Helicobacter pylori (H. pylori) is a Gram-negative urease producing microaerophilic spiral bacterium first discovered in 1983. It has a strong affinity for the gastric mucosa and is associated with chronic active gastritis, peptic ulcer disease (PUD), and gastric adenocarcinoma. Infection is typically acquired in early childhood and persist throughout the life, as spontaneous eradication is rare [1,2]. H. pylori infects at least 50% of the world’s population [3]. Among those infected, approximately 10–15% may develop peptic ulcer disease, and 1–3% may progress to gastric adenocarcinoma. However, in children, the infection is often asymptomatic, and such complications are uncommon [4].

Transmission occurs primarily through direct person-to-person contact via oral–oral, fecal–oral, or gastric-oral routes. Children acquire infection mainly through the faecal–oral route as H. pylori has been cultured from the stool of infected children [5]. H. pylori is a marker of sanitation status, with declining prevalence in developed countries but prevalence remains high in developing countries ranging from 18.9-87.7%. In India it is estimated to be 63.5% [1]. The rising rates of antibiotic resistance globally is alarming and pose a challenge to effective management. This update highlights evolving recommendations for diagnosis and management of H. pylori infection in children based on the latest guidelines by the European/North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition 2024.

H. pylori infection in children remains asymptomatic. Therefore, the primary goal of clinical investigations for evaluating gastrointestinal symptoms should be directed towards underlying causes rather than solely focussing on H. pylori as a causative agent. The esophagogastroduodenoscopy (EGD) with gastric biopsies remains the cornerstone of diagnosis. Non-invasive testing has no role in the initial evaluation. Treatment is clearly indicated if endoscopy detects H. pylori positive gastric or duodenal ulcers and/or erosions. If H. pylori is detected incidentally on biopsies (RUT, histopathology, culture, or molecular tests) without endoscopic lesions, treatment may be offered after discussing potential risks and benefits with caregivers. In children with refractory iron deficiency anemia, the guidelines recommend endoscopy-based H. pylori testing and treatment can be offered if infection is confirmed. A new recommendation in the 2024 guidelines is to consider non-invasive testing in asymptomatic children with a first-degree relative with gastric cancer.

When is H. pylori Testing Not Recommended?

The guidelines clearly advise against testing for H. pylori testing in the following situation such as children with disorder of gut–brain interaction, children undergoing endoscopy for other gastrointestinal condition (e.g., celiac, inflammatory bowel disease, and eosinophilic esophagitis), those with chronic immune thrombocytopenic purpura, and in short stature evaluation when other causes ruled out.

How to Test for H. pylori?

H. pylori testing can be done using either invasive methods (via esophagogastroduodenoscopy) or non-invasive tests (such as stool antigen test, urea breath test, and serology). The initial diagnosis of H. pylori should be made using invasive, gastric biopsy-based methods such as culture or molecular tests and histopathological evaluation as per the Sydney system. A minimum of 6 gastric biopsies (three from the corpus (body) and three from the antrum) should be taken and labelled by specific site for histopathological evaluation, culture or molecular tests, and rapid urease test (RUT). Care should be taken while taking biopsy, as active bleeding decreases the sensitivity of biopsy-based tests.

Symptom relief alone is not a reliable marker of eradication success. To ensure eradication, non-invasive test such as urea (13-C) breath test (13C-UBT), or a two-step monoclonal stool antigen test are preferred [6]. The guideline recommends using either of these two tests to ensure eradication of infection. The 13C-UBT has a negative predictive value of 99.2% and may give false positive result in children < 6 years due to lower distribution volume and different CO2 production rates [7]. Similarly, the monoclonal stool antigen test shows excellent sensitivity of 100% and sensitivity of 92.3% [8]. Among the non-invasive tests, serological assays are not recommended because they cannot distinguish between current and past infections [9].

The potential benefit and risk of H. pylori eradication therapy should be clearly discussed with caregivers, particularly in cases with incidental finding of H. pylori-associated gastritis (including nodular gastritis) with other GI diseases. Potential benefits include the prevention of future gastric complications (peptic ulcer disease, atrophy/intestinal metaplasia, gastric MALT lymphoma, and gastric cancer), as well as reducing parental anxiety due to nontreatment. Risks such as increased antibiotic resistance, potential drug side effects, and disruption of gut microbiota, and the possibility of treatment failure/reinfection.

Global antibiotic resistance to H.pylori is rising, with metronidazole (MTZ) and clarithromycin (CLA) resistance rates reported to be 35.3% and 32.6% respectively [10]. Given this, eradication therapy should ideally be guided by CLA susceptibility testing (CLA-AST) to improve treatment success and reduce resistance. If CLA-AST is not available, CLA should not be used empirically. Metronidazole-AST is not routinely recommended, as there is a lack of reliable molecular diagnostic method for MET-AST and culture-methods are not promising. CLA-AST can be performed using culture-based methods or molecular methods such as PCR. PCR-based methods are preferable as they are more sensitive and rapid turnaround times.

Proton pump inhibitor (PPI) forms the cornerstone of management. The first line regimens include AST-guided triple therapy which consists of a high dosage of PPIs, a high dosage of amoxicillin (AMO) and either CLA or MTZ, based on susceptibility, for duration of 14 days. In patients with allergy to penicillin, alternative agents should be considered. Among PPIs, esomeprazole is preferred as it is less susceptible to degradation by rapid metabolizers with relevant cytochrome polymorphisms. In the absence of AST, bismuth-based quadruple therapy (bismuth, PPIs, AMO, MET) is recommended as the empirical first line regimen. When the strain is resistant to CLA and patient is allergic to penicillin, Bismuth based quadruple therapy with tetracycline (TET) is suggested (Tetracycline is reserved for children >8 years of age). (see figure 1) AST-guided triple therapy is suggested over sequential-quadruple therapy. Drug dosages based on body weight are summarized in Table 1.

Figure 1: CLA-AST Based Treatment Regimens for H. pylori Infection in Children.

Abbreviations: CLA: Clarithromycin, PPI: proton pump inhibitor, AMO: amoxicillin, MET: metronidazole, Children (>8years) TET can replace AMO; however, pediatric data is lacking, ^# Bismuth quadruple regimens are preferred due to higher eradication rates.

Table 1: Drug Doses According to Bodyweight.

  ^# Esomeprazole preferred because unaffected by CYP2C19 polymorphisms.

Rescue Therapy

There is no recommendation regarding rescue therapy in a recent guideline; however, as per expert consensus, children who fail on initial therapy should be treated again with an alternative regimen. Cause for failure must be evaluated (non-compliance, inadequate dosing or treatment not tailored to CLA-AST). CLA or fluoroquinolones should be avoided, if the child has a prior history of using it. MET resistance can be overcome by using higher dosage of MET for a longer duration. If two consecutive regimens fail, then H. pylori susceptibility testing should be reconsidered. (figure 2).

Figure 2: Rescue Therapies.

Newer Drugs

Potassium-competitive acid blockers such as Vonoprazan have emerged as promising alternative to traditional PPIs. It has shown favorable outcomes in adult studies and is now approved for H. pylori eradication in Japan and the United States. However, pediatric data are currently lacking, and Vonoprazan is not yet approved for use in children [11].

Check for Eradication 

Testing for H. pylori eradication should be performed 6–8 weeks after completion of therapy. The current guidelines recommend use of non-invasive tests like 13 C-UBT or a two-step monoclonal stool antigen test (SAT) to confirm eradication. Follow-up endoscopy is not routinely indicated and is reserved for cases of complicated PUD.

A detailed comparison of the 2011, 2016, and 2024 guidelines is shown in Table 1.

• Elimination of pylori testing in chronic ITP (previously considered)
• Introduction of non-invasive testing recommendation for children with a family history of gastric cancer
• Clarification on testing/treatment if pylori is found incidentally during EGD for other GI conditions
• Acceptance of molecular diagnostic methods for diagnosis and resistance testing
• Bismuth-based quadruple therapy preferred in case of unknown susceptibility

Table 2: Comparison of the 2011, 2017 and 2024 Guidelines for Management of H. pylori Infection in Children and Adolescents.

H. pylori infection is common in children, although the majority remain asymptomatic. Current evidence does not support an association between H. pylori and disorder of gut–brain interaction, chronic immune thrombocytopenic purpura, or short stature. For diagnosis invasive testing with esophagogastroduodenoscopy is recommended and eradication therapy is required in presence of PUD and or erosion. To ensure eradication, non-invasive tests such as the urea breathe test or two step monoclonal antigen test should be performed 6-8 weeks after completion of therapy. Follow up endoscopy is recommended in cases of complicated PUD. In view of rising global antibiotic resistance, AST is mandatory before initiating antibiotic therapy. A CLA-AST-guided triple therapy is recommended for 14 days of duration. In settings where AST is unavailable, bismuth-based quadruple therapy (bismuth, PPI, amoxicillin, and metronidazole) should be used empirically as the first-line regimen.

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