PONE-D-22-02970Epidemiology of dengue, chikungunya and Zika virus infection in travellers: a 16-year retrospective single-centre descriptive studyPLOS ONE

Dear Dr. Grebenyuk,

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.

As requested by the reviewer, try to provide a better clinical description of the various cases you count and in the same time please shorten as far as possible the description by providing synthetic tables as suggested by the reviewer.

Please submit your revised manuscript by Jun 04 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,

Pierre Roques, Ph.D.

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. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ

3. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide

4. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

"Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter

Additional Editor Comments (if provided):

Please indicated in the title that you refer to a Czech Republic institution

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

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

**********

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

Reviewer #1: Yes

**********

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: No

**********

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

**********

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: In this study, authors describe the epidemiological characteristics of imported cases

of dengue (DENV), chikungunya (CHIKV), and Zika virus (ZIKV) infections in Czech travelers: 313 patients with DENV, 30 with CHIKV, and 19 with ZIKV infections. Most patients travelled as tourists – 263 (84.0%), 28 (93.3%), and 17 (89.5%), respectively. The median duration of stay was 20 (IQR 14-27), 21 (IQR 14-29), and 15 days (IQR 14-43), respectively.

The epidemiological and clinical characteristics described in the manuscript reflect the epidemiological situation of the countries visited and are not sufficiently precise. Important data are missing:

It would be interesting to describe more precisely the clinical manifestations of patients and to use the international classifications for dengue, chikungunya and Zika virus infection.

The breakdown between direct and serological diagnosis should be indicated for each arbovirus. For dengue, serological data should make it possible to differentiate primary dengue cases from others. It would also be interesting to know the dengue serotypes and compare them with the serotypes circulating in the countries visited at the time of travel.

In the end, Guadeloupe is not located in South America but in the Caribbean.

**********

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

[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-22-02970R1Epidemiology of dengue, chikungunya and Zika virus infection in travellers: a 16-year retrospective descriptive study at a tertiary care centre in Prague, Czech RepublicPLOS ONE

Dear Dr. Grebenyuk,

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.

The interest of such a study as outlined by the reviewer 2 and remembered by the reviewer 3 deserved to be better explained in the introduction of this article to answer to the very well and sharp comment of the reviewer 3. Please correct some of the mistake indicated by the reviewer 2 to correctly described al the figures or table included in the article within the result text. IN addition take care to answer point by point to the reviewer 2 and to correctly report the limitation of the retrospective study (not international but national with a potential impact on international reader).

Please submit your revised manuscript by Oct 01 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,

Pierre Roques, Ph.D.

Academic Editor

PLOS ONE

[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 #2: All comments have been addressed

Reviewer #3: (No Response)

**********

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 #2: Yes

Reviewer #3: Partly

**********

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

Reviewer #2: Yes

Reviewer #3: N/A

**********

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 #2: Yes

Reviewer #3: No

**********

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 #2: Yes

Reviewer #3: No

**********

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 #2: I. Personalized summary of the research work carried out

This is a 16-year prospective study from 2004 to 2019, which took place in a tertiary care center in Prague, Czech Republic. As part of this work, during the relevant study period, the authors propose:

In a first step, to notify the annual number of cases of imported and diagnosed infections, as well as their monthly distribution over the twelve months of the year. These infections concern the three arboviruses dengue, chikungunya and Zika;

In a second step, to define some epidemiological characteristics and clinical features (reasons for travel, region or localities visited, associated clinical manifestations) of patients infected with these three arboviruses already mentioned.

Finally, in the case of dengue fever, to determine the associated serotypes from 2015 to 2017.

II. Summary of the interest of this research article

This study relating to the epidemiological description of cases of infections by dengue, chikungunya and Zika viruses imported to Prague in the Czech Republic through travelers, finds its interest and its relevance, in the context of globalization and the search for solutions at the international level to overcome emerging or re-emerging infectious and vector-borne diseases. These diseases, whether associated or not, are responsible for a heavy burden in terms of morbidity in the world in general and in tropical countries with limited resources in particular.

This work has the merit of giving some visibility on the distribution of infections due to arboviruses and imported from endemic tropical areas to Europe more generally and to the Czech Republic more particularly due to population movements via travel. Indeed, these imported infections such as Dengue, Chikungunya and Zika, which constitute tropical diseases with epidemic potential, require monitoring and scientific research not only at the national level in endemic countries but also internationally in view of their eradication.

In this work, the authors document the regions and countries most visited by patients with DENV, CHIKV, and ZIKV infections, which gives an overview of the impact of these contaminations in terms of public health on a scale of the Czech Republic but more generally suggests the significant impact on a global scale due to travel resulting in significant population movements.

In addition, the results of this work show the need for effective surveillance of populations returning from travel to prevent the spread of these infections in Europe due to the existence of a potentially competent transmission vector.

In countries with limited resources, the clinical manifestations associated with dengue, for example, have similarities to those due to malaria. Also, due to limited resources, in these countries patients are most often treated on the basis of clinical signs alone. Also, the differential diagnosis of infections due to these different arboviruses is not carried out and many of these tropical diseases such as dengue fever are classified in the group of neglected tropical diseases. This present work has the merit of carrying out laboratory research and diagnosis. This makes it possible to give the true incidence of these different vector-borne infectious diseases and to trace their possible international spread through travellers.

III. Problems and comments raised

Some comments have already been taken into account by the previous reviewer, however the following points should be noted.

1#. The case of infection or re-infection or vaccination of the patients in the study are not documented, certainly because of the retrospective nature of the study, which limits the scientific exploitation of the results of this work.

2#. The same is true of the Caucasian or non-Caucasian nature of the study population. Indeed, this information could make it possible to verify whether or not there is a link between the severity of the clinical manifestations and the natural history of the disease in the two study groups.

3#. In the context of this study, patients with, among other things, other imported infections were excluded from the study. However, taking this information into account would have added to the knowledge of co-infections such as malaria-dengue fever and zika-dengue fever, sometimes noted in the literature. This could have documented the correlation between the clinical signs and the share of each of these tropical infections according to the geographical origin of the travel of the infected patients. Something that is often difficult to do in endemic areas due to the lack of laboratory diagnostic means.

4#. The results of figure 1 do not appear explicitly in the results, not even those mentioned in particular in the discussion (line 226-228 in other).

5#. The title of figure 4: "Seasonality of imported arboviral" lacks precision. The seasons are known as for example summer, spring, autumn and winter. In fact, the title could be "January to December distribution of imported arboviral".

IV. Conclusion

Despite the limitations due to insufficiently documented information, certainly linked to the retrospective nature of the study, this work, which meets the publication criteria required by PLOS One, also presents a notorious interest already indicated, for which it deserves to be accepted for publication.

Reviewer #3: This manuscript describes the epidemiological characteristics of imported human arbovirus infections (dengue, chikungunya and Zika virus) in a tertiary care centre in Prague, Czech Republic in 2004 to 2019. There is strength in the work, with particularly contribution evident in providing an indication of the situation of arbovirus infections in Prague. However, the work does not accurately reflect the epidemiological situation of the infections neither on local (Prague) nor national (Czech Republic) level. The author did not mention whether these records represent all the arbovirus notifications reported in the Prague/ Czech. So, the scope of the work deals with ‘local’ topic, rather than genuinely ‘international’ one. I encourage authors to publish this paper as a national report or in a national journal after improving the manuscript.

The topic is interesting, and there are the foundations for a useful study. However, there is a lack of proper structure (especially in background and discussion) and detail about the knowledge gap, aims and objectives the methodology (collecting and recording the notifications). The analysis of data is also very much underdone (i.e. overly simple analysis has been performed). Further, the manuscript needs extensive revision for language and grammar

to improve the readability.

The author did not discuss the risk of local transmission of these infections in Czech Republic by way of infected travellers and evaluate the other risk factors that might coincide in time or space to trigger a local outbreak. The risk of local transmission is always more critical the than the importation risks of arboviruses. A better contextualise the work in terms of public health risk would greatly improve the value of the work. Hopefully the author can remedy these points and improve the manuscript.

**********

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 #2: No

Reviewer #3: No

**********

[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.

Attachments

Attachment

Submitted filename: Final Review by Pr Juliette TRANCHOT-DIALLO.pdf

Attachment

Submitted filename: Manuscript (Clean copy).docx

Epidemiology of dengue, chikungunya and Zika virus infections in travellers: a 16-year retrospective descriptive study at a tertiary care centre in Prague, Czech Republic

PONE-D-22-02970R2

Dear Dr. Grebenyuk,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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 onepress@plos.org.

Kind regards,

Pierre Roques, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Sorry for the delay

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 #2: All comments have been addressed

**********

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 #2: Yes

**********

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

Reviewer #2: Yes

**********

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 #2: 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 #2: 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 #2: Tropical arboviruses constitute an important cause of potentially serious microbial infections not only in indigenous populations of the tropics but also in travelers who stay in these tropical regions, in particular the Cheques.

This work presents the interest of describing the epidemiological monitoring of these infections in these travellers. This information is important in the but to provide reliable and regular data allow in a "One Health" context not only to measure in view of controlling the introduction of pathogenic agents with vector transmission in many parts of Europe but also to raise the alarm about the occurrence of future epidemics in popular tourist destinations around the world that do not always have effective surveillance systems.

**********

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 #2: No

**********