hp infections and were treated. Mean age+/-SD was 14.2+/-2.8 years, and duration of diabetes at Hp diagnosis was 6.2 +/-2.3 years. Hp infection was eradicated in 38/49 subjects (78%). Eleven (22%) remained infected and required a second treatment. The two subgroups did not differ for age, duration of diabetes or pretreatment HbA1c levels (7.3+/-1.5% versus 7.8+/-0.8%; p=0.16). Mean HbA1c levels in the 49 infected subjects did not differ significantly in the year before and after eradication (7.4+/-1.3% versus 7.9+/-1.1%; p=0.08). Prevalence of infection was higher among youth of North African than European ancestry (47% versus 22%; p<0.001). Their HbA1c levels, however, did not differ (7.3+/-1.5% versus 7.7+/-0.9%; p=0.31), nor did age or duration of diabetes. Among the 100 Hp-seropositive patients, vague abdominal pain was reported by 45 of them; only 24 had active Hp infections.

Before treatment, patients seropositive for Hp did not differ in HbA1c levels or abdominal complaints according to whether they had active Hp infection. Hp infection was twice as frequent in Moghrabin Caucasians than in European Caucasians, perhaps associated with their lower socioeconomic status. HbA1c levels were similar in patients with and without Hp eradication after one treatment. After a one-year follow-up, Hp eradication had no significant effect on HbA1c levels.

The possible improvement of efficacy and tolerability of a 7-day dual antibiotherapy amoxicillin-clarithromycin (AC) on the eradication of Helicobacter pylori (H. pylori) gastritis in children by the adjunction of omeprazole (OAC) was studied.

Forty-six children presenting with H. pylori gastritis, assessed at inclusion by endoscopy, H. pylori urease test, histology and/or culture were randomised to a twice-daily regimen of AC or OAC. A (13)C-urease breath test was performed 4-6 weeks after the end of the treatment period to evaluate H. pylori eradication.

A larger proportion of patients was H. pylori negative (69%) in the OAC regimen treatment 4-6 weeks after eradication treatment compared with those who received dual AC therapy (15%). A total of seven patients (three in the OAC and four in the AC group) reported adverse events (AEs). Only vomiting was reported in more than one patient (one in each treatment regimen) and only one AE was severe (urticaria: in the OAC group, but considered not related to treatment).

A larger eradication rate of H. pylori was obtained in the triple OAC group than in the dual AC group. Both therapy regimens can be safely administered to children for 7 days.

The 13C-methacetin breath test (MBT) measures the activity of the cytochrome P450 dependent enzyme system and has been developed to assess the functional hepatic mass. We evaluated simple modifications of the 13C-MBT to further increase its practicability and therefore clinical acceptance.

One hundred and four patients with different chronic liver diseases (including 35 patients with histologically proven cirrhosis) and 65 healthy controls underwent the 13C-MBT. Breath test results of 2-point measurements were compared with conventional breath test results (cumulative recovery after 30 min) and liver histology.

The 2-point-measurement at 0 and 15 minutes (with a cut-off <14.6 per thousand delta over baseline) had 92.6% sensitivity and 94.1% specificity in identifying the presence of cirrhosis compared with liver histology. The 2-point-measurements at 5 and 10 minutes also provided good discrimination between cirrhotic and noncirrhotic patients.

The 13C-MBT using 2-point-measurement of breath samples at baseline and after 15 minutes reliably indicates decreased liver function in liver cirrhosis. This simplification of the 13C-MBT will increase practicability and cost efficiency, thus facilitating its clinical acceptability.

To validate the (13)C-urea-breath-test (UBT) and stool antigen test (HpSA) in children aged 5 years or younger, against invasive histologic study and rapid-urease-testing or culture.

On all consecutive children aged 5 years or younger undergoing endoscopy in 1 single center during the last 7.5 years, UBT and HpSA were performed.

Of a total of 184 children (median age 2.2 years, range 0.2-5.5), 30 were Helicobacter pylori-positive (16.3%). Sensitivity and specificity of UBT were 93.3% (95%CI 77.9%-99.2%) and 95.5% (90.9-98.2), with a cutoff of 5 per thousand, but specificity increased to 98.1% (94.4%-99.6%) with a cutoff of 8 per thousand. Sensitivity and specificity of HpSA were 93.3% (77.9%-99.2%) and 98.7% (95.4%-99.8%).

Accuracy of noninvasive tests in our single-center study were satisfactory: specificity of UBT improved with a cutoff at 8%, and sensitivity of HpSA was high when determined locally without transportation after long or inadequate storage that could impair results.

High seroprevalence rates for Helicobacter pylori have been reported in developing countries, yet few studies exist determining the pattern of change in the epidemiology of H. pylori infection in children. The knowledge of acquisition and loss rates of H. pylori and the relevance to the sociodemographic properties and the symptomatology of infection may provide clues for lifestyle changes that might protect children from infection, and also, it may provide rationale for eradication, screening, and protection policies. Our aim was to conduct a prospective study to elucidate the outcome, rate of acquisition, and loss of H. pylori infection in a population of healthy children.

This study is based on follow-up of 327 healthy Turkish children aged 3 to 12 years. The follow-up was conducted 6 years after the baseline examination. Helicobacter pylori status was determined by C-urea breath test. Children were investigated for sociodemographic variables and several symptoms.

Data from 136 (41%) of 327 children were available. The prevalence of infection increased from 52.9% to 56.6%, mainly increasing in children younger than 10 years. The incidence of H. pylori infection among previously uninfected children was 14%, and the loss rate of infection among previously infected children was 5.5% during the follow-up. Socioeconomic status, household density, and antibiotic use during last 6 months were inversely related to H. pylori prevalence. Children infected with H. pylori were complaining more often of headache but not of abdominal pain or dyspepsia.

In this study, the acquisition rate of H. pylori infection was 2.5-fold higher than the loss of infection, and the acquisition mostly occurred before 10 years of age. Data regarding acquisition and loss of H. pylori infection are critical for understanding the epidemiology of infection and development of preventive and treatment strategies.

The (13)C-urea breath test ((13)C-UBT) is the most accurate non-invasive method for diagnosis of Helicobacter pylori infection. However, several methodological issues have not been resolved yet. The aim of this study was to test different protocols of (13)C-UBT to find the optimal test drink and sampling interval.

(13)C-UBT was performed at 3-day intervals in 27 healthy volunteers using citric acid (test A), orange juice (B) and still water (C) as test drinks. Breath samples were collected from time 5 to 60 min. A total number of 2106 breath samples were analysed by isotope ratio mass spectrometry (cut-off value 3.5).

Differences in delta values were greater than would be expected by chance (A versus B and A versus C at times 20, 25, 30, 35 and 40 min, p<0.05, Dunnett's method). There were no grey zone- or false-negative results among H. pylori-positive persons in test A at any time, but some were found in tests B and C. Optimal intervals for breath sampling are at times 20 or 25 min after (13)C-urea ingestion.

Citric acid solution as a test drink and 20- or 25-min breath sampling intervals are optimal for the (13)C-UBT in healthy volunteers.

The aim of the current study was to assess the reliability of two enzyme immunoassays in detecting the Helicobacter pylori status of stool specimens of Turkish dyspeptic patients in the post-treatment period. Forty-eight patients with non-ulcer dyspepsia who were positive for H. pylori underwent a 1 week regimen of triple therapy. Stool samples of patients were obtained 2 and 6 weeks after eradication therapy and a [13C]urea breath test was performed 6 weeks after therapy in order to assess the reliability of mAb-based (Amplified IDEIA HpStAR, DakoCytomation) and polyclonal-antiserum-based (Premier Platinum HpSA, Meridian Diagnostics) stool antigen test kits and to compare their diagnostic accuracies. Using a minimum cutoff OD450 value of 0.19 for Amplified IDEIA HpStAR and 0.16 for Premier Platinum HpSA the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of the tests were determined 2 and 6 weeks after completion of eradication therapy. At both the second and the sixth week in the post-treatment period the diagnostic accuracy of Amplified IDEIA HpStAR was significantly better than the Premier Platinum's (75% versus 50%, S2=6.4; P=0.011, and 90% versus 69%, S2=6.316; P=0.012, respectively). In light of these findings the mAb-based Amplified IDEIA HpStAR has a high diagnostic accuracy for H. pylori infection in Turkish dyspeptic patients 6 weeks after completion of eradication therapy.

Data concerning the effectiveness of Helicobacter pylori eradication regimens based in antibiotic susceptibility testing are scanty in children.

To identify the prevalence of antibiotic resistance in H. pylori strains isolated from Portuguese children in 1999-2003; to evaluate eradication rate after antibiotic susceptibility testing-based treatment; and to identify factors associated with resistance and eradication outcome.

Included were 109 children with a gastric biopsy culture positive for H. pylori. First treatment (amoxicillin, omeprazole and clarithromycin or metronidazole) was guided by susceptibility testing (E test), and eradication was assessed by [C]urea breath test.

Strains were susceptible to amoxicillin and tetracycline; 39.4% were resistant to clarithromycin, 16.5% to metronidazole and 4.5% to ciprofloxacin. No significant association was found between resistance and sex, age, clinical status, gastritis scores, H. pylori density scores and genotype. Clarithromycin resistance was significantly associated with European origin [odds ratio (OR), 3.9], previous H. pylori empiric therapy (OR 2.8) and amoxicillin minimal inhibitory concentration, > or =0.016 (OR 6.0). Eradication rate after susceptibility-based treatment was 74.7% (59 of 79; 95% confidence interval, 65.9-82.9), and a significant association was found between eradication failure and presence of resistance to 1 or more antibiotics (P < 0.05).

The prevalence of H. pylori antibiotic resistance was high in the studied population. The modest therapeutic success of clarithromycin and metronidazole susceptibility-based regimens suggests that in addition to resistance, other factors may be involved. The need of susceptibility-based treatment studies in children and of antimicrobial resistance surveillance in high prevalence areas for H. pylori are emphasized.

The (13)C-urea breath test ((13)C-UBT) is a reliable non-invasive method of diagnosing Helicobacter pylori infection in adults and children. However, only a few validation studies have been performed on the (13)C-UBT in very young children. The purpose of the present study was to evaluate the diagnostic accuracy of the (13)C-UBT according to age, and to determine the optimal cut-off value in children.

A total of 307 (13)C-UBT were performed in 274 children. All were compared with the results of endoscopic biopsy-based methods to confirm H. pylori infection. Seventy-five milligrams of (13)C-urea was ingested without a test meal. Two breath samples were collected at 0 and 30 min. The optimal cut-off value of the (13)C-UBT was assessed by determining the sensitivity, specificity, false negative, and false positive results, at cut-off values ranging from 2.0 to 10.0 per thousand.

The delta over baseline (DOB) values of the (13)C-UBT showed a significant negative correlation with age in both the H. pylori-positive group (r = -0.309; P = 0.005) and the H. pylori-negative group (r = -0.162; P = 0.015). High false positive results and low specificity were noted in children aged 6 years or less compared with children older than 6 years at a cut-off value of 4.0 per thousand (false positives; 8.3%vs 0.85%, specificity; 89.8%vs 98.8%). After adjusting the cut-off value, the optimal cut-off values were found to be 4.0 per thousand in children older than 6 years and 7.0 per thousand in children aged 6 years or less.

The cut-off value of the (13)C-UBT recommended regardless of age must be adjusted in preschool children to reduce the false positive results.

Helicobacter pylori infection is acquired in childhood and plays a causative role in chronic gastritis, peptic ulcer disease and the development of gastric cancer. The present review focuses on recent advances in the management of H pylori infection in children and provides an update of current Canadian guidelines regarding clinical sequelae, diagnosis and treatment.

The urea breath test is a non-invasive, simple and safe test which provides excellent accuracy both for the initial diagnosis of Helicobacter pylori infection and for the confirmation of its eradication after treatment. Some studies have found no differences between urea breath test performed under non-fasting conditions. The simplicity, good tolerance and economy of the citric acid test meal probably make its systematic use advisable. The urea breath test protocol may be performed with relatively low doses (<100 mg) of urea: 75 mg or even 50 mg seem to be sufficient. With the most widely used protocol (with citric acid and 75 mg of urea), excellent accuracy is obtained when breath samples are collected as early as 10-15 min after urea ingestion. A unique and generally proposed cut-off level is not possible because it has to be adapted to different factors, such as the test meal, the dose and type of urea, or the pre-/post-treatment setting. Fortunately, because positive and negative urea breath test results tend to cluster outside of the range between 2 and 5 per thousand, a change in cut-off value within this range would be expected to have little effect on clinical accuracy of the test.

The urea breath test (UBT) is a non-invasive diagnostic test to detect the presence of Helicobacter pylori in the stomach, and is the simplest way to confirm eradication after treatment. The test is based on the capacity of H. pylori to secrete the enzyme urease, which hydrolyses urea to ammonia and carbon dioxide. The aim of this study was to determine whether there is an advantage in expressing the results of UBTs in terms of urea hydrolysis rate (UHR), rather than breath 13C enrichment alone. Retrospective analysis of data collected between 1995 and 2002 from 260 patients undergoing UBTs was performed. The cut-offs for positive tests using breath 30-minute enrichment (E30), UHR calculated using VCO2 estimated from height and weight (H/WT) and VCO2 estimated from weight only were determined using two-graph receiver operator characteristic (TG-ROC) analysis. The cut-off points were 3.5/1000 or 38.7 ppm 13C excess, 7.04 micromol/h and 7.08 micromol/h, respectively. There was no advantage in expressing the results as UHR (theta0, Theta-zero, where sensitivity = specificity = 0.97 (UHR H/WT), 0.98 (UHR WT) and 1.00 (E30)) rather than breath 13CO2 enrichment alone. Differences in the extent of H. pylori colonisation and urease activity are more important than variation in VCO2 in determining breath 13CO2 enrichment in the UBT.

To investigate the prevalence of Helicobacter pylori infection in a randomly selected population of children from a low income community in Brazil and the risk factors for infection.

A cross-sectional, randomised study of prevalence and risk factors.

Children living in an urban community in north-east Brazil.

H. pylori infection was determined using the C-urea breath test. Risk factors were assessed using a structured interview schedule.

The overall prevalence of H. pylori was 56% (197/353). The infection was most common for those aged 12-14 years. In this group 75.4% (49/65) (95% CI, 63.1-85) of all children were positive for H. pylori, while in children less than 2 years of age 35.1% (13/37) (95% CI, 20.2-52.5) were positive. The prevalence of H. pylori increased significantly with age (P < 0.0001). In the bivariate analysis, a significant difference was found in the prevalence of H. pylori infection and age, number of persons per room, the number of children per household, cup sharing, and type of drinking water (P < 0.05). However, after logistic regression modelling only age (odds ratio (OR) = 1.3; 95% confidence interval (CI), 1.07-1.65), and number of persons per room (OR = 2.58; 95% CI, 1.4-4.6) were risk factors for H. pylori infection.

H. pylori is highly prevalent among children in a north-eastern Brazilian community characterised by poor living conditions, and this infection is largely acquired during early childhood. The infection increased with age, and domestic overcrowding. Further longitudinal studies must examine in depth the possible modes of transmission of the organism in young children.

Recent studies of urine-based enzyme-linked immunosorbent assays (ELISA) for detection of antibody to Helicobacter pylori (H. pylori) have already shown high sensitivity and specificity in adults. The diagnostic accuracy of these assays in children was investigated.

The results of serum and urine-based ELISAs were compared with those of 13C-urea breath tests (13C-UBT) and/or detection of faecal H. pylori antigen in 68 children. The effect of urine total immunoglobulin G (IgG) levels on the ELISA results for anti-H. pylori antibodies in urine was also examined.

The sensitivity, specificity and accuracy of the serum ELISA were 72.7%, 96.3%, and 92.3% respectively, while those of the urine-based ELISA were 92.3%, 76.4%, and 79.4% respectively. The level of urine total IgG in children with false-positive results in the urine-based ELISA, was significantly higher than that in children who showed negative results in both the urine-based ELISA and the 13C-UBT and/or faecal H. pylori antigen tests. Human gamma-globulin affected the urine-based ELISA results at final concentrations of 2.0 mg/dL, 3.0 mg/dL, and 4.0 mg/dL; the anti-H. pylori antibody values were significantly higher than the ELISA values without the addition of human gamma-globulin.

The findings suggested that the specificity of urine-based ELISA for detection of H. pylori antibodies is low in children, since high urinary levels of total IgG increase the likelihood of false-positive results.

The recognition of the role of Helicobacter pylori in gastric diseases has led to the widespread use of antibiotics in the eradication of this pathogen. The most advocated therapy, triple therapy, often includes clarithromycin. It is well known that clarithromycin resistance is one of the major causes of eradication failure. The development of a rapid noninvasive technique that could easily be performed on fecal samples and that could also provide information about the antibiotic resistance of this microorganism is therefore advisable. Previous findings have demonstrated that clarithromycin resistance is due to a single point mutation in the 23S rRNA. All the mutations described have been associated with specific restriction sites, namely BsaI (A2143G), MboII (A2142C/G), and HhaI (T2717C). On this basis we have developed a new method, a seminested PCR, allowing screening for clarithromycin resistance of H. pylori directly on stool samples. This method furnished a 783-bp fragment of the 23S rRNA, which was subsequently digested by MboII, BsaI, and HhaI, in order to identify single point mutations associated with clarithromycin resistance. Of a total of 283 stool samples examined, 125 were H. pylori positive and two of them were shown to contain clarithromycin-resistant strains due to the presence of a mutation at position 2717, whereas no PCR products contained mutations at position 2142 or 2143. In order to evaluate the reliability of the new system, we compared the results of restriction analysis of the PCR products with the MICs shown by the H. pylori isolates by culturing gastric biopsies from the same patients.

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.

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.

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).

Social and familial factors play a major role but not H. pylori infection in RAP.

The 13C-urea breath test is an accurate, noninvasive method for the diagnosis of in adults. A dose of 75 to 100 mg of urea is generally used, especially in adults, but the optimal dose in children is still unknown. Our aim was to determine whether urea breath test performed with a single 50-mg dose of 13C-urea was sufficient and accurate for diagnosing infection in children.

Consecutive children 4 to 14 years of age undergoing upper intestinal endoscopy to evaluate symptoms of recurrent abdominal pain were prospectively included. Exclusion criteria included use of antibiotics or proton pump inhibitors during the last month, gastric surgery, and previous eradication therapy. Reference criteria for diagnosis of infection were based on histology, culture, and serology. Urea breath test (TAU-KIT; Isomed, S.L., Madrid, Spain) was performed as follows: citric acid (Citral pylori) dissolved in 100 mL of water was initially given. Ten minutes later, a baseline exhaled breath sample was collected, and thereafter 50 mg of 13C-urea dissolved in 50 mL of water was given. A second breath sample was obtained 30 minutes later. Breath samples were analyzed by isotope ratio mass spectrometry. The endoscopist, the pathologist, the microbiologist, and the person responsible for reading the serology and the urea breath test were all unaware of status by the other diagnostic methods.

One hundred children were included (40% males; mean age, 9.2 +/- 2 years; mean weight, 33.9 +/- 12 kg). Based on the reference criteria, 45% were infected, 37% were not infected, and 18% were indeterminate. Sensitivity, specificity, positive predictive value, and negative predictive value were, respectively, 91% (95% confidence interval [CI], 79%-96%), 97% (95% CI, 86%-99%), 98% (95% CI, 87%-91%), and 90% (95% CI, 76%-96%). Positive and negative likelihood ratios were of 33 and 0.09. Any cutoff point between 2 and 14 delta units had the same high diagnostic accuracy. The area under the receiver operating characteristic curve was 0.94. No adverse effects were reported.

Urea breath test using 50 mg of urea is sufficient and accurate for the diagnosis of infection in children. Use of a small test dose significantly lowers the cost of the test.

Helicobacter pylori infection is a frequent infection mainly acquired in childhood. Even if the infection is almost invariably associated with mild to severe gastro-duodenal lesions, no specific clinical picture has been identified. The aim of this study was to evaluate the presence of dyspeptic symptoms and their relationship with the presence of H. pylori infection in the first two decades of life.

A school-population sample size of 808 subjects from 6- to 19-year-olds was investigated for the presence of gastrointestinal tract symptoms and evaluated by a 13C-urea breath test for H. pylori infection. The relationship between clinical findings and H. pylori infection was evaluated by chi2 statistic or Fisher's exact test, as appropriate.

Symptoms of dyspepsia were identified in 45% of subjects, while the picture of ulcer-like and dysmotility-like forms were present in 3-4%. H. pylori infection was demonstrated in 95 (11.8%) subjects, 49.5% of them without symptoms. Severe epigastric pain and ulcer-like dyspepsia were significantly associated with H. pylori infection, while recurrent abdominal pain or dysmotility-like dyspepsia were not.

Dyspeptic symptoms are frequent in children, and its association with H. pylori infection is more evident than with recurrent abdominal pain. The age at which the infection is acquired seems to be under 6 years of age.

Studies support the accuracy of 13C-urea breath test for diagnosing and confirming cure of Helicobacter pylori infection in children. Three methods are used to assess 13CO2 increment in expired air: mass spectrometry, infrared spectroscopy, and laser-assisted ratio analysis. In this study, the 13C-urea breath test performed with infrared spectroscopy in children and adolescents was evaluated.

Seventy-five patients (6 months to 18 years old) were included. The gold standard for diagnosis was a positive culture or positive histology and a positive rapid urease test. Tests were performed with 50 mg of 13C-urea diluted in 100 mL orange juice in subjects weighing up to 30 kg, or with 75 mg of 13C-urea diluted in 200 mL commercial orange juice for subjects weighing more than 30 kg. Breath samples were collected just before and at 30 minutes after tracer ingestion. The 13C-urea breath test was considered positive when delta over baseline (DOB) was greater than 4.0%.

Tests were positive for H. pylori in 31 of 75 patients. Sensitivity was 96.8%, specificity was 93.2%, positive predictive value was 90.9%, negative predictive value was 97.6%, and accuracy was 94.7%.

13C-urea breath test performed with infrared spectroscopy is a reliable, accurate, and noninvasive diagnostic tool for detecting H. pylori infection.

In adults, the 13C-urea breath test (UBT) has been widely used as a noninvasive test of Helicobacter pylori infection because of its high sensitivity and specificity. However, this test is less well established in pediatric practice. The optimum cutoff value and test protocol of the 13C-UBT remains to be established in the pediatric population. The primary purpose of this study was to evaluate diagnostic accuracy of the 13C-UBT for children and to determine its optimum cutoff value.

A total of 220 Japanese children aged 2-16 yr (mean = 11.9) who underwent upper GI endoscopy and gastric biopsies were finally studied. Endoscopic diagnoses included gastritis (n = 131), gastric ulcer (n = 15), duodenal ulcer (n = 72), and combined ulcer (n = 2). H. pylori infection status was confirmed by biopsy tests including histology, urease test, and culture. With the 13C-UBT, breath samples were obtained at baseline and at 20 min after ingestion of 13C-urea without a test meal and were analyzed by isotope ratio mass spectrometry. Based on biopsy tests, a cutoff value was determined using a receiver operating characteristic curve. In 26 children (seven children infected and 19 noninfected), paired breath samples were also measured by nondispersive infrared spectometry (NDIRS).

Biopsy tests demonstrated that 89 children (40%) were infected with H. pylori and 131 children were not infected. There were no statistical differences in mean delta 13C values at 20 min between male and female H. pylori-infected and noninfected patients. A receiver operating characteristic analysis defined the best cutoff value as 3.5 per thousand. The overall sensitivity and specificity at a cutoff value of 3.5 per thousand were 97.8% (95% CI = 92.1-99.7%) and 98.5% (95% CI = 96.4-100%), respectively: high sensitivity and specificity were demonstrated in all three age groups (< or =5, 6-10, and > or = 11 yr). There was a close correlation between the values with isotope ratio mass spectrometry and NDIRS methods (r = 0.998, p < 0.001).

The 13C-UBT with a cutoff value of 3.5 per thousand is an accurate diagnostic method for active H. pylori infection. The test with the NDIRS method is inexpensive and might be widely applied in clinical practice.

The effectiveness of Helicobacter pylori eradication regimens is influenced by antibiotic susceptibility of infecting strains. Data concerning antibiotic resistance in children are limited. We report the evolution of primary and secondary resistance in a series of Belgian children during the last 12 years.

From 1989 through 2000, H. pylori gastritis was diagnosed in 569 children, and antibiotic susceptibility tests were performed in 555. Eradication, using different schemes, failed in 128 of 457 treated children. After eradication failure antibiotic susceptibility determination was performed in 87 of 128. Comparison of antibiotic susceptibility of strains isolated from the gastric body and from the antrum was performed in 238 samples.

Resistance to amoxicillin was not observed. The rate of primary resistance to nitroimidazole derivatives was 18.0% (101 of 555) and remained constant throughout this period, whereas primary resistance to macrolides increased from an average of 6.0% (range, 0 to 10%) before 1995 to 16.6% (range, 10 to 25%, P < 0.001) thereafter. Antibiotic consumption in Belgium, especially macrolides, did not show important fluctuations during the study period. Secondary resistance developed in 39 of 87 patients (46%). Strains isolated from different gastric locations show identical susceptibility testing in all but 5 of 238.

Resistance of H. pylori to macrolides increased in our pediatric population which did not appear to correlate with macrolides prescription habits in our country. After eradication failure acquired secondary resistance was observed in one-half of the patients.

Reliable non-invasive tests that are feasible in early childhood are essential to the study of transmission of Helicobacter pylori, since most individuals get infected during the first years of life. New tests are validated by comparison with a "gold standard", but no single test for detection of H. pylori infection can be used as a fully reliable reference method. Therefore, concordant results of at least two biopsy-based tests (histology, culture, rapid urease test) are considered as the "gold standard". Most of the validation studies in children included only a few infants and toddlers, with low numbers particularly for H. pylori-infected individuals. Only when increasing numbers of patients were tested and separated into subgroups by age it became apparent that the accuracy of most tests is lower in young children if the same cut-off values are used as established for older children or adults. Therefore, statements such as "a test has been validated with good results in children" must be interpreted with caution, unless different age groups are considered with sufficient numbers of infected and non-infected children in each age group.

Helicobacter pylori (H. pylori) infection is usually acquired in early childhood. Noninvasive methods for detection of H. pylori infection are required to study its incidence, transmission, and clearance. They should be easy to perform, inexpensive, and have a high diagnostic accuracy, especially in infants and toddlers. Both serology and the 13C-urea breath test (13C-UBT) do not fulfill all these requirements. The aim of this study was to evaluate a new enzyme immunoassay for detection of H. pylori antigen in stool (Premier Platinum HpSA, Meridian Diagnostics, Cincinnati, OH) in a large cohort of children and to compare it to invasive techniques and the 13C-UBT.

HpSA was performed in 310 stool samples of 274 children divided into three groups. Group A consisted of 145 children and adolescents (0.5-19.8 yr, 66/145 <6 yr) who underwent upper endoscopy for various gastrointestinal symptoms. H. pylori status was defined by histology, culture, and rapid urease test from biopsies of the antrum and corpus. A 13C-UBT was performed in 133 of 145 children. Group B consisted of 22 patients (5.7-16.1 yr) who were retested with both noninvasive tests 8 wk after anti-H. pylori triple therapy. Group C consisted of 129 healthy infants and toddlers (0.9-3.1 yr) who were tested with the 13C-UBT. Children with discrepant or positive test results were retested after 2 and 12 months. Results of the HpSA were read at 450/620 nm by spectrophotometry. An optical density <0.100 was defined as negative, >0.120 as positive, and values between 0.100 and 0.120 were considered as equivocal.

In Group A, the HpSA gave false-negative results in five of 45 infected children and false-positive results in four of 100 noninfected children, whereas four patients (2.8%) showed equivocal results. In both infected and noninfected children, no relation between the optical density values and age was found. The 13C-UBT was correct in 132 of 133 children tested. In Group B, there was complete concordance between the HpSA and 13C-UBT: 19 children tested negative and three positive. In Group C, concordant results between the two noninvasive methods were found in 124 of 129 (96%) toddlers (122 negative and two positive). Retesting of five children with discrepant results revealed that, on initial testing, the HpSA was incorrect in two (one false-positive, one false-negative), and the 13C-UBT was incorrect in three (always false-positive).

In symptomatic children, the HpSA revealed a sensitivity of 88.9% (95% CI 77.3-96.3) and a specificity of 94.0% (88.1-97.7) compared to the 13C-UBT, 100% (94.0-100) and 98.9% (94.7-100), respectively. However, in healthy toddlers, the HpSA performed as well as the 13C-UBT with excellent concordance between the two noninvasive tests. There was no age dependency of the stool test results, and changing the cutoff would not have improved accuracy. Thus, the HpSA test seems suitable to monitor the success of anti-H. pylori therapy.

The present study evaluated two non-invasive diagnostic methods for H. pylori infection in children, i.e. an in-house ELISA using sonicated Campylobacter jejuni antigen for absorption of cross-reacting antibodies and an immunoblot kit (Helico Blot 2.0, Genelabs, Singapore). 13C -Urea breath test (13C-UBT) was used as reference

Sera and questionnaires were collected from 695/858 (81%) Swedish school children with mixed ethnic backgrounds within a cross-sectional, community-based study. Of 133 children with an ELISA OD value of > or = 0.1, all were screened with immunoblot and 107 made a 13C-UBT. The negative controls were 34/37 children from three school classes with an ELISA OD value of < 0.1 and volunteering for a 13C-UBT. An adjusted cut-off level for the ELISA of OD value 0.22 resulted in a sensitivity of 97.8%, a specificity of 95.8% and a concordance index of 97.2%. The Helico Blot 2.0 had a sensitivity of 97.8%, a specificity of 93.8% and a concordance index of 96.5%. The best concordance was seen for the 26.5 kDa (98.6%), 30 kDa (95.7%) and 19.5 kDa (91.5%) antigens. The corresponding concordance index for CagA was 78%, for VacA 73.8% and for the 35kDa antigen 68.8%. A significant difference in the distribution of the 19.5 and 26.5 kDa bands but not of CagA/VacA was noted by ethnic background. With an adjusted cut-off level for the enzyme-linked immunosorbent assay (ELISA), both non-invasive methods were found to have an adequate performance in a pediatric population. The differences in antibody response patterns by ethnic background represent a caveat in the interpretation of serological studies.

Hardly any other bacterial infection can be diagnosed with a similar variety of non-invasive and invasive tests as infection with H. pylori. Efficacy and specificity of well-proven tests such as urease test in biopsy specimens, histology, culture, and 13C breath test have been uniformly evidenced in numerous studies. Novel tests include molecular microbiological procedures, providing new opportunities for rapid detection of virulence factors and resistance genes, as well as antigen detection in feces. Though some open questions still need to be clarified, the latter test will gain major importance in the future. With the availability of the breath test and antigen detection in stool the need for the use of serological tests has been reduced, all the more so as the majority of the available quick tests have been shown to be of inadequate reliability. Well defined indications for the treatment of H. pylori infections are a major prerequisite for a reasonable use of this diagnostic armory.

This study of pediatric patients was intended to determine the suitability of stool PCR and two antigen enzyme immunoassays (EIAs; Premier Platinum HpSA and the novel FemtoLab H. pylori), which detect Helicobacter pylori antigens in feces, as pretreatment diagnostic tools and especially as posttreatment control. Forty-nine H. pylori-infected children with dyspepsia received eradication therapy. Successful treatment was determined by a negative [(13)C]urea breath test 4 and 12 weeks after discontinuation of therapy. Fecal specimens were collected prior to eradication therapy as well as 4 weeks after the end of treatment. Successfully treated children delivered stool samples at 6, 8, and 12 weeks posttreatment also. Specimens were examined by seminested PCR and Premier Platinum HpSA and were reexamined by both EIAs as soon as FemtoLab H. pylori was available. In the first test series, the overall sensitivities of PCR and Premier Platinum HpSA were 93.0 and 91.1%, respectively. With specimens collected at 4 weeks after treatment, the respective specificities were 68.8 and 79.3%. After longer follow-up periods, however, they gradually increased to 100 and 96.9%, respectively. In the new test series, Premier Platinum HpSA delivered a considerably lower number of false-positive results (4 versus 18), indicating intertest variations. The overall test sensitivity was 94.6%, and the overall specificity was 97.5%. FemtoLab H. pylori showed an excellent performance with an overall sensitivity and specificity of 98.2 and 98.1%, respectively. Thus, in contrast to PCR, both EIAs were shown to be suitable for early posttreatment control.

Across populations of children, Helicobacter pylori prevalence ranges from under 10% to over 80%. Low prevalence occurs in the U.S., Canada, and northern and western Europe; high prevalence occurs in India, Africa, Latin America, and eastern Europe. Risk factors include socioeconomic status, household crowding, ethnicity, migration from high prevalence regions, and infection status of family members. H. pylori infection is not associated with specific symptoms in children; however, it is consistently associated with antral gastritis, although its clinical significance is unclear. Duodenal ulcers associated with H. pylori are seldom seen in children under 10 years of age. H. pylori-infected children demonstrate a chronic, macrophagic, and monocytic inflammatory cell infiltrate and a lack of neutrophils, as compared with the response observed in adults. The effect of H. pylori infection on acid secretion in children remains poorly defined. The events that occur during H. pylori colonization in children should be studied more thoroughly and should include urease activity, motility, chemotaxis, adherence, and downregulation of the host response. The importance of virulence determinants described as relevant for disease during H. pylori infection has not been extensively studied in children. Highly sensitive and specific methods for the detection of H. pylori in children are needed, especially in younger pediatric populations in which colonization is in its early phases. Criteria for the use of eradication treatment in H. pylori-infected children need to be established. Multicenter pediatric studies should focus on the identification of risk factors, which can be used as prognostic indicators for the development of gastroduodenal disease later in life.

Helicobacter pylori infection causes chronic digestive diseases with a major public-health impact, yet the design of prevention measures is hampered by limited knowledge of transmission pathways. We studied the effect of family composition on H. pylori prevalence among rural Colombian children aged 2-9 years.

684 children were screened for H. pylori with the 13C-urea breath test. For each child, birth order, birth spacing, number of 2-9-year-old siblings, and number of H-pylori-positive 2-9-year-old siblings was recorded. Odds ratios were estimated by logistic regression, controlling for hygiene-related exposures, socioeconomic indicators, and the number of children in the household.

The odds of infection increased with the number of 2-9-year-old siblings in the household (odds ratios 1.4, 2.3, 2.6, and 4.3 for one, two, three, and four to five siblings, respectively). Compared with first-born children, odds ratios for children born second and third to ninth were 1.8 (95% CI 1.0-3.3) and 2.2 (1.0-4.3), respectively. Compared with children born 10 or more years after the next older household member, those born within 4 years were 4.1 times (CI 2.0-8.6) more likely to be infected; the age gap to the next younger household member displayed a weaker effect. The number of H-pylori-positive 2-9-year-old siblings had a particularly strong effect gradient (1.5, 3.2, 5.6, and 7.1, for one, two, three, and four positive siblings, respectively).

Among rural Andean children younger than 10 years, H. pylori infection seems to be transmitted most readily among siblings who are close in age, and most frequently from older siblings to younger ones.

Combination antimicrobial therapies for the effective eradication of Helicobacter pylori infection have been identified and are commercially available. Ongoing studies to improve eradication rates are based on modification of currently approved treatments. Management of H. pylori infection now focuses on which patients should be treated and, by extension, which should be tested, because all patients should have a positive test result for H. pylori before starting antimicrobial therapy. Peptic ulcer disease was believed to be caused by acid abnormalities until about two decades ago, when H. pylori was successfully cultured; the clinical records of an early proponent of an infectious cause of peptic ulcer disease were recently discovered. The role of H. pylori infection in gastroesophageal disease and in ulcer disease associated with nonsteroidal anti-inflammatory drugs have become intensely investigated topics. Consensus conferences among pediatric physicians are establishing practice guidelines for H. pylori management in children and adolescents.

The 13C-urea breath test for diagnosis of Helicobacter pylori infection has not been validated in infants and young children. The influence of age on the test results was studied by conventional validation against invasive methods and by mathematical estimation in a large pediatric population.

The breath test was performed in 1499 children aged 2 months to 18 years. After a fasting period of 4 hours or more, 75 mg 13C-urea was ingested with cold apple juice, breath samples were taken at baseline and at 15 and 30 minutes. The distribution of the natural logarithms of the delta-over baseline (DOB) values were calculated, and the optimal cutoff values between positive and negative test results and gray zones with a risk of misclassification more than 10% were determined for both time points. In a subgroup of 149 children results of the breath test were compared with concordant results of histology and rapid urease test; 53 of them were less than 6 years of age.

Logarithmic results of 1499 breath tests revealed two normally distributed subgroups with minimal overlap. The calculated optimal cutoff values were 4.7/1000 at 15 minutes and 5.0/1000 at 30 minutes. At 30 minutes, only 2.6% of all results were in the calculated gray zone (2.6-6.5/1000). Age was negatively correlated to DOB values of both negative (r = -0.223) and positive results (r = -0.291; P < 0.001). Breath test-negative and -positive children 6 or less years of age had significantly higher mean DOB values (P < 0.02) and a larger proportion of results within the gray zone than older children. Compared with biopsy-based results, the least discrepancies occurred at a cutoff of 5.0/1000: 0 of 61 infected (sensitivity 100%) and 6 of 88 noninfected children. Because five of the false-positive results were obtained in children less than 6 years of age, specificity and positive predictive values were lower in this age group than in older patients (88.1% vs. 97.8% and 68.8% vs. 98.0%, respectively).

Under the applied conditions, the 13C-urea breath test shows an excellent separation between positive and negative results. Because of some overlap and a strong age effect, definition of a gray zone appears more meaningful than a threshold value. Because infants and young children have a high risk for false-positive breath test results, the values for cutoff and gray zones may have to be adapted. Further validation studies against invasive methods are warranted in this age group.

Because in children Helicobacter pylori colonization could differ as compared to that in adults, gastric metabolism of urea and the reliability of the breath test must be evaluated. The aim of this study was to quantify the relationship between breath test and colonization.

We studied data from 50 endoscopies performed in 39 children and adolescents (20 girls, 19 boys, aged 3-18 years); 28 were infected with H. pylori. Biopsies were analyzed for histological and microbiological diagnosis of infection and for quantitative antral culture of H. pylori. A 13C urea breath test was performed on the same day as that of endoscopy (n = 33) or delayed between 2 and 90 days (n = 17).

Using a cut-off value of 3 delta/1000, sensitivity was 96.5%, and specificity was 91.5%. The three children showing discrepancies between breath test and biopsy results had a delta/1000 value close to the cut-off. For the 26 cases with a positive culture, we noted a significant correlation (r = 0.63; p < .001) that was not affected by the delay between breath test and gastroscopy.

This quantitative relation between bacterial density and delta/1000 permits increasing the reliability of the test by interpreting carefully those results that approach the cut-off value.