Reemergence of Congenital Syphilis in the United States: A Narrative Review

Round 1

Reviewer 1 Report

Firstly, it is important to highlight the relevance of the manuscript in pointing out the increase in the number of syphilis cases in the USA in the last decade and consequently the increase in the number of episodes of congenital syphilis. The topic deserves attention as the disease can lead to serious consequences for the mother and her newborn. The advancement of the disease in developing countries is also a reality, however, due to several socioeconomic and behavioral factors associated with the reality of countries with few resources, the control and treatment of the disease becomes more difficult, which in theory should be easier in countries highly developed.

The authors of the manuscript described several aspects of the disease, such as epidemiology, clinical characterization, diagnostic methods and current treatment. Furthermore, the authors cite some factors that may be directly influencing this re-emergence of syphilis in the USA. However, in my view, there was a lack of a more specific and detailed description of the possible hypotheses for this phenomenon. For example:

1- Why the increase in the number of cases in young women (15-44)? What social, economic or behavioral factors may be involved with this increase in this age group?

2- Why was the increase in the number of cases greater in states in the southern region of the country?

3- What would be the real lack of knowledge among health professionals regarding the disease? If this lack of knowledge exists, what is its impact on the diagnosis, treatment and management of infected women?

4- Are public health strategies aimed at controlling the increase in the number of cases being implemented? What measures are being taken for control? Over the years, have these control measures changed?

5- Is the increase in the number of cases of other sexually transmitted infections accompanying this increase observed in syphilis?

6- What could explain the differences in the prevalence of CS between different ethnicities (Blacks, Hispanics, African Americans)?

7- 7- Are there epidemiological characteristics that could be specific to the re-emergence of syphilis in developed countries when compared to countries with few resources? What do studies carried out in other countries cite as factors that could be associated with vulnerability to infection?

Ultimately, I think that factors such as those mentioned could provide a broader view of the real scenario that could explain and help identify the factors associated with the re-emergence of this infection in the country.

Author Response

Please see the attachment. 

Author Response File: Author Response.pdf

Reviewer 2 Report

Thank you for the opportunity to review this manuscript. The authors address an important and timely issue. Overall, the paper is well written and understandable to both the specific reader audience as well as other social and bio-related fields. I appreciate that. Please pay attention to your use (or lack of usage) of commas. They can really change, enhance, or clarify the meanings of sentences. Although I list a very specific case below, please check the paper throughout and insert commas after clauses that require them. Below, I have listed a few more specific minor corrections that would strengthen the paper and polish it even more.

Introduction

“A main cause of the rise in CS cases in the US is due to a lack of adequate maternal treatment despite appropriate diagnosis and lack of timely prenatal care [1].” Does this mean that even though women are getting appropriate diagnosis, mothers are not getting adequate maternal treatment? The word “despite” implies this. I see that it is cited, but just wanted to clarify that was intended meaning of the clause.

“Globally, congenital syphilis was found to be 425 cases /1, 00,000 cases in 2020 which 38 was much higher than the WHO’s 2007 target of 50 cases /1, 00,000 cases.”  Please correct the comma placements for the rates above. Should read 100,000 cases in both instances.

“Historically, most congenital syphilis cases were reported from a few states, but in 2021, almost all states reported at least one case of congenital syphilis [6].” Please state how many states are “a few?” Please state how many states constitutes “almost all?” Few and almost all varies in the minds of the audience readers.

“Necrotizing umbilical periphelbiitis is an admixture of necrotic debris and eosinophilic precipitate around the umbilical vein.” Please correct the misspelling of periphlebitis.

“In general, the trend in the literature suggests that if a series of placentas in cases of confirmed congenital syphilis is studied the proportion of placentas with pathology will be high [11, 12]; whereas if a series of cases of maternal gestational syphilis is looked at the proportion of placentas with pathology will be low [14]” These two statements need commas and proper if-then insertions to be better understood. Should read:  In general, the trend in the literature suggests that if a series of placentas in cases of confirmed congenital syphilis is studied, then the proportion of placentas with pathology will be high [11, 12]; whereas if a series of cases of maternal gestational syphilis is looked at, then the proportion of placentas with pathology will be low [14].

Method

Please state 1) exactly how many (English) articles this search produced and 2) an approximation of the time you conducted the search (e.g., …between March 2023 and June 2023).

Conclusion

I appreciate the authors’ attention to health disparities regarding this issue, and it is timely and very appropriate. However, the conclusion is missing main points or a bottom line regarding the rest of the report. The conclusion is solely focused on disparity, speaking mostly to the social determinants of health. Please do keep this. But also, (perhaps before this paragraph), summarize some of the recommendations from your studies on this (e.g., 1^st AND 3^rd trimester testing preferred and why; the type(s) of test(s) that is standard best-practice, or stating that if there is no standard best-practice diagnostic, then what is the optimal combination of tests from what you understand it to be; and/or more research needed on placenta and stillborn specimens and why.)

Please pay attention to your use (or lack of usage) of commas. They can really change, enhance, or clarify the meanings of sentences. Please check the paper throughout and insert commas after clauses that require them. Perhaps have a colleague proofread with an eye toward proper comma usage where needed.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf