Review: Epidemiology of Helicobacter pylori infection

This review summarizes recent publications on the epidemiology of Helicobacter pylori. Two major systemic analyses, from Malaysia and Ethiopia, were published. The Brazilian Consensus Conference has stated that H pylori infection is an infectious disease with an indication for antimicrobial therapy. A continuous decrease in H pylori prevalence was reported from many regions worldwide, including Korea, China, Iran, and Austria. A cross‐sectional H pylori prevalence study conducted in the United Arab Emirates found 41% prevalence in a group of healthy children and adults. Several studies from Asia addressed H pylori prevalence in adults undergoing regular checkup. The largest of such studies, performed in Korea, involved 24 471 subjects and reported 41.5% seroprevalence. A relatively smaller study from East China on 3252 subjects reported 27.5% prevalence. In contrast, a study from Spain reported 87.2% seroprevalence. A report on the association between smoking and H pylori seropositivity was published on behalf of the Stomach Cancer Pooling (StoP) Project—a consortium of epidemiological studies of gastric cancer. Also, other potential risk factors, including occupational risk factors, water supply, and food were analyzed. Gastroesophageal reflux and sexual partners has been associated with a higher risk for H pylori acquisition, and gut microbiota was suggested to play a role in intrafamilial transmission of H pylori. Finally, in a few studies (from Mexico and Japan), the catalytic model for predicting the potential risk of acquiring H pylori infection in the future was used. As anticipated, a further decline in H pylori‐related disease was demonstrated by applying the modeling.     

Helicobacter pylori recurrence in developed and developing countries: meta-analysis of 13C-urea breath test follow-up after eradication

Objective: Recurrence of Helicobacter pylori infection after eradication is rare in developed countries and more frequent in developing countries. Most recurrent cases are attributed to recrudescence (recolonization of the same strain within 12 months) rather than to reinfection (colonization with a new strain after more than 12 months). The aim of the study was to analyze recurrence rates in developed and developing countries and to deduce the relative roles of recrudescence and reinfection. Methods: The PubMed database was searched up to January 31, 2007 using the keywords “Helicobacter pylori” or “H. pylori” and “recurrence” or “recrudescence,” or “reinfection.” Only prospective case studies in adults that used the ¹³C‐urea breath test (¹³CUBT) were included. Meta‐analyses were performed with statdirect Statistical software, version 2.6.1, StatsDirect Ltd, Chesire, UK. Results: The literature search yielded 10 studies of H. pylori recurrence in developed countries (3014 patients followed for 24–60 months) and 7 studies in developing countries (2071 patients followed for 12–60 months). The calculated annual recurrence rates were 2.67% and 13.00%, respectively. Nested meta‐analysis of cases with a longer follow‐up after eradication revealed an annual recurrence rate of 1.45% (RR 0.54) in developed countries and 12.00% (RR 0.92) in developing countries. Conclusions: The similarity of the annual recurrence rates during the first year after eradication and the annual recurrence rates in the second year after successful eradication in developing countries supports reinfection as the main cause in the second period. Therefore, a different approach for follow‐up of H. pylori eradication may be needed between developed and developing countries.     

Impact factors that modulate gastric cancer risk in Helicobacter pylori‐infected rodent models

Gastric cancer causes a large social and economic burden to humans. Helicobacter pylori (H pylori) infection is a major risk factor for distal gastric cancer. Detailed elucidation of H pylori pathogenesis is significant for the prevention and treatment of gastric cancer. Animal models of H pylori‐induced gastric cancer have provided an invaluable resource to help elucidate the mechanisms of H pylori‐induced carcinogenesis as well as the interaction between host and the bacterium. Rodent models are commonly used to study H pylori infection because H pylori‐induced pathological processes in the stomachs of rodents are similar to those in the stomachs of humans. The risk of gastric cancer in H pylori‐infected animal models is greatly dependent on host factors, bacterial determinants, environmental factors, and microbiota. However, the related mechanisms and the effects of the interactions among these impact factors on gastric carcinogenesis remain unclear. In this review, we summarize the impact factors mediating gastric cancer risk when establishing H pylori‐infected animal models. Clarifying these factors and their potential interactions will provide insights to construct animal models of gastric cancer and investigate the in‐depth mechanisms of H pylori pathogenesis, which might contribute to the management of H pylori‐associated gastric diseases.     

Is the recurrence of Helicobacter pylori infection after eradication therapy resultant from recrudescence or reinfection,in Japan

Background. Reinfection of Helicobacter pylori after eradication is rare in developed countries but most often occurs within 1 year. In the present study, we attempted to differentiate between reinfection and recrudescence of H. pylori strains between 6 months and 6 years after successful eradication in Japan, a country with a high prevalence of H. pylori infection. Materials and Methods. After successful eradication of H. pylori, 274 patients were followed up by endoscopy and urea breath test. In recurrent patients, H. pylori strains isolated initially and after recurrence were compared using PCR‐based restriction fragment length polymorphism (RFLP) analysis. Results. Recurrence of H. pylori occurred in 15 of 274 patients (5.5%) at 6 months after eradication and the annual recurrence rate was 2.0% per patient year (between 1 and 6 years). PCR‐based RFLP analysis of H. pylori strains isolated initially and after recurrence showed that 62.5% (at 6 months) and 100% (after 1 years) of bacteria were of different strains. Conclusion. Reinfection of H. pylori was not as rare at 6 months after eradication as reported previously, and up to 6 years after eradication, the annual reinfection rate is 2.0% per patient year in Japan.     

Review: Helicobacter pylori and non‐malignant upper gastrointestinal diseases

This review covers recent publications investigating the relationship between Helicobacter pylori infection and gastroesophageal reflux disease, Barrett's esophagus, eosinophilic esophagitis, peptic ulcer disease (PUD), H pylori gastritis, and functional dyspepsia. In the area of gastroesophageal reflux disease, new data suggest that reflux may have a role in the transmission of H pylori infection. In addition to several observational studies, data on alterations in esophageal physiology in patients with H pylori infection are presented. Further evidence for the inverse relationship between H pylori infection and Barrett's esophagus is available in the form of a meta‐analysis from the North American Barrett's and Esophageal Carcinoma Consortium. The relationship between H pylori infection and eosinophilic esophagitis remains uncertain. Although new data do not indicate a significantly lower prevalence of H pylori among patients with eosinophilic esophagitis, a meta‐analysis showed a 37% reduced risk of eosinophilic esophagitis among H pylori‐infected patients. Novel data are presented on the genetic variability of bacterial virulence factors and their relationship with PUD. We also report data on plasma biomarkers, which may detect progression to gastric cancer in H pylori‐associated PUD. A new meta‐analysis was published, which assessed the risk of PUD in low‐dose aspirin users with H pylori infection. Finally, we report on the ongoing attempts to stratify patients with gastritis using endoscopic methods when compared to standard biopsy examination.     

Review: Epidemiology of Helicobacter pylori

This review summarizes the recent knowledge on the epidemiology of Helicobacter pylori and the potential modes of transmission. In addition to English language publications, the authors have included original full‐text publications from Russia and Latin America published in the original languages. High H pylori prevalence has been reported in Russia, Jordan, Iran, China, and Latin American countries as well as in Arctic populations in Canada. Indigenous inhabitants in the Arctic were found to be infected substantially more frequently than non‐indigenous inhabitants. In Amsterdam, the Netherlands, the ethnic minority groups were at a significantly higher risk of being H pylori seropositive compared to the Dutch population. For the first time, data on the prevalence from Armenia have been published indicating 41.5% H pylori prevalence. Convincing evidence on the decline of H pylori prevalence in Southeast Hungary and Taiwan was published. A study from Chile suggested high infection rates in newborns during the first month after birth. Two meta‐analyses covered the potential correlation between H pylori and periodontal diseases, therefore addressing the potential oro‐oral transmission rates. Periodontal disease was found to be more prevalent in H pylori‐infected subjects. Other studies addressed the potential role of drinking water and food products as well as socioeconomic factors in transmitting the infection. Several studies in Asia addressed annual reinfection rates of H pylori, ranging from 1.5% in China to 3.1% in Korea. Finally, a review was published on the current evidence and future perspective of analysing H pylori in ancient human remains by a metagenomic approach.     

Review: Helicobacter pylori in pediatrics

Despite a decrease in the prevalence of Helicobacter pylori infection, it still poses a significant health burden worldwide. This review summarizes important pediatric studies on H pylori published from April 2018 to March 2019. Epidemiologic studies have reported different prevalences in different parts of the world and have mainly confirmed traditional risk factors. Several studies on pathophysiology attempted to identify risk markers in childhood for gastric cancer development later in life. One of the most interesting studies evaluated the relationship between eosinophilic esophagitis and H pylori infection; however, an inverse relationship was not confirmed. The high resistance of H pylori and, consequently, low eradication rates, is still a major concern and susceptibility testing before treatment has again been highlighted. Potassium‐competitive acid blockers are promising new acid‐suppressant drugs but their role in H pylori eradication schemes is still to be determined.     

Review: Clinical Management of Helicobacter pylori Infection in China

Helicobacter pylori (H. pylori) infection has been associated with gastric disorders. The situation of H. pylori infection in China—where a high prevalence of H. pylori infection, a high incidence of gastric cancer, and widespread resistance to clarithromycin, metronidazole, and levofloxacin exist—is quite different from that in Western countries. In order for Chinese clinicians to better manage H. pylori infection, a Chinese Study Group on H. pylori published four consensus reports regarding the management of H. pylori infection in China between 1999 and 2012. The eradication rate with standard triple therapy was <80% in most areas of China. Bismuth is available in China, and bismuth‐containing quadruple therapy has been shown to produce a high eradication rate; thus, bismuth quadruple therapy could be recommended both as an initial and as a rescue therapy in China. There is no advantage of sequential therapy over triple therapy in Chinese patients, but the efficacy of concomitant therapy must be studied further. This review introduces the epidemiology, diagnosis, indicators, and therapies for the eradication of H. pylori in China in recent years.     

Helicobacter pylori Infection – A Boon or a Bane: Lessons from Studies in a Low‐Prevalence Population

Helicobacter pylori (H. pylori) infection is etiologically associated with gastric cancer and peptic ulcer diseases which are both important public health burdens which could be largely eliminated by H. pylori eradication. However, some investigators urge caution based on the hypothesis that eradication of H. pylori may result in an increase in the incidence of gastroesophageal reflux disease, esophageal adenocarcinoma, and childhood asthma. The ethnic Malays of northeastern Peninsular Malaysia have long had a low prevalence of H. pylori infection and, as expected, the incidence of gastric cancer and its precursor lesions is exceptionally low. The availability of a population with a low H. pylori prevalence and generally poor sanitation allows separation of H. pylori from the hygiene hypothesis and direct testing of whether absence of H. pylori is associated with untoward consequence. Contrary to predictions, in Malays, erosive esophagitis, Barrett's esophagus, distal esophageal cancers, and childhood asthma are all of low incidence. This suggests that H. pylori is not protective rather the presence of H. pylori infection is likely a surrogate for poor hygiene and not an important source of antigens involved in the hygiene hypothesis. Helicobacter pylori in Malays is related to transmission from H. pylori‐infected non‐Malay immigrants. The factors responsible for low H. pylori acquisition, transmission, and burden of H. pylori infection in Malays remain unclear and likely involves a combination of environmental, host (gene polymorphisms), and strain virulence factors. Based on evidence from this population, absence of H. pylori infection is more likely to be boon than a bane.     

Prevalence of Helicobacter pylori among Alaskans: Factors associated with infection and comparison of urea breath test and anti‐Helicobacter pylori IgG antibodies

Background

Helicobacter pylori is one of the most common human infections in the world, and studies in Alaska Native people, as well as other Indigenous peoples, have shown a high prevalence of this gastric infection. This study was undertaken to determine the prevalence of H. pylori infection by urea breath test (UBT) and anti‐ H. pylori IgG among Alaskans living in four regions of the state and to identify factors associated with infection.

Methods

A convenience sample of persons > 6 months old living in five rural and one urban Alaskan community were recruited from 1996 to 1997. Participants were asked about factors possibly associated with infection. Sera were collected and tested for anti‐ H. pylori IgG antibodies; a UBT was administered to participants > 5 years old.

Results

We recruited 710 people of whom 571 (80%) were Alaska Native and 467 (66%) were from rural communities. Rural residents were more likely to be Alaska Native compared with urban residents (P < .001). Of the 710 people, 699 (98%) had a serum sample analyzed, and 634 (97%) persons > 5 years old had a UBT performed. H. pylori prevalence was 69% by UBT and 68% by anti‐ H. pylori IgG. Among those with a result for both tests, there was 94% concordance. Factors associated with H. pylori positivity were Alaska Native racial status, age ≥ 20 years, rural region of residence, living in a crowded home, and drinking water that was not piped or delivered.

Conclusions

Helicobacter pylori prevalence is high in Alaska, especially in Alaska Native persons and rural residents. Concordance between UBT and serology was also high in this group. Two socioeconomic factors, crowding and drinking water that was not piped or delivered, were found to be associated with H. pylori positivity.     

Review ‐ Helicobacter pylori and non‐malignant upper gastro‐intestinal diseases

This review takes into account recent publications focusing on the relationship between Helicobacter pylori infection and non‐malignant diseases of the upper gastro‐intestinal tract. The authors have summarized current knowledge on associations between the H pylori infection and non‐malignant upper GI conditions including gastroesophageal reflux disease (GERD), Barrett's esophagus, eosinophilic esophagitis (EOE), peptic ulcer disease (PUD), H pylori gastritis, celiac disease and functional dyspepsia. In the field of GERD, current data focusing on different locations of H pylori infection detect significant differences between antrum‐ and corpus predominant gastritis explainable by different changes in acid secretion in different gastric niches. High volume studies from Sweden and Brazil underline the safety of H pylori eradication concerning the risk of Barret's esophagus or adenocarcinoma. The relationship betweenH pylori infection and EOE remains uncertain, but current data supports the concept of expected positive and protective effects of H pylori exposure reducing the risk of EOE. Analyzing biomarkers might be helpful to identify subjects under risk for the development of precancerous lesions after H pylori infection, where microRNAs, IL‐9 and IL‐4, and also Tc17/9 and Th17/9 and microbiota profiles showed promising results to identify subgroups under risk.     

Review: Helicobacter pylori infection in children

Helicobacter pylori infection in children and adolescents differs in comparison to adults with respect to epidemiology, host responses, and disease manifestations. Furthermore, treatment options are limited in this population and antibiotic resistance rates continue to increase. Therefore, ongoing research is vital to understand disease pathogenesis and provide optimal management of children with infection. This review summarizes relevant publications from April 2019 to March 2020. Similar to adults, recent studies show a decreasing prevalence of infection in the pediatric population. Studies of pathogenesis investigated serum immune responses and the potential inverse association of infection and allergy. Several studies investigated the effect of H pylori and related inflammation on the gut microbiome. The recommendation of endoscopy‐based testing to identify the cause of symptoms and not just H pylori, reserving noninvasive UBT or stool antigen tests for post‐eradication follow‐up, was supported by the current literature.     

Review: Pathogenesis of Helicobacter pylori infection

The original strategies developed by Helicobacter pylori to persistently colonise its host and to deregulate its cellular functions make this bacterium an outstanding model to study host‐pathogen interaction and the mechanisms responsible for bacterial‐induced carcinogenesis. During the last year, significant results were obtained on the role of bacterial factors essential for gastric colonisation such as spiral shape maintenance, orientation through chemotaxis and the formation of bacteria clonal population islands inside the gastric glands. Particularities of the H pylori cell surface, a structure important for immune escape, were demonstrated. New insights in the bacterial stress response revealed the importance of DNA methylation‐mediated regulation. Further findings were reported on H pylori components that mediate natural transformation and mechanisms of bacterial DNA horizontal transfer which maintain a high level of H pylori genetic variability. Within‐host evolution was found to be niche‐specific and probably associated with physiological differences between the antral and oxyntic gastric mucosa. In addition, with the progress of CryoEM, high‐resolution structures of the major virulence factors, VacA and CagT4SS, were obtained. The use of gastric organoid models fostered research revealing, preferential accumulation of bacteria at the site of injury during infection. Several studies further characterised the role of CagA in the oncogenic properties of H pylori, identifying the activation of novel CagA‐dependent pathways, leading to the promotion of genetic instabilities, epithelial‐to‐mesenchymal transition and finally carcinogenesis. Recent studies also highlight that microRNA‐mediated regulation and epigenetic modifications, through DNA methylation, are key events in the H pylori‐induced tumorigenesis process.     

Review: Helicobacter: Inflammation,immunology, and vaccines

Chronic inflammation induced by Helicobacter pylori infection is a critical factor in the development of peptic ulcer disease and gastric cancer. Central to this inflammation is the initiation of pro‐inflammatory signaling cascades within epithelial cells, in particular those mediated by two sensors of bacterial cell wall components, nucleotide‐binding oligomerization domain‐containing protein 1 (NOD1) and alpha‐protein kinase 1 (ALPK1). H pylori is, however, also highly adept at mitigating inflammation in the host, thereby restricting tissue damage and favoring bacterial persistence. H pylori modulates host immune responses by altering cytokine signaling in epithelial and myeloid cells, which results in increased proliferation of regulatory T cells and downregulation of effector T‐cell responses. H pylori vacuolating cytotoxin A (VacA) has been shown to play an important role in the dampening of immune responses and induction of immune tolerance capable of protecting against asthma. It is also possible to generate protective immune responses by immunization with various H pylori antigens or their epitopes, in combination with an adjuvant, though this for now has only been shown in mouse models. Novel non‐toxic adjuvants, consisting of modified bacterial enterotoxins or nanoparticles, have recently been developed that may not only enhance vaccine efficacy, but also help translate candidate vaccines to the clinic. This review will summarize the main discoveries in the past year regarding host immune responses to H pylori infection, as well as the design of new vaccine approaches against this infection.     

Review: Helicobacter pylori and extragastric diseases

In the last year, many studies have demonstrated a potential role of Helicobacter pylori in the pathogenic mechanisms of different extragastric diseases. While the role of H pylori in idiopathic thrombocytopenic purpura, idiopathic iron deficiency anemia, and vitamin B12 deficiency has already been demonstrated, there is growing evidence of other related conditions, especially cardiovascular, metabolic, and neurologic disorders, including neurodegenerative diseases. A summary of the results of the most relevant studies published over the last year on this attractive topic is presented in this review.     

Review ‐ Helicobacter,inflammation, immunology and vaccines

Understanding the mechanisms involved in induction and regulation of the immune and inflammatory response to Helicobacter pylori is extremely important in determining disease outcomes. H pylori expresses a plethora of factors that influence the host response. Vaccines against H pylori are desperately needed for the prevention of gastric carcinogenesis, especially with the increasing trends in antimicrobial resistance. This review summarizes some important findings, published between 1 April 2019 and 31 March 2020, in the areas of H pylori‐mediated inflammation, immunity and vaccines.     

Seroprevalence of Helicobacter pylori in Korea: A multicenter,nationwide study conducted in 2015 and 2016

Background

The Korean College of Helicobacter and Upper Gastrointestinal Research has studied Helicobacter pylori (H. pylori) prevalence since 1998 and found a dynamic change in its prevalence in Korea. The aim of this study was to determine the recent H. pylori prevalence rate and compare it with that of previous studies according to socioeconomic variables.

Methods

We planned to enroll 4920 asymptomatic Korean adults from 21 centers according to the population distribution of seven geographic areas (Seoul, Gyeonggi, Gangwon, Chungcheong, Kyungsang, Cholla, and Jeju). We centrally collected serum and tested H. pylori serum IgG using a chemiluminescent enzyme immunoassay.

Results

We analyzed 4917 samples (4917/4920 = 99.9%) from January 2015 to December 2016. After excluding equivocal serologic results, the H. pylori seropositivity rate was 51.0% (2414/4734). We verified a decrease in H. pylori seroprevalence compared with previous studies performed in 1998, 2005, and 2011 (P < .0001). The H. pylori seroprevalence rate differed by area: Cholla (59.5%), Chungcheong (59.2%), Kyungsang (55.1%), Jeju (54.4%), Gangwon (49.1%), Seoul (47.4%), and Gyeonggi (44.6%). The rate was higher in those older than 40 years (38.1% in those aged 30‐39 years and 57.7% in those aged 40‐49 years) and was lower in city residents than in noncity residents at all ages.

Conclusions

Helicobacter pylori seroprevalence in Korea is decreasing and may vary according to population characteristics. This trend should be considered to inform H. pylori‐related policies.     

Review: Pathogenesis of Helicobacter pylori infection

In this review, we shall focus on the last year progression understanding the pathogenesis of Helicobacter pylori infection in the light of recent data related to adaptation of H pylori to the harsh acidic environment in the stomach, colonization of gastric mucosa via interaction with mucin 5 (MUC5AC) and other host cell receptors, the ability to form biofilm, interference with the host metabolic pathways, and induction of neuroimmune cross‐talk as well as downregulation of gastric barrier homeostasis and its consequences for the disease development. The role of the membrane vesicles of these bacteria has been emphasized as an important source of virulence factors. Furthermore, we shall describe molecular and functional studies on new aspects of VacA and CagA virulence, including the role of urease in the upregulation of VacA toxicity, an epithelial‐mesenchymal transition mediated by CagA, and the role of interaction of HopQ adhesin with carcinoembryonic antigen‐related cell adhesion molecules (CEACAMs) in CagA translocation into the host cells by the type IV secretion system (T4SS). The role of molecular mimicry between a common sequence (ATVLA) of H pylori heat shock protein (Hsp) B and human Hsp60 in the induction of potentially autoreactive antibodies is discussed. All these new data illustrate further progress in understanding H pylori pathogenicity and facilitate the search for new therapeutic targets as well as development of immunoprophylaxis methods based on new chimeric UreB and HpA proteins.     

Helicobacter pylori in School Children From the Western Province of Sri Lanka

Background. Little is known about the prevalence of Helicobacter pylori in Sri Lanka and nothing is known about its prevalence in children. Therefore the prevalence of H. pylori in a group of school children in Sri Lanka was determined. Materials and Methods. The presence of H. pylori colonisation was determined by detection of faecal antigen and salivary antibody (IgG) by enzyme immuno assay, in 184 children aged between 5 and 19 years, in the Western Province‐Colombo district of Sri Lanka. Results. Overall, only 12/184 (6.5%) had detectable H. pylori antigen in their stools and were considered infected with H. pylori, while 51/184 (27.7%) had H. pylori IgG in saliva. H. pylori salivary IgG declined with age while H. pylori antigen detection increased with age. H. pylori infection, as determined by salivary antibody (66%), was greater in children living in overcrowded conditions, although this was not statistically significant. Conclusion. The prevalence of H. pylori among school children in Sri Lanka was 6.5% by detection of faecal antigen and 27.7% by detection of salivary antibody, respectively. Initial infection with H. pylori appeared to occur in early childhood whilst active disease began in late childhood. Overcrowding appears to facilitate the transmission of the organism. Overall the prevalence of H. pylori was low in Sri Lanka compared with other countries in South‐east Asia.     

Fifth Chinese National Consensus Report on the management of Helicobacter pylori infection

Background

Since the ‘Fourth Chinese National Consensus Report on the management of H. pylori infection’ was published in 2012, three important consensuses (Kyoto global consensus report on H. pylori gastritis, The Toronto Consensus for the Treatment of H. pylori Infection in Adults and Management of H. pylori infection—the Maastricht V/Florence Consensus Report) have been published regarding the management of H. pylori infection.

Materials and Methods

A Delphi method was adopted to develop the consensus of relevant ‘statements’. First, the established ‘statements’ were sent to experts via email. Second, after undergoing two rounds of consultation, the initial statements were discussed face to face and revised in the conference item by item on 16 December 2016. Finally, 21 core members of conferees participated in the final vote of statements. Voting for each statement was performed using an electronic system with levels of agreements shown on the screen in real time.

Results

Consensus contents contained a total of 48 “statements” and related 6 parts, including indications for H. pylori eradication, diagnosis, treatment, H. pylori and gastric cancer, H. pylori infection in special populations, H. pylori and gastrointestinal microbiota.

Conclusions

Recommendations are provided on the basis of the best available evidence.