INTRODUCTION — Chronic infection with Helicobacter pylori is an important cause of gastrointestinal pathology in adults and children. However, severe gastroduodenal disease in pediatric patients is uncommon. Compared with adults, children are much less likely to develop complications of infection such as duodenal and gastric ulcers. Furthermore, there is no evidence that H. pylori infection causes functional abdominal pain in children and that treatment improves functional gastrointestinal pain-related symptoms. As a result, different strategies for screening, diagnosis, and treatment of H. pylori should be used for children than for adults.
This topic review will provide an overview of screening, diagnosis, and management of H. pylori infection in children and adolescents, highlighting differences in management compared with adults. Evaluation and management of H. pylori in adults are discussed separately. (See "Indications and diagnostic tests for Helicobacter pylori infection in adults" and "Treatment regimens for Helicobacter pylori in adults".)
EPIDEMIOLOGY — The prevalence of H. pylori is declining worldwide, and particularly in resource-abundant settings. However, H. pylori remains one of the most common human infections worldwide. The prevalence varies widely according to different geographic areas and within specific regions as well as by age and socioeconomic factors. In low- and middle-income countries or other disadvantaged populations, up to 75 percent of the population is infected, likely due to environmental factors including crowding and problems with water sanitation and transmission of the organism by fecal-oral, oral-oral, and gastro-oral routes [1-3].
Among children (<18 years), the global prevalence of H. pylori infection rates is 32 to 36 percent; prevalence ranges from <5 percent (eg, in Scandinavian countries) to >70 percent (eg, in several countries in Africa [Benin, Nigeria] and Latin America [Peru]), with rates of 30 to 40 percent in the United States, Canada, and the United Kingdom [4]. When grouped by socioeconomic regions (as defined by the World Bank), infection rates among children are approximately 22 percent in high-income countries and 43 percent in low- and middle-income countries. The prevalence of H. pylori infection is associated with lower socioeconomic status of the family in which a child is raised, higher number of persons sharing a home, room sharing, lack of access to a sewer system, drinking water that is not boiled or treated, and having household members with H. pylori infection [4,5]. The lower prevalence in children compared with adults is likely due to socioeconomic improvements (ie, in infrastructure) rather than newly acquired infections as adults. Similarly, socioeconomic factors likely contribute to the decreasing rates of H. pylori infection over time in many regions. In some settings, H. pylori infection rates may also be influenced by earlier diagnosis and treatment of H. pylori among adults, driven by the increasingly recognized relationship between H. pylori infection and gastric cancer [6,7].
H. pylori infection is predominantly acquired during early childhood. Most infections occur before 10 years of age [1,2,5,8,9], especially in resource-limited countries where infection acquisition often occurs prior to three years of age [10-13]. As an example, a study in Irish children demonstrated that the greatest risk period for acquiring infection was prior to three years of age and the risk for new primary infection decreased after five years of age [14].
Children also have high rates of reinfection if the initial H. pylori infection is eradicated. Reinfection rates are approximately 20 percent or more in high-prevalence populations [15]. Risk factors for reinfection are similar to those for primary infection [16,17]. For older children, household contact with siblings younger than five years is a risk factor for reinfection [18-20]. In contrast with children, reinfection is rare after successful eradication in adults. (See "Bacteriology and epidemiology of Helicobacter pylori infection".)
NATURAL HISTORY
●Phases of infection – The natural history of H. pylori infection appears to occur in phases, at least in adults with newly acquired infection. Adult volunteers who ingest a dose of H. pylori experience:
•Initial phase – Intense bacterial proliferation with gastric inflammation, sometimes associated with transient upper gastrointestinal symptoms and hypochlorhydria.
•Chronic phase – The inflammatory response subsides to either a chronic diffuse superficial gastritis with normal or reduced gastric acid production, or antral-predominant gastritis, which results in increased gastric acid production and increased risk for peptic ulcer disease. For unclear reasons, some chronically infected individuals remain free of symptoms for years or even a lifetime. (See "Acute and chronic gastritis due to Helicobacter pylori".)
Whether a similar pattern of transient gastroduodenal inflammation occurs after H. pylori acquisition in children or in populations in high-endemic regions remains unclear. However, indirect evidence suggests that H. pylori infection in children is associated with limited clinical symptoms, a different phenotype of gastric inflammation than that in adults, and/or biomarkers of gastric or intestinal inflammation and intestinal permeability [21,22]. (See "Acute and chronic gastritis due to Helicobacter pylori".)
●Risk of persistent infection – The likelihood that primary H. pylori infection persists varies depending on the child's age and the population studied. Persistent infection is most common for young children in populations where H. pylori is endemic [2,23]. As an example, in a study of children in Chile, two-thirds of children who acquired the infection during the first five years of life become persistently infected [23].
●Protective factors – Innate factors that may protect against H. pylori infection (eg, TLR4 gene polymorphisms) have been described but not firmly established [24].
CLINICAL MANIFESTATIONS AND CONSEQUENCES
●Symptoms and signs – The majority of children infected with H. pylori are asymptomatic (ie, no symptoms such as abdominal pain that are reported to the parents or health care provider). Most children with infection have gastric mucosal inflammation, typically described as chronic-active and/or nodular gastritis (picture 1), which is more common in children than in adults [25-29]. In most cases, the nodular gastritis is asymptomatic and complications of infection do not occur. However, in a small number of cases, frank mucosal erosions and duodenal or, to a lesser extent, gastric ulcers develop.
If gastroduodenal ulcers develop, these can cause epigastric abdominal pain. However, children with gastric or duodenal ulcers more often have alarm signs (eg, occult blood in stool, weight loss or vomiting, or nighttime wakening with pain) that distinguish them from children with functional abdominal pain [30-33]. Therefore, screening for H. pylori infection is not recommended for children with a typical presentation of functional abdominal pain without alarm signs, as discussed below. (See 'Indications for testing in children' below and "Chronic abdominal pain in children and adolescents: Approach to the evaluation".)
●Adverse consequences of H. pylori infection – H. pylori infection is strongly associated with peptic ulcer disease in children, as it is in adults [34]. It is also associated with mucosa-associated lymphoid tissue (MALT) lymphoma [35-37], chronic (but not acute) immune thrombocytopenic (ITP) purpura [38-46], and iron deficiency anemia that is refractory to treatment [47-49], based on low-quality evidence. These associations form the indications for testing in children. (See 'Indications for testing in children' below.)
By contrast, in adults, chronic H. pylori infection is associated with functional dyspepsia in addition to the above conditions. There is also an association, and likely causative link, between H. pylori infection and iron deficiency in adults [50]. H. pylori infection is an important risk factor for gastric cancer in adults [50,51], although the overall risk of gastric cancer in infected individuals is low. These associations inform the broader indications for H. pylori testing in adults as well as what has been termed a "screen and treat" management strategy. (See "Indications and diagnostic tests for Helicobacter pylori infection in adults" and "Association between Helicobacter pylori infection and duodenal ulcer" and "Association between Helicobacter pylori infection and gastrointestinal malignancy" and "Helicobacter pylori and gastroesophageal reflux disease".)
●Possible benefits of H. pylori infection – Epidemiologic studies suggest an inverse association between H. pylori infection and atopic diseases in children [52-54]. However, this association likely reflects the fact that H. pylori infection has declined and, conversely, that allergic or atopic diseases have increased significantly. Thus, H. pylori is probably a surrogate epidemiologic marker for infrastructure improvement rather than a primary factor that protects against atopic disease. Inverse associations with H. pylori infection have also been suggested for inflammatory bowel disease [55,56], celiac disease [57,58], and eosinophilic esophagitis [59,60], all of which have increasing prevalence and incidence. Although chronic H. pylori infection sometimes reduces gastric acid production, it does not appear to be protective against gastroesophageal reflux or esophageal or proximal gastric cancer [61]. (See "Clinical manifestations and diagnosis of eosinophilic esophagitis (EoE)", section on 'Epidemiology' and "Helicobacter pylori and gastroesophageal reflux disease".)
EVALUATION
Indications for testing in children — Our approach to testing for H. pylori infection in children is outlined below. If the test for active infection is positive, we take steps to eradicate the infection.
●Definite indications – Important indications for testing for H. pylori in children are:
•Peptic ulcer disease (ie, gastric or duodenal ulcers) – Test all children with peptic ulcer disease. This condition is clearly associated with H. pylori infection in children, as it is in adults, although other factors such as nonsteroidal antiinflammatory drugs may contribute [34].
•Family history of gastric cancer – Test for H. pylori in children who have first-degree relatives with gastric cancer. Chronic H. pylori infection is the most important risk factor for development of gastric cancer, and studies demonstrate that eradication is beneficial for patients with a first-degree relative with gastric cancer in H. pylori-infected adult populations [51]. (See "Association between Helicobacter pylori infection and gastrointestinal malignancy".)
•Mucosa-associated lymphoid tissue (MALT) lymphoma – Test all children with MALT lymphoma. Several case reports in children describe MALT lymphoma associated with H. pylori, which resolved after treatment of the infection, and similar cases have been described in adults [35-37]. Although this is low-quality evidence, the potential benefit of this treatment is substantially higher than its risks. (See "Association between Helicobacter pylori infection and gastrointestinal malignancy", section on 'Gastric lymphoma'.)
●Relative indications – H. pylori testing is also appropriate in selected children with the following conditions [46]:
•Chronic immune thrombocytopenia (ITP) – Test for H. pylori in children with chronic ITP but not acute ITP. Case reports describe improvement in chronic ITP after H. pylori eradication [38-45].
•Refractory iron deficiency anemia – Test for H. pylori in children with iron deficiency anemia that is refractory to treatment with iron supplementation and when other possible causes of refractory iron deficiency anemia (eg, celiac disease, inflammatory bowel disease, or eosinophilic gastrointestinal diseases) have been ruled out. Several case reports describe resolution of refractory iron deficiency anemia after eradication of H. pylori [47-49,62,63].
●Testing not indicated – For children, diagnostic testing for H. pylori is not indicated for the following conditions:
•Chronic abdominal pain (without alarm signs)
•Gastroesophageal reflux disease or other peptic symptoms (regardless of whether it is responsive to acid suppression)
•Growth failure or short stature
•Iron deficiency anemia (initial presentation and without alarm signs)
These conditions do not predict the presence of H. pylori infection in children, and, if H. pylori is detected, eradication is unlikely to improve symptoms. Moreover, poorly targeted treatment of H. pylori increases the risk for antibiotic resistance in the population. For some children with functional abdominal pain, a positive test may contribute to anxiety and worsen symptoms. Finally, if H. pylori is treated and eradicated, reinfection can occur, especially in young children and in high-prevalence countries [16,17,64].
For children with epigastric abdominal pain or iron deficiency anemia, performing noninvasive tests for H. pylori is not indicated. Endoscopic evaluation may be indicated if certain alarm signs such as gastrointestinal bleeding, persistent vomiting, or anorexia are present. The goal of the endoscopy is to determine the cause of the symptoms, which include several gastrointestinal conditions in addition to H. pylori-related gastroduodenal disease [65]. If endoscopy is performed, then the decision to test for H. pylori depends on the endoscopic findings (ie, whether peptic ulcer disease or gastric nodularity are identified). (See "Chronic abdominal pain in children and adolescents: Approach to the evaluation", section on 'Patients with alarm findings'.)
Indications for H. pylori testing in adults are broader due to stronger evidence for disease associations in this population and lower rates of reinfection. (See "Indications and diagnostic tests for Helicobacter pylori infection in adults", section on 'Indications for testing'.)
How to test
Pretesting conditions — Ideally, patients should have no exposure to antibiotics for at least four weeks, no proton pump inhibitors (PPIs) for at least two weeks, and no histamine 2 receptor antagonists for at least one day before undertaking H. pylori testing [65]. Exposure to these drugs decreases the sensitivity of any of the below tests for active infection.
Endoscopic tests (recommended) — Endoscopic tests should generally be used for diagnosis of H. pylori in children, rather than noninvasive tests [65]. Endoscopic testing for H. pylori is appropriate because the indication for testing usually arises during a diagnostic endoscopy, when peptic ulcer disease or nodular gastritis are recognized. Moreover, endoscopic-based tests permit antibiotic sensitivity testing and provide the most diagnostic certainty compared with noninvasive tests.
When endoscopic testing for H. pylori is undertaken, at least six gastric biopsies should be performed, with samples for histology, rapid urease testing, and H. pylori culture. Where available, a molecular-based test (polymerase chain reaction [PCR] or fluorescence in situ hybridization [FISH]) can be substituted for the rapid urease test. These molecular tests are more accurate than the rapid urease test in the setting of active upper gastrointestinal bleeding [66,67].
Most children with H. pylori infection have both endoscopic (grossly visible changes such as nodularity, hyperemia, and edema (picture 1)) and histologic evidence of gastritis (picture 2), but some have normal-appearing mucosa [68]. Histopathology should be scored using the updated Sydney System classification for gastritis [65]. In addition, foveolar hyperplasia is a common characteristic of H. pylori-associated gastritis [69].
Noninvasive tests (supportive) — Noninvasive testing is not recommended for the initial diagnosis of H. pylori in children. An exception for noninvasive testing is for the diagnosis of H. pylori in a patient with ITP or family history of gastric cancer in a first-degree relative because these children would not otherwise require an endoscopy [65]. Noninvasive tests are also appropriate to confirm eradication after treatment. (See 'Follow-up' below.)
When noninvasive testing is performed, either of the following may be used:
●H. pylori stool antigen assay – Consisting of a two-step monoclonal enzyme immunoassay. This test is valid for all age groups and is preferred for younger children (rather than the urea breath test) [70].
●Urea breath test – This test is an acceptable alternative for children >6 years who can cooperate with the testing protocol; it has a higher false-positive rate in younger or uncooperative children (due to contamination from oral urease-producing organisms).
In contrast with guidelines for children, noninvasive testing is often used for the initial diagnosis of H. pylori in adults (ie, where breath testing is a principle component of the algorithm for undiagnosed dyspepsia) [71]. This is because there are broader indications for H. pylori testing in adults, several of which do not also require endoscopy. (See "Indications and diagnostic tests for Helicobacter pylori infection in adults", section on 'Diagnostic tests'.)
Serology (not recommended) — Serologic testing for H. pylori has no place in the management of H. pylori infection in children and is not recommended for either diagnosis or follow-up after treatment. These tests have poor sensitivity and specificity and, therefore, low positive predictive value in low-prevalence settings. In addition, these tests do not distinguish between active and past infection.
DIAGNOSIS
●Patients undergoing upper endoscopy – The gold standard for diagnosis is based on tests on biopsies of the gastric antrum (see 'Endoscopic tests (recommended)' above). Criteria for the initial diagnosis of H. pylori infection in children are [65]:
•Positive culture for H. pylori, or
•Evidence of H. pylori on histopathology plus one of the following biopsy-based tests (where available):
-Rapid urease test
-Polymerase chain reaction (PCR)
-Fluorescence in situ hybridization (FISH)
•If histopathology is positive and no other biopsy-based test is available, then a noninvasive test can be used to support the diagnosis
Once the diagnosis is established, a noninvasive test (urea breath or stool antigen test) can be used for follow-up testing post-treatment. (See 'Follow-up' below.)
●Patients in whom endoscopy is not indicated or is contraindicated – A urea breath test or stool antigen assay (preferably monoclonal test and not polyclonal or rapid office-based test) provide reliable evidence of active infection. (See 'Noninvasive tests (supportive)' above.)
These tests can be used to diagnose H. pylori infection in children under the following limited circumstances:
•Patients with a family history of gastric cancer (see 'Noninvasive tests (supportive)' above)
•Follow-up testing to confirm eradication after treatment for documented H. pylori infection (see 'Follow-up' below)
This limited use of noninvasive diagnosis in children reflects the narrow indications for treatment in this age group, for whom treatment is recommended only if there is strong evidence of H. pylori-related pathology. (See 'Indications for treatment in children' below.)
TREATMENT
Indications for treatment in children — In the pediatric age group, H. pylori infection should only be treated if there is a strong suspicion of H. pylori-related disease complications; indications are the same as those for diagnostic testing. (See 'Indications for testing in children' above.)
●Definite indications – The primary indications for treatment are duodenal or gastric ulcers with biopsy-proven H. pylori infection. For these children, it is likely that the peptic ulcer disease is related to H. pylori and treatment of the infection will be beneficial [34,72,73]. The combination of mucosa-associated lymphoid tissue (MALT) lymphoma with H. pylori infection is also an indication for treatment of the infection, although this is very rare and based only on case reports describing resolution of the lymphoma after treatment for H. pylori. Having a first-degree relative with gastric cancer is now an indication for testing for H. pylori infection because evidence demonstrates a reduction in gastric cancer incidence following H. pylori eradication, with no change in all-cause mortality [51].
●Relative indications – Relative indications for treatment are incidental H. pylori infection identified during endoscopy and refractory iron deficiency anemia. For these patients, the decision to treat should be made by the patient and their family after a detailed discussion of the potential benefits and risks of treatment. The family should understand that treatment may not improve symptoms (especially nonspecific abdominal pain), the possibility of treatment failure or reinfection, and the need for close adherence to a complicated treatment regimen for two weeks.
Similarly, the situation occasionally arises where noninvasive testing for H. pylori (eg, stool antigen test) has been performed for a child with functional abdominal pain, although this is not a recommended diagnostic approach (see 'Noninvasive tests (supportive)' above). If the result is positive, the clinician should discuss the pros and cons of further investigation (eg, endoscopy) and/or treatment with the patient and their family.
Anticipatory guidance — For all patients and their families, provide the following anticipatory guidance before embarking on treatment:
●Treatment fails to eradicate H. pylori in at least 20 percent of patients in the real-world setting.
●Effective treatment requires close adherence to a regimen of at least three medicines for two weeks. Missing doses increases the risk for treatment failure and antibiotic resistance [16].
●Even if eradication is successful, some patients may be reinfected, especially young children.
Treatment regimens
●Selection of regimen – Appropriate treatment regimens for children are outlined in the algorithm (algorithm 1) tables (table 1A-B) [65].
Because antibiotic resistance is common, selection of an appropriate regimen should be made based upon antibiotic susceptibility testing for the individual patient, if at all possible [65,73].
If antibiotic susceptibility testing is not available, then quadruple therapy with bismuth should be first-line therapy (where bismuth is available). Eradication rates with bismuth-based quadruple therapy are superior to high-dose amoxicillin triple regimen, based on indirect comparisons in adults with risk factors for macrolide resistance and one small study in Korean children [65,73-77]. The patient's history of antibiotic therapy is also relevant to selecting an appropriate regimen, given the high likelihood of induced resistance. If there is a history of any prior treatment with macrolides (clarithromycin, azithromycin, or others), clarithromycin-based regimens should be avoided. Prior use of amoxicillin does not preclude its use, since amoxicillin resistance is uncommon. (See "Treatment regimens for Helicobacter pylori in adults", section on 'Patients with risk factors for macrolide resistance'.)
●Duration of therapy – We suggest a 14-day course for any of these regimens, based on several lines of indirect evidence: For triple therapy, a 14-day course is associated with significantly higher eradication rates compared with shorter courses of therapy, based primarily on studies in adults [75,78]. For bismuth-based quadruple therapy, a meta-analysis conducted in 2013 showed only marginal benefits of a 14-day versus a shorter treatment course [78]. Moreover, the benefit of the 14-day course is expected to increase with the prevalence of antibiotic-resistant strains, which continues to increase since these studies were conducted [77]. Adherence to therapy is critical to optimize eradication and reduce the risk of inducing antibiotic resistance [65,79].
FOLLOW-UP
Confirmation of eradication — All children who have been treated for H. pylori should undergo follow-up testing to determine whether the infection was eradicated [65]. This testing should be performed at least four weeks after completion of the treatment using a noninvasive test (unless a follow-up endoscopy is otherwise indicated) [65]. Appropriate tests for this purpose are the urea breath test or stool antigen testing [80]. For young children, stool antigen tests are probably more accurate than breath testing. (See 'Noninvasive tests (supportive)' above.)
Antibody testing for H. pylori (in blood, urine, or saliva) is not recommended for diagnosis or follow-up, due to poor sensitivity and specificity and because these tests do not distinguish between active and past infection. (See 'Serology (not recommended)' above.)
If the follow-up test is negative, then no further testing is needed. If the patient remains symptomatic, further evaluation should be tailored to the symptoms and this may include upper endoscopy. Additional courses of treatment should be given only if there is laboratory evidence of persistent H. pylori infection; treatment should not be given empirically based on symptoms.
Rescue therapy for persistent H. pylori infection — Children who have persistent H. pylori infection after completing initial therapy should be treated again with an alternate regimen. Treatment options are limited compared with those for adults since some antibiotic options are not approved or not appropriate for use in children [65].
Examples of appropriate rescue regimens are shown in the table (table 2). The rescue therapy should be tailored to the initial antibiotic susceptibility patterns (if known). If either clarithromycin or metronidazole was included in the initial regimen, that antibiotic should be avoided in the rescue regimen because use of these antibiotics often induces secondary resistance. Similarly, clarithromycin should be avoided if there is a history of any prior treatment with macrolides and levofloxacin should be avoided if there is a history of any prior treatment with fluoroquinolones. By contrast, resistance to amoxicillin or tetracycline is rare and regimens containing these medications can be considered for subsequent rescue therapies. If the patient is thought to have a penicillin allergy but has no history of anaphylaxis, penicillin allergy testing should be considered to confirm or refute penicillin as an allergy and potentially enable its use.
When amoxicillin or metronidazole is used for rescue therapy (ie, if a prior attempt at treatment was unsuccessful), we typically use higher doses (metronidazole 50 mg/kg/day divided three times daily and amoxicillin 75 mg/kg/day divided three or four times daily to avoid low trough levels). Other antibiotic doses are similar to those used for initial therapy, as shown in the table (table 1B).
In addition to selecting a regimen tailored to the antibiotic susceptibility testing and antibiotic history of the individual patient, clinicians should attempt to identify other contributing factors, including inadequate adherence to therapy and insufficient gastric acid suppression, which can occur even with proton pump inhibitors (PPIs). Because inadequate acid suppression is associated with failure of H. pylori eradication, high-dose and more potent PPIs, if available, should be considered in cases of refractory H. pylori infection.
If two treatment attempts are unsuccessful despite good adherence to the regimen, we suggest repeat endoscopy and repeat antibiotic susceptibility testing of the H. pylori strain to guide the selection of subsequent regimens [81]. In some cases, there should be shared decision-making regarding ongoing attempts to eradicate H. pylori. The potential benefits of H. pylori eradication should be weighed carefully against the likelihood of adverse effects and inconvenience of repeated exposure to antibiotics and high-dose acid suppression, particularly in vulnerable populations.
Alternative regimens that have been studied in adults with H. pylori infection include acid suppression with potassium-competitive acid blockers such as vonoprazan, rather than PPIs. Randomized studies in adults and prospective studies in adolescents suggest possible benefits over PPI-based regimens [82,83]. These strategies are discussed separately. (See "Treatment regimens for Helicobacter pylori in adults", section on 'Adjuvant therapies with unclear role'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Helicobacter pylori".)
SUMMARY AND RECOMMENDATIONS
●Clinical manifestations and consequences – H. pylori infection in children is usually asymptomatic. Rarely, H. pylori causes peptic ulcer disease in children, which can manifest as epigastric abdominal pain. However, most children with peptic ulcer disease will have alarm signs (eg, nighttime wakening, occult blood in stool, weight loss or vomiting) that distinguish them from children with functional abdominal pain. (See 'Clinical manifestations and consequences' above.)
●Evaluation
•Testing indicated – The only definite indications for diagnostic testing for H. pylori in children are duodenal and gastric ulcers, ie, peptic ulcer disease, first-degree relative with gastric cancer, and, possibly, mucosa-associated lymphoid tumor (MALT) lymphoma. Relative indications include incidental findings of histopathologic or nodular gastritis during endoscopy (picture 1) and refractory iron deficiency anemia.
•Testing not indicated – Diagnostic testing for H. pylori is not indicated for patients with functional abdominal pain (in the absence of alarm signs such as occult blood in stool, weight loss, or vomiting) or other gastrointestinal symptoms, newly diagnosed iron deficiency anemia, or poor growth. These conditions do not predict the presence of H. pylori infection in children. If H. pylori is detected, eradication is unlikely to improve symptoms and reinfection is common. Moreover, poorly targeted treatment of H. pylori increases the risk for antibiotic resistance in the population. (See 'Indications for testing in children' above.)
•Technique – For initial diagnosis of H. pylori in children:
-Before performing diagnostic testing, patients should have no recent exposure to antibiotics or acid-suppressing medications. (See 'Pretesting conditions' above.)
-In most cases, endoscopic biopsy with confirmatory testing should be used, rather than noninvasive tests. Serology or other antibody-based tests are not recommended. (See 'How to test' above.)
●Diagnostic criteria – Criteria for the initial diagnosis of H. pylori infection in children are a positive culture for H. pylori or evidence of H. pylori on histopathology plus a rapid urease test (or molecular testing on a biopsy sample). A urea breath test or stool antigen assay can be used to diagnose H. pylori infection in children with a first-degree relative with gastric cancer or for follow-up testing after treatment. (See 'Diagnosis' above.)
●Treatment
•Indications – We suggest treatment for any patient in whom the diagnosis of H. pylori infection has been confirmed (Grade 2C), provided that testing was performed for one of the indications listed above.
For patients who are found to have H. pylori infection as an incidental finding of infection at endoscopy, the decision to treat is individualized and depends on the reason for the endoscopy. Individualized decision-making about treatment or further evaluation is also required in the situation where noninvasive testing for H. pylori (eg. stool antigen test) has been performed in a child with functional abdominal pain and the test result is positive (this is not a recommended diagnostic approach). (See 'Indications for treatment in children' above.)
If treatment is undertaken, it is important to educate the family that treatment may not improve symptoms (especially nonspecific abdominal pain) and the need for close adherence to a complicated treatment regimen for two weeks. (See 'Anticipatory guidance' above.)
•Regimens – Appropriate regimens for treating H. pylori in children are outlined in the algorithm (algorithm 1) and tables (table 1A-B). (See 'Treatment regimens' above.)
-We suggest a targeted treatment regimen based upon antibiotic susceptibility testing rather than an empiric regimen (Grade 2C). Targeted therapy is more likely to successfully eradicate the infection and less likely to cause adverse effects or induce antibiotic resistance.
-If the strain is resistant to both clarithromycin and metronidazole or if antibiotic susceptibility is not known, we suggest quadruple therapy with bismuth, a proton pump inhibitor (PPI), and at least two antibiotics (typically amoxicillin and tetracycline for children over the age of eight) rather than triple therapy with high-dose amoxicillin (Grade 2C). Quadruple therapy including bismuth generally has the highest eradication rates in populations with high risk for macrolide resistance, based primarily on studies in adults and on indirect comparisons with other regimens.
-We suggest a 14-day treatment course rather than a shorter course (Grade 2C). This is based on evidence that a 14-day course is more effective for several specific treatment regimens and the increasing prevalence of antibiotic-resistant strains, for which a longer course of antibiotics is likely to be more effective. Adherence to the full course of therapy optimizes eradication and reduces the likelihood of inducing antibiotic resistance.
●Confirmation of eradication – All children who have been treated for H. pylori should undergo follow-up testing to determine whether the infection was eradicated. This testing should be performed at least four weeks after completion of the treatment, using a stool antigen assay or urea breath test (unless a follow-up endoscopy is otherwise indicated). (See 'Confirmation of eradication' above.)
●Rescue therapy – Children who have persistent H. pylori infection after completing initial therapy should be treated again with an alternate regimen (rescue therapy), as outlined in the table (table 2). (See 'Rescue therapy for persistent H. pylori infection' above.)
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