PGPH-D-22-01932

Diagnostic performance of PfHRP2/pLDH CareStart malaria rapid diagnostic tests in elimination setting, northwest Ethiopia

PLOS Global Public Health

Dear Dr. Zeleke

Thank you for submitting your manuscript to PLOS Global Public Health. After careful consideration, we feel that it has merit but does not fully meet PLOS Global Public Health’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Please submit your revised manuscript by May 04 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at globalpubhealth@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pgph/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Om Prakash Singh, PhD

Academic Editor

PLOS Global Public Health

Journal Requirements:

1. Please indicate the full and correct funding information for your study and confirm the order in which funding contributions should appear.

Additional Editor Comments (if provided):

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does this manuscript meet PLOS Global Public Health’s publication criteria? Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe methodologically and ethically rigorous research with conclusions that are appropriately drawn based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available (please refer to the Data Availability Statement at the start of the manuscript PDF file)?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS Global Public Health does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for the opportunity to review this paper. Here are some comments for authors' consideration, hopefully to further strengthen the paper.

Major comments:

1. CareStart is a trademark protected by applicable laws. Please strongly justify the use of trademarked names, instead of just saying PfHRP2/pLDH, in your manuscript, otherwise please omit them.

2. Please elaborate what is known about malaria transmission intensity, parasite and vector diversity in the catchment area and population served by Andassa Health Center (AHC). This critical for a better understanding of the diagnostic performance of PfHRP2/pLDH.

3. A lot more descriptive data needs to be shown before the diagnostic performance results can be credibly interpreted. Please add a table first to describe your study population ( children vs. adults) and study site ( non-malaria areas vs malarious areas) and stratify the diagnostic performance findings across these variables.

4. The authors state AHC was purposively selected, so please justify the use of inferential statistics in your analysis? If your sample was purposively selected the 95% confidence interval and p-values become uninterpretable. Please justify or revise accordingly.

Minor comments:

1. The term “rate” should not be used to describe proportions or percentages. In descriptive epidemiology the term “rate” implies person-time, which is not the case in this manuscript. Please appropriately revise.

2. Please define the term ‘elimination settings”.

3. Line 99: what does “als” mean. One should not have to guess what it means.

4. Please support suspected malaria case definition with relevant references.

5. Please clearly state how consent was sought from under-age population (children).

6. Line 126: the test does not detect plasmodium it detects certain antigens of the plasmodium. Please rephrase for clarity and accuracy.

7. Laboratory methods: Please support all your laboratory methods (RDTs, microscopy and PCR) with references to reflect that standardized protocols were followed. Any deviations from standardized protocols should be clearly stated.

8. Formulas for diagnostic accuracy should be supported with relevant references.

9. Fig1 and methods section should also clearly state and show how many suspected malaria cases were screened and how many were excluded for receiving antimalarials within 4 weeks before arriving at the sample size of 310.

10. Table 4. Please clearly justify class interval used in the frequency table. Parasite density cutoffs and class intervals needs to reflect underlying biological, pathological, or operational basis.

Reviewer #2: 1. In discussing study area, line 97 describes Andassa health center as a representative of all transmission settings. Please clarify this.

2. Please include a picture of the nomogram as a figure in the publication

3. In the methods discussing parasite density calculation, lines 169-174 does not include information on how the standard curve generated via PCR was used to arrive at contents of table 4

4. Table 4 should be part of results and not discussion.

5. Specific mention should be made about the benefits and opportunities for use of Malaria RDTs in your discussions and conclusion to avoid giving the impression that they are diagnostically useless

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Reviewer #1: No

Reviewer #2: Yes: Anthony Agbakizu Ahumibe

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PGPH-D-22-01932R1

Diagnostic performance of PfHRP2/pLDH malaria rapid diagnostic tests in elimination setting, northwest Ethiopia.

PLOS Global Public Health

Dear Dr. Zeleke 

Thank you for submitting your manuscript to PLOS Global Public Health. After careful consideration, we feel that it has merit but does not fully meet PLOS Global Public Health’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jun 23 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at globalpubhealth@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pgph/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Om Prakash Singh, PhD

Academic Editor

PLOS Global Public Health

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments (if provided):

***Please revise the article as this revised version of draft has errors. For examples- Line 199: references is still missing, table 4 is still in discussion section etc.

Reviewers' comments:

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Diagnostic performance of PfHRP2/pLDH malaria rapid diagnostic tests in elimination setting, northwest Ethiopia.

PGPH-D-22-01932R2

Dear Dr. Zeleke,

We are pleased to inform you that your manuscript 'Diagnostic performance of PfHRP2/pLDH malaria rapid diagnostic tests in elimination setting, northwest Ethiopia.' has been provisionally accepted for publication in PLOS Global Public Health.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they'll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact globalpubhealth@plos.org.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Global Public Health.

Best regards,

Om Prakash Singh, PhD

Academic Editor

PLOS Global Public Health

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Reviewer Comments (if any, and for reference):