Diagnostic de l’infection à Helicobacter pylori chez l’enfant : quoi de neuf en 2003 ?Helicobacter pylori (H. pylori) infection in childhood: what is new in 2003?

A high prevalence and early colonization of Helicobacter pylori (H. pylori) infection in childhood characterizes the developing countries in contrast to developed ones. Upper gastrointestinal endoscopy including gastric biopsies is the diagnostic gold standard method. Non invasive tests can be used in children, including serology, ¹³C-urea breath test and immunoassay enzyme stool antigen test (HpSA). They present good performance in adults, but less in children under 6 years of age. They can be used for screening, epidemiological studies. Only the ¹³C-urea breath test and the immunoassay enzyme stool antigen test (HpSA) are recommended for the control of eradication. The infection remains often asymptomatic in children and the role of this bacterium in clinical manifestations is the subject of conflicting reports. The treatment of H. pylori infection is influenced by the resistance to the antibiotics used. We suggest that eradication of H. pylori infection should take place only after susceptibility testing since the resistance rate for the metronidazole is of 43% and for the clarithromycine 21% in France. The association of proton pump inhibitor and two antibiotics for 1–2 weeks seems to give the best eradication rates. The crucial question is whether asymptomatic children should be treated to prevent cancer in the future.     

Peptic ulcer disease

Peptic ulcer disease (PUD) is an uncommon disease of childhood. Peptic ulceration of the stomach or duodenum is usually associated with abnormalities of the gastric mucosa such as gastritis and/or gastropathy. Gastritis and ulcers of the stomach and duodenum can be classified into either primary or secondary depending on their aetiologies. The majority of primary or unexplained peptic ulcers are the result of chronic inflammation caused by Helicobacter pylori infection. However, an increasing number of children with PUD without evidence of H. pylori infection are now being seen. Rarely PUD is caused by hypersecretory states. Secondary ulceration occurs in response to acute stress from severe systemic illnesses such as sepsis, head injury, burns, and as sequelae to use of certain drugs. The prognosis for recovery from peptic ulcers is good as most patients will respond to treatment.     

Current views of the relationship between Helicobacter pylori and Henoch-Schonlein purpura in children

Helicobacter pylori (H. pylori) is one of the factors involved in the pathogenesis of various gastrointestinal diseases and may play a potential role in certain extra-intestinal diseases. H. pylori infection are mainly acquired during childhood, and it has been reported that in endemic areas of China the infection rates are extraordinarily higher in HSP children, particular those with abdominal manifestations. Furthermore, eradication therapy may ameliorate Henoch-Schonlein purpura (HSP) manifestations and decrease the recurrence of HSP. Therefore, results suggested that detection of H. pylori infection by appropriate method ought to be applied in HSP children. Current evidences indicate that local injury of gastric mucosa and immunological events induced by H. pylori infection are involved in the development of HSP. Increased serum IgA, cryoglobulins, C3 levels, autoimmunity, proinflammatory substances and molecular mimicry inducing immune complex and cross-reactive antibodies caused by H. pylori infection might play their roles in the course of HSP. However, there are no investigations confirming the causality between H. pylori infection and HSP, and the pathogenesis mechanism is still unclear. More bench and clinical studies need to be executed to elaborate the complex association between H. pylori and HSP.     

Reinfection Rate after Successful Helicobacter pylori Eradication in Children

Objective

Reinfection rate of Helicobacter pylori after successful eradication is low in developed countries. This study was performed to determine the reinfection rate of H. pylori during a follow up period of 12 months in Iranian children.

Methods

In this prospective study, children with H. pylori infection were treated with triple omeprazole based regimen. Patients with negative ¹³C urea breath test (UBT) performed after 8 weeks of therapy, were followed up by the same test after 1 year.

Findings

Thirty seven patients, aged 5 to 17 years, were studied. Among them 25 (67.5%) were boys. After eradication therapy of H. pylori, 34 patients had negative ¹³C UBT. Reinfection occurred in 5 (14.7%) patients. Reappearance or continuing symptoms after treatment were associated with higher rate of recurrence (P=0.042).

Conclusion

Recurrence rate of H. pylori was high in our children. Successful eradication significantly decreased complaints and further symptoms. Follow up and reevaluation of patients is necessary especially when there are symptoms after eradication.     

Antibiotic resistance and antibiotic sensitivity based treatment in Helicobacter pylori infection: advantages and outcome

AIMS—To compare two strategies for the eradication of Helicobacter pylori infection.METHODS—Groups 1 and 2 each consisted of 75 consecutive patients. Patients in group 1 were treated with two antibiotics based on antibiotic susceptibility testing; those in group 2 received amoxycillin and clarithromycin for eight days, together with either ranitidine or omeprazole. Eradication rate was assessed in both groups six months after treatment.RESULTS—In group 1, H pylori grew in culture in 63/75 cases. Susceptibility testing showed that 35/63 isolates were resistant to metronidazole, 10/63 to clarithromycin, 2/63 to ampicillin, 1/63 to tetracycline, and 5/63 to both clarithromycin and metronidazole. In group 1the infection was eradicated in 96% of the initial 75 subjects, and in 98% of the subjects treated according to the antibiotic assay (62/63). As two patients were lost at follow up the overall eradication rate was 99%. In group 2, eradication was achieved in 61/75 subjects (81%). This was significantly lower than the percentage of eradication observed in group 1 (81% versus 99%).CONCLUSIONS—Antibiotic susceptibility tests are useful in childhood as a very high percentage of subjects are cured. This approach is costly, but selective antibiotic treatment contributes to limit further development of antibiotic resistance, and money is saved in terms of reinvestigation and further repeated treatments.     

Early Helicobacter pylori colonisation: the association with growth faltering in The Gambia

Background: Helicobacter pylori is one of the commonest causes of chronic infection of mankind, yet the natural history of acute infection is poorly understood. Some studies suggest that gastric colonisation with H pylori is associated with suboptimal nutrition and growth in childhood. Aims: To describe the clinical features of early H pylori colonisation and assess its role in the development of infant malnutrition and growth faltering. Methods: Two consecutive prospective longitudinal cohort studies were conducted at the Medical Research Council Laboratories in a rural community in The Gambia, West Africa. The first birth cohort of 125 infants was followed by a second of 65 children from the same community. H pylori colonisation was detected by sequential ¹³C urea breath tests, and infant growth was monitored by serial measurements. Results: Children with early H pylori colonisation became significantly lighter, shorter, and thinner than their peers in late infancy. The association was found in both cohorts. No socioeconomic or demographic confounding variables were identified to explain this, and the weight deficit was no longer detectable when the children were aged 5–8 years. Conclusions: Results suggest that H pylori colonisation in early infancy predisposes to the development of malnutrition and growth faltering, although the effect did not persist into later childhood.     

Effect of Helicobacter pylori eradication on the natural history of duodenal ulcer disease

BACKGROUND—Duodenal ulcer disease is strongly associated with Helicobacter pylori infection of the gastric mucosa. Eradication of H pylori from the gastric mucosa in adults is associated with long term healing of ulcers.AIMS—To follow a cohort of children with duodenal ulcer disease for a minimum of two years after the eradication of H pylori.PATIENTS AND METHODS—Over a three year period, all children diagnosed with duodenal ulcer disease had their symptoms documented and their H pylori status evaluated. The histories of these children were carefully screened to determine previous symptoms and to document previous treatment regimens.RESULTS—Sixteen children were diagnosed with ulcers and 15 were available for treatment and long term follow up. The median age at which symptoms first occurred was 10.5 years (range, 6-14) and the median duration of symptoms was 24 months (range, 2-60). Ten of the children had been treated with H₂ receptor antagonists for a median of 3.5 months (range, 1-60). Duodenal ulcers healed in all children after eradication of H pylori and all children have remained asymptomatic for a median of 37 months (range, 26-62). No child has required subsequent admission to hospital.CONCLUSION—Eradication of H pylori is very effective in the long term healing of duodenal ulcer disease. H pylori eradication should be the standard treatment for all infected children who present with duodenal ulcer disease.     

Primary Antibiotic Resistance to Helicobacter pylori Strains Isolated From Children in Northern Iran: A Single Center Study

Background:

Initial resistance to antibiotics is the main reason for the failure of Helicobacter pylori (H. pylori) eradication in children.

Objectives:

As we commonly face high antibiotic resistance rates in children, we aimed to determine the susceptibility of H. pylori to common antibiotics.

Patients and Methods:

In this cross-sectional in vitro study, 169 children younger than 14 years with clinical diagnosis of peptic ulcer underwent upper gastrointestinal endoscopy. Biopsy specimens from stomach and duodenum were cultured. In isolated colonies, tests of catalase, urease, and oxidase as well as gram staining were performed. After confirming the colonies as H. pylori, the antibiogram was obtained using disk diffusion method.

Results:

Culture for H. pylori was positive in 12.3% of the specimens, urease test in 21.3%, serological test in 18.9% and stool antigen test was positive in 21.9%. We could show high specificity but moderate sensitivity of both histological and H. pylori stool antigen tests to detect H. pylori. The overall susceptibility to metronidazole was 42.9%, amoxicillin 95.2%, clarithromycin 85.7%, furazolidone 61.9%, azithromycin 81.0%, and tetracycline 76.2% with the highest resistance to metronidazole and the lowest to clarithromycin.

Conclusions:

In our region, there is high resistance of H. pylori to some antibiotics including metronidazole and furazolidone among affected children. To reduce the prevalence of this antibiotic resistance, more controlled use of antibiotics should be considered in children.     

Meta-analysis of randomized controlled trials on the efficacy of probiotics in Helicobacter pylori eradication therapy in children

The efficacy of probiotics supplementation in children undergoing Helicobacter pylori (H. pylori) eradication therapy remains controversial. This study aimed to meta-analyze whether probiotics supplementation in triple therapy could improve H. pylori eradication rates and reduce therapy-related side effects in children. Electronic databases PubMed and Embase were searched to identify all randomized controlled trials in pediatric patients comparing probiotics supplementation with placebo or no extra intervention in H. pylori eradication therapy. Two authors independently extracted the data. Results were expressed as odds ratios (ORs) and accompanying 95 % confidence intervals (CIs). Stata version 12.0 was used to perform all statistical analyses. Seven studies consisting of 508 pediatric patients were included in our study. The pooled ORs (studies n?=?7) of eradication rates by intention-to-treat and per-protocol analysis in the probiotics group versus the control group were 1.96 (95 % CI 1.28–3.02) and 2.25 (95 % CI 1.41–3.57), respectively. The pooled OR (studies n?=?5) of incidence of total side effects was 0.32 (95 % CI 0.13–0.79), with significant heterogeneity observed (I ²?=?71.9 %). Conclusion: Probiotics supplementation in triple therapy for H. pylori infection may have beneficial effects on eradication and therapy-related side effects, particularly diarrhea, in children.     

儿童新诊断免疫性血小板减少症与幽门螺杆菌感染的相关性研究

目的明确幽门螺杆菌(H.pylori)感染对儿童新诊断免疫性血小板减少症(ITP)的影响。方法选取2011年1月至2013年12月间首次住院并新诊断为ITP的495例患儿为病例组;随机选取无血小板减少及其他血液系统疾病的普通呼吸道感染住院患儿123例作为对照组。依据年龄将两组患儿分为1岁组(n=219)、1岁~组(n=161)、3岁~组(n=76)和7~14岁组(n=39)。回顾性分析各年龄段患儿H.pylori感染率,以及H.pylori感染阳性及阴性ITP患儿经过相同治疗后的预后情况。结果病例组中H.pylori感染率随着ITP患儿年龄的增长而增加,与对照组各年龄段H.pylori感染率比较差异均无统计学意义(均P0.05)。H.pylori感染阳性ITP患儿均未接受针对H.pylori的相关治疗,而针对血小板减少经丙种球蛋白和/或激素治疗后缓解率随着年龄的增长而呈现逐渐下降趋势,与各年龄段H.pylori阴性的ITP患儿治疗后缓解率比较差异均无统计学意义(均P0.05)。结论 H.pylori感染可能不是ITP患儿发病的一个主要致病因素;是否治疗H.pylori并不影响儿童急性ITP的治疗效果。     

Saccharomyces Boulardii in Helicobacter Pylori Eradication in Children: A Randomized Trial From Iran

Background:

Helicobacter pylori infects around 50% of the human population and is asymptomatic in 70% of the cases. H. pylori eradication in childhood will not only result in peptic symptoms relief, but will also prevent late-term complications such as cancer. Today, probiotics are being increasingly studied in the treatment of gastrointestinal infections as an alternative or complement to antibiotics.

Objectives:

In this study we aimed to assess the effect of S. boulardii supplementation on H. pylori eradication among children in our region.

Patients and Methods:

In this randomized double-blind placebo-controlled clinical trial 28 asymptomatic primary school children with a positive H. pylori stool antigen (HpSA) exam were randomly allocated into the study group, receiving Saccharomyces boulardii, and the control group receiving placebo capsules matched by shape and size, for one month. The children were followed up weekly and were reinvestigated four to eight weeks after accomplished treatment by HpSA testing. The significance level was set at P < 0.05.

Results:

24 children completed the study. The mean HpSA reduced from 0.40 ± 0.32 to 0.21 ± 0.27 in the study group, indicating a significant difference (P = 0.005). However, such difference was not observed in the control group (P = 0.89). Moreover, the HpSA titer showed a 0.019 ± 0.19 decrease in the study group whereas the same value was 0.0048 ± 0.12 for the controls, again stating a significant difference (P = 0.01).

Conclusions:

Saccharomyces boulardii has a positive effect on reducing the colonization of H. pylori in the human gastrointestinal system but is not capable of its eradication when used as single therapy.     

A review of current guidelines for the management of Helicobacter pylori infection in children and adolescents

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

Helicobacter pylori infection and growth delay in older children

Accepted 18 March 1997
It is thought that Helicobacter pylori infection may influence growth rate in children. The aim of this study was to evaluate the prevalence of H pylori infection in healthy Italian children, and to look for differences in height between infected and non-infected subjects. Two hundred and sixteen children, aged 3 to 14 years, were tested for H pylori infection by ¹³C-urea breath test. Centile values for height were calculated. Composite indices for socioeconomic class and household crowding were also determined. Forty nine of 216 children (22.7%) were H pylori positive. The prevalence of infection increased with age. Eight of 49 H pylori positive children (16.3%) were below the 25th centile for height, compared with 13 of 167 H pylori negative children (7.8%). This difference became significant in children aged 8.5 to 14 years; in this group (n = 127), eight of 31 infected children (25.8%) were below the 25th centile for height, compared with eight of 96 non-infected children (8.3%). A significant correlation was found between socioeconomic conditions, household crowding, and H pylori status. By using stepwise logistic regression, only the centile value for height was significantly related to H pylori status in older children. Thus H pylori infection was associated with growth delay in older children, poor socioeconomic conditions, and household overcrowding. This finding is consistent with the hypothesis that H pylori infection is one of the environmental factors capable of affecting growth.

     

Growth in children with Helicobacter pylori infection and dyspepsia

Aims: To compare the height, weight, and body mass index (BMI) of children presenting with dyspeptic symptoms and Helicobacter pylori infection, to those with dyspepsia but without the infection. Methods: A retrospective chart review of 257 children was performed. ¹³C urea breath test was performed to detect H pylori infection; weight and height were recorded and BMI was calculated. Weight, height, and BMI SD scores were determined using the 1990 UK normative data. The Index of Multiple Deprivation 2004 (IMD 2004) scores, which measure deprivation at small area level, were calculated from the patients'' postcodes. Results: Ninety seven of the 257 children were H pylori positive. The mean age at diagnosis and presenting symptoms of H pylori positive and negative patients were similar. The mean IMD 2004 scores for children with H pylori infection were significantly higher compared to H pylori negative patients, suggesting that children with the infection came from relatively more deprived areas. The mean weight and height SD score were significantly lower for children with H pylori infection compared to those without. However, this difference was no longer significant after adjusting for socioeconomic deprivation and ethnic differences between the groups. Conclusion: Children with dyspepsia and H pylori infection were shorter and lighter than patients with similar symptoms but no infection. The differences in anthropometry may be due to socioeconomic and ethnic factors rather than H pylori infection.     

Is Helicobacter pylori infection associated with Henoch-Schonlein purpura in Chinese children? a meta-analysis

Background

The prevalence of Helicobacter pylori (H. pylori) infection is high in China. It not only causes the damage of gastric epithelium, but also plays a potential pathogenic role in several extraintestinal diseases. Henoch-Schonlein purpura (HSP) is one of the most common vasculitis syndromes affecting children. Although its cause is unclear, HSP is often considered to be associated with infectious agents. This metaanalysis of previously published studies was conducted using a predefined protocol to evaluate the underlying association between H. pylori infection and HSP in Chinese children.

Methods

Predefined search strategy and inclusion criteria were set up to select studies reporting the prevalence of H. pylori infection among HSP children and control groups. Included studies were subjected to quality assessment and data extraction by two independent reviewers. The pooled odds ratio (OR) was calculated as the effect size via both traditional and cumulative meta-analysis. Heterogeneity was investigated by subgroup analysis, and the nonparametric ??trim and fill?? method was performed to adjust the overall estimate for the existence of publication bias.

Results

Ten eligible studies covering 749 HSP children and 560 controls were included for metaanalysis. Observational epidemiology studies clearly aimed at detecting the potential association between H. pylori infection and HSP with retrospective data collection from the children enrolled consecutively. Overall, 49.27% (369/749) of HSP children had evidence of H. pylori infection compared with 23.39% (131/560) of children in the control group. The pooled OR of H. pylori infection in HSP children (10 studies with 749 HSP children) was 3.80 [95% confidence interval (CI): 2.54?C5.68, P<0.001], and the overall estimate from the cumulative meta-analysis confirmed the association with more narrow confidence interval (OR=3.35, 95% CI: 2.95?C3.81). In HSP children mainly with abdominal manifestations (8 studies with 337 HSP children), the pooled OR was 4.62 (95% CI: 2.66?C8.01, P<0.001). The adjusted pooled OR was 2.04 (95% CI: 1.48?C2.82, P<0.001), determined by the nonparametric ??trim-andfill?? method for eliminating the effect of publication bias. H. pylori eradication therapy (4 studies with 266 HSP children) was capable of reducing the recurrence of HSP (RR=0.38, 95% CI: 0.25?C0.58, P<0.001). Although the subgroup analysis for heterogeneity suggested that diagnostic methods and geographical diversity might be account for the heterogeneity, statistical analysis of differences revealed no differences between subgroups, indicating their limited impact on the overall estimates.

Conclusions

These results suggest the necessity of screening H. pylori infection in HSP children, particularly in those with gastrointestinal manifestations in China. Eradication therapy may reduce the recurrence of HSP in children with H. pylori infection. However, further mechanistic and more clinical studies in different populations and regions are needed to confirm this association and the effect of eradication of H. pylori in HSP children.     

Diagnosis ofHelicobacter Pylori

In view of its potential risk for the development of gastrointestinal disease or even gastric cancer at a later age, the study ofHelicobacter pylori infection in childhood is gaining increasing importance andH. pylori infection is being considered a major issue of public health.H. pylori infection can be detected by a variety of methods. Because of its easy use, affordability, and overall availability, serology is the preferred diagnostic test, especially for large epidemiological studies. Based on our results, one might consider treating a child with recurrent abdominal pain and positive serology forH. pylori without further work-up, and only perform additional investigations when an anti-W.pylori therapy fails to resolve the complaints. According to this proposition, endoscopy of the upper gastrointestinal tract remains indicated in children if the noninvastive tests forHelicobacter pylori are negative in the absence of a diagnosis, or if symptomatology persists despite treatment.     

Helicobacter pylori diagnostic tests in children: review of the literature from 1999 to 2009

The array of tests that can be used for diagnosis of Helicobacter pylori infection is large, and it can be confusing to define which test to use particularly in children where results may not be comparable to those obtained in adult patients. Using PubMed, we reviewed the English literature from January 1999 to May 2009 to identify articles that determined sensitivity and specificity of H. pylori invasive and non-invasive diagnostic tests in children. We excluded articles that presented a review of the literature, abstracts, case reports, or series where children’s results could not be separated from adult populations. Of the tissue based methods, rapid urease tests have better sensitivity than histology to detect presence of H. pylori; however, histology can detect the pathology associated with disease including gastritis, intestinal metaplasia, and other conditions that could be the cause of the child’s symptoms. Culture of gastric tissues or stool has 100% specificity but sensitivity is low. Of the serologic tests, immunoblot has the best sensitivity. The urea breath tests have >75% sensitivity for detection of H. pylori before and after treatment. Immunoassays in stool using monoclonal antibodies have >95% sensitivity for detection of H. pylori before and after treatment. PCR testing can be performed in tissue and stool samples and can detect genes associated to antibiotic resistance. In summary, the current commercial non-invasive tests have adequate sensitivity and specificity for detecting the presence of H. pylori; however, endoscopy with histopathology is the only method that can detect H. pylori and lesions associated with the infection.     

Growth parameters in children with dyspepsia symptoms and Helicobacter pylori infection

Controversy exists about relationship of H. pylori infection and somatic growth retardation of children. The aim of this study was to evaluate the relationship between H. pylori infection and growth parameters in children. 113 children with dyspepsia (4–18 years) were enrolled. C₁₃ urea breath test was performed for determination of H.pylori infection. Height, weight, body mass index (BMI) and standard deviation score (SDS) was calculated and growth parameters were compared between two groups of H.pylori positive and those with negative results. The prevalence of H.pylori infection was 52.2%. There was no meaningful relation between calculated SDS (for height and BMI) and H.pylori infection.     

Is peptic ulcer a common cause of upper gastrointestinal symptoms?

 The aim of the study was to investigate retrospectively a cohort of children with peptic ulcer disease during a period that covers the recent changes in diagnosis and management of the disease. Over a period of 9 years, 2550 children underwent upper gastrointestinal endoscopy for various reasons. All children, in whom a diagnosis of primary peptic ulcer was established, were included in the study. Previous and current medical history, family history, endoscopic and histological outcome were evaluated and the children were regularly followed-up on an out-patient basis. Primary peptic ulcer was diagnosed in 52 (10 gastric and 42 duodenal, 2%) out of 2550 children. The median age of children with gastric ulcer was 6.5 years, whereas of those with duodenal ulcer was 10.5 years (P=0.04). With regard to clinical symptoms no significant difference was found between children with and without ulcer. The prevalence of Helicobacter pylori infection was significantly higher in children with duodenal ulcer (62%) compared to those with gastric ulcer (20%; P<0.001). At first follow-up visit, 1 month after the end of treatment, 19 symptomatic children underwent a repeat endoscopy, which showed ulcer healing in 95% and failure in H. pylori eradication in 27%. During the long-term follow-up (median 3.5 years), six children became symptomatic. Two of them had duodenal ulcer associated with positive H. pylori. Conclusion Peptic ulcer disease is an uncommon disorder in childhood with non specific clinical features; it seems that efficient treatment and successful Helicobacter pylori eradication result in clinical improvement and cure as well as in long-term healing of ulcers. Received: 25 September 2000 and in revised form: 22 February and 28 March 2001 / Accepted: 29 March 2001     

Helicobacter pylori stool antigen test

Objective :Helicobacter pylori (H.pylori) infection is usually acquired in early childhood. Invasive techniques used for diagnosis ofH.pylori infection require endoscopic examination which is expensive and inconvenient and may cause complications. the aim of this study was to evaluate the performance of a new noninvasive diagnostic method, stool antigen test forH.pylori in untreated children with recurrent abdominal pain.Methods: Eighty children (35 female, 45 male) who have undergone upper gastrointestinal endoscopy due to recurrent abdominal pain were included in the study. theH.pylori stool antigen test (HpSA) is based on a sandwich enzyme immunoassay with antigen detection. HpSA sensitivity, specificity, and positive and negative predictive values were determined with reference to the results of both histology and rapid urease test as a gold standard (H. pylori status).Results: While 49 of the 80 children (61%) tested were positive forH.pylori according to the results of both histology and rapid urease test, 28 children had negativeH.pylori status. Among those 49 children, 48 were found to be positive by HpSA. Of 28 patients with negativeH.pylori status, 28 were H.py/ori-negative also in the stool test. the sensitivity, specificity, and positive and negative predictive values of HpSA were found to be 98%, 100%, 100%, and 96.5%, respectively.Conclusion: these findings have demonstrated that HpSA as a relatively simple, inexpensive and time saving noninvasive test is a reliable method for detection ofH.pylori infections in children.