Gas 31#5 2000

Journal of Pediatric Gastroenterology and Nutrition
31:490–497 November 2000 Lippincott Williams & Wilkins, Inc., Philadelphia
Medical Position Statement: The North American Society for Pediatric Helicobacter pylori Infection in Children: Recommendations for *Benjamin D. Gold, †Richard B. Colletti, ‡Myles Abbott, §Steven J. Czinn, ࿣Yoram Elitsur, ¶Eric Hassall, #Colin Macarthur, **John Snyder, and ††Philip M. Sherman Division of *Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; †Pediatric Gastroenterology, University of Vermont, Fletcher Allen Health Center, Burlington, Vermont; ‡Berkeley California; §Pediatric Gastroenterology, Rainbow Babies and Children’s Hospital, Cleveland, Ohio; ࿣Division of Gastroenterology, Marshall University School of Medicine, Huntington, West Virginia; ¶Division of Gastroenterology, BC Children’s Hospital, Vancouver, British Columbia, Canada; Divisions of #General Pediatrics and ††Gastroenterology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada; and **Pediatric Gastroenterology, University of California San Francisco, San Francisco, California, U.S.A. Helicobacter pylori infects at least 50% of the world’s been infected for many years before clinical symptoms human population (1). However, most individuals in- appeared (6). The incidence of H. pylori infection in fected with H. pylori do not experience symptoms or industrialized countries is estimated to be approximately have signs of recognizable disease. In most children, the 0.5% of the susceptible population per year. In contrast, presence of H. pylori infection does not lead to clinically there is a significantly higher estimated incidence of H. apparent disease, even when the organism colonizing the pylori infection in developing countries of approximately gastric mucosa causes chronic active gastritis (2).
3% to 10% per year (7). The limited data on the inci- Knowledge about H. pylori infection is evolving, par- dence of H. pylori infection in children consist largely of ticularly in the pediatric age group for which there are retrospective seroprevalence studies.
Humans appear to be the primary natural reservoir of Additional multicenter, randomized, placebo- H. pylori infection. Other reservoirs that have been pro- controlled treatment trials in children infected by H. py- posed include water, domestic cats, and houseflies (8– lori are critically needed to definitively characterize the 10). The risk factors described for acquiring infection effect of H. pylori eradication treatment during child- include residence in a developing country, poor socio- hood on symptoms and gastroduodenal mucosal disease.
economic conditions, family overcrowding, and possibly There is compelling evidence that this organism is an ethnic or genetic predisposition. In North America, associated with a significant proportion of duodenal ul- the prevalence rates of H. pylori among Asian-Ameri- cers and, to a lesser extent, with gastric ulcers in children cans, African-Americans and Hispanics are similar to (3). There are epidemiologic data linking chronic H. py- those of residents of developing countries (11). The route lori infection, probably beginning in childhood, with the of transmission of H. pylori in humans is not known but development of gastric adenocarcinoma and gastric lym- is postulated to be fecal-oral, gastric-oral (in vomitus), or phoma (4). Findings in recently reported animal models support the role of H. pylori in the pathogenesis of gas- Although H. pylori infection may be acquired during childhood, there are limited guidelines regarding its di- There are many studies describing the prevalence of agnosis and treatment in children and adolescents. Such H. pylori infection. Most epidemiologic studies of H. evidence-based consensus guidelines are needed for both pylori infection have been performed in adults who had primary care and specialty medical providers to ensurejudicious use of diagnostic testing and appropriate thera-peutic regimens for the management of children with H. Received and accepted September 8, 2000.
pylori infection. Therefore, the North American Society Address correspondence and reprint requests to Dr. Benjamin Gold, for Pediatric Gastroenterology and Nutrition (NASPGN) Emory University School of Medicine, 2040 Ridgewood Drive, NE, appointed the Helicobacter pylori Infection Guideline Atlanta, GA 30322, U.S.A.; or to Dr. Richard B. Colletti, University of Committee to develop a clinical practice guideline for Vermont, Department of Pediatrics, A-121 Given Medical Building,Burlington, VT 05405-5557, U.S.A.
the child with H. pylori infection.
TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION These clinical practice guidelines are designed to as- TABLE 1. Summary of recommendations and the quality of
sist primary care physicians, nurse practitioners, physi- cian assistants, and pediatric gastroenterologists in the evaluation and treatment of suspected or diagnosed H. pylori–associated disease. The desired outcomes of these How reliable are tests for H. pylori infection?
recommendations are the detection of children and ado- Currently, the diagnosis of H. pylori-mediated disease lescents with H. pylori who need treatment. These rec- can be made reliably only through the use of ommendations are applicable to children in developed countries where the prevalence of infection is low but Presently available commercial serologic tests are may not be directly relevant to children living in com- frequently unreliable for screening children for thepresence of H. pylori infection.
munities where there is a higher frequency of gastric Urea breath testing, although promising, has not been colonization by H. pylori. These recommendations have been endorsed by the Executive Council of NASPGN When is testing indicated?
and by the American Academy of Pediatrics. They are It is recommended that testing be performed in children with endoscopically diagnosed, or general guidelines to assist medical care providers in the radiographically definitive, duodenal or gastric ulcers.
diagnosis and treatment of H. pylori infection in chil- It is recommended that children with recurrent dren. They are not intended as a substitute for clinical abdominal pain, in the absence of documented judgment or as a protocol for the management of all ulcer disease, not be tested for H. pylori infection.
Testing for H. pylori infection is not recommended in In its deliberations, the committee addressed four is- Routine screening of children with a family history of sues about H. pylori infection in children: How reliable gastric cancer or recurrent peptic ulcer disease is are tests to detect H. pylori? When is testing for H. pylori indicated? When is treatment of H. pylori infection in- Testing following treatment of documented H. pylori is recommended, especially with complicated dicated? What is the preferred treatment of H. pylori? A peptic ulcer disease (i.e., bleeding, perforation, or summary of the recommendations of the H. pylori Infec- obstruction). For patients who remain symptomatic tion Guideline Committee is presented in Table 1.
after treatment, it is recommended that endoscopyand biopsy be performed to evaluate for thepersistence of H. pylori-associated peptic ulcer If pathological evidence of MALT lymphoma is The H. pylori Infection Guideline Committee consisted of a documented, then testing for H. pylori is primary care pediatrician, a clinical epidemiologist, and seven pediatric gastroenterologists. To develop evidence-based When is treatment of H. pylori infection indicated?
guidelines, articles published in English from January 1966 Eradication treatment is recommended for children who through May 1999 on H. pylori in children were searched.
have a duodenal ulcer or gastric ulcer identified atendoscopy and H. pylori detected on histology.
Articles on diagnosis and treatment were sought separately.
A prior history of documented duodenal or gastric Letters, editorials, case reports, abstracts, and reviews were ulcer disease is an indication for treatment if active excluded. Evidence tables were prepared based on 16 articles H. pylori infection is documented.
on clinical presentation, 9 articles on diagnostic studies, and 30 There is no compelling evidence for treating articles on therapy. Subsequently, additional articles were iden- children with H. pylori infection and non-ulcer tified and reviewed. When the pediatric literature was insuffi- dyspepsia or functional recurrent abdominal pain.
cient, the adult literature was also considered. Articles were Treatment is not recommended for H. pylori-infected evaluated using published criteria (13). The Committee based children residing in chronic care facilities; children its recommendations on an integration of a review of the medi- with unexplained short stature; or children atincreased risk for acquisition of infection, including cal literature and expert opinion. Consensus was achieved by asymptomatic children who have a family member using the nominal group technique, a structured quantitative with either peptic ulcer disease or gastric cancer.
method, as described previously (14,15). By using the methods What is the preferred treatment of H. pylori infections in children?
of the Canadian Preventive Services Task Force (16), the qual- It is recommended that treatment consist of three or ity of evidence of each of the recommendations made by the four medications, given once or twice daily, for committee was determined and is summarized (Table 1).
a Categories of the quallity of evidence: I Evidence obtained from at HOW RELIABLE ARE TESTS FOR
least one properly designed randomized controlled study. II-1 Evidence H. PYLORI INFECTION?
obtained from well-designed cohort or case-controlled trials withoutrandomization. II-2 Evidence obtained from well-designed cohort orcase-control analytic studies, preferably from more than one center or Several invasive and noninvasive tests are available to research group. II-3 Evidence obtained from multiple time series with detect H. pylori infection (Table 2). An ideal test for H. or without the intervention. Dramatic results in uncontrolled experi- pylori is noninvasive or minimally invasive, highly ac- ments (such as the results of the introduction of penicillin treatment in curate, inexpensive, and readily available and enables the 1940’s) could also be regarded as this type of evidence. III Opinionsof respected authorities, based on clinical experience, descriptive stud- differentiation between active or past infection with the ies, or reports of expert committees.
J Pediatr Gastroenterol Nutr, Vol. 31, No. 5, November 2000 TABLE 2. Tests for Helicobacter pylori and
study. The optimal staining of biopsy sections is best determined by local expert pathologists. Endoscopic ex-amination of and specimens obtained in the esophagus, stomach, and duodenum also provide information about Biopsies and histologyRapid urease testing other upper gastrointestinal disorders that may be the cause of clinical symptoms including, for example, Polymerase chain reaction of bacterial DNA esophagitis and peptic ulcer disease that is not due to H. Serum and whole blood antibodySaliva antibody There are drawbacks to diagnostic gastrointestinal en- doscopy. It is a relatively invasive procedure requiring sedation or anesthesia. Furthermore, the test remains relatively expensive in many centers, and access to anendoscopist with specific pediatric expertise is limited inmany geographic areas.
organism. In addition, such a test enables discriminationbetween the presence of H. pylori infection and H. py-lori–associated disease. Because no such ideal test cur- Rapid Urease Testing of Biopsy Tissues rently exists, the advantages and drawbacks of tests that Urease testing (CLO, TriMed, Kansas City, MO; Hp- are available require critical appraisal and must be as- Fast, GI Supply, Division of ChekMed Systems Inc., sessed for their suitability for use in children.
Camphill, PA; PyloriTek, Horizons International, Agua- Failure to reach an accurate diagnosis carries consid- dilla, Puerto Rico) provides indirect identification of H. erable financial and social costs including the expense of pylori infection within a few hours of endoscopy (20).
more tests, repeated visits to health care providers, inap- However, these tests have a poor positive predictive propriate treatment, and missed school or work. A de- value (as low as 50%) in children, even though the nega- finitive test, even if it is expensive, may result in overall tive predictive value is high (97–98%) (20,21). The ac- curacy of the test is dependent on the number of tissue It is important to emphasize that the accuracy of a specimens tested, the location of biopsy sites, bacterial diagnostic test is greatly impacted by the prevalence of load, and previous usage of antibiotics and proton pump H. pylori in the population tested. There is a need for inhibitors, as well as the prevalence of H. pylori in the studies to assess the accuracy and potential utility of various noninvasive diagnostic tests in populations inNorth America that differ in demographic factors thatmay influence the prevalence and natural history of H. Culture of H. pylori from the gastric mucosa provides an opportunity to obtain a profile of antibiotic sensitivity Invasive Testing Through Endoscopy
that could identify potential treatment failure due to an-tibiotic resistance (22). Culture also provides a bacterial strain for use in epidemiologic studies to examine asso-ciations of virulence characteristics with disease out- The definitive diagnosis of H. pylori and the evidence come. However, bacterial culture for H. pylori is rela- of the consequences of infection can be made reliably tively expensive and success rates for recovery of the only by endoscopy with multiple biopsy specimens ob- organism in many clinical laboratories are low (23). Cur- tained in one or more regions of the stomach including rently, standardization of culture procedures has not been antrum, body, and transition zones (i.e., cardia and inci- established, and bacterial cultures are only obtained rou- sura). Histology provides information regarding the pres- ence of H. pylori and the severity and topographic dis-tribution of gastritis including the presence of atrophic gastritis, intestinal metaplasia, and mucosa-associatedlymphoid tissue (MALT) lymphoma (3). As in adults, Polymerase chain reaction (PCR) is a highly sensitive biopsy specimens obtained in the prepyloric antrum have technique that can be used to detect the presence of H. the highest yield in H. pylori infection. Tissue specimens pylori in body fluids (e.g., gastric juice and stool), tissues often are also obtained from the body and the transition (e.g., gastric mucosa), and water (24). Testing of H. py- zones of the stomach, particularly if the patient has re- lori genomic DNA by PCR can be used to advance cently taken acid-suppressing medication (19). It is rec- knowledge at the molecular level—for example, by pro- ommended that multiple biopsies be performed in chil- viding information about point mutations conferring dren with endoscopically documented peptic ulcer dis- resistance to antibiotics and about putative bacterial ease or peptic ulcer suspected as a result of radiographic virulence factors. However, PCR is expensive, the assay J Pediatr Gastroenterol Nutr, Vol. 31, No. 5, November 2000 TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION is difficult to set up, specificity may be compromised by cation therapy. However, patients may be reluctant to inadvertent contamination, and it is not widely available collect stool specimens. In addition, refrigerated stools are more difficult to test. Additional pediatric studiesevaluating the accuracy of stool antigen testing for bothinitial diagnosis and posttreatment follow-up are re- Noninvasive Testing
quired before specific recommendations can be consid- Immunoassay Tests to Detect H. pylori Antibodies Enzyme-linked immunosorbent assays (ELISAs) to detect H. pylori antibodies are relatively inexpensive andeasy to implement in the clinical setting. Many tests areavailable for use to test whole blood, plasma, or serum.
Urea breath tests are noninvasive and have high sen- However, compared with histology, the sensitivity and sitivity and specificity (>95%) both in adults (33) and specificity of serologic assays are poor in both adults and children (34,35). The test requires the ingestion of either children unless used in the populations in which they radiolabeled 14C-urea or urea tagged with the stable iso- were initially developed (25). In general, the accuracy of tope 13C. Test results may be influenced by concurrent serum-based immunoassays and whole-blood tests for use of antibiotics and acid-suppressing medications and use in the physician’s office in symptomatic children in by the presence of other urease-producing organisms developed countries is poor, with a range of sensitivity of present in the oral cavity. Test parameters are currently only 60% to 70% (26–28). Furthermore, age-related cut- laboratory-specific (e.g., dosages for differing ages of off values for commercial immunologic tests have not children, cutoff values, duration of fasting, use of a test been established for children. One immunoassay devel- meal, times of sampling, and timing of posttherapy test- oped in a research center to detect H. pylori–specific ing) and have not been well standardized for children immunoglobulin (Ig)G in children was 91% sensitive (36). In addition, urea breath testing is technically more compared with sensitivity of less than 70% in three com- difficult to perform in small children and infants, with mercially available assays (28). In areas with low preva- failure rates in collection up to 10%, especially outside lence of H. pylori infection, such as in developed coun- tries, testing of serum and whole blood is not sufficiently In summary, the diagnosis of H. pylori–associated dis- accurate to diagnose H. pylori infection in children. Ac- eases currently can be made reliably only by endoscopy cordingly, treatment regimens based on the results of with biopsies. The most commonly used noninvasive test these tests cannot be recommended. Serologic tests may to screen adults for H. pylori infection is serology. Un- not be used reliably to verify eradication of H. pylori, fortunately, currently available commercial serologic because antibody titers can remain positive for months, tests are frequently unreliable for screening children for the presence of H. pylori infection. Current whole-blood,saliva, and urinary immunoassays are insufficiently sen-sitive or specific to be effective as diagnostic tools. In- Saliva and Urine Tests for H. pylori Antibodies sufficient data are available in children to confirm theaccuracy of the recently approved H. pylori stool antigen Similar to serologic tests, saliva-based tests also detect test. The urea breath test has the promise to provide the presence of H. pylori–specific IgG antibodies. The noninvasive and accurate diagnosis of H. pylori infec- tests are easy to perform, painless, and inexpensive. Sa- tion; but currently, there is insufficient evidence that it liva tests are less sensitive than assays of serum or whole can be used to reliably diagnose or exclude H. pylori– blood (29). The protein concentration of saliva appears to affect the accuracy of test results. Urine-based assays areeasy to perform, require minimal labor for collection,and are painless (30). However, these assays are highlyvariable and are not yet commercially available. There- WHEN IS TESTING INDICATED?
fore, saliva and urine assays for the detection of H. pyloriantibodies cannot be recommended.
The primary goal of testing is to diagnose the cause of clinical symptoms and not simply to detect the presence Stool Test for H. pylori Antigens of H. pylori infection. Testing is not helpful unless it willalter the management of the disease.
Testing of H. pylori antigens in stools has shown A variety of invasive and noninvasive tests exist for promising results in adults for the noninvasive diagnosis the detection of H. pylori infection, but their degree of of gastric infection using a commercially available kit sensitivity and specificity vary, as do their suitability for (31). Testing for H. pylori antigens in feces also appears clinical use in children. Thus, there is potential for inap- to be accurate for use in monitoring the success of eradi- propriate testing or misuse of tests in children.
J Pediatr Gastroenterol Nutr, Vol. 31, No. 5, November 2000 Endoscopically Diagnosed or Radiographically
dicates that there is a link between gastric cancers (both Definitive Peptic Ulcer
adenocarcinoma and lymphoma) and H. pylori infection.
However, no studies have shown that H. pylori eradica- The causal relationship between H. pylori infection tion during childhood prevents subsequent development and primary duodenal ulcers is compelling (37). There- of gastric malignancies. Until evidence is available to fore, it is recommended that testing for the presence of H. better define the role of H. pylori in a variety of gastric pylori infection be performed in children with endo- cancers and the role of H. pylori eradication in disease scopically diagnosed or radiographically definitive duo- prevention, routine screening of children with a family denal ulcer. Although the data in children are less com- history of gastric cancer or recurrent peptic ulcer disease plete, evidence from studies in adults (38) supports the recommendation that testing for H. pylori also be per-formed in subjects with a documented gastric ulcer.
Histologic Evidence of Lymphoma
Abdominal Pain Unrelated to Peptic Ulcers
In the rare circumstance in which histopathologic evi- Several lines of evidence, including serologic surveys, dence of MALT lymphoma is documented in a child, endoscopic evaluations, and treatment trials indicate that testing for H. pylori is recommended.
H. pylori is not a frequent cause of recurrent abdominalpain in children. There have been six studies performedin North America, Europe, and Australia, with 2715 chil- Follow-up of Therapy for H. pylori Infection
dren evaluated by esophagogastroduodenoscopy and bi-opsy, serology, or urea breath test (39–44). Although 5% Testing to confirm eradication of infection and the to 17% of children with abdominal pain had evidence of resolution of associated symptoms and disease sequelae infection with H. pylori, 5% to 29% of children without is advisable in selected children. Guidelines in adults abdominal pain were also infected with H. pylori. There recommend testing after treatment of complicated peptic are no convincing data to support routine testing of chil- ulcer (52), but studies in children are limited. As such, dren with recurrent abdominal pain (39–45). Investiga- few data are available on the effectiveness of therapy in tors have also looked for specific symptom patterns in H. children, testing after treatment is recommended in those pylori–infected children, but none so far has been de- with complicated peptic ulcer disease (i.e., bleeding, per- tected (46–50). Future studies are needed to determine foration, or obstruction) or lymphoma. For patients who whether subsets of children with abdominal pain can be remain symptomatic, it is recommended that endoscopy identified in whom signs and symptoms are caused by H. and biopsy be performed to evaluate for the persistence pylori infection. It is recommended that children with of H. pylori-associated peptic ulcer disease. For patients recurrent abdominal pain, in the absence of documented with an uncomplicated ulcer who are asymptomatic after ulcer disease, not be tested for H. pylori infection.
completion of eradication therapy, testing for persistenceof infection is not necessary. However, some physicians Asymptomatic Children, Including Those at
advocate the use of urea breath testing in this clinical Increased Risk of Acquiring H. pylori Infection
There are no compelling data to support routine testing in asymptomatic children. Testing for H. pylori infection WHEN IS TREATMENT OF H. PYLORI
is not recommended in children without clinical symp- INFECTION INDICATED?
toms, including those residing in long-term care facili-ties, children with short stature, and those at increased Eradication therapy is recommended for children who risk of acquiring H. pylori infection. In addition, pur- have both known active H. pylori infection and symp- ported extraintestinal manifestations of H. pylori infec- tomatic gastrointestinal disease. Known active H. pylori tion have not been demonstrated in a convincing fashion infection is defined as identification of the organisms by (51). Accordingly, a test-and-treat approach is not rec- histopathologic examination or as a positive culture from endoscopic gastric biopsy. Serology is not a reliable testfor active disease, because it may indicate past but not Family History of Gastric Cancer or Recurrent
current infection with H. pylori.
Peptic Ulcer Disease
There are no randomized controlled trials in children that determine the precise clinical settings in which No currently available data support routine testing in eradication therapy is indicated. Although additional children with a positive family history of diseases related studies in children are needed (53), the available evi- to H. pylori infection (52). Epidemiologic evidence in- dence supports the following recommendations.
J Pediatr Gastroenterol Nutr, Vol. 31, No. 5, November 2000 TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION Duodenal and Gastric Ulcers
cost of care. Therefore, the H. pylori Infection GuidelineCommittee concludes that there is insufficient evidence Eradication treatment is recommended for children to support either initiating or withholding eradication who have a duodenal ulcer or gastric ulcer identified at endoscopy and H. pylori documented by histopathology.
A prior history of duodenal or gastric ulcer disease is alsoan indication for treatment if active H. pylori infection is Recurrent Abdominal Pain and
documented. If a definitive ulcer is present on contrast Asymptomatic Children
radiography (e.g., an ulcer crater is present), eradicationtherapy is indicated if either a noninvasive or invasivetest result is positive for H. pylori.
There is no compelling evidence, at the present time, for treating children with H. pylori infection and either Lymphoma
nonulcer dyspepsia or functional recurrent abdominalpain. There is also no convincing evidence currently The rare child with pathologic evidence of MALT available that asymptomatic children who have a family lymphoma and H. pylori infection should be treated with member with H. pylori infection, peptic ulcer, or gastric eradication therapy. Further studies of pediatric patients with lymphoma should be performed to monitor the re-currence, progression, or remission of the tumor aftertherapy.
WHAT IS THE PREFERRED TREATMENT OF
H. PYLORI INFECTION IN CHILDREN?
Atrophic Gastritis With Intestinal Metaplasia
The optimum treatment regimen for eradicating H. py- Eradication treatment is recommended for the rare lori in children has not been determined (59). Effective child who has pathologically proven atrophic gastritis therapy in adults is defined as successful eradication of with intestinal metaplasia, according to the updated Syd- H. pylori infection in a minimum of 80% of treated sub- ney classification of gastritis (54), plus coexisting H. jects (60). Although it appears that treatment options that pylori infection. Because of the preneoplastic nature of have been effective in adults will also be efficacious in these pathologic changes, follow-up endoscopy is rec- children, controlled studies in pediatric populations are ommended to confirm that the H. pylori infection has needed to confirm or refute this supposition. Unfortu- been eradicated and to ensure that there is no subsequent nately, the limited data currently available in children are progression of gastric mucosal disease.
open-label, case series and uncontrolled, anecdotal ob-servations that do not meet the minimum criteria for Gastritis Without Peptic Ulcer Disease
determining efficacy. In vitro sensitivity of H. pylori to aspecific drug does not guarantee that the bacterium will The finding of H. pylori–associated gastritis in the be effectively eradicated from the human stomach.
absence of peptic ulcer disease during diagnostic endos- Therefore, current treatment strategies to eradicate H. copy poses a dilemma for the endoscopist. The decision pylori have been developed primarily by trial-and-error to treat H. pylori–associated gastritis without duodenal or gastric ulcer in this situation is subject to the judgment of The single most important determinant of successful the clinician and deliberations with the patient and fam- eradication therapy is compliance with the prescribed ily. Studies in adults on the effect of eradication treat- combination treatment regimen (62). There are well- ment on abdominal symptoms have produced conflicting described treatment failures due to suboptimal compli- results (55–58). There are no randomized controlled tri- ance. To enhance adherence to the treatment regimen, als in children. The long-term impact of the eradication the number of medications prescribed, the frequency of of H. pylori and the healing of gastritis on the subsequent administration, and the duration of therapy are best kept development of peptic ulcer disease, adenocarcinoma, or to the minimum required for successful treatment.
lymphoma is uncertain. Although there is a small life- It is recommended that initial treatment consist of time risk of development of peptic ulcer disease associ- three medications, administered twice daily, for 1 to 2 ated with H. pylori gastritis, there are no randomized weeks (63). Specifically, as shown in Table 3, three first- controlled trials demonstrating that eradication of H. py- line therapy options are recommended for use in children lori results in prevention of peptic ulcer disease. In ad- and adolescents. For patients in whom initial treatment dition, there are no data showing that eradication therapy has failed, two other options are recommended, includ- influences the long-term risk for development of gastric ing one option with four medications. It is recommended cancers. Antibiotic treatment can result in adverse drug that monotherapy and two-drug regimens be avoided, reactions, promote antibiotic resistance, and increase the because they are ineffective and increase the likelihood J Pediatr Gastroenterol Nutr, Vol. 31, No. 5, November 2000 TABLE 3. Recommended eradication therapies for H. pylori
pump inhibitor also reduces the effectiveness of eradica- tion treatment protocols. Studies are needed to determinethe relative importance of these risk factors in pediatric REFERENCES
1. 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. 2. Drumm B. Helicobacter pylori in the pediatric patient. Gastroen- terol Clin North Am. 1993;22:169–82.
3. Dohil R, Hassall E, Jevon G, et al. Gastritis and gastropathy of childhood. J Pediatr Gastroenterol Nutr. 1999;29:378–94.
4. Huang J-Q, Sridhars CY, Hunt RH. Meta-analysis of the relation- ship between Helicobacter pylori seropositivity and gastric cancer.
Gastroenterology. 1998;114:1169–79.
5. Watanabe T, Tada M, Nagai H, et al. Helicobacter pylori infection induces gastric cancer in Mongolian gerbils. Gastroenterology. 6. Webb PM, Knight T, Greaves S, et al. Relation between infection with Helicobacter pylori and living conditions in childhood: evi- dence for person to person transmission in early life. BMJ. 1994; 7. Parsonnet J. The incidence of Helicobacter pylori infection. Ali- ment Pharmacol Ther. 1995;9:45–51.
8. Handt LK, Fox JG, Stalis IH, et al. Characterization of feline Helicobacter pylori strains and associated gastritis in a colony of domestic cats. J Clin Microbiol. 1995;33:2280–9.
9. Grubel P, Hoffman JS, Chong FK, et al. Vector potential of house- flies (Musca domestica) for Helicobacter pylori. J Clin Microbiol. 10. Klein PD, Graham DY, Gaillour A, et al. Water source as a risk factor for Helicobacter pylori infection in Peruvian children. Lan- 11. Staat MA, Kruszon-Moran D, McQuillan GM, et al. A population- based serologic survey of Helicobacter pylori infection in children and adolescents in the United States. J Infect Dis. 1996;174: 12. Goodman KJ, Correa P. The transmission of Helicobacter pylori: a critical review of the evidence. Int J Epidemiol. 1995;24:875–87.
13. Sackett DL, Richardson WS, Rosenberg W, et al. Evidence-based Medicine: How to Practice and Teach EBM. Edinburgh: Churchill 14. McMurray AR. Three decision-making aids: brainstorming, nomi- nal group, and Delphi technique. J Nurs Staff Dev. 1994;10:62–5.
15. Cockeram AW. Clinical practice guidelines: help or hindrance? J Pediatr Gastroenterol Nutr. 1999;28:362–3.
16. Canadian Task Force on the Periodic Health Examination: the Initial treatment should be provided in a twice daily regimen (to periodic health examination. Can Med Assoc J. 1979;121:1193– enhance compliance) for 7 to 14 days.
Only for children 12 years of age or older.
17. Olson AD, Fendrick AM, Deutsch D, et al. Evaluation of initial bid, twice daily; qid, four times daily.
noninvasive therapy in pediatric patients presenting with suspectedulcer disease. Gastrointest Endosc. 1996;44:554–1.
of acquired antibiotic resistance (64). Primary antimicro- 18. Rothman KJ, Greenland S. Modern Epidemiology. 2nd ed. Phila- bial resistance also can result in treatment failure even when a three- or four-drug regimen is used. Resistance of 19. Genta RM, Graham DY. Comparison of biopsy sites for the his- topathologic diagnosis of Helicobacter pylori: a topographic study H. pylori to nitroimidazoles causes an increase in the rate of H. pylori density and distribution. Gastroenterology. 1997;112: of treatment failures in regimens using metronidazole.
An increasing prevalence of resistance to clarithromycin, 20. Elitsur Y, Neace C. Detection of Helicobacter pylori organisms by documented in the past few years, particularly in Europe, Hp-fast in children. Dig Dis Sci. 1999;44:1169–72.
could eventually impair the therapeutic effectiveness of 21. Elitsur Y, Hill I, Lichtman SN, et al. Prospective comparison of rapid urease tests (Pyloritek, CLO test) for the diagnosis of Heli- this antibiotic in H. pylori treatment regimens. Results in cobacter pylori infection in symptomatic children: a pediatric mul- some studies suggest that prior therapy with a proton ticenter study. Am J Gastroenterol. 1998;93:217–9.
J Pediatr Gastroenterol Nutr, Vol. 31, No. 5, November 2000 TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION 22. van der Hulst RW, van der Ende A, Homan A, et al. Influence of pain and Helicobacter pylori in a community-based sample of metronidazole resistance on efficacy of quadruple therapy for Heli- London children. Acta Paediatr. 1996;85:961–4.
cobacter pylori eradication. Gut. 1998;42:166–9.
44. Hardikar W, Feekery C, Smith A, et al. Helicobacter pylori and 23. Holton J. Clinical relevance of culture: why, how, and when. Heli- recurrent abdominal pain in children. J Pediatr Gastroenterol Nutr. cobacter. 1997;2(suppl 1):S25–33.
24. Westblom TU. Molecular diagnosis of Helicobacter pylori. Immu- 45. Macarthur C, Saunder N, Feldman W. Helicobacter pylori, gas- nol Invest. 1997;26:163–74.
troduodenal disease, and recurrent abdominal pain in children.
25. Breslin NP, O’Morain CA. Noninvasive diagnosis of Helicobacter pylori: a review. Helicobacter. 1997;2:111–7.
46. Gormally SM, Prakash N, Durnin MT, et al. Association of symp- 26. De Oliveira AMR, Rocha GA, Queiroz DMM, et al. Evaluation of toms with Helicobacter pylori infection in children. J Pediatr. enzyme-linked immunosorbent assay for the diagnosis of Helico- bacter pylori infection in 157 children from different age groups 47. Hardikar W, Davidson PM, Cameron DJ, et al. Helicobacter pylori with and without duodenal ulcer. J Pediatr Gastroenterol Nutr. infection in children. J Gastroenterol Hepatol. 1991;6:450–4.
48. Glassman MS, Schwarz Sm, Medow MS, et al. Campylobacter 27. Czinn SJ. Serodiagnosis of Helicobacter pylori in pediatric pa- pylori-related gastrointestinal disease in children. Incidence and tients. J Pediatr Gastroenterol Nutr. 1999;28:132–4.
clinical findings. Dig Dis Sci. 1989;34:1501–4.
28. Khanna B, Cutler A, Israel NR, et al. Use caution with serologic 49. Reifen R, Rasooly I, Drumm B, et al. Helicobacter pylori infection testing for Helicobacter pylori infection in children. J Infect Dis. in children: is there specific symptomatology. Dig Dis Sci. 1994; 29. Fallone CA, Elizov M, Cleland P, et al. Detection of Helicobacter 50. Snyder JD, Hardy SC, Thorne GM, et al. Primary antral gastritis in pylori infection by saliva IgG testing. Am J Gastroenterol. 1996; young American children: low prevalence of Helicobacter pylori.
Dig Dis Sci. 1994;39:1859–63.
30. Alemohammad MM, Foley TJ, Cohen H. Detection of immuno- 51. Leontiadis GI, Sharma VK, Howden CW. Non-gastrointestinal globulin G antibodies to Helicobacter pylori in urine by an enzyme tract associations of Helicobacter pylori infection. What is the immunoassay method. J Clin Microbiol. 1993;31:2174–7.
evidence? Arch Intern Med. 1999;159:925–40.
31. Vaira D, Malfertheiner P, Megraud F, et al. Diagnosis of Helico- 52. Howden CW. For what conditions is there evidence-based justifi- bacter pylori with a new non-invasive antigen-based assay. Lancet. cation for treatment of Helicobacter pylori infection? Gastroen- terology. 1997;113:S107–112.
32. Oderda G, Rapa A, Ronchi B, et al. Detection of Helicobacter 53. Sherman PM, Hunt RH. Why guidelines are required for treatment pylori in stool specimens by non-invasive antigen enzyme immu- of Helicobacter pylori infection in children. Clin Invest Med. 1996; noassay in children: multicentre Italian study. BMJ. 2000;320: 54. Dixon MF, Genta RM, Yardley JH, et al. Classification and grad- 33. Cutler AF, Havstad S, Ma CK, et al. Accuracy of invasive and ing of gastritis: the updated Sydney system. Am J Surg Pathol. noninvasive tests to diagnose Helicobacter pylori infection. Gas- troenterology. 1995;109:136–41.
55. Blum AL, Talley NJ, O’Morain C, et al. Lack of effect of treating 34. Rowland M, Lambert I, Gormally S, et al. Carbon 13-labeled urea Helicobacter pylori infection in patients with nonulcer dyspepsia: breath test for the diagnosis of Helicobacter pylori infection in omeprazole plus clarithromycin and amoxicillin effect one year children. J Pediatr. 1997;131:815–20.
after treatment (OCAY) study group. N Engl J Med. 1998;339: 35. Bode G, Rothenbacher D, Brenner H, et al. Variation in the 13C- urea breath test value by nationality in Helicobacter pylori-infected 56. McColl K, Murray L, El-Omar E, et al. Symptomatic benefit from children. Scand J Gastroenterol. 1998;33:468–72.
eradicating Helicobacter pylori infection in patients with nonulcer 36. Jones NL, Bourke B, Sherman PM. Breath testing for Helicobacter dyspepsia. N Engl J Med. 1998;339:1869–74.
pylori infection in children: a breath of fresh air? J Pediatr. 1997; 57. Talley NJ, Janssens J, Lauritsen K, et al. Eradication of Helico- bacter pylori in functional dyspepsia: randomized double blind 37. Sherman PM, Hassall E, Hunt RH, et al. Canadian Helicobacter placebo controlled trial with 12 months follow up. The Optimal study group consensus conference on the approach to Helicobacter Regimen Cures Helicobacter Induced Dyspepsia (ORCHID) study pylori infection in children and adolescents. Can J Gastroenterol. group. BMJ. 1999;318:833–7.
58. Talley NJ, Vakil N, Ballard D, et al. Absence of benefit from 38. Hunt R, Thomson AB. Canadian Helicobacter pylori consensus eradicating Helicobacter pylori in patients with nonulcer dyspep- conference. Can J Gastroenterol. 1998;12:31–41.
sia. N Engl J Med. 1999;3412:15:1106–11.
39. Van der Meer SB, Forget PP, et al. The prevalence of Helicobacter 59. Blecker U, Gold BD. Treatment of Helicobacter pylori infection: pylori serum antibodies in children with recurrent abdominal pain.
a review. Pediatr Infect Dis J. 1997;16:391–9.
Eur J Pediatr. 1992;151:799–801.
60. Harris A. Current regimens for treatment of Helicobacter pylori 40. McCallion WA, Bailie AG, Ardill JE, et al. Helicobacter pylori, infection. Br Med Bull. 1998;54:195–205.
hypergastrinemia, and recurrent abdominal pain in children. J Pe- 61. Peura D. Helicobacter pylori: rational management options. Am J 41. Chong SK, Lou Q, Asnicar MA, et al. Helicobacter pylori infec- 62. Huang H-Q, Hunt RH. Treatment after failure: the problem of tion in recurrent abdominal pain in childhood: comparison of di- non-responders. Gut. 1999;45:140–5.
agnostic tests and therapy. Pediatrics. 1995;96:211–5.
63. Rowland M, Imrie C, Bourke B, et al. How should Helicobacter 42. Bode G, Rothenbacher D, Brenner H, et al. Helicobacter pylori and pylori infected children be managed? Gut. 1999;45:1336–9.
abdominal symptoms: a population based study among preschool 64. Behrens R, Lang T, Keller KM, et al. Dual versus triple therapy of children in southern Germany. Pediatrics. 1998;101:634–7.
Helicobacter pylori infection: results of a multicentre trial. Arch 43. O’Donahoe JM, Sullivan PB, Scott R, et al. Recurrent abdominal J Pediatr Gastroenterol Nutr, Vol. 31, No. 5, November 2000

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