Emergence of clarithromycin-resistant Helicobacter pylori (CRHP) with a high prevalence in children compared with their parents

Background. Clarithromycin‐resistant Helicobacter pylori (CRHP) is increasing worldwide. Clarithromycin resistance in H. pylori from familial members has not been investigated. Materials and Methods. Biopsy specimens were taken from 13 families living in Tokyo, Yokohama, and Niigata between 1998 and 2001. Drug resistance was tested with the replica plating method. The minimum inhibitory concentrations of antimicrobial agents for H. pylori strains were determined by the agar dilution method. Molecular analyses of H. pylori strains were performed by ribosomal RNA gene restriction pattern analysis. The DNA region, associated with clarithromycin resistance, was analyzed by PCR and sequencing. Results. Helicobacter pylori strains isolated from a 5‐year‐old‐son displayed clarithromycin resistance with a mutation (A → G at position 2143) in the 23S ribosomal RNA, whereas H. pylori strains from his parents did not. DNA analyses revealed that the boy was infected with his father's strain. The boy had repeatedly developed otitis media and received clarithromycin since the age of 2 years. Studies on an additional 12 families demonstrated that clarithromycin resistance in the children's strains reached 42.9% and was significantly higher than those of H. pylori strains from their parents (0%) or from adult patients (11.1%) (p < .05). Conclusions. The rate of clarithromycin resistance in H. pylori strains from Japanese children was extremely high, in contrast to those from their parents or adult patients. Prior history of clarithromycin usage in a child suggested development of clarithromycin resistance in resident H. pylori, which was originated from a parent.     

Younger siblings play a major role in Helicobacter pylori transmission among children from a low-income community in the Northeast of Brazil

Background and Aims: To further evaluate intrafamilial transmission of H. pylori infection during childhood, we investigated the prevalence of H. pylori in family members from a poor H. pylori high‐prevalence urban community in the Northeast of Brazil. Methods: H. pylori infection was investigated in 570 members of 128 households, by ¹³C‐urea breath test in children and by ELISA in mothers and other adult relatives. Results: The overall prevalence of H. pylori infection (376/570) increased with age (p < .001) and ranged from 28.9%, in children aged 6 months to 5 years, to 82% in adults over 40 years. An H. pylori positive mother and the number of infected siblings are independent risk factors for childhood H. pylori infection (OR = 2.2, 95% CI = 1.0–4.6 and OR = 4.3, 95% CI = 2.3–8.1, respectively) The number of siblings, number of younger siblings, and number of infected younger siblings were also associated with the infection in the univariate analysis. The number of infected younger siblings remained independently associated with the infection (p = .000), even after controlling for all the above cited variables, in addition to the H. pylori status of siblings and mothers, age, number of people per room, and number of children in the household. Conclusion: The transmission of H. pylori occurs from infected mothers to their offspring and among siblings, notably from younger siblings to the older ones.     

Helicobacter pylori infection: further evidence for the role of feco-oral transmission

BACKGROUND: Helicobacter pylori infection is recognized as a major cause of chronic digestive diseases with a major public health impact, yet the knowledge of transmission pathways is limited. We studied the transmission in employees taking care of institutionalized persons with mental disabilities with a documented high prevalence of H. pylori. MATERIALS AND METHODS: Six hundred and seventy-one health-care workers were screened for H. pylori serology. For each employee, information was collected on age, sex, father's and mother's education level, number of household members and number of children sleeping in the same bedroom during childhood, as well as lifestyle factors such as smoking and tropical journeys and occupational exposure data such as type of contact with inhabitants (changing napkins with stools, washing inhabitants, feeding inhabitants, personal contact) and seniority in the institution. RESULTS: Seroprevalence for H. pylori increased significantly with age. In univariate analysis, risk factors for H. pylori positivity were (age-adjusted): father's education, mean length of employment, smoking, contact with fecal materials of inhabitants, washing and feeding of inhabitants. Controlling for confounders, in multiple logistic regression analysis, only fecal contact remained as a significant risk factor for H. pylori infection. CONCLUSIONS: In health-care workers caring for a population with a high prevalence of H. pylori infection, there is an association with fecal transmission. This, however, does not rule out the possibility of other ways of transmission.     

Intrafamilial spread of Helicobacter pylori: a genetic analysis

Background. A high incidence of Helicobacter pylori among family members of children with H. pylori gastritis has previously been documented on biopsy material. The main objective of this study was the genetic clarification of H. pylori strains involved in intrafamilial dispersion. Materials and Methods. Formalin‐fixed, paraffin‐embedded material of antral mucosa from 32 members of 11 families was studied for the presence of genetic homogeneity. To achieve this goal, the entire genome of H. pylori was studied by the polymerase chain reaction (PCR)‐based random amplified polymorphic DNA (RAPD) fingerprinting method. Furthermore, the Urease A gene was analyzed using a multiplex PCR‐assay and an alternative mutation detection method based on the Hydrolink? analysis. Results. RAPD fingerprinting confirmed that closely related H. pylori strains were involved in the intrafamilial dispersion. Mutations and small deletions in Urease A gene were found in 22 out of 32 individuals. Conclusions. The homology of the H. pylori genome in members of the same family strongly supports the hypothesis of transmission of H. pylori from person‐to‐person or from a common source.     

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.     

Evaluation of a Western blot test,Helico blot 2.1, in the diagnosis of Helicobacter pylori infection in a pediatric population

Background. Noninvasive diagnostic tests are useful as screening tools for Helicobacter pylori infection in pediatric populations. The aim of this study was to evaluate performance of the immunoblot assay, Helico Blot 2.1, for the diagnosis of H. pylori infection in symptomatic children. Materials and Methods. Immunoblot assay was used for detection of IgG antibodies to specific H. pylori proteins and to a recombinant H. pylori antigen, CIM marker. The study was performed on sera collected from 134 symptomatic, untreated children (mean age, 9.1 ± 3.2 years; range, 1–14 years). H. pylori infection status was determined by culture, histology and rapid urease test. Results. Immunoblot assay yielded a positive result in 71 of the 72 infected patients (sensitivity 98.6%) and in eight of the 62 noninfected ones (specificity 87.1%). The predictive values for a positive and a negative result were 89.9% and 98.2%, respectively. The performance of the CIM band alone, as a marker for H. pylori infection status, was also evaluated. This band was present on the blot of 71 infected patients and on four of the 62 H. pylori‐negative patients. The sensitivity, specificity, PPV and NPV of the CIM antigen were 98.6%, 93.5%, 94.7% and 98.3%, respectively. Conclusions. The immunoblot assay Helico Blot 2.1 is a suitable noninvasive test for the serodiagnosis of H. pylori infection in children. The good level of performance demonstrated by the novel recombinant antigen CIM suggests it may be a useful contribution to the qualitative and quantitative performance of the Helico Blot 2.1 in pediatric populations.     

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.     

幽门螺杆菌感染的分子机制

幽门螺杆菌(Helicobacterpylori)是居留于人胃上皮组织并引起胃炎、消化性胃溃疡和胃癌的病原菌。近年来,随着幽门螺杆菌全基因组序列的报道和功能基因的研究深入,对幽门螺杆菌的感染的分子、免疫等机制逐渐阐明。现对幽门螺杆菌基因组特点和幽门螺杆菌黏附、毒性因子等对人体感染的分子机制等方面的研究进展做一综述。     

Annual Change of Primary Resistance to Clarithromycin among Helicobacter pylori Isolates from 1996 through 2008 in Japan

Background: Recent studies have shown that the combination of proton pump inhibitor, amoxicillin and clarithromycin is one of the best choices for Helicobacter pylori eradication therapy. However, increasing number of cases of H. pylori infection showing resistance to clarithromycin therapy has been reported and this is currently the main cause of eradication failure. We investigated the annual changes of the antimicrobial susceptibility to clarithromycin, amoxicillin and minocycline during a period of 12 years in Japan. Methods: This study comprised 3521 patients (mean age (SD), 55.4 (13.7) years‐old, 2467 males and 1054 females) positive for H. pylori as assessed by microaerobic bacterial culture from 1996 through 2008. All patients were previously untreated for H. pylori and were enrolled in the study to assess primary resistance to the three antibiotics. Results: The overall primary resistance to clarithromycin, amoxicillin and minocycline were 16.4%, (577/3521), 0.03% (1/3521) and 0.06% (2/3521), respectively. From1996 through 2004, the resistance rate to clarithromycin increased gradually to approximately 30% and then it remained without marked fluctuation since 2004. Analysis by gender showed a significant increase (p < .0001) in resistance rate to clarithromycin among females (217/1057, 20.6%) compared to males (360/2467, 14.6%). Analysis by age, disclosed significantly (p < .0001) higher resistance rate to clarithromycin in patients of more than 65‐years‐old compared to the younger population. Conclusions: The resistance rate of H. pylori infection to clarithromycin in Japan has increased gradually to approximately 30% from 1996 through 2004, and remained unchanged since 2004. Elderly and females were at high risk of having resistance to clarithromycin. Our results suggested that the level of clarithromycin resistance in Japan has now risen to the point where it should no longer be used as empiric therapy.     

Novel monoclonal antibody-based Helicobacter pylori stool antigen test

BACKGROUND: A number of noninvasive tests have been developed to establish the presence of Helicobacter pylori infection. Although polyclonal antibody-based stool antigen testing has a good sensitivity and specificity, it is less accurate than urea breath testing. Recently, a monoclonal antibody-based stool antigen test demonstrated an excellent performance in diagnosing H. pylori infection in adults and in pediatric populations. AIM: To evaluate the diagnostic accuracy of a novel stool test based on monoclonal antibodies to detect H. pylori antigens in frozen human stool in the pretreatment setting. PATIENTS AND METHODS: Stool specimens were prospectively collected from 78 patients undergoing gastroscopy and stored at -20 degrees C until tested. Helicobacter pylori infection was evaluated by histology, rapid urease testing and urea breath tests ((13)C-UBT). Positivity of the three tests was considered the gold standard for H. pylori active infection. Patients with no positive test were considered negative. The gold standard was compare to the results of the monoclonal antibody stool antigen test. Frozen stool specimens were tested using a novel monoclonal-antibody-based enzyme immunoassay (HePy-Stool, Biolife-Italiana, Milan, Italy). RESULTS: The sensitivity and specificity of the monoclonal stool antigen test were 97%[95% confidence interval, (CI) 86-100] and 94% (95% CI: 81-99), respectively. Negative and positive predictive values were 97% (95% CI: 85-99), and 95% (95% CI: 83-99), respectively. The diagnostic accuracy was 96% (95% CI: 88-99). The likelihood ratio for a positive test was 17 and for a negative test was 0. CONCLUSIONS: Although the (13)C-UBT is the most accurate among the available noninvasive tests, our results show that an H. pylori stool test using monoclonal antibody might be an excellent alternative.     

The prevalence and incidence of Helicobacter pylori infections among young recruits during service in the Hungarian Army

BACKGROUND: A vast number of data indicate that the prevalence of Helicobacter pylori infections is positively correlated with age and is different in various countries. Although our knowledge of transmission of H. pylori is very limited, it is reasonable to assume that it could be much more contagious in closed communities, for example in garrisons, than in normal populations. METHODS: Young male recruits (aged 19-23 years) in the Hungarian Army were tested for seropositivity at the beginning and at the end of their military service. RESULTS: The prevalence of H. pylori seropositivity was found to be 23% (*CI95%: 21-24%) among the young male recruits. Seroconversion among the formerly seronegative persons after completing either their 9-month or 6-month military service was 30% (CI95%: 25-35%) and 23% (CI95%: 8-45%), respectively. In those groups, where either the H. pylori infection was eradicated by antibiotics or hygienic countermeasures were introduced, the infection rate was reduced from 23% to 11% (CI95%: 3-25%) and to 0% (CI95%: 0-6%); p > .2 and p < .002, respectively. CONCLUSION: Our data suggest that, although H. pylori has a very high contagiosity in closed communities, its spread can be reduced or even prevented by medication of the infected persons and/or by improving the hygienic conditions and introducing anti-infective sanitary regulations.     

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.