PONE-D-20-39516

TREATMENT OUTCOMES OF PATIENTS WITH MDR-TB AND ITS DETERMINANTS AT REFERRAL HOSPITALS IN ETHIOPIA

PLOS ONE

Dear Dr. WAKJIRA,

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.

As suggested by reviewers, the manuscript needs to be rewritten. The text has to be shortened and made more crisp and clear.There are some additional comments:

1. The period of study is from 26th Dec, 2012 to 17th Sep,2017. During this period a total of 182 patients with MDR-TB were enrolled to treatment of which 46 patients did not meet the inclusion criteria. The inclusion and exclusion criteria should be specified.

2. The data was collected from 10th Nov,2016 to 7th Feb 2017. How was the 24 months follow up assessed for patients enrolled in Sep, 2017?

3. Abstract- Background- 3rd line may be modified to 'Thus, this study investigated the determinants responsible for poor treatment outcome in patients with MDR-TB at referral hospitals in Ethiopia.

4. Abstract- Results-4th line- Delete 'were' after 27%, also elsewhere also in the manuscript

5. Materials and Methods-Findings- General characteristics of patients- Employment status is given for 132/136 patients although there is heading 'other'

6. Clinical characteristics of the participants-'135 (99%) of the total patients had a drug-susceptibility test result for rifampicin and were resistant to it. Only fifty-eight (43%) of the patients had drug susceptibility

test result for both rifampicin and isoniazid and were resistant to both drugs'- How was DST performed? Was RR determined by GeneXpert? If so why only 58(43%) samples tested against both drugs?

7. Table 3- Please correct whether a total of 30 patients died or 34 died? Similarly, comorbidity has been shown as 41/136 in Table 1 and 34 (favourable+unfavourable outcome). Also, HIV positive patients are 34 in Table 1 and 27 in Table 3.

8. Discussion-'...it was documented that presence of any comorbidity with MDR-TB is associated with poor treatment outcome and high mortality among patients treated for drug-resistant tuberculosis. In this view, the high level of comorbidity with MDR-TB (31%) revealed in this study could be a risk factor for the observed high prevalence of adverse drug-reactions higher proportion of death among patients included in this study.'- '...64% prevalence of malnutrition among patients included in this study might explain the significantly higher rate of death and high prevalence of adverse drug reactions observed among patients included in this

study.

The association of comorbidity and malnutrition for adverse drug reaction seems inappropriate unless suitable references can be cited.

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Kind regards,

Shampa Anupurba, MD

Academic Editor

PLOS ONE

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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: Yes

Reviewer #2: No

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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: No

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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: Yes

Reviewer #2: No

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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: 1. The study topic is relevant.

2.The Abstract is well written.

3. Aim & Objectives are clear.

Materials & Methods: The study design needs clarification about sample size, how the sample size was calculated.

Duration of the study is confusing as in section "study setting & sampling" it is mentioned as between 26th of Dec 2012 to 17th of Sept. 2016. however in section "data collection & analysis" the duration is different. This should be clarified.

The inclusion and exclusion criteria has not been given. How the data was collected, details should be included.

Table 1 HIV/ AIDS mentioned at two places .

Table2. Culture Positive 0% , written twice. If 27 cases died within 6months total cases remained are 109 not 110. hence this should be clarified; and in 24 months period 30 cases died. so total cases remain 109-30=79, The calculation is not clear,

Table 3 & table 4: overlapping data should be removed.

References: The page No. are missing in few articles.

Reviewer #2: 1. The study is based on data from 2012 till September 2016. It is a relatively old data. To make the study more relevant in the present scenario, the authors are advised to include data at least till December 2020.

2. There is discrepancy in data throughout the text, e.g., at one place it is mentioned there are total 30 deaths, at another place it is mentioned it includes 19 males and 15 females that amounts to 34. In table also it is mentioned as 19 and 15. The article should be read thoroughly and the statistical errors need to be resolved.

3. The ‘Structural Questionnaire’ that was used to collect data should have been shared as an appendix/supplement.

4. The study design is not clear. In one sentence it is written-‘both deductive and inductive approaches were used’. However, in the next sentence it is written- ‘Only deductive approach was used’. This needs clarification.

5. There is non-uniformity in writing numerical values-at some place in text, it is written as digits and at some places as words.

6. What drug regimen was provided to MDR-TB patients? Is it the same regimen prescribed to all patients or it is different for pulmonary and extrapulmonary cases and also in the same group? If different regimes are given to different patients, then it would be a major confounding factor in analyzing the disease outcome.

7. Does the patient need to pay for the treatment of TB or the drugs are provided free of cost by government of Ethiopia?

8. The reference for classification of initial bacillary load as ‘scanty, moderate or high’ is required. It needs clear objective definition.

9. Which drug was responsible for suicide due to clinical psychiatric problem as an adverse drug reaction? How the causal relationship was established?

10. The analysis should also be done comparing urban and rural population and its correlation with disease outcome.

11. The English language of the article needs to be corrected and improved.

12. There was no new information in the conclusion of the study. These are already established facts that malnutrition, poor socio-economic status, unemployment, co-infection with HIV and co-morbidities are responsible for poor disease outcome in MDR-TB cases.

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: Review PONE-D-20-39516.pdf

TREATMENT OUTCOMES OF PATIENTS WITH MDR-TB AND ITS DETERMINANTS AT REFERRAL HOSPITALS IN ETHIOPIA

PONE-D-20-39516R1

Dear Dr. WAKJIRA,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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Kind regards,

Shampa Anupurba, MD

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 #2: All comments have been addressed

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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 #2: Yes

**********

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

Reviewer #2: Yes

**********

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 #2: 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 #2: Yes

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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 #2: This is a re-review of the manuscript. I have read all the answers of the authors and their justification for being unable to incorporate some of the suggestions. The authors have appropriately answered and incorporated comments made by the reveiwer.

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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 #2: No