Prevalence and Factors Associated with Tuberculosis Among Healthcare Workers: A Systematic Review with Meta-Analysis

Round 1

Reviewer 1 Report (New Reviewer)

Comments and Suggestions for Authors

1. The main concern of this manuscript is Table 3. In Table 3, the definitions of TB infection vary in different articles, including the tuberculin skin test (TT) or IGRA. And the influence of BCG should also be considered in the TT method. Further explanation and discussion should be addressed in this issue.
2. The definition and criteria for active TB disease should be addressed in the method section and for Figure 2.
3. More discussion to compare the preventive measurements worldwide and in Brazil should be addressed in the discussion section.

Comments on the Quality of English Language

1. The paragraph on page 13 was stated in Portuguese.
2. Mixed "LTBI" and "ILTB" in table 3 and Line 264 & 268 should be corrected.

Author Response

Dear Reviewer,

We sincerely appreciate your valuable suggestions and the time you dedicated to reviewing this manuscript. All recommendations have been carefully considered, and detailed responses are provided in the response letter.

We hope to have met your expectations and remain available for any further clarifications.

Sincerely,

Author Response File: Author Response.pdf

Reviewer 2 Report (New Reviewer)

Comments and Suggestions for Authors

 

​​Overall Assessment​​

This systematic review and meta-analysis addresses a critical public health issue by examining the prevalence and risk factors of tuberculosis (TB) among healthcare workers (HCWs). The study is timely and aligns with global efforts to combat TB, particularly in high-burden settings. However, several methodological and presentation issues require substantial revision before the manuscript can be considered for publication. Below is a detailed critique with recommendations for improvement.

​​Major Concerns Requiring Major Revision​​

1. ​​Search Strategy Clarity​​

   • ​​Issue:​​ The "Search strategy" section in the Methods is overly abbreviated and lacks transparency. The use of verbose search strings in the main text disrupts readability.
   • ​​Recommendation:​​ Move detailed search terms to ​​Supplementary Material​​ (e.g., Appendix A). In the main text, summarize the strategy concisely, specifying databases, keywords, and Boolean operators used. Ensure compliance with PRISMA guidelines for reproducibility.

2. ​​Figure 1 Annotation​​

   • ​​Issue:​​ Symbols (* and ​**​) in Figure 1 lack explanation in the legend, causing confusion.
   • ​​Recommendation:​​ Clarify symbols in the figure caption. For example:
     *"Studies included (n=32): High quality (JBI score 7–9), ​**​Medium quality (JBI score 4–6)."

3. ​​Table 1 Redesign​​

   • ​​Issue:​​ The table header is excessively cluttered, hindering comprehension.
   • ​​Recommendation:​​ Simplify the header using numerical codes (1–9) for JBI criteria. Add a footnote explaining each code (e.g., "1 = Sampling frame appropriate"). Retain criteria descriptions in the footnote rather than repeating them in the header.

4. ​​Table 2 Redundancy and Mislabeling​​

   • ​​Issue:​​
     • The "ID" column is unnecessary and should be removed.
     • Columns "Title," "Authors/Years," and "Journal" duplicate information better handled in a reference list.
     • "Sample" column likely refers to sample size but is mislabeled.
     • Key findings from individual studies are absent, limiting utility.
   • ​​Recommendation:​​
     • Replace "Title," "Authors/Years," and "Journal" with a single "Reference" column formatted as superscript numbers linking to a consolidated reference list.
     • Add columns for ​​Key Results​​ (e.g., prevalence, odds ratios) and ​​Quality Score (JBI)​​.
     • Example redesign:

ID	Country	Study Design	Sample Size	Prevalence (95% CI)	Key Risk Factors Identified	JBI Score
1	Indonesia	Cross-sectional	792	12.3% (8.5–17.1)	Low education, long service tenure	9

5. ​​Table 3 Duplication and Redundancy​​

   • ​​Issue:​​ Table 3 appears to replicate data from Table 2 without adding new insights.
   • ​​Recommendation:​​ Merge Tables 2 and 3 into a single, streamlined table focusing on ​​key study characteristics​​, ​​prevalence estimates​​, and ​​associated factors​​. Prioritize concise presentation of critical data over exhaustive replication.

6. ​​Figure 3 Resolution​​

   • ​​Issue:​​ Figure 3 (factors associated with TB) lacks clarity due to low resolution.
   • ​​Recommendation:​​ Replace with a ​​high-resolution image (≥300 DPI)​​. Ensure fonts, symbols, and labels are legible in print.

​​Minor Recommendations​​

• ​​Methodological Quality Assessment:​​ Clarify why studies with low JBI scores (e.g., ID 6321, 6330) were included despite methodological flaws. Discuss potential biases introduced by heterogeneous study quality.
• ​​Geographic Analysis:​​ Table 4 presents TB incidence by country but lacks contextualization. Link findings to HCW prevalence data (e.g., discuss how high TB incidence in Myanmar/Indonesia correlates with HCW prevalence).
• ​​Discussion Limitations:​​ Address gaps in regional representation (e.g., limited African studies) and temporal trends (e.g., older studies may reflect outdated practices).
• ​​Language Polishing:​​ Improve flow and conciseness in sections like the Introduction and Discussion (e.g., redundant phrases like "it is important to highlight" should be condensed).

​​Conclusion​​

While the study addresses a vital topic, significant revisions are needed to enhance rigor, clarity, and readability. A ​​major revision​​ is recommended to address methodological transparency, data presentation, and alignment with PRISMA/STROBE guidelines. Addressing these concerns will strengthen the manuscript’s contribution to the field.

Author Response

Dear Reviewer.

We thank you for your valuable feedback. Please find attached the response letter with the corresponding clarifications, as well as the revised version of the manuscript with all changes highlighted in red. We remain at your disposal for any further questions or comments.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report (New Reviewer)

Comments and Suggestions for Authors

Table 3 was not mentioned in the main text.

The last part of the Discussion, References, and other parts may be lost; I can not see them.

Author Response

We appreciate your recognition of the revisions already incorporated into the manuscript.
Your contributions have been essential in enhancing the quality and robustness of this work.

Below, we provide point-by-point responses to the new comments:

Comment 1: Table 3 was not mentioned in the main text.

Response 1: Thank you for pointing this out. We agree with the comment. A typographical error occurred after the deletion and merging of tables during the revision process. As a result, the numbering was not correctly updated. The manuscript now contains only three tables, not four as previously indicated.

Comment 2: The final part of the Discussion, References, and other sections may be missing; I cannot see them.

Response 2: Thank you for pointing this out. We agree with the comment. We conducted a thorough review of the manuscript to identify any possible issues. The final paragraph of the Discussion section begins on page 443, the Conclusion is on page 451, and the References section starts on page 469. If this was not the concern raised, we remain available for further clarification.

We remain at your disposal for any additional information.

Sincerely,
Alessandro

Round 3

Reviewer 2 Report (New Reviewer)

Comments and Suggestions for Authors

The authors have addressed all my concerns. 

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Increased probability of LTBI and active TB among HCW has been reported in many parts of the world. Nevertheless meta-analysis of published data is difficult due to different epidemiological situation of different countries.  Therefore, the presented study should take into account these discrepancies. My remarks concern as follows:

Methods:

1.The authors describe the methods of articles selection (fig 1). I don’t understand the reasons for exclusion of 5589 records out of 6468 screened. Moreover the final analysis concerned only 32 studies, published from 1985 to 2023. Therefore, I suppose that the selection bias might be considerable, and should be discussed by the authors.

2. The authors should state if they analysed the prevalence of LTBI or active TB ( based on results section I suppose that some of selected papers concerned LTBI).

Results:

1.      It is important to list the studies showed in  table 1 in the references,  introducing the citation numbers into the table 1.

2.      As expected, the results concerning the prevalence of TB among HCW are very heterogeneous ( from 0.14% to 100% - Figure 2). I suppose that these discrepancies were caused by including studies from countries with different epidemiological situation of TB and conducted at different periods of time. I suggest the authors to introduce into the table the data concerning TB prevalence in general population of chosen countries at the time of study, to show the real increase of TB prevalence in HCW, thus making these studies comparable.

3.      Figure 3 is not described properly. The explanations should concern the content of graphs 3A-3D separately. The described results are not corresponding with the graph. Only graphs 3A and 3B show significant differences ( 3C – concerning education level (?) and 3D - concerning>10 years of professional experience (?) - are not significant).

4.      The analysis of gender as risk factor of TB was not showed, nevertheless the authors conclude that females are more prone to develop active TB. Nurses and technicians are usually females, I wonder how many males HCW with TB were included into the study?

Abstract.

The data included in the abstract are not the same as in the section results.

Discussion.

The discussion should concern the obtained results, not the general information concerning TB risk and prophylaxis in HCW. The weakness and strengths of the analysis should be discussed.    

From my point of view, the most interesting data that were probably included in the presented studies concern the effectiveness of different prophylactic policies in reducing the prevalence of TB  in HCW. This was not the aim of the study but could be mentioned in the discussion.

In many parts of  the text “LTBI” not “ILTB” should be included.

In summary: the article could be published but it deserves major revision.

Author Response

 

Dear Reviewer,

We sincerely appreciate your valuable contributions and the care you took during the evaluation. We have worked to address all the questions and have incorporated the suggestions made. The changes are highlighted in red within the manuscript, as described in the response letter. We are available for any further clarifications.

Kind regards,

Alessandro Scholze

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

1. There is high heterogeneity between the studies on the prevalence of tuberculosis (I ²=99%, p=0), which may affect the reliability and stability of the results, and also make further comparison and analysis difficult. Although the author used a random effects model, high heterogeneity is still an issue that cannot be ignored, which may reduce the generalizability of research conclusions.

2. The authors concluded that early diagnosis of tuberculosis in the workplace and the implementation of continuing education programs with preventive strategies are essential to control contamination and the spread of the disease. There is no specific indication of the evidence supporting the association between these factors and the prevalence of tuberculosis. For some identified risk factors, such as education level, gender, educational level, years of professional experience, occupational environment, diabetes, hepatitis and other comorbidities, although their association with tuberculosis was mentioned, their mechanism of action and differences in the degree of influence were not further explored. This may lead to a lack of comprehensive understanding of these factors, making it difficult to provide more detailed theoretical support for targeted preventive measures.

3. Insufficient consideration of regional differences: The study included articles from different countries and regions, but did not fully explore the potential impact of regional differences on the research results during the analysis process. The medical environment, prevalence of tuberculosis, and implementation of preventive measures in different regions may be very different. These factors may interfere with the consistency of research results, but the analysis in this regard is insufficient

4. In discussion, the prevalence of active TB among workers was 15.98% [9.00 – 26.78]. The value of incidence rate is inconsistent with the data showed in result and abstract, please confirm.

 

 

Author Response

Dear Reviewer,

We sincerely appreciate your valuable contributions and the care you took during the evaluation. We have worked to address all the questions and have incorporated the suggestions made. The changes are highlighted in red within the manuscript, as described in the response letter. We are available for any further clarifications.

Kind regards,

Alessandro Scholze

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors partly improved the manuscript according to my remarks. I still have objections concerning the methodology as the articles included in the meta-analysis have been published in the broad time span of 1985-2023, and concern the populations with different tuberculosis incidence rate (e.g. Brasil 36/100 000, US 4/100 000, Germany 8/100 000).

Nevertheless I doubt if the paper could be further improved in this respect.  Therefore in my opinion the present version could be published with editorial comment concerning the above mentioned epidemiological problems.

The description of Figure 3 is still lacking. Factors related to HCW Tb should be listed under the figure: 3A – gender, 3B – age, 3C- education level, 3D -

The discussion contains many repeated fragments and it is not logical. I tried to do my best to suggest the corrections.

I suggest to delete the parts marked in orange and reorganize the discussion in the following order: 308-312 - first paragraph, 296-302 - second paragraph, 313-318 - third paragraph (please see the attachment).

Comments for author File: Comments.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The articles included in the study  showed high heterogeneity  on the prevalence of tuberculosis. The authors stated that they aimed to present the results broadly. Therefore, it is essential to do a thorough investigation of heterogeneity to clarify the potential impact of regional differences on the prevalence.  Random-effects meta-analysis is not a substitute for a thorough investigation of heterogeneity. However, the author failed to explore the heterogeneity  neither by conducting subgroup analyses, nor incorparated with alternative mathematical model.