PONE-D-22-16035Gestational and congenital syphilis across the international border in Brazil Syphilis in Brazilian land bordersPLOS ONE

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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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: No

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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: Dear Editor,

In this manuscript, the distribution of acquired syphilis, syphilis in pregnancy, and congenital syphilis was analyzed at the Brazilian border with other nine countries from 2010 to 2020. The results show that the number of cases for all three variables is increasing throughout the Brazilian border area. This is nothing new, as the number of syphilis cases has increased dramatically worldwide in recent years. However, given the lack of data on developing country borders, I believe that this manuscript should be considered for publication after some modifications as described below:

Abstract:

I suggest inserting a space between several words: pregnancy (SP), syphilis (CS), syphilis (AS), Brazil(38.4%), North(18.3%), South(65.7%), 427(72.6%), 441(75.3%), 422(72%).

Introduction:

- Why "Discussions about the border have intensified in recent decades due to the regionalization processes"?

- About "Despite the importance of the border region in Brazil and the congenital syphilis as a public health problem, few studies explored the epidemiology of this infection in the region." Are AS and SP a public health problem in Brazil? Or not?

Results:

- Note Figures 2 and 3. In the text below the figure, words are underlined. What does "2010 a 2020" mean?

- "Syphilis in pregnancy was reported in 61.4% (361) of border municipalities and 27.8% (164) have a detection rate ≥ national rate (21.6/1000 LB). Most municipalities, 67.5% (397), did not report cases of congenital syphilis in 2020 and 14.3% (84 municipalities ) have an incidence of congenital syphilis ≥ 7.7/1000 LB (Figure 5)." Define LB.

Discussion:

- Italianize Treponema pallidum: "CS is the result of the transmission of the spirochete of the Treponema pallidum from the infected pregnant woman's ..."

Reviewer #2: The manuscript is of relevance, it points out updated aspects with the syphilis theme. However, it presents internal and external biases. Title: adequate; Abstract: incomplete with the need for adaptation of items as presented throughout the text; Introduction: presents issues that belong to another topic such as the research scenario, the knowledge gap is fragile, without articulation with the uniqueness of the research. Methods: The research design is inadequate. According to Morgenstern (2011), ecological studies can be divided into: multiple group designs (exploratory and etiological), time trend designs (exploratory and etiological), mixed designs (between multiple groups and time trend, but also with sub-classifications between exploratory and etiological). By the detailing of the methods, the study is more articulated with an exploratory ecological study with multiple group designs. Results: are very well designed, but not validated with explanatory tests. The statistics are simple and make the text uncompetitive. Discussion: well elaborated with the inclusion of limitations. However, limited to the results, which in fact is not inconsistent, but does not address aspects related to the health model, the treatment of partners who are in another border country, the mobility of the standardization of treatment and availability of supplies among other aspects that interfere in the occurrence of the grievance in all its scopes, acquired syphilis, in pregnant women and congenital. I hope that the comments provided will help you with the publication elsewhere or to resubmit after adaptations.

MORGENSTERN, Hal. Ecologic Study. In: ROTHMAN, Kenneth L.; GREENLAND, Sander; LASH, Timothy L. Modern Epidemiology, 3rd Edition, 2008.

Reviewer #3: Syphilis represents a highly relevant issue globally. It remains a global challenge, the second most commonly reported STI. In Brazil, syphilis persists as a public health problem, particularly due to limited access to timely diagnosis and treatment, as well as limited monitoring of cases in the Unified Health System health care network, especially in Primary Health Care. The challenge is amplified when the critical political and institutional moment of the country is recognized. One of the great challenges has been to implement these health care actions integrated with surveillance and control, ensuring wide access to diagnosis, treatment, and monitoring in the Primary Health Care setting. These aspects are even more critical in border areas in the context of South America.

There is great variation in the operational performance of disease control in the country. This variation has been associated with operational factors such as access to testing via rapid tests, but also to the lower use of condoms, the reduced use of penicillin in routine PHC, and the period in which there was a shortage of the drug. These aspects should have been better described in the manuscript.

Moreover, both acquired syphilis, syphilis in pregnant women, and congenital syphilis are compulsorily notifiable diseases in the country but have registered systematic under-reporting, which compromises health planning actions, despite the improvement over time. This aspect should have been studied in depth.

It is important to bring the impacts related to congenital syphilis to society.

For a broader look at the real epidemiological and operational situation of syphilis control, the analyses should include the quality of prenatal care in the public and private sectors. This aspect should be discussed.

Expand the debate on the ethnic-racial clippings performed, as differentials in the three arches analyzed.

Include the debates on recently published articles:

Saes MO, Duro SMS, Gonçalves CS, Tomasi E, Facchini LA. Assessment of the appropriate management of syphilis patients in primary health care in different regions of Brazil from 2012 to 2018. Cad Saude Publica. 2022 May 16;38(5):EN231921. doi: 10.1590/0102-311XEN231921. PMID: 35584428.

Ramos AN Jr. Persistence of syphilis as a challenge for the Brazilian public health: the solution is to strengthen SUS in defense of democracy and life. Cad Saude Publica. 2022 May 16;38(5):PT069022. doi: 10.1590/0102-311XPT069022. PMID: 35584431.

Reiterate the relevance of PMAQ-AB as an innovative and useful action to induce quality improvement of PHC in SUS. This program was interrupted by the federal government in 2019 within the process of deconstruction of public health policies, having been replaced by the PREVINE Brazil Program. The authors need to discuss the effect of this change, implying a considerable setback in the process of evaluation and financing of PHC.

For the abstract, it is recommended to qualify the description of border arcs, to better situate the analyzed scenarios. The objectives of the study should have been clearly listed, as in the introduction. Thus, the objectives of the study are partially articulated with a clear testable hypothesis stated. In principle, the focus is on the spatial and temporal description in Brazilian municipalities in border contexts. The conclusions of the abstract as well as of the manuscript should be adjusted to this perspective: the epidemiological and operational patterns of syphilis control are not satisfactory. The way it is described gives the wrong message of assumed control.

The introduction needs to be enhanced with better-contextualized data in operational and epidemiological terms of syphilis control in the country and in border areas, especially over the period 2010 to 2020. In Brazil, the changes in the definition of syphilis case for compulsory notification purposes delimited the temporal scope of the study. It is important to signal which changes were undertaken and their impacts, particularly the change in the definition of appropriate treatment of pregnant women with syphilis, excluding as a criterion the concomitant treatment of the sexual partner, in terms of the sensitivity/specificity of the case definition criteria.

In the introduction, the authors should be clearer when referring to the fact that discussions about the border have intensified in recent decades due to regionalization processes, including more consistent references.

The description of the study design needs to be qualified. In principle, the study design is appropriate to address the possible objective.

In addition, a detailed map of the study area could have been presented, while in the text, the indication of the territorial and population, as well as the economic relevance of this territorial cut-out adopted in the study.

It is recommended to detail the scope of the syphilis indicator panel with its linked databases, as well as the Health Information System for Primary Health Care, clearly demonstrating the role of care and surveillance and to what extent the interfaces between these systems. The population is clearly described and appropriate for the hypothesis being tested.

Qualify correctly and better the reference in the text to SPSS version 20.0 and TabWin (version???), according to the developers' specification. The correct statistical analysis is used to support conclusions.

There are concerns about ethical requirements being met.

The results are clearly and completely presented. The figures (Tables, Images) are of sufficient quality for clarity.

In the discussion, the reduction seen in the last two years analyzed does not allow one to clearly establish that there was a reduction in the detection rates analyzed. The limitations of the analysis are clearly described.

The authors discuss partially how these data can be helpful to advance our understanding of the topic under study.

The public health relevance is addressed. However, the conclusions are partially supported by the data presented.

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Reviewer #1: Yes: Fred Luciano Neves Santos

Reviewer #2: No

Reviewer #3: No

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Gestational and congenital syphilis across the international border in Brazil

PONE-D-22-16035R1

Dear Dr. Miranda,

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.

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Kind regards,

Everton Falcão de Oliveira, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #3: All comments have been addressed

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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 #3: Yes

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

Reviewer #1: Yes

Reviewer #3: Yes

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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 #3: Yes

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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 #3: Yes

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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: The authors have made all suggested changes, so the manuscript can be accepted for publication in Plos One.

Reviewer #3: The authors made the suggested changes, which improved this version. I have no additional suggestions for changes to the article.

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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: Yes: Fred Luciano Neves Santos

Reviewer #3: No

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