The symptoms of infection by H. pylori are nonspecific, and the evidence to date has not established an association between this infection and upper gastrointestinal symptoms in children. Clinicians must investigate the cause of these symptoms by means of upper endoscopy as opposed to only testing for H. pylori. The main indication to test for H. pylori in children with gastrointestinal symptoms is the finding of gastric or duodenal ulcers or erosions on endoscopy, although these features are only found in 5% of the total cases of infection.3,4

In children, infection by H. pylori causes chronic inflammation predominantly in the antrum, which usually exhibits a nodular appearance on endoscopy. The presence of antral nodularity in the absence of ulcers does not entail risk to the paediatric patient if H. pylori is not treated and eradicated, but culture of a gastric mucosa specimen should be performed in case the patient undergoes eradication treatment in the future to avoid empirical therapy.3

Chronic or recurrent abdominal pain is one of the most frequent presenting complaints in paediatric care. In most cases, abdominal pain is indicative of a functional disorder, as noted in the Rome IV criteria for functional gastrointestinal disorders, which are characterised by the absence of any identifiable sign of organic disease (Table 1). The diagnosis of these disorders is usually based in the presence of symptoms rather than ruling out other diseases, and therefore it does not always require performance of diagnostic tests.

Since the publication of the most recent ESPGHAN/NASPGHAN guidelines,3 several observational studies in large samples of paediatric patients have assessed the association between chronic abdominal pain and infection by H. pylori and have found no evidence of it.5–7 Therefore, we do not consider that testing is indicated in cases of abdominal pain in the absence of signs or symptoms suggestive of an organic disorder.

There is evidence of an association between H. pylori infection and other diseases, but the association has only been reported consistently for some diseases, while the evidence regarding the rest is inconclusive or indirect (Table 2). With the exception of refractory iron-deficiency anaemia,8 chronic primary immune thrombocytopenia (cPIT)9 or mucosa-associated lymphoid tissue (MALT) lymphoma,10 the presence of another disease is not sufficient indication for testing for H. pylori.

No study to date has evaluated the benefits of H. pylori eradication therapy in asymptomatic children with a family history of gastric or duodenal ulcer or stomach cancer in a first-degree relative. In the case of cancer, the ESPGHAN/NASPGHAN guidelines removed the recommendation for testing in 20173 because the issue rarely arises in clinical paediatric gastroenterology practice.

The test and treat strategy involves delivery of H. pylori eradication therapy based on positive results of a non-invasive test, such as the H. pylori breath test or stool antigen test. This strategy is commonly used in the management of adults with dyspepsia in the absence of warning signs, which achieves a small but significant benefit in symptom control.11 However, since similar studies have not been conducted in children, these results cannot be extrapolated to the paediatric population. This practice has resulted in a significant increase in the prevalence of H. pylori resistant to the antibiotics commonly used for its eradication.12

Based on data from the Pediatric European register for treatment of H. pylori, the prevalence of primary resistance to clarithromycin in countries in Southern Europe is substantially greater than 15%, and therefore the use of this drug for empirical therapy is contraindicated. After first-line treatment failure, the prevalence of secondary resistance exceeds 50%, both for clarithromycin and for metronidazole.4 Considering that the range of antimicrobials that can be used in the paediatric population is limited in children, it is key to achieve eradication with the initial treatment, and therefore the selection of drugs for first-line treatment should be based on the results of antibiotic susceptibility testing.

Table 3 presents the recommendations concerning the diagnostic evaluation of H. pylori infection.

The initial diagnosis of H. pylori in children should be based on the findings of upper endoscopy.13–15 This examination allows investigation of the aetiology of the presenting symptoms and a definitive diagnosis, and offers the opportunity to obtain a biopsy sample for culture and antimicrobial susceptibility testing to guide treatment, a histological assessment of the severity of the infection and performance of additional testing, such as the urease or polymerase chain reaction (PCR) tests.16,17

The only patients in who diagnosis of infection and subsequent treatment based on non-invasive tests are acceptable are patients with cPIT or at risk of severe complications of upper endoscopy performed under anaesthesia or sedation.

The diagnosis should be based on culture of a gastric mucosa biopsy specimen or, when the latter is not available or in the absence of growth, on the identification of H. pylori in the histological examination in addition to a positive result of another invasive test (rapid urease test or PCR).15,16,18,19 The use of PCR techniques that can provide information on the resistance to clarithromycin and/or levofloxacin is preferred over methods that can only detect the presence of the bacterium.20 Likewise, we recommend performance of a Gram-stain test in a biopsy sample to strengthen the diagnosis, an option that is particularly valuable when the culture does not grow. Table X in Appendix B (online Supplemental material) presents the different tests that can be performed on biopsy samples.19,21–27

Patients should not take antibiotics for a minimum of 4 weeks before performance of upper endoscopy. Proton pump inhibitors must be suspended at least 2 weeks before collection of biopsy samples.3,11,24 If the patient cannot discontinue treatment due to the persistence of symptoms, the PPI can be switched to an H2 antagonist, to be suspended 48h before the test. Ranitidine tablets are no longer commercially available, but hospital pharmacies continue to carry the active ingredient and can make capsules with the amount prescribed by the paediatrician (we recommend a dose of 2mg/kg/12h) or solutions of different concentrations.

A minimum of 6 biopsy samples of gastric mucosa should be collected: 2 each from the antrum and the corpus for pathology, and 1 each from the antrum and the corpus for culture.3 However, we recommend collection of at least one other antrum specimen for performance of additional tests (rapid urease or PCR).

When it comes to sample collection, given the difficulty of growing H. pylori in culture, it is important to take the biopsies before advancing to the duodenum, collecting the samples for culture first with a clean forceps (which should not have been previously inserted in tubes with formalin) and putting them together in a single tube with 1–2mL of normal saline or a specific transport medium. Samples collected for pathology should be placed in tubes with formalin, separating antrum and corpus specimens.19,21,28,29

Since H. pylori is a fastidious bacterium and dies easily, appropriately enriched transport media have been formulated to maintain the viability of the samples until they are examined in the microbiology laboratory. When such a medium is not available, normal saline can be used to temporarily prevent drying of the biopsy specimen. In addition, cold temperatures extend the viability of samples and inhibit the proliferation of other microbes contaminating the medium, so if the seeding is going to be delayed, biopsy samples should be stored at a temperature of −20°C or lower if seeding is to happen within 24h and at −70°C or in liquid nitrogen in case of longer delay.29

Given the fragility of H. pylori, there is a high risk that the bacterium will not grow in culture and failure due to contamination by other bacteria, so we recommend culture and antimicrobial susceptibility testing of all samples submitted to the microbiology department (at least 1 corpus and 1 antrum sample). On the other hand, although rare, there may be cases of colonization by 2 strains with different drug resistance profiles, an additional reason to perform susceptibility testing in every sample.

Table 4 presents the recommendations for diagnosis of H. pylori infection.

The first-line treatment for H. pylori eradication in paediatric patients is triple therapy combining one PPI and two antibiotics (amoxicillin plus clarithromycin or metronidazole) given in 2 daily doses for 14 days. The selection of antibiotics is based on the results of susceptibility testing (Table 5), although in Spain the use of metronidazole as opposed to clarithromycin is recommended unless there is evidence of resistance to metronidazole. The dose should be adjusted based on the weight of the patient, and a high dose of the PPI is recommended to achieve adequate acid suppression (Table 6). The aim is to achieve a high eradication rate (>90%) to prevent the development of secondary antibiotic resistances and reduce the need of salvage therapy.3,11

Esomeprazole and rabeprazole are less susceptible than omeprazole to degradation by rapid metabolizers with CYP2C19 variants, which are more frequent in the Caucasian population (56%–81%), and therefore their use is preferred when they are available.3

The initial treatment should be adapted to the antimicrobial susceptibility profile of the isolated strain, but in case susceptibility is not known, we recommend the following:

• 1.

  Adapting treatment to regional or national antimicrobial resistance trends and prescribing the eradication regimen that has proven most effective at the local level.3,14,30

• 2.

  First-line triple therapy should not include clarithromycin due to the high prevalence of antimicrobial resistance (>15%). Sequential therapy is also not recommended.3,11,31,32

• 3.

  Table 5 presents the recommended empiric therapy regimens.1

The 2017 ESPGHAN/NASPGHAN3 guidelines concluded that more studies of greater quality were needed to support the recommendation of adjunctive probiotic supplementation during H. pylori eradication therapy.

In our search of the literature published in the past 5 years, we found several studies and systematic reviews with meta-analyses with contradictory results on the efficacy of different strains and combinations of probiotics used as adjunctive therapy during H. pylori eradication treatment. Some studies have found beneficial effects in the prevention of adverse events associated with antibiotic treatment.10,33–35

The effectiveness of eradication therapy must always be assessed.3,13–15 To this end, we recommend the use of validated non-invasive tests: stool antigen test (monoclonal antibody-based enzyme immunoassay) or the 13-C urea breath test.13 In children aged less than 6 years, the stool test is preferable due to the higher frequency of false positives with the breath test and the practical difficulties in performing that test in younger children (Appendix B, Table Y, online Supplemental material).

The 2017 ESPGHAN/NASPGHAN guidelines3 state that the selection of second-line treatment should be guided by antimicrobial susceptibility testing results or, when these are not available, salvage therapy should include antibiotics not used for first-line treatment and/or greater doses or longer courses of treatment. The proposed salvage regimens were triple therapy with PPI+amoxicillin (75mg/kg/day)+metronidazole or quadruple therapy, adding bismuth, for a total of 14 days.3,15

If antimicrobial susceptibility is not known at the time of first-line treatment, a new upper endoscopy examination and biopsy should be performed to carry out antimicrobial susceptibility testing and prescribe therapy guided by the results. If susceptibility testing is still not available, the strain should be considered double resistant (Table 5).

Also, the use of esomeprazole or rabeprazole is recommended if they were not included in the first-line regimen.11

It is crucial that the physician explain to the family and the patient, too, if age-appropriate, that the success of treatment hinges on adherence, which is associated with a substantial increase in the rate of eradication, with the latter nearing 90% in case of adequate adherence.13,36 Close monitoring during treatment may help achieve this goal.

There are tools that may help prevent missed doses and promote adherence, such as the patient parent guide for treatment of H. pylori developed by the Helicobacter pylori Working Group of the ESPGHAN, which includes a diary to report drug intake, side effects and special events during treatment. A translation to Spanish of this booklet can be downloaded at <https://www.espghan.org/knowledge-center/education/H-Pylori-Patient-Parent-Guide> (Appendix B, Fig. Z, online Supplemental material).

On the other hand, efforts should be made to minimise the side effects of drugs to the extent possible, which is why the use of probiotics is recommended.

Table 7 presents the recommendations for treatment of infection by H. pylori.

Fig. 1 presents the algorithm for the management of paediatric patients with infection by H. pylori.

Figure 1.

Algorithm for management of H. pylori infection in children.

PPI, proton pump inhibitor.

1High-dose amoxicillin: 75mg/kg/day to a maximum of 3g/day.

2In children aged more than 8 years, tetracycline may be substituted for amoxicillin.

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