PONE-D-19-30772

Association Between Tuberculosis and Depression on Negative Outcomes of Tuberculosis Treatment: A Systematic Review and Meta-Analysis

PLOS ONE

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Major Revision

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Reviewer #1: Ruiz-Grosso etal. have submitted a review and meta-analysis exploring the association of TB treatment via the DOTS program and depression resulting in negative outcomes such as non-adherence and death.

While the subject matter of the article is interesting, it occurs that the authors have been extremely careless with their citations. These must be fixed and extensively updated if this can be a published article.

On numerous occasions the cited paper appears to be incorrect and the way the papers are called out in text "Theron etal., Yan etal. Tola etal.) are papers that do not even appear in the list of references! How can the handful of papers cited for the analysis not appear in the references? The years for studies reported on appear to change between figures for example in Figure 2 Ambaw is 2016, and in Figure 3 its 2018. Even worse is that the only "Ambaw" paper in the references is a 2015 BMJ open study protocol, not even the actual findings of those authors.

Other major comments:

- The authors should expand on DOTS - what is the therapy? What drugs does it comprise? What is the length? How many times and how frequently does the patient need to see a healthcare worker? This would help identify to the reader what non-adherence means.

- Have there been any studies to show how much non-adherence is acceptable? If DOTS is a 9 month program then if drugs are taken for only 8 months, is that sufficient or still completely non-adherent?

- Page 2, line 36: State that MDR-TB is multi-drug resistant when the term is first introduced.

- Reference 7 appears to be incorrect. Double check the 121 million figure.

- Reference 8 is limited to a study in Singapore and may not apply as broadly as used in this context. The authors must find better references to support their claims.

- Reference 12 appears to be a circular reference not citing an actual research article that can be used to support the author's claims.

- Page 9 Line 198: state that 'depressive symptoms' are (DS) and psychological distress are (PD) here.

- Can the authors comment on the age of the study participants included in the studies that they used for the meta-analyses. Especially, when death is a primary outcome, it would be important to state such information.

In sum, the authors should fix the citations and the text in the figures extensively and address the additional comments outlined above.

Reviewer #2: Though the total collected dhruv's were more but those selected for the review and analysis were a small number. Understandably as the rest would not have met the required criteria.

Vital point is to address the heterogeneity in the studies including the definition of depression and treatment outcomes.

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Reviewer #1: No

Reviewer #2: No

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Association between tuberculosis and depression on negative outcomes of tuberculosis treatment: A systematic review and meta-analysis

PONE-D-19-30772R1

Dear Dr. Dr. Ugarte-Gil,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

HASNAIN SEYED EHTESHAM

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

This manuscript is a review describing the association between TB and depression on negative outcomes on TB treatment. The Authors have carried out extensive revision addressing all comments of the reviewers. Table 2 & 3 have been modified. I recommend this manuscript for publication.

Reviewers' comments: