Silvio Kazuo Ogata

Evaluation of invasive and non-invasive methods for the diagnosis of Helicobacter pylori infection in symptomatic children and adolescents

CONTEXT Multiple diagnostic methods are available for the detection of Helicobacter pylori infection, but at present no single one can be used as the gold standard. OBJECTIVE The aim of this study was to evaluate the diagnostic accuracy of 3 invasive and 2 non-invasive methods for detection of Helicobacter pylori infection in symptomatic children and adolescents. DESIGN Prospective cohort study SETTING Peptic Disease outpatients service, Discipline of Pediatric Gastroenterology, Universidade Federal de São Paulo / Escola Paulista de Medicina. PATIENTS Forty-seven patients who underwent endoscopy because of dyspeptic symptoms. DIAGNOSTIC METHODS Endoscopy with gastric biopsies for 3 invasive (rapid urease test, histology and culture) and 2 non-invasive methods (a commercial ELISA serology and 13carbon urea breath test - isotope ratio mass spectrometry) for detection of Helicobacter pylori infection. MAIN MEASUREMENTS Sensitivity, specificity, positive and negative predictive values of each method and agreement and disagreement rates between the methods. RESULTS Forty-seven patients [mean age, 11y9mo (SD 2y10mo), 27 female and 20 male]; 62% of them were Helicobacter pylori-positive. All methods agreed in 61%, and were negative in 21% and positive in 40%. The greatest concordance between 2 methods occurred between the invasive methods: histology and rapid urease test (89.6%) and histology and culture (87.5%). The greatest sensitivity, considering Helicobacter pylori-positive cases, for any combination of 3 or more tests, was achieved by the rapid urease test (S=100%), followed by histology, serology and 13carbon-urea breath test (S=93.1%) and lastly by culture (S=79.3%). The highest specificity was obtained by histology (100%) and culture (100%), followed by the rapid urease test (84.2%), serology (78.9%) and 13carbon-urea breath test (78.9%). CONCLUSIONS Our results suggest that among invasive methods, an association between the rapid urease test and histology constituted the best choice for the detection of Helicobacter pylori infection. If results of histology and the rapid urease test are different, serology may be recommended.

Decrease in prevalence of Helicobacter pylori infection during a 10-year period in Brazilian children

BACKGROUND Decreasing prevalence of H pylori infection has been reported in some countries. AIM To evaluate the prevalence of Helicobacter pylori infection in a 10-year period in children submitted to upper digestive endoscopy. METHODS It was a retrospective observational study. The records of 1,165 endoscopies performed during a 10-year period in a public hospital of the City of São Paulo, SP, Brazil, in patients up to 18-year-old. Only the first endoscopy was considered. Helicobacter pylori infection was defined by the rapid urease test, performed with one fragment of antral mucosa. Chi-square for trend has been estimated to compare Helicobacter pylori prevalence across the period. RESULTS The main indication for endoscopy was epigastric pain (47.4%). There were 392 patients with H pylori infection (33.6%), 12.8% being infants, 19.4% toddlers, 28.8% schoolchildren and 46.3% adolescents. Prevalence was 60.47% in the first year of the study and 30.43% in the last. Among the less than 6-year-old patients there was a decrease in infection prevalence from 25% for the 1993--6 period to 14.3% in the 2000--02 period, while among the over 12-year-old patients the decrease was from 55.5% in the first period to 39.6% in the latter. The decrease in H pylori infection prevalence was more intense within patients with epigastric pain, in which prevalence has decreased from 48.2% (92/191) in 1993--6, to 41.9% (65/155) in 1997--9 and 27.7% (57/206) in 2000--02. CONCLUSION The study suggests a significant decrease in the prevalence of H pylori infection regarding the studied patients. The trend was mainly observed in the younger age group and in patients with epigastric pain.

Triple therapy with clarithromycin, amoxicillin and omeprazole for Helicobacter pylori eradication in children and adolescents

BACKGROUND Helicobacter pylori infection presents high prevalence in developing countries, but there are few pediatric assays evaluating antimicrobial treatment. OBJECTIVE The aim of this study was to investigate Helicobacter pylori eradication rate using a short regimen (7 and 10 days) of triple therapy with clarithromycin, amoxicillin and omeprazole. PATIENTS AND METHODS Twenty-five Hp positive patients who presented severe epigastralgia, were submitted to antimicrobial treatment with amoxicillin (50 mg/kg/day--maximum dose 1 g bid), clarithromycin (30 mg/kg/day--maximum dose 500 mg bid) and omeprazole (0.6 mg/kg/day--maximum dose 20 mg bid) during 7 or 10 days. After 2 months, clinical symptoms were evaluated and gastric biopsies were taken to test Hp eradication. RESULTS Overall eradication rate was achieved in 16/25 patients (64%--IC(95% = 45-83%), in 11/15 (73%--IC(95%) = 51-95%) patients who used 10 days therapy course and in 5/10 (50%--IC(95%) = 19-81%) who used 7 days therapy course. Eradication drugs were well accepted and adverse effects were reported in two patients (8%). CONCLUSIONS This triple therapy regimen had moderate efficacy (64%). The data suggests that 10 days therapy course achieves better eradication rate (73%) than 7 days course (50%) to treat Hp infection in our population.

Validation of a monoclonal stool antigen test for diagnosing Helicobacter pylori infection in young children.

Background and Objective: The monoclonal stool antigen test for diagnosing Helicobacter pylori infection in children has been tested in developed countries, showing sensitivity and specificity higher than 90%. However, its accuracy in young children from developing countries is not well established. The aim of the study was to determine the accuracy of the monoclonal stool antigen test for diagnosing H pylori infection in children up to 7 years old. Patients and Methods: Two hundred seventy-six patients (53.6% female; ages 0.35–6.99 years) were evaluated. Gold standard positive culture or positive histology and rapid urease tests were performed. The test (Amplified IDEIATM Hp StAR) was done according to the manufacturers instructions. Results were expressed as optical density (OD) and an OD more than or equal to 0.190 was considered positive. Additionally, a receiver operating characteristic curve was used to find the best cutoff. Results: The monoclonal stool antigen test for diagnosing H pylori infection showed 100% sensitivity (95% confidence interval [CI] 92.7%–100%) and 76.2% specificity (95% CI 70.1%–81.4%), considering the manufacturers cutoff. After setting a new cutoff with the receiver operating characteristic curve (OD = 0.400), sensitivity remained 100% (95% CI 92.7%–100%), but the specificity improved to 97.7% (95% CI 94.7%–99%). At ages up to 2 years, sensitivity was 100% (95% CI 43.8%–100%) and specificity was 100% (95% CI 92.4%–100%); at ages 2 to 4 years, 100% (95% CI 80.6%–100%) and 97.6% (95% CI 96%–99.2%); at ages older than 4 years, 100% (95% CI 88.6%–100%) and 96.6% (95% CI 94.7%–98%), respectively. Conclusions: The monoclonal stool antigen test is accurate for diagnosing H pylori in children younger than 7 years old, but it must be locally validated in order to find the best cutoff for each population.

High Helicobacter pylori resistance to metronidazole and clarithromycin in Brazilian children and adolescents.

Objective: The aim of the present study was to assess the primary and secondary resistance of Helicobacter pylori strains to clarithromycin, amoxicillin, furazolidone, tetracycline, and metronidazole, the conventional antibiotics presently used in Brazilian children and adolescents. Methods: Seventy-seven consecutive H pylori strains, 71 of 77 strains obtained from patients without previous eradication treatment for H pylori infection, and 6 strains from patients in whom previous eradication treatment had failed. Results: Global rate of resistance was 49.3% (38/77): 40% of strains were resistant to metronidazole, 19.5% to clarithromycin, and 10.4% to amoxicillin. All of the tested H pylori strains were susceptible to furazolidone and tetracycline. Multiple resistance were detected in 18.2% (14/77 patients) of the strains: 6 of 14 (43%) simultaneously resistant to clarithromycin and metronidazole; 5 of 14 (36%) to amoxicillin and metronidazole; 2 of 14 (14%) to amoxicillin, clarithromycin, and metronidazole; and 1 of 14 (7%) to clarithromycin and amoxicillin. Conclusions: The high resistance rate to metronidazole and clarithromycin observed in clinical H pylori isolates can exclude these antimicrobials in empirical eradication treatment in Brazil. Otherwise, furazolidone and tetracycline presented no resistance. Properly assessing the risks and benefits, these 2 antimicrobials and their derivatives could be used in empirical eradication schedules, both associated with amoxicillin, which showed a low resistance rate despite its wide use in pediatric patients.

Antimicrobial susceptibility testing for Helicobacter pylori isolates from Brazilian children and adolescents: comparing agar dilution, E-test, and disk diffusion

Antimicrobial susceptibility testing for Helicobacter pylori is increasingly important due to resistance to the most used antimicrobials agents. Only agar dilution method is approved by CLSI, but it is difficult to perform routinely. We evaluated the reliability of E-test and disk diffusion comparing to agar dilution method on Helicobacter pylori antimicrobial susceptibility testing. Susceptibility testing was performed for amoxicillin, clarithromycin, furazolidone, metronidazole and tetracycline using E-test, disk-diffusion and agar dilution method in 77 consecutive Helicobacter pylori strains from dyspeptic children and adolescents. Resistance rates were: amoxicillin - 10.4%, 9% and 68.8%; clarithromycin - 19.5%, 20.8%, 36.3%; metronidazole - 40.2%33.7%, 38.9%, respectively by agar dilution, E-test and disk diffusion method. Furazolidone and tetracycline showed no resistance rates. Metronidazole presented strong correlation to E-test (r = 0.7992, p < 0.0001) and disk diffusion method (r=-0.6962, p < 0.0001). Clarithromycin presented moderate correlation to E-test (r = 0.6369, p < 0.0001) and disk diffusion method (r=−0.5656, p < 0.0001). Amoxicillin presented weak correlation to E-test (r = 0.3565, p = 0.0015) and disk diffusion (r=−0.3565, p = 0.0015). Tetracycline presented weak correlation with E-test (r = 0.2346, p = 0.04) and furazolidone to disk diffusion (r=−0.0288, p = 0.8038). E-test presented better agreement with gold standard. It is an easy and reliable method for Helicobacter pylori susceptibility testing. Disk diffusion method presented high disagreement and high rates of major errors.

Diagnosis of Helicobacter pylori infection by means of reduced-dose ¹³C-urea breath test and early sampling of exhaled breath.

Objective: The aim of this study was to evaluate the accuracy of reduced-dose 13C-urea breath test (13C-UBT) and early sampling of exhaled breath for the detection of Helicobacter pylori infection in children and adolescents. Methods: Patients up to 20 years old that underwent upper gastrointestinal endoscopy with gastric biopsies were included. The 13C-UBT was performed after a 4-hour fasting period with 4 points of collection: baseline (T0), and at 10, 20, and 30 minutes (T10, T20, and T30) after ingestion of 25 mg 13C-urea diluted in 100 mL of apple juice. The infection status was defined through 3 invasive methods, and a patient was considered infected with a positive culture or concomitant positive histology and rapid urease test. The absence of infection was defined by all negative histology, rapid urease test, and culture. Analysis of exhaled breath samples was performed with an isotope-selective infrared spectrometer. A receiver-operating characteristic curve analysis was done to define cutoff delta over baseline (DOB) values. Results: A total of 129 patients between the ages of 2.1 and 19 years (median 11.6 years; mean age ± standard deviation 11.5 ± 3.8 years; F:M 85:44) were included. The prevalence of infection was 41.1%. The sensitivity (S) and specificity (Sp) were at T10 (cutoff DOB 2.55‰), S 94.7% (95% confidence interval [CI] 90.9–98.5) and Sp 96.8% (95% CI 93.4–100); at T20 (DOB 2.5‰), S 96.2% (95% CI 92.9–99.5) and Sp 96.1% (95% CI 93.7–99.8); and at T30 (DOB 1.6‰), S 96.2% (95% CI 92.9–99.5) and Sp 94.7% (95% CI 90.8–98.6). Conclusions: Low-dose 13C-UBT with early sampling is accurate for diagnosing H pylori infection in children and adolescents.

High Rate of Clinical and Endoscopic Relapse After Healing of Erosive Peptic Esophagitis in Children and Adolescents

Objectives: The aim of the present study was to estimate the rate of clinical and endoscopic relapse after initial treatment of erosive peptic esophagitis in children and adolescents. Methods: A total of 24 patients (2.1–16.4 years old, mean ± standard deviation [SD] 9.9 ± 3.1; male:female 3) with healed endoscopic erosive esophagitis and without gastroesophageal reflux disease (GERD)–predisposing conditions were followed up for 4 to 32.9 months (mean 20.8 ± 10.6 years). Structured clinical evaluation was performed every other week during the initial treatment and maintenance, and every 3 months after that. Whenever a clinical relapse happened, a new endoscopic evaluation was performed. Severity and frequency were scored on 10-point and 6-point semiquantitative scales, respectively. Results: At baseline, epigastric pain was the most reported symptom (70.8%), with intensity scored as >5 in 88.3% of patients, and median frequency of 3 (weekly; daily in 5, 20.8%). Clinical relapse was detected in 20 of 24 (83.3%) patients after a median period of 14.65 months (95% confidence interval [CI] 6.7–25.7 months). Endoscopic relapse was observed in 9 of 20 (45%) patients after a median of 25.7 months. The dose of lansoprazole needed to heal the esophagitis was not significantly associated with the risk for clinical relapse (hazard ratio [HR] 1.74, 0.94, 7.72, P = 0.06), whereas the body mass index (BMI) was directly associated with endoscopic relapse (HR 1.3, 1, 1.69, P = 0.05). Conclusions: Children with healed erosive esophagitis have up to 83% clinical relapse and of the 83%, 45% had endoscopic relapse. Correlation of endoscopic relapse with clinical symptom is poor. Higher grades of esophagitis and higher BMI are risk factors for endoscopic relapse.