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Helicobacter pylori is a common component of the human stomach microbiota, possibly dating back to the speciation of Homo sapiens. A history of pathogen evolution in allopatry has led to the development of genetically distinct H. pylori subpopulations, associated with different human populations, and more recent admixture among H. pylori subpopulations can provide information about human migrations. However, little is known about the degree to which some H. pylori genes are conserved in the face of admixture, potentially indicating host adaptation, or how virulence genes spread among different populations. We analyzed H. pylori genomes from 14 countries in the Americas, strains from the Iberian Peninsula, and public genomes from Europe, Africa, and Asia, to investigate how admixture varies across different regions and gene families. Whole-genome analyses of 723 H. pylori strains from around the world showed evidence of frequent admixture in the American strains with a complex mosaic of contributions from H. pylori populations originating in the Americas as well as other continents. Despite the complex admixture, distinctive genomic fingerprints were identified for each region, revealing novel American H. pylori subpopulations. A pan-genome Fst analysis showed that variation in virulence genes had the strongest fixation in America, compared with non-American populations, and that much of the variation constituted non-synonymous substitutions in functional domains. Network analyses suggest that these virulence genes have followed unique evolutionary paths in the American populations, spreading into different genetic backgrounds, potentially contributing to the high risk of gastric cancer in the region., This work was supported by “Consejo Nacional de Ciencia y Tecnología” (CONACYT; no. 576951) grant to ZYM-R, and by Magnus Bergvalls Foundation and Swedish Society for Medical Research (SSMF) to KT. SKS and BP are funded by the Medical Research Council (MR/L015080/1). Supported in part by the US National Cancer Institute National Cancer Institute to DRM (P01 CA028842, R01 CA190612, K07 CA125588, P30 CA068485). We are very grateful to Daniel Falush (Unit of Statistical Genetics of Bacteria, Institut Pasteur of Shanghai) for his critical input during the analysis of the presented data. We acknowledge the Aklavik H. pylori Project Planning Committee (Northwest Territories, Canada) for providing input on our presentation of this analysis.

Background. Methylmercury contamination of the environment represents a substantial environmental health concern. Human exposure to methylmercury occurs primarily through consumption of fish and marine mammals. Heavily exposed subgroups include sport or subsistence fishers residing in Arctic communities. We aimed to estimate the association of fish/whale consumption patterns of Canadian Arctic subsistence fishers with the internal dose of methylmercury as measured in hair. Methods. This research was conducted within ongoing community projects led by the CANHelp Working Group in Aklavik and Fort McPherson, Northwest Territories and Old Crow, Yukon. We interviewed each participant using a fish-focused food-frequency questionnaire during September-November 2016 and collected hair samples concurrently. Methylmercury was measured in the full-length of each hair sample using gas chromatography inductively-coupled plasma-mass spectrometry. Multivariable linear regression estimated beta-coefficients and 95% confidence intervals (CIs) for the effect of fish/whale consumption on hair-methylmercury concentrations. Results. Among 101 participants who provided hair samples and diet data, the mean number of fish/whale species eaten was 3.5 (SD:1.9). The mean hair-methylmercury concentration was 0.60μg/g (SD:0.47). Fish/whale consumption was positively associated with hair-methylmercury concentration, after adjusting for sex, hair length and use of permanent hair treatments. Hair-methylmercury concentrations among participants who consumed the most fish/whale in each season ranged from 0.30- 0.50μg/g higher than those who consumed Conclusions. In this population of Canadian Arctic subsistence fishers, hair-methylmercury concentration increased with fish/whale consumption, but the maximum concentrations were below Health Canada’s 6.0μg/g threshold for safe exposure.

Background Our community-driven projects address concerns of Canadian Arctic Indigenous communities about Helicobacter pylori (Hp) infection, responsible for elevated gastric cancer mortality in the region. Community research partners wished to learn whether bacterial characteristics determine severity of Hp-related disease in their communities. We aimed to describe gastric histopathology by cagA genotype of Hp isolated from residents of 7 Indigenous communities in the Northwest Territories and Yukon. Methods Participants underwent gastroscopy with 5-6 biopsies taken for histopathological assessment and 2 biopsies taken for tissue culture during 2008-2017. We used multiple PCR reactions and DNA sequence analysis to classify Hp genotypes as cagA+ or cagA-. A single pathologist used the updated Sydney classification system to grade severity of 5 gastric pathology outcomes: Hp density; chronic gastritis; active gastritis; atrophy; and intestinal metaplasia. We estimated prevalence of each outcome with 95% confidence intervals (CI) by gastric subsite and cagA status. Results Of 262 Hp isolates assessed, 142 (54%) were cagA+. Prevalence of moderate-high Hp density, severe chronic gastritis, moderate-severe active gastritis, atrophy, and metaplasia were (%[CI]): respectively, 78[70-85], 44[36-53], 65[56-72], 55[46-63], 25[18-33] in cagA+ participants and 61[52-70], 35[27-44], 31[23-40], 32[23-41], 8[4-15] in cagA- participants. cagA+ participants had higher prevalence of all outcomes in antrum and corpus. Conclusion Hp-infected Indigenous residents of Arctic Canada who harbored cagA-positive strains had higher prevalence of more severe gastric pathology than those with cagA-negative strains. Key messages Community-driven research answers questions posed by those who bear the disease burden.

Background Indigenous communities across the circumpolar north have elevated H. pylori (Hp) prevalence and stomach cancer incidence. We aimed to describe the Hp-associated disease burden among western Canadian Arctic participants in community-driven projects that address concerns about health risks from Hp infection. Methods During 2008–2013, participants underwent Hp screening by urea breath test and gastroscopy with gastric biopsies. We estimated Hp prevalence and prevalence by Hp status of endoscopic and histopathologic diagnoses. Results Among 878 participants with Hp status data, Hp prevalence was: 62% overall; 66% in 740 Indigenous participants; 22% in 77 non-Indigenous participants (61 participants did not disclose ethnicity); 45% at 0–14 years old, 69% at 15–34 years old, and 61% at 35–96 years old. Among 309 participants examined endoscopically, visible mucosal lesions were more frequent in the stomach than the duodenum: the gastric to duodenal ratio was 2 for inflammation, 8 for erosions, and 3 for ulcers. Pathological examination in 308 participants with gastric biopsies revealed normal gastric mucosa in 1 of 224 Hp-positive participants and 77% (65/84) of Hp-negative participants with sharp contrasts in the prevalence of abnormalities between Hp-positive and Hp-negative participants, respectively: moderate-severe active gastritis in 50 and 0%; moderate-severe chronic gastritis in 91 and 1%; atrophic gastritis in 43 and 0%; intestinal metaplasia in 17 and 5%. Conclusions The observed pattern of disease is consistent with increased risk of stomach cancer and reflects substantial inequity in the Hp-associated disease burden in western Arctic Canadian hamlets relative to most North American settings. This research adds to evidence that demonstrates the need for interventions aimed at reducing health risks from Hp infection in Indigenous Arctic communities.

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection. Stool donors are essential, but difficult to recruit and retain. We aimed to identify factors influencing willingness to donate stool. This multi-center study with a 32-item questionnaire targeted young adults and health care workers via social media and university email lists in Edmonton and Kingston, Canada; London and Nottingham, England; and Indianapolis and Boston, USA. Items included baseline demographics and FMT knowledge and perception. Investigated motivators and deterrents included economic compensation, screening process, time commitment, and stool donation logistics. Logistic regression and linear regression models estimated associations of study variables with self-assessed willingness to donate stool. 802 respondents completed our questionnaire: 387 (48.3%) age 21-30 years, 573 (71.4%) female, 323 (40%) health care workers. Country of residence, age and occupation were not associated with willingness to donate stool. Factors increasing willingness to donate were: already a blood donor (OR 1.64), male, altruism, economic benefit, knowledge of how FMT can help patients (OR 1.32), and positive attitudes towards FMT (OR 1.39). Factors decreasing willingness to donate were: stool collection unpleasant (OR 0.92), screening process invasive (OR 0.92), higher stool donation frequency, negative social perception of stool, and logistics of collection/transporting feces. We conclude that 1) blood donors and males are more willing to consider stool donation; 2) altruism, economic compensation, and positive feedback are motivators; and 3) screening process, high donation frequency, logistics of collection/transporting feces, lack of public awareness, and negative social perception are deterrents. Considering these variables could maximize donor recruitment and retention.

Background Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required. Methods A systematic review of the literature (time period: 2009-2014) was performed. Representatives of both societies evaluated the quality of evidence using GRADE (Grading of Recommendation Assessment, Development, and Evaluation) to formulate recommendations, which were voted upon and finalized using a Delphi process and face-to-face meeting. Results The consensus group recommended that invasive diagnostic testing for H pylori be performed only when treatment will be offered if tests are positive. To reach the aim of a 90% eradication rate with initial therapy, antibiotics should be tailored according to susceptibility testing. Therapy should be administered for 14 days, emphasizing strict adherence. Clarithromycin-containing regimens should be restricted to children infected with susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with proton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should be monitored after 4 to 8 weeks by reliable noninvasive tests. Conclusions The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection. Therefore, we recommend against a test and treat strategy. Decreasing eradication rates with previously recommended treatments call for changes to first-line therapies and broader availability of culture or molecular-based testing to tailor treatment to the individual child.

Summary of Problem Alaska Native (AN) people experience higher incidence of, and mortality from, gastric cancer compared to other U.S. populations1, 2. Compared to the general U.S. population, gastric cancer in AN people occurs at a younger age, is diagnosed at later stages, is more evenly distributed between the sexes, and is more frequently signet-ring or diffuse histology3. It is known that the prevalence of Helicobacter pylori (Hp) infection, a risk factor for gastric cancer, is high in AN people4; however, high antimicrobial resistance combined with high reinfection rates in Alaska make treatment at the population level complex5. In addition, health issues in AN people are uniquely challenging due to the extremely remote locations of many residents. A multiagency workgroup hosted a symposium in Anchorage that brought internationally-recognized experts and local leaders together to evaluate issues around gastric cancer in the AN population. The overall goal of this symposium was to identify the best strategies to combat gastric cancer in the AN population through prevention and early diagnosis.

SUMMARYHelicobacter pyloriinfection is a major cause of peptic ulcer and is also associated with chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, and adenocarcinoma of the stomach. Guidelines have been developed in the United States and Europe (areas with low prevalence) for the diagnosis and management of this infection, including the recommendation to ‘test and treat’ those with dyspepsia. A group of international experts performed a targeted literature review and formulated an expert opinion for evidenced-based benefits and harms for screening and treatment ofH. pyloriin high-prevalence countries. They concluded that in Arctic countries whereH. pyloriprevalence exceeds 60%, treatment of persons withH. pyloriinfection should be limited only to instances where there is strong evidence of direct benefit in reduction of morbidity and mortality, associated peptic ulcer disease and MALT lymphoma and that the test-and-treat strategy may not be beneficial for those with dyspepsia.

The role of environmental reservoirs in H. pylori transmission remains uncertain due to technical difficulties in detecting living organisms in sources outside the stomach. Residents of some Canadian Arctic communities worry that contamination of the natural environment is responsible for the high prevalence of H. pylori infection in the region. This analysis aims to estimate associations between exposure to potential environmental sources of biological contamination and prevalence of H. pylori infection in Arctic Canada. Using data from 3 community-driven H. pylori projects in the Northwest and Yukon Territories, we estimated effects of environmental exposures on H. pylori prevalence, using odds ratios (OR) and 95% confidence intervals (CI) from multilevel logistic regression models to adjust for household and community effects. Investigated exposures include: untreated drinking water; livestock; dogs; cats; mice or mouse droppings in the home; cleaning fish or game. Our analysis did not identify environmental exposures associated clearly with increased H. pylori prevalence, except any exposure to mice or mouse droppings (OR = 4.6, CI = 1.2–18), reported by 11% of participants. Our multilevel models showed H. pylori clustering within households, but environmental exposures accounted for little of this clustering; instead, much of it was accounted for by household composition (especially: having infected household members; number of children). Like the scientific literature on this topic, our results do not clearly implicate or rule out environmental reservoirs of H. pylori; thus, the topic remains a priority for future research. Meanwhile, H. pylori prevention research should seek strategies for reducing direct transmission from person to person.

BACKGROUND:Helicobacter pyloriinfection occurs more frequently in Arctic Aboriginal settings than elsewhere in North America and Europe. Research aimed at reducing health risks fromH pyloriinfection has been conducted in the Aboriginal community of Aklavik, Northwest Territories.OBJECTIVE: To compare the effectiveness of the Canadian standard therapy with an alternative therapy for eliminatingH pyloriinfection in Aklavik.METHODS: Treatment-naiveH pylori-positive individuals were randomly assigned to a 10-day regimen (oral twice-daily doses) with rabeprazole (20 mg): standard triple therapy (proton pump inhibitor, added clarithromycin [500 mg] and amoxicillin [1 g] [PPI-CA]); sequential therapy (ST) added amoxicillin (1 g) on days 1 to 5, and metronidazole (500 mg) and clarithromycin (500 mg) on days 6 to 10. Participants with clarithromycin-resistantH pyloriwere randomly assigned to ST or quadruple therapy. Treatment effectiveness was estimated as per cent (95% CI) with a negative urea breath test at least 10 weeks after treatment.RESULTS: Of 104 (53 PPI-CA, 51 ST) randomized participants, 89 (49 PPI-CA, 40 ST) had post-treatment results. Per-protocol treatment effectiveness was 59% (95% CI 45% to 73%) for PPI-CA and 73% (95% CI 58% to 87%) for ST. Based on intention to treat, effectiveness was 55% (95% CI 41% to 69%) for PPI-CA and 57% (95% CI 43% to 71%) for ST. Of 77 participants (43 PPI-CA, 34 ST) with 100% adherence, effectiveness was 63% (95% CI 43% to 82%) for PPI-CA and 81% (95% CI 63% to 99%) for ST.CONCLUSIONS: While additional evidence is needed to confirm that ST is more effective for Arctic Aboriginal communities than the Canadian standardH pyloritreatment, these results show standard PPI-CA treatment to be inadequate for communities such as Aklavik.

The aim of the present study was to estimate the incidence and spontaneous clearance rate of Helicobacter pylori infection and the effect of some variables on these outcomes in schoolchildren.From May 2005 to December 2010, 718 schoolchildren enrolled in 3 public boarding schools in Mexico City participated in the follow-up. At the beginning of the study and every 6 months thereafter, breath samples were taken to detect H pylori infection; blood samples and anthropometric measurements were taken to evaluate nutritional status. Data on sociodemographic characteristics were collected.The prevalence of H pylori infection was 38%. The incidence rate was 6.36%/year. Schoolchildren with anemia or iron deficiency at the beginning of the study (who received iron supplements) showed a higher infection acquisition rate than those with normal iron nutritional status, hazard ratio (HR) 12.52 (95% confidence interval [CI] 4.01%-39.12%), P0.001 and HR 2.05 (95% CI 1.09%-3.87%), P = 0.027, respectively. The spontaneous clearance rate of the infection was 4.74%/year. The spontaneous clearance rate was higher in children who had iron deficiency (who received iron supplements), HR 5.02 (95% CI 1.33%-18.99%), P = 0.017, compared with those with normal nutritional iron status. It was lower in schoolchildren with ≥ 2 siblings compared with schoolchildren with 1 or no siblings, HR 0.23 (95% CI 0.08%-0.63%), P = 0.004.H pylori infection status is dynamic in schoolchildren. Variables related to health status and infection transmission, such as iron status and number of siblings, are important for the incidence and spontaneous clearance of H pylori infection.

This article presents a review of the literature on the epidemiology and public health implications of Helicobacter pylori infection published from April 2008 through to March 2009. The authors used MeSH terms "Helicobacter infections epidemiology,""Helicobacter infections prevention and control" to search multiple databases (PubMed, Embase, Cochrane, Cochrane Library, EBMR, BIOSIS), and independently searched PubMed using the term "Helicobacter" with "Epidemiology,""Transmission,""Prevalence" or "Environment." Articles without topical relevance were excluded. Two additional papers known to the authors were added. The identified literature is summarized by subtopic: reviews; prevalence; incidence; transmission; risk factors; and public health policy.

Purpose Factors that determine persistence of untreated Helicobacter pylori (H. pylori) infection in childhood are not well understood. We estimated risk differences for the effect of incidental antibiotic exposure on the probability of a detected clearance at the next test after an initial detected H. pylori infection. Methods The Pasitos Cohort Study (1998–2005) investigated predictors of H. pylori infection in children from El Paso, Texas, and Juarez, Mexico. Children were screened for infection at 6-month target intervals from 6 to 84 months of age, using the 13C-urea breath test corrected for body-size-dependent variation in CO2 production. Exposure was defined as courses of any systemic antibiotic (systemic) or those with anti-H. pylori action (HP-effective) reported for the interval between initial detected infection and next test. Binomial regression models included country of residence, mother's education, adequacy of prenatal care, age at infection, and interval between tests. Results Of 205 children with a test result and antibiotic data following a detected infection, the number of children who took ≥1 course in the interval between tests was 74 for systemic and 33 for HP-effective. The proportion testing negative at the next test was 66% for 0 courses, 72% for ≥1 systemic course, and 79% for ≥1 HP-effective course. Adjusted risk differences (95%CI) for apparent clearance, comparing ≥1 to 0 courses were 10% (1–20%) for systemic and 11% (0–21%) for HP-effective. Conclusions Incidental antibiotic exposure appears to influence the duration of childhood H. pylori infection but seems to explain only a small portion of spontaneous clearance. Copyright © 2009 John Wiley & Sons, Ltd.

Summary The uncertain accuracy of methods for detecting Helicobacter pylori infection in young children complicates research on this infection in early life. The aim of the present report was to describe the correspondence between positive serology and positive urea breath test (UBT) in children followed from age 0 to 24 months in the Pasitos Cohort Study, conducted along the US–Mexico border at El Paso and Juarez. Children were recruited before birth during 1998–2000 and examined at target ages of 6, 12, 18 and 24 months. H. pylori infection was detected using an enzyme immunoassay for serum immunoglobulin G antibodies and the 13C-urea breath test corrected for age-dependent variation in CO2 production. Of 472 children, 125 had one or more positive UBT results and 46 had one or more positive serology results. The prevalence of H. pylori infection at target ages of 6, 12, 18 and 24 months was 7%, 14%, 16% and 19%, respectively, by UBT and 8%, 2%, 3% and 3%, respectively, by serology. Few (

Summary Background Several meta-analyses assessing the efficacy of anti-Helicobacter pylori treatment in adults have been published but a comparable meta-analysis in children is lacking. Aims To summarize the efficacy of treatments aimed at eradicating H. pylori in children and to identify sources of variation in treatment efficacy across studies. Methods We searched Medline, reference lists from published study reports, and conference proceedings for anti-H. pylori treatment trials in children. Weighted meta-regression models were used to find sources of variation in efficacy. Results Eighty studies (127 treatment arms) with 4436 children were included. Overall, methodological quality of these studies was poor with small sample sizes and few randomized-controlled trials. The efficacy of therapies varied across treatment arms, treatment duration, method of post-treatment assessment and geographic location. Among the regimens tested, 2–6 weeks of nitroimidazole and amoxicillin, 1–2 weeks of clarithromycin, amoxicillin and a proton pump inhibitor, and 2 weeks of a macrolide, a nitroimidazole and a proton pump inhibitor or bismuth, amoxicillin and metronidazole were the most efficacious in developed countries. Conclusions Before worldwide treatment recommendations are given for eradication of H. pylori, additional well-designed randomized placebo-controlled paediatric trials are needed, especially in developing countries where both drug resistance and disease burden is high.

We report here the complete genome sequences of two Amerind Helicobacter pylori strains from Aklavik, Northwest Territories, Canada. One strain contains extra iron-cofactored urease genes and ~140 rearrangements in its chromosome relative to other described strains (typically differing from one another by H. pylori .

Background The Pasitos Cohort Study has followed children in El Paso, Texas and Ciudad Juarez, Mexico since 1998 to identify determinants of Helicobacter pylori infection. This paper describes patterns of acquisition and elimination of H. pylori infection in 468 children from birth to 24 months. Methods Mothers were recruited during pregnancy at maternal-child clinics; children were targeted for follow-up examinations every 6 months after birth. H. pylori infection was detected using the 13 C-urea breath test, corrected for age-dependent variation in CO 2 production. Results Test results were available for 359, 341, 269, and 215 children around target ages of 6, 12, 18, and 24 months, respectively. The person-time at risk of a first detectable infection was 7742 person-months; 128 first infections were detected, thus the incidence rate was 1.7% per month (95% confidence interval 1.4-2.0%). Rates were similar in boys and girls and on both sides of the border; evidence suggests, however, that this similarity could be due to selection bias. Among children with follow-up after a positive test, 77% tested negative at a later visit. Conclusions The initial acquisition of detectable H. pylori infection occurred at a rate of 20% per year among Pasitos Cohort children from birth to 24 months of age. A key finding, with implications for clinical, community health, and research settings, is that most of these infections did not persist. The transient nature of early H. pylori infection should be considered when designing research or contemplating therapeutic intervention for this age group.

We used data from a randomized placebo-controlled clinical trial to examine the relationship between Helicobacter pylori and reflux symptoms in nonulcer dyspepsia patients randomly assigned anti-Helicobacter pylori triple therapy alone, calcium carbonate alone, or in combination with triple therapy, tetracycline, or placebo. We compared risk differences for posttreatment Helicobacter pylori status and increased reflux symptoms from crude, multivariable and stratified multivariable analyses. In crude analyses, 54% of subjects without Helicobacter pylori after-treatment reported an increase in reflux compared to 41% of those with persistent infection (risk difference = 13%; P = 0.07). Only subjects with multifocal atrophic gastritis assigned to calcium carbonate reported an increase in reflux symptoms more frequently when Helicobacter pylori was absent versus when it persisted (risk difference = 52%; P = 0.0001). Therefore, the interaction of calcium carbonate use, chronic multifocal atrophic gastritis, and the absence of Helicobacter pylori may increase reflux symptoms.

For this study, we isolated Helicobacter pylori from wastewater by a series of steps beginning with immunomagnetic separation and cell culture. After Gram staining and three standard microbial tests, the 16S rRNA sequences of a total of 23 out of 37 putative H. pylori isolates were verified by PCR. Eleven H. pylori isolates were genotyped and fell into four vacA classes: those with the vacA allelic variants s1a and m1 , s1b and m1 , s2 and m2 , or s2 and m1 . Most H. pylori isolates were of the vacA s1a / m1 type, which has been shown to be associated with advanced diseases based on genotyping of H. pylori from gastric cancer patients. These results demonstrated that H. pylori survives in water and may be a potential source of H. pylori transmission, especially where water is not adequately treated.

Background A vast number of Helicobacter pylori treatment trials have been conducted. Regimens may vary in efficacy in different patient populations. Methods We identified sources of treatment effect variation from 618 treatment groups using weighted cross-classified multi-level meta-regression models. Summary effect estimates were calculated within groups that lacked identified heterogeneity. Results Overall, treatment was less successful with shorter treatment duration and dual drug (versus triple or quadruple drug) therapies. For nitroimidazole-based regimens, treatment was less successful in populations with frequent childhood H. pylori infection or metronidazole resistance and more successful in northeastern Asia. Non-nitroimidazole treatments of longer duration and those from less recent reports were most successful. Some one-week regimens--(nitroimidazole/ tetracycline/bismuth, ranitidine bismuth citrate/amoxicillin/clarithromycin, and clarithromycin/amoxicillin/proton pump inhibitor) were highly successful in northeastern Asia regardless of metronidazole resistance. The most successful regimen in populations with both a high prevalence of metrondiazole resistance and frequent infection in children (metronidazole/furazolidone/amoxicillin) eliminated fewer than 70% of infections. Conclusions More effective treatments are needed for most populations of the world where H. pylori infection in children and drug resistance are common. Current treatment guidelines do not coincide with the best treatment regimens identified in this meta-analysis.

Helicobacter pylori infection has been linked to a spectrum of gastroduodenal diseases of broad public health impact, yet the natural history of this frequently asymptomatic infection remains poorly understood. Evidence suggests that initial acquisition occurs primarily during childhood and may persist throughout life. The seroprevalence of H. pylori antibodies was examined in 365 primary schoolchildren aged 4-7 years in a low-income United States/Mexico border community from January to May 1996. Overall, 21% of the 365 children tested positive, with a significant monotonic decrease in seroprevalence by 1-year age intervals (36% in children aged 4 years, 24% in those aged 5 years, 20% in those aged 6 years, and 14% in those aged 7 years). The odds ratio for each 1-year age increase was 0.76 (95% confidence interval: 0.6, 1.0) after adjustment for relevant covariates. Given that H. pylori antibodies diminish after infection clears, this trend suggests that transient infection may be common in young children. In contrast, hepatitis A virus seroprevalence increased with age. There was a moderate association (odds ratio = 1.47, 95% confidence interval: 0.8, 2.9) of H. pylori with hepatitis A virus seroprevalence that weakened after adjustment for age and socioeconomic status (odds ratio = 1.26, 95% confidence interval: 0.6, 2.5). Follow-up studies are needed to clarify the natural history of Helicobacter pylori infection and identify predictors of initial acquisition, persistence, and recurrence.

Accumulating evidence has implicated Helicobacter pylori, an established cause of chronic gastritis and peptic ulcer, in the etiology of gastric cancer. Control of this infection would reduce the occurrence of chronic gastritis and peptic ulcer and might substantially lower the risk of stomach cancer as well. The public health impact of this infectious agent warrants efforts to identify preventive measures. This paper reviews the evidence linking H. pylori infection to gastric cancer and evaluates the potential for control in high-risk populations. Current obstacles to H. pylori control are discussed, including the link to poor socioeconomic conditions, difficulty in identifying incident cases, lack of natural immunity to reinfection, limited effectiveness of antibiotic therapy in high-prevalence populations, and incomplete knowledge regarding the reservoir of infection, mode of transmission, host susceptibility factors, and the potential for developing an effective vaccine. Worthwhile avenues of research include studies designed to identify modifiable risk factors for acquisition of the infection, modifiable host factors that may increase resistance to chronic infection, more effective antibiotic therapies, and effective vaccines.

Introduction . Helicobacter pylori infection is an emerging health concern to some northern Canadian Aboriginal communities and their clinicians. Clinicians in the north perceive H. pylori infection to be a major clinical problem because they find H. pylori infection in many patients evaluated for common stomach complaints, leading to frequent demand for treatment, which often fails. Moreover, public health authorities identified the need for information to develop locally appropriate H. pylori control strategies. We described adherence and identified barriers to completing treatment among H. pylori -positive participants in a community-based project inspired by local concerns about H. pylori infection risks. Methods . In 2008, 110 H. pylori -positive participants (diagnosed by a breath test, histopathology and/or culture) of the Aklavik H. pylori project were randomised to standard-of-care or sequential treatment. We ascertained adherence by interviewing participants using a structured questionnaire. We estimated adherence frequencies as the proportion of participants who reported taking either 100% of doses (perfect adherence) or ≥80% of doses (good adherence). To compare the proportion with perfect or good adherence in subgroups, we report proportion differences and 95% confidence intervals (CI). Results . Of 87 participants who were interviewed, 64% reported perfect adherence and 80% reported good adherence. We observed more frequent perfect adherence for: standard therapy (67%) versus sequential (62%); males (76%) versus females (52%); participants 40–77 years (79%) versus 17–39 (50%). Proportion differences were 5% (CI: −15, 25) for standard versus sequential therapy; 23% (CI: 4, 43) for male versus female; and 29% (CI: 10, 48) for 40–77 versus 15–39 years for perfect adherence. Of the 29 participants who reported poor adherence (

Helicobacter pylori testing and treatment has become a subject of intense debate and confusion worldwide in recent years, for both laboratory scientists and clinicians. The gastric pathogen H. pylori is believed to infect up to half of the world's population disproportionately, yet it remains a challenging diagnosis for many physicians worldwide. New testing mechanisms have been introduced, but no single universal approach for testing and treating H. pylori has been established to date. In effect, no population on earth has been spared from these chronic infections, but regional differences in prevalence and associated disease severity do exist. Not unexpectedly, there also exist regional approaches in the diagnosis, treatment, and management of these patients. This Q&A borrows the experience of 3 international experts in the field of H. pylori to reflect on the current status of H. pylori management and challenges on 3 separate continents, specifically Australia, Europe, and North America. Several different guidelines exist for the diagnosis/treatment of H. pylori infections. What controversy or challenges do you perceive with current guidelines? Barry Marshall: Guidelines for the treatment of H. pylori infections are aimed toward achieving a cure rate of at least 85%. In the past 10 years, because of gradually increasing resistance to macrolides, the very successful and popular combination treatment using a proton pump inhibitor (PPI),6 clarithromycin, and amoxicillin has declined in effectiveness from greater than an 85% cure rate originally, to the region of 70%–80% in some areas where long-acting macrolides have been used for 10 or more years. This has created research interest in the evaluation of newer and more intensive therapies, often with extra antibiotics added to hopefully eradicate the H. pylori without the emergence of resistant isolates. Over the years, shorter and more-intensive treatments for H. pylori infection have been tried, and these are …

This paper critically reviews the reported data regarding the transmission of Helicobacter pylori. The mode of transmission remains poorly understood ; no single transmission pathway has been clearly identified. Laboratory studies have experienced difficulty in isolating this organism from material other than gastric tissue. The problematic detection of this bacterium has presented obstacles to pinpointing portals of entry and exit and to implicating or ruling out environmental reservoirs. It is shown additionally that knowledge of H. pylori transmission is limited due to lack of solid epidemiological evidence from population-based analyses that adequately consider confounding. Reported observations in general support a person-to-person mode of transmission that occurs most frequently early in life ; H. pylori is consistently linked to conditions associated with residential crowding in childhood. Laboratory studies have yielded evidence in favour of both faecal-oral and oral-oral pathways. However, a role for either waterborne or zoonotic transmission has not been ruled out. The failure of investigations to single out a mode of transmission for H. pylori signals the possibility of multiple transmission pathways.

A new Helicobacter pylori infection affects growth velocity negatively, and clearing the infection produces a small significant rebound, but it is not known whether height and weight in children are impacted over the long term.We investigated 295 school-age children followed in 2 cohorts, treated (150) and untreated (145), from 2004 for 3.7 years with 1105 child-years of observation. Follow-up intervals were 3 months for anthropometry measurements and 6 months for H. pylori status ascertained by urea breath test. Height in centimeters and weight in kilograms were analyzed using growth models.A multivariate mixed model that adjusted for age, sex, father's education, and number of siblings found no significant differences in height or weight at baseline by H. pylori status. The same model showed a significant impact of clearing H. pylori across time, with increasing significant differences in average height and weight as the follow-up progressed.Children who were always negative or who cleared the infection grew significantly faster than those who stayed positive after adjusting for other covariates. This study suggests that school-age children's growth benefits from being treated for H. pylori infection.

Background Helicobacter pylori infection affects about half of the world's population and is usually acquired in childhood. The infection has been associated with chronic gastritis, peptic ulcer, and stomach cancer in adulthood. Little is known, however, about its consequences on child health. We examined the effect of H. pylori infection on growth among school-age children in the Colombian Andes by comparing growth velocity in the presence and absence of H. pylori infection. Methods Children who were 4-8 years old in 2004 were followed up in a community where infected children received anti-H. pylori treatment (n = 165) and a comparison community (n = 161) for a mean of 2.5 years. Anthropometry measurements were made every 3 months and H. pylori status ascertained by urea breath test every 6 months. Growth velocities (cm/month) were compared across person-time with and without infection, using mixed models for repeated measures. Results In the untreated community, 83% were H. pylori-positive at baseline and 89% were -positive at study end. The corresponding prevalences were 74% and 46%, respectively, in the treated community. Growth velocity in the pretreatment interval was 0.44 (standard deviation [SD] = 0.13) cm/month. Models that adjusted for age, sex, and height estimated that H. pylori-positive children grew on average 0.022 cm/month (95% confidence interval = 0.008 to 0.035) slower than H. pylori-negative children, a result that was not appreciably altered by adjustment for socioenvironmental covariates. Conclusions This study suggests that chronic H. pylori infection is accompanied by slowed growth in school-age Andean children.

OBJECTIVES Cross-sectional studies suggest that Helicobacter pylori may be transmitted between siblings. The present study aimed to estimate the effect of an H pylori-infected sibling on the establishment of a persistent H pylori infection. MATERIALS AND METHODS The authors used data collected from a Texas-Mexico border population from 1998 to 2005 (the "Pasitos Cohort Study"). Starting at age 6 months, H pylori and factors thought to be associated with H pylori were ascertained every 6 months for participants and their younger siblings. Hazard ratios were estimated from proportional hazards regression models with household-dependent modeling. RESULTS Persistent H pylori infection in older siblings always preceded persistent infection in younger siblings. After controlling for mother's H pylori status, breast-feeding, antibiotic use, and socioeconomic factors, a strong effect was estimated for persistent H pylori infection in an older sibling on persistent infection in a younger sibling (hazard ratio 7.6, 95% confidence interval 1.6-37], especially when the difference in the age of the siblings was less than or equal to 3 years (hazard ratio 16, 95% confidence interval 2.5-112). CONCLUSIONS These results suggest that when siblings are close in age, the older sibling may be an important source of H pylori transmission for younger siblings.

The mode of transmission of Helicobacter pylori, a bacterium causing gastric cancer and peptic ulcer disease, is unknown although waterborne transmission is a likely pathway. This study investigated the hypothesis that access to treated water and a sanitary sewerage system reduces the H. pylori incidence rate, using data from 472 participants in a cohort study that followed children in Juarez, Mexico, and El Paso, Texas, from April 1998, with caretaker interviews and the urea breath test for detecting H. pylori infection at target intervals of six months from birth through 24 months of age. The unadjusted hazard ratio comparing bottled/vending machine water to a municipal water supply was 0.71 (95% confidence interval (CI): 0.50, 1.01) and comparing a municipal sewer connection to a septic tank or cesspool, 0.85 (95% CI: 0.60, 1.20). After adjustment for maternal education and country, the hazard ratios decreased slightly to 0.70 (95% confidence interval: 0.49, 1.00) and 0.77 (95% confidence interval: 0.50, 1.21), respectively. These results provide moderate support for potential waterborne transmission of H. pylori.

Rapid immunochromatographic tests for Helicobacter pylori infection have been developed to allow "near-patient" testing. We therefore performed a pilot study to test a rapid immunochromatographic stool antigen test for the diagnosis of H. pylori infection in asymptomatic children. We tested stool specimens collected from children participating in a cohort study in the United States and Mexico. H. pylori-positive status was defined by positivity on at least 2 tests: a commercial H. pylori stool antigen enzyme immunoassay, an immunoglobulin G antibody enzyme immunoassay, and the C-urea breath test. Negative H. pylori status was defined by negative findings of all of these tests. Of 52 children (22 girls, 30 boys) 25 were H. pylori-positive, 19 H. pylori-negative, and 8 uncertain (eg, presumably negative; positive findings on 1 of the 3 noninvasive tests). The sensitivity and specificity of the new stool antigen test for those with definite H. pylori status were 100% (exact 95% CI 86.3%-100% and 82.4%-100%, respectively). This rapid stool antigen test may prove useful for point-of-care testing and epidemiological field studies. Larger prospective studies are needed in symptomatic and asymptomatic children for more precise estimates.

Rates of Helicobacter pylori infection are traditionally higher in developing countries than in developed countries, but the specific reasons for these differences are not fully clear. While chronic diseases resulting from H. pylori are generally of adult onset, chronic infection usually begins in childhood. In this cross-sectional study (1998-2000), the authors compared prevalences of H. pylori infection among children under age 6 years on both sides of the Rio Grande. Participants included 264 children of women from low-income families who were receiving services at health clinics in Juarez, Mexico, or El Paso, Texas, from April 1998 through October 2000. Data were collected through personal interviews and serologic testing for H. pylori antibodies. The crude odds ratio for H. pylori prevalence among Mexican children as compared with US children was 3.94 (95% confidence interval: 1.72, 9.06). After adjustment for covariates, the odds ratio decreased to 1.70 (95% confidence interval: 0.64, 4.52). The adjustments that produced the greatest reduction in the odds ratio for location were those for household crowding and maternal education. This study identified specific factors that may explain geographic variation in H. pylori prevalence among children.

Background: The Canadian North Helicobacter pylori (CANHelp) Working Group conducts community Helicobacter pylori projects to address public concerns about health risks from this infection in Arctic Canada, where H.pylori prevalence and stomach cancer rates are elevated. At the request of community leaders of Fort McPherson, Northwest Territories (population~800, ~95% Aboriginal), the ongoing Fort McPherson H. pylori Project launched in 2012 to investigate the disease burden related to H.pylori infection and identify strategies for reducing related health risks. Methods: A local planning committee guided the design and implementation of the project, which includes six components: surveys of risk factors, urea breath test (UBT) screening for H. pylori infection, upper gastrointestinal endoscopy with biopsies collected and histopathology, treatment, knowledge exchange, and policy development. During 2012-13, all residents of Fort McPherson were invited to participate in UBT screening and questionnaire-based risk factor interviews; residents ≥15 years of age were invited to undergo endoscopy in temporary endoscopy units in the local health centre. Participants could also enrol in a randomized trial comparing two 10-day H.pylori therapies: sequential therapy (ST) consisted of a proton pump inhibitor (PPI) and amoxicillin for days 1-5, followed by a PPI, clarithromycin, and metronidazole for days 6-10; quadruple therapy (QT) consisted of a PPI, bismuth, metronidazole, and tetracycline for days 1-10. Treatment outcomes were classified by UBT at >=10 weeks after treatment. Results: To date, 226 residents, aged 4-98 years, have consented to participate. Parental consent and child's assent were obtained for residents

Helicobacter pylori infects one-half or more of the world population and causes chronic gastritis, peptic ulcer, and probably gastric cancer as well. The public-health impact of this infection is far from trivial. Chronic gastritis and peptic ulcer disease are common across populations. Gastric cancer rates have declined during this century, but this cancer remains second among causes of cancer deaths worldwide. Much has been learned about biological and clinical aspects of H. pylori, but key epidemiologic questions have not been answered. How infection results in diverse diseases, the precise modes of transmission, and a comprehensive solution to H. pylori as a public-health problem remain elusive. In this paper, we highlight methodologic challenges and outline an agenda for future research. Challenges include improving validation of detection methods and considering the limitations of these methods when interpreting epidemiologic data. The role of cofactors in H. pylori-induced diseases requires extensive exploration. Many intriguing areas of H. pylori research require the skills of epidemiologists. The discovery of an infectious etiology of common chronic diseases presents a promising opportunity for improving public health.

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.

The long-term efficacy of hepatitis B vaccination among high-risk infants was determined in 805 vaccine responders, immunized at birth in Taiwan during 1981-1984 and followed to age 10 years, via life table survival and Cox multivariate analyses. At 10 years, cumulative persistence of antibody to hepatitis B surface antigen (anti-HBs) was 85%, and cumulative incidence of hepatitis B virus (HBV) infection was 15%. Three children became carriers. Twelve-month anti-HBs titer was the strongest predictor of efficacy. The higher the initial titer, the lower the risk of anti-HBs loss (relative risk [RR], 0.26 for titer of 100-999 mIU/ mL; RR, 0.08 for titer >1000 mIU/mL; P

Helicobacter pylori infection occurs most frequently in impoverished populations; however, little is known about specific determinants of susceptibility. This report describes the relationship between H. pylori infection and nutritional indicators among children from a rural village in the Colombian Andes, where a prevalence of 69% was observed in children from 2 to 9 years old.In a cross-sectional study of 684 children, comprising 92% of the 2- to 9-year-old population of Aldana, Colombia, information was obtained on dietary factors by questionnaire, height and weight by direct measurement, and H. pylori status using the carbon-13 urea breath test. Multivariate logistic regression was used to estimate relative risks for nutritional indicators.The infection was least frequent among children who are several servings of fruits and vegetables daily, drank two or more cups of milk daily, and were in the upper quintile of height for their age. The odds of infection increased 19-fold (95% confidence interval, 4.0-91.9) among children who consumed less than two daily servings of fruits and vegetables compared with the modal intake of three to five daily servings. Children whose daily vitamin C intake from fruits and vegetables was less than 40 mg had greatly increased odds of infection (odds ratio, 7.2; 95% confidence interval, 1.5-34.1) compared to the modal intake of 80-119 mg; for beta-carotene, the odds ratio was 3.1 (95% confidence interval, 1.2-7.9) for intakes of less than 300 IU per day, compared with the modal daily intake of 900 IU or more.The results of this population-based study suggest that nutritional factors may play a role in determining susceptibility to H. pylori infection.

Background. The Aklavik H. pylori Project (AHPP) (www.canhelpworkinggroup.ca) is a community-driven project examining Helicobacter pylori infection and its influence on health in a diverse Aboriginal community in the Northwest Territories. Initial research revealed that 58% of 333 participants who underwent a urea breath test (UBT) between 2007 and 2010 were H. pylori-positive. From 2008 to 2010, we offered treatment to H. pylori-positive participants and 113 consented to this treatment. Objective. We estimated H. pylori incidence in AHPP participants who initially tested negative and the re-infection frequency in initially positive participants who were successfully treated to clear the infection. Methods. Participants who were initially H. pylori-negative or negative after treatment during 2008-2010 were eligible for inclusion. From November 2011 to June 2012, participants were offered a UBT and the samples were analyzed using infrared spectroscopy (IRIS). Participants with a positive test result were classified as new cases for estimating incidence among participants testing negative at baseline and re-infection among those successfully treated for H. pylori infection. Results. Among 38 initially negative participants, follow-up UBT showed that 33 remained negative, 3 were positive, and 2 had uncertain status. The estimated incidence proportion during the follow-up period was 8.3% (95% CI: 1.8-22.0%). Among 43 participants with a negative post-treatment UBT, 41 remained negative and 2 were positive. The estimated re-infection proportion during the follow-up period was 4.7% (95% CI: 0.6-16.0%). The frequency of new cases was similar in males and females. Aboriginal participants had a combined re-infection/incidence rate of 2.4% per year (95% CI: 0.8-5.9% per year). All 9 non-Aboriginal participants remained free from infection throughout the study period, as did all 23 participants aged 55 years and above. Conclusions. The AHPP has substantially reduced the burden of infection in Aklavik since 2008. Continued monitoring, treatment, community engagement and knowledge translation activities are needed to ensure a lasting benefit of the project. Keywords: Helicobacter pylori infection; Aboriginal health; collaborative research; epidemiology; incidence; Arctic (Published: 5 August 2013) This paper is part of Supplement 1, 2013, ICCH15 Proceedings . More papers from this Supplement can be found here . Citation: Int J Circumpolar Health 2013, 72 : 21594 - http://dx.doi.org/10.3402/ijch.v72i0.21594

In 1992, the authors studied Helicobacter pylori infection and exposures relevant to person-to-person, waterborne, foodborne, and zoonotic transmission in a census sample of 684 2-9-year-old children in Aldana, Narino, a rural community in the Colombian Andes. H. pylori prevalence, as determined by the 13C-urea breath test, was 69%, and prevalence increased from 53% in 2 year-olds to 87% in 9 year-olds. Beginning at 3 years of age, a higher percentage of males compared with females were infected. Odds ratios were estimated by multivariate logistic regression to control for mutual confounding by transmission-pathway proxy variables and socioeconomic indicators. Among transmission-pathway proxies, the strongest predictor of H. pylori status was the number of persons who lived in the home, with the number of children apparently being of greater importance than the number of adults. Swimming in rivers, streams, or pools increased the odds of infection, as did using streams as a drinking water source. Children who frequently consumed raw vegetables were more likely to have the infection, and children who had contact with sheep also had increased prevalence odds. Because the results did not implicate a single mode of transmission, the possibility of multiple pathways is indicated.

Background: The rate of gastric cancer in the Northwest Territories Aboriginal population is higher than the rest of the Canada. The aims of this study were to determine theHelicobacter pylori (Hp) prevalence and antibiotic resistance pattern in this community. Methods: As part of a community health project focused on Hp risks, including urea breath test (UBT) screening, residents (age ≥ 9 yrs) of Aklavik, a remote town of 620 inhabitants in the Northwest Territories of Canada, were invited to undergo endoscopy in February 2008. An on-site unit was assembled in the local health centre to perform upper gastrointestinal endoscopy with gastric biopsies for Hp culture and antibiotic susceptibility. Positive Hp cultures were tested using the E-test method for susceptibility to metronidazole, clarithromycin, amoxicillin, ciprofloxacin, tetracycline, nitrofurantoin, and rifampin. Results: Hp prevalence was 55% among the 240 residents who had a UBT. Of all eligible participants, 35% (n = 194) underwent endoscopy and biopsies for culture, with UBT-positive residents more likely to consent to endoscopy. The mean (±SD) age of the participants was 40 (±17) years and 59% were female. Hp culture results were available from 170; 117 (69%) were Hp positive. Antibiotic resistance was found in 33% (n = 33) of 99 Hp-positive cultures tested. Resistance to only metronidazole, clarithromycin, or amoxicillin was present in 23% (n = 23), 4% (n = 4), 0% (n = 0), respectively. There were no cases of resistance to rifampin and tetracycline. Multi-drug (≥ 2) resistance was present in 6 cases (6%). Conclusion: There is a high prevalence of Hp infection with relatively low levels of antibiotic resistance and occasional multi-drug resistance to antibiotics among residents in this Canadian arctic hamlet. A randomized control trial is being conducted to determine the optimal treatment to cure Hp infection in this community.

We concur overall with Taylor's presentation of what is known about the dynamics of Helicobacter pylori infection in childhood (1). but we would like to emphasize that many more questions than answers remain. Because H. pylori infection is not normally detectable at onset, information about incidence must be inferred from age-specific prevalence or repeated screening for prevalent infection over time (2). The infection does not appear to confer lasting immunity, and currently, there is no way to determine whether uninfected individuals have been infected in the past (3). Thus, the average duration of naturally acquired infections and the proportion that are self-limiting is not known for any population or age group. Few studies have examined the infection status of asymptomatic individuals over time. Prospective studies that observe infection status at frequent time intervals have been particularly rare; thus, detailed information regarding the natural history of the infection, peak age ranges for acquisition, and factors that may differentially influence acquisition, persistence, and recurrence is limited. Taylor speculates that antibiotics and characteristics of H. pylori strains may account for spontaneous elimination of infection in children. Emerging evidence suggests that factors that influence the ecology of the gastric niche or the immune response may also influence persistence. In recent laboratory studies, feeding H. pylori-infected mice algae meals with a high antioxidant concentration induced immune changes associated with reduced bacterial load (4). This finding complements an observed inverse association between consumption of fruits and vegetables and H. pylori prevalence in Colombian children (5). We would expect the age-related peaks in acquisition and elimination to vary considerably across popu