AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

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). 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.

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.

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.

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 and enhances the ability of H pylori to colonize the stomach.

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 peptic ulcer disease (PUD).² 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 recently 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.³ 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.

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 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.
• 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.⁴

Race

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

Sex

Infection rates are similar in males and females.

Age

Infection in young children is rare.

• 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.
• See Mortality/Morbidity.

CLINICAL

Section 3 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

History

When obtaining the history, 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 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
• Family and social stressors
• Alcohol ingestion and smoking habits

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 vital signs.
• Assess perfusion, with attention to mental status, heart rate, pulses, and capillary refill.
• Assess hydration status, with attention to the presence of moisture in the mucous membranes and skin turgor.
• 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.
• Perform pelvic examination in the sexually active female patient with pain.

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. Mother-to-child transmission was strongly suggested in a study of DNA analysis of the H pylori strains.⁵ The data showed identical H pylori strains between mothers and their toddler-aged children.
  • 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.
• Genetic factors may play a role in H pylori infection.
• • The incidence of H pylori infection is increased in first-degree relatives of children with PUD.
  • Concordance for PUD is higher in monozygotic than in dizygotic twins.
• Data from only one study links an increased prevalence of H pylori infection with a community's water supply.⁶
• H pylori isolates are found more often in personnel who work in the endoscopy suite than in the general population.

DIFFERENTIALS

Section 4 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Other Problems to be Considered

Eosinophilic esophagitis
Eosinophilic gastroenteritis
Gastritis, induced by nonsteroidal anti-inflammatory drugs (NSAIDs)
Gastritis, stress induced
Functional abdominal pain
Functional dyspepsia
Celiac disease

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Lab Studies

• Serologic assay of H pylori  immunoglobulin G 
• • This test has good specificity, but its sensitivity is rather poor, with better correlation with active disease in adults than in children.
  • In the pediatric population, serology has a sensitivity of 69%, a specificity of 78%, but a positive predictive value of only 31%.
  • The test is most useful when the result is negative and excludes H pylori.
  • Antibody levels are persistently high long (6-12 mo) after treatment.
• Fecal H pylori-antigen test: A test to detect H pylori antigen in feces is available as both a pretreatment tool and, especially, as a posttreatment diagnostic tool.
• Antibody testing of urine and H pylori DNA polymerase chain reaction (PCR) in saliva⁷
• • The sensitivity is lower than that of serology.⁸
  • A PCR assay in which primers are used against part of the H pylori urease gene (urea) has been developed and reportedly has a sensitivity and a specificity similar to that of histologic examination.

Imaging Studies

• Upper-GI series findings help in detecting PUD in approximately 70% of children with the disease. A double-contrast study has a detection rate higher than that of a single-contrast study, but the child must be older and cooperative, and the test increases the radiation exposure.
• No radiologic test is equal to esophagogastroduodenoscopy (EGD) in assessing PUD (see Procedures).
• Radiologic findings of duodenal ulcers include filling defects or deformities of the duodenal bulb.
• A fibrinous clot in the ulcer may lead to a false-normal radiologic appearance. False-positive findings with barium studies have been noted to be especially high in pediatric patients.
• Findings on an upper-GI series can depict gastric-outlet obstruction, the result of pyloric lesions.

Other Tests

• Urea breath test: The patient ingests a test meal that contains urea labeled with carbon-13 (¹³C), which is a nonradioactive isotope. H pylori urease activity produces labeled ¹³C 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. Its most useful application is to verify H pylori eradication after treatment.

Procedures

• 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.⁹ 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.
  • Therapeutic endoscopy for acute bleeding (ie, the injection of sclerosing or vasoconstricting agents) is only rarely necessary for patients with H pylori but is another important indication for EGD.
• 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

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.

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical Care

Treatment of H pylori infection is indicated in children with associated PUD. Iron-deficiency anemia that is refractory to treatment is another indication for testing and treatment of H pylori infection. Whether H pylori screening is necessary in asymptomatic children is unclear because the risk of gastric cancer is low. The risk of gastric cancer in patients with H pylori infection is about 1%, and the risk of MALT is even lower at 0.7 cases per 100,000 patients. The current approach is to treat patients with H pylori infection with a family history of gastric cancer and documented MALT lymphoma.

Initial treatment typically requires a triple therapy with 2 antibacterial agents and an acid inhibitor, typically a proton-pump inhibitor (PPI). Drug regimens most often include 2 weeks of antibacterial therapy concomitant with 4 weeks of acid suppression.

In adults, standard Maastricht triple therapy includes a combination of a PPI, amoxicillin, and clarithromycin. In the event eradication fails, a quadruple therapy that includes a PPI or a histamine-2 (H2) blocker, bismuth, metronidazole, and a tetracycline has been suggested. Other second-line regimens for adults are available, such as a regimen that includes a PPI, furazolidone, and clarithromycin or a 7-day course of a PPI, levofloxacin, and clarithromycin.

In children, the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) has recommended the following 3 first-line regimens for children: (1) amoxicillin, clarithromycin, and a PPI; (2) amoxicillin, metronidazole, and a PPI; and (3) clarithromycin, metronidazole, and a PPI. The recommended duration of therapy is 14 days of the antimicrobial agents and 1 month of the PPI. In a double-blind clinical trial, the eradication rate was decreased with a 7-day course of therapy, although the doses of the antibiotics used in the trial were lower than those the NASPGHAN recommended.¹⁰

Eradication failures in children are mostly due to noncompliance because of adverse effects or resistance to metronidazole and clarithromycin. Adverse effects can be reduced by probiotic supplementation such as Lactobacillus GG. If treatment fails, antimicrobial sensitivities can be helpful in selecting antibiotics. Stool antigen testing may also have a role in predicting H pylori antibiotic resistance. Reinfection after successful eradication of H pylori is uncommon in developed countries.

Surgical Care

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

• 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

Foods such as berry juice and some dairy products may have modest bacteriostatic effect on H pylori. Probiotics may have a role as an adjunct to standard triple-therapy regimens because they have been shown to decrease adverse effects. For the child with symptomatic gastritis or an ulcer, restrictions of spicy or caffeine-containing foods and beverages are recommended.

Activity

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

MEDICATION

Section 7 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Drug Category: Antibiotics, beta-lactams

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.

Drug Category: Antibiotics, macrolides

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.

Drug Category: Antibiotics, antiprotozoals

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

Drug Category: Antibiotics, tetracyclines

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.

Drug Category: H2-receptor antagonists

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

Drug Category: PPIs

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, PPI therapy alone does not eradicate H pylori infection; however, bacteriostatic activity against H pylori occurs.

Drug Name	Lansoprazole (Prevacid)
Description	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.
Adult Dose	30 mg/d PO
Pediatric Dose	1-2 mg/kg/d PO
Contraindications	Documented hypersensitivity
Interactions	May decrease effects of ampicillin, iron salts, digoxin, itraconazole and ketoconazole; sucralfate delays and decreases absorption by 30% (should be taken at least 30 min before sucralfate); mildly increases theophylline clearance (about 10%); may increase warfarin effects
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Common adverse effects are headaches, nausea, diarrhea, and vomiting; do not chew granules

Drug Category: Bismuths

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.

FOLLOW-UP

Section 8 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Further Inpatient Care

In the child with 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 PPIs at full dosage
• Appropriate consultation with specialists for endoscopy or other procedures
• In the child with stress-induced PUD, treatment of underlying severe medical illness or traumatic injury

Further Outpatient Care

• 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.
• Screening of all household members for H pylori infection is recommended because of the high rate of spreading of the infection in a closed community, particularly among those living in crowded conditions. However, H pylori reinfection from family members after successful eradication is unlikely.

In/Out Patient Meds

• Patients should avoid all irritating medications, including NSAIDs, aspirin, and corticosteroid preparations.
• Iron-replacement therapy is needed for iron-deficiency anemia.

Transfer

• 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

• 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
  • Human vaccines against H pylori infection (in early in phase II clinical trials)
  • With described family clusters of disease or disease recurrence in patients, possible screening and treatment of family members of the infected patient

Complications

• PUD - Perforation, GI bleeding
• Iron-deficiency anemia
• Malignancy
• • Gastric MALT lymphoma
  • Adenocarcinoma of the gastric body and antrum
• Gastric-outlet obstruction
• Growth failure
• Increased susceptibility to enteric infections such as salmonellosis and giardiasis due to H pylori-induced hypochlorhydria

Prognosis

• 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

• 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.

MISCELLANEOUS

Section 9 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to consider H pylori infection as the source of symptoms
• Failure to appropriately refer patients for diagnostic testing
• Failure to use a multidrug regimen to eradicate infection

ACKNOWLEDGMENTS

Section 10 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Meta Carroll, MD to the development and writing of this article.

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Media file 1:  Helicobacter pylori infection revealed by endoscopy.
	View Full Size Image
Media type:  Image

Media file 2:  Histologic examination by using hematoxylin and eosin stain (left) and Diff-Quick stain (right).
	View Full Size Image
Media type:  Image

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

1. Blecker U. Helicobacter pylori-associated gastroduodenal disease in childhood. South Med J. Jun 1997;90(6):570-6; quiz 577. [Medline].
2. Baysoy G, Ertem D, Ademoglu E, et al. Gastric histopathology, iron status and iron deficiency anemia in children with Helicobacter pylori infection. J Pediatr Gastroenterol Nutr. Feb 2004;38(2):146-51. [Medline].
3. Williams MP, Pounder RE. Helicobacter pylori: from the benign to the malignant. Am J Gastroenterol. Nov 1999;94(11 Suppl):S11-6. [Medline].
4. Ashorn M, Rago T, Kokkonen J, et al. Symptomatic response to Helicobacter pylori eradication in children with recurrent abdominal pain: double blind randomized placebo-controlled trial. J Clin Gastroenterol. Sep 2004;38(8):646-50. [Medline].
5. Konno M, Fujii N, Yokota S, et al. Five-year follow-up study of mother-to-child transmission of Helicobacter pylori infection detected by a random amplified polymorphic DNA fingerprinting method. J Clin Microbiol. 43(5):2246-50. [Medline]. [Full Text].
6. Ahmed KS, Khan AA, Ahmed I, et al. Impact of household hygiene and water source on the prevalence and transmission of Helicobacter pylori: a South Indian perspective. Singapore Med J. Jun 2007;48(6):543-9. [Medline].
7. Booka M, Okuda M, Shin K, et al. Polymerase chain reaction--restriction fragment length polymorphism analysis of clarithromycin-resistant Helicobacter pylori infection in children using stool sample. Helicobacter. Jun 2005;10(3):205-13. [Medline].
8. Bonamico M, Strappini PM, Bonci E, et al. Evaluation of stool antigen test, PCR on ORAL samples and serology for the noninvasive detection of Helicobacter pylori infection in children. Helicobacter. Feb 2004;9(1):69-76. [Medline].
9. Bujanover Y, Konikoff F, Baratz M. Nodular gastritis and Helicobacter pylori. J Pediatr Gastroenterol Nutr. Jul 1990;11(1):41-4. [Medline].
10. Bhasin DK, Sharma BC, Ray P, et al. Comparison of seven and fourteen days of lansoprazole, clarithromycin, andamoxicillin therapy for eradication of Helicobacter pylori: a report from India. Helicobacter. Jun 2000;5(2):84-7. [Medline].
11. Ables AZ, Simon I, Melton ER. Update on Helicobacter pylori treatment. Am Fam Physician. Feb 1 2007;75(3):351-8. [Medline].
12. Blecker U, Hauser B, Lanciers S, et al. The prevalence of Helicobacter pylori-positive serology in asymptomatic children. J Pediatr Gastroenterol Nutr. Apr 1993;16(3):252-6. [Medline].
13. Cammarota G, Cianci R, Cannizzaro O, et al. High-dose versus low-dose clarithromycin in 1-week triple therapy, including rabeprazole and levofloxacin, for Helicobacter pylori eradication. J Clin Gastroenterol. Feb 2004;38(2):110-4. [Medline].
14. Chong SK, Lou Q, Asnicar MA, et al. Helicobacter pylori infection in recurrent abdominal pain in childhood: comparison of diagnostic tests and therapy. Pediatrics. Aug 1995;96(2 Pt 1):211-5. [Medline].
15. Czinn SJ. Helicobacter pylori infection: detection, investigation, and management. J Pediatr. Mar 2005;146(3 Suppl):S21-6. [Medline].
16. Drumm B. Helicobacter pylori in the pediatric patient. Gastroenterol Clin North Am. Mar 1993;22(1):169-82. [Medline].
17. El-Omar EM, Oien K, Murray LS, et al. Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylori. Gastroenterology. Jan 2000;118(1):22-30. [Medline].
18. Ernst PB, Gold BD. Helicobacter pylori in childhood: new insights into the immunopathogenesis of gastric disease and implications for managing infection in children. J Pediatr Gastroenterol Nutr. May 1999;28(5):462-73. [Medline].
19. Farrell MK. Dr. Apley meets Helicobacter pylori. J Pediatr Gastroenterol Nutr. Feb 1993;16(2):118-9. [Medline].
20. Feydt-Schmidt A, Kindermann A, Konstantopoulos N, et al. Reinfection rate in children after successful Helicobacter pylori eradication. Eur J Gastroenterol Hepatol. Oct 2002;14(10):1119-23. [Medline].
21. Fiedorek SC, Casteel HB, Pumphrey CL, et al. The role of Helicobacter pylori in recurrent, functional abdominal pain in children. Am J Gastroenterol. Mar 1992;87(3):347-9. [Medline].
22. Gillen D, el-Omar EM, Wirz AA, et al. The acid response to gastrin distinguishes duodenal ulcer patients from Helicobacter pylori-infected healthy subjects. Gastroenterology. Jan 1998;114(1):50-7. [Medline].
23. Glassman MS. Helicobacter pylori infection in children. A clinical overview. Clin Pediatr (Phila). Aug 1992;31(8):481-7. [Medline].
24. Gormally S, Drumm B. Helicobacter pylori and gastrointestinal symptoms. Arch Dis Child. Mar 1994;70(3):165-6. [Medline].
25. Graham DY, Rakel RE, Fendrick AM, et al. Practical advice on eradicating Helicobacter pylori infection. Postgrad Med. Mar 1999;105(3):137-40, 145-8. [Medline].
26. Graham DY, Shiotani A. The time to eradicate gastric cancer is now. Gut. Jun 2005;54(6):735-8. [Medline].
27. Guo CY, Wu YB, Liu HL, et al. Clinical evaluation of four one-week triple therapy regimens in eradicating Helicobacter pylori infection. World J Gastroenterol. Mar 1 2004;10(5):747-9. [Medline].
28. Hardikar W, Feekery C, Smith A, et al. Helicobacter pylori and recurrent abdominal pain in children. J Pediatr Gastroenterol Nutr. Feb 1996;22(2):148-52. [Medline].
29. Heldenberg D, Wagner Y, Heldenberg E, et al. The role of Helicobacter pylori in children with recurrent abdominal pain. Am J Gastroenterol. Jun 1995;90(6):906-9. [Medline].
30. Horvitz G, Gold BD. Gastroduodenal diseases of childhood. Curr Opin Gastroenterol. Nov 2006;22(6):632-40. [Medline].
31. Huang FC, Chang MH, Hsu HY, et al. Long-term follow-up of duodenal ulcer in children before and after eradication of Helicobacter pylori. J Pediatr Gastroenterol Nutr. Jan 1999;28(1):76-80. [Medline].
32. Huebner ES, Surawicz CM. Probiotics in the prevention and treatment of gastrointestinal infections. Gastroenterol Clin North Am. June 2006;35:355-65. [Medline].
33. Israel DM, Hassall E. Treatment and long-term follow-up of Helicobacter pylori-associated duodenal ulcer disease in children. J Pediatr. Jul 1993;123(1):53-8. [Medline].
34. Judd RH. Helicobacter pylori, gastritis, and ulcers in pediatrics. Adv Pediatr. 1992;39:283-306. [Medline].
35. Kimia A, Zahavi I, Shapiro R, et al. The role of Helicobacter pylori and gastritis in children with recurrent abdominalpain. Isr Med Assoc J. Feb 2000;2(2):126-8. [Medline].
36. Kiyota K, Habu Y, Sugano Y, et al. Comparison of 1-week and 2-week triple therapy with omeprazole, amoxicillin,and clarithromycin in peptic ulcer patients with Helicobacter pylori infection: results of a randomized controlled trial. J Gastroenterol. 1999;34 Suppl 11:76-9. [Medline].
37. Knippig C, Arand F, Leodolter A, et al. Prevalence of H. pylori-infection in family members of H. pylori positive and its influence on the reinfection rate after successful eradication therapy: a two-year follow-up. Z Gastroenterol. Jun 2002;40(6):383-7. [Medline].
38. Koivisto TT, Rautelin HI, Voutilainen ME, et al. First-line eradication therapy for Helicobacter pylori in primary health care based on antibiotic resistance: results of three eradication regimens. Aliment Pharmacol Ther. Mar 15 2005;21(6):773-82. [Medline].
39. Logan RP, Gummett PA, Schaufelberger HD, et al. Eradication of Helicobacter pylori with clarithromycin and omeprazole. Gut. Mar 1994;35(3):323-6. [Medline].
40. Long SS, Pickering LK, Prober CG, eds. Helicobacter pylori. In: Principles and Practice of Pediatric Infectious Diseases. New York, NY: Churchill Livingstone; 1997:1029-33.
41. Moshkowitz M, Reif S, Brill S, et al. One-week triple therapy with omeprazole, clarithromycin, and nitroimidazole for Helicobacter pylori infection in children and adolescents. Pediatrics. Jul 1998;102(1):e14. [Medline]. [Full Text].
42. Nista EC, Candelli M, Cremonini F, et al. Levofloxacin-based triple therapy vs. quadruple therapy in second-line Helicobacter pylori treatment: a randomized trial. Aliment Pharmacol Ther. Sep 15 2003;18(6):627-33. [Medline].
43. Parsonnet J. Helicobacter pylori. Infect Dis Clin North Am. Mar 1998;12(1):185-97. [Medline].
44. Parsonnet J, Hansen S, Rodriguez L, et al. Helicobacter pylori infection and gastric lymphoma. N Engl J Med. May 5 1994;330(18):1267-71. [Medline]. [Full Text].
45. Siberry GK, Iannone R, eds. Formulary: drug doses. In: The Harriet Lane Handbook. 15^th ed. St Louis, MO: Mosby; 2000:622, 630, 645-6, 674-5, 772-3, 795, 837.
46. Helicobacter pylori. In: Feigin RD, Cherry JD, Fletcher J, eds. Textbook of Pediatric Infectious Diseases. 1998. Philadelphia, PA: WB Saunders; 1488-94.
47. Vinette KM, Gibney KM, Proujansky R, Fawcett PT. Comparison of PCR and clinical laboratory tests for diagnosing H. pylori infection in pediatric patients. BMC Microbiol. Jan 27 2004;4:5. [Medline]. [Full Text].
48. Wewer V, Andersen LP, Paerregaard A, et al. Treatment of Helicobacter pylori in children with recurrent abdominal pain. Helicobacter. Sep 2001;6(3):244-8. [Medline].
49. Windle HJ, Kelleher D, Crabtree JE. Childhood Helicobacter pylori infection and growth impairment in developing countries: a vicious cycle?. Pediatrics. Mar 2007;119(3):e754-9. [Medline].

Article Last Updated: Mar 26, 2008