PONE-D-23-02503Assessing afebrile malaria and bed-net use in a high-burden region of India - Findings from multiple rounds of mass screeningPLOS ONE

Dear Dr. Garg,

Thank you for submitting your manuscript to PLoS ONE. After careful consideration, we felt that your manuscript requires substantial revision, following which it can possibly be reconsidered, thus governing the decision of a “major revision”. According to the reviewer # 1 – who has expertise in this field – the authors need to address several concerns, particularly related to the data analysis and methods. Por example, the reviewer complains about a link between results of the test and the symptoms of the participants, especially  if this was collected some weeks after by direct interview with the participants.  

For your guidance, a copy of the reviewers' comments was included below. We therefore invite you to submit a revised version of the manuscript paying close attention to the specific points raised by the reviewer. 

Please submit your revised manuscript by Apr 27 2023 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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We look forward to receiving your revised manuscript.

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Luzia H Carvalho, Ph.D.

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

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

Reviewer #1: 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: 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

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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: The manuscript submitted by Garg et al. describes the results of an observational study on malaria and LLIN use conducted during 6-time points, and it relates these results to the results of six waves of mass screening for malaria parasite carriers in a high-burden region of India. The study is highly powered with more than 15,000 participants in each round. I would like to congratulate the authors for their great effort in this massive study and for wrapping up together an analysis and a manuscript describing these results, which are relevant for understanding malaria epidemiology in India and can be used for malaria control and elimination programmes.

I would like to point out some issues for discussion:

- In my opinion, the main issue of this study is how the information on fever and the results of the tests were collected, like the authors point out in the Limitations section. I find very difficult to link the results of the test with the symptoms of the participants if this was collected some weeks after by direct interview with the participants only. I would like to see some justification in the manuscript to the following questions:

1. Is somehow possible to know the real MSaT results per each of the participants in your survey?

2. Was Body Temperature checked during the MSaT?

3. How was collected the febrile/afebrile information for your survey? Did you ask the participants for fever symptoms or for the Body Temperature register on the test day?

4. What was the mean time between each MSaT round and the household survey?

5. This sentence in the Methods section “The completion of each round of MSaT was followed immediately by a wave of household survey” and the sentence in the Limitations section “the recall period was not more than two months of screening” are somehow vague, I would like to understand this period of time.

- I like the fact that the authors choose to talk about “afebrile malaria”, instead of using “asymptomatic malaria”. As explained in the Introduction section, although not having fever, human population can be clinically affected by this undiagnosed Plasmodium spp parasitaemia such as anaemia, maternal and neonatal mortality, neuronal impairment, or splenomegaly. However, I would like to see the consistent use of this concept all along the manuscript, especially in the Discussion section where the authors switch between the two concepts when describing results of previous studies, and in the Conclusions section.

- In the Introduction section, please define the acronym RDK (Rapid Diagnostic Test Kit).

- In the Introduction section, please define the diagnostic method used in the examples you report on studies checking prevalence. I believe that the study of Ganguly et al. used PCR for diagnostic of parasitaemia while most of the others reported RDT or microscopy results.

- In the Results section, “In the first round of the MSaT, 72.1% of those tested for malaria reported that their test had been performed by the Mitanin CHWs. The share of Mitanin CHWs in the malaria tests conducted in the 2nd, 3rd, 4th, 5th and 6th rounds was….” This reviewer does not understand who did performed the tests that were not done by the Mitanin, if the MSaT was conducted by these CHWs. Does this mean that the test for the rest of participants was conducted by the household survey team or that the test was performed in a health centre as part of a patient visit inside/outside the MSaT strategy? Please, develop this sentence (maybe it can also be done in the Methods section).

- The variable “Number of LLIN received by the Government” gives very few information about LLIN coverage in the households (participants could have bought LLINs aside of the given by Government? Do they conserve the nets at the moment of the survey? are those houses with more inhabitants receiving more nets?). Following the recommendations of the Roll Back Malaria Monitoring and Evaluation group, it would be nice to understand variables of LLIN coverage (1), such as Proportion of households with at least one LLIN, or Proportion of households with at least one LLIN for every two people, or Proportion of population with adequate access (≥ 1 LLIN/2 individuals) to a LLIN in their household.

- Your results report lower parasitaemia prevalence and afebrile malaria than in the nearby Odisha state, being such similar settings. It would be nice to understand the differences in the antimalarial programmes between both states (if any) to understand possible explanations. Also, is any other vector control strategy aside of LLIN distribution (example, IRS) being deployed in the study area?

- In the Discussion section, “Those studies had reported the afebrile malaria prevalence at 4.8% to 22% [13, 14]”. I believe there is a typo error in this sentence, because the reported prevalence of malaria in the Ganguly et al. article is 8.4%, no 4.8%.

- It would be nice to have some discussion on the different techniques to be used for the MSaT strategy or for detecting afebrile population with parasitaemia, effectiveness in detecting submicroscopic parasitaemia or cost-effectiveness of these strategies using molecular tools. If the authors wish, they can find some references to use at the end of this review of studies conducted in India (2, 3) and elsewhere (4, 5, 6, 7, 8).

- In the Discussion section, “The area covered in the current study had a large share of vulnerable communities and poor households and free distribution by government can improve the equity in access to LLINs.” It would be nice to see in the Results if the households with lowest socioeconomical outcome were related with having less LLIN coverage (aside of individual use reported).

- There is missing Journal information in Reference number 12.

- I cannot see in the text where the authors cited references numbered 34-35 and 38-40.

- References for authors’ consideration:

1. Roll Back Malaria Monitoring and Evaluation Reference Group. Household survey indicators for malaria control 2018 [Available from: Household Survey Indicators for Malaria Control_FINAL.pdf (endmalaria.org).

2. Singh A, Rajvanshi H, Singh MP, Bhandari S, Nisar S, Poriya R, et al. Mass screening and treatment (MSaT) for identifying and treating asymptomatic cases of malaria-malaria elimination demonstration project (MEDP), Mandla, Madhya Pradesh. Malar J. 2022;21(1):395.

3. Kaura T, Kaur J, Sharma A, Dhiman A, Pangotra M, Upadhyay AK, et al. Prevalence of submicroscopic malaria in low transmission state of Punjab: A potential threat to malaria elimination. J Vector Borne Dis. 2019;56(1):78-84.

4. Aydin-Schmidt B, Xu W, Gonzalez IJ, Polley SD, Bell D, Shakely D, et al. Loop mediated isothermal amplification (LAMP) accurately detects malaria DNA from filter paper blood samples of low density parasitaemias. PLoS One. 2014;9(8):e103905.

5. Hopkins H, Gonzalez IJ, Polley SD, Angutoko P, Ategeka J, Asiimwe C, et al. Highly sensitive detection of malaria parasitemia in a malaria-endemic setting: performance of a new loop-mediated isothermal amplification kit in a remote clinic in Uganda. The Journal of infectious diseases. 2013;208(4):645-52.

6. Morris U, Khamis M, Aydin-Schmidt B, Abass AK, Msellem MI, Nassor MH, et al. Field deployment of loop-mediated isothermal amplification for centralized mass-screening of asymptomatic malaria in Zanzibar: a pre-elimination setting. Malaria journal. 2015;14:205.

7. Oriero EC, Van Geertruyden JP, Nwakanma DC, D'Alessandro U, Jacobs J. Novel techniques and future directions in molecular diagnosis of malaria in resource-limited settings. Expert Rev Mol Diagn. 2015;15(11):1419-26.

8. Oriero EC, Jacobs J, Van Geertruyden JP, Nwakanma D, D'Alessandro U. Molecular-based isothermal tests for field diagnosis of malaria and their potential contribution to malaria elimination. J Antimicrob Chemother. 2015;70(1):2-13.

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Reviewer #1: No

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PONE-D-23-02503R1Assessing afebrile malaria and bed-net use in a high-burden region of India - Findings from multiple rounds of mass screeningPLOS ONE

Dear Dr. Garg,

After careful consideration, we feel that your manuscript will likely be suitable for publication if the authors revise it to address specific points raised now by the reviewer. According to the reviewers, there are some specific areas where further improvements would be of substantial benefit to the readers.   A major concern is related to English language. At this time, we strongly suggest a professional copy-editing service. For your guidance, a copy of the reviewers' comments was included below. 

Please submit your revised manuscript by Jun 23 2023 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,

Luzia H Carvalho, Ph.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: 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

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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: 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: Dear Authors,

This reviewer is happy with the answers given to the scientific questions raised at the first revision.

However, as suggested by the editorial during the first revision, I think that the manuscript would be benefited of a thorough scientific and English language revision. There are many sentences difficult to read and the text does not flow well at all. It happens with some verb structures and there is an abuse of phrasal verbs. One example is the use of the verb "tally", it is not clear what you mean by this, it has the meaning of "counting" or the meaning of "recording"? Changing some sentences to a more scientific standard language will help your manuscript to flow in a better way.

I suggest to the authors to check similar manuscripts that have been published in this journal:

- https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232874

- https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210578

- https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0282209

Other suggestion that you may like to take into account is to add at least one figure to the manuscript, I understand the issue with the copyright of Figure 1. Maybe you would like to built a similar figure by your own so we can understand the geographical setting of the study, or maybe some of the main data can be shown in a barr diagram or something similar.

Thank you.

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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: No

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[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.

PONE-D-23-02503R2Assessing afebrile malaria and bed-net use in a high-burden region of India - Findings from multiple rounds of mass screeningPLOS ONE

Dear Dr. Garg,

Thank you for submitting your manuscript for review to PLoS ONE. After careful consideration, we feel that your manuscript will likely be suitable for publication if the authors revise it to address critical points raised previously  by the reviewer.   A major concern is still related to English language. At this time, we strongly suggest a professional copy-editing service.  Finally, it seems to be essential to include figures to represent study settings (there are free software that the authors can use to build their own figure) and also main data. For your guidance, a copy of the reviewers' comments was included below.  

Please submit your revised manuscript by Jul 07 2023 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,

Luzia H Carvalho, Ph.D.

Academic Editor

PLOS ONE

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[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.

Assessing afebrile malaria and bed-net use in a high-burden region of India - Findings from multiple rounds of mass screening

PONE-D-23-02503R3

Dear Dr. Garg,

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.

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 onepress@plos.org.

Kind regards,

Luzia H Carvalho, Ph.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: 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

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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

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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: Dear authors, thanks for addressing the previous comments.

In my opinion the manuscript has significantly improved; it now reflects much better the efforts and findings of your research. Congratulations for the work done.

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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: No

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