Helicobacter pylori infection and immune thrombocytopenic purpura: an update

Data are accumulating on the association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) and the significant increase in platelet count after bacterial eradication. The aim of this review was to consider the studies so far published on H. pylori infection and ITP in order to evaluate a possible correlation between these two conditions. A review of the literature showed that 278 out of the 482 ITP patients investigated (58%) were positive for H. pylori infection and that the bacterium was eradicated in 88% of cases. Eradication therapy was accompanied by a complete or partial platelet response in approximately half the cases. Overall, these data show that H. pylori eradication in patients with ITP is effective in increasing platelet count. However, because the studies so far published are few, are sometimes controversial and involve small series of patients, further studies on larger numbers of patients with longer follow-up are needed to confirm these preliminary findings.     

The role of genome diversity and immune evasion in persistent infection with Helicobacter pylori

Helicobacter pylori is an important human pathogen that chronically colonizes the stomach of half the world's population. Infection typically occurs in childhood and persists for decades, if not for the lifetime of the host. How is bacterial persistence possible despite a vigorous innate and adaptive immune response? Here we describe the complex role of bacterial diversity and specific mechanisms to avoid or subvert host immunity in bacterial persistence. We suggest that H. pylori finely modulates the extent to which it interacts with the host in order to promote chronic infection, and that it uses diverse mechanisms to do so.     

Epidemiology of Helicobacter pylori infection in the Czech Republic

BACKGROUND: Prevalence of Helicobacter pylori infection has been estimated to range from 60 to 95% in the former communist countries of Central and Eastern Europe. The aim of this study was to evaluate H. pylori infection prevalence in a representative sample of the Czech population. The second objective was to describe difference of H. pylori prevalence between different social groups of children and adults. MATERIALS AND METHODS: A total of 2509 persons aged 5-100 years, randomly selected out of 30,012 persons of the general population, took part in the study. H. pylori infection was investigated by means of 13C-urea breath test. Breath samples were analyzed by isotope ratio mass spectrometry. Social and demographic characteristics were based on data from self-completed questionnaires. RESULTS: Using the total Czech population as a standard, we estimated the age-standardized prevalence of H. pylori in males aged 5+ years at 41.9% (95% CI 39.0%, 44.8%) and in females aged 5+ years at 41.4% (95% CI 38.6%, 44.3%) in 2001. Prevalence of H. pylori increased with age but was not related to gender. Children of mothers with basic or lower education, living in crowded accommodations, without access to running warm water, and residing in smaller towns appear to be at the highest risk. Low education and heavy smoking are most strongly associated with prevalence of H. pylori positivity in adults and adolescents. CONCLUSIONS: This is a unique study based on a representative sample of the general population in a Central European country. The overall prevalence of H. pylori is lower than previously assumed and could partly reflect a substantial recent decrease in H. pylori prevalence in the Czech Republic. Consistent with earlier studies, H. pylori infection is strongly influenced by socioeconomic conditions and childhood poverty.     

Antibacterial effects of the urushiol component in the sap of the lacquer tree (Rhus verniciflua Stokes) on Helicobacter pylori

Background: Urushiol is a major component of the lacquer tree which has been used as a folk remedy for the relief of abdominal discomfort in Korea. The aim of this study was to evaluate the antibacterial effects of the urushiol on Helicobacter pylori. Materials and Methods: Monomer and 2–4 polymer urushiol were used. In the in vitro study, pH‐ and concentration‐dependent antibacterial activity of the urushiol against H. pylori were investigated. In addition, the serial morphological effects of urushiol on H. pylori were examined by electron microscopy. In vivo animal study was performed for the safety, eradication rate, and the effect on gastritis of urushiol. The expression of pro‐inflammatory cytokines was checked. Results: All strains survived within a pH 6.0–9.0. The minimal inhibitory concentrations of the extract against strains ranged 0.064–0.256 mg/mL. Urushiol caused separation of the membrane and lysis of H. pylori within 10 minutes. Urushiol (0.128 mg/mL × 7 days) did not cause complications on mice. The eradication rates were 33% in the urushiol monotherapy, 75% in the triple therapy (omeprazole + clarithromycin + metronidazole), and 100% in the urushiol + triple therapy, respectively. H. pylori‐induced gastritis was not changed by urushiol but reduced by eradication. Only the expression of interleukin‐1β in the gastric tissue was significantly increased by H. pylori infection and reduced by the urushiol and H. pylori eradication (p = .014). Conclusions: The urushiol has an antibacterial effect against H. pylori infection and can be used safely for H. pylori eradication in a mouse model.     

Intrafamilial transmission of Helicobacter pylori among the population of endemic areas in Japan

BACKGROUND: Helicobacter pylori (H. pylori) infection is a worldwide phenomenon related to several gastrointestinal diseases. However, because many aspects concerning the route of transmission remain unclear, we performed this epidemiologic study to clarify the route of intrafamilial transmission of H. pylori. MATERIALS AND METHODS: A retrospective study was performed in three widely separate areas in Japan to investigate the prevalence of H. pylori infection. In 1993, 613 residents were tested as were 4136 in 2002, including 1447 family members of 625 families. Antibody to H. pylori (anti-H. pylori) was determined by enzyme-linked immunosorbent assay. RESULTS: In 2002, the age-adjusted anti-H. pylori prevalence in Hoshino Village (67.5%) was significantly higher than in Kasuya Town (55.0%) and in Ishigaki City (54.7%) (p < .0001, p = .0039, respectively). The age-adjusted anti-H. pylori prevalence of Ishigaki City significantly decreased from 1993 (68.4%) to 2002 (52.5%), showing an age cohort effect. However, the prevalence did not significantly differ in children aged 0-6 years of Ishigaki City between 1993 (9.6%) and 2002 (10.3%). A familial analysis in 2002 demonstrated that the prevalence of anti-H. pylori was significantly higher in children with anti-H. pylori-positive (21.6%, 22 of 102) than with -negative mothers (3.2%, 3 of 95) (p < .0001, by Mantel-Haenszel test), whereas there was no significant difference between children with anti-H. pylori-positive and -negative fathers. Moreover, the prevalence was significantly higher in wives with anti-H. pylori-positive (64.0%, 208 of 325) than with -negative husbands (46.5%, 80 of 172) (p = .0071, by Mantel-Haenszel test) and in husbands with anti-H. pylori-positive (72.2%, 208 of 288) than with -negative wives (56.0%, 117 of 209) (p = .0106, by Mantel-Haenszel test). CONCLUSIONS: In the last decade, H. pylori infection decreased in the general population of Japan by improvement of general hygiene conditions, but did not differ in young children, most likely because of mother-to-child transmission.     

Current information on the association of Helicobacter pylori with autophagy and gastric cancer

Helicobacter pylori (H. pylori) is a Gram-negative bacterium and causative agent of gastric cancer. H. pylori induce defective autophagy or inhibit it by means of CagA and vacuolating cytotoxin A (VacA) toxins leading to the gastric cancer induction. Impaired or defective autophagy leads to the accumulation of cytotoxic materials, such as ROS and P62 that lead to increased mutations in the DNA, genome instability, and risk of cancer formation. H. pylori CagA may inhibit autophagy through the c-Met-PI3k/Akt-mTOR signaling pathway. However, VacA induces autophagy by some signaling pathways. In the gastric epithelial cells, VacA is a necessary and sufficient factor for the creation of autophagy. While CagA is a negative regulator of this phenomenon, the elimination of this gene from H. pylori has increased autophagy and the production of inflammatory cytokines is reduced. In gastrointestinal cancers, some of the microRNAs (miRNAs) act as tumor suppressors and some other are oncogenes by regulating various genes expression. H. pylori can also modify autophagy through a mechanism that includes the function of miRNAs. In autophagy, oncogenic miRNAs inhibit activation of some tumor suppressor signaling pathways (e.g., ULK1 complex, Beclin-1 function, and Atg4 messaging), whereas tumor suppressor miRNAs can block the activation of oncogenic signaling pathways. For instance, Beclin-1 is negatively regulated by miRNA-376b (oncogenic miRNA) and miRNA-30a (tumor suppressor miRNA). Similarly, Atg4 by miRNA-376b (oncogenic miRNA) and miRNA-101 (tumor suppressor miRNA). So, this apparent paradox can be explained as that both Beclin-1 and Atg4 play different roles in a particular cell or tissue.     

Helicobacter pylori Reinfection in Brazilian Patients with Peptic Ulcer Disease: A 5-Year Follow-Up

Background:  The Helicobacter pylori reinfection seems to be higher in developing countries, than in developed ones. The aim of the study was to determine the annual recurrence rate of H. pylori , in Brazilian patients with peptic ulcer disease, in a 5-year follow-up.
Methods:  Patients, with peptic ulcer disease diagnosed by upper digestive endoscopy (UDE) and H. pylori infection verified by histological analysis, rapid urease test, polymerase chain reaction, and urea breath test (UBT), were treated for bacterial eradication. The cure of the infection was verified using the same tests, 3 months after. Clinical evaluation and UBT were performed after sixth and ninth month. After 1 year of follow-up, UBT and UDE were repeated. Up to the fifth year, patients were assessed twice a year and an UBT was performed annually. The patients included and all the reinfected were tested for 15 different genes of the H. pylori .
Results:  One hundred and forty-seven patients were followed: 19 for 1 year, eight for 2 years, four for 3 years, five for 4 years, and 98 for 5 years, totaling 557 patients/years. Recurrence did not occur in the first year. In the second year, two patients were reinfected; in the third, four patients; in the fourth, three patients; and in the fifth, one patient. The total of reinfected patients was 10. The annual reinfection rate was 1.8%.
Conclusion:  Brazil presents a low prevalence of H. pylori reinfection, similar to the developed countries.     

The role of interleukin-17 in the Helicobacter pylori induced infection and immunity

Background: Helicobacter pylori infection is regarded as the major cause of various gastric diseases and induces the production of several cytokines including interleukin‐17 (IL‐17) recently recognized as an important player in the mammalian immune system. Objective: This review deals with the role of IL‐17 on the H. pylori‐induced infection and immunity in humans and experimental animals. Results: H. pylori infection increases IL‐17 in the gastric mucosa of humans and experimental animals. In humans, IL‐17 induces the secretion of IL‐8 by activating the ERK 1/2 MAP kinase pathway and the released IL‐8 attracts neutrophils promoting inflammation. IL‐23 is increased in patients with H. pylori‐related gastritis and regulates IL‐17 secretion via STAT3 pathway. Studies in H. pylori‐infected mice indicate that IL‐17 is primarily associated with gastric inflammation. The early events in the immune response of immunized and challenged mice include the recruitment of T cells and the production of IL‐17. Neutrophil attracting chemokines are released, and the bacterial load is considerably reduced. IL‐17 plays a dual role in infection and vaccination. In infection, T regulatory cells (Tregs) suppress the inflammatory reaction driven by IL‐17 thereby favoring bacterial persistence. Immunization produces Helicobacter‐specific memory T‐helper cells that can possibly alter the ratio between T‐helper 17 and Treg responses so that the IL‐17‐driven inflammatory reaction can overcome the Treg response leading to bacterial clearance. Conclusion: IL‐17 plays an important role in H. pylori‐related gastritis and in the reduction of Helicobacter infection in mice following immunization.     

Helicobacter pylori, asthma and allergy

Bronchial asthma and allergic diseases are orchestrated by T-cells producing T-helper type 2 (Th2) cytokines, such as interleukin-4 (IL-4) and IL-5, and are inhibited by Th1 responses. Helicobacter pylori has chronically infected the human population for c . 100 000 years and preferentially elicits a Th1 mucosal immune response with the production of interferon-γ and IL-12. Among several bacterial factors, the neutrophil-activating protein of H. pylori (HP-NAP) not only plays a key role in driving Th1 inflammation but it is also able to inhibit Th2 responses in vitro and in vivo in allergic bronchial asthma, in humans and mice. Both systemic and mucosal administrations of HP-NAP are successful in reducing eosinophilia, immunoglobulin E and systemic Th2 cytokines at the bronchial level. Thus, these results identify HP-NAP as a candidate for novel strategies for the prevention and treatment of allergic diseases.     

Prevalence and risk factors for Helicobacter pylori infection in Chinese populations

Background:  The prevalence of Helicobacter pylori is higher in developing countries. The aim of this study was to investigate the prevalence and risk factors of H. pylori infection in areas with high prevalence of gastric cancer in Jiangsu Province, China.
Methods:  A prospective epidemiologic survey of H. pylori infection was accomplished in a natural population of 1457 individuals in Xiangshui and Gaoyou counties, Jiangsu Province, China. Questionnaires and laboratory tests for H. pylori infection (¹³C-urea breath test and serum IgG antibodies to H. pylori ) were used and performed, respectively.
Result:  Among 1371 subjects who completed questionnaires and H. pylori detection, 851 (62%) were H. pylori positive. The prevalence reached a peak at the age of 30–40 years (67%). There was no sex difference. The annual family income level was shown to be positively correlated with the risk of H. pylori infection. The prevalence of H. pylori infection was also associated with family size, education level, and several diet-related factors, such as the number of times cooked rice and potatoes eaten per week, and a family history of stomach diseases. Compared to nonsymptomatic individuals, people with dyspeptic symptoms (nausea, vomiting, and belching) presented a low prevalence of H. pylori infection. No association between H. pylori prevalence and smoking or drinking was found. Using multivariate logistic regression analysis, annual family income and education level were the independent predictors for H. pylori infection.
Conclusion:  High prevalence of H. pylori infection was found in areas with a high risk of gastric cancer and was related to several risk factors. The underlying mechanisms need to be further investigated.     

Helicobacter pylori and the birth cohort effect: evidence for stabilized colonization rates in childhood

Background: The prevalence of Helicobacter pylori has declined over recent decades in developed countries. The increasing prevalence with age is largely because of a birth cohort effect. We previously observed a decline in H. pylori prevalence in 6‐ to 8‐year‐old Dutch children from 19% in 1978 to 9% in 1993. Knowledge about birth‐cohort‐related H. pylori prevalence is relevant as a predictor for the future incidence of H. pylori‐associated conditions. Aim: The aim of this study was to investigate whether the birth cohort effect of H. pylori observed between 1978 and 1993 continued in subsequent years. Methods: Anti‐H. pylori IgG antibodies and anti‐CagA IgG antibodies were determined in serum samples obtained in 2005/2006 from 545 Dutch children aged 7–9 years who participated in the Prevention and Incidence of Asthma and Mite Allergy birth cohort. The H. pylori and CagA antibodies were determined by enzyme‐linked immunosorbent assays that have been extensively validated in children, with a 94% sensitivity for H. pylori colonization and a 92.5% sensitivity for colonization with a cagA‐positive strain. Results: Of the 545 children (M/F 300/245), most (91.5%) were of Dutch descent. The H. pylori positivity rate was 9% (95% CI 6.6–11.4%). The prevalence of CagA antibodies was 0.9% (95% CI 0.1–1.6%). No significant differences were demonstrated in H. pylori and cagA prevalence in relation to gender or ethnicity. Conclusion: The prevalence of H. pylori in childhood has remained stable in the Netherlands from 1993 to 2005, suggesting a stabilization of the previously decreasing trend in subsequent birth cohorts. This finding may reflect stabilization in determinants such as family size, housing, and hygienic conditions (or offset by day care). If confirmed in other populations in developed countries, it implies that colonization with H. pylori will remain common in the coming decades. Remarkably however, the rate of colonization with cagA⁺H. pylori strains has become very low, consistent with prior observations that cagA⁺ strains are disappearing in Western countries.     

Cardiovascular risk factors in subjects with Helicobacter pylori infection

Background. It has been proposed that Helicobacter pylori infection is related to cardiovascular disease, although this has not been fully investigated. The aim of this study was to investigate whether H. pylori in‐fection is associated with cardiovascular risk factors. Subjects and Methods. One thousand six hundred and fifty people undergoing annual medical checks at Shimane Institute of Health Science between September 1998 and August 1999 were enrolled. Gender, age, body mass index, habitual smoking and drinking, systolic and diastolic blood pressure, serum level of total cholesterol, triglyceride, high‐density lipoprotein cholesterol (HDLC), blood glucose, leukocyte count and hemoglobin were compared between H. pylori seropositive and seronegative cases. Results. In H. pylori seropositive individuals, HDLC was significantly lower than that in seronegative individuals. After adjustment for possible confounding factors (gender, age, BMI, smoking and drinking habits), mean HDLC in H. pylori‐seropositive and seronegative individuals were 56.1 and 58.2 mg/dl, respectively (p < .005). The percentage of the elderly (over 50 years old) individuals with HDLC < 35 mg/dl in H. pylori seropositive and seronegative groups were 7.4% and 4.7%, respectively (p < .001). In addition, the lower HDLC level was accompanied by an increased leukocyte count. Conclusion. Long‐term infection with H. pylori may have an important role in decreasing the serum HDLC concentration.     

Phenotypic changes of Helicobacter pylori components during an experimental infection in mice

The bacterial pathogen Helicobacter pylori is highly adapted to the human stomach and the clinical isolates show a high diversity which could be due to adaptative changes of the strains passing from one host to another. In order to study these variations, experimental infection of mice was developed and provided three out of the eleven tested strains able to infect C57BL/6 mice: the Sydney strain which is known to be well adapted to mice and two freshly isolated strains from infected patients. Mice were orally infected with one of these three strains (infecting strains) and were killed 45 days later. H. pylori strains were isolated from the stomachs of mice (emerging strains). The three infecting strains were compared to the three emerging strains for protein and lipopolysaccharide profiles, antigenic profiles revealed by Western blot with monospecific sera and genetic status by testing for the cagA gene and the vacA genotype. During the 45 days of infection, H. pylori underwent phenotypic variations which may be attributed to the adaptation from a human to a mouse environment or from an in vitro to a mouse environment. Those variations consisted of an over-expression at the cell surface of a 180-kDa protein and of a decreased expression of proteins of 260 and 120 kDa. Moreover, antigenic variations were shown for the two freshly isolated strains from human: the CagA and VacA antigens were in the saline extracts of the infecting strains only while the UreA, UreB, HspA and HspB were in the saline extracts of both the infecting and the emerging strains. These variations may contribute to the adaptation of the strains to the mouse environment.     

Progress in vaccine development against Helicobacter pylori

Based on the very high prevalence of diseases caused by Helicobacter pylori, particularly in the developing world, and the rapid emergence of antibiotic resistance among clinical isolates, there is a strong rationale for an effective vaccine against H. pylori. In this review we describe recent promising candidate vaccines and prophylactic or therapeutic immunization strategies for use against H. pylori, as well as studies to identify immune responses that are related to protection in experimental animals. We also describe identification of different types of immune responses that may be related to protection against symptoms based on comparisons of H. pylori-infected patients with duodenal ulcers or gastric cancer and asymptomatic carriers. We conclude that there is still a strong need to clarify the main protective immune mechanisms against H. pylori as well as to identify a cocktail of strong protective antigens, or recombinant bacterial strains that express such antigens, that could be administered by a regimen that gives rise to effective immune responses in humans.     

Variables Influencing Outcome of Helicobacter pylori Eradication Therapy in South China

Background: Therapy combining a proton pump inhibitor (PPI), clarithromycin and either amoxicillin or metronidazole is widely recommended for first‐line treatment for Helicobacter pylori infection. The purpose of this study was to examine the outcomes of PPI‐containing triple therapy and identify factors influencing the cure rate of H. pylori infection in South China. Materials and Methods: H. pylori positive patients with different occupations from 25 hospitals in five provinces of South China were enrolled. They received a PPI, metronidazole and amoxicillin triple therapy for a week. H. pylori eradication was evaluated by ¹³C‐urea breath test 4 weeks after therapy. Association between H. pylori eradication with occupation, gender, age, educational level, and protocol compliance was evaluated by Logistic regression. Results: Six hundred and seventy‐five were enrolled. The intention‐to‐treat and per‐protocol analyses showed overall cure rates of 60% (95% CI = 56.3–63.7%) and 64.5% (95% CI = 60.7–68.3%), respectively. Multivariate logistic regression showed that occupation, gender and protocol compliance were positively associated with the eradication rate (p < .01). The cure rate for those who took 80% or more of the prescribed drugs was 64.5% (95% CI = 60.7–68.3%) versus 14.6% (95% CI = 6–29%, p < .001) for those who took less. Lower eradication rates were also observed in farmers and women. Conclusions: The eradication rate with a PPI, metronidazole and amoxicillin triple therapy was unacceptably low in South China. These results suggest that studies of the eradication of H. pylori infection in China must take into account antibiotic resistance as well as patient occupation, gender, and protocol compliance. Gastric cancer and peptic ulcer disease are both important in China making methods to effectively and efficiently eradicate H. pylori a priority.     

影响幽门螺杆菌根除疗效相关因素

幽门螺杆菌（Hp）是慢性活动性胃炎和消化性溃疡的主要病因,并与胃癌、MALT淋巴瘤的发生密切相关,其根除治疗在临床上具有重要的意义。大量研究显示Hp的根除疗效在下降,本文就有关影响Hp根除疗效的相关因素做一简要概述。     

Identification of a new segment involved in cagA 3' region variation of Helicobacter pylori

The cagA 3' region shows marked variation among Helicobacter pylori strains. Two segments of 102 bp and 57 bp are reportedly responsible for this variation. We analysed the cagA 3' region in 70 H. pylori strains using polymerase chain reaction and sequencing. We found that another segment, namely beta segment, was also involved in the variation of this region. The beta segment was 105 bp long and located between the aforementioned two segments. Six genotypes were identified based on the structure of the cagA 3' region. No relationship was found between these genotypes and the clinical outcomes or vacA genotypes. The numbers of tyrosine phosphorylation sites within the cagA 3' region varied among strains, but this was not related to the cagA genotypes. Our data suggest that the cagA 3' region is significantly variable. It appears that the variation of the cagA 3' region might contribute to the modification of virulence.