Follow-up of Helicobacter pylori infection in children over two decades (1988-2007): persistence, relapse and acquisition rates.

Helicobacter pylori culture on gastric biopsy was performed on 4964 subjects aged <18 years from 1988 to 2007 at a central laboratory in Brussels. The total number of biopsies increased markedly from 941 in 1988-1993 to 1608 in 2004-2007. Biopsies were repeated at least once for 922 subjects (603 initially negative and 319 initially positive for H. pylori). Persistence rate of H. pylori at 1 year after initial positive biopsy was greater in the 1998-2007 cohort than in the 1988-1997 cohort (72.7% vs. 45.8%, P = 0.002), suggesting a tailored selection of candidates for biopsy with non-invasive tests (13C urea breath test). Of 68 subjects initially positive and re-examined subsequently after a documented cure, re-infection/relapse rate was 48.6% within 5 years post-elimination of H. pylori. Acquisition rate over 10 years follow-up in the initially negative cohort (603 patients) was 38.7% (re-infection/relapse vs. acquisition: P < 0.001). Multivariate analysis showed a fourfold greater risk of H. pylori acquisition in children of non-European origin vs. European origin (P < 0.001). Clarithromycin and metronidazole susceptibility were determined in 226 and 223 paired positive cultures in cases of re-infection/relapse or persistence. An initial non-susceptibility profile was highly predictive of a subsequent non-susceptibility profile, and the non-susceptible proportion increased markedly from 13.3% to 21.2% for clarithromycin (P < 0.001) and from 27.3% to 35.0% for metronidazole (P = 0.014), with no difference regarding European or non-European origin.

Bismuth-based quadruple therapy versus standard triple therapy for the eradication of Helicobacter pylori in Belgium: a multicentre, non-blinded randomized, prospective study.

Background: Helicobacter pylori (Hp) infection predisposes to malignant and non-malignant diseases warranting eradication. In Belgium, resistance rates for clarithromycin demonstrate regional variations making the use of standard triple therapy (STT) borderline acceptable. According to a recent Belgian survey, STT and bismuth-based quadruple therapy (BQT), are equally frequent prescribed as first line treatment for treatment naïve Hp positive patients. This study aims to evaluate the eradication rates (ER) of BQT versus STT. Methods: Multicentre, non-blinded randomized, prospective study comparing ER in treatment-naïve Hp positive patients. ER were compared by intention to treat (ITT) and per protocol (PP) analysis. Results: Overall 250 patients were included (STT 126, BQT 124). Seventeen patients were lost to follow-up (6,8%). No significant difference in ER between BQT and STT was observed in ITT (73% vs 68%, p= 0,54) neither in PP analysis (81% vs 75%, p= 0,33). Side effects and endoscopic findings were comparable between groups. Post-hoc analysis showed no differences according to gender or site allocation. Conclusion: The numerical advantage of BQT did not translate in a significant improvement of ER when compared with STT. These results question the cost-effectiveness of BQT, while confirming the suboptimal eradication rates on STT. A nationwide monitoring of resistance patterns, maximal investments in treatment adherence as well as a detailed follow-up of the changing treatment landscape are mandatory to continuously optimise Hp ER in Belgium.

Multicenter survey of routine determinations of resistance of Helicobacter pylori to antimicrobials over the last 20 years (1990 to 2009) in Belgium.

We analyzed the rates of antimicrobial resistance of Helicobacter pylori strains isolated from patients from 1990 to 2009 and identified risk factors associated with resistance. Gastric biopsy specimens were collected from several digestive disease centers in Brussels, Belgium. We routinely performed antimicrobial susceptibility testing for clarithromycin (CLR), metronidazole, amoxicillin, tetracycline, and ciprofloxacin. Evaluable susceptibility testing was obtained for 9,430 strains isolated from patients who were not previously treated for Helicobacter pylori infection (1,527 isolates from children and 7,903 from adults) and 1,371 strains from patients who were previously treated (162 isolates from children and 1,209 from adults). No resistance to amoxicillin was observed, and tetracycline resistance was very rare (<0.01%). Primary metronidazole resistance remained stable over the years, with significantly lower rates for isolates from children (23.4%) than for isolates from adults (30.6%). Ciprofloxacin resistance remained rare in children, while it increased significantly over the last years in adults. Primary clarithromycin resistance increased significantly, reaching peaks in 2000 for children (16.9%) and in 2003 for adults (23.7%). A subsequent decrease of resistance rates down to 10% in both groups corresponded to a parallel decrease in macrolide consumption during the same period. Multivariate logistic regression revealed that female gender, age of the patient of 40 to 64 years, ethnic background, the number of previously unsuccessful eradication attempts, and the different time periods studied were independent risk factors of resistance to clarithromycin, metronidazole, and ciprofloxacin. Our study highlights the need to update local epidemiological data. Thus, the empirical CLR-based triple therapy proposed by the Maastricht III consensus report remains currently applicable to our population.

Marching cohort of Helicobacter pylori infection over two decades (1988-2007): combined effects of secular trend and population migration.

The prevalence of Helicobacter pylori infection is decreasing in developed countries. In this study we included 22,612 patients in whom a first culture of gastric biopsy (routinely performed in our medical centres) yielded an interpretable result over a 20-year period (1988-2007) in Brussels. The effects of patients' age, gender and ethnic background were analysed. The overall proportion of H. pylori-infected patients was 37·7%, with a progressive decline over time (P<10(-5)). A gender effect was observed in adults. The lowest infection rate was observed in Western European patients (n=11,238) with respectively 36·2% and 15·2% infected subjects in 1988 and 2007, compared to 71·7% and 40% in North African patients (n=3200) (P<10(-5)). However, no trend of decline was observed over time in North African children aged ≤9 years. These data show the effects of time, age and ethnicity on the prevalence of H. pylori infection, and its complex heterogeneity in the same cosmopolitan urban area.

Contribution of the 13C-urea breath test to the detection of Helicobacter pylori gastritis in children.

Serology, 13C-urea breath test, histology, Campylobacter-like organism testing, and culture were performed in 95 consecutive children to evaluate the contribution of these tests to the detection of Helicobacter pylori infection. In analyses considering any combination of three positive tests as "gold standard" for diagnosing H pylori infection, 26 children were Helicobacter positive (27%), which is only one patient more than the number of children with only a positive culture. The accuracy of culture was excellent when "any combination of three positive tests" was used as the gold standard (sensitivity 96%, specificity 100%, positive predictive value 100% [false positivity 0%], negative predictive value 99% [false-negative results 1%]). The results of invasive and noninvasive tests were comparable. When culture was considered as "gold standard," the sensitivity of serology and 13C-urea breath test was 96%; the specificity was 96% and 93%, respectively; the positive predictive value was 89% and 83% (false-positive results in 11% and 17%); and the negative predictive value for both was 99% (false-negative results in 1%). It is concluded that culture can be used as gold standard, but that non-invasive tests such as serology and/or 13C-urea breath test can be used to diagnose H pylori infection in children, since each has at least 95% sensitivity and 92% specificity.

Gastroesophageal scintiscanning in children.

Four patients' positions were tested in search of increased sensitivity of gastroesophageal scintiscanning for the detection of reflux in children: supine, prone, left lateral, and 30 degrees right posterior oblique. The sensitivity was highest when the child was placed in supine position. A 60-min recording period increased the sensitivity of the technique, and is thus preferred to a shorter recording time.

Arousals induced by proximal esophageal reflux in infants.

We investigated whether acid reflux in the proximal esophagus can induce arousal from sleep in infants. Fifty normal infants with occasional regurgitations were studied at the age of 8 weeks (range 4-26 weeks). In each child a pH probe was placed in the proximal portion of the thoracic esophagus, in front of the third vertebra, under radiologic control. Polygraphic monitoring of state of alertness and of proximal esophageal pH changes was recorded continuously during one night. The data were analyzed blind. For 41 of the 50 infants, a total of 97 drops below pH 4 was computed. Reflux was more frequently associated with wakefulness (41% of the episodes), or rapid eye movement (REM) sleep (39%), than with nonREM (19%) or indeterminate sleep (1%). Comparing the fifth and the last minutes preceding the pH drops, a significant increase in the number of behavioral arousals was observed (p = 0.003). In comparison with the minute before the drop in esophageal pH, a further significant increase in the number of arousals occurred during the first minutes following the pH drop (p = 0.001). Although the first minutes following the 97 episodes of reflux represented only 0.4% of the total sleep time, 76% of all arousals (74 out of 97) took place during this time period (p = 0.001). Five minutes after the pH drops, the behavioral changes tended to return to prereflux values. It is concluded that in infants, during sleep, proximal gastroesophageal reflux can act as a strong arousal stimulus.

Accuracy of serology and 13C-urea breath test for detection of Helicobacter pylori in children.

BACKGROUND: Indirect noninvasive methods, such as the 13C-urea breath test and serology, can be useful for the detection of Helicobacter pylori infection in children. We analyzed retrospectively the diagnostic accuracy of these two methods. PATIENTS AND METHODS: Between September, 1989, and October, 1996, H. pylori status was determined in 139 children by means of culture and histologic study of gastric biopsies. We performed 146 13C-urea breath tests and serologic assays (Cobas core; Roche). RESULTS: H. pylori infection was detected in 91 of 139 (65%) children. The 13C-urea breath test was discordant with H. pylori status in 4 of 146 tests; serology was discordant in 24 and indeterminate in 7 of 146. The 13C-urea breath test was more sensitive than serology (98% vs. 79%, P < 0.01) but comparable in specificity (96% vs. 92%). The serology yielded false negative results more often in children younger than 5 years of age (P < 0.05). CONCLUSIONS: The 13C-urea breath test is more reliable than serology for the detection of active H. pylori infection in children. Below 10 years of age serology is insufficiently sensitive for clinical purposes, whereas the 13C-urea breath test remains a reliable test.

Twelve year observation of primary and secondary antibiotic-resistant Helicobacter pylori strains in children.

BACKGROUND: The effectiveness of Helicobacter pylori eradication regimens is influenced by antibiotic susceptibility of infecting strains. Data concerning antibiotic resistance in children are limited. We report the evolution of primary and secondary resistance in a series of Belgian children during the last 12 years. PATIENTS AND METHODS: From 1989 through 2000, H. pylori gastritis was diagnosed in 569 children, and antibiotic susceptibility tests were performed in 555. Eradication, using different schemes, failed in 128 of 457 treated children. After eradication failure antibiotic susceptibility determination was performed in 87 of 128. Comparison of antibiotic susceptibility of strains isolated from the gastric body and from the antrum was performed in 238 samples. RESULTS: Resistance to amoxicillin was not observed. The rate of primary resistance to nitroimidazole derivatives was 18.0% (101 of 555) and remained constant throughout this period, whereas primary resistance to macrolides increased from an average of 6.0% (range, 0 to 10%) before 1995 to 16.6% (range, 10 to 25%, P < 0.001) thereafter. Antibiotic consumption in Belgium, especially macrolides, did not show important fluctuations during the study period. Secondary resistance developed in 39 of 87 patients (46%). Strains isolated from different gastric locations show identical susceptibility testing in all but 5 of 238. CONCLUSIONS: Resistance of H. pylori to macrolides increased in our pediatric population which did not appear to correlate with macrolides prescription habits in our country. After eradication failure acquired secondary resistance was observed in one-half of the patients.

Effects of prednisolone and dexamethasone in children with alkali burns of the oesophagus.

We compared the efficacies of prednisolone and dexamethasone for treatment of children with oesophageal burns due to ingestion of caustic substances. The criteria of efficacy used were a) stricture severity by 3 weeks post-ingestion, b) reduction in burn severity by 3 weeks post-ingestion and c) number of dilatations required over the first year post-ingestion. Thirty-six children (24 boys and 12 girls; mean age 23.6 +/- 7.4 months) were selected from a total of 63 patients admitted over a ten-year period to the General Hospital of Galicia with second- or third-degree oesophageal burns due to accidental ingestion of liquid alkali preparations. The patients were divided into two groups of 18, one group for treatment with prednisolone (2 mg/kg/day) and the other for treatment with dexamethasone (1 mg/kg/day). Strictures developed in 12 (66.7%) of the children in the prednisolone-treated group and only 7 (38.9%) of the children in the dexamethasone-treated group. Severe strictures developed in 10 (55.6%) of the children in the prednisolone-treated group and only 5 (27.8%) of the children in the dexamethasone treated group. However, there was no significant difference between the groups in the posttreatment distribution of stricture-severity ratings. Burn healing was significantly better in the dexamethasone-treated group. Similarly, the number of dilatations necessary during the first year of treatment was significantly lower in the dexamethasone-treated group. Our results thus indicate that, by comparison with prednisolone, dexamethasone leads to improved burn healing and reduced need for dialatations during the first year post-injury.

Motor function of the esophagus after caustic burn.

During the subacute and chronic phases of esophagitis due to ingestion of a caustic substance, the patient commonly displays stricture, esophageal rigidity and dysphagia. We used esophageal manometry, radiology, pH monitoring and 99mTc scintigraphy to investigate esophageal motor function in 25 children (mean age 24 +/- 7 months) with chronic esophagitis after second- and/or third-degree caustic burns. The results were compared with those for a control group of 12 children (mean age 32 +/- 19 months) under surveillance for suspected gastroesophageal reflux (GER) but for whom this pathology was later ruled out. Seventeen (68%) of the lesioned-group children showed esophageal dysfunction as revealed by monitoring of pH over a 24-hour period. Over this period, the mean percentage of time with pH below 4 was 19 +/- 10%, the mean number of reflux episodes was 48 +/- 52, the mean number of reflux episodes lasting longer than 5 min was 10 +/- 5, and the mean duration of the longest reflux episode was 51 +/- 21 min. Manometry indicated that, in the lesioned group, an average of 77 +/- 18% of peristaltic waves were nonpropulsive, while the mean Esophageal Work Index (number of propulsive waves per hour x mean maximum pressure developed during propulsive waves) was 227 +/- 192 units. All of the above means were significantly different (p < 0.01) from the corresponding control-group means. Esophageal strictures were observed in 60% (15) of the children. In 2 cases it was minimal, 2 cases moderate and 11 cases had severe strictures. 99mTc scintigraphy indicated that esophageal transit was slightly delayed in four, moderately delayed in five and severely delayed in 16 of the lesioned-group subjects. There was close correspondence between the results of manometry and scintigraphy as regards severity of esophageal dysfunction. These results indicate that motility disturbances and GER are very frequent sequelae of caustic burns of the esophagus, and should be taken into account when evaluating symptoms and deciding on the therapeutic strategy (including diet) to be followed.

[Is upper gastro-intestinal endoscopy required for diagnosis and treatment of Helicobacter pylori infection in childhood? Pro and cons]. / Faut-il pratiquer une endoscopie digestive pour faire le diagnostic (et le traitement) de l'infection à Helicobacter pylori chez l'enfant ? Le pour et le contre.

Non invasive tests are available and accurate for the diagnosis of H. pylori infection in children. They are safer and cheaper than endoscopy. Peptic ulcer and severe gastro-intestinal lesions associated with H. pylori infection are rare in childhood. However since the resistance to antibiotics is steadily increasing, biopsies are still required to assess sensitivity of germs to antibiotics. Search of H. pylori infection should be limited to the children presenting digestive symptoms severe enough to justify endoscopy and treatment.

Joint ESPGHAN/NASPGHAN guidelines for the management of helicobacter pylori in children and adolescents (Update 2016)

BACKGROUND: Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required. METHODS: A systematic review of the literature (time period: 2009-2014) was performed. Representatives of both societies evaluated the quality of evidence using GRADE (Grading of Recommendation Assessment, Development, and Evaluation) to formulate recommendations, which were voted upon and finalized using a Delphi process and face-to-face meeting. RESULTS: The consensus group recommended that invasive diagnostic testing for H pylori be performed only when treatment will be offered if tests are positive. To reach the aim of a 90% eradication rate with initial therapy, antibiotics should be tailored according to susceptibility testing. Therapy should be administered for 14 days, emphasizing strict adherence. Clarithromycin-containing regimens should be restricted to children infected with susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with proton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should be monitored after 4 to 8 weeks by reliable noninvasive tests. CONCLUSIONS: The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection. Therefore, we recommend against a test and treat strategy. Decreasing eradication rates with previously recommended treatments call for changes to first-line therapies and broader availability of culture or molecular-based testing to tailor treatment to the individual child.

Improvement of the eradication rate of Helicobacter pylori gastritis in children is by adjunction of omeprazole to a dual antibiotherapy.

AIM: The possible improvement of efficacy and tolerability of a 7-day dual antibiotherapy amoxicillin-clarithromycin (AC) on the eradication of Helicobacter pylori (H. pylori) gastritis in children by the adjunction of omeprazole (OAC) was studied. METHODS: Forty-six children presenting with H. pylori gastritis, assessed at inclusion by endoscopy, H. pylori urease test, histology and/or culture were randomised to a twice-daily regimen of AC or OAC. A (13)C-urease breath test was performed 4-6 weeks after the end of the treatment period to evaluate H. pylori eradication. RESULTS: A larger proportion of patients was H. pylori negative (69%) in the OAC regimen treatment 4-6 weeks after eradication treatment compared with those who received dual AC therapy (15%). A total of seven patients (three in the OAC and four in the AC group) reported adverse events (AEs). Only vomiting was reported in more than one patient (one in each treatment regimen) and only one AE was severe (urticaria: in the OAC group, but considered not related to treatment). CONCLUSION: A larger eradication rate of H. pylori was obtained in the triple OAC group than in the dual AC group. Both therapy regimens can be safely administered to children for 7 days.

Measurement of urinary sugars by HPLC in the estimation of intestinal permeability: evaluation in pediatric clinical practice.

Determinations of the permeability of the intestine to various sugars have been used to assess intestinal mucosal abnormalities, but the widespread application of such tests has been prohibited by the complexity of most classically used techniques. In this study, we evaluated the sensitivity and practicability of using HPLC to estimate intestinal permeability, with mannitol and lactulose as mono- and disaccharides, respectively. The results of the permeability tests were compared with those of intestinal biopsy in 20 children. All patients with an abnormal intestinal biopsy showed a low mannitol recovery, and the patients with allergic symptoms showed a high lactulose recovery. Our preliminary data suggest that HPLC is reliable, gives results comparable with those of other methods, and is a practical way to determine intestinal permeability noninvasively.

Copper deficiency in infants with active celiac disease.

Celiac disease was diagnosed in two unrelated infants aged 7 and 7.5 months with severe malnutrition. They showed typical clinical, biological, and histological signs of the disease. Moreover, accompanying copper deficiency was suggested by severe hypocupremia and persistent neutropenia; bone radiographs were also compatible with this diagnosis. Rapid and complete correction of these anomalies could only be obtained after addition of oral copper sulfate to the gluten-free diet. Mechanisms possibly involved in the development of copper deficiency in young infants with celiac disease are: chronic malabsorption; high copper needs in rapidly growing infants; and possibly increased biliary and digestive losses. It is therefore suggested that young children with severe celiac disease should be monitored for their copper status.

Total parenteral nutrition in bone marrow transplant: what is the appropriate energy level?

OBJECTIVES: Total parenteral nutrition (TPN), recommended during bone-marrow transplant (BMT), is often withheld following complications. We aim to determine the effective amount of energy supplied and its short-term effects in children requiring BMT. METHODS: Twenty children (11 males, 9 females, mean age 8 years, range 1-18 years) receiving 13 allogenic and 7 autologous BMT for malignant (13) and nonmalignant (7) diseases, were retrospectively evaluated for energy/protein intakes, weight changes, time to engraftment and on TPN, occurrence of complications, and metabolic abnormalities. RESULTS: Each child received approximately 72% of the prescribed calories, an average of 0.87 +/- 0.2 x basal-metabolic rate, 1.14 +/- 0.4 g protein/kg/day, and 176 +/- 34:1 nonprotein calories:nitrogen ratio. Body weight improved during the 35 days (range 14-62) of TPN, with loss thereafter. Engraftment occurred in 20 +/- 7.5 days. Caloric intake and time to engraftment were related (p = 0.002). Ten central-venous-line and 12 gastrointestinal infections occurred. Among laboratory abnormalities, liver function tests resulted temporarily altered in 10 patients, and permanently in 1 child with cholestasis. Eight children developed graft-versus-host disease. Five died of cancer. CONCLUSIONS: The energy supplied with TPN in BMT is less than expected and approximately covers the BMR with mixed effects. Energy intake needs to be calibrated during TPN and adjusted during feeding resumption to expedite recovery.