Arab Republic of Egypt

Evidence-based clinical practice guidelines for

diagnosis and treatment of H pylori related diseases in children and adolescent
 EVIDENCE-BASEDCLINICAL PRACTICE GUIDELINES
For the diagnosis and treatment of H pylori related diseases in children and adolescent

FIRST EDITION
August 2021

Adapted from the source guidelines

1. The updated JSPGHAN guidelines for the management of Helicobacter pylori
infection in childhood.Pediatrics International (2020) 62, 1315–1331

2. Joint ESPGHAN/NASPGHAN Guidelines for theManagement of Helicobacter

pylori in Children andAdolescents (Update 2016)

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 Authorship group (the Authors) & Editorial Board

Names Affiliations
Gastroenterology team
1. Suzan Samir Gad (moderator) MD, Suez Canal University
2. Ahmed Foad MD, Alexandria University
3. Ahmed Hamdy MD, Ain Shams University
4. Amal Mahfouz MD, Alexandria University
5. Ayman Emil Eskandr MD, Cairo University
6. Gihan Bebars MD, Minia University
7. HalaHussien Mansour MD, Cairo University
8. Hanan Fathy MD, Cairo University
9. MahaAbouZekri MD, Cairo University
10. Mohamed Ezz MD, Mansoura University
11. Naglaa Abu Faddan MD, Assuit University
12. Sara Tarek MD, Cairo University
Methodology Supervision Group
Ashraf Abdel Baky Chair of EPG
Prof. of Pediatrics, Ain Shams University
Tarek Omar MD, Alexandria University
Yasser Sami Amer MD, Alexandria University

Printed in Cairo, Egypt in 2021

Introduction and background

Helicobacter pylori (H. pylori) is one of the most common bacterial infections
worldwide1. It is a Gram-negative microaerophilic bacteria colonises the gastric mucosa2,
The prevalence of infection in pediatric age is high and varies from country to country. 3 In
Egypt, the overall H. pylori prevalence was 72.38%. and the burden of H. pylori infection

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is high in rural areas than in urban areas (82.5%).4&5 Its main risk factor is residing in an
overcrowded home and socially deprived area1. Seroprevalence of H. pylori was
significantly age-dependent: 60.6% of patients aged more than 5 years and 25.9% of
patients aged less than 5 years.6
The infection is acquired during childhood, usually through a household contact,
and in most cases persists through adulthood.7 The most frequent form of disease in
children is chronic gastritis, and complications are rare during childhood. 8 Most infected
children are asymptomatic. There is no evidence of an association between infection by H.
pylori with chronic abdominal pain compatible with functional disorders as noted in the
Rome IV criteria. However, ulcers associated with H. pylori infection may cause
abdominal pain and upper gastrointestinal bleeding, which is the main indication for
diagnostic testing for H. pylori infection.3 The development of the disease is related to the
virulence of the strain, the genetic predisposition, the host’s immune response, the time of
exposure and environmental factors. 9&10 There is evidence of an association between H.
pylori infection and many extra-gastroduodenal diseases. With the exception of refractory
iron-deficiency anemia, or mucosa-associated lymphoid tissue (MALT) lymphoma, the
presence of another disease is not sufficient indication for testing for H. pylori11&12.
Several diagnostic tests for detection of H. pylori have been widely used in clinical
practice. These diagnostic methods may be classified as invasive, which require endoscopy
to obtain biopsies of gastric tissues, and non-invasive. The invasive methods include
histological examination, culture, urease test and molecular methods, while the non-
invasive methods include urea breath testing, serology and stool antigen testing. 13,14&15
Diagnosis in children requires the use of invasive methods with endoscopy. Non-
invasive assessment methods are reserved to determine whether H. pylori has been
eradicated.7 The test and treat strategy involve delivery of H. pylori eradication therapy
based on positive results of a non-invasive test, such as the H. pylori breath test or stool
antigen test. This strategy is commonly used in the management of adults cannot be
extrapolated to the pediatric population. This practice has resulted in a significant increase
in the prevalence of H. pylori resistant to the antibiotics commonly used for its
eradication.16
After confirmation of symptomatic H pylori infection, treatment should be
started.Treatments targeting H. pylori infection consist of combinations of a Proton pump

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inhibitors and several antimicrobial agents. Therapy should be guided by antibiotic
resistance profiles. Culture with sensitivities can guide treatment. Treatment should
provide adequate doses of medication for 14 days. 17
The recommended goal for H pylori treatment is an eradication rate of at least 90% to
avoid further investigations and antibiotic use. Confirmation of eradication should be
performed in all patients due to increased antibiotic resistance. 1

Health Questions used to develop this Adapted CPGL

1. What are the GI symptoms which highly suspected of H. pylori related diseases in
children?
2. What endoscopic findings are especially recommended for H. pylori tests for
children who underwent upper gastrointestinal endoscopy for abdominal symptoms
or anemia?
3. Which tests are recommended for the diagnosis of H. pylori infection in children?
4. What are the uses of non-invasive? (1) The 13C-UBT. (2) A 2-step monoclonal
stool H pylori antigen test?
5. Is diagnostic testing for H. pylori‐infection recommended in children with
functional abdominal pain?
6. Is diagnostic testing for H. pylori‐infection recommended in children with iron def
anemia?
7. Is diagnostic testing for H. pylori‐infection recommended in children with
refractory iron def anemia?
8. Is diagnostic testing for H. pylori‐infection recommended in children with chronic
ITP?
9. Is diagnostic testing for H. pylori‐infection recommended children with short
stature?
10. Is diagnostic testing for H. pylori‐infection recommended for asymptomatic
children to protect gastric cancer development?
11. Is diagnostic testing for H. pylori‐infection recommended for asymptomatic
children living in the household of infected adult?
12. Who should be treated?

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13. Is eradication therapy recommended in H. pylori-infected children with gastric
MALT lymphoma.?
14. Is eradication therapy recommended in H. pylori-infected children with chronic
idiopathic urticaria?
15. Is eradication therapy recommended If H pylori is an incidental finding at
endoscopy?
16. Is eradication therapy recommended in H. pylori-infected children who have a
family history of gastric cancer in their first- or second-degree relatives?
17. Which eradication regimens are recommended as the first‐line therapies for H.
pylori infection in children?
18. What is the duration of therapy?
19. Which eradication regimens are recommended as the second‐line therapies in H.
pylori‐infected children in whom the first‐line therapy failed?
20. Is a combination of probiotics with triple therapy eradication regimens effective
for H. pylori treatment in children?
21. What kinds of adverse effects associated with eradication therapy should be
considered?
22. When should we perform H. pylori testing to determine whether eradication of H.
pylori was successful?
23. What are the tests used to determine whether H pylori treatment was successful?
24. Which diagnostic test for H. pylori is recommended to determine whether
eradication of H. pylori was successful?
25. Is endoscopic biopsy needed to confirm eradication of infection?
26. Are serological tests needed to confirm eradication of infection?
• this cut-off date.

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 Recommendations

Key Recommendations
Health Recommendation Level of evidence
questions
1-What are H. pylori related diseases in children including chronic
the GI gastritis, gastric and/or duodenal ulcers. GI symptoms Strength of
recommendation:
symptoms which highly suspected of H. pylori related diseases in
Strong. Evidence
which children are epigastric pain or tenderness on level: A.
Agreement: 100%.
highly examination, nausea, emesis, hematemesis, and
suspected melena- or guaiac-positive stools.
of H.
pylori Refractory IDA and Chronic ITP
related
diseases in
children?
JESPGHA
N
Page 3

1A. What
are the
non-GIT
symptoms
that may be
related to
H. pylori
related
diseases in
children?

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1B- We recommend that testing for H pylori be performed GRADE: Strong
ESPGHAN in children with gastric or duodenal PUD. If H pylori recommendation.
Page 4 infection is identified then treatment should be Quality of
administered and eradication confirmed. evidence:
high. Agreement:
100%.
2-What Strong. Evidence
We recommend H. pylori tests when the following
endoscopic level: C.
endoscopic findings are observed at diagnostic upper
findings Agreement: 100%
endoscopy: antrum‐predominant nodularity,
are Japanese
ulcerations or erosions in the stomach or duodenum
especially
and / or disappearance of regular arrangement of
recommen
collecting venules (RAC) in the gastric body.
ded for H.
pylori tests
for
children
who
underwent
upper
gastrointest
inal
endoscopy
for
abdominal
symptoms
or anemia?
3-Which Strong
We recommend that the diagnosis of H pylori infection
tests are recommendation.
should be based on either (a) histopathology (H pylori–
recommen Quality of
positive gastritis) plus at least 1 other positive biopsy-
ded for the evidence: high.
based test or (b) positive culture.
diagnosis Agreement: 100%.
of H. 3A.We recommend considering the performance of a ESPGHAN

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pylori infec rapid urease test directly on gastric biopsies to
tion in determine presence / absence of H . pylori as a
children? diagnostic test for active infection. Weak. Evidence
japanese level: C.
3B.We recommend histological examination of gastric
Agreement: 100%.
biopsies as a biopsy‐based diagnostic test for active H.
Japanese
pylori infection.

3C.We recommend H. pylori culture because the Weak. Evidence

culture method is the gold standard biopsy‐based test level: B.
for active infection and it can also be used for Agreement: 100%.
antimicrobial susceptibility testing for optimization of Japanese
eradication therapy. Strong. Evidence
level: Not
3D. We recommend that at least 6 gastric biopsies
applicable.
should be obtained for the diagnosis of H pylori
Agreement:
infection during upper endoscopy.
100%.japanese

Quality of
evidence: low.
Agreement: 93%.
ESPGHAN
4-What are Strong
We recommend against a ‘‘test and treat’’ strategy for
the uses of recommendation.
H pylori infection in children
non- Quality of
invasive? We recommend against antibody-based tests evidence: low
(1) The (immunoglobulin G [IgG], IgA) for H pylori in serum, (indirect).
13C-UBT. whole blood, urine, and saliva in the clinical setting Agreement: 100%
(2) A 2-
step
monoclona Strong
l stool H recommendation.

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pylori Quality of
antigen evidence: high.
test. Agreement: 86%.
ESPGHAN

Is We recommend against diagnostic testing for H pylori GRADE: Strong

diagnostic infection in children with functional abdominal pain recommendation.
testing disorders. Quality of
for H. evidence: high.
pylori‐infe Agreement: 100%.
ction
recommen
ded in
children
with
functional
abdominal
pain
Is We recommend against diagnostic testing for H pylori GRADE: Strong
diagnostic infection as part of the initial investigation in children recommendation.
testing with iron deficiency anemia (IDA). Quality of
for H. evidence:
pylori‐infe moderate.
ction Agreement: 93%.
recommen
ded in
children
with iron
def anemia

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Is We suggest that in children with refractory IDA in GRADE: Weak
diagnostic which other causes have been ruled out, testing forH recommendation.
testing pylori during upper endoscopy may be considered. Quality of
for H. evidence:
pylori‐infe low. Agreement:
ction 100%.
recommen
ded in
children
with
refractory
iron def
anemia

Is We suggest that noninvasive diagnostic testing for H GRADE: Weak

diagnostic pylori infection may be considered when investigating recommendation.
testing causes of chronic immune thrombocytopenic Quality of
for H. purpura (ITP) evidence:
pylori‐infe low. Agreement:
ction 93%.
recommen
ded in
children
with
chronic
ITP

Is We recommend against diagnostic testing for H pylori GRADE: strong

diagnostic infection when investigating causes of short stature. recommendation.
testing Quality of
for H. evidence:
pylori‐infe moderate.

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ction Agreement: 79%
recommen
ded
children
with short
stature?
Is We recommend against a “test-and treat” strategy for Strength of
diagnostic H. pylori infection for asymptomatic children to recommendation:
testing protect gastric cancer development Not determined.
for H. Evidence
pylori‐infe level: C.
ction Agreement: 100%.
recommen
ded for
asymptoma
tic
childrento
protect
gastric
cancer
developme
nt?
Is We recommend against a “test-and treat” strategy for Strength of
diagnostic asymptomatic children living in the household of an H. recommendation:
testing pylori-infected adult who received eradication therapy Weak. Evidence
for H. to prevent re-infection in that adult. level: B.
pylori‐infe Agreement: 100%
ction
recommen
ded for
asymptoma
tic children

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living in
the
household
of infected
adult?
- Who Weak. Evidence
Eradication therapy should be considered for children,
should be level: C.
5 years of age or more, determined to be infected
treated? Agreement:
with H. pylori by a test for active infection, taking
92%.Japanese
account possible re‐infection.

We recommend eradication therapy for H.

pylori‐infected children with gastric and/or duodenal Strong. Evidence
ulcers. level: A.
Agreement:100%.J
We recommend consideration of eradication therapy
apanese
for H. pylori‐infected children who underwent
Weak. Evidence
diagnostic upper gastrointestinal endoscopy for
level: D.
abdominal symptoms.
Agreement:
100%.Japanese.

We recommend consideration of eradication therapy Weak. Evidence

for H. pylori‐infected children with histological level: B.

evidence of chronic gastritis, in the absence of ulcers, Agreement: 100%.

to improve mucosal inflammation in the stomach. Japanese.

We recommend eradication therapy for H.

Strong. Evidence
pylori‐infected children with IDA when the iron
level: A.
deficiency is recurrent or refractory to iron supplement
Agreement: 100%
therapy.
Japanese.
We recommend eradication therapy for H.
pylori‐infected children with chronic ITP as the Strong. Evidence

first‐line therapy. level: B.

Agreement: 100%

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 Japanese..

3B To confirm eradication, we recommend that before GRADE: Strong

Precautions testing for H pylori, wait at least 2 weeks after recommendation.
of stool stopping PPIs and 4 weeks after stopping antibiotics. Quality of
antigen? evidence:
ESPGHAN low. Agreement:
Page 6 100%.
Is We recommend eradication therapy for H. pylori- Strength of
eradication infected children with gastric MALT lymphoma. recommendation:
therapy Strong. Evidence
recommen level: B.
ded in H. Agreement: 100%.
pylori-
infected
children
with
gastric
MALT
lymphoma.
?

Is We do not recommend eradication therapies for H. Strength of

eradication pylori-infected children with chronic idiopathic recommendation:
therapy urticaria. Not determined.
recommen . Evidence
ded in H. level: C.
pylori- Agreement: Not
infected reached
children
with

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chronic
idiopathic
urticaria?
Is If H pylori is an incidental finding at endoscopy Weak
eradication treatment may be considered following careful recommendation
therapy discussion of the risks and benefits of H pylori
recommen treatment with the patient/parents. When H pylori is
ded If H detected by biopsy-based methods in absence of PUD,
pylori is an treatment may be considered
incidental
finding at
endoscopy
?

Is We recommend consideration of eradication Strength of

eradication therapies for children who have a family history of recommendation:
therapy gastric cancer in their first- or second-degree relatives Weak. Evidence
recommen and in whom active H. pylori infection has been found. level: B.
ded in H. Agreement: 100%.
pylori-
infected
childrenwh
o have a
family
history of
gastric
cancer in
their first-
or second-
degree
relatives?
1- A proton pump inhibitor- based triple regimen Strength of

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Which with amoxicillin and clarithromycin as the first- recommendation:
eradication line therapy if H. pylori strains are susceptible Strong.
regimens to clarithromycin or the antimicrobial Evidence level: D.
are susceptibility of the strains is unknown. Agreement: 100%.
recommen 2- a proton pump inhibitor- based triple regimen
ded as the with amoxicillin and metronidazole as the first-
first‐line line therapy, if H. pylori strains are shown to be
therapies resistant to clarithromycin.
for H.
pylori infec
tion in
children?
JESPGHA max.
daily
N dose
dosage per day mg/kg/day mg/d
(twice per day) ay
proton
pump
inhibitors
lansoprazo
le 1.5 60
omeprazol
e 1 40
rabeprazol
e 0.5 20
>4 years BW<30kg
esomepraz 20mg/kg/day BW>30kg
ole 40mg/kg/day 40
antibiotics
amoxicillin 50 1500
clarithromy
cin 15-20 800
metronidaz
ole 10--20 500
What is the Regarding the duration of eradiation regimen in Strength of
duration of children, a 7-day course of treatment regimen is recommendation:
therapy? basically recommended. However, if clinicians judge Strong.
that there is a therapeutic need according to individual Evidence level: B.
risk of eradication failure, then the eradication regimen Agreement: 100%.
should be employed as a longer duration regimen for

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 up to 14 days.
Which second-line therapies in H. pylori-infected children in Strength of
eradication whom the first-line therapy failed recommendation:
regimens 1-a proton pump inhibitor- based triple regimen Strong.
are with amoxicillin and metronidazole was shown to Evidence level: D.
recommen be successful in children who failed in eradicating Agreement: 100%.
ded as the H. pylori with clarithromycin containing triple
second‐line therapy.
therapies 2- In patients with second-line eradication failure,
in H. antimicrobial susceptibility should be obtained
pylori‐infe for the infecting H. pylori strain and salvage
cted therapy should be tailored accordingly
children in
whom the
first‐line
therapy
failed?
Is a Improvement of the eradication rate by a combination Strength of
combinatio of probiotics is not clear. However, it has been shown recommendation:
n of to be effective for the prevention of side effects Not applicable.
probiotics including diarrhea. Evidence
with triple level: C.
therapy Agreement: Not
eradication applicable
regimens
effective
for H.
pylori treat
ment in
children?
What kinds Individual side-effect such as diarrhea, nausea, Strength of
of adverse vomiting, dyspepsia or dysphagia, which occurred with recommendation:

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effects the conventional eradication therapy, significantly Not applicable.
associated decreased by combining with probiotics Evidence level: C.
with Agreement: Not
eradication applicable.
therapy
should be
considered
When We recommend that the outcome of anti–H pylori strong
should we therapy be assessed at least 4 weeks after completion recommendation.
perform H. of therapy. Quality of
pylori testi evidence:
ng to moderate.
determine Agreement: 100%.
whether
eradication
of H.
pylori was
successful?
What are We recommend that one of the following tests be used Strong
the tests to determine whether H pylori treatment was recommendation.
used to successful: Quality of
determine (1) The 13C-UBT. evidence:
whether H (2) A 2-step monoclonal stool H pylori antigen test. high. Agreement:
pylori 93%. ESPGHAN
treatment
was
successful?

JAPANES We recommend that the 13C-urea breath test or stool Strength of

page 9 antigen ELISA test using a monoclonal antibody be recommendation:
Which employed to confirm eradication Strong. Evidence
diagnostic level: A.

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test for H. Agreement: 100%.
pylori is
recommen
ded to
determine
whether
eradication
of H.
pylori was
successful?
Is We recommend against H. pylori tests using Strength of
endoscopic endoscopic biopsy specimens (rapid urease test, recommendation:
biopsy histological examination, and the culture method) to Not determined.
needed to confirm the eradication of the infection. Evidence
confirm level: C.
eradication Agreement: 100%.
of
infection?

Are We recommend against serological tests to detect anti- Strength of

serological H. pylori antibodies as a single test to confirm recommendation:
tests eradication. Strong. Evidence
needed to level: A.
confirm Agreement: 100%.
eradication
of
infection?

External reviewers:
Who was asked to review the clinical content of the CPG (External Review Panel?
members):-

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 Names Affiliations
Dr. Mohamed El Guindy MD, Menofiya University
Dr. Mostafa Hodhod MD, Ain Shams University
Dr. Ahmed Megahed MD, Mansoura University

Example of Dissemination and Implementation Proposed Resources

Educational materials based on this Adapted CPG forH. pylori related diseases are
made available in flow chart, including

*Alarm signs include persistent right upper or right lower quadrant pain, dysphagia, odynophagia, persistent vomiting,
gastrointestinal blood loss, involuntary weight loss, deceleration of linear growth, delayed puberty, unexplained fever,
and a family history (Jones NL et al., 2017)

**Refractoriness to oral iron is defined as failure to respond to treatment at a dose of at least 100 mg of elemental iron
per day after 4 to 6 weeks of therapy (Hershko C and Camaschella C.2014)

***Chronic ITP is defined by ITP persistence beyond 12 months, with spontaneous recovery occurring in less than 10%
of adults (William B and Mitchell MD, 2019)

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****Functional bowel disorders are heterogeneous group of disorder, the most prevalent of which is irritable bowel
syndrome (IBS) and functional abdominal pain (FAP) syndrome. FAP characterized by frequent or continuous
abdominal pain associated with a degree of loss of daily activity, in the absence in change in bowel habits (Farmer AD
and Aziz Q.2014)

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