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.     

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。     

Breastfeeding and Helicobacter Pylori Infection in Children with Digestive Symptoms

Objective

This study aims to evaluate the role of breastfeeding in the acquisition of Helicobacter pylori (H. pylori) infection in Iran and to compare the histopathologic changes occurring in children feeding on breast milk with those in infants feeding on formula.

Methods

In a case-control study parents of children with and without H. pylori infection who had undergone endoscopic survey and gastric biopsy in the Children''s Medical Center, Tehran, were asked about their feeding practices during the first 6 months after birth, the duration of breastfeeding period, the symptoms, and the duration of symptoms and concomitant diseases.

Findings

A total of 154 children were included in this study. From this sample, 77 children formed the case group and 77 children formed the control group. A significant difference was found between H. pylori infection and feeding with formula (P=0.045). In case group, a significant difference was found between breastfeeding and age of the infected child (P=0.034), shorter duration of symptoms (P=0.016), and finally degree of H. pylori colonization (P=0.021).

Conclusion

It appears that breastfeeding in the first 6 months after birth can decrease the degree of H. pylori colonization, postpone infection until older age, shorten the duration of symptoms, and be concomitant with milder gastritis.     

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.     

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.     

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.

     

Analysis of Genomic Diversity among Helicobacter pylori Strains Isolated from Iranian Children by Pulsed Field Gel Electrophoresis

Objective:

Presence of genomic diversity among Helicobacter pylori (H. pylori) strains have been suggested by numerous investigators. Little is known about diversity of H. pylori strains isolated from Iranian children and their association with virulence of the strains. Our purpose was to assess the degree of genomic diversity among H. pylori strains isolated from Iranian-children, on the basis of vacA genotype, cagA status of the strains, sex, age as well as the pathological status of the patients.

Methods:

Genomic DNA from 44 unrelated H. pylori strains isolated during 1997–2009, was examined by pulse-field gel electrophoresis (PFGE). Pathological status of the patients was performed according to the modified Sydney-system and genotype/status of vacA/cagA genes was determined by PCR. PFGE was performed using XbaI restriction-endonuclease and the field inversion-gel electrophoresis system.

Findings:

No significant relationship was observed between the patterns of PFGE and the cagA/vacA status/genotype. Also no relationship was observed between age, sex, and pathological status of the children and the PFGE patterns of their isolates. Similar conclusion was obtained by Total Lab software. However, more relationship was observed between the strains isolated in the close period (1997–2009, 2001–2003, 2005–2007, and 2007–2009) and more difference was observed among those obtained in the distant periods (1997 and 2009).

Conclusion:

H. pylori strains isolated from children in Iran are extremely diverse and this diversity is not related to their virulence characteristics. Occurrence of this extreme diversity may be related to adaptation of H. pylori strains to variable living conditions during transmission between various host individuals.     

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.     

根除幽门螺杆菌疗法治疗过敏性紫癜患儿的预后分析

目的 分析根除幽门螺杆菌（Hp）治疗对过敏性紫癜（HSP）患儿预后的影响。方法 153 例HSP 患儿分为Hp 感染治疗组（22 例）,在常规治疗基础上加用1 周“三联”根除Hp 方案治疗;Hp 感染对照组（21例）及Hp 感染阴性组（110 例）,均给予常规治疗。随访3 组患儿预后情况。结果 治疗组有效率为86%（19/22）,对照组有效率为90%（19/21）,阴性组有效率为85%（94/110）,3 组患儿有效率比较差异无统计学意义（P>0.05）。治疗组HSP 复发率为14%（3/22）,对照组复发率为24%（5/21）,阴性组复发率为31%（34/110）,3 组患儿复发率比较差异亦无统计学意义（P>0.05）。阴性组（36%,40/110）和对照组患儿（33%,7/21）紫癜性肾炎（HSPN）发生率均明显高于治疗组（5%,1/22）（均P<0.05）,而对照组与阴性组间HSPN 发生率比较差异无统计学意义（P>0.05）。结论 对Hp 感染的HSP 患儿予1 周“三联”根除Hp 方案治疗,可能有助于降低HSPN 的发生率。     

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.     

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.     

Clinical Practice: Helicobacter pylori infection in childhood

Helicobacter pylori infection is recognised as a cause of gastritis and peptic ulcer disease (PUD) and usually acquired during the first years of life. While there is a decline in the prevalence of H. pylori infection in northern and western European countries, the infection is still common in southern and eastern parts of Europe and Asia. Symptoms of H. pylori-related PUD are nonspecific in children and may include epigastric pain, nausea and/or vomiting, anorexia, iron deficiency anaemia and hematemesis. Besides, only a small proportion of children develop symptoms and clinically relevant gastrointestinal disease. H. pylori infection can be diagnosed either by invasive tests requiring endoscopy and biopsy or non-invasive tests including the ¹³C-urea breath test, detection of H. pylori antigen in stool and detection of antibodies in serum, urine and saliva. The aim of treatment is at least 90 % eradication rate of the bacteria, and a combination of two antibiotics plus a proton pump inhibitor has been recommended as first-line treatment. However, frequent use of antibiotics during childhood is associated with a decline in eradication rates and the search for new treatment strategies as well. This is an overview of the latest knowledge and evidence-based guidelines regarding clinical presentation, diagnosis and treatment of H. pylori infection in childhood.     

儿童腹型过敏性紫癜与幽门螺杆菌感染的关系探讨

目的：探讨腹型过敏性紫癜(HSP)的发病及反复发作与幽门螺杆菌(HP)感染的关系。方法对36例腹型HSP及32例非腹型HSP中的16例进行胃、十二指肠内镜检查并行快速尿素酶试验,另设30例健康儿童作为对照组。3组均进行14C尿素呼气试验、血清抗HP抗体检测。结果36例腹型HSP患儿HP阳性21例（58.3%）, 其中反复发作16例,HP阳性13例（81.3%）,首次发作20例HP阳性9例（45.0%）。32例非腹型HSP患儿HP阳性9例（28.1%）;对照组HP阳性2例（6.7%）。三组比较差异具有非常显著性意义（χ2=14.7,P<0.01）,反复发作与首次发作比较差异具有显著性意义（χ2 =4.49,P<0.05）。结论 腹型HSP的发病及反复发作与HP感染有关。［中国当代儿科杂志,2007,9（4）：367-369］     

Consideration of Helicobacter pylori infection in childhood: Immune response,endoscopic and morphological findings

Seventy-five children (aged 9–14 years) infected with Helicobacter pylori were studied endoscopically and morphologically for the signs of infection and immune response by ELISA technique (total IgE and specific IgG against H. pylori); a control group of 36 children (not infected with H. pylori) were studied simultaneously. Helicobacter pylori positive children examined endoscopically revealed a number of mucous membrane changes including erythema, erosions, lymphoid nodular hyperplasia and ulcers. Gastritis was confirmed by histology in 58 children; 6% were termed ‘active’, others were ‘non-active’. When studying the concentrations of anti-H. pylori IgG in children from the control group they were considered to be seronegative but in children infected with H. pylori a considerable increase was noted. An evaluation of the interaction between anti-H. pylori IgG titers and age, endoscopic signs and histology was carried out. Suppositions were made about the presence of links between these characteristics. Children with H. pylori infection showed a considerable increase of total IgE titers in comparison with the control group. The role of IgG and IgE in the development of chronic gastroduodenal diseases associated with H. pylori is discussed.     

Symptomatology of Helicobacter pylori infection in children

In a retrospective evaluation we reviewed the symptomatology of 143 children (age 2–15 years, mean 8.9 years) who were referred to us for upper gastrointestinal endoscopy because of recurrent abdominal pain with a duration of 6 weeks or longer. Helicobacter pylori infection was diagnosed in 36 out of 143 patients (25.2%). No statistically significant differences could be detected between the symptoms experienced by the 36 H. pylori-infected children and those experienced by the remaining 107 H.pylori-negative pediatric patients (p = 0.18–0.60). We conclude that no specific symptoms are associated with H. pylori gastritis in children. Our observations suggest that the recurrent abdominal complaints found in children with H. pylori infection seem to be caused by the secondary gastroduodenal pathology, rather than by H. pylori infection itself.     

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.     

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.     

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.     

Breastfeeding and Helicobacter pylori Infection in Early Childhood: a Continuing Dilemma

Objective:

Helicobacter pylori (H. pylori) is the most common chronic bacterial infection in humans. Chronic colonization increases the risk of duodenal ulcer and gastric cancer. The risk factors for acquiring the infection have been extensively studied. However, there are conflicting results on the role of breastfeeding in the prevention of H. pylori infection. We conducted a study to evaluate the effects of breastfeeding on the H. Pylori infection in Kurdish children in Sanandaj, IR Iran.

Methods:

A historical cohort study was carried out from January 2011 through December 2012. Totally 221 children who were going to attain 2 years old during the study period were randomly enrolled. They were divided into two groups, i.e. breastfed and non-breastfed. We used H. pylori stool antigen test to detect infection in the selected group of children after age of 2 years and cessation of breastfeeding. Each group was subdivided into two subgroups, infected and non-infected. The associations of breastfeeding with H. pylori infection was assessed using statistical software.

Findings:

We found no difference in the odds of infection between breastfed and non-breastfed groups (OR=0.809, 95% CI [0.453–1.444]). An association between age and the prevalence of infection was found (P=0.008). There was an increase in the odds of infection as the family size grew (OR=1.93, 95% CI [1.04–3.6]) as well as increasing housing density (OR=2.12, 95% CI [1.10–4.10]).

Conclusion:

The data suggests that breastfeeding in infancy does not protect against H. pylori infection for long duration among studied children in Iran. The protective effects of breastfeeding, if any, are at most transient.     

A Localized Case–Control Study of Extra-Gastric Manifestations of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection in Children

Objective  

To study extra- gastric manifestations of H. pylori infection among children in Egypt.