PGPH-D-22-00623

Risk Factors for Melioidosis in Udupi District, Karnataka, India, August 2018

PLOS Global Public Health

Dear Dr. Dikid,

Thank you for submitting your manuscript to PLOS Global Public Health. After careful consideration, we feel that it has merit but does not fully meet PLOS Global Public Health’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.

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

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Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Raquel Muñiz-Salazar, Ph.D.

Academic Editor

PLOS Global Public Health

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Additional Editor Comments (if provided):

Three reviewers agree that this is a critical manuscript highlighting the need for public health intervention to decrease melioidosis incidence in India. It is essential to improve the manuscript by attending to the reviewers' comments.

REVIEWER 1

Overall this is an important manuscript highlighting the need for public health intervention to decrease the incidence of melioidosis in India. I believe this manuscript could be improved and have included my comments below.

Major:

Line 149: please explain why only 19 of the 50 cases were analyzed. It might be best to include a flow diagram with inclusions and exclusions for clarity.

Line 202: there is no mention of severity in the case definition, but is mentioned as a factor in the limitation sections. Please clarify.

It has been mentioned that melioidosis is not a notifiable condition in India. There are a number of instances in the manuscript where the term “reported” or “reporting” has been used, for example in Figure 2. For clarity are these the cases identified by the investigation or the cases sporadically reported to the NCDC?

There is no mention of additional investigations relating to the case. Did he have pneumonia? Was he bacteremic? Was a swab of the abrasion site taken, and if so was it culture positive for B. pseudomallei?

There is a very limited description of patient presentation: “The most common type was bacteremic melioidosis (53%).” This should be expanded, preferably in a table, to include: bacteremia, pneumonia, skin & soft tissue, organ involvement (i.e. liver abscess etc.), neuromelioidosis, no focus.

What was the difference between those with pneumonia vs no pneumonia in the context of the various environmental risk factors? It would be important to mention this information as inhalation is a common route of acquisition.

What was the predominant presentation in the dry season compared to the wet season?

Table 1 should include the specific risk factors included in the results section.

Minor:

Title: “August 2018” suggests that only this month was assessed. Consider rephrasing.

Line 86: I assume the Gram stain revealed bipolar Gram negative staining?

Line 88: incubated in room air/aerobic conditions or in 5% CO2?

Line 93: reference

Data analysis section: consider removing “we”

Line 133: transferred to intensive care

Line 139 – 141: suggest rewrite

Line 154: neuromeliodosis should not be counted as a chronic comorbidity

Line 154: “the most common type” suggest rewriting this sentence.

Line 165: “and having” with

Line 205: this sentence is misleading as there is no definition of fever of unknown origin mentioned in this manuscript. In this context it is more likely that the disease is either misdiagnosed or undiagnosed, and not a fever of unknown origin (e.g. a fever that lasts for >3 weeks or failure to reach a diagnosis after 1 week of appropriate investigations)

Line 206 – 209: grammar

Figure 2: it would be great if rainfall data could be included in this figure to demonstrate the correlation with the wet season.

REVIEWER 2

Authors have investigated the risk factors for acquiring melioidosis in Udupi district in India. It will be helpful in future implementations of control and preventive strategies for melioidosis.

My specific comments are as follows.

Major point:

Point 1: Line 202: “However, we tried to ensure comparability of exposures by enrolling controls during the rainy season, a time of high risk” It is not clear why authors tried to ensure comparability of exposure. Why were the controls not distributed throughout the year, as it would have brought out the seasonal risk factor, and risk factors associated with exposure better. Authors should not have tried to match the exposure.

Point 2: Line 139-141: The MRI description is not accurate. It cannot be “right side” of the corticospinal tract. Authors are directed to quote the case report which describes the same case from the region elaborately with MRI pictures in a previous publication that was published by the clinicians involved in case management- Chatterjee A, Saravu K, Mukhopadhyay C, Chandran V. Neurological Melioidosis Presenting as Rhombencephalitis, Optic Neuritis, and Scalp Abscess with Meningitis: A Case Series from Southern India. Neurol India. 2021 Mar-Apr;69(2):480-482. doi: 10.4103/0028-3886.314590. PMID: 33904481

Minor points:

Line 65-66: In India, sporadic case reports of melioidosis have been mostly from Karnataka and Tamil Nadu due to better diagnostic capacity in these regions. Authors fail to quote this paper which has for the first time described a case series of 25 patients from the same region as study setting, which has also described seasonal preponderance. Saravu K, Mukhopadhyay C, Vishwanath S, Valsalan R, Docherla M, Vandana KE, Shastry BA, Bairy I, Rao SP. Melioidosis in southern India: epidemiological and clinical profile. Southeast Asian J Trop Med Public Health. 2010 Mar;41(2):401-9. PMID: 20578524.

Line 154: Why is neuromeliodosis written as “other chronic co morbidity”? It is the very subject of investigation.

Grammar and Typos are to be corrected in the manuscript

Line 184. A systematic review from India for the period 1991-2018 found diabetes mellitus (to be ) a major predisposing condition in 70% of reported cases

Line 193-194 “children and adolescents have poor outcomes, frequently resulting in either death or neurological impairment (37%) (5, 25)”. What is the possible explanation for this finding?

Line 315: Muthusamy KA, Waran V, Puthucheary SD. Spectra of central nervous system melioidosis. J Clin 316 Neurosci. 2007;14:1213-5. A very old sole reference (2007) has been quoted while there are newer reports of neuromeliodosis.

Newer references and unique presentations that are reported recently(2015 and 2021) may be included for neuromeliodosis.

1.Chatterjee A, Saravu K, Mukhopadhyay C, Chandran V. Neurological Melioidosis Presenting as Rhombencephalitis, Optic Neuritis, and Scalp Abscess with Meningitis: A Case Series from Southern India. Neurol India. 2021 Mar-Apr;69(2):480-482. doi: 10.4103/0028-3886.314590. PMID: 33904481

2. Saravu K, Kadavigere R, Shastry AB, Pai R, Mukhopadhyay C. Neurologic melioidosis presented as encephalomyelitis and subdural collection in two male labourers in India. J Infect Dev Ctries. 2015 Nov 30;9(11):1289-93. doi: 10.3855/jidc.6586. PMID: 26623640.

1) Page 5 - Abstract. - The methodology seems to be misleading as only 19 cases underwent logistic matched case-control analysis. Yet, you have stated that 50 cases were identified. If I am not wrong, this maybe the incident cases for the retrospective epidemiological survey, all of which were not included in the statistical analysis. Please consider clarifying how many cases underwent the specified analysis.

2) Page 6 , Introduction - Line 64-66. I have to disagree with the statement that melioidosis reporting was limited to Karnataka and Tamil Nadu due to diagnostic limitations in other south-indian states in general. I believe diagnostic limitation may instead be tertiary care centres, that most south indian states do feature albeit far and between and due to the general unawareness of the condition. Citations no. 14 and 15 are quite outdated. I recommend citing more recent published reports from other states such as https://doi.org/10.1155/2021/8154810, https://doi.org/10.3390/idr12030011 or even our published paper from https://doi.org/10.1155/2021/8154810.

3) Page 9 - Results - I - Case investigation - It would have been "nice" to have a MRI image of the patient with neuro-melioidosis - Completely optional but can improve reader engagement.

4) Page 10 - Descriptive epidemiology - Only minimal baselines information is given on the 50 cases identified from 2013 to 2018. It would have been helpful to delve deep into the clinical presentation and cause of mortality of these patients ( and not just the 19), as data is probably already available from hospital record. Since objective evidence is available, I doubt recall bias would have limited the descriptive analysis.

5) Page 11 - III- Case control study - Since there was no minimum sample size calculation, I am doubtful of the statistical power the regression analysis contains due to the relatively small sample analysed (wide confidence inferences noted for risk factors, many with statistical non-significance at alpha of 0.05). I recommend adding the power analysis and goodness-of-fit report, as it may inform the readers on the strength of the inferences made as the effect sizes (mOR) are quite large.

6) The discussion is well drafted with a succinct comparison with existing literature, pragmatic suggestions to policy makers, with strengths and weaknesses of the study described in detail.

Reviewer no. 3

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does this manuscript meet PLOS Global Public Health’s publication criteria? Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe methodologically and ethically rigorous research with conclusions that are appropriately drawn based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Partly

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

**********

3. Have the authors made all data underlying the findings in their manuscript fully available (please refer to the Data Availability Statement at the start of the manuscript PDF file)?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception. 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

Reviewer #3: No

**********

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

PLOS Global Public Health 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

Reviewer #3: Yes

**********

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: Overall this is an important manuscript highlighting the need for public health intervention to decrease the incidence of melioidosis in India. I believe this manuscript could be improved and have included my comments below.

Major:

Line 149: please explain why only 19 of the 50 cases were analyzed. It might be best to include a flow diagram with inclusions and exclusions for clarity.

Line 202: there is no mention of severity in the case definition, but is mentioned as a factor in the limitation sections. Please clarify.

It has been mentioned that melioidosis is not a notifiable condition in India. There are a number of instances in the manuscript where the term “reported” or “reporting” has been used, for example in Figure 2. For clarity are these the cases identified by the investigation or the cases sporadically reported to the NCDC?

There is no mention of additional investigations relating to the case. Did he have pneumonia? Was he bacteremic? Was a swab of the abrasion site taken, and if so was it culture positive for B. pseudomallei?

There is a very limited description of patient presentation: “The most common type was bacteremic melioidosis (53%).” This should be expanded, preferably in a table, to include: bacteremia, pneumonia, skin & soft tissue, organ involvement (i.e. liver abscess etc.), neuromelioidosis, no focus.

What was the difference between those with pneumonia vs no pneumonia in the context of the various environmental risk factors? It would be important to mention this information as inhalation is a common route of acquisition.

What was the predominant presentation in the dry season compared to the wet season?

Table 1 should include the specific risk factors included in the results section.

Minor:

Title: “August 2018” suggests that only this month was assessed. Consider rephrasing.

Line 86: I assume the Gram stain revealed bipolar Gram negative staining?

Line 88: incubated in room air/aerobic conditions or in 5% CO2?

Line 93: reference

Data analysis section: consider removing “we”

Line 133: transferred to intensive care

Line 139 – 141: suggest rewrite

Line 154: neuromeliodosis should not be counted as a chronic comorbidity

Line 154: “the most common type” suggest rewriting this sentence.

Line 165: “and having” with

Line 205: this sentence is misleading as there is no definition of fever of unknown origin mentioned in this manuscript. In this context it is more likely that the disease is either misdiagnosed or undiagnosed, and not a fever of unknown origin (e.g. a fever that lasts for >3 weeks or failure to reach a diagnosis after 1 week of appropriate investigations)

Line 206 – 209: grammar

Figure 2: it would be great if rainfall data could be included in this figure to demonstrate the correlation with the wet season.

Reviewer #2: Authors have investigated the risk factors for acquiring melioidosis in Udupi district in India. It will be helpful in future implementations of control and preventive strategies for melioidosis.

My specific comments are as follows.

Major point:

Point 1: Line 202: “However, we tried to ensure comparability of exposures by enrolling controls during the rainy season, a time of high risk” It is not clear why authors tried to ensure comparability of exposure. Why were the controls not distributed throughout the year, as it would have brought out the seasonal risk factor, and risk factors associated with exposure better. Authors should not have tried to match the exposure.

Point 2: Line 139-141: The MRI description is not accurate. It cannot be “right side” of the corticospinal tract. Authors are directed to quote the case report which describes the same case from the region elaborately with MRI pictures in a previous publication that was published by the clinicians involved in case management- Chatterjee A, Saravu K, Mukhopadhyay C, Chandran V. Neurological Melioidosis Presenting as Rhombencephalitis, Optic Neuritis, and Scalp Abscess with Meningitis: A Case Series from Southern India. Neurol India. 2021 Mar-Apr;69(2):480-482. doi: 10.4103/0028-3886.314590. PMID: 33904481

Minor points:

Line 65-66: In India, sporadic case reports of melioidosis have been mostly from Karnataka and Tamil Nadu due to better diagnostic capacity in these regions. Authors fail to quote this paper which has for the first time described a case series of 25 patients from the same region as study setting, which has also described seasonal preponderance. Saravu K, Mukhopadhyay C, Vishwanath S, Valsalan R, Docherla M, Vandana KE, Shastry BA, Bairy I, Rao SP. Melioidosis in southern India: epidemiological and clinical profile. Southeast Asian J Trop Med Public Health. 2010 Mar;41(2):401-9. PMID: 20578524.

Line 154: Why is neuromeliodosis written as “other chronic co morbidity”? It is the very subject of investigation.

Grammar and Typos are to be corrected in the manuscript

Line 184. A systematic review from India for the period 1991-2018 found diabetes mellitus (to be ) a major predisposing condition in 70% of reported cases

Line 193-194 “children and adolescents have poor outcomes, frequently resulting in either death or neurological impairment (37%) (5, 25)”. What is the possible explanation for this finding?

Line 315: Muthusamy KA, Waran V, Puthucheary SD. Spectra of central nervous system melioidosis. J Clin 316 Neurosci. 2007;14:1213-5. A very old sole reference (2007) has been quoted while there are newer reports of neuromeliodosis.

Newer references and unique presentations that are reported recently(2015 and 2021) may be included for neuromeliodosis.

1.Chatterjee A, Saravu K, Mukhopadhyay C, Chandran V. Neurological Melioidosis Presenting as Rhombencephalitis, Optic Neuritis, and Scalp Abscess with Meningitis: A Case Series from Southern India. Neurol India. 2021 Mar-Apr;69(2):480-482. doi: 10.4103/0028-3886.314590. PMID: 33904481

2. Saravu K, Kadavigere R, Shastry AB, Pai R, Mukhopadhyay C. Neurologic melioidosis presented as encephalomyelitis and subdural collection in two male labourers in India. J Infect Dev Ctries. 2015 Nov 30;9(11):1289-93. doi: 10.3855/jidc.6586. PMID: 26623640.

Reviewer #3: Thank you for the opportunity to review this scientific article. The article seems to present a case report of a recent mortality with neuro-melioidosis and further presents a case-control analysis of 19 cases between 2013 and 2018. This is an important epidemiological survey on a neglected tropical disease, which is all the more likely to exacerbate due to climate change and natural calamities. I have a few concerns that when addressed could potentially improve the manuscript.

1) Page 5 - Abstract. - The methodology seems to be misleading as only 19 cases underwent logistic matched case-control analysis. Yet, you have stated that 50 cases were identified. If I am not wrong, this maybe the incident cases for the retrospective epidemiological survey, all of which were not included in the statistical analysis. Please consider clarifying how many cases underwent the specified analysis.

2) Page 6 , Introduction - Line 64-66. I have to disagree with the statement that melioidosis reporting was limited to Karnataka and Tamil Nadu due to diagnostic limitations in other south-indian states in general. I believe diagnostic limitation may instead be tertiary care centres, that most south indian states do feature albeit far and between and due to the general unawareness of the condition. Citations no. 14 and 15 are quite outdated. I recommend citing more recent published reports from other states such as https://doi.org/10.1155/2021/8154810, https://doi.org/10.3390/idr12030011 or even our published paper from https://doi.org/10.1155/2021/8154810.

3) Page 9 - Results - I - Case investigation - It would have been "nice" to have a MRI image of the patient with neuro-melioidosis - Completely optional but can improve reader engagement.

4) Page 10 - Descriptive epidemiology - Only minimal baselines information is given on the 50 cases identified from 2013 to 2018. It would have been helpful to delve deep into the clinical presentation and cause of mortality of these patients ( and not just the 19), as data is probably already available from hospital record. Since objective evidence is available, I doubt recall bias would have limited the descriptive analysis.

5) Page 11 - III- Case control study - Since there was no minimum sample size calculation, I am doubtful of the statistical power the regression analysis contains due to the relatively small sample analysed (wide confidence inferences noted for risk factors, many with statistical non-significance at alpha of 0.05). I recommend adding the power analysis and goodness-of-fit report, as it may inform the readers on the strength of the inferences made as the effect sizes (mOR) are quite large.

6) The discussion is well drafted with a succinct comparison with existing literature, pragmatic suggestions to policy makers, with strengths and weaknesses of the study described in detail.

**********

6. 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.

Do you want your identity to be public for this peer review? If you choose “no”, your identity will remain anonymous but your review may still be made public.

For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Manu Pradeep

**********

[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.

PGPH-D-22-00623R1

Risk Factors for Melioidosis in Udupi District, Karnataka, India, January 2017-July 2018

PLOS Global Public Health

Dear Dr. Dikid,

Thank you for submitting your manuscript to PLOS Global Public Health. After careful consideration, we feel that it has merit but does not fully meet PLOS Global Public Health’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.

Please submit your revised manuscript by Oct 26 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 globalpubhealth@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pgph/ 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 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'.

Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Raquel Muñiz-Salazar, Ph.D.

Academic Editor

PLOS Global Public Health

Journal Requirements:

1. 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.

2. Please provide a/amend your detailed Financial Disclosure statement. This is published with the article. It must therefore be completed in full sentences and contain the exact wording you wish to be published.

a. State the initials, alongside each funding source, of each author to receive each grant.

If you did not receive any funding for this study, please simply state: “The authors received no specific funding for this work."

Additional Editor Comments (if provided):

Dear author.

Because all comments have been addressed satisfactorily, the reviewers have decided to accept the manuscript after a Minor Revision.

[Note: HTML markup is below. Please do not edit.]

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

Reviewer #4: (No Response)

**********

2. Does this manuscript meet PLOS Global Public Health’s publication criteria? Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe methodologically and ethically rigorous research with conclusions that are appropriately drawn based on the data presented.

Reviewer #2: Yes

Reviewer #4: Yes

**********

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

Reviewer #2: Yes

Reviewer #4: (No Response)

**********

4. Have the authors made all data underlying the findings in their manuscript fully available (please refer to the Data Availability Statement at the start of the manuscript PDF file)?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception. 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: No

Reviewer #4: (No Response)

**********

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

PLOS Global Public Health 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

Reviewer #4: 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 #2: The authors have addressed reviewers comments satisfactorily

Reviewer #4: Reviewer Comments: RE: Singh et al, melioidosis risk factors

Reviewing revised manuscript with tracked changes.

Major:

I think the article reads well after the first round of revisions. I do not have any major comments!

Flow diagram in appendix is good.

Minor:

1. Line 10: change title to “January 2017-July 2018” (rather than August 2018).

2. Line 52: “in the tropics”

3. Line 62: Tsunamis

4. Line 66-67: Why is this the case? Is it because laboratory diagnosis is limited in other centres?

5. Line 77-78: Suggest rewording along lines of “identify risk factors to inform the initial public health response”.

6. Line 86: “automated system” – which system? BacT/ALERT as per CSF or different?

7. Line 91: I think type 3 secretion system should be abbreviated: TTSS or T3SS not TTSI as brackets.

8. Line 186-187: How significant was this association? Worth putting in the text?

9. Line 190: Suggest removing the word bacteria and just having “aerosolized B. pseudomallei”

10. Line 218: “We recommend sensitizing medical doctors..”- while I understand what you mean by this, it reads like a medical procedure! Would suggest something along the lines of “We recommend increased education of medical..”

11. Table 1, line 370: Multiple chronic comorbidities is a listed risk factor, however is this 2 or more comorbidities? How was this defined? I think this should be defined better including potentially listing (as an endnote) what you called a comorbidity.

**********

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.

Do you want your identity to be public for this peer review? If you choose “no”, your identity will remain anonymous but your review may still be made public.

For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: Yes: Kavitha Saravu

Reviewer #4: 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.

Risk Factors for Melioidosis in Udupi District, Karnataka, India, January 2017-July 2018

PGPH-D-22-00623R2

Dear Dr Dikid,

We are pleased to inform you that your manuscript 'Risk Factors for Melioidosis in Udupi District, Karnataka, India, January 2017-July 2018' has been provisionally accepted for publication in PLOS Global Public Health.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they'll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact globalpubhealth@plos.org.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Global Public Health.

Best regards,

Raquel Muñiz-Salazar, Ph.D.

Academic Editor

PLOS Global Public Health

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After two revision processes, the authors have addressed all comments.

The decision is to ACCEPT it.

Reviewer Comments (if any, and for reference):

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 #4: All comments have been addressed

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2. Does this manuscript meet PLOS Global Public Health’s publication criteria? Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe methodologically and ethically rigorous research with conclusions that are appropriately drawn based on the data presented.

Reviewer #4: Yes

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

Reviewer #4: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available (please refer to the Data Availability Statement at the start of the manuscript PDF file)?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception. 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 #4: (No Response)

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

PLOS Global Public Health 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 #4: 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 #4: Happy that all of my comments addressed.

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Reviewer #4: No

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