Role of 13C-urea breath test in experimental model of Helicobacter pylori infection in mice

Background: Animal models have been widely used to study Helicobacter pylori infection. Evaluation of H. pylori infection status following experimental inoculation of mice usually requires euthanasia. The ¹³C‐urea breath test (¹³C‐UBT) is both sensitive and specific for detection of H. pylori in humans. Thus, it would be very useful to have such a test with the same accuracy for the follow‐up of this infection in animal models of gastric infection. Accordingly, the purpose of this study was to develop and evaluate a ¹³C‐UBT method for following the course of H. pylori infection in a mouse model. Material and Methods: A total of 50 female C57BL/6 mice were gavaged three times with either 10⁸ colony‐forming units of H. pylori (n = 29) or saline solution only (n = 21). After 2 months of infection, mice were fasted for 14 hours and ¹³C‐UBT was performed using 300 μg of ¹³C‐urea. The mice were killed, and the stomach was removed and processed for immunohistochemistry and PCR. Results: The optimal time for breath sample collection in mice was found to be 15 minutes. The ¹³C‐UBT cutoff was set at 3.0‰δPDB. Using PCR as the gold standard, the sensitivity of ¹³C‐UBT and immunohistochemistry was 96.6 and 72.4%, respectively, while the specificity was 85.7 and 95.2%, respectively. Conclusions: ¹³C‐UBT was shown to be a reliable method for the detection of H. pylori infection in C57BL/6 mice and was even more accurate than immunohistochemistry. The use of ¹³C‐UBT in the mouse model of H. pylori infection can be very useful to detect the bacterium without the need to kill the animals in long‐term time course studies.     

An evaluation of a serologic test with a current infection marker of Helicobacter pylori before and after eradication therapy in Chinese

Background and Aims: Development of an accurate and less cumbersome noninvasive method to detect current Helicobacter pylori infection is essential in clinic. The aim of this study was to evaluate the performance of the CIM test, also known as the Assure®H. pylori Rapid Test (Genelabs Diagnostics Pty. Ltd., Singapore), for the diagnosis of current H. pylori infection before and after eradication therapy in Chinese population. Methods: A total of 452 eligible people were recruited for this study in Jiangsu Province, China. Each individual underwent a ¹³C urea breath test (¹³C‐UBT). For the evaluation of CIM test after eradication, 115 H. pylori‐positive outpatients were treated with 1‐week triple therapy. One month after the end of therapy, the patients underwent ¹³C‐UBT again, and the CIM‐test was performed 1, 3, and 6 months after the end of therapy. Its performance (sensitivity, specificity, positive and negative predictive values, and accuracy) were determined using the ¹³C‐UBT as a gold standard for H. pylori diagnosis. Results: H. pylori was detected in 221 (65.6%) of the 337 people by ¹³C‐UBT. The sensitivity, specificity, positive and negative predictive values, and accuracy of the CIM test were 93.2%, 90.5%, 94.9%, 87.5%, and 92.3%, respectively, using ¹³C‐UBT as a gold standard. One month after eradication therapy, the sensitivity, specificity of CIM test were only 50% and 66.7%, 66.7% and 84.6% 3‐month after eradication therapy and the sensitivity, specificity increased to 85.7% and 96.9%, respectively, when CIM test was used 6 months after the end of anti‐H. pylori therapy. Conclusions: The CIM test is a simple, rapid, accurate, cheap, and near‐people test. It may be satisfactory for detecting H. pylori infection in cases without eradication therapy, but it could not differentiate the past or current infection correctly within 6 months after anti‐H. pylori therapy.     

Gastrointestinal Symptoms and Helicobacter pylori Infection in School-Age Children Residing in Porto Torres, Sardinia, Italy

Background: Helicobacter pylori infection is typically acquired in childhood, and following the acute event, it is thought that most infections remain asymptomatic. H. pylori has been suggested to protect against diarrhea in childhood. Aim: To examine the role of H. pylori in gastrointestinal symptoms in children. Materials and Methods: A cross‐sectional sero‐epidemiologic study was conducted in Porto Torres, Sardinia, Italy. Demographic information, socioeconomic factors, and the frequency of upper gastrointestinal symptoms during the previous 3 months (e.g., abdominal pain, diarrhea, nausea, heartburn, halitosis, slow digestion, belching, and weight loss) were evaluated by a questionnaire. H. pylori status was determined by ELISA. Results: Approximately 95% (N = 1741) of school children between the age of 6 and 15 years from Porto Torres participated. The sero‐prevalence of H. pylori infection was 13.3% (229/1727) and similar in boys (13%) and girls (14%) (p = .57). Nausea/vomiting (odds ratio (OR) = 2.2 (95% CI = 1.2–5.1)) and diarrhea (OR = 2.1 (95% CI = 1.3–2.8)) were each significantly associated with H. pylori infection, and these associations remained significant after controlling for other study variables. There was no significant association between H. pylori and abdominal pain or heartburn (p > .25). Conclusions: The study does not support either a role of H. pylori infection in abdominal pain in children or a protective role against diarrheal illnesses or nausea/vomiting.     

13C-urea breath test for the diagnosis of Helicobacter pylori infection in children: a systematic review and meta-analysis

Background: The ¹³C‐urea breath test (¹³C‐UBT) is a safe, noninvasive and reliable method for diagnosing H. pylori infection in adults. However, the test has shown variable accuracy in the pediatric population, especially in young children. We aimed to carry out a systematic review and meta‐analysis to evaluate the performance of the ¹³C‐UBT diagnostic test for H. pylori infection in children. Methods: We conducted a systematic review of the PubMed, Embase and Liliacs databases including studies from January 1998 to May 2009. Selection criteria included studies with at least 30 children and reporting the comparison of ¹³C‐UBT against a gold standard for H. pylori diagnosis. Thirty‐one articles and 135 studies were included for analysis. Children were stratified in subgroups of <6 and ≥6 years of age, and we considered variables such as type of meal, cutoff value, tracer dose, and delta time for the analysis. Discussion: The ¹³C‐UBT performance meta‐analyses showed 1, good accuracy in all ages combined (sensitivity 95.9%, specificity 95.7%, LR+ 17.4, LR? 0.06, diagnostic odds ratio (DOR) 424.9), 2, high accuracy in children >6 years (sensitivity 96.6%, specificity 97.7%, LR+ 42.6, LR? 0.04, DOR 1042.7), 3, greater variability in accuracy estimates and on average a few percentage points lower, particularly specificity, in children ≤6 years (sensitivity 95%, specificity 93.5%, LR+ 11.7, LR? 0.12, DOR 224.8). Therefore, the meta‐analysis shows that the ¹³C‐UBT test is less accurate for the diagnosis of H. pylori infection in young children, but adjusting cutoff value, pretest meal, and urea dose, this accuracy can be improved.     

幽门螺杆菌感染促进胃炎儿童胃粘膜细胞的增殖

本研究旨在探讨幽门螺杆菌感染对小儿慢性胃炎患者细胞增殖的影响,使用内镜检查消化不良患者的上消化道症状,使用改良的Giemsa染色检测胃粘膜活组织中幽门螺杆菌,用苏木精/曙红和改良的吉姆萨染色活组织,并通过光学显微镜研究染色后胃粘膜样品组织病理学变化,RT-PCR检测各组胃粘膜细胞中调控细胞凋亡的Bcl-2、Bcl-xl、Bax和PCNA的mRNA表达,提取胃粘膜细胞蛋白质,利用蛋白质免疫印迹分析蛋白质浓度。组织化学染色结果表明,与对照相比,患有胃炎和幽门杆菌感染后的胃炎患者胃粘膜细胞明显增加,且幽门螺杆菌感染后细胞增殖更显著(p<0.05);幽门螺杆菌感染后Bcl-2和Bcl-xl,PCNA在患者体内表达显著上调(p<0.05),而细胞促凋亡因子Bax基因在胃炎患者感染幽门螺杆菌后被显著下调(p<0.05),蛋白免疫印迹分析Bcl-2,Bcl-xl,Bax和PCNA蛋白表达趋势与基因表达一致,说明结果可靠。幽门螺杆菌感染会显著提高慢性胃炎儿童患者胃粘膜细胞的增殖。     

13C-urea breath test results in pigs challenged with Helicobacter pylori or other urease producing bacteria

The gastric bacterial flora and its influence on the 13C-urea breath test (UBT) for detection of Helicobacter pylori infection was studied in a pig model. Seven SPF minipigs were used. H. pylori or a mix of other urease positive bacteria were administered orally. UBT, serum and biopsies for histology and culture were collected. Our results show that UBT is not specific for H. pylori in pigs as the gastric bacterial flora is responsible for the high UBT values observed. Furthermore, the Ellegaard G?ttingen SPF minipigs are not useful in an animal model for H. pylori studies.     

A population-based survey on gastrointestinal tract symptoms and Helicobacter pylori infection in children and adolescents

Background. Helicobacter pylori infection is a frequent infection mainly acquired in childhood. Even if the infection is almost invariably associated with mild to severe gastro‐duodenal lesions, no specific clinical picture has been identified. The aim of this study was to evaluate the presence of dyspeptic symptoms and their relationship with the presence of H. pylori infection in the first two decades of life. Materials and Methods. A school‐population sample size of 808 subjects from 6‐ to 19‐year‐olds was investigated for the presence of gastrointestinal tract symptoms and evaluated by a ¹³C‐urea breath test for H. pylori infection. The relationship between clinical findings and H. pylori infection was evaluated by χ² statistic or Fisher's exact test, as appropriate. Results. Symptoms of dyspepsia were identified in 45% of subjects, while the picture of ulcer‐like and dysmotility‐like forms were present in 3–4%. H. pylori infection was demonstrated in 95 (11.8%) subjects, 49.5% of them without symptoms. Severe epigastric pain and ulcer‐like dyspepsia were significantly associated with H. pylori infection, while recurrent abdominal pain or dysmotility‐like dyspepsia were not. Conclusions. Dyspeptic symptoms are frequent in children, and its association with H. pylori infection is more evident than with recurrent abdominal pain. The age at which the infection is acquired seems to be under 6 years of age.     

First-time urea breath tests performed at home by 36,629 patients: a study of Helicobacter pylori prevalence in primary care

Background: The aim of the current study was (1) to describe the use of a ¹³C‐urea breath test (UBT) that was performed by patients at their homes as a part of a test‐and‐treat strategy in primary care and (2) to investigate the prevalence of Helicobacter pylori in patients taking a first‐time UBT. Material and Methods: The patients performed UBTs at home based on the discretion of the general practitioner and mailed the breath bags to a central laboratory for analysis. Each patient was identified by a unique civil registration number. The study was population‐based, and the background population was approximately 700,000 people. Results: From 2003 to 2009, 44,487 UBTs were performed. Of these, 36,629 were first‐time UBTs. In total, 726 of 45,213 breath bags received (1.6%) were unable to be analyzed because of errors with the bags. For both women and men who were ≤45 years of age, positive H. pylori declined over the time course of the study (women: 19.6% in 2003 to 17.6% in 2009, p < .01; men: 20.7% in 2003 to 16.9% in 2009, p < .001). Patients who were older than 45 years had significantly higher positive H. pylori results than younger patients. Conclusions: A test‐and‐treat system was possible to implement that allowed patients to perform UBTs at their homes. The results of the first‐time UBTs demonstrated that approximately one of five patients who presented with dyspepsia in the clinical setting of Danish primary care was infected with H. pylori.