Kyoko Ozawa

Accuracy of the Stool Antigen Test for the Diagnosis of Childhood Helicobacter pylori Infection: A Multicenter Japanese Study

OBJECTIVE:The 13C-urea breath test (UBT) has been accepted as a reliable noninvasive test for detecting Helicobacter pylori infection. Recently, another noninvasive test, a new enzyme immunoassay for H. pylori antigens in stool, has been widely investigated for its clinical usefulness. The purpose of this multicenter study was to evaluate the diagnostic accuracy of the stool antigen test in Japanese children.METHODS:A total of 264 children (148 male and 116 female; mean age 9.2 yr, range 2–17 yr) who underwent 13C-UBT and the stool antigen test were studied. The diagnosis in these patients was gastritis (n = 49), gastric ulcer (n = 4), duodenal ulcer (n = 24), recurrent abdominal pain (n = 43), and other conditions (n = 144). The stool antigen test was performed using the HpSA ELISA (Premier Platinum HpSA, Meridian Diagnostics). According to manufacturers instructions, an absorbance at 450/630 nm of <0.100, ≥0.120, and 0.100–0.119 was defined as negative, positive, and indeterminate, respectively. Based on the 13C-UBT with a cutoff value of 3.5 per mil, the performance of HpSA was studied. In 21 patients who received eradication therapy, the HpSA was performed at baseline and at 1, 2, and 6 months after completion of therapy. Eradication of H. pylori was confirmed by 13C-UBT at 2 or 3 months of follow-up.RESULTS:13C-UBT showed that 76 children were infected with H. pylori and 188 were not infected. In these same children, HpSA results were positive in 77 children, negative in 183, and indeterminate in four. The overall sensitivity, specificity, and accuracy of the test were 96.0% (95% CI = 88.6–99.2%), 96.8% (95% CI = 94.2–99.3%), and 96.5% (95% CI = 94.3–98.8%), respectively. There were no significant differences in these results among age groups of ≤5, 6–10, and ≥11 yr. Receiver operating characteristic curve analysis demonstrated that the best cutoff value of absorbance at 450/630 nm was 0.110. When a single cutoff value of 0.110 without indeterminate results was used, the sensitivity, specificity, and accuracy were 96.1% (95% CI = 90.8–99.7%), 96.3% (95% CI = 93.6–99.0%), and 96.2% (95% CI = 93.9–98.5%), respectively. In 19 patients in whom H. pylori was successfully eradicated, HpSA results were negative at 1 month of follow-up and remained negative through 6 months.CONCLUSIONS:The HpSA is an accurate test for the detection of H. pylori infection in all age groups of children.

Diagnostic accuracy of the 13C-urea breath test for childhood Helicobacter pylori infection: a multicenter Japanese study

OBJECTIVES:In adults, the 13C-urea breath test (UBT) has been widely used as a noninvasive test of Helicobacter pylori infection because of its high sensitivity and specificity. However, this test is less well established in pediatric practice. The optimum cutoff value and test protocol of the 13C-UBT remains to be established in the pediatric population. The primary purpose of this study was to evaluate diagnostic accuracy of the 13C-UBT for children and to determine its optimum cutoff value.METHODS:A total of 220 Japanese children aged 2–16 yr (mean = 11.9) who underwent upper GI endoscopy and gastric biopsies were finally studied. Endoscopic diagnoses included gastritis (n = 131), gastric ulcer (n = 15), duodenal ulcer (n = 72), and combined ulcer (n = 2). H. pylori infection status was confirmed by biopsy tests including histology, urease test, and culture. With the 13C-UBT, breath samples were obtained at baseline and at 20 min after ingestion of 13C-urea without a test meal and were analyzed by isotope ratio mass spectrometry. Based on biopsy tests, a cutoff value was determined using a receiver operating characteristic curve. In 26 children (seven children infected and 19 noninfected), paired breath samples were also measured by nondispersive infrared spectometry (NDIRS).RESULTS:Biopsy tests demonstrated that 89 children (40%) were infected with H. pylori and 131 children were not infected. There were no statistical differences in mean Δ 13C values at 20 min between male and female H. pylori-infected and noninfected patients. A receiver operating characteristic analysis defined the best cutoff value as 3.5‰. The overall sensitivity and specificity at a cutoff value of 3.5‰ were 97.8% (95% CI = 92.1–99.7%) and 98.5% (95% CI = 96.4–100%), respectively: high sensitivity and specificity were demonstrated in all three age groups (≤5, 6–10, and ≥11 yr). There was a close correlation between the values with isotope ratio mass spectrometry and NDIRS methods (r = 0.998, p < 0.001).CONCLUSIONS:The 13C-UBT with a cutoff value of 3.5‰ is an accurate diagnostic method for active H. pylori infection. The test with the NDIRS method is inexpensive and might be widely applied in clinical practice.

The prevalence of Helicobacter pylori in Japanese children with gastritis or peptic ulcer disease

BackgroundAlthough Helicobacter pylori infection is typically acquired in childhood, the role of H. pylori infection in gastroduodenal diseases in childhood remains to be defined. The purpose of this study was to evaluate the prevalence of H. pylori infection in children with gastritis, duodenal ulcer, and gastric ulcer.MethodsThis was a retrospective analysis of 283 Japanese children (mean age, 11.5 years) with non-nodular gastritis (n = 73), nodular gastritis (n = 67), duodenal ulcer (n = 100), and gastric ulcer (n = 43). H. pylori status was based on biopsy tests. Clinical symptoms at the time of endoscopy were analyzed with regard to a possible association with the infection.ResultsThe prevalence of H. pylori in non-nodular gastritis, nodular gastritis, duodenal ulcer, and gastric ulcer was 28.8%, 98.5%, 83.0%, and 44.2%, respectively. H. pylori was significantly linked to duodenal ulcer and gastric ulcers in the age group of 10–16 years, but not in the age group of 9 years and under. In children with H. pylori infection, nodular gastritis was observed in 26.3% of gastric ulcer patients and in 74.7% of duodenal ulcer patients (P < 0.001). H. pylori infection was significantly associated with the prevalence of anemia (P < 0.05).ConclusionsH. pylori is the most important causal factor for the development of duodenal ulcer in childhood. While H. pylori infection appears to be a risk factor in gastric ulcer, other causes are responsible for most cases. Nodular gastritis is the most common type of H. pylori gastritis in childhood. Chronic infection with H. pylori is associated with anemia.

Multicenter Comparison of Rapid Lateral Flow Stool Antigen Immunoassay and Stool Antigen Enzyme Immunoassay for the Diagnosis of Helicobacter pylori Infection in Children

Background and Aim.  The stool antigen enzyme immunoassay (EIA) methods are widely used for diagnosing Helicobacter pylori infection. Recently, a novel, rapid stool antigen test, the lateral flow immunoassay (LFI) method, has been developed. The primary purpose of this study was to compare the EIA method with the LFI method for the diagnosis of H. pylori infection in children.

Association between gastric atrophy and Helicobacter pylori infection in Japanese children: A retrospective multicenter study

The purpose of this study was to determine whether Helicobacter pylori infection and mucosal inflammation result in gastric atrophy in Japanese children. A total of 196 patients ages 1–16 years were retrospectively studied: 131 patients were infected with H. pylori and 65 patients were uninfected. Antral (n = 196) and corpus biopsy specimens (n = 70) were investigated based on the Updated Sydney system. In both the antrum and corpus, H. pylori-infected patients showed significantly higher degrees of inflammation and activity of gastritis, compared with noninfected patients. The prevalence of grade 2 or 3 atrophy in the antrum was 10.7% in H. pylori-infected patients and 0% in the noninfected patients (P < .01) and in corpus 4.3% and 0%, respectively (P = .20). The frequency of intestinal metaplasia in the 2 study groups was 4.6% and 4.6% in the antrum and 0% and 4.2% in the corpus, respectively. Among H. pylori-infected patients, the antrum showed significantly higher degrees of H. pylori density, inflammation and activity of gastritis, and atrophy than the corpus. In the antrum, atrophy was significantly correlated with activity, whereas in the corpus, atrophy correlated with H. pylori density, inflammation, and activity. H. pylori-induced gastric inflammation can cause atrophy in Japanese children, predominantly in the antrum. It remains to be determined whether H. pylori-infected children with gastric atrophy are at increased risk for gastric cancer.

Helicobacter heilmannii infection in a child after successful eradication of Helicobacter pylori: case report and review of literature

An 11-year-old boy with Helicobacter pylori-associated duodenal ulcer was successfully treated with a combination of lansoprazole, amoxicillin, and clarithromycin. Endoscopy and gastric biopsies were repeated 2 and 12 months later, showing ulcer healing and eradication of H. pylori. However, a 3-year follow-up study demonstrated H. heilmannii in the antral mucosa based on its characteristic morphology and positive urease test and negative culture. The patient had no contact with domestic animals such as cats and dogs. A 7-day course with lansoprazole, amoxicillin, and clarithromycin was performed again, resulting in successful eradication of the organism. Pediatric cases with H. heilmannii infection reported are reviewed.

Gastric epithelial cell turnover and mucosal protection in Japanese children with Helicobacter pylori infection

BackgroundIn adults, epithelial cell proliferation and apoptosis of the gastric mucosa are induced by Helicobacter pylori infection and are associated with gastric atrophy or gastric carcinoma. In children, there are few studies about such epithelial changes. To elucidate the role of H. pylori infection in gastric mucosal inflammation, we immunohistochemically examined gastric mucosa of Japanese children.MethodsBiopsy specimens obtained from the gastric antrum and corpus of H. pylori-infected (n = 13) and noninfected children (n = 15) were studied for immunolocalization of Ki-67, single-strand DNA, manganese superoxide dismutase (Mn-SOD), and CD68, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. In 10 patients with successful eradication, pre- and posttreatment results were compared.ResultsIn both gastric antrum and corpus, neutrophil and mononuclear cell infiltration, epithelial cell proliferation, and apoptosis significantly increased in H. pylori-infected patients, predominantly in the antrum. In the antrum of H. pylori-infected patients, there was positive correlation between the degrees of neutrophil infiltration and cell proliferation (P < 0.05) or apoptosis (P < 0.05). H. pylori eradication improved mucosal inflammation, cell proliferation (P < 0.001), and apoptosis (P < 0.01) in the antrum. Mn-SOD immunoreactivity and CD68-positive macrophages in the antrum, which significantly increased in H. pylori-infected patients, decreased after the eradication.ConclusionsH. pylori infection induced gastric mucosal inflammation and epithelial cell turnover in children. Moreover, gastric mucosal defense mechanism against H. pylori infection was activated. H. pylori eradication in childhood might prevent the accumulation of gastric epithelial cell damage.

Immunoglobulin A enteropathy: a possible variant of Henoch-Schönlein purpura.

This study calls attention to a new syndrome presenting with gastrointestinal symptoms including abdominal pain, vomiting, and/or hematemesis and endoscopic multiple lesions predominantly in the descending duodenum, without the skin rash observed in Henoch–Schönlein purpura. We examined the gastrointestinal mucosa for IgA deposits in nine children and compared the results with those for three patients with Henoch–Schönlein purpura. In addition, gastroduodenal biopsy specimens of 11 patients with various diseases were studied as controls for IgA staining. Intestinal histology showed nonspecific mucosal inflammation without vasculitis. In six patients without rash (67%), IgA deposition was observed in the capillary wall with the same staining pattern as seen in two patients with Henoch–Schönlein purpura. Compared with the controls (9%), the positive rate of IgA deposition was significantly higher in nonrash patients (P&<0.01). Deposited IgA showed immunoreactivities of polymeric IgAl containing J chain. IgA deposits were ultrastructually seen along the plasma membranes of the endothelial cells. Overall, the data suggest that IgA deposition played a pathogenetic role in the gastrointestinal damage in this group of patients presenting primarily with gastrointestinal complaints. Further studies are needed to clarify whether this patient population has a variant of Henoch–Schönlein purpura or a distinct “IgA enteropathy.”

Influence of rifampicin on Helicobacter pylori prevalence in patients with mycobacterial infection.

Influence of rifampicin on Helicobacter pylori prevalence in patients with mycobacterial infection Helicobacter pylori eradication has been performed by the proton pump inhibitor-based triple therapy with high eradication rates. However, eradication failure due to clarithromycin or metronidazole resistance of H. pylori is a common problem in clinical practice. In cases with eradication failure, an efficient second-line therapy has not been established. Besides the antimicrobial agents mentioned above, the discovery of potential agents is urgent for the therapeutic strategy of H. pylori infection. Pilotto et al. [1] reported in vitro activity of rifabutin against H. pylori strains resistant to metronidazole and/or clarithromycin. Recently, we have reported that rifampicin has in vitro activity against the organism [2]. The purpose of this study was to evaluate in vivo activity of rifampicin against H. pylori.