Elisabete Kawakami

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.

13C-Urea Breath Test With Infrared Spectroscopy for Diagnosing Helicobacter pylori Infection in Children and Adolescents

Background and Objective Studies support the accuracy of 13C-urea breath test for diagnosing and confirming cure of Helicobacter pylori infection in children. Three methods are used to assess 13CO2 increment in expired air: mass spectrometry, infrared spectroscopy, and laser-assisted ratio analysis. In this study, the 13C-urea breath test performed with infrared spectroscopy in children and adolescents was evaluated. Methods Seventy-five patients (6 months to 18 years old) were included. The gold standard for diagnosis was a positive culture or positive histology and a positive rapid urease test. Tests were performed with 50 mg of 13C-urea diluted in 100 mL orange juice in subjects weighing up to 30 kg, or with 75 mg of 13C-urea diluted in 200 mL commercial orange juice for subjects weighing more than 30 kg. Breath samples were collected just before and at 30 minutes after tracer ingestion. The 13C-urea breath test was considered positive when delta over baseline (DOB) was greater than 4.0%. Results Tests were positive for H. pylori in 31 of 75 patients. Sensitivity was 96.8%, specificity was 93.2%, positive predictive value was 90.9%, negative predictive value was 97.6%, and accuracy was 94.7%. Conclusions 13C-urea breath test performed with infrared spectroscopy is a reliable, accurate, and noninvasive diagnostic tool for detecting H. pylori infection.

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.

13C-Urea Breath Test to Diagnose Helicobacter pylori Infection in Children Aged up to 6 Years

Background.  13C‐urea breath test (13C‐UBT) is an accurate noninvasive tool for diagnosis of Helicobacter pylori infection. It is considered the best method for epidemiological studies, but there are few studies to evaluate the 13C‐UBT in infants and toddlers.

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.

Evaluation of the Stool Antigen Test for Helicobacter pylori in Children and Adolescents

The stool antigen test for Helicobacter pylori is a noninvasive immunoassay to diagnose active infection with Helicobacter pylori in human fecal samples. Its performance in children and teenagers has been tested in some developed countries, showing a sensitivity and specificity above 90%, however, its accuracy in developing countries and in children under 6 years is not well established. To determine the accuracy of the test for diagnosing Helicobacter pylori infection in children and teenagers, we evaluated 133 patients (4 months to 17 years old). The gold standard was a positive culture or positive histology and rapid urease test. The test was done according to the manufacturer’s instructions. However, modifications were introduced for better reproducibility. Samples were analyzed twice and results are expressed as optical density (OD) determined spectrophotometrically at 450 nm. HpSA was considered positive at OD ≥0.160 and negative at OD < 0.140. One hundred twenty-seven of the 133 (95.5%) patients were included. There were no infected infants. The test showed a 94.6% sensitivity (95% CI: 90.6–98.5) and a 96.5% specificity (95% CI: 93.3–99.7). At ages 2 to 6 years the specificity was 96.4% (95% CI: 85.1–99.2) and the sensitivity was 80.0% (95% CI: 64.8–89.7), at ages 6 to 10 years the sensitivity was 100.0% and the specificity 95.7%, and above 10 years the sensitivity and specificity were 100.0%. We conclude that the test is efficient in adolescents and children, however there is a need for further studies with a greater number of patients for evaluation of its accuracy in infants.

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.

Seroprevalence of Helicobacter pylori infection among children of low socioeconomic level in São Paulo

CONTEXT AND OBJECTIVE Helicobacter pylori infection is mainly acquired during childhood, and is associated with significant morbidity in adults. The aim here was to evaluate the seroprevalence and risk factors of H. pylori infection among children of low socioeconomic level attended at a public hospital in São Paulo, Brazil. DESIGN AND SETTING Cross-sectional study, among patients attended at an outpatient clinic. METHODS 326 children were evaluated (150 boys and 176 girls; mean age 6.82 ± 4.07 years) in a cross-sectional study. Patients with chronic diseases or previous H. pylori treatment, and those whose participation was not permitted by the adult responsible for the child, were excluded. The adults answered a demographic questionnaire and blood samples were collected. The serological test used was Cobas Core II, a second-generation test. Titers > 5 U/ml were considered positive. RESULTS H. pylori infection was diagnosed in 116 children (35.6%). Infected children were older than uninfected children (7.77 ± 4.08 years versus 5.59 ± 3.86 years; p < 0.0001). The seroprevalence increased from 20.8% among children aged two to four years, to 58.3% among those older than 12 years. There were no significant relationships between seropositivity and gender, color, breastfeeding, number of people in the home, number of rooms, bed sharing, living in a shantytown, maternal educational level, family income or nutritional status. In multivariate analysis, the only variable significantly associated with H. pylori seropositivity was age. CONCLUSION Infection had intermediate prevalence in the study population, and age was associated with higher prevalence.

Prevalência de parasitoses intestinais em crianças do Parque Indígena do Xingu

OBJECTIVE: To evaluate the prevalence of intestinal parasitoses in Native Brazilian children from 2 to 9 years old. METHODS: A search for ova and parasites was conducted in the stools of children between 2 to 9 years old living in six indigenous villages located in the Middle and Lower Xingu River, to wit: Pavuru, Moygu, Tuiarare, Diauarum, Capivara, and Ngojwere. The study utilized the Paratest kit® (Diagnostek, Brazil) to preserve collected stools. Fecal samples were shipped to the Laboratory of the Pediatric Gastroenterology Division of the UNIFESP/EPM, in Sao Paulo, for analysis. The search for ova and parasites was performed utilizing the Hoffman method, and later through optical microscopic evaluation. Fecal samples were collected one year apart from each other. RESULTS: There were no significant statistical differences between the mean ages of the children from the six indigenous villages studied. The search for ova and parasites found positive results for the stools of 97.5% (198/202) and 96.1% (98/102) of children in the first and second collections, respectively. There was no statistical association with the childrens age. The search performed one year later found no differences in the proportion of parasites identified in the first collection for protozoa (93.3% in 2007 versus 93.3% in 2008, McNemar = 0.01, p = 0.1) or for helminths (37.1% in 2007 versus 38.2% in 2008, McNemar = 0.03, p = 0.85). There were significant differences in prevalence of Entamoeba coli between 2007 (43.8%) and 2008 (61.8%) (McNemar Chi 6.1; p = 0.0135). There were no significant differences for other parasites when comparing the results of the two studies. CONCLUSION: The high prevalence of intestinal parasitosis matched the elevated rates of environmental contamination in this indigenous community.