Helicobacter pylori infection found during upper endoscopy performed for the diagnosis of celiac, inflammatory bowel diseases, and eosinophilic esophagitis: A multicenter pediatric European study.

BACKGROUND: Helicobacter pylori may be found during upper gastrointestinal endoscopy (UGE) performed to diagnose celiac disease (CeD), inflammatory bowel disease (IBD), and eosinophilic esophagitis (EoE). We aimed to describe the frequency of H. pylori in children undergoing UGE for CeD, IBD, and EoE and the number of children receiving eradication treatment. MATERIALS AND METHODS: A retrospective multicenter study from 14 countries included pediatric patients diagnosed with CeD, IBD, and EoE between January 2019 and December 2021. DATA COLLECTED: age, gender, hematologic parameters, endoscopic, histologic, and H. pylori culture results, and information on eradication treatment. RESULTS: H. pylori was identified in 349/3890 (9%) children [167 (48%) male, median 12 years (interquartile range 8.1-14.6)]. H. pylori was present in 10% (173/1733) CeD, 8.5% (110/1292) IBD and 7.6% (66/865) EoE patients (p = NS). The prevalence differed significantly between Europe (Eastern 5.2% (28/536), Southern 3.8% (78/2032), Western 5.6% (28/513)) and the Middle East 26.6% (215/809) [odds ratio (OR) 7.96 95% confidence interval (CI) (6.31-10.1) p < 0.0001]. Eradication treatment was prescribed in 131/349 (37.5%) patients, 34.6% CeD, 35.8% IBD, and 56.1% EoE. Predictors for recommending treatment included erosions/ulcers [OR 6.45 95% CI 3.62-11.47, p < 0.0001] and nodular gastritis [OR 2.25 95% CI 1.33-3.81, p 0.003]. Treatment rates were higher in centers with a low H. pylori prevalence (<20%) [OR 3.36 95% CI 1.47-7.66 p 0.004]. CONCLUSIONS: Identifying H. pylori incidentally during UGE performed for the most common gastrointestinal diseases varies significantly among regions but not among diseases. The indications for recommending treatment are not well defined, and less than 40% of children received treatment.

Helicobacter pylori Infections in Children.

In the context of epidemiology, host response, disease presentation, diagnosis, and treatment management, the manifestation of Helicobacter pylori (H. pylori) infection diverges between children and adults. H. pylori infection stands out as one of the most prevalent bacterial infections globally, and its prevalence in both children and adults is decreasing in many developing countries but some still struggle with a high prevalence of pediatric H. pylori infection and its consequences. The majority of infected children are asymptomatic and pediatric studies do not support the involvement of H. pylori in functional disorders such as recurrent abdominal pain. The pathophysiology of H. pylori infection relies on complex bacterial virulence mechanisms and their interaction with the host immune system and environmental factors. This interaction gives rise to diverse gastritis phenotypes, which subsequently influence the potential development of various gastroduodenal pathologies. In clinical settings, the diagnosis of this infection in childhood requires an upper gastrointestinal endoscopic exam with mucosal biopsy samples for histology and culture, or Polymerase Chain Reaction (PCR) at the very least. When warranted, eradication treatment should be given when good compliance is expected, and there should be systematic use of a treatment adapted to the antimicrobial susceptibility profile. To combat the burgeoning threat of multidrug resistance, vigilant surveillance of resistance patterns and strategic antibiotic management are paramount.

Antibiotic resistance, heteroresistance, and eradication success of Helicobacter pylori infection in children.

BACKGROUND: Antibiotic resistance is a well-known factor of Helicobacter pylori eradication failure. Heteroresistance indicates the coexistence of resistant and susceptible strains and might lead to underestimating antimicrobial resistance. This study aims to evaluate the susceptibility profile, the frequency of heteroresistance of H. pylori strains, and their effect on eradication success in a pediatric population. MATERIALS AND METHODS: Children aged 2-17 years who underwent an upper gastrointestinal endoscopy from 2011 to 2019 with positive H. pylori status were included. Susceptibility was measured by disk diffusion and E-test. The difference in susceptibility profiles between isolates from the antrum and the corpus was used to detect heteroresistance. For those who received eradication treatment, we evaluated eradication rate and factors affecting treatment success. RESULTS: Inclusion criteria were met by 565 children. Strains susceptible to all antibiotics were detected in 64.2%. Primary resistance rates for clarithromycin (CLA), metronidazole (MET), levofloxacin (LEV), tetracyclin (TET), and amoxicillin (AMO) were 11%, 22.9%, 6.9%, 0.4%, and 0% and secondary resistance rates were 20.4%, 29.4%, 9.3%, 0%, and 0%. Heteroresistance was present in untreated children in 2%, 7.1%, 0.7%, 0.7%, and 0% for CLA, MET, LEV, TET, and AMO. First-line eradication rates were 78.5% in intention-to-treat (ITT), 88.3% in full-analysis-set (FAS), and 94.1% in per-protocol (PP). Factors affecting eradication success were the duration of treatment when the triple-tailored treatment was used, the number of daily doses of amoxicillin administered, and the patient's adherence to treatment. CONCLUSIONS: This study shows the presence of relatively low primary resistance rates for H. pylori isolates but demonstrates the presence of heteroresistance in our population. Routine biopsies from the antrum and corpus must be considered for susceptibility testing to allow tailored treatments and increase eradication rates. Treatment success is affected by treatment choice, correct dosing of medications, and adherence. All these factors should be considered when evaluating the efficacy of an eradication regimen.

Complications of Percutaneous and Surgical Gastrostomy Placements in Children: a Single-Centre Series.

Gastrostomy placement is a standard procedure for children requiring enteral feeding for more than 3-6 weeks. Various techniques have been described (percutaneous endoscopic, laparoscopy, and laparotomy), and many complications have been reported. In our center, gastrostomy placement is performed either percutaneously by pediatric gastroenterologists, by laparoscopy/laparotomy by the visceral surgery team, or jointly, that is laparoscopic-assisted percutaneous endoscopic gastrostomy. This study aims to report all complications and identify risk factors and ways to prevent them. Methods: This is a monocentric retrospective study including children younger than 18 years who underwent gastrostomy placement (percutaneous or surgical) between January 2012 and December 2020. Complications that occurred up to 1 year after placement were collected and classified according to their time of onset, degree of severity, and management. A univariate analysis was conducted to compare the groups and the occurrence of complications. Results: We established a cohort of 124 children. Sixty-three (50.8%) presented a concomitant neurological disease. Fifty-nine patients (47.6%) underwent endoscopic placement, 59 (47.6%) surgical placement, and 6 (4.8%) laparoscopic-assisted percutaneous endoscopic gastrostomy. Two hundred and two complications were described, including 29 (14.4%) major and 173 (85.6%) minor. Abdominal wall abscess and cellulitis were reported 13 times. Patients who underwent surgical placement presented more complications (major and minor combined) with a statistically significant difference compared with the endoscopic technique. Patients with a concomitant neurological disease had significantly more early complications in the percutaneous group. Patients with malnutrition had significantly more major complications requiring endoscopic or surgical management. Conclusion: This study highlights a significant number of major complications or complications requiring additional management under general anesthesia. Children with a concomitant neurological disease or malnutrition are at greater risk of severe and early complications. Infections remain a frequent complication, and prevention strategies should be reviewed.

Management of Helicobacter pylori infection in paediatric patients in Europe: results from the EuroPedHp Registry.

PURPOSE: The EuroPedHp-registry aims to monitor guideline-conform management, antibiotic resistance, and eradication success of 2-week triple therapy tailored to antibiotic susceptibility (TTT) in Helicobacter pylori-infected children. METHODS: From 2017 to 2020, 30 centres from 17 European countries reported anonymized demographic, clinical, antibiotic susceptibility, treatment, and follow-up data. Multivariable logistic regression identified factors associated with treatment failure. RESULTS: Of 1605 patients, 873 had follow-up data (53.2% female, median age 13.0 years, 7.5% with ulcer), thereof 741 (85%) treatment naïve (group A) and 132 (15%) after failed therapy (group B). Resistance to metronidazole was present in 21% (A: 17.7%, B: 40.2%), clarithromycin in 28.8% (A: 25%, B: 51.4%), and both in 7.1% (A: 3.8%, B: 26.5%). The majority received 2-week tailored triple therapy combining proton pump inhibitor (PPI), amoxicillin with clarithromycin (PAC) or metronidazole (PAM). Dosing was lower than recommended for PPI (A: 49%, B: 41%) and amoxicillin (A: 6%, B: 56%). In treatment naïve patients, eradication reached 90% (n = 503, 95% CI 87-93%) and 93% in compliant children (n = 447, 95% CI 90-95%). Tailored triple therapy cured 59% patients after failed therapy (n = 69, 95% CI 48-71%). Treatment failure was associated with PAM in single clarithromycin resistance (OR = 2.47, 95% CI 1.10-5.53), with PAC in single metronidazole resistance (OR = 3.44, 95% CI 1.47-8.08), and with low compliance (OR = 5.89, 95% CI 2.49-13.95). CONCLUSIONS: Guideline-conform 2-weeks therapy with PPI, amoxicillin, clarithromycin or metronidazole tailored to antibiotic susceptibility achieves primary eradication of ≥ 90%. Higher failure rates in single-resistant strains despite tailored treatment indicate missed resistance by sampling error.

Efficacy and safety of bismuth-based quadruple therapy for Helicobacter pylori eradication in children.

OBJECTIVES: To evaluate the efficacy and safety of a 10-day quadruple therapy containing colloidal bismuth sub-citrate (CBS), esomeprazole (ESO), amoxicillin (AMO), and metronidazole (MET) for Helicobacter pylori (H. pylori) eradication in children. METHODS: Monocentric, open-label, prospective, single-arm clinical trial in children aged 6-17 years with H. pylori infection. The study was carried out on consecutive patients with upper gastrointestinal symptoms and H. pylori infection confirmed by histology and culture of gastric biopsies. The outcome was evaluated using a 13 C-urea breath test 8-10 weeks post-therapy. Adverse events and compliance were evaluated by daily journal and pill counting. RESULTS: A total of 36 children fulfilling the inclusion criteria were enrolled. Eight (22.2%) of them had a prior H. pylori eradication treatment. Thirteen (36.1%) patients were infected by a strain resistant to MET and 8 (22.2%) by a strain resistant to both MET and Clarithromycin (CLA). In the intention-to-treat population (ITT), eradication was achieved in 35/36 patients (95%CI: 85%-99%). Twenty-three children reported at least one adverse event (63.8%), mostly mild (nausea, vomiting, abdominal pain, diarrhea, dark stool, metallic taste, headache, and rash). The compliance rate was high, with 30 (83.3%) patients taking >90% of the treatment. CONCLUSION: 10-day quadruple therapy containing CBS, ESO, AMO, and MET for H. pylori eradication in children is a safe and very effective solution, especially for previously treated patients and those infected with double resistant strains.

Evolution of Helicobacter pylori associated with gastroduodenal ulcers or erosions in children over the past 23 years: Decline or steady state?

BACKGROUND: Recent data suggest that in children, the proportion of gastroduodenal ulcers/erosions associated with Helicobacter pylori infection is currently lower than expected. In this study, we trace this proportion over two decades. METHODS: We reviewed the reports of all upper gastrointestinal endoscopies with biopsies for histology and culture over the past 23 years. H pylori status was assessed using several invasive methods. The infection rate during different time periods was compared between children with lesions and controls. RESULTS: A total of 7849 endoscopies were performed in 5983 children (2874 F/3109 M, median age 7.6 years, range 0.1-17.9 years). The endoscopy report was missing in 316 patients. At the first upper gastrointestinal endoscopy, 12.1% of the children presented with gastric and/or duodenal ulcers or erosions with an H pylori infection rate of 35.4%, whereas no such lesions were observed in 87.9% of children in whom the H pylori infection rate was 21.3%. The risk factors associated with such lesions were older age (P < 0.001), male sex (P = 0.002), and H pylori infection (P < 0.0001). Gastric ulcers were not significantly associated with H pylori (24% infected), whereas 52% of duodenal ulcers, 33% of gastric erosions, and 38% of duodenal erosions were associated with H pylori. The proportion of gastroduodenal lesions associated with H pylori remained stable over time. Children with H pylori infection and ulcers were older than those with H pylori infection without ulcers (P < 0.001). CONCLUSIONS: Our study indicates that in our pediatric population, the proportion of ulcers without H pylori infection is higher than previously suggested, and this prevalence has not changed over the past two decades.

Epidemiology, Diagnosis and Risk Factors of Helicobacter pylori Infection.

Helicobacter pylori is a human-specific pathogen, which leads to gastric pathologies including gastric cancer. It is a highly unique bacterium considered as a carcinogenic agent. H. pylori remains a major human health problem, responsible for ~90% of the gastric cancer cases. Approximately four billion individuals have been detected for H. pylori infection worldwide in 2015. At the turn of the twenty-first century, the prevalence of H. pylori has been declining in highly industrialized countries of the Western world, whereas prevalence has plateaued at a high level in developing and newly industrialized countries. However, the infection status remains high in immigrants coming from countries with high prevalence of H. pylori infection. H. pylori can be diagnosed both by invasive and non-invasive methods. Urea breath test and stool antigens detection are among the most commonly used non-invasive ones. Although the way H. pylori is transmitted remains still not fully clear, the level of contamination is strongly dependent on the familial and environmental context, with a drastic impact of living conditions with poor hygiene and sanitation. However, familial socioeconomic status is the main risk factor for H. pylori infection among children. In addition, food and water source have a high impact on the prevalence of H. pylori infection worldwide. This chapter highlights the latest knowledge in the epidemiology of H. pylori infection, its diagnosis and critical risk factors responsible for its high prevalence in some populations and geographic areas.

Management of esophageal motility disorders in children : a review.

Diagnostic criteria for esophageal motor disorders have recently been updated with the advent of high-resolution manometry that gives a precise mapping of peristaltic abnormalities and an indirect view of bolus transit problems. Achalasia, the best-defined motor disorder, is now divided in subsets of manometric phenotypes that predict outcome of treatment and guide our therapeutic approach. Pharmacological therapy using smooth muscle relaxants for spastic esophageal disorders remains poorly effective and used only as a bridge to more effective therapies : endoscopic balloon dilation and surgical myotomy are both effective therapies in achalasia, myotomy being considered as the preferred approach in children because it is aimed to be definitive, while dilations usually have to be repeated. Recently, peroral endoscopic myotomy was introduced as an alternative to surgical myotomy for achalasia, and was rapidly adopted in tertiary referral centers. Showing excellent short-term results, this technique might be also proposed for other esophageal spastic disorders. Gastroesophageal reflux disease and eosinophilic esophagitis, two prevalent diseases in children that may be associated with hypotensive and hypertensive peristaltic abnormalities, have to be searched because specific effective therapies exist for these diseases that may cure the motility disorders.

Helicobacter pylori Infection in Pediatric Patients: Update on Diagnosis and Eradication Strategies.

Helicobacter pylori infection is acquired mainly in childhood and remains an essential cause of peptic ulcer disease and gastric cancer. This article provides commentary on the last ESPGHAN/NASPGHAN guidelines and on publications made after the consensus conference of 2015. The majority of infected children are asymptomatic and pediatric studies do not support a role for H. pylori in functional disorders such as recurrent abdominal pain. The role of H. pylori infection in failure to thrive, children's growth, type I diabetes mellitus (T1DM), and celiac disease remains controversial. The diagnosis of infection should be based on upper-digestive endoscopy with biopsy-based methods. Eradication control after treatment should be based on validated non-invasive tests. Nodular gastritis is the main endoscopic finding of childhood H. pylori infection, but gastroduodenal erosions/ulcers are seen in some children, especially after 10 years of age. When indicated, eradication treatment should be given when good compliance is expected and based on the antimicrobial susceptibility profile.

Eradication rate of Helicobacter Pylori infection is directly influenced by adherence to therapy in children.

BACKGROUND: Current commonly accepted strategies to eradicate Helicobacter pylori in children are a 10-day sequential treatment or a triple therapy for 7-14 days. To avoid further expensive and possibly risky investigations as well as induction of secondary antimicrobial resistance, a success rate of elimination strategies over 90% in a per-protocol analysis is the target goal but rates observed in clinical trials are lower. Antimicrobial resistance is a well-recognized risk factor for treatment failure; therefore, only a treatment tailored to susceptibility testing should be recommended. Adherence to therapy is also a risk factor for treatment failure but that has been poorly studied. The purpose of this study was to evaluate the influence of adherence to therapy on the elimination rates obtained with different treatment regimens. METHODS: Cohort study analysis of children, aged 2-17 years, treated for Helicobacter pylori infection between October 2011 and December 2013. As a routine clinical practice, children infected with a strain susceptible to clarithromycin and to metronidazole received either a sequential regimen or a 10-day triple therapy while children infected with a strain resistant to clarithromycin or metronidazole received a 10-day triple regimen tailored to antimicrobial susceptibility. The eradication rate was assessed by a negative 13 C-urea breath test performed at least 8 weeks after the end of the treatment and adherence evaluated using a diary. RESULTS: One hundred forty-five children (67 girls/78 boys, median age 9.7 years) fulfilled the inclusion criteria, 118 being infected with a strain susceptible to both clarithromycin and metronidazole, 10 with a clarithromycin resistant, and 17 with a metronidazole resistant strain. A sequential regimen was prescribed in 44, a triple therapy containing clarithromycin in 84 and containing metronidazole in 17. Follow-up data were available for 130/145 and clearance of the infection observed in 105 of them. A concordance of more than 90% between the prescribed and the ingested drugs was observed in 109 children, between 50 and 90% in eight, less than 50% in 11 while these data were unknown for 2/130. A successful eradication was achieved for 89.9% of patients that received at least 90% of the prescribed drugs, whereas the eradication rate for nonadherent patients was 36.6%. Adherence above 90% was significantly higher in the absence of chronic concomitant disease, in the absence of adverse event and results in a significantly higher eradication rate. With the proposed strategy and an adherence higher than 90%, eradication was obtained in 98/109 children, the rate being only significantly superior to 90% with the sequential regimen. CONCLUSION: Adherence to therapy is a very important factor for the outcome and has to be assessed when evaluating the outcome of an H. pylori eradication regimen in order to understand the reasons of treatment failure. As we treated only after evaluation of the resistance of the H. Pylori strains, we were expecting to reach the given objective of 90% successful treatment. Children with adherence to treatment above 90% had a successful outcome of 89,9%, whereas nonadherent had a successful outcome of 36,8%. This is the first time that adherence has been assessed accurately.

Successful sublingual cobalamin treatment in a child with short-bowel syndrome.

Vitamin B12 (B12) is essential for deoxyribonucleic acid synthesis, to maintain normal hematologic and neurologic functions. Studies suggest that cobalamin deficiency in children is more common than previously recognized. Main causes are decreased intake, abnormal absorption, and inborn errors of metabolism. The classic treatment for cobalamin deficiency is intramuscular administration of B12. There are no data concerning the use of alternative routes of cobalamin administration in children. This report shares the experience of sublingual administration of B12 to a patient with short-bowel syndrome and B12 malabsorption. We report the case of successful treatment of cobalamin deficiency by sublingual administration in a 9-year-old patient who had undergone intestinal resection and jejunum-colon, with anastomosis of 32 cm of residual small intestine and absence of distal jejunum and ileocecal junction. We determined a B12 deficiency because low serum cobalamin levels (<200 pg/mL) were shown in 2 consecutive tests (130 pg/mL and 170 pg/mL). The patient presented with neither clinical nor hematological manifestations. He received sublingual cobalamin preparation, 1000-mcg sublingual nuggets per day for 1 month. Normalization of serum cobalamin was obtained (790 pg/mL) after 1 month of treatment. The sublingual route of administration not only improved the quality of life of this patient by avoiding monthly painful injections but also reduced the cost of treatment and the number of hospital visits.