Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Authors, correct the written part:    therapeutic delays persist as major contributors to preventable morbidity,

 

Author Response

Comments:

Authors’ answers:

Reviewer #1: Authors, correct the written part: therapeutic delays persist as major contributors to preventable morbidity. The manuscript fits the journal’s scope.

We thank the Reviewer for the comment and we rephrased as follow: “Delays in diagnosis and treatment continue to significantly contribute to preventable morbidity, sustained disease transmission, unnecessary healthcare costs, and the emergence of drug resistance”.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript fits the journal’s scope.

Correct article but of limited originality, reiterates the content of Ref. 2, for the benefit of the audience, with no particular innovation. See also Brehm TT, et al. Clinical standards for antimicrobial stewardship in TB care. IJTLD Open. 2025 Dec 10;2(12):716-726. doi: 10.5588/ijtldopen.25.0522. PMID: 41395320; PMCID: PMC12699960. Missed in References.

The eight papers used should be clearly and punctually identified.

Figure not at level appropriate for publications. Lacks a Legend, arrow links lack logic and consistency, does not correspond to the text in 3.4, excessive capitalization. Diagnosis (the result) is used in red box instead of diagnostic investigation (the means). “Missed” and “Reinforce” boxes are not actions of an algorithm. The “active screening” box is not consistent with the algorithm.

Missing cost evaluation of delayed diagnosis and cost of proposed strategy.

Author Response

Reviewer #2

Correct article but of limited originality, reiterates the content of Ref. 2, for the benefit of the audience, with no particular innovation. See also Brehm TT, et al. Clinical standards for antimicrobial stewardship in TB care. IJTLD Open. 2025 Dec 10;2(12):716-726. doi: 10.5588/ijtldopen.25.0522. PMID: 41395320; PMCID: PMC12699960. Missed in References.

The eight papers used should be clearly and punctually identified.

We thank the Reviewer and we added the missed references to the list. Furthermore, we adde a table with the 9 selected references, updating the manuscript accordingly. References 2 is about treatment stewarship.

Figure not at level appropriate for publications. Lacks a Legend, arrow links lack logic and consistency, does not correspond to the text in 3.4, excessive capitalization. Diagnosis (the result) is used in red box instead of diagnostic investigation (the means). “Missed” and “Reinforce” boxes are not actions of an algorithm. The “active screening” box is not consistent with the algorithm.

 

We thank the Reviewer for the suggestion and we have updated the Figure.

 

Missing cost evaluation of delayed diagnosis and cost of proposed strategy.

We agree with the Reviewer about this missing point, which will require a proper research on large scale (for all high income, low TB incidence countries) and we would like to collaborate with her/him to do it.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The fight against TB, meaning an annual case rate of less than one per million people, is becoming a realistic goal in many high-income countries with low TB rates. But there are still challenges to this goal, especially in places where TB disproportionately affects disadvantaged and marginalized communities with poor health knowledge and limited access to care, like migrants, people with substance abuse issues, and those who don't have a fixed address. These populations often delay seeking healthcare, so they start TB treatment later and are less likely to finish it due to social factors. This raises the risk of drug-resistant TB and widens health and social gaps, making it harder to eliminate TB altogether. In this publication, the authors present an analysis of literature published over the past six years on delays in the diagnosis of TB in low-incidence and high-income settings. The authors view these delays through the lens of an asymptomatic presentation of the disease, and propose a management-focused approach that combines targeted screening, enhanced clinical vigilance, simplified diagnostic procedures, and strategies to facilitate patient referral to appropriate TB treatment centers. Ultimately, the goal is to provide timely and efficient medical care for patients. The review is clear, comprehensive, and relevant to the field. Most of the cited references are recently published and relevant.

Major concern.

As a conclusion the authors state that “Although pro-active screening and system redesign require initial investment, these approaches are likely to be cost-effective by preventing disease progression, averting catastrophic patient costs, and reducing inappropriate antimicrobial use”. Unfortunately, the article does not provide any calculations to allow for an approximate estimation of the scale of necessary costs and their economic impact on the cost of TB treatment. Without these calculations, the conclusions drawn in the article seem unjustified.

Author Response

Reviewer #3

 

The fight against TB, meaning an annual case rate of less than one per million people, is becoming a realistic goal in many high-income countries with low TB rates. But there are still challenges to this goal, especially in places where TB disproportionately affects disadvantaged and marginalized communities with poor health knowledge and limited access to care, like migrants, people with substance abuse issues, and those who don't have a fixed address. These populations often delay seeking healthcare, so they start TB treatment later and are less likely to finish it due to social factors. This raises the risk of drug-resistant TB and widens health and social gaps, making it harder to eliminate TB altogether. In this publication, the authors present an analysis of literature published over the past six years on delays in the diagnosis of TB in low-incidence and high-income settings. The authors view these delays through the lens of an asymptomatic presentation of the disease, and propose a management-focused approach that combines targeted screening, enhanced clinical vigilance, simplified diagnostic procedures, and strategies to facilitate patient referral to appropriate TB treatment centers. Ultimately, the goal is to provide timely and efficient medical care for patients. The review is clear, comprehensive, and relevant to the field. Most of the cited references are recently published and relevant.

 

Major concern.

 

As a conclusion the authors state that “Although pro-active screening and system redesign require initial investment, these approaches are likely to be cost-effective by preventing disease progression, averting catastrophic patient costs, and reducing inappropriate antimicrobial use”. Unfortunately, the article does not provide any calculations to allow for an approximate estimation of the scale of necessary costs and their economic impact on the cost of TB treatment. Without these calculations, the conclusions drawn in the article seem unjustified.

 

We thank the Reviewer for the evaluation of our manuscript and for this comment. We modified the sentence and added a reference about cost effectiveness of TB screening. We intended cost-effectiveness not only economically but also in terms of catastrophic costs for patients.

Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

Benevento et al. raised a pressing issue in modern epidemiology and phthisiology in their manuscript. Despite advances in modern medicine, the issue of delayed diagnosis of tuberculosis infection still presents a number of challenges. The development of a unified preventive approach at the primary care would help address these issues. The manuscript is well planned and written. The problem is clearly identified and a solution is proposed. The manuscript is well organized and clearly presented. However, there are a number of minor inaccuracies, the correction of which would significantly improve the quality of the manuscript. In particular, Figure 1 raises numerous questions. After correcting these inaccuracies, I can recommend the manuscript for publication.

 

Suggestions:

1. Line 40. Please provide the abbreviation "HIV."
2. Adding a discussion of the Diaskintest, as well as Interferon Gamma Release Assays (QuantiFERON test and T-SPOT) in the "Improving Clinical Recognition and Diagnostic Pathways" section, would significantly improve the quality of the manuscript.
3. Line 44. The reference to Figure 1 should be better reflected in the chapter itself, not in its title.
4. Figure 1. Please improve the quality of the figure. Display all abbreviations used in the figure in the legend. The patient-no symptoms-diagnosis axis is not entirely clear. What does it mean? It is also unclear whether the diagram is intended for all patients or only for risk groups. This should be stated in the figure title or shown on the figure. If I understand correctly, according to the proposed concept, a diagnosis can be missed in the absence of screening diagnostics, so why are there arrows in the diagram leading from "symptoms/no symptoms" directly to the diagnosis? Please review and revise Figure 1.
5. In the manuscript, the authors provide reference "16" without citing it. Please correct this mistake.

Author Response

Reviewer #4

Benevento et al. raised a pressing issue in modern epidemiology and phthisiology in their manuscript. Despite advances in modern medicine, the issue of delayed diagnosis of tuberculosis infection still presents a number of challenges. The development of a unified preventive approach at the primary care would help address these issues. The manuscript is well planned and written. The problem is clearly identified and a solution is proposed. The manuscript is well organized and clearly presented. However, there are a number of minor inaccuracies, the correction of which would significantly improve the quality of the manuscript. In particular, Figure 1 raises numerous questions. After correcting these inaccuracies, I can recommend the manuscript for publication.

 

We thank the Reviewer for the appreciance of our manuscript and for the suggestions.

 

Suggestions:

 

Line 40. Please provide the abbreviation "HIV."

 

Done

 

Adding a discussion of the Diaskintest, as well as Interferon Gamma Release Assays (QuantiFERON test and T-SPOT) in the "Improving Clinical Recognition and Diagnostic Pathways" section, would significantly improve the quality of the manuscript.

Thank you for the comment, we added a paragraph on immunological testing.

 

 

Line 44. The reference to Figure 1 should be better reflected in the chapter itself, not in its title. Figure 1. Please improve the quality of the figure. Display all abbreviations used in the figure in the legend. The patient-no symptoms-diagnosis axis is not entirely clear. What does it mean? It is also unclear whether the diagram is intended for all patients or only for risk groups. This should be stated in the figure title or shown on the figure. If I understand correctly, according to the proposed concept, a diagnosis can be missed in the absence of screening diagnostics, so why are there arrows in the diagram leading from "symptoms/no symptoms" directly to the diagnosis? Please review and revise Figure 1.

 

We updated the figure taking in account suggestion of both Reviewer 1 and 3.

 

In the manuscript, the authors provide reference "16" without citing it. Please correct this mistake.

 

We have added reference 16 to the text.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors responded acceptably to all the remarks. However, in the new Table 1, apart from lines 7 and 9, no article in the Table is included in the bibliography. This hinders even spot-checking of sources.

Author Response

Dear Editor,

 

Thank you for your kind re-assessment of our manuscript.

 

We are here enclosing a point-by-point response to the Reviewer’s comment.

 

 

Comments:

Authors’ answers:

Reviewer #1

 

The authors responded acceptably to all the remarks. However, in the new Table 1, apart from lines 7 and 9, no article in the Table is included in the bibliography. This hinders even spot-checking of sources.

 

We have updated the references list as suggested.

Author Response File: Author Response.pdf