SlideShare a Scribd company logo
1 of 8
Download to read offline
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
                              Gastroenterology and Nutrition

Helicobacter pylori Infection in Children: Recommendations for
                   Diagnosis and Treatment
     *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.
still large gaps in knowledge.                                                      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                           oral-oral (12).
support the role of H. pylori in the pathogenesis of gas-                           Although H. pylori infection may be acquired during
tric cancers (5).                                                                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 ensure
                                                                                 judicious 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,
Atlanta, GA 30322, U.S.A.; or to Dr. Richard B. Colletti, University of
                                                                                 appointed the Helicobacter pylori Infection Guideline
Vermont, Department of Pediatrics, A-121 Given Medical Building,                 Committee to develop a clinical practice guideline for
Burlington, VT 05405-5557, U.S.A.                                                the child with H. pylori infection.

                                                                           490
TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION                                                             491


   These clinical practice guidelines are designed to as-            TABLE 1. Summary of recommendations and the quality of
sist primary care physicians, nurse practitioners, physi-                         the supporting evidence
cian assistants, and pediatric gastroenterologists in the                                                                           Quality of
evaluation and treatment of suspected or diagnosed H.                                    Recommendations                            evidencea
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                     endoscopy with biopsy.                                     II, III
countries where the prevalence of infection is low but                Presently available commercial serologic tests are
                                                                         frequently unreliable for screening children for the
may not be directly relevant to children living in com-                  presence of H. pylori infection.                             II
munities where there is a higher frequency of gastric                 Urea breath testing, although promising, has not been
colonization by H. pylori. These recommendations have                    studied sufficiently in children.                             II
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.      I
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.        II
                                                                      Testing for H. pylori infection is not recommended in
patients.                                                                asymptomatic children.                                        II
   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             not recommended.                                              II
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 endoscopy
                                                                         and biopsy be performed to evaluate for the
                                                                         persistence of H. pylori-associated peptic ulcer
                         METHODS                                         disease.                                                    I, II
                                                                      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          recommended.                                                 II
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 at
                                                                         endoscopy and H. pylori detected on histology.                I
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.                            I
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.            III
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 at
                                                                         increased 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.          III
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).                    one to two weeks.                                             I
                                                                        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
                                                                     obtained from well-designed cohort or case-controlled trials without
            H. PYLORI INFECTION?                                     randomization. II-2 Evidence obtained from well-designed cohort or
                                                                     case-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 Opinions
                                                                     of 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
492                                                           GOLD ET AL.

          TABLE 2. Tests for Helicobacter pylori and                 study. The optimal staining of biopsy sections is best
               Helicobacter-related disorders                        determined by local expert pathologists. Endoscopic ex-
            Invasive tests requiring endoscopy
                                                                     amination of and specimens obtained in the esophagus,
              Biopsies and histology                                 stomach, and duodenum also provide information about
              Rapid urease testing                                   other upper gastrointestinal disorders that may be the
              Bacterial culture                                      cause of clinical symptoms including, for example,
              Polymerase chain reaction of bacterial DNA             esophagitis and peptic ulcer disease that is not due to H.
            Non-invasive tests
              Serum and whole blood antibody                         pylori.
              Saliva antibody                                           There are drawbacks to diagnostic gastrointestinal en-
              Urine antibody                                         doscopy. It is a relatively invasive procedure requiring
              Stool antigen                                          sedation or anesthesia. Furthermore, the test remains
              Urea breath testing
                                                                     relatively expensive in many centers, and access to an
                                                                     endoscopist with specific pediatric expertise is limited in
                                                                     many geographic areas.
organism. In addition, such a test enables discrimination
between 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-
cost savings (17).                                                   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              population tested.
various noninvasive diagnostic tests in populations in
North America that differ in demographic factors that
may influence the prevalence and natural history of H.                                    Bacterial Culture
pylori infection (18).                                                  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
                  Biopsies and Histopathology                        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-            tinely in research settings.
ence of H. pylori and the severity and topographic dis-
tribution of gastritis including the presence of atrophic                           Polymerase Chain Reaction
gastritis, intestinal metaplasia, and mucosa-associated
lymphoid 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                                                       493


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
outside the research laboratory.                                are more difficult to test. Additional pediatric studies
                                                                evaluating the accuracy of stool antigen testing for both
                                                                initial diagnosis and posttreatment follow-up are re-
                  Noninvasive Testing
                                                                quired before specific recommendations can be consid-
   Immunoassay Tests to Detect H. pylori Antibodies             ered (32).

   Enzyme-linked immunosorbent assays (ELISAs) to                                   Urea Breath Testing
detect H. pylori antibodies are relatively inexpensive and
easy to implement in the clinical setting. Many tests are
available 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-        the clinical research setting (34).
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
despite resolution of infection.                                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 the
                                                                accuracy 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      associated diseases.
affect the accuracy of test results. Urine-based assays are
easy to perform, require minimal labor for collection,
and are painless (30). However, these assays are highly
variable and are not yet commercially available. There-                  WHEN IS TESTING INDICATED?
fore, saliva and urine assays for the detection of H. pylori
antibodies 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 will
                                                                alter 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
494                                                           GOLD ET AL.


    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             is not recommended.
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 abdominal
pain in children. There have been six studies performed
in 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 persistence
                                                                     of 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                   setting.

   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
ommended in these circumstances.                                     endoscopic gastric biopsy. Serology is not a reliable test
                                                                     for 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                                                       495


             Duodenal and Gastric Ulcers                        cost of care. Therefore, the H. pylori Infection Guideline
                                                                Committee 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        treatment in this situation.
endoscopy and H. pylori documented by histopathology.
A prior history of duodenal or gastric ulcer disease is also
an 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), eradication
therapy is indicated if either a noninvasive or invasive
test 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 abdominal
                                                                pain. 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      cancer need treatment.
with lymphoma should be performed to monitor the re-
currence, progression, or remission of the tumor after
therapy.                                                         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 a
                                                                specific 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     methodology (61).
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
496                                                                    GOLD ET AL.

TABLE 3. Recommended eradication therapies for H. pylori                      pump inhibitor also reduces the effectiveness of eradica-
                disease in children                                           tion treatment protocols. Studies are needed to determine
First-line
                                                                              the relative importance of these risk factors in pediatric
 options                Medications                           Dosage          populations.
    1        amoxicillin                           50 mg/kg/day up to
                                                     1 g bid                                           REFERENCES
             clarithromycin                        15 mg/kg/day up to
                                                     500 mg bid                1. Ernst PB, Gold BD. Helicobacter pylori in childhood: new insights
             proton pump inhibitor:                1 mg/kg/day up to 20           into the immunopathogenesis of gastric disease and implications
               omeprazole (or comparable             mg bid                       for managing infection in children. J Pediatr Gastroenterol Nutr.
               acid inhibitory doses of                                           1999;28:462–73.
               another PPI)                                                    2. Drumm B. Helicobacter pylori in the pediatric patient. Gastroen-
    2        amoxicillin                           50 mg/kg/day up to             terol Clin North Am. 1993;22:169–82.
                                                     1 g bid                   3. Dohil R, Hassall E, Jevon G, et al. Gastritis and gastropathy of
             metronidazole                         20 mg/kg/day–500               childhood. J Pediatr Gastroenterol Nutr. 1999;29:378–94.
                                                     mg bid                    4. Huang J-Q, Sridhars CY, Hunt RH. Meta-analysis of the relation-
             proton pump inhibitor:                1 mg/kg/day up to 20           ship between Helicobacter pylori seropositivity and gastric cancer.
                omeprazole (or comparable            mg bid                       Gastroenterology. 1998;114:1169–79.
                acid inhibitory doses of                                       5. Watanabe T, Tada M, Nagai H, et al. Helicobacter pylori infection
                another PPI)                                                      induces gastric cancer in Mongolian gerbils. Gastroenterology.
    3        clarithromycin                        15 mg/kg/day up to             1998;115:642–8.
                                                     500 mg bid                6. Webb PM, Knight T, Greaves S, et al. Relation between infection
             metronidazole                         20 mg/kg/day up to             with Helicobacter pylori and living conditions in childhood: evi-
                                                     500 mg bid                   dence for person to person transmission in early life. BMJ. 1994;
           proton pump inhibitor:                  1 mg/kg/day up to 20           308:750–3.
              omeprazole (or comparable              mg bid                    7. Parsonnet J. The incidence of Helicobacter pylori infection. Ali-
              acid inhibitory doses of                                            ment Pharmacol Ther. 1995;9:45–51.
              another PPI)                                                     8. Handt LK, Fox JG, Stalis IH, et al. Characterization of feline
Second-line options                                                               Helicobacter pylori strains and associated gastritis in a colony of
   4       bismuth subsalicylate                   1 tablet (262 mg) qid          domestic cats. J Clin Microbiol. 1995;33:2280–9.
                                                      or 15 ml (17.6           9. Grubel P, Hoffman JS, Chong FK, et al. Vector potential of house-
                                                      mg/mL qid)                  flies (Musca domestica) for Helicobacter pylori. J Clin Microbiol.
             metronidazole                         20 mg/kg/day–500               1997;35:1300–3.
                                                      mg bid
                                                                              10. Klein PD, Graham DY, Gaillour A, et al. Water source as a risk
             proteon pump inhibitor:               1 mg/kg/day up to 20
                                                                                  factor for Helicobacter pylori infection in Peruvian children. Lan-
               omeprazole (or comparable              mg bid
                                                                                  cet. 1991;337:1503–6.
               acid inhibitory doses of
                                                                              11. Staat MA, Kruszon-Moran D, McQuillan GM, et al. A population-
               another PPI)
                                                                                  based serologic survey of Helicobacter pylori infection in children
             pus, an additional antibiotic:        50 mg/kg/day up to
                                                                                  and adolescents in the United States. J Infect Dis. 1996;174:
               amoxicillin                            1 g bid
                                                                                  1120–3.
             or tetracyclinea                      50 mg/kg/day up to
                                                                              12. Goodman KJ, Correa P. The transmission of Helicobacter pylori:
                                                      1 g bid
                                                                                  a critical review of the evidence. Int J Epidemiol. 1995;24:875–87.
             or clarithromycin                     15 mg/kg/day–500
                                                                              13. Sackett DL, Richardson WS, Rosenberg W, et al. Evidence-based
                                                      mg bid
                                                                                  Medicine: How to Practice and Teach EBM. Edinburgh: Churchill
    5        ranitidine bismuth-citrate            1 tablet qid
                                                                                  Livingston; 1998.
             clarithromycin                        15 mg/kg/day–500
                                                      mg bid                  14. McMurray AR. Three decision-making aids: brainstorming, nomi-
             metronidazole                         20 mg/kg/day–500               nal group, and Delphi technique. J Nurs Staff Dev. 1994;10:62–5.
                                                      mg bid                  15. Cockeram AW. Clinical practice guidelines: help or hindrance? J
                                                                                  Pediatr Gastroenterol Nutr. 1999;28:362–3.
  Initial treatment should be provided in a twice daily regimen (to           16. Canadian Task Force on the Periodic Health Examination: the
enhance compliance) for 7 to 14 days.                                             periodic health examination. Can Med Assoc J. 1979;121:1193–
  a
    Only for children 12 years of age or older.                                   254.
  bid, twice daily; qid, four times daily.                                    17. Olson AD, Fendrick AM, Deutsch D, et al. Evaluation of initial
                                                                                  noninvasive therapy in pediatric patients presenting with suspected
                                                                                  ulcer 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                         delphia: Lippincott–Raven; 1998.
                                                                              19. Genta RM, Graham DY. Comparison of biopsy sites for the his-
when a three- or four-drug regimen is used. Resistance of                         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.                            2108–10.
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.
                                                                              21. Elitsur Y, Hill I, Lichtman SN, et al. Prospective comparison of
could eventually impair the therapeutic effectiveness 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                                                                  497

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.                                             1996;22:148–52.
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                JAMA. 1995;273:729–34.
    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-                1995;126:753–6.
    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.
    1999;28:157–61.                                                         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;
    1998;178:460–5.                                                               39:1488–92.
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.
    91:1145–9.                                                                    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-
    1999;354:30–3.                                                                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:                19:362–7.
    347–8.                                                                  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-             1994;20:1161–81.
    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-               1875–81.
    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-
    131:791–3.                                                                    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.
    1999;13:553–9.                                                          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
    diatr Surg. 1995;30:427–9.                                                    Med. 1998;105:424–30.
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                Dis Child. 1999;81:68–70.




                                                                                             J Pediatr Gastroenterol Nutr, Vol. 31, No. 5, November 2000

More Related Content

What's hot

Clinical chacateristics of novel coronavirua in newborns, infants, and children
Clinical chacateristics of novel coronavirua in newborns, infants, and childrenClinical chacateristics of novel coronavirua in newborns, infants, and children
Clinical chacateristics of novel coronavirua in newborns, infants, and childrengisa_legal
 
Childhood Tuberculosis and Community Healthcare_Kechi Achebe_5.8.14
Childhood Tuberculosis and Community Healthcare_Kechi Achebe_5.8.14Childhood Tuberculosis and Community Healthcare_Kechi Achebe_5.8.14
Childhood Tuberculosis and Community Healthcare_Kechi Achebe_5.8.14CORE Group
 
Hepatitis - Epidemiology Assignment
Hepatitis - Epidemiology AssignmentHepatitis - Epidemiology Assignment
Hepatitis - Epidemiology AssignmentJames Lewis
 
Diarrea and dehydration
Diarrea and dehydrationDiarrea and dehydration
Diarrea and dehydrationabiyotdejene2
 
126553270 amoebiasis-case
126553270 amoebiasis-case126553270 amoebiasis-case
126553270 amoebiasis-casehomeworkping8
 
Hiv _case_presentation(1)
 Hiv _case_presentation(1) Hiv _case_presentation(1)
Hiv _case_presentation(1)9751111158
 
Congenital Tuberculosis (Updated in 2020)
Congenital Tuberculosis (Updated in 2020)Congenital Tuberculosis (Updated in 2020)
Congenital Tuberculosis (Updated in 2020)Sonali Paradhi Mhatre
 
Impact of Hepatitis B Virus (HBV) Vaccination in Childrens Born to HBV Positi...
Impact of Hepatitis B Virus (HBV) Vaccination in Childrens Born to HBV Positi...Impact of Hepatitis B Virus (HBV) Vaccination in Childrens Born to HBV Positi...
Impact of Hepatitis B Virus (HBV) Vaccination in Childrens Born to HBV Positi...IOSR Journals
 
How did the Baby Boomers get afflicted with hepatitis C?
How did the Baby Boomers get afflicted with hepatitis C?How did the Baby Boomers get afflicted with hepatitis C?
How did the Baby Boomers get afflicted with hepatitis C?Sunny Meredith
 
Mc4 hc allergies
Mc4 hc allergiesMc4 hc allergies
Mc4 hc allergiesstellablue
 
7 pediatric research
7   pediatric research7   pediatric research
7 pediatric researchJuan R Farro
 
Investigation of an epidemic
Investigation of an epidemicInvestigation of an epidemic
Investigation of an epidemicDevyani Wanjari
 

What's hot (20)

Clinical chacateristics of novel coronavirua in newborns, infants, and children
Clinical chacateristics of novel coronavirua in newborns, infants, and childrenClinical chacateristics of novel coronavirua in newborns, infants, and children
Clinical chacateristics of novel coronavirua in newborns, infants, and children
 
Who guidelines ari
Who guidelines ariWho guidelines ari
Who guidelines ari
 
Childhood Tuberculosis and Community Healthcare_Kechi Achebe_5.8.14
Childhood Tuberculosis and Community Healthcare_Kechi Achebe_5.8.14Childhood Tuberculosis and Community Healthcare_Kechi Achebe_5.8.14
Childhood Tuberculosis and Community Healthcare_Kechi Achebe_5.8.14
 
Hepatitis - Epidemiology Assignment
Hepatitis - Epidemiology AssignmentHepatitis - Epidemiology Assignment
Hepatitis - Epidemiology Assignment
 
Diarrea and dehydration
Diarrea and dehydrationDiarrea and dehydration
Diarrea and dehydration
 
126553270 amoebiasis-case
126553270 amoebiasis-case126553270 amoebiasis-case
126553270 amoebiasis-case
 
Unit 3 health and illness ppt
Unit 3 health and illness pptUnit 3 health and illness ppt
Unit 3 health and illness ppt
 
Hiv _case_presentation(1)
 Hiv _case_presentation(1) Hiv _case_presentation(1)
Hiv _case_presentation(1)
 
Congenital Tuberculosis (Updated in 2020)
Congenital Tuberculosis (Updated in 2020)Congenital Tuberculosis (Updated in 2020)
Congenital Tuberculosis (Updated in 2020)
 
The subject of food poisoning
The subject of food poisoningThe subject of food poisoning
The subject of food poisoning
 
Impact of Hepatitis B Virus (HBV) Vaccination in Childrens Born to HBV Positi...
Impact of Hepatitis B Virus (HBV) Vaccination in Childrens Born to HBV Positi...Impact of Hepatitis B Virus (HBV) Vaccination in Childrens Born to HBV Positi...
Impact of Hepatitis B Virus (HBV) Vaccination in Childrens Born to HBV Positi...
 
How did the Baby Boomers get afflicted with hepatitis C?
How did the Baby Boomers get afflicted with hepatitis C?How did the Baby Boomers get afflicted with hepatitis C?
How did the Baby Boomers get afflicted with hepatitis C?
 
Communicable disease control
Communicable disease controlCommunicable disease control
Communicable disease control
 
HIV IN PREGNANCY
HIV IN PREGNANCYHIV IN PREGNANCY
HIV IN PREGNANCY
 
Mc4 hc allergies
Mc4 hc allergiesMc4 hc allergies
Mc4 hc allergies
 
7 pediatric research
7   pediatric research7   pediatric research
7 pediatric research
 
Investigation of an epidemic
Investigation of an epidemicInvestigation of an epidemic
Investigation of an epidemic
 
Covid 19
Covid 19Covid 19
Covid 19
 
60422493 case-study
60422493 case-study60422493 case-study
60422493 case-study
 
Covid19 and pregnancy
Covid19 and pregnancyCovid19 and pregnancy
Covid19 and pregnancy
 

Similar to Diagnosi e trattamento delle infezioni da H. Pylori in pediatria

Helicobacter Pylori Research Papers
Helicobacter Pylori Research PapersHelicobacter Pylori Research Papers
Helicobacter Pylori Research PapersCourtney Bennett
 
Symptoms And Treatment Of Laryngopharyngeal Reflux ( Lpr )
Symptoms And Treatment Of Laryngopharyngeal Reflux ( Lpr )Symptoms And Treatment Of Laryngopharyngeal Reflux ( Lpr )
Symptoms And Treatment Of Laryngopharyngeal Reflux ( Lpr )Mandy Hebert
 
Helicobacter Pylori Research Paper
Helicobacter Pylori Research PaperHelicobacter Pylori Research Paper
Helicobacter Pylori Research PaperNicole Savoie
 
Research Paper On Helicobacter Pylori
Research Paper On Helicobacter PyloriResearch Paper On Helicobacter Pylori
Research Paper On Helicobacter PyloriShannon Wright
 
Regional Antibiotic Resistance Of Helicobacter Pylori
Regional Antibiotic Resistance Of Helicobacter PyloriRegional Antibiotic Resistance Of Helicobacter Pylori
Regional Antibiotic Resistance Of Helicobacter PyloriMelissa Dudas
 
annurev-med-042220-020814.pdf
annurev-med-042220-020814.pdfannurev-med-042220-020814.pdf
annurev-med-042220-020814.pdfArlenElisa1
 
Current Understanding of the Transmission, Diagnosis, and Treatment of H. pyl...
Current Understanding of the Transmission, Diagnosis, and Treatment of H. pyl...Current Understanding of the Transmission, Diagnosis, and Treatment of H. pyl...
Current Understanding of the Transmission, Diagnosis, and Treatment of H. pyl...AI Publications
 
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...Prof.Louay Labban
 
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...Prof.Louay Labban
 
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...Prof.Louay Labban
 
Helicobacter Pylori
Helicobacter PyloriHelicobacter Pylori
Helicobacter PyloriIvani Rosado
 
Mycobacterium Avium Paratuberculosis (Johne’s Disease)
Mycobacterium Avium Paratuberculosis (Johne’s Disease)Mycobacterium Avium Paratuberculosis (Johne’s Disease)
Mycobacterium Avium Paratuberculosis (Johne’s Disease)K.M. Smith, Ph.D.
 
Helicobacter Pylori And Gastric Cancer
Helicobacter Pylori And Gastric CancerHelicobacter Pylori And Gastric Cancer
Helicobacter Pylori And Gastric CancerAngie Lee
 
Peptic Ulcer Disease And Pediatric Patients
Peptic Ulcer Disease And Pediatric PatientsPeptic Ulcer Disease And Pediatric Patients
Peptic Ulcer Disease And Pediatric PatientsElena
 
Antibiotic treatment of_acute_gastroenteritis_in_c
Antibiotic treatment of_acute_gastroenteritis_in_cAntibiotic treatment of_acute_gastroenteritis_in_c
Antibiotic treatment of_acute_gastroenteritis_in_cDINYAULIYAROHMAH
 
H Pylori Management 2023 .pptx
H Pylori Management 2023 .pptxH Pylori Management 2023 .pptx
H Pylori Management 2023 .pptxDrChernHaoChong
 
H. pylori past, present and future
H. pylori past, present and futureH. pylori past, present and future
H. pylori past, present and futureSameh Badr
 

Similar to Diagnosi e trattamento delle infezioni da H. Pylori in pediatria (20)

Helicobacter Pylori Research Papers
Helicobacter Pylori Research PapersHelicobacter Pylori Research Papers
Helicobacter Pylori Research Papers
 
Symptoms And Treatment Of Laryngopharyngeal Reflux ( Lpr )
Symptoms And Treatment Of Laryngopharyngeal Reflux ( Lpr )Symptoms And Treatment Of Laryngopharyngeal Reflux ( Lpr )
Symptoms And Treatment Of Laryngopharyngeal Reflux ( Lpr )
 
Helicobacter Pylori Research Paper
Helicobacter Pylori Research PaperHelicobacter Pylori Research Paper
Helicobacter Pylori Research Paper
 
Research Paper On Helicobacter Pylori
Research Paper On Helicobacter PyloriResearch Paper On Helicobacter Pylori
Research Paper On Helicobacter Pylori
 
Cirrhotic Essay
Cirrhotic EssayCirrhotic Essay
Cirrhotic Essay
 
Regional Antibiotic Resistance Of Helicobacter Pylori
Regional Antibiotic Resistance Of Helicobacter PyloriRegional Antibiotic Resistance Of Helicobacter Pylori
Regional Antibiotic Resistance Of Helicobacter Pylori
 
annurev-med-042220-020814.pdf
annurev-med-042220-020814.pdfannurev-med-042220-020814.pdf
annurev-med-042220-020814.pdf
 
Current Understanding of the Transmission, Diagnosis, and Treatment of H. pyl...
Current Understanding of the Transmission, Diagnosis, and Treatment of H. pyl...Current Understanding of the Transmission, Diagnosis, and Treatment of H. pyl...
Current Understanding of the Transmission, Diagnosis, and Treatment of H. pyl...
 
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...
 
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...
 
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...
C:\Documents And Settings\Louay Labban Uok\Desktop\All\Powerpoints\Helicopact...
 
ASI johne's publication
ASI johne's publicationASI johne's publication
ASI johne's publication
 
Helicobacter Pylori
Helicobacter PyloriHelicobacter Pylori
Helicobacter Pylori
 
Mycobacterium Avium Paratuberculosis (Johne’s Disease)
Mycobacterium Avium Paratuberculosis (Johne’s Disease)Mycobacterium Avium Paratuberculosis (Johne’s Disease)
Mycobacterium Avium Paratuberculosis (Johne’s Disease)
 
Helicobacter Pylori And Gastric Cancer
Helicobacter Pylori And Gastric CancerHelicobacter Pylori And Gastric Cancer
Helicobacter Pylori And Gastric Cancer
 
Peptic Ulcer Disease And Pediatric Patients
Peptic Ulcer Disease And Pediatric PatientsPeptic Ulcer Disease And Pediatric Patients
Peptic Ulcer Disease And Pediatric Patients
 
H. pylori
H. pyloriH. pylori
H. pylori
 
Antibiotic treatment of_acute_gastroenteritis_in_c
Antibiotic treatment of_acute_gastroenteritis_in_cAntibiotic treatment of_acute_gastroenteritis_in_c
Antibiotic treatment of_acute_gastroenteritis_in_c
 
H Pylori Management 2023 .pptx
H Pylori Management 2023 .pptxH Pylori Management 2023 .pptx
H Pylori Management 2023 .pptx
 
H. pylori past, present and future
H. pylori past, present and futureH. pylori past, present and future
H. pylori past, present and future
 

More from MerqurioEditore_redazione

Stomatite aftosa ricorrente classificazione e trattamenti
Stomatite aftosa ricorrente classificazione e trattamentiStomatite aftosa ricorrente classificazione e trattamenti
Stomatite aftosa ricorrente classificazione e trattamentiMerqurioEditore_redazione
 
Le onicopatie. prevenzione, diagnosi differenziale e trattamento
Le onicopatie. prevenzione, diagnosi differenziale e trattamentoLe onicopatie. prevenzione, diagnosi differenziale e trattamento
Le onicopatie. prevenzione, diagnosi differenziale e trattamentoMerqurioEditore_redazione
 
Sondaggi e analisi di mercato online e telefonici: efficienza e rapidità
Sondaggi e analisi di mercato online e telefonici: efficienza e rapidità Sondaggi e analisi di mercato online e telefonici: efficienza e rapidità
Sondaggi e analisi di mercato online e telefonici: efficienza e rapidità MerqurioEditore_redazione
 
Phone-detailing: efficienza nell’informazione scientifica ed efficacia nella ...
Phone-detailing: efficienza nell’informazione scientifica ed efficacia nella ...Phone-detailing: efficienza nell’informazione scientifica ed efficacia nella ...
Phone-detailing: efficienza nell’informazione scientifica ed efficacia nella ...MerqurioEditore_redazione
 
Gruppo Merqurio: Merqurio Pharma – Merqurio Servizi – Merqurio Editore
Gruppo Merqurio: Merqurio Pharma – Merqurio Servizi – Merqurio EditoreGruppo Merqurio: Merqurio Pharma – Merqurio Servizi – Merqurio Editore
Gruppo Merqurio: Merqurio Pharma – Merqurio Servizi – Merqurio EditoreMerqurioEditore_redazione
 
Medical Information Service: servizio di consulenza scientifica in ricerche B...
Medical Information Service: servizio di consulenza scientifica in ricerche B...Medical Information Service: servizio di consulenza scientifica in ricerche B...
Medical Information Service: servizio di consulenza scientifica in ricerche B...MerqurioEditore_redazione
 
CSO Merqurio: la rete di informazione scientifica conto terzi oggi è dotata d...
CSO Merqurio: la rete di informazione scientifica conto terzi oggi è dotata d...CSO Merqurio: la rete di informazione scientifica conto terzi oggi è dotata d...
CSO Merqurio: la rete di informazione scientifica conto terzi oggi è dotata d...MerqurioEditore_redazione
 
Canali online: la comunicazione scientifica professionale sul web
Canali online: la comunicazione scientifica professionale sul webCanali online: la comunicazione scientifica professionale sul web
Canali online: la comunicazione scientifica professionale sul webMerqurioEditore_redazione
 
e-Detailing: la comunicazione medico scientifica con efficacia promozional
e-Detailing: la comunicazione medico scientifica  con efficacia promozionale-Detailing: la comunicazione medico scientifica  con efficacia promozional
e-Detailing: la comunicazione medico scientifica con efficacia promozionalMerqurioEditore_redazione
 
Supplemento di ferro e vitamnine in donne anemiche in gravidanza
Supplemento di ferro e vitamnine  in donne anemiche in gravidanzaSupplemento di ferro e vitamnine  in donne anemiche in gravidanza
Supplemento di ferro e vitamnine in donne anemiche in gravidanzaMerqurioEditore_redazione
 
Ulipristal acetato, nuovo farmaco per la contraccezione d'emergenza
Ulipristal acetato, nuovo farmaco per la contraccezione d'emergenzaUlipristal acetato, nuovo farmaco per la contraccezione d'emergenza
Ulipristal acetato, nuovo farmaco per la contraccezione d'emergenzaMerqurioEditore_redazione
 
Ulipristal acetato, nuovo farmaco per la contraccezione d'emergenza
Ulipristal acetato, nuovo farmaco per la contraccezione d'emergenzaUlipristal acetato, nuovo farmaco per la contraccezione d'emergenza
Ulipristal acetato, nuovo farmaco per la contraccezione d'emergenzaMerqurioEditore_redazione
 
Approcci bioenergetici per la neuroprotezione nella malattia parkinsoniana
Approcci bioenergetici per la neuroprotezione nella malattia parkinsonianaApprocci bioenergetici per la neuroprotezione nella malattia parkinsoniana
Approcci bioenergetici per la neuroprotezione nella malattia parkinsonianaMerqurioEditore_redazione
 
La conduzione del nervo surale dorsale in pazienti con carenza di vitamina B1...
La conduzione del nervo surale dorsale in pazienti con carenza di vitamina B1...La conduzione del nervo surale dorsale in pazienti con carenza di vitamina B1...
La conduzione del nervo surale dorsale in pazienti con carenza di vitamina B1...MerqurioEditore_redazione
 

More from MerqurioEditore_redazione (20)

Stomatite aftosa ricorrente classificazione e trattamenti
Stomatite aftosa ricorrente classificazione e trattamentiStomatite aftosa ricorrente classificazione e trattamenti
Stomatite aftosa ricorrente classificazione e trattamenti
 
Micosi e amorolfina
Micosi e amorolfinaMicosi e amorolfina
Micosi e amorolfina
 
Antimicotici
AntimicoticiAntimicotici
Antimicotici
 
Il controllo delle micosi gli antifungini
Il controllo delle micosi  gli antifunginiIl controllo delle micosi  gli antifungini
Il controllo delle micosi gli antifungini
 
Le onicopatie. prevenzione, diagnosi differenziale e trattamento
Le onicopatie. prevenzione, diagnosi differenziale e trattamentoLe onicopatie. prevenzione, diagnosi differenziale e trattamento
Le onicopatie. prevenzione, diagnosi differenziale e trattamento
 
Sondaggi e analisi di mercato online e telefonici: efficienza e rapidità
Sondaggi e analisi di mercato online e telefonici: efficienza e rapidità Sondaggi e analisi di mercato online e telefonici: efficienza e rapidità
Sondaggi e analisi di mercato online e telefonici: efficienza e rapidità
 
Phone-detailing: efficienza nell’informazione scientifica ed efficacia nella ...
Phone-detailing: efficienza nell’informazione scientifica ed efficacia nella ...Phone-detailing: efficienza nell’informazione scientifica ed efficacia nella ...
Phone-detailing: efficienza nell’informazione scientifica ed efficacia nella ...
 
Gruppo Merqurio: Merqurio Pharma – Merqurio Servizi – Merqurio Editore
Gruppo Merqurio: Merqurio Pharma – Merqurio Servizi – Merqurio EditoreGruppo Merqurio: Merqurio Pharma – Merqurio Servizi – Merqurio Editore
Gruppo Merqurio: Merqurio Pharma – Merqurio Servizi – Merqurio Editore
 
Medical Information Service: servizio di consulenza scientifica in ricerche B...
Medical Information Service: servizio di consulenza scientifica in ricerche B...Medical Information Service: servizio di consulenza scientifica in ricerche B...
Medical Information Service: servizio di consulenza scientifica in ricerche B...
 
CSO Merqurio: la rete di informazione scientifica conto terzi oggi è dotata d...
CSO Merqurio: la rete di informazione scientifica conto terzi oggi è dotata d...CSO Merqurio: la rete di informazione scientifica conto terzi oggi è dotata d...
CSO Merqurio: la rete di informazione scientifica conto terzi oggi è dotata d...
 
Canali online: la comunicazione scientifica professionale sul web
Canali online: la comunicazione scientifica professionale sul webCanali online: la comunicazione scientifica professionale sul web
Canali online: la comunicazione scientifica professionale sul web
 
e-Detailing: la comunicazione medico scientifica con efficacia promozional
e-Detailing: la comunicazione medico scientifica  con efficacia promozionale-Detailing: la comunicazione medico scientifica  con efficacia promozional
e-Detailing: la comunicazione medico scientifica con efficacia promozional
 
Emostasi
EmostasiEmostasi
Emostasi
 
Emostasi
EmostasiEmostasi
Emostasi
 
Supplemento di ferro e vitamnine in donne anemiche in gravidanza
Supplemento di ferro e vitamnine  in donne anemiche in gravidanzaSupplemento di ferro e vitamnine  in donne anemiche in gravidanza
Supplemento di ferro e vitamnine in donne anemiche in gravidanza
 
Linee guida per la fibrillazione atriale
Linee guida per la fibrillazione atrialeLinee guida per la fibrillazione atriale
Linee guida per la fibrillazione atriale
 
Ulipristal acetato, nuovo farmaco per la contraccezione d'emergenza
Ulipristal acetato, nuovo farmaco per la contraccezione d'emergenzaUlipristal acetato, nuovo farmaco per la contraccezione d'emergenza
Ulipristal acetato, nuovo farmaco per la contraccezione d'emergenza
 
Ulipristal acetato, nuovo farmaco per la contraccezione d'emergenza
Ulipristal acetato, nuovo farmaco per la contraccezione d'emergenzaUlipristal acetato, nuovo farmaco per la contraccezione d'emergenza
Ulipristal acetato, nuovo farmaco per la contraccezione d'emergenza
 
Approcci bioenergetici per la neuroprotezione nella malattia parkinsoniana
Approcci bioenergetici per la neuroprotezione nella malattia parkinsonianaApprocci bioenergetici per la neuroprotezione nella malattia parkinsoniana
Approcci bioenergetici per la neuroprotezione nella malattia parkinsoniana
 
La conduzione del nervo surale dorsale in pazienti con carenza di vitamina B1...
La conduzione del nervo surale dorsale in pazienti con carenza di vitamina B1...La conduzione del nervo surale dorsale in pazienti con carenza di vitamina B1...
La conduzione del nervo surale dorsale in pazienti con carenza di vitamina B1...
 

Recently uploaded

Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024Peter Embi
 
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdfSGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdfHongBiThi1
 
Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.kishan singh tomar
 
Red Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdfRed Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdfMedicoseAcademics
 
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdfSGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdfHongBiThi1
 
historyofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusanguhistoryofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusangu Medical University
 
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfCONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfDolisha Warbi
 
Adenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisAdenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisSujoy Dasgupta
 
Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Vaikunthan Rajaratnam
 
Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu Medical University
 
MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.whalesdesign
 
Using Data Visualization in Public Health Communications
Using Data Visualization in Public Health CommunicationsUsing Data Visualization in Public Health Communications
Using Data Visualization in Public Health Communicationskatiequigley33
 
High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)kishan singh tomar
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets barmohitRahangdale
 
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaSujoy Dasgupta
 
Unit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptUnit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptPradnya Wadekar
 

Recently uploaded (20)

Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024
 
American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...
 
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdfSGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
 
Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.
 
Red Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdfRed Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdf
 
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdfSGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
 
historyofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusanguhistoryofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusangu
 
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfCONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
 
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
 
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
 
Adenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisAdenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosis
 
Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.
 
Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu
 
MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.
 
Using Data Visualization in Public Health Communications
Using Data Visualization in Public Health CommunicationsUsing Data Visualization in Public Health Communications
Using Data Visualization in Public Health Communications
 
High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets bar
 
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
 
How to master Steroid (glucocorticoids) prescription, different scenarios, ca...
How to master Steroid (glucocorticoids) prescription, different scenarios, ca...How to master Steroid (glucocorticoids) prescription, different scenarios, ca...
How to master Steroid (glucocorticoids) prescription, different scenarios, ca...
 
Unit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptUnit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.ppt
 

Diagnosi e trattamento delle infezioni da H. Pylori in pediatria

  • 1. 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 Gastroenterology and Nutrition Helicobacter pylori Infection in Children: Recommendations for Diagnosis and Treatment *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. still large gaps in knowledge. 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 oral-oral (12). support the role of H. pylori in the pathogenesis of gas- Although H. pylori infection may be acquired during tric cancers (5). 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 ensure judicious 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, Atlanta, GA 30322, U.S.A.; or to Dr. Richard B. Colletti, University of appointed the Helicobacter pylori Infection Guideline Vermont, Department of Pediatrics, A-121 Given Medical Building, Committee to develop a clinical practice guideline for Burlington, VT 05405-5557, U.S.A. the child with H. pylori infection. 490
  • 2. TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION 491 These clinical practice guidelines are designed to as- TABLE 1. Summary of recommendations and the quality of sist primary care physicians, nurse practitioners, physi- the supporting evidence cian assistants, and pediatric gastroenterologists in the Quality of evaluation and treatment of suspected or diagnosed H. Recommendations evidencea 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 endoscopy with biopsy. II, III countries where the prevalence of infection is low but Presently available commercial serologic tests are frequently unreliable for screening children for the may not be directly relevant to children living in com- presence of H. pylori infection. II munities where there is a higher frequency of gastric Urea breath testing, although promising, has not been colonization by H. pylori. These recommendations have studied sufficiently in children. II 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. I 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. II Testing for H. pylori infection is not recommended in patients. asymptomatic children. II 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 not recommended. II 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 endoscopy and biopsy be performed to evaluate for the persistence of H. pylori-associated peptic ulcer METHODS disease. I, II 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 recommended. II 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 at endoscopy and H. pylori detected on histology. I 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. I 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. III 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 at increased 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. III 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). one to two weeks. I 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 obtained from well-designed cohort or case-controlled trials without H. PYLORI INFECTION? randomization. II-2 Evidence obtained from well-designed cohort or case-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 Opinions of 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
  • 3. 492 GOLD ET AL. TABLE 2. Tests for Helicobacter pylori and study. The optimal staining of biopsy sections is best Helicobacter-related disorders determined by local expert pathologists. Endoscopic ex- Invasive tests requiring endoscopy amination of and specimens obtained in the esophagus, Biopsies and histology stomach, and duodenum also provide information about Rapid urease testing other upper gastrointestinal disorders that may be the Bacterial culture cause of clinical symptoms including, for example, Polymerase chain reaction of bacterial DNA esophagitis and peptic ulcer disease that is not due to H. Non-invasive tests Serum and whole blood antibody pylori. Saliva antibody There are drawbacks to diagnostic gastrointestinal en- Urine antibody doscopy. It is a relatively invasive procedure requiring Stool antigen sedation or anesthesia. Furthermore, the test remains Urea breath testing relatively expensive in many centers, and access to an endoscopist with specific pediatric expertise is limited in many geographic areas. organism. In addition, such a test enables discrimination between 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- cost savings (17). 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 population tested. various noninvasive diagnostic tests in populations in North America that differ in demographic factors that may influence the prevalence and natural history of H. Bacterial Culture pylori infection (18). 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 Biopsies and Histopathology 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- tinely in research settings. ence of H. pylori and the severity and topographic dis- tribution of gastritis including the presence of atrophic Polymerase Chain Reaction gastritis, intestinal metaplasia, and mucosa-associated lymphoid 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
  • 4. TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION 493 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 outside the research laboratory. are more difficult to test. Additional pediatric studies evaluating the accuracy of stool antigen testing for both initial diagnosis and posttreatment follow-up are re- Noninvasive Testing quired before specific recommendations can be consid- Immunoassay Tests to Detect H. pylori Antibodies ered (32). Enzyme-linked immunosorbent assays (ELISAs) to Urea Breath Testing detect H. pylori antibodies are relatively inexpensive and easy to implement in the clinical setting. Many tests are available 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- the clinical research setting (34). 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 despite resolution of infection. 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 the accuracy 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 associated diseases. affect the accuracy of test results. Urine-based assays are easy to perform, require minimal labor for collection, and are painless (30). However, these assays are highly variable and are not yet commercially available. There- WHEN IS TESTING INDICATED? fore, saliva and urine assays for the detection of H. pylori antibodies 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 will alter 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
  • 5. 494 GOLD ET AL. 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 is not recommended. 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 abdominal pain in children. There have been six studies performed in 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 persistence of 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 setting. 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 ommended in these circumstances. endoscopic gastric biopsy. Serology is not a reliable test for 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
  • 6. TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION 495 Duodenal and Gastric Ulcers cost of care. Therefore, the H. pylori Infection Guideline Committee 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 treatment in this situation. endoscopy and H. pylori documented by histopathology. A prior history of duodenal or gastric ulcer disease is also an 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), eradication therapy is indicated if either a noninvasive or invasive test 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 abdominal pain. 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 cancer need treatment. with lymphoma should be performed to monitor the re- currence, progression, or remission of the tumor after therapy. 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 a specific 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 methodology (61). 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
  • 7. 496 GOLD ET AL. TABLE 3. Recommended eradication therapies for H. pylori pump inhibitor also reduces the effectiveness of eradica- disease in children tion treatment protocols. Studies are needed to determine First-line the relative importance of these risk factors in pediatric options Medications Dosage populations. 1 amoxicillin 50 mg/kg/day up to 1 g bid REFERENCES clarithromycin 15 mg/kg/day up to 500 mg bid 1. Ernst PB, Gold BD. Helicobacter pylori in childhood: new insights proton pump inhibitor: 1 mg/kg/day up to 20 into the immunopathogenesis of gastric disease and implications omeprazole (or comparable mg bid for managing infection in children. J Pediatr Gastroenterol Nutr. acid inhibitory doses of 1999;28:462–73. another PPI) 2. Drumm B. Helicobacter pylori in the pediatric patient. Gastroen- 2 amoxicillin 50 mg/kg/day up to terol Clin North Am. 1993;22:169–82. 1 g bid 3. Dohil R, Hassall E, Jevon G, et al. Gastritis and gastropathy of metronidazole 20 mg/kg/day–500 childhood. J Pediatr Gastroenterol Nutr. 1999;29:378–94. mg bid 4. Huang J-Q, Sridhars CY, Hunt RH. Meta-analysis of the relation- proton pump inhibitor: 1 mg/kg/day up to 20 ship between Helicobacter pylori seropositivity and gastric cancer. omeprazole (or comparable mg bid Gastroenterology. 1998;114:1169–79. acid inhibitory doses of 5. Watanabe T, Tada M, Nagai H, et al. Helicobacter pylori infection another PPI) induces gastric cancer in Mongolian gerbils. Gastroenterology. 3 clarithromycin 15 mg/kg/day up to 1998;115:642–8. 500 mg bid 6. Webb PM, Knight T, Greaves S, et al. Relation between infection metronidazole 20 mg/kg/day up to with Helicobacter pylori and living conditions in childhood: evi- 500 mg bid dence for person to person transmission in early life. BMJ. 1994; proton pump inhibitor: 1 mg/kg/day up to 20 308:750–3. omeprazole (or comparable mg bid 7. Parsonnet J. The incidence of Helicobacter pylori infection. Ali- acid inhibitory doses of ment Pharmacol Ther. 1995;9:45–51. another PPI) 8. Handt LK, Fox JG, Stalis IH, et al. Characterization of feline Second-line options Helicobacter pylori strains and associated gastritis in a colony of 4 bismuth subsalicylate 1 tablet (262 mg) qid domestic cats. J Clin Microbiol. 1995;33:2280–9. or 15 ml (17.6 9. Grubel P, Hoffman JS, Chong FK, et al. Vector potential of house- mg/mL qid) flies (Musca domestica) for Helicobacter pylori. J Clin Microbiol. metronidazole 20 mg/kg/day–500 1997;35:1300–3. mg bid 10. Klein PD, Graham DY, Gaillour A, et al. Water source as a risk proteon pump inhibitor: 1 mg/kg/day up to 20 factor for Helicobacter pylori infection in Peruvian children. Lan- omeprazole (or comparable mg bid cet. 1991;337:1503–6. acid inhibitory doses of 11. Staat MA, Kruszon-Moran D, McQuillan GM, et al. A population- another PPI) based serologic survey of Helicobacter pylori infection in children pus, an additional antibiotic: 50 mg/kg/day up to and adolescents in the United States. J Infect Dis. 1996;174: amoxicillin 1 g bid 1120–3. or tetracyclinea 50 mg/kg/day up to 12. Goodman KJ, Correa P. The transmission of Helicobacter pylori: 1 g bid a critical review of the evidence. Int J Epidemiol. 1995;24:875–87. or clarithromycin 15 mg/kg/day–500 13. Sackett DL, Richardson WS, Rosenberg W, et al. Evidence-based mg bid Medicine: How to Practice and Teach EBM. Edinburgh: Churchill 5 ranitidine bismuth-citrate 1 tablet qid Livingston; 1998. clarithromycin 15 mg/kg/day–500 mg bid 14. McMurray AR. Three decision-making aids: brainstorming, nomi- metronidazole 20 mg/kg/day–500 nal group, and Delphi technique. J Nurs Staff Dev. 1994;10:62–5. mg bid 15. Cockeram AW. Clinical practice guidelines: help or hindrance? J Pediatr Gastroenterol Nutr. 1999;28:362–3. Initial treatment should be provided in a twice daily regimen (to 16. Canadian Task Force on the Periodic Health Examination: the enhance compliance) for 7 to 14 days. periodic health examination. Can Med Assoc J. 1979;121:1193– a Only for children 12 years of age or older. 254. bid, twice daily; qid, four times daily. 17. Olson AD, Fendrick AM, Deutsch D, et al. Evaluation of initial noninvasive therapy in pediatric patients presenting with suspected ulcer 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 delphia: Lippincott–Raven; 1998. 19. Genta RM, Graham DY. Comparison of biopsy sites for the his- when a three- or four-drug regimen is used. Resistance of 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. 2108–10. 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. 21. Elitsur Y, Hill I, Lichtman SN, et al. Prospective comparison of could eventually impair the therapeutic effectiveness 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
  • 8. TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION 497 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. 1996;22:148–52. 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 JAMA. 1995;273:729–34. 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- 1995;126:753–6. 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. 1999;28:157–61. 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; 1998;178:460–5. 39:1488–92. 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. 91:1145–9. 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- 1999;354:30–3. 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: 19:362–7. 347–8. 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- 1994;20:1161–81. 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- 1875–81. 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- 131:791–3. 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. 1999;13:553–9. 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 diatr Surg. 1995;30:427–9. Med. 1998;105:424–30. 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 Dis Child. 1999;81:68–70. J Pediatr Gastroenterol Nutr, Vol. 31, No. 5, November 2000