Pediatric Helicobacter Pylori Infection 

Updated: Nov 16, 2018
Author: Mutaz I Sultan, MBChB, MD; Chief Editor: Carmen Cuffari, MD 

Overview

Background

Helicobacter pylori (Hp) is a gram-negative bacillus responsible for one of the most common infections found in humans worldwide.[1] Warren and Marshall first cultured and identified the organism as Campylobacter pylori in 1982. By 1989, it was renamed and recognized to be associated closely with antral gastritis (gastric and duodenal ulcers in adults and children). In recognition of this crucial discovery, they were awarded the Nobel Prize for medicine in 2005. By the early-to-mid 1990s, further evidence supported a link between chronic gastritis of H pylori infection in adults and malignancy, specifically gastric lymphoma and adenocarcinoma.

A fascinating study using the ability of molecular fingerprinting (multilocus sequence typing [MLST]) reported on following the spread of H pylori by human ancestral roots from Africa. Moodley et al estimated that H pylori is approximately as old as modern humans and that migration out of Africa occurred in several waves, the first one 60,000 years ago and the second 52,000 years ago.[2]

Objectives of current and future research on H pylori include improving the understanding of the immunopathogenesis of gastric disease associated with H pylori infection, elucidating the modes of transmission, and improving the safety and efficacy of vaccines to prevent H pylori infection.

Children differ from adults with respect to H pylori infection in terms of the prevalence of the infection, the complication rate, the near-absence of gastric malignancies, age-specific problems with diagnostic tests and drugs, and a higher rate of antibiotic resistance. These and other differences explain why some of the recommendations for adults may not apply in children.[3]


Helicobacter pylori infection revealed by endosco Helicobacter pylori infection revealed by endoscopy (nodular gastropathy).

Helicobacter pylori–associated peptic ulcer in th Helicobacter pylori–associated peptic ulcer in the duodenal bulb.

Pathophysiology

H pylori organisms are spiral-shaped gram-negative bacteria that are highly motile because of multiple unipolar flagella. They are microaerophilic and potent producers of the enzyme urease. H pylori inhabits the mucus adjacent to the gastric mucosa.

Important adaptive features that enhance survival of the organism in an acidic environment include its shape and motility, its reduced oxygen requirement, its adhesion molecules that are trophic to certain gastric cells, and its urease production. Bacterial urease converts urea to ammonium and bicarbonate, neutralizing gastric acid and providing protection in the hostile, highly acidic gastric environment. Some of the lipopolysaccharide of the organism mimics the Lewis blood group antigens in structure. This molecular mimicry also helps in the continued existence of H pylori in the unfavorable gastric environment.[4]

H pylori produces suspected disease-inducing factors, including urease, vacuolating cytotoxin, catalase, and lipopolysaccharide (LPS). Urease, a potent antigen, induces increased immunoglobulin G and immunoglobulin A production. Expression of vacuolating cytotoxin, which induces inflammatory cytokines, may be associated with more pronounced inflammation and increased propensity to cause disease. Catalase helps H pylori survive in the host by preventing the formation of reactive oxygen metabolites from hydrogen peroxide. The LPS outer membrane of H pylori is a less potent inducer of the host complement cascade.

Cytotoxin-associated antigen (CagA) is probably the most important virulence factor in H pylori infection . An individual infected with CagA-negative strains is likely only to develop chronic gastritis and have only a small chance of developing peptic ulcer disease or gastric cancer. In contrast, infection with CagA-positive strains greatly increases the risk of peptic ulcer disease and gastric cancer. Translocating the CagA protein into the gastric epithelial cells causes rearrangement of the host cytoskeleton and alters cell signaling and perturbs cell cycle control. Furthermore, CagA-positive strains are known to induce the expression of a DNA-editing enzyme, which leads to accumulation of mutations in the tumor suppressor p53.[5]

CagA in situ expression is increased in children with H pylori infection who have peptic ulcers and may play a role in the pathogenesis of peptic ulcer disease (PUD).[6]

CagA can be divided in 2 types, the East-Asian type and the Western type, according to the repeat sequences of the 3′ region of cagA. Individuals infected with East-Asian type cagA strains are reported to have higher risk of PUD or gastric cancer than those with Western-type cagA strains.[7]

The association between serum anti-CagA antibodies and gastric cancer in East Asian countries (Japan, Korea, and China) was clarified in a meta-analysis of case-control studies with age and sex-matched controls, in which 10 studies with a total of 4325 patients were identified.[8] CagA seropositivity was associated with gastric cancer compared with gastritis, even in East Asian countries, although the odds ratio (OR) in East Asian countries was smaller than that of another meta-analysis, which included Western countries.

Duodenal ulcer–promoting gene (DupA) is the first genetic factor of H pylori detected to be associated with a differential susceptibility to duodenal ulcer and gastric cancer. Thus, it can be considered a disease-specific virulence marker.[7] The prevalence of dupA was significantly higher in strains from patients with duodenal ulcer but lower in those with gastric cancer (42% vs 9%, on average).

H pylori colonizes the stomach, induces inflammatory cytokines, and causes gastric inflammation. Individuals with H pylori– associated antral-predominant gastritis with increased gastric acid production are prone to PUD.[9] In contrast, H pylori pan-predominant gastritis or corpus-predominant gastritis with decreased gastric acid production are more prone to developing gastric atrophy (intestinal metaplasia and gastric adenocarcinoma).

H pylori has been associated with iron-deficiency anemia. The 2 main hypotheses that potentially explain this relation are (1) sequestration of iron due to antral H pylori infection and (2) decreased non-heme iron absorption caused by hypochlorhydria.

H pylori infection and its association with gastric malignancy have been well described in several epidemiologic studies.[10] However, the course of progression from inflammation to cancer remains unclear. One model describes the stepwise progression of H pylori infection to hypochlorhydria, chronic gastritis, atrophic gastritis, intestinal metaplasia, and gastric cancer. Increased production of the cytokine interleukin 1β has been linked to an increased risk of hypochlorhydria and gastric cancer in infected subjects.

A study found that helicobacter pylori increases cellular proliferation and alters tight junctions by changing the expression of several cancer-related proteins such as beta-catenin, claudin-7, and snail.[11]

A growing area of research interest investigates the hypothesis that H pylori infection may be protective against autoinflammatory diseases such as asthma or inflammatory bowel disease. For example, epidemiologic data suggest that H pylori infection is less common in patients with inflammatory bowel disease, leading investigators to delineate the potential mechanisms underlying these clinical findings.

Epidemiology

Frequency

United States

Overall, approximately one-third of the population is infected with H pylori, increasing with age. See Age.

International

In general, the prevalence is high in developing countries and the infection is acquired at a young age. The incidence is 3-10% of the population each year in developing countries compared with 0.5% in developed countries.[12] The prevalence of H pylori infection is not only lower in industrialized countries than in developing countries, but the incidence of H pylori infection, gastric cancer, and ulcer disease are also declining. Worldwide, more than 1 billion people are estimated to be infected with H pylori. See Age.

Mortality/Morbidity

Most children infected with H pylori are asymptomatic. Antral gastritis is the most common manifestation in children. Duodenal and gastric ulcers may be associated with H pylori gastritis in adults but is uncommon in children. The risk of gastric cancers, including non-Hodgkin lymphoma (eg, mucosa-associated lymphoid tissue [MALT]) and adenocarcinoma, is increased in adults. A study by Lee et al associated eradication of H pylori infection with a reduced incidence of gastric cancer.[13, 14]

The majority of studies have reported a decrease in the incidence and/or prevalence of PUD over time, presumably because of a decrease in H pylori –associated PUD. H pylori was initially responsible for up to 95% of all gastroduodenal ulcers, but more recent studies have reported that the prevalence of H pylori in patients with PUD ranges from 36-73%, depending on ethnicity, geographic factors, and socioeconomic factors.[15]

The relationship between H pylori gastritis and recurrent abdominal pain (RAP) is controversial. The incidence of H pylori gastritis in patients with RAP is not significantly higher than the incidence of H pylori infection in the general population. Although some studies demonstrate an improvement in symptoms in children with RAP and H pylori gastritis after eradication therapy for H pylori, data from a recent double-blind controlled trial did not confirm that finding.[16] The heterogenicity of their definition of RAP and the varying study methodologies may have led to different results and conclusions. The medical positional statement of the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition regarding H pylori infection in children also found no convincing data to support the routine testing of children with RAP for H pylori.[17]

A meta-analysis reviewed published evidence for an association between H pylori infection and GI symptoms in children and found no association between RAP and H pylori infection and found conflicting evidence for an association between epigastric pain and H pylori infection.[18]

Some studies suggest that H pylori protects human subjects from developing gastroesophageal reflux disease, whereas others postulate a causative association between them. A meta-analysis of studies in adults found no association between H pylori eradication and development of new cases of gastroesophageal reflux disease in the population of dyspeptic patients.[19]

One pediatric retrospective study revealed a significantly higher prevalence of reflux esophagitis in children with H pylori infection.[20]

A meta-analysis summarized the existing literature examining the effect that H pylori has on Barrett esophagus. Only few studies without obvious selection and information bias have been conducted to examine the effect of H pylori on Barrett esophagus, but, in these, H pylori infection is associated with a reduced risk of Barrett esophagus.[21]

Controversy exists concerning the relationship of H pylori infection and somatic growth retardation in children. The gastrointestinal hormone ghrelin is a gut-brain peptide that regulates food intake in humans and has strong growth hormone–releasing activity. Decreased appetite in H pylori –infected children has been related to low plasma ghrelin levels, which returned to normal after H pylori eradication.[22]

H pylori infection has also been associated with extraintestinal manifestations, such as immune thrombocytopenic purpura. For adults with immune thrombocytopenic purpura, systematic reviews of past literature have shown an overall platelet response in more than 50% of the patients successfully treated for the infection and increased response rates in countries with a high prevalence of H pylori infection in background populations.[23]

Race

The prevalence is increased in black, Hispanic, Asian, and Native American populations.

Sex

Infection rates are similar in males and females.

Age

In developed countries, less than 10% of children younger than 12 years are infected; however, seropositivity increases with age at a rate of 0.3-1% per year. Studies of seropositivity in adults in developed countries revealed prevalences of 30-50%. In the United States, the estimated prevalence is 20% for people younger than 30 years and 50% for those older than 60 years. In developing countries, the prevalence rates are much higher. The serological prevalence rates of H pylori were 15% and 46% in Gambian children younger than 20 months and age 40-60 months, respectively.[24]

Muhsen et al examined the age of acquisition of H pylori infection in a prospective study on Israeli Arab children in 2 villages with different socioeconomic statuses. Prevalence was 6% in the high socioeconomic status village and 10% in the low socioeconomic village in the first 6 months of life; at 18 months, it increased to 9.6% and 51.9%, respectively.[25]

 

Presentation

History

When obtaining the history of patients with Helicobacter pylori infection, one should pay particular attention to anorexia and weight loss, pallor or laboratory findings of anemia, vomiting, abdominal pain associated with meals or nighttime, and any description of GI bleeding. A history of such findings raises the concern of peptic ulcer disease (PUD).

In the child in whom H pylori infection is suspected, the history should include the following:

  • Character, location, frequency, duration, severity, and exacerbating and alleviating factors of abdominal pain

  • Bowel habits and description of stool

  • Appetite, diet, and weight changes

  • Halitosis, vomiting, and description of gastric material

  • Family history of ulcer disease or GI conditions (eg, Crohn disease)

  • Medications (prescribed and over the counter)

  • Previous diagnostic testing and specific therapy in the GI tract

Physical

Physical examination of an asymptomatic child with H pylori infection usually yields unremarkable findings. In the child with chronic gastritis, duodenitis, and PUD, important examination findings include epigastric tenderness or findings consistent with GI bleeding (eg, guaiac-positive stools, tachycardia, pallor).

Children with PUD leading to complications (eg, severe blood loss in the GI tract, perforation, obstruction) can appear ill and have evidence of hemodynamic instability or signs of an acute abdomen. Children with long-standing PUD from H pylori may become profoundly anemic from undetected chronic bleeding and have no complaints.

  • Assess the general appearance of the child.

  • Assess perfusion, with attention to mental status, heart rate, pulses, and capillary refill.

  • Assess the skin and conjunctivae for pallor.

  • Perform a thorough heart and lung examination.

  • Inspect, auscultate, and palpate the abdomen.

  • Perform rectal examination and a stool guaiac test.

Causes

Epidemiologic studies have addressed various factors, such as bacterial, host, genetic, and environmental factors, to determine the causative links to H pylori infection. Data support person-to-person spread of infection, possibly related to dental plaque, but knowledge of reservoirs and transmission modes is incomplete.

Causes of H pylori infection include the following:

  • Person-to-person transmission of H pylori infection is noted.

    • Infection clusters are noted, particularly in families with infected children. The possible routes are fecal-oral, oral-oral and gastro-oral. Mother-to-child transmission was strongly suggested in a study of DNA analysis of the H pylori strains.[26] The data showed identical H pylori strains between mothers and their toddler-aged children. Moreover, the mother’s symptoms of nausea and vomiting and the use of pacifier were significantly associated with the risk of H pylori infection in children.

    • In a very interesting longitudinal study from the US-Mexican border, Cervantes et al showed that a younger sibling was 4 times more likely to become infected with H pylori if the mother was infected with H pylori compared with an uninfected mother. Younger siblings were 8 times more likely to become infected if their older index sibling had persistent H pylori infection.[27]

    • The possibility of H pylori transmission among children in daycare centers or kindergarten, where interpersonal contacts are common, was also proposed. A meta-analysis of 16 studies did not confirm this hypothesis. The summary OR was 1.12 (95% confidence interval, 0.82–1.52). However, the authors highlighted the limitations of the published studies, including different types of childcare, different age groups, and lack of differences in the exposure duration, with exposure giving a high heterogeneity to the meta-analysis results.[28]

    • Crowding and poor personal hygiene may also play a role.

    • An increased prevalence of H pylori infection is noted in developing countries. This may reflect the combined effects of poor living conditions, poor hygiene, and crowding.

    • In the United States, socioeconomic level is strongly and inversely related to the prevalence of H pylori infection, a finding that may also reflect the same factors as those noted in developing countries.

  • Bacterial factors may play a role in the clinical manifestations of H pylori infection.

    • Patients with H pylori infection have 2 basic phenotypes based on the presence or absence of a vacuolating cytotoxin.

    • People with cytotoxin-positive infection have endoscopically proven inflammation that is more pronounced than those of patients with cytotoxin-negative H pylori infection.

  • Host factors may play a role in the acquisition of H pylori infection.

    • Children may be better able to clear acute infection than adults (2% per year).

    • Hypochlorhydria may be necessary to allow H pylori to colonize in the stomach.

    • Normal gastric epithelial cells that line the stomach are necessary for H pylori persistence. H pylori is not found in atrophied metaplastic epithelium.

  • Data from only one study links an increased prevalence of H pylori infection with a community's water supply.[29]

  • Other possible ways of transmission include vector-borne transmission.[30]

  • H pylori isolates are found more often in personnel who work in the endoscopy suite than in the general population.

 

DDx

 

Workup

Laboratory Studies

The European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition made the following recommendations in 2017 for the Management of Helicobacter pylori in Children and Adolescents[31] :

1. The primary goal of clinical investigation of gastrointestinal symptoms should be to determine the underlying cause of the symptoms and not solely the presence of H pylori infection.

2a. Additional biopsies for rapid urease test and culture should only be taken during endoscopy if treatment is to be offered upon confirmation of infection.

2b. If H pylori infection is an incidental finding at endoscopy, treatment may be considered after a thorough discussion of the risks and benefits of treatment with the patient and or parents.

2c. The guidelines do not recommend a ‘‘test and treat’’ strategy for pediatric H pylori infection.

3. Testing for H pylori should be performed in children with gastric or duodenal ulcers. If H pylori infection is identified, then treatment should be advised and eradication be confirmed.

4. Diagnostic testing for H pylori infection in children with functional abdominal pain is not recommended.

5a. Diagnostic testing for H pylori infection as part of the initial investigation in children with iron deficiency anemia is not recommended.

5b. Testing for H pylori during upper endoscopy may be considered for children with refractory iron deficiency anemia in which other causes have been ruled out.

6. Noninvasive diagnostic testing for H pylori infection may be considered when investigating causes of chronic immune thrombocytopenic purpura.

7. Diagnostic testing for H pylori infection when investigating causes of short stature is not recommended.

8. Wait at least 2 weeks after stopping proton pump inhibitor and 4 weeks after stopping antibiotics before testing for H pylori.

9a. Diagnosis of H pylori infection should be based on either (a) histopathology (H pylori–positive gastritis) plus at least 1 other positive biopsy-based test or (b) positive culture.

9b. During upper endoscopy, at least 6 gastric biopsies should be taken for the diagnosis of H pylori infection.

10. Using antibody-based tests (IgG, IgA) for H pylori in serum, whole blood, urine, and saliva in the clinical setting is not recommended. 

Imaging Studies

See the list below:

  • Imaging studies are not helpful in the diagnosis of H pylori infection. They may be useful in patients with complicated disease (eg, ulcer disease, gastric cancer, MALToma).

Other Tests

See the list below:

  • Urea breath test: The patient ingests a test meal that contains urea labeled with carbon-13 (13 C), which is a nonradioactive isotope. H pylori urease activity produces labeled13 C dioxide that can be detected in exhaled air. A positive result confirms urease activity and H pylori infection. This test is very specific and sensitive in patients older than 6 years. Its most useful application is to verify H pylori eradication after treatment. Experience in children 5 years or younger, particularly in infants, is relatively limited and needs further validation.

Procedures

See the list below:

  • Upper endoscopy (EGD) is the procedure of choice for detecting gastritis, duodenitis, and PUD in the pediatric population.

    • EGD allows for direct visualization of the mucosa; for localization of the source of bleeding; for the detection of H pylori by means of biopsy, culture, and cytology analysis; and for DNA testing by using PCR.

    • In addition, a quick test based on detection of urease activity (a highly specific marker of H pylori) can be performed. The test, termed the Campylobacter -like organism (CLO) test allows for a diagnosis of H pylori infection within 24 hours.

    • Two modified, rapid urease test kits are now commercially available and are reported to have better accuracy, a shorter reaction time, and better cost-effectiveness than those of the CLO test.

    • In children, endoscopy may reveal a nodular appearance in the gastric antrum resulting from lymphoid hyperplasia.[32] However, only approximately 50% of affected children have endoscopic evidence of changes of H pylori gastritis.

    • The gross appearance of an active ulcer is a round or oval, punched-out lesion with a smooth, white base and with surrounding mucosa that is red and edematous. In H pylori infection, the most common location for ulceration is the duodenal bulb.

    • Biopsy specimens obtained in the prepyloric antrum have the highest yield in H pylori infection. Tissue specimens are often also obtained from the body and the transition zones of the stomach, particularly if the patient has recently taken acid-suppressing medication.

  • Endoscopic biopsy is indicated for the following reasons:

    • Histologic examination of gastric tissue

    • Rapid urease testing (eg, CLO test)

    • Culture of organisms

    • PCR testing to identify H pylori DNA

Histologic Findings

See the list below:

  • Histologic findings include a superficial infiltrate with substantial numbers of plasma cells and lymphocytes within the gastric mucosa and organisms visible on Giemsa, Diff-Quick, or hematoxylin and eosin staining. Sensitive staining for small numbers of bacteria is possible using silver stains such as Genta or Warthin-Starry.

Staging

See the list below:

  • Although a staging system for the H pylori infection has not been established, several steps in disease progression are well described.

  • The first step is chronic gastritis, which is followed by the second step, atrophic gastritis. The third step is intestinal metaplasia, which may evolve into dysplasia. The last step in this process is gastric adenocarcinoma.

  • This process is very slow (ie, decades) and may stop at any step because gastric cancers probably require several other factors to develop, not only an H pylori infection.

 

Treatment

Medical Care

Antibiotic resistance is the major cause of failure in the treatment of H pylori infection.[44, 45] Most of the studies worldwide confirmed an increase in macrolide resistance, while metronidazole resistance either decreased or remained stable. In a prospective multicenter European study, primarily comprised of adults, Megraud et al found a 31.8% resistance rate to clarithromycin and 25.7% to metronidazole in the 311 H pylori isolates from children from the 8 countries included in the study.[33]

If the strain is resistant to one of the antibiotics used, treatment success will be compromised. As a result therapies that are recommended should be based on antibiotic susceptibility testing. If this testing is not available, then clarithromycin-based triple therapy should not be used as part of first-line therapy due to high rates of clarithromycin resistance rates.[31]

The European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition made the following recommendations in 2017 for the Management of Helicobacter pylori in Children and Adolescents[31] :

1. Antimicrobial sensitivity should be obtained for the infecting H pylori strain (s), and eradication therapy tailored accordingly.

2. The effectiveness of first-line therapy should be evaluated in national/regional centers.

3. The physician should explain to the patient/family the importance of adherence to the anti–H pylori therapy to enhance successful eradication.

The recommendations also included practice points for the first-line therapy for H pylori infection:

  • If the strain is susceptible to clarithromycin (CLA) and to metronidazole (MET), triple therapy (PPI, amoxicillin [AMO], CLA) for 14 days is the preferred choice.
  • Sequential therapy for 10 days (proton pump inhibitor (PPI) with amoxicillin for 5 days followed by proton pump inhibitor with clarithromycin and metronidazole for 5 days) is equally effective in patients infected with fully susceptible strains. However, sequential therapy has the disadvantage of exposing the child to 3 different antibiotics. Sequential therapy should not be given if the strain is resistant to metronidazole (MET) or clarithromycin (CLA), or if susceptibility testing is not available. The most recent adult guidelines recommend against the use of sequential therapy as first- or second-line therapy.
  • Doses of proton pump inhibitor and antibiotics should be calculated based on the bodyweight.
  • A higher degree of acid suppression improves the success rate of amoxicillin- and clarithromycin-based therapy. Younger children need a higher PPI dose per kg bodyweight compared to adolescents and adults to obtain sufficient acid suppression.
  • Esomeprazole and rabeprazole are less susceptible to degradation by rapid metabolizers with CYP2C19 genetic polymorphism, and therefore, may be preferred when available.
  • For children younger than 8 years, bismuth quadruple therapy refers to bismuth, PPI, AMO, and MET. In children older than 8 years, bismuth quadruple therapy refers to bismuth, PPI, MET, and tetracycline.
  • Current evidence does not support the routine addition of either single or combination probiotics to eradication therapy to reduce side effects and/or improve eradication rates.
  • The outcome of anti–H pylori therapy should be assessed at least 4 weeks after completion of therapy using one of the following tests:
    • (a) The 13C-urea breath (13C-UBT) test or (b) a 2-step monoclonal stool antigen test.
  • When H pylori treatment fails, rescue therapy should be individualized considering antibiotic susceptibility, the age of the child, and available antimicrobial options.

Rescue therapy should be based on antibiotic resistance profiles when it is possible. Studies in adults suggest that increasing acid suppression and metronidazole dose may improve efficacy of eradication therapy. One study showed that in children infected with clarithromycin- and metronidazole-resistant strains, the eradication rate using high dose amoxicillin and PPI with metronidazole was 66% in intention to treat analysis.[31]

In a recent multicenter, open-label, single-arm, clinical trial of H pylori–positive adults who had failed more than one previous course of omeprazole-amoxicillin-clarithromycin therapy, a quadruple regimen of bismuth, metronidazole, and tetracycline plus omeprazole produced a high eradication rate (up to 95.8%).[34]

 

 

Surgical Care

See the list below:

  • Surgical procedures are rarely necessary in the treatment of patients with H pylori infection. However, in ulcer disease, surgery may be necessary for certain complications unresponsive to medical therapies, including intractable abdominal pain, gastric outlet obstruction, perforation, and severe bleeding.

Consultations

See the list below:

  • Pediatric gastroenterologist - For evaluation, endoscopy, and biopsy testing to confirm H pylori infection and exclude other causes of abdominal pain or bleeding

  • Surgeon - For intervention in patients with severe or intractable pain or bleeding or in patients with GI tract perforation or obstruction

  • Radiologist - For patients who require upper-GI imaging with contrast-enhanced studies

Diet

See the list below:

  • Foods such as berry juice and some dairy products may have modest bacteriostatic effect on H pylori.

  • Two randomized, placebo-controlled trials evaluated the effect of probiotic food as an adjuvant to the standard triple therapy for eradication of H pylori infection in children and showed conflicting results.[35, 36]

  • In a recent prospective study in adults, addition of vitamin C to an H pylori treatment regimen of amoxicillin, metronidazole, and bismuth can significantly increase H pylori eradication rate.[37]

Activity

See the list below:

  • No specific restrictions of activities are necessary for the child with H pylori infection.

Prevention

A study by Zeng et al aimed to assess the efficacy, safety, and immunogenicity of a three-dose oral recombinant H pylori vaccine in children in China. The study tested the effectiveness of the vaccine on 4,446 children with a three-dose vaccination schedule. The study recorded 64 events of H pylori infection within the first year which resulted in a vaccine efficacy of 71.8%. 157 (7%) participants in the vaccine group and 161 (7%) participants in the placebo group reported at least one adverse reaction that were reported as mild.[38, 39]

 

Guidelines

Guidelines Summary

Previous guideline recommendations of triple or sequential therapy for treatment-naïve H pylori–infected children and adolescents can no longer be supported. Instead, to achieve an initial eradication success rate of 90% and higher, therapy should be based on knowledge of antibiotic resistance profiles and therapy tailored accordingly using sufficiently high doses and treatment durations of 10 to 14 days. Clarithromycin-containing regimens should be restricted to those infected with clarithromycin-susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with PPI, amoxicillin, and metronidazole for 14 days is recommended as first-line therapy. Bismuth-based quadruple therapy can also be considered for first-line therapy in countries where it is licensed for use in children.[31]

 

Medication

Antibiotics, beta-lactams

Class Summary

The beta-lactam used to treat patients with H pylori infection is stable in an acid environment, binds to proteins within bacterial cell walls, induces direct wall lysis, and inhibits cell-wall synthesis.

Amoxicillin (Amoxil, Polymox, Trimox, Wymox)

Bactericidal activity against H pylori. Available as gtt 50 mg/mL; susp 125, 200, 250, or 400 mg/5 mL; cap 250 or 500 mg; and chewable tab 125, 200, 250, or 400 mg.

Antibiotics, macrolides

Class Summary

The macrolide used in the treatment of H pylori infection is stable in the gastric environment, enters the bacterial cell, binds to receptors on the ribosomal subunits, and inhibits bacterial protein synthesis.

Clarithromycin (Biaxin)

Provides bacteriocidal activity against H pylori with antimicrobial spectrum similar to that of erythromycin but more stable in acid environment and has fewer adverse GI effects. Available as granules for susp 125 or 250 mg/5 mL and film tab: 250 or 500 mg.

Antibiotics, antiprotozoals

Class Summary

This antibiotic, used in the treatment of patients with H pylori infection, produces intracellular products that damage bacterial DNA.

Metronidazole (Flagyl, Protostat)

Metronidazole diffuses into all tissues well, is stable in an acidic pH environment, and provides bactericidal activity against H pylori. Available as compounded extemporaneous susp 50 or 100 mg/5 mL, tab 250 or 500 mg, and cap 375 mg.

Antibiotics, tetracyclines

Class Summary

Tetracyclines bind to ribosomal subunits and inhibit protein synthesis of susceptible bacteria. Use in pediatric patients should be restricted to children in whom other antibiotic regimens fail.

Tetracycline HCL (Achromycin, Sumycin, Terramycin)

Bacteriostatic, but may be bactericidal at high concentrations. Available as tab 250 or 500 mg, cap 100, 250, or 500 mg, and susp 125 mg/5 mL.

H2-receptor antagonists

Class Summary

Receptors for H2 are located on the acid-producing parietal cells. Blocking histamine action suppresses gastric acid secretion.

Ranitidine (Zantac)

H2 antagonists prescribed for 8 wk, when most non– H pylori -associated ulcers heal. H2 blockers have no antibacterial effect; therefore, must be used with antibiotics to eradicate H pylori. Available as syr 15 mg/mL, tab 75, 150, or 300 mg; and effervescent tab 150 mg.

PPIs

Class Summary

This class of drugs, which includes acid inhibitors more potent than the H2-receptor antagonists, blocks gastric acid secretion at the proton (Na+/H+ ATPase) pump, the final common pathway of secretion. This class is recommended as part of a drug regimen in symptomatic patients with H pylori infection. Similar to H2-receptor blockade, proton pump inhibitor (PPI) therapy alone does not eradicate H pylori infection; however, bacteriostatic activity against H pylori occurs.

Omeprazole (Prilosec)

Potent blocker of gastric acid. Best administered just before first meal of day. Enteric-coated granules in cap ensure appropriate bioavailability. For children unable to swallow intact cap, open and place granules in acidic substance (eg, apple sauce or apple juice), which is preferred to administering less bioavailable susp. Available as SR cap 10 or 20 mg and granules for PO susp 20 or 40 mg/packet.

Lansoprazole (Prevacid)

Potent blocker of gastric acid. Best administered just before first meal of day. Enteric-coated granules in the cap ensure appropriate bioavailability. For children unable to swallow intact cap, open and place granules in acidic substance (eg, apple sauce or apple juice), which is preferred to administering less bioavailable susp. Available as delayed-release cap 15 or 30 mg and granules for PO susp 15 mg or 30 mg/packet.

Bismuths

Class Summary

Bismuth subsalicylate and bismuth subcitrate have complementary effects with most antimicrobials. Bismuth disrupts bacterial cell walls. Bismuth is particularly effective in lysing the cell wall of the organism when the organism is close to the gastric epithelium and relatively inaccessible to most antimicrobial agents.

Bismuth subsalicylate (Pepto-Bismol)

Lyses bacterial cell walls, prevents organism adhesion to epithelium, and inhibits urease.

Available as (subsalicylate) chewable tab 262 mg and liquid 262 mg or 525 mg/15 mL.

 

Follow-up

Further Outpatient Care

See the list below:

  • Further outpatient care includes monitoring patient symptoms, assessing patient tolerance for the treatment regimen, and follow-up testing to confirm efficacy of treatment. Follow-up testing should occur at least 6 weeks and preferably 3 months after the completion of therapy.

Further Inpatient Care

In the child with Helicobacter pylori infection who has complications of ulcer disease, including bleeding, severe pain, perforation, or obstruction, inpatient care must include the following:

  • Attention to airway, breathing, and circulatory status

  • Monitoring and fluid resuscitation, with consideration of transfusion

  • Careful nasogastric lavage in the setting of upper-GI bleeding

  • Antacid therapy with proton pump inhibitors (PPIs) at full dosage

  • Appropriate consultation with specialists for endoscopy or other procedures

  • In the child with stress-induced peptic ulcer disease (PUD), treatment of underlying severe medical illness or traumatic injury

Inpatient & Outpatient Medications

See the list below:

  • Patients should avoid all irritating medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, and corticosteroid preparations.

  • Iron-replacement therapy is needed for iron-deficiency anemia.

Transfer

See the list below:

  • Transfer to a tertiary care children's hospital may be required for the child who is seriously ill and requires critical care or for the patient who needs emergency subspecialty diagnostic and therapeutic intervention.

Deterrence/Prevention

See the list below:

  • The mode of transmission of H pylori infection is not fully understood.

  • Data from epidemiologic studies suggest the following measures may help reduce transmission:

    • Policies that support the improvement of living conditions, particularly in developing countries

    • For all patients with chronic GI tract symptoms, appropriate referral for definitive diagnosis and treatment, which may help effect a cure and prevent exposure to family members and close contacts

    • Vaccines against H pylori infection: Several studies, performed with urease-based vaccines, showed limited immunogenicity and scarce efficacy in humans. The vaccine based on recombinant CagA–VacA–NAP proteins showed good immunogenicity and safety profile in phase I, but no subsequent efficacy trials were reported. No further results on clinical trials of H pylori vaccines were disclosed in the most recent years. Presently, there is no licensed anti– H pylori vaccine.[40]

Complications

See the list below:

  • PUD - Perforation, GI bleeding

  • Iron-deficiency anemia

  • Malignancy

    • Gastric mucosa-associated lymphoid tissue (MALT) lymphoma

    • Adenocarcinoma of the gastric body and antrum

  • Gastric-outlet obstruction

  • Increased susceptibility to enteric infections such as salmonellosis and giardiasis due to H pylori- induced hypochlorhydria

Prognosis

See the list below:

  • The outlook for eradicating H pylori infection with multidrug therapy is good, with reported efficacy rates as high as 95%.

  • Unsuccessful therapy often results from the patient's noncompliance with the medication regimen or from antimicrobial resistance.

  • Once cure is achieved, long-term reinfection rates are low. Among children living in developing countries or among families with infected members, reinfection rates may be increased.

Patient Education

See the list below:

  • At present, the nature of transmission of H pylori infection is not fully understood. Therefore, the ability to implement appropriate infection control or preventive measures is limited.

  • The theory that H pylori requires person-to-person transmission, supported by data from epidemiologic studies, may prove instrumental in promoting policies that improve living conditions and sanitation and to reduce crowding.

  • The true effect of educational efforts to reduce H pylori transmission in the patient's family (eg, teaching children about appropriate hygiene and toilet practices) is unknown. However, such efforts may be a part of a common-sense approach to reducing transmission of all pathogens infecting the GI tract.

 

Questions & Answers

Overview

What is pediatric Helicobacter pylori (Hp) infection?

What is the pathophysiology of pediatric Helicobacter pylori (Hp) infection?

Which conditions are associated with Helicobacter pylori (Hp) infection?

What is the role of Helicobacter pylori (Hp) infection in the development of autoinflammatory diseases?

What is the prevalence of Helicobacter pylori (Hp) infection in the US?

What is the global prevalence of Helicobacter pylori (Hp) infection?

What is the morbidity associated with Helicobacter pylori (Hp) infection?

What are the racial predilections of Helicobacter pylori (Hp) infection?

What are the sexual predilections of Helicobacter pylori (Hp) infection?

Which age groups have the highest prevalence of Helicobacter pylori (Hp) infection?

Presentation

What is the focus of clinical history for pediatric Helicobacter pylori (Hp) infection?

Which physical findings are characteristic of pediatric Helicobacter pylori (Hp) infection?

What is included in the physical exam of pediatric Helicobacter pylori (Hp) infection?

What causes pediatric Helicobacter pylori (Hp) infection?

What are the risk factors for person-to-person transmission of pediatric Helicobacter pylori (Hp) infection?

What is the role of bacterial factors in the etiology of Helicobacter pylori (Hp) infection?

Which host factors increase the risk for Helicobacter pylori (Hp) infection?

What are the less common causes of Helicobacter pylori (Hp) infection?

DDX

What are the differential diagnoses for Pediatric Helicobacter Pylori Infection?

Workup

What are the ESPGHAN/NASPGH diagnostic guidelines for pediatric Helicobacter pylori (Hp) infection?

What is the role of imaging studies in the diagnosis of pediatric Helicobacter pylori (Hp) infection?

What is the role of a urea breath test in the diagnosis of pediatric Helicobacter pylori (Hp) infection?

What is the role of upper endoscopy (EGD) in the diagnosis of pediatric Helicobacter pylori (Hp) infection?

When is endoscopic biopsy indicated for the diagnosis of pediatric Helicobacter pylori (Hp) infection?

Which histologic findings are characteristic of pediatric Helicobacter pylori (Hp) infection?

How is pediatric Helicobacter pylori (Hp) infection staged?

Treatment

How are pediatric Helicobacter pylori (Hp) infections treated?

What are the ESPGHAN/NASPGH treatment guidelines for pediatric Helicobacter pylori (Hp) infection?

What is the efficacy of combination therapies for the treatment of pediatric Helicobacter pylori (Hp) infection?

What is the role of surgery in the treatment of pediatric Helicobacter pylori (Hp) infection?

Which specialist consultations are beneficial in the treatment of pediatric Helicobacter pylori (Hp) infection?

Which dietary modifications are used in the treatment of pediatric Helicobacter pylori (Hp) infection?

Which activity modifications are used in the treatment of pediatric Helicobacter pylori (Hp) infection?

What is the efficacy of vaccines against pediatric Helicobacter pylori (Hp) infection?

Guidelines

What is the role of triple or sequential therapy in the treatment of pediatric Helicobacter pylori (Hp) infection?

Follow-up

What is included in long-term monitoring of pediatric Helicobacter pylori (Hp) infections?

What is included in inpatient care for the complications of Helicobacter pylori (Hp) infection?

Which medications should be avoided during the treatment of pediatric Helicobacter pylori (Hp) infection?

When is iron-replacement therapy indicated in the treatment of pediatric Helicobacter pylori (Hp) infection?

When is patient transfer indicated for the treatment of pediatric Helicobacter pylori (Hp) infection?

How is pediatric Helicobacter pylori (Hp) infection prevented?

What are the possible complications of pediatric Helicobacter pylori (Hp) infection?

What is the prognosis of pediatric Helicobacter pylori (Hp) infection?

What is included in patient educations about Helicobacter pylori (Hp) infection?

Medications

Which medications in the drug class Bismuths are used in the treatment of Pediatric Helicobacter Pylori Infection?

Which medications in the drug class PPIs are used in the treatment of Pediatric Helicobacter Pylori Infection?

Which medications in the drug class H2-receptor antagonists are used in the treatment of Pediatric Helicobacter Pylori Infection?

Which medications in the drug class Antibiotics, tetracyclines are used in the treatment of Pediatric Helicobacter Pylori Infection?

Which medications in the drug class Antibiotics, antiprotozoals are used in the treatment of Pediatric Helicobacter Pylori Infection?

Which medications in the drug class Antibiotics, macrolides are used in the treatment of Pediatric Helicobacter Pylori Infection?

Which medications in the drug class Antibiotics, beta-lactams are used in the treatment of Pediatric Helicobacter Pylori Infection?