Reviewer’s report
Title: 
Assessment of a novel method to detect clarithromycin-resistant
Helicobacter pylori using a stool antigen test reagent
Version: 
1 
Date: 
23 Jun 2020
Reviewer's report:
Kakiuchi and colleagues have performed a study which assessed a novel method
to detect clarithromycin-resistant H. pylori. The authors reported that this
method could be useful for non-invasively detecting CAM-R mutations in H.
pylori by using residual solution of stool antigen test, particularly for children
who receive heavy burden by conventional(using the strains that are cultured
from gastric biopsy tissue) method.
This novel method doesn't need to perform esophagogastroduodenoscopy and
may be useful in the high CAM-R rate area, like Japan. In this report, the authors
confirmed the clinical usefulness of novel Nested PCR-QP method that used
stool specimens comparing conventional method. After that, the authors
investigated the clinical usefulness for children using stool specimens without
EGD and performed eradication therapy. 
This manuscript provides new data regarding new non-invasive method to detect
CAM-R H. pylori. Nevertheless, the work suffers from several minor weakness:
this new method can detect only CAM-R, so discussions about the usefulness in
several situations (e.g. the area where a CAM-R rate is low or high, the area
where other drug resistance is high) and the reasons why there was no significant
difference in the success rate between those with and without a CAM-R
mutation (e.g. number of cases, vonoprazan ) are needed.
These and other specific points for the authors' consideration are listed below.
1) (p4, line7-11) It's needed to describe the information of where.
2) (p8, line5-7) It's needed to describe the breakpoint values. 
3) (p11, line16-17) The authors describe "No CAM resistance mutation was
detected in Nested PCR-QP for two adults with a negative stool H. pylori
antigen test result.", but in Table 3 Nested PCR-QP, statement is "Not tested",
Were Nested PCR-QP tested for these 2 samples?
4) Table3: What is the meaning of the number 1,2 in sex field and 3+, 2+ in
Result field? 
Publons Reviewer Recognition
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No
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Reviewer’s report
Title: 
Assessment of a novel method to detect clarithromycin-resistant
Helicobacter pylori using a stool antigen test reagent
Version: 
1 
Date: 
23 Jun 2020
Reviewer's report:
Kakiuchi and colleagues have performed a study which assessed a novel method
to detect clarithromycin-resistant H. pylori. The authors reported that this
method could be useful for non-invasively detecting CAM-R mutations in H.
pylori by using residual solution of stool antigen test, particularly for children
who receive heavy burden by conventional(using the strains that are cultured
from gastric biopsy tissue) method.
This novel method doesn't need to perform esophagogastroduodenoscopy and
may be useful in the high CAM-R rate area, like Japan. In this report, the authors
confirmed the clinical usefulness of novel Nested PCR-QP method that used
stool specimens comparing conventional method. After that, the authors
investigated the clinical usefulness for children using stool specimens without
EGD and performed eradication therapy. 
This manuscript provides new data regarding new non-invasive method to detect
CAM-R H. pylori. Nevertheless, the work suffers from several minor weakness:
this new method can detect only CAM-R, so discussions about the usefulness in
several situations (e.g. the area where a CAM-R rate is low or high, the area
where other drug resistance is high) and the reasons why there was no significant
difference in the success rate between those with and without a CAM-R
mutation (e.g. number of cases, vonoprazan ) are needed.
These and other specific points for the authors' consideration are listed below.
1) (p4, line7-11) It's needed to describe the information of where.
2) (p8, line5-7) It's needed to describe the breakpoint values. 
3) (p11, line16-17) The authors describe "No CAM resistance mutation was
detected in Nested PCR-QP for two adults with a negative stool H. pylori
antigen test result.", but in Table 3 Nested PCR-QP, statement is "Not tested",
Were Nested PCR-QP tested for these 2 samples?
4) Table3: What is the meaning of the number 1,2 in sex field and 3+, 2+ in
Result field? 
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons upon publication of the manuscript. If you have already registered at
Publons, they will notify you of the receipt of this review and update your profile
as per your settings and their policy. If you are not registered with Publons, you
will receive an email from them asking you to register in order for them to be
able to recognize your review on your new profile page. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help
editors to identify candidate reviewers. Please find the details of processing in
Publons’ privacy policy 
https://publons.com/about/terms
No
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Please review this paper.
user
Reviewer’s report
Title: 
Assessment of a novel method to detect clarithromycin-resistant
Helicobacter pylori using a stool antigen test reagent
Version: 
1 
Date: 
23 Jun 2020
Reviewer's report:
Kakiuchi and colleagues have performed a study which assessed a novel method
to detect clarithromycin-resistant H. pylori. The authors reported that this
method could be useful for non-invasively detecting CAM-R mutations in H.
pylori by using residual solution of stool antigen test, particularly for children
who receive heavy burden by conventional(using the strains that are cultured
from gastric biopsy tissue) method.
This novel method doesn't need to perform esophagogastroduodenoscopy and
may be useful in the high CAM-R rate area, like Japan. In this report, the authors
confirmed the clinical usefulness of novel Nested PCR-QP method that used
stool specimens comparing conventional method. After that, the authors
investigated the clinical usefulness for children using stool specimens without
EGD and performed eradication therapy. 
This manuscript provides new data regarding new non-invasive method to detect
CAM-R H. pylori. Nevertheless, the work suffers from several minor weakness:
this new method can detect only CAM-R, so discussions about the usefulness in
several situations (e.g. the area where a CAM-R rate is low or high, the area
where other drug resistance is high) and the reasons why there was no significant
difference in the success rate between those with and without a CAM-R
mutation (e.g. number of cases, vonoprazan ) are needed.
These and other specific points for the authors' consideration are listed below.
1) (p4, line7-11) It's needed to describe the information of where.
2) (p8, line5-7) It's needed to describe the breakpoint values. 
3) (p11, line16-17) The authors describe "No CAM resistance mutation was
detected in Nested PCR-QP for two adults with a negative stool H. pylori
antigen test result.", but in Table 3 Nested PCR-QP, statement is "Not tested",
Were Nested PCR-QP tested for these 2 samples?
4) Table3: What is the meaning of the number 1,2 in sex field and 3+, 2+ in
Result field? 
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons upon publication of the manuscript. If you have already registered at
Publons, they will notify you of the receipt of this review and update your profile
as per your settings and their policy. If you are not registered with Publons, you
will receive an email from them asking you to register in order for them to be
able to recognize your review on your new profile page. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help
editors to identify candidate reviewers. Please find the details of processing in
Publons’ privacy policy 
https://publons.com/about/terms
No
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
assistant