PONE-D-22-00257Bacteriologically confirmed extrapulmonary tuberculosis and the associated risk factors among extrapulmonary tuberculosis suspected patients in Ethiopia: A systematic review and meta-analysisPLOS ONE

Dear Dr. Diriba,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Both reviewers felt that the paper had merit. Both did however identify concerns with the methodology. Specifically, there was a concern that the denominator of the study (all PTB cases) was not realistic and undefined and 1 reviewer felt strongly that the review question needed to be tightened. There were also concerns with the construction of the forest plots which reviewer 1 felt should be ordered from low to high. Both reviewers highlighted a number of small stylistic errors which should also be corrected.

Please submit your revised manuscript by Apr 24 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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We look forward to receiving your revised manuscript.

Kind regards,

Elizabeth S. Mayne, M.D.

Academic Editor

PLOS ONE

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Additional Editor Comments:

Both reviewers felt that the paper had merit. Both did however identify concerns with the methodology. Specifically, there was a concern that the denominator of the study (all PTB cases) was not realistic and undefined and 1 reviewer felt strongly that the review question needed to be tightened. There were also concerns with the construction of the forest plots which reviewer 1 felt should be ordered from low to high. Both reviewers highlighted a number of small stylistic errors which should also be corrected.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: N/A

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Line

22 lack of a strong…

24 insert full stop

27 spread across

29 insert full stop

31 “majority”: what is the percentage?

31 substitute “articles” for “research”

32 variations

33 “medium/high risk”: the funnel plot in fig 3 for the 20 papers shows 10 papers above the 95% upper limit and 5

below the 95% lower limit and only 5 within the CI. More discussion is required for your assessment. Is this justified

by the standard error of the effect size on the y-axis?

34 Delete “having”. PTB must be in full here, that is, “pulmonary tuberculosis”

35 Delete “being”

41 Keywords:… “Pulmonary Tuberculosis” for Tuberculosis…

49 Use “EPTB”; this has already been defined

54 EPTB

55 15%

61 Delete “and”

62 Delete extra space after “resource- “

64 turnaround times

70 “had started” for “have been started”

72 (11) for [11]

76 et seq. Remove end full stops in numbering, for example, 2. and 2.1. should be 2 and 2.1

86 Delete “the”

88 Delete “language”

93 “using a Microsoft Excel worksheet” should be “Microsoft Excel® 2016” (or whatever version was used)

96 “resolved inconsistencies that arose”

99-102 The WHO definition of a positive test result was applied. This states that a positive diagnostic test result using

smear microscopy, culture, Xpert MTM/RIF or nucleic acid amplification test is a bacteriological confirmation of an

EPTB infection.

104 Delete “included”

105-107 Persistent disagreements indicate a lack of clarity in applying the Newcastle-Ottawa scale. Should the scale be

modified and would different interpretations be applied by researchers on similar studies. The nature of the

disagreements and outcomes of using alternative interpretations should be discussed especially in light of the

small sample of 20 papers

112 STATA® 14.2 StataCorp LLC, Texas, USA

113 a 95% confidence interval. Random-effects

114 The ‘metaprop’ command in STATA was used.

115-116 A forest plot shows distributional information not prevalence

119-127 This requires the editing out of excess detail in light of the PRISMA diagram. The PRISMA diagram is important

and sets out clearly the process in reducing the 938 articles to 20 used in this study

123 The 36 non-Ethiopian papers should either be included as controls in the forest plots or in separate forest plots. These

could indicate possible biases, inconsistencies or differences in interpretation of data in Ethiopian papers (for example

see disagreements in 105-107 above). This applies to funnel plots as well

135 Delete “was”

142 Delete “another”

Page 8 Some hyphens missing in “cross-sectional”. Associated factors column requires some editing (spaces and spacing

of commas)

148 The frequency of EPFB varied widely over the 20 studies. The prevalence ranged from 9% (21) to 78% (32). See also

general comment below on superscript of paper reference.

150 random-effects

157 using a random-effects model

157 “Effect size” should appear in full in the x-axis label

158 “twenty studies”, delete used.

158-159 Standard error of effect size should appear in full on the y-axis

160 The subgroups of the 20 studies should be shown in the PRISMA diagram to ensure completeness and intelligibility

170 Pooled proportion of culture-positive EPTB using random-effects model

172 Same style as 170

174 Same style as 170

184 Funnel plot of subgroup of 15 of the 20 selected studies

184 Standard error of effect size and effect size should appear in the axis labels

186 Same style as 184

188 Same style as 184

192 A history of PTB infection

200 Delete “of”

196 HIV should be HIV-1

204 A history of PTB infection ("history" implies previous history)

210 … similar to that…

214 “systemic” should be “systematic”

217 HIV-1

218 …risk factors associated with EPTB infection…

219 HIV-1

220 … EPTB patients were HIV-1 infected,…

223 TB-HIV-1 co-infection

227 … with a history of… (“history” implies previous history)

235 Firstly,

237 Secondly,

238 Statistical power and its reduction has not been discussed in the paper. What is the estimate of the reduction and has

this invalidated the paper? (Does statistical power here refer to I^2, p-value or items outside the 95% pseudo-

confidence gradients in the funnel plots?

238 “poor quality of several studies” – I am not sure this has been sufficiently discussed (if at all)

244 HIV-1

General: number references to papers should preferably be shown as superscripts to avoid with number in the paper. For example, line 49, …region (8%) (3) should be …region (8%)3 (3 as superscript)

References: Journal references should be italicised. Latinisms like et.al. should be italicised

Figure 1: PRISMA diagram should show the subgroups budding off the “Final analysis” box. Reference to this in the main body of the paper will simplify some of the wording in the main body

Figure 2: Forest plot should be sorted by ES and show ranking from lowest to highest ES. Metaferia et. al. would be at the bottom and Iwnetu et.al. at the top

Figure 3: Axis-labels to be described in full

Figure 4: Sort the publications as in figure 2

Figure 5: Sort the publications as in figure 2

Figure 6: Sort the publications as in figure 2

Figures 7, 8 and 9 – same as in figure 3

Reviewer #2: This is a well written article, and findings will be helpful to Ethiopian health care workers, and others working in a LMIC/African context.

However, I have a difficulty with the foundational methodology (meta-analysis) of the study.

o It is not stated what the research questions for the descriptive studies of EPTB which were included in the meta-analysis were.

o Studies which were included could have identified EPTB as a subset of all PTB, or they may have described EPTB alone, from persons with clinical criteria matching only those in whom EPTB is suspected.

o Without specifying which approach the authors of this meta-analysis wanted de novo, the selection criteria results in a wide range of approaches to EPTB diagnosis being selected, which will lead to enormous heterogeneity, and lack of meaningful comparison.

Before conducting a meta-analysis, it is critical to given to formulate the review question clearly. I think the review question ‘to investigate the prevalence of EPTB in Ethiopia’ is too broad. It will be helpful to say ‘Investigate the prevalence of EPTB amongst persons with non-pulmonary TB’. The results are then clearly applicable to persons in whom PTB has been excluded.

As the current aim stands, it implies that that the aim is to identify the burden of TB amongst all TB cases in Ethiopia. This begs the question of a denominator. Assessing the prevalence of EPTB requires that one knows the total burden of TB. How is it possible to assess the prevalence by identifying only studies that described EPTB? These studies would have identified persons who were suspected of EPTB as the starting point. Equally, an ascertainment of risk factors can only be done by comparison with non-EPTB groups.

Without narrowing the research question, it is not meaningful to present or interpret Forest plots.

Other minor comments

A small consideration re methodology, search strategy – are there articles published by Ethiopians in literature that would not be listed in pubmed, Science Direct or on google scholar?

Line 49 Extrapulmonary Tuberculosis – ‘tuberculosis’ should be lower case.

Line 64 Turnaround Time – T should be lower case,

Line 70 Anti-TB medicine – rather ‘anti-tuberculosis therapy’

Line 108 The NewCastle Ottowa quality assessment scale is a checklist for cohort and case control studies. What motivated the use of this scale, over and above the PRISMA guidelines which are sufficient for meta-analyses and systematic reviews.

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If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-22-00257R1Bacteriologically confirmed extrapulmonary tuberculosis and the associated risk factors among extrapulmonary tuberculosis suspected patients in Ethiopia: A systematic review and meta-analysisPLOS ONE

Dear Dr. Diriba,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

Although both readers felt that the manuscript was substantially improved, there were still significant issues with the statistical analysis as highlighted by Reviewer 1. This, given that the rationale for the study was also unclear and the fact that there are concerns regarding incorrect usage of p values, this manuscript still requires extensive editing.

==============================

Please submit your revised manuscript by Jul 07 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Elizabeth S. Mayne, M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

Although both readers felt that the manuscript was substantially improved, there were still significant issues with the statistical analysis as highlighted by Reviewer 1. This, given that the rationale for the study was also unclear and the fact that there are concerns regarding incorrect usage of p values, this manuscript still requires extensive editing.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1 Reviewer 1 comments in the first review have been addressed and the original document has been extensively revised or rewritten. As a result, the revised document is more readable. The revised document has however highlighted additional significant matters and some minor issues. In view of the novelty and importance of the study, it is well worthwhile to resolve these matters and issues.

2 Lines refer to the revised document.

3 Lines 29, 33, 36, 37,117,163,164,180,181,182, and 212. The I^2 test for heterogeneity has values of 98.45%, 98.56%, 98.73% and 96.43%. In terms of Cochran’s Q statistic I^2=((Q-df)/Q*100% (see Cochrane Handbook, 2011), heterogeneity greater than 75% means that studies in the forest plot are not sufficiently comparable and that a meta-analysis may be invalid. A possible remedy is to ignore heterogeneity and adopt a fixed effects model.

4 Lines 170, 183, 184, 185 and Figures 4, 5, and 6. In terms of point 3 (for a I^2 statistic > 75%) a fixed effects model is usually applied unless a suitable analytical justification is given for the application of a random effects model (see Cochrane Handbook, 2011).

5 Lines 116 and 117, a rule of thumb for heterogeneity of I^2 of 50% is moderate and I^2 ≥ 75% is high – see point 3 above. The unqualified statement in line 117 of I^2 ≥ 50% would seem to imply that high heterogeneity is desirable.

6 Lines 180 to 182. P-values of <0.01 are given. P-values as given are incorrectly associated with I^2 tests, which are applied as broad-based categories (see Cochrane Handbook, 2011). P-values are associated with the alternative chi-square test in which a p-value of <0.01 is indicative of a chi-square value in excess of the table value, which indicates high heterogeneity in values and like a high I^2 value (75%), requires further analysis to justify the use of a forest plot (see above).

7 Repetition of statistics in 5 places - see lines in point 3 above. This suggests that the document requires editing.

8 Inconsistency in presentation of statistics. The repetitions of statistics in point 7 are inconsistent. Lines 180 to 182, 164 and 212 give p-values, which are not given in the other lines in point 3 above.

9 The forest plots in Figures 4, 5 and 6 in support of the data in point 3 above have I^2 values >75% which, with p-values <0.01 (presumably relating to a chi-square test), which indicates high heterogeneity. The plots do not indicate if a random effects model or a fixed effects model have been applied. An analysis justifying the relevance of forest plots is required in light of high heterogeneity.

10 Lines 35 to 37 which refer to smear microscopy, Xpert MTB/RIF, culture as separate categories with statistics for each, does not agree with line 106 which adds nucleic acid amplification as an additional test.

11 Lines 35 to 37, tests do not agree with the categories in lines 136 to 138, which combine categories. For example, in line 136, three studies combined culture, Xpert MTB/RIF and smear microscopy. The same combination of categories in lines 152 to 157 is at odds with the separate categories in lines 35 to 37. Proposed categories do not agree with tested categories and evaluated categories.

12 Lines 32, 34, 163, 174, 180-182, 211, 216 do not explain how pooled estimates were computed. Is this a weighted average by subject or by study? How are the 95% confidence intervals computed, are they also weighted by subject or by study?

13 Line 202 risk factors are live animals, raw milk, HIV, male, less income, urban. Line 215 adds contact with EPTB patients and line 258 adds underlying disease as a risk factor. Line 75 risk of misdiagnosis of tuberculosis is also a risk factor as is line 66 – resource limited settings. Line 243 refers to women with lymphadenitis with a higher rate of EPTB than men and Line 245 as women with a higher rate of EPTB than men contrary to line 202 which regards maleness as being an outright risk.

14 Lines 256 to 259, in the conclusion, leaves out male, live animals, raw milk, lymphadenitis, and misdiagnosis as risk factors without justification. Consistency in the set of risk factors, from proposal to testing and conclusion should be maintained. Adding or dropping risk factors has not been explained or justified.

Minor points

15 ‘Previous history’ in lines 37, 41, 212, 237, 239, 256, 258 should be ‘history’.

16 /EPTB/ in lines 25 and 80 should be omitted.

17 Line 45 capitalise f in factors.

18 Line 99 space between 2010 and worksheet.

19 Line 120 …software (STATA) so that line 122 refers to ‘STATA’.

Reviewer #2: The authors have clarified the aim of the study, and it is now possible to make comments on the rest of the paper. Please see detailed comments in word document which are summarised here.

Firstly, the rationale for the study could be made clearer.

Secondly, in table 1, it is not clear what 'associated factors' refer to. I think the authors mean 'risk factors', but it is not clear if the factors listed are 'risk factors for EPTB (as opposed to PTB) or 'risk factors for bacteriologically-confirmed TB (vs non-bacteriologically confirmed TB). Following on from this, in the discussion, the authors have made incorrect comparisons with international iterature, and have focused the discussion on prevalence of EPTB amongst all TB cases. Therefore the discussion does not have bearing on the aim of the paper (to discuss % of EPTB that is bacteriologically confirmed, as opposed to the % which is not bacteriologically confirmed). The authors point out that diagnostic tests in Ethiopia are limited, and that understanding the % of EPTB that is bacteriologically confirmed will guide policy. It's not clear in what direction this policy should go. This could be (should be?) brought up in the discussion.

Thirdly, correction of grammatical/syntax errors will make aspects of the paper easier to understand.

Fourthly, all legends to figures and tables should refer to the context of the figure/table in the paper.

Fifthly, once the above are corrected, a statistical reviewer should assess the validity of the tests that have been conducted and how they have been interpreted.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Anthony Leland Hamilton Mayne

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

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PONE-D-22-00257R2Bacteriologically confirmed extrapulmonary tuberculosis and the associated risk factors among extrapulmonary tuberculosis suspected patients in Ethiopia: A systematic review and meta-analysisPLOS ONE

Dear Dr. Diriba,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

The reviewers were generally satisfied that the majority of their comments were addressed but there are some minor issues that still need correction. A comprehensive list is included.

Please submit your revised manuscript by Oct 24 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Elizabeth S. Mayne, M.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: No

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1 Please insert spaces or remove spaces as indicated in the red or blue underlines on the document

2 line 117 "the presence of publication bias..." is a repetition of the previous sentence

3 line 124 remove STATA 14... details, this has already been defined in line 121

4 line 171 bacteriologically

5 line 121 remove (STATA)

6 line 100 facility-based

7 line 215 meta-analysis

8 line 169 Figure 2: pooled not pooed

9 Table 1 last column is 12 point type, the preceding columns are point 8

10 The document needs a final edit for typos and set-out

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Reviewer #1: Yes: Anthony L. H. Mayne

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Bacteriologically confirmed extrapulmonary tuberculosis and the associated risk factors among extrapulmonary tuberculosis suspected patients in Ethiopia: A systematic review and meta-analysis

PONE-D-22-00257R3

Dear Dr. Diriba,

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

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Elizabeth S. Mayne, M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: ***please edit spacing and ensure consistent font size is used in tables

Already submitted (review no 2)

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Anthony Leland Hamilton Mayne

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