Helicobacter pylori is one of the most common chronic bacterial infections worldwide. Available evidence suggests that >50% of the world's population is colonized by H. pylori (1,2). Since the isolation of H. pylori by Warren and Marshall (3), an explosion of research has implicated it in the pathogenesis of atrophic gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma of mucosa-associated lymphoid tissue type (MALT) (1,2). To clarify the available data for practicing physicians, a number of prominent national organizations have released recommendations and practice guidelines for the diagnosis and management of H. pylori infection in adults. These include the American College of Gastroenterology (ACG), American Digestive Health Foundation (ADHF), National Institutes of Health (NIH), and Centers for Disease Control and Prevention (CDC) (1,4–8).
Although most people acquire H. pylori infection during childhood (2,9), there have been no specific clinical practice or consensus guidelines for the diagnosis and management of H. pylori in infants, children, and adolescents until recently. The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) recently published treatment guidelines for children (10). In addition, two evidence-based consensus guidelines from Canada and Europe have recently been published with specific focus on pediatric H. pylori infection (10,11). Before those guidelines were published, we conducted this Internet-based knowledge, attitudes, and practice styles (KAPS) survey of pediatric gastroenterologists in North America, who were NASPGHAN members, to assess their level of understanding of H. pylori infection and their current management of the infection.
MATERIALS AND METHODS
We designed an Internet-based questionnaire that assessed the KAPS of North American pediatric gastroenterologists as they pertain to H. pylori infection. The survey contained questions regarding the responders' personal demographics, indications used for testing for H. pylori infection, use and choice of available diagnostic tests, indications for treating H. pylori infection, choice of treatment regimen, knowledge about rates of antibiotic resistance, and sources of information on H. pylori. We sent personalized e-mail communications to all members of NASPGHAN to request their participation in the on-line survey. Five cash awards, to be selected from a random drawing, were offered as incentive for completing the survey. The members of NASPGHAN received no advance notice about the questionnaire, and all surveys were completed anonymously.
Participating pediatric gastroenterologists were asked for their age and title, and whether they had graduated from a North American medical school. They were asked if they performed outpatient testing for H. pylori, the type(s) of diagnostic tests they offered or used, the patient age at which they started testing, and if they would test for H. pylori in the absence of upper gastrointestinal symptoms. In addition, they were asked if they agreed with the statement “. . . all patients found to have H. pylori infection need to be treated for the infection.”
We depicted 14 different, brief clinical scenarios on the survey instrument and asked whether the respondents would offer testing for H. pylori infection and, if the test results were positive, whether they would treat the infection. In addition, respondents were asked for their opinions on how best to manage eight different hypothetical patients. In each case, the three management options available were empiric treatment with an H-2 receptor antagonist (H2RA), empiric treatment with a proton pump inhibitor (PPI), and a test for H. pylori infection.
A list of nine combination drug regimens for the management of H. pylori infection was provided, and each respondent was asked to select his or her top three choices. If respondents used a PPI-based triple regimen, we asked if they would treat patients for 7, 10, 14, or 28 days. We also asked them to estimate the resistance rates of H. pylori to amoxicillin, clarithromycin, metronidazole, and tetracycline. In each case, the available options included <1%, 1% to 5%, 6% to 10%, and >10%.
Last, we inquired whether the respondents believed that the amount of H. pylori-related information available to them was adequate and whether they thought the quantity of published H. pylori-related research in children was sufficient. They were also asked to choose the top three sources of H. pylori-related information that they used from a list that included pediatric medical journals, conferences, newsletters, the Internet, and pharmaceutical company-sponsored symposia. They were also asked whether they were aware of—and had read—various important publications on H. pylori. These included the NIH consensus statement (5), the ADHF international update conference statement (1), the ACG practice guidelines (6), the American Academy of Pediatrics Red Book 2000—Report of the Committee on Infectious Disease (7), and the CDC report on H. pylori and peptic ulcer disease (8).
One hundred nine of 514 (21%) members of NASPGHAN completed the Internet-based survey. The mean age of respondents was 43.5 years (range, 30–65). One hundred eight (99%) had an M.D. degree, and 69 (63%) had graduated from a medical school in North America.
Eighty-two percent offered outpatient testing for H. pylori. Of these, 81% used serum antibody tests, 9% used whole blood tests, 60% used urea breath tests, and 19% used the stool antigen test. These numbers total more than 100% because some respondents used more than one test. Only 31% of respondents would restrict testing for H. pylori to children aged >5 years; 26% would test children regardless of age; 8% would test patients aged >1 month; and 35% would test patients aged >1 year.
Forty-seven percent agreed with the statement, “. . . all patients found to have H. pylori infection need to be treated for the infection.” However, 10% would consider testing for H. pylori in the absence of upper gastrointestinal symptoms, and 40% would offer treatment if the test results were positive.
From the 14 clinical scenarios depicted, the percentages of respondents who would test for H. pylori infection and offer treatment based on a positive test result are listed in Table 1. The treatment practices of pediatric gastroenterologists for eight hypothetical patients are listed in Table 2. The responses received are compared with the optimal responses as described in the NASPGHAN Clinical Practice Guidelines in Tables 1 and 2 (10).
Treatment regimens of choice are listed in Table 3; 78% of respondents used a triple regimen that included a PPI, and 80% used a regimen recommended for adult use in the ACG guidelines (6). If using a PPI-based triple regimen, 4% would treat patients for 7 days, 12% for 10 days, 75% for 14 days, and 9% for 28 days. Knowledge about H. pylori antimicrobial resistance rates was limited (Table 4). The percentages of respondents who correctly estimated the antimicrobial resistance rates to amoxicillin, clarithromycin, metronidazole, and tetracycline were 10%, 17%, 43%, and 12%, respectively.
The principal sources of information on H. pylori were medical journals (81%) and conferences (17%). Most respondents (87%) believed that the amount of information on H. pylori available to them was sufficient. However, only 14% thought that there had been sufficient research on H. pylori in children. The percentages of respondents aware of the various guidelines on H. pylori management were 72% for the NIH consensus statement, 39% for the ADHF international update conference statement, 53% for the ACG practice guidelines, 69% for the Red Book report, and 53% for the CDC guidelines on H. pylori. The percentages of respondents who said they had read each of them were 64%, 14%, 35%, 49%, and 32%, respectively.
Although it is disappointing that only 109 members of the NASPGHAN completed our survey, the results could possibly approximate practice patterns of pediatric gastroenterologists in North America. The 109 respondents were broadly distributed in cities from across the United States and Canada. It is possible that that the persons with the most knowledge of, or the greatest interest in, H. pylori infection would have been more likely to complete the survey. If so, our data may be biased by the inclusion of better informed pediatric gastroenterologists and thereby may not reflect a true cross-section of practicing pediatric gastroenterologists.
We previously published the results of a postal survey of the perceptions and practices of adult American gastroenterologists related to H. pylori infection (13). We found that most of these gastroenterologists appropriately tested adult peptic ulcer patients for H. pylori infection and treated the infection when present using effective regimens. However, we documented suboptimal understanding of antibiotic resistance rates and indications for testing and managing H. pylori. Our present survey demonstrated similar KAPS assessments among pediatric gastroenterologists in North America.
Most pediatric gastroenterologists who completed the survey offered testing for H. pylori infection in the outpatient setting and predominantly used serologic tests. However, serologic testing was not recommended in the NASPGHAN guidelines or in the other two consensus conferences. Commercially available serologic and whole blood assays used in physicians' offices are relatively poor for detecting H. pylori infection in children. The sensitivity may be only 60% to 70%, with similarly low specificity (14–16). Furthermore, commercially available serologic tests do not have established age-related reference values for children (15) and have not been validated for patients outside the populations in which they were initially developed (predominantly white men) (10,15). The NASPGHAN clinical practice guidelines recommend making a definitive diagnosis of H. pylori infection through endoscopy with multiple biopsies from different regions of the stomach (10). Similar recommendations were made by the European and Canadian consensus conferences based on the level of available evidence (11,12).
Although serology was the predominant choice of testing for H. pylori infection, 60% of the respondents also used the 13C-labeled urea breath test (UBT). This percentage is substantially higher than that found in our survey of adult gastroenterologists in the United States, of whom only 10% used a UBT (13). The higher usage of the UBT by pediatric gastroenterologists may reflect their more frequent use of other breath tests in clinical practice. Furthermore, with the passage of time since our survey of adult gastroenterologists, there may have been improved understanding that the UBT is an effective means for diagnosing active infection and for confirming eradication after treatment (6). However, despite the high sensitivity and specificity of the 13C-UBT in children (17), its operating characteristics are specific to individual laboratories and have not been well standardized for all children, particularly those aged <5 years (18). The UBT may become the test of choice for the accurate, noninvasive diagnosis of H. pylori infection in children after multicenter controlled trials with sufficient power have been performed. However, there was insufficient evidence for the NASPGHAN guidelines committee to recommend the UBT as the first step in the evaluation of a child with suspected H. pylori infection (10).
Only 31% of respondents confined testing for H. pylori infection to children aged >5 years. Noninvasive testing for H. pylori infection in younger children may not be useful or appropriate given the relatively low prevalence of primary infection among children born and raised in North America. The prevalence of H. pylori infection among children born in North America and Europe may be as low as 6% to 16% according to age (19). In industrialized countries, the estimated H. pylori incidence appears to be about 1% per year after infancy, reaching a prevalence of 15% to 20% by the end of adolescence (20–22). In Bolivia (20) and among Alaskan Natives (21), infection prevalence rates of 70% are demonstrated by age 10 years and by increased rates of gastric cancer.
In a multisite investigation of seropositivity for H. pylori in US children, a prevalence rate of 17% was observed (16). A previous population-based study of pediatric H. pylori infection using NHANES III sera demonstrated an overall seropositivity of 24.8% (23). Infection was strongly associated with increasing age and nonwhite ethnicity (17.0% of non-Hispanic whites vs. 40.1% of non-Hispanic blacks and 42.0% of Mexican Americans infected). Clearly, further epidemiologic research in North American children is needed to determine the optimal testing strategies based on prevalence of disease and infection.
Previous surveys have reported “significant” misunderstanding among internal medicine residents, primary care physicians, and gastroenterologists of some issues related to testing and treating H. pylori infection (13,24,25). Pediatric gastroenterologists share some of these misunderstandings. Most who completed our survey would test patients with gastric ulcer (GU) or duodenal ulcer (DU) for H. pylori infection. However, it is of concern that many would not treat the infection, even if a positive result were found. The percentages of respondents who would not treat documented H. pylori infection in patients with a new DU, a history of DU, or a new GU were 14%, 40%, and 24%, respectively. This finding is disappointing because, with the possible exception of low-grade gastric MALT lymphoma, peptic ulcer disease is the only condition in adults for which a benefit of eradication of H. pylori infection has been definitively proven in sufficiently powered randomized, controlled treatment trials (4). Although published data in children largely consist of single center case series, they support eradication therapy for ulcer disease. Single center studies have demonstrated resolution of gastritis after H. pylori eradication (26,27). The association of H. pylori infection with GU is not as well documented as for DU because of the low prevalence of GU in children (27). Nonetheless, NASPGHAN strongly recommends testing for H. pylori infection in children with documented GU or DU and treating the infection if it has been documented by histopathology (10).
Our data also indicated that many pediatric gastroenterologists would test for H. pylori infection in children with abdominal pain without evidence of peptic ulcer disease, especially when warning signs are present (Table 2). The NASPGHAN guidelines currently endorse testing for H. pylori infection in children with documentation of peptic ulcer or MALT lymphoma and in children with complicated peptic ulcer disease to confirm eradication of infection. However, routine testing for H. pylori is not currently recommended for children with abdominal pain unrelated to peptic ulcer, in asymptomatic children, or in children with a family history of gastric cancer or recurrent peptic ulcer disease (10).
Thirty-nine percent of respondents would test for H. pylori infection in children with gastroesophageal reflux disease (GERD) prescribed chronic PPI treatment, and 33% would test children who were starting PPI treatment for GERD. These rates are surprisingly high given that none of the national guidelines for adult or pediatric populations has recommended testing for H. pylori in patients with GERD (1,6,10). In children, there may be an association between H. pylori infection and histologic esophagitis (28,29). At this time, the NASPGHAN guidelines do not recommend testing for H. pylori infection in children with GERD.
To date, the optimum treatment regimen for the eradication of H. pylori infection in children has not been determined because of a lack of controlled studies in pediatric populations. Recommendations for treatment strategies from the European and Canadian Consensus statements (11,12) and the NASPGHAN guidelines (10) were primarily developed through extrapolations from level 1 randomized controlled treatment trials in adults and from single center case series and anecdotal observations in children. Despite the lack of available data from controlled studies in children, NASPGHAN's formal recommendations for first-line therapy include a PPI and two antibiotics for 1 to 2 weeks (10). Most of our respondents used drug regimens that are endorsed by NASPGHAN. However, 20% used either a PPI-based dual regimen or another treatment regimen that was not FDA-approved in adults. Monotherapy and dual regimens have been determined to be ineffective and likely promote antibiotic resistance (30).
As with similar surveys in other groups of physicians (13,24,25), most respondents to this survey underestimated the resistance rates to clarithromycin and metronidazole. Recent estimates of the rate of clarithromycin resistance in the United States are between 8% and 12.6% (31). Only 16% of our respondents believed the frequency of clarithromycin resistance to be more than 10%. Recently reported resistance rates to metronidazole have been between 33% and 54% (4,32). However, only 43% of our respondents thought that it was more than 10%. In contrast, most respondents overestimated resistance rates to amoxicillin and tetracycline. Only 10% and 12% of respondents selected correct estimates for amoxicillin and tetracycline resistance rates, respectively.
Follow-up KAPS studies are planned for the future now that clinical practice guidelines and two consensus statements (10–12) have been published. Moreover, randomized placebo-controlled clinical trials and multicenter epidemiologic studies assessing infection prevalence and disease impact are critically needed in the pediatric population. In addition, studies comparing practice styles with treatment outcomes of H. pylori-infected children as a measure of practice effectiveness are clearly needed. Such studies would aid in the development of cost-effective, appropriate clinical practice guidelines for treating H. pylori-infected infants, children, and adolescents.
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