PONE-D-21-08415

Knowledge Attitudes and Practices toward seasonal influenza vaccine among pregnant women in Tunisia

PLOS ONE

Dear Dr. Bettaieb,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’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.

This study is focusing on assessing the Knowledge Attitudes and Practices toward seasonal influenza vaccine among pregnant women in Tunisia which provides valuable support for the decision makers. However, revising the methodology section is very fundamental for accepting this article.  The concerns were mainly for the methodology section. 

Please note that your manuscript was reviewed by 5 experts in the field. There is consensus agreement that the idea of the article is interesting. Meanwhile, they have identified some important problems and provided copious comments. 

 The manuscript could be greatly strengthened by considering editing according to the specific attached Reviewers’ comments.

Please submit your revised manuscript by July 31 2021 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 plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ 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 academic 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'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Ammal Mokhtar Metwally, Ph.D (MD)

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Thank you for stating in the text of your manuscript "Ethical approval for this survey was obtained from the Biomedical Ethics Committee of the

Pasteur Institute of Tunis. Approval was also obtained from the Tunisian Ministry of Health. All women included in the survey were informed about the objectives and modalities of the study. Women who agreed to be interviewed provided written informed consent." Please also add this information to your ethics statement in the online submission form.

3. Please list the names of all of the public health centers where participants were recruited from.

4. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed the survey or questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information. If the questionnaire is published, please provide a citation to the (1) questionnaire and/or (2) original publication associated with the questionnaire.

5. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

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.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: I Don't Know

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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

PLOS ONE 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

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: 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: 1. Sampling method - needs more clarity, because the author claims that the sample is a representative of the total population and also able generalize

2. How they arrive at Eight governorates out of 24 were randomly selected - Please clarify because the representation from all regions was not proportionate

3. This study included only qualitative data that were presented as numbers and percentages - Explain.

4. First, the status of influenza vaccination was self-reported by the participants – Self reporting could have been done with EVIDENCE CROSS CHECKED BY VACCINATION CARDS, MCH CARDS ETC. ???

Reviewer #2: 1. The Discussion section paragraph 1 and 2 are the repetitions of Aim and Results of the previous sections. I would consider it as redundant and may i suggest to remove it.

2. Suggested to reason out why the Flu shots uptake are high in U.S,UK and Ireland. This may give a lead to adopt it in Tunisia.

Suggested to correct as Strengths and Limitations and NOT as Strength and Limitations -Plural is required

Reviewer #3: This is an interesting manuscript about pregnant women's attitudes towards having an influenza vaccine in Tunisia. A major concern I have about the paper is that while information about women's attitudes to the vaccine have been sought, it appears that the main reason women do not get the vaccine is because it is not offered to them and it is not free of charge. However, I appreciate that the aim of the manuscript is to form an evidence base for the promotion of the vaccine to pregnant women. I think the manuscript could be enhanced by providing some context in the introduction about what vaccines pregnant women in Tunisia are/are not offered and any associated costs to the women. Even if the vaccine was offered access to getting the influenza vaccine could be a barrier to women, especially those who live rurally. This could also be touched on in the introduction.

Minor comments

Study design - Is March to May winter in Tunisia? Add in details about the season.

Study population - Is it normal for pregnant women to attend a public health center? Provide a figure on how many women usually attend these clinics.

Sample size - leave out the equation, just include the sentence about the sample size. This sentence could go with your study population information rather than under its own heading.

Data analysis - Move the sentences together to make two paragraphs.

Ethical considerations - "the" before data is not needed. "will be analyzed" should be "would be analyzed" "is voluntary" should be "was voluntary"

Results

First paragraph "Age" should be "age"

Discussion

You mention that the uptake of other low-income countries are similar to Tunisia. What are the reasons for this? Is it also because the vaccine is not offered/available? Does it cost money?

Reviewer #4: 1.Subject to qualitative data availability and usage, the authors have used two year old data for qualitative study.

2.Sampling among all the three regions are not appropriate, it can be elaborated to give a clear understanding. And what percentage of population has been used in sampling.

3.The study population targeted is all pregnant women more than or equal to 18 years, so less than 18 years of pregnant women can not be the part of sampling.

4.Elaborate the criteria on which the status of influenza vaccination was reported by the targeted population.

Reviewer #5: This paper presents the results of a national survey of attitudes toward influenza vaccination among pregnant women attending antenatal care in Tunisia. The authors report that the majority of women had heard of the vaccine, but only a small minority had been vaccinated, which was related to concerns about the safety and effectiveness of the vaccine. The authors conclude that health care professionals working in antenatal care can increase vaccination rates by encouraging their patients to get vaccinated.

The paper is well-written, with a well-justified aim and an interesting discussion. My main concern is that it is difficult to evaluate whether the results are generalizable to the study population (i.e., to all pregnant women attending antenatal care in the Tunisian public health care sector), as the sampling procedure is not described in detail and the response rate has not been reported. My specific comments can be found below.

Abstract/Introduction:

1. Should vaccine uptake be included in the aims?

2. In reference 16, I cannot find the WHO:s target of 80% of pregnant women being vaccinated.

Methods:

3. The authors write that sampling was stratified by region, but how was the number of governorates sampled from each region determined?

4. What was the second sampling stage? Were hospitals/health care centers sampled within governorates? According to the text, after governorates had been sampled, “stratified sampling was conducted based on the selected governorates”. Could the authors please clarify what was sampled and what the stratification variable(s) was (were)?

5. How were hospitals/health care centers within governorates sampled?

6. Were all women attending antenatal care at the sampled hospitals/health care centers asked to participate, or was a sample of women taken?

7. The authors write that the sample was self-weighted and that “[t]he sample size was distributed according to the distribution of the target population in the different regions.” Does this mean that the number of sampled patients in each governorate was proportional to the size of the total population size?

8. Was the sampling design taken into account in the data analysis? If not, please explain why.

9. The authors explain that the interviewers were trained. However, it is unclear who the interviewers were. Were they, for example, nurses or other health care professionals already working at the hospitals/health care centers, or were they external staff?

10. In the Data Analysis section, I think “qualitative data” should say “qualitative variable”, as the data are quantitative (i.e., numbers), but the variables are qualitative (i.e., ordinal/nominal).

11. In the Data Analysis section, it would be good to mention that odds ratios and 95% confidence intervals were calculated.

Results:

12. How many health care centers/hospitals were sampled?

13. How many health care centers/hospitals were asked to participate in the survey? How many were willing to participate?

14. How many women were assessed for eligibility? How many were considered eligible? How many were excluded? What was the response rate in the survey?

15. In the second paragraph, should the word “nearly” be replaced with “more than”?

16. In the third paragraph, please include not only the percentage, but also the number, of women who received the vaccine in the past or during their current pregnancy.

17. In the third paragraph, should “FIV” be “FV”?

18. In the sixth paragraph, should the word “except” be deleted or replaced with another word?

19. In the last paragraph of the Results section, the authors mention two reasons why women refused getting vaccinated (fear of side effects and concerns regarding self-harm/harm to the fetus). Was this question open-ended? If it was, did the authors consider categorizing all responses, instead of just two? If it was not open-ended, what were the possible responses? The answers “fear of side effects” and “concerns regarding self-harm/harm to the fetus” seem identical to me. Could these answers be combined?

20. In the last paragraph of the Results section, it says that the main reason that patients were not willing get vaccinated was concerns about adverse effects. However, in Table 2, it looks like vaccinated and non-vaccinated women differ more in their beliefs about vaccine effectiveness than vaccine safety. Could this result mean that concerns about lack of effectiveness are an even more important reason for the women’s unwillingness to get vaccinated than concerns about adverse effects?

Discussion/Conclusion:

21. Would it be interesting to mention that only 48% of women claim that they would take the vaccine if it were recommended by a health care professional and provided free of charge, which is substantially lower than the target of 80% vaccinated among pregnant women, even if this would be a large improvement from the current 4%? In addition, would it be interesting to mention that as many as 75% say they would be willing to take it if it was recommended by a doctor, but only 34% if it was recommended by another health care professional?

22. Page 8, Paragraph 3: Is “avail” the right word here?

23. Page 8, last paragraph: Most questions do not seem to be open-ended, as they are multiple-choice.

Table 2:

24. Is there a round-off error in the odds ratio for the first question (“Do you know anyone who has been severely ill with influenza?”)? I get an odds ratio of 0.95 (=136*360/272*189), which rounds up to 1.0.

References

25. Parts of the references are in French.

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6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

Reviewer #4: Yes: Rupam Bharti

Reviewer #5: Yes: Jonathan Bergman

[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.

PONE-D-21-08415R1Knowledge Attitudes and Practices toward seasonal influenza vaccine among pregnant women during the 2018/2019 influenza season in TunisiaPLOS ONE

Dear Dr. Bettaieb,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’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.

Great effort was made by the authors to utilize the feedback that was provided for them to correct for resubmission. I find it interesting and improved with respect to the original submission. There are still some issues to be clarified and things to adjust mainly for the methodology section to achieve the aim (enclosed). 

Please note the following:

You are invited to publish the peer review history of your articles. Please note that, if this manuscript is accepted for publication and you and your authors opt-in to publishing the peer review history, all decision letters - which may include all comments will be published, along with your responses to reviewer comments.

Please also note that PLOS ONE is currently running a Call for Papers on the theme of Influenza Prevention (https://collections.plos.org/call-for-papers/influenza/).

While during your submission, you did not specifically submit to this Call for Papers, we feel that the manuscript falls within its scope. If you and your co-authors would like your manuscript to be considered by the Guest Editors for inclusion in the Influenza Collection or if you have any questions about this matter, or on this Call for Papers more generally, do not hesitate to email shepp@plos.org.

Please submit your revised manuscript by Nov 28 2021 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 plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ 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 academic 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'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Ammal Mokhtar Metwally, Ph.D (MD)

Academic Editor

PLOS ONE

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.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

Reviewer #5: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #5: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #5: I Don't Know

********** 

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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 Response)

Reviewer #5: Yes

********** 

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

PLOS ONE 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

Reviewer #5: Yes

********** 

6. 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: Congrats to the authors on the KAP study on Infleunza vaccine and the same can be attempted towards COVID 19 vaccines

Reviewer #2: The authors have addressed all the comments and suggestions. Look forward to similar works in the future.

Reviewer #5: The authors have improved their paper, but I still have a few questions and comments. Some of the comments concern minor unclarities or inconsistencies in the data that I did not notice the first time, which I apologize for. Other comments concern the description of the sampling procedure, which has been improved but can still be clarified further.

Major issues:

1. Methods, Line 113: How did the authors determine that 8 governorates should be sampled? In their rebuttal, they explain that this was determined by budget constraints, as 8 corresponds to 1/3 of Tunisia’s 24 governorates. Pease add this information to the manuscript.

2. Methods, Lines 112-113: It could be clarified how the number of governorates sampled per region was determined. I know this information is provided in Lines 120-123, but the authors provide a much clearer explanation in their rebuttal (i.e. 8 * % of Tunisia’s women of childbearing age living in a region). I recommend that the authors be as clear in the manuscript as they are in their rebuttal.

3. Methods, 118-119: It is unclear how area of residence (urban/rural) was relevant to the sampling procedure. According to the authors’ rebuttal, all public health centers in the sampled governorates were included. If so, shouldn’t area of residence be irrelevant?

4. Methods, Sampling procedure: In the authors’ rebuttal, it sounds like they performed region-stratified, cluster sampling, meaning that they first randomly sampled governorates from each region and then included all pregnant women attending any public health center in the sampled governorates. If so, this could be clarified in the Sampling Procedure section.

5. Results, Line 169: The number of survey respondents was 1200, which is identical to the calculated sample size reported in the Methods section. This seems unlikely if the authors really did recruit all pregnant women attending any public health center during a 3-month period. Are the authors’ sure they didn't recruit consecutive patients and then stop when the calculated sample had been reached?

6. S1 Appendix: The sampling method illustrated here looks like it is stratified sampling by region, governorate, and area of residence. As mentioned above, however, only region seems to have been a stratification variable.

7. Rebuttal: The authors explain that that they did not take the sampling procedure into account during the analysis due to a lack of information to do so. However, ignoring cluster sampling in an analysis can lead to confidence intervals that are too narrow. Have the authors considered this possibility?

Minor issues:

8. Abstract, Line 48: The lower bound of the confidence interval is 57.7% here, but it is 57.6% in the main text (Results, Line 182). Please check this.

9. Abstract, Lines 48-49: The text states that 4.4% of women who were aware of the vaccine received it during their current pregnancy; however, this percentage seems to be calculated based on all 1157 included women (51/1157=4.4%). The same was done in Results, Lines 182-184, both for women who had received the vaccine during the current pregnancy and for those who had received it sometime in the past. Please check this.

10. Results, Line 163: Could the ID numbers be linked to personal identifiers? If so, the data would be coded/pseudo-anonymized rather than anonymized.

11. Results, Lines 181-182: Is there a round-off error in the percentage of women who had heard of influenza, 85.5%? I get 988/1157=84.4%. Is there an error in the calculation of women who had heard of the vaccine, 60.3%? I get 694/1157=60.0%.

12. Results, Line 187: Consider adding the number of women who would be willing to receive the vaccine, instead of just reporting the percentage.

13. Discussion, Line 307: How was 6.5% calculated (numerator/denominator)? According to Table 2, 72 patients reported having enough information about side effects. Is 72 the numerator used?

14. References: There are still French words here.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #5: Yes: Jonathan Bergman

[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.

PONE-D-21-08415R2Knowledge Attitudes and Practices toward seasonal influenza vaccine among pregnant women during the 2018/2019 influenza season in TunisiaPLOS ONE

Dear Dr. Bettaieb,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’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 Jan 31 2022 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 plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ 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 academic 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'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Ammal Mokhtar Metwally, Ph.D (MD)

Academic Editor

PLOS ONE

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.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #5: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #5: Yes

**********

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

Reviewer #5: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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 #5: Yes

**********

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

PLOS ONE 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 #5: Yes

**********

6. 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 #5: I thank the authors for further clarifying their paper. I have only three minor comments left.

Minor comments:

1. Page 4: In their rebuttal letter, the authors confirm my previous suspicion that the only stratification variable was region. However, now that the authors have further clarified their work, I think that the sampling procedure was also stratified by area of residence, as healthcare centers were selected from both urban and rural areas.

2. Page 4, Lines 126-127: The authors explain that patients were randomly selected at healthcare centers, but the authors may also want to explain how this was done in practice. For example, did the study staff enter the total number of patients on the patient list into a computer, which then returned a certain number of randomly selected patients, such as patients 2, 5, and 6 on the list?

3. Page 5: The authors have not addressed my question of whether it is appropriate to ignore the sampling procedure in the analysis. If I am not mistaken, Appendix S1 contains all the information required to incorporate this information. (The percentages at each stage of the sampling procedure could be used to construct sampling weights, could they not?)

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Reviewer #5: Yes: Jonathan Bergman

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Knowledge Attitudes and Practices toward seasonal influenza vaccine among pregnant women during the 2018/2019 influenza season in Tunisia

PONE-D-21-08415R3

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