PONE-D-20-06687

Treatment success for patients with tuberculosis receiving care in areas severely affected by Hurricane Matthew – Haiti, 2016

PLOS ONE

Dear Dr. Charles,

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.

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Kind regards,

Anna Maria Mandalakas, MD

Academic Editor

PLOS ONE

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3. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. If you developed and/or translated a questionnaire as part of this study and it is not under a copyright license more restrictive than Creative Commons Attribution (CC-BY), please include a copy, in both the original language and English, as Supporting Information.

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Additional Editor Comments (if provided):

Thank you for submitting your manuscript to Plos One. The authors should be commended on their work which could potentially add to the paucity of data regarding the impact of natural disasters on TB control. Nevertheless, based on editorial and external review, the manuscript is requires major revision before it can be considered further for publication.

In addition to responding to the useful suggestions provided by the external reviewers, the manuscript may be strengthen by consideration of the following recent publication:

Prevalence of Tuberculosis in Children After Natural Disasters, Bohol, Philippines.

Murray KO, Castillo-Carandang NT, Mandalakas AM, Cruz AT, Leining LM, Gatchalian SR; PEER Health Bohol Pediatric Study Team.

Emerg Infect Dis. 2019 Oct;25(10):1884-1892. doi: 10.3201/eid2510.190619.

PMID: 31538561

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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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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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: Yes

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: Dear authors,

Thank you for the opportunity to review your work. This study of treatment success for patients with drug-sensitive TB at the time of Hurricane Matthew has value to help communities develop disaster resilience for TB treatment as well as learn how to best respond after a disaster. There is a wealth of data available and most of it is well presented, but there are changes that could be made to make the results of the study more useful for readers:

1. With the relative success in treating TB despite the damage from Hurricane Matthew, it is important to describe the aspects of facilities that maintained equivalent treatment success both before and after the hurricane. Therefore, since details about unassessed facilities are unknown, the authors should delve into the different characteristics of the assessed facilities and do analyses to assess how variable aspects of the facilities and providers contributed to individual facility treatment success rates. Assessed facilities should be divided into those with equivalent treatment rates before and after the hurricane, and those with lower rates after the hurricane. Then, analyses should be done to determine if damage to the facility or other assessed factors correlated with the treatment success rate.

2. 69: Please explain why patients were included whose treatment started April 1-4, since those patients should have had their treatment completed prior to the hurricane. Please also address this in the discussion and limitations, since it affects the results.

3. 79-81: S1 Appendix does not show the form used to assess the facility; it is the patient tracking form. Would the authors please include the form for facility assessment? Please also keep the patient tracking form as an appendix, as well as the line item form.

4. 157: Please clarify for how much time there was a drug shortage. It would also help the reader to know how many days’ worth of medications each patient was given at every clinic visit and how often they were expected to return for follow-up.

5. 173: Was the TB success rate determined only from PNLT data or from individual facility records, as well? When was the data accessed to determine treatment success? This would be prospective for most cases, since the target patients were identified within a few weeks after the hurricane and then followed to see if they were treated successfully. Was there a possibility that data entry into PNLT was delayed and results would have been different if the database had been accessed later?

6. 188-189: The difference could also have been due to treatment failure or not completing treatment, correct? Please clarify.

7. 200 and Table 3: Please describe what was included in the multivariable analysis.

8. 221-222: Please explain the specific actions taken by TB providers. This will help readers consider how this could be replicated in similar settings.

9. 234-235: If you choose to keep the comparison between assessed and unassessed facilities (the deeper dive into assessed facilities seems most important but this could be valuable as well), there is a need to further elucidate their differences. In other words, were assessed facilities larger than unassessed? Did they have more people from outside the commune of residence? What other aspects differed between the groups?

10. 258-260: The intent of this sentence is not clear. Would you kindly rewrite it to convey the information in a different way?

11. In your conclusion, please provide specific recommendations (based on what was learned from this study) on how facilities and providers of TB care can be better prepared in case of future hurricanes or other disasters, acknowledging the limits of generalizability.

12. Beyond the outcome of treatment success, is there data available on how many of the patients experienced interruptions in treatment? If so, for how long were the interruptions? Were any at least 2 weeks in duration? Is so, was it the initiation or continuation phase? Did any develop drug resistance? These outcomes are important to report, if possible.

13. In general, please scrutinize the grammar in detail as there are a few typos. In addition, please include the bracketed references before the period at the end of the sentence being referenced.

14. What are the possible reasons why patients with HIV or unknown HIV status had lower treatment success? Was this different before and after the hurricane or the same throughout?

Thank you for undertaking this research and putting together a great paper. With minor revisions, this would be a helpful addition to the literature.

Reviewer #2: Comments to the author:

General:

This is an interesting and well-done study in a low resource setting describing an impressive and successful public health activity and highlighting the important relationship between natural disasters and TB control. If natural disasters become more prevalent, as is predicted by climate change science, understanding and mitigating the impacts of these disasters on TB control will be critical in ensuring progress towards global TB elimination.

Major comments:

(1) better clarify the goals and objectives of the project and study and reformat the sections based on these goals and objectives,

(2) build up the discussion section further, and emphasize the significance and applicability of your findings to other similar settings outside of Haiti.

Specific comments:

Introduction

• Lines 56-60 seem out of place and doesn’t really fit in with the flow of the introduction. Specifically, it seems that in this paragraph, the authors are outlining the argument of why TB outcomes may worsen following a natural disaster. Citing WHO guidelines on restarting TB treatment after interruption doesn’t seem to fit with this argument.

• Lines 61-63 The goal doesn’t seem to me as a goal but rather the activities you conducted in this important public heath surveillance project. It seems that the goal of this project was to evaluate the impact that hurricane Matthew had on TB services and outcomes in the three departments of Haiti. After you identify this goal, then you can delineate the specific objectives of this manuscript. It seems that the objectives were to (1) assess the impact of the hurricane on TB facilities and services and describe the public health activities implemented to mitigate this impact, (2) assess the impact of the hurricane on treatment outcomes of those who were linked to TB therapy prior to the disaster, and (3) identify individual-related factors associated with treatment success or failure following the hurricane.

• I would add a sentence emphasizing the importance of this study to the general reader, i.e. why are the findings important. I would focus on how many low resource settings are struck by both high TB prevalence and preponderance of devastating natural disasters and understanding how these phenomena are related can inform TB control activities.

Methods

• Lines 73-75 I would be more specific on how this comparison is a representation of the impact of the hurricane on treatment outcomes. You could say something like “treatment started in quarter 1 would probably not be disrupted by the hurricane (unless the treatment was prolonged) and therefore represents a comparison group. While treatment started in quarters 2 and 3 represents the exposure group since treatment started in those quarters would have been disrupted since it would not have been completed until after the hurricane occurred.” I think this will make it clearer how you plan to compare treatment success before and after the hurricane.

• Lines 99-100 Please include citation for WHO definitions

• Lines 105-107 Did you use both chi square tests and odd ratios to determine association between risk factors and success. I would reword this sentence by saying you conducted bivariate analysis using odds ratios (and or chi square) with p-value<0.05.

• Lines 108-109 I am confused about the order of things in your analysis. It seems that from your results that you chose the appropriate epidemiologically relevant factors and conducted both bivariable and multivariable analysis on the same factors. If this is the case I would specifically say that.

Results

• Table 1 Should include chi-square testing with p-values to determine if there were statistical differences between those subjects assessed and those that weren’t assessed

• It would be interesting to include estimates of treatment success

• Table 2 Should include chi-square testing with p-values to determine if there were statistical differences between treatment outcomes among the different sites. Also I would reword the title emphasizing that these are outcomes prior to the hurricane (i.e. Treatment initiated in quarters 1-3 before hurricane Matthew).

• Lines 186-189 This assertion fits better in the discussion, specifically in the paragraph lines 229-233

• Table 3 I would eliminate the columns with p-values and denote the statistical significance of the ORs with asterisks. For example * for p-value<0.05 and ** for p-value<0.01.

Discussion

• Lines 225-228 Please include citation, whether it is a publication or based on anecdotal discussions with stakeholders

• Lines 229-233 I know you mention in the introduction how the hurricane primarily stuck the areas that were assessed. But I would further describe how the geography of the hurricane, and perhaps other factors explain your findings, specifically that those in the assessed areas had a higher chance of treatment failure than those in areas that weren’t assessed. Perhaps you could use geospatial analysis to illustrate where the hurricane hit hardest and the percentage of treatment success in those areas.

• Lines 241-243, I would try to identify references or data from other settings that further explore the financial and travel-related restrictions placed on patients who live far from their healthcare facilities. This will add strength to your argument and perhaps improve the generalizability of your findings to other post-disaster settings.

• Can you also comment on the role of HIV status on TB treatment success. You identify it as a statistically significant factor in the results but don’t mention it in the discussion.

• Can you discuss further generalizability of your findings to other post disaster settings and possible limitation of applying your findings to other settings. An important take away readers will likely want to make from this study is how do these findings compare with those of other low resource, high burden Tb settings struck by natural disasters and how your findings could be used to inform mitigation efforts after future disasters.

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Reviewer #1: No

Reviewer #2: No

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Treatment success for patients with tuberculosis receiving care in areas severely affected by Hurricane Matthew – Haiti, 2016

PONE-D-20-06687R1

Dear Dr. Charles,

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,

Anna Maria Mandalakas, MD

Guest Editor

PLOS ONE

Additional Editor Comments (optional):

Thank you for submitting your revised manuscript for consideration. The editors and the reviewers found the revised manuscript much improved and highly responsive to the original review comments. I am pleased to inform you that your revised manuscript has been accepted for publication in Plos One contingent upon completion of the few remaining reviewer comments shared below.

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: All comments have been addressed

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 #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

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 #1: Yes

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 #1: Yes

Reviewer #2: 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: Dear authors,

Congratulations on an excellent revision. I have two minor comments to share: 1) in Table 1, please be sure to place the correct symbols next to Accompagnateur and Previously treated; 2) please consistently use the "less than" (<) symbol to describe your p-values, instead of "less than or equal to."

Reviewer #2: The authors have done a nice job incorporating the reviewers' comments to make this a more rigorous and interesting manuscript. The coherence and structure of the manuscript is much improved. The relevance and generalizability to TB programs in other low resource settings is much more apparent.

There are still some sections where grammatical corrections should be made and arguments could be improved (see below) but otherwise I recommend this manuscript for publication.

Minor revisions:

Line 156-159: sentence is a little unclear. I had to read it a few times to understand it. I would add a word like "all" before the "20 in Sud" and "4 in Nippes" to emphasize that all facilities in those two departments suffered minimal to no damage while only a little over half the facilities in Grand'Anse had minimal or no damage.

lines 232 and 252: need to replace commas with "and"

lines 275-278: this paragraph seems like speculation. I recommend adding evidence to support this assertion. One possible suggestion is to analyze the sample of new TB patients following the hurricane and determine if there was an association between where these patients were seen and severity of damage on these facilities (i.e. was most of the drop in new patients seen at the facilities with severe damage). If so, you could combine the paragraphs 275-278 and 297-304 and make an assertion like "Persons with newly diagnosed TB and those already receiving care were both less likely to be seen at the facilities with severe damage..."

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Reviewer #1: Yes: Karla Fredricks

Reviewer #2: No