Knowledge, Attitudes, and Practices Associated with Syphilis Infection Among Physicians in Armenia

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is an interesting article. In the introduction, the authors should at least cite the fact that syphilis may have atypical manifestations that make the diagnosis challenging. A recent study found that 25% of all the T.pallidum infections diagnosed during 10 years in two Italian Dermatologic Clinics were atypical in presentation.
Outpatient physicians should know this possibility to avoid misdiagnoses and delay in the correct diagnosis.
Consider:
Ciccarese G, Facciorusso A, Mastrolonardo M, Herzum A, Parodi A, Drago F. Atypical Manifestations of Syphilis: A 10-Year Retrospective Study. J Clin Med. 2024 Mar 11;13(6):1603. doi: 10.3390/jcm13061603. PMID: 38541829; PMCID: PMC10971508.

Author Response

Comment 1․ This is an interesting article. In the introduction, the authors should at least cite the fact that syphilis may have atypical manifestations that make the diagnosis challenging. A recent study found that 25% of all the T.pallidum infections diagnosed during 10 years in two Italian Dermatologic Clinics were atypical in presentation.
Outpatient physicians should know this possibility to avoid misdiagnoses and delay in the correct diagnosis.

Thank you for your valuable comment. We appreciate your suggestion and agree that acknowledging the atypical manifestations of syphilis is important for understanding the challenges in diagnosis. Based on your feedback, we have incorporated this point into the introduction and cited relevant literature to highlight the diagnostic difficulties.

• In the introduction, L 50-51 (blue color) we added: Frequent atypical manifestations present additional challenges in clinical practice [5].

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Estimated Authors,

first of all, thank you for the opportunity to review this interesting paper. Syphilis is far from being a new medical condition, but it is also far from disappearing not only in developing countries, but also across developed ones. As a consequence, an appropriate understanding of this condition and preventive / management options are both useful and significant from a Public Health Point of View.

According to the present, nationwide report, Armenian primary care providers are far from being able to share with their patients an appropriate understanding of this condition. Authors, tentatively, provide some explanations, but some other remain unexplored. For example: is in Armenia the study of STI included into the core curriculum of medical schools?

Albeit interesting, the present paper could benefit from some improvements. For example:

1) Methods section: please provide a more accurate description of statistical analysis you did perform. For example, which test do the p values refer to? Statistical analysis must be declared before the reporting of main data;

2) results section: a translation of the questionnaire is provided as annex material, and its analysis suggests that Authors shared with their participants a closed-option questionnaire: as a consequence, Authors should provide a more accurate reporting for questions having more than a dichotomous option (e.g. 406, 407, etc). This information could be shared also as annex material.

3) Categories on the work department are very specific, leading to the definition of several subgroups, some of them with very reduced sampling size! For example, Emergency Dep. has only 3 participants. As a consequence, the analyses may be biased. I would suggest to revise the groups (e.g. ICU and Emergency department may be merged).

4) Please provide a map of Armenia in order to better understand where participants were actually distributed across the national territory;

5) It is unclear how groups of poor, moderate, and good status regarding knowledge, attitudes and practices were defined. Please refine and include within the label of figure 6.

Thank you again for providing this very interesting paper!

Author Response

Comment 1. Methods section: please provide a more accurate description of statistical analysis you did perform. For example, which test do the p values refer to? Statistical analysis must be declared before the reporting of main data;

• Thank you for your comment.
  We have made changes to the last paragraph of the Methods section (L 195-199).

To assess differences in KAP scores across multiple independent groups (e.g., different medical specialties, years of experience) we used the Kruskal-Wallis test. To examine the relationship between practice and knowledge scores, we applied the Spearman correlation test [10]. At 95% Confidence Interval, p-value < 0.05 was considered to be statistically significant.

Comment 2. 

results section: a translation of the questionnaire is provided as annex material, and its analysis suggests that Authors shared with their participants a closed-option questionnaire: as a consequence, Authors should provide a more accurate reporting for questions having more than a dichotomous option (e.g. 406, 407, etc). This information could be shared also as annex material.

• Thank you for your insightful comment.

We have carefully reviewed the questionnaire and identified the questions with more than two options (e.g., questions 406, 407, etc.). In response to your suggestion, we have provided a more detailed breakdown of the responses for these questions. This additional information is now included in the Appendix C of the manuscript. We believe that this will enhance the clarity of the reported results and offer more accurate insights into the participants’ answers.

When introducing table 4, we add L 226-227 the sentence “Answers to questions with all possible responses are detailed in supplementary material Appendix C”.

Comment 3. Categories on the work department are very specific, leading to the definition of several subgroups, some of them with very reduced sampling size! For example, Emergency Dep. has only 3 participants. As a consequence, the analyses may be biased. I would suggest to revise the groups (e.g. ICU and Emergency department may be merged).

Thank you for your comment.
I have merged the ICU and Emergency Department in tables 3. and table 5. and highlighted the changes, including the scores.

Comment 4. Please provide a map of Armenia in order to better understand where participants were actually distributed across the national territory;

• Thank you for the suggestion; it was very relevant. I have included the map of Armenia as Appendix B. L 418-420

Comment 5. It is unclear how groups of poor, moderate, and good status regarding knowledge, attitudes and practices were defined. Please refine and include within the label of figure 6. 

• Thank you for your comment.

Table 6 shows the number of participants, also expressed as a percentage, who recorded poor, moderate, and good knowledge according to the defined criteria 0-<30% (Poor), 30-<70% (Moderate), and >70% (Good). I have made changes to Table 6 and added the scores based on the cut off values. L 248-251

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review this work.

The authors clearly articulate the research problem and have done a good job to put together this report. Here are my comments for improvement:

1. The English language in this manuscript requires substantial improvement before it can be considered for publication
2. L20-21 – rephrase for clarity
3. L15 – What do the authors mean by syphilis diagnosis in Armenia is unreliable?
4. L53-54 is redundant
5. L56-66 all statements there require citations
6. L73 requires citations
7. Overall, the introduction could be improved by adding more literature on the topic. For example, how do the country guidelines compare with international recommendation? What have previous researchers done on this topic in the country and what were their findings?
8. The justification of the study could be strengthened further.
9. The materials and methods section is not reported using any standard reporting guidelines and that results in several important points. I recommend authors to use the STROBE checklist for cross sectional studies available from https://www.strobe-statement.org/checklists/
10. Under results, authors may consider reducing the number of Tables to have only the standard reporting tables in the main manuscript i.e. key finds and move the rest to supplementary files.
11. In the discussion section, authors can further expand on their own interpretation of the findings and their implications to the country STI program in addition to the comparison and contrasting previous studies.
12. Overall, the number of references cited seems too small for a full-length paper. Authors are encouraged to engage more with literature in both introduction and discussion sections.

Comments on the Quality of English Language

The English language in this manuscript requires substantial improvement before it can be considered for publication

Author Response

Comment 1. The English language in this manuscript requires substantial improvement before it can be considered for publication.

Thank you for your comment. We have made corrections regarding the language issue.

Comment 2.  L20-21 – rephrase for clarity

• Thank you for your comments.

We changed the sentence from 'We randomly selected 24 clinics in six regions, sent an online questionnaire randomly selected from employee registries' to 'We randomly selected 24 clinics in six regions. In each clinic we randomly selected respondents from employee registries.” in L21-23

Comment 3. L15 – What do the authors mean by syphilis diagnosis in Armenia is unreliable?

Thank you for your question. We add in L 15-17: “Syphilis diagnosis in Armenia is unreliable due to inconsistent testing methods, limited access to confirmatory tests and underutilization of healthcare services due to stigma and lack of awareness.”

Comment 4. L53-54 is redundant

Thank you.

• To avoid repetition, we changed the sentence in from “The World Health Organization (WHO) emphasizes the importance of regular screening, [3] especially for pregnant women, to prevent mother-to-child transmission [4,5]. Congenital syphilis can result in premature birth, miscarriage, or severe infant health issues. The World Health Organization (WHO) continues to work globally toward the elimination of mother-to-child transmission of HIV, syphilis, and hepatitis B. Syphilis continues to be a significant global health concern, with its burden increasing over the past decades [6,7].” to "The World Health Organization (WHO) emphasizes the importance of regular screening, especially for pregnant women, to prevent mother-to-child transmission of HIV, syphilis, and hepatitis B [6,7,8]. Congenital syphilis can result in premature birth, miscarriage, or severe infant health issues. Despite ongoing efforts, syphilis remains a significant global health concern, with its burden increasing over the past decades [9,10]." in L 52-56.

Comment 5. L56-66 all statements there require citations

• "In lines 56-66 we added relevant citation to documents in Armenian

Comment 6. L73 requires citations.

• "In line 73, we added relevant citation to documents in Armenian

Comment 7. Overall, the introduction could be improved by adding more literature on the topic.

1) For example, how do the country guidelines compare with international recommendation? 

To address this suggestion, we added the following information in L 69-80.

• “The World Health Organization (WHO) provides comprehensive guidelines for syphilis screening and treatment in pregnant women. These guidelines emphasize the importance of early detection and treatment to prevent adverse pregnancy outcomes and mother-to-child transmission [6]. Unfortunately, Armenia lacks specific guidelines for the early diagnosis, detection, and treatment of syphilis in pregnant women, where healthcare providers could find answers to their questions. However, the Ministry of Health, in collaboration with the Yerevan Municipality, launched the "Do Not Guess, Get Tested" campaign in 2020. This initiative provided free, anonymous, and rapid testing for HIV, syphilis, hepatitis B, and C in all outpatient clinics across Yerevan. The program aims to increase awareness and early detection of these infections. In addition, the European guidelines on the management of syphilis include recommendations on the diagnosis and management of syphilis in Europe [12,13].”

2) What have previous researchers done on this topic in the country and what were their findings?

We add the following information in L 86-107

• “Previous research in Armenia has primarily focused on the epidemiology of syphilis, with studies showing an increase in syphilis cases until the 2010s [15].”

Comment 8. The justification of the study could be strengthened further.

Thank you for your comments. Overall, the study justifications are presented in the text, and to avoid repetition, we prefer to leave them unchanged.

Comment 9. The materials and methods section are not reported using any standard reporting guidelines and that results in several important points. I recommend authors to use the STROBE checklist for cross sectional studies available from https://www.strobe-statement.org/checklists/

Thank you for your comments

• We made changes according to the STROBE in the Methods in L 115; L126-128; L150-165; L179-182.

Comment 10. Under results, authors may consider reducing the number of Tables to have only the standard reporting tables in the main manuscript i.e. key finds and move the rest to supplementary files.

Thank you for your comments. 

• We would prefer to keep the tables. We believe they provide information necessary for our argumentation.

Comment 11. In the discussion section, authors can further expand on their own interpretation of the findings and their implications to the country STI program in addition to the comparison and contrasting previous studies.

• Thank you for your valuable comment.

There have been no studies in Armenia examining physicians' knowledge, attitudes, and practices regarding syphilis. We identified that our findings could contribute to policy changes, improvements in public health programs, and the guidance of healthcare practices in alignment with international best practices.

Comment 12. Overall, the number of references cited seems too small for a full-length paper. Authors are encouraged to engage more with literature in both introduction and discussion sections.

• Thank you for your valuable comment. We have added 10 references.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Suitable for publication in present form.

Author Response

Thank you!

Reviewer 2 Report

Comments and Suggestions for Authors

The paper has been properly improved, therefore I'm delighted to share my endorsement for acceptance

Author Response

Thank you!

Reviewer 3 Report

Comments and Suggestions for Authors

Thank you for making efforts to revise your work. It has greatly improved. A few additional concerns/clarifications.

1. Again, language concerns persist. For instance, line 151 - the opening sentence is not grammatically correct
2. Line 158: exactly how did the the study account for the limited or no
   prior syphilis training of some participants to reduce bias from prior knowledge?
3. In section 2.5, authors only list age and number of years' experience as the only quantitative variables. This is not correct. 

Comments on the Quality of English Language

Must be improved.

Author Response

Dear Reviewer,

We are grateful to you for your relevant suggestions. We reviewed the text again and carefully edited it for clarity and grammar. Several redundant words and sentences were removed, and the corrections were added in red.
We would also like to inform you that a native speaker has proofread the manuscript to improve its grammar. If you find only minor corrections throughout the text, this should serve as proof that the entire manuscript has been improved.

Comment 1. Thank you for your comment, we add new sentence in L151:

Several efforts were made to minimize potential sources of bias.

Comment 2. Thank you for your comment, We removed the sentence in line 158, and add new sentences in L158-161. We agree that the original sentence was not informative. We used this opportunity to rephrase the entire section 2.4.

Additionally, the research accounted for the limited or no prior syphilis training of some participants by designing the questionnaire to assess fundamental knowledge, attitudes, and practices that are relevant regardless of prior training.

Comment 2. Thank you for your comment. We have made some revisions regarding section 2.5, L 163-169

Quantitative variables such as age, professional experience, and KAP scores were used in the analysis. Age was grouped into categories: <30, 30-39, 40-49, 50-59, and >60 years. Professional experience was categorized into <1 year, 1-5 years, 6-10 years, 11-15 years, and >16 years. For categorical variables, we considered factors such as sex, work department and region. These were used to assess demographic differences in knowledge, attitudes, and practices. KAP scores were treated as continuous measures but were also categorized into poor, moderate, and good for comparative purposes.