The TIRS trial: Enrollment procedures and baseline characterization of a pediatric cohort to quantify the epidemiologic impact of targeted indoor residual spraying on Aedes-borne viruses in Merida, Mexico

James T. Earnest; Oscar D. Kirstein; Azael C. Mendoza; Gloria A. Barrera-Fuentes; Henry Puerta-Guardo; Manuel Parra-Cardeña; Kevin Yam-Trujillo; Matthew H. Collins; Norma Pavia-Ruz; Guadalupe Ayora-Talavera; Gabriela Gonzalez-Olvera; Anuar Medina-Barreiro; Wilberth Bibiano-Marin; Audrey Lenhart; M. Elizabeth Halloran; Ira Longini; Natalie Dean; Lance A. Waller; Amy M. Crisp; Fabian Correa-Morales; Jorge Palacio-Vargas; Pilar Granja-Perez; Salha Villanueva; Hugo Delfın-Gonzalez; Hector Gomez-Dantes; Pablo Manrique-Saide; Gonzalo M. Vazquez-Prokopec

doi:10.1371/journal.pone.0310480

Peer Review History

Original SubmissionJanuary 18, 2024
18 Jan 2024 Author Response Transfer Alert This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present. Attachments Attachment Submitted filename: 091523 PNTD Rebuttal.docx https://doi.org/10.1371/journal.pone.0310480.r001
22 Jul 2024 Decision Letter - André Ricardo Ribas Freitas, Editor PONE-D-24-00764The TIRS trial: enrollment procedures and baseline characterization of a pediatric cohort to quantify the epidemiologic impact of targeted indoor residual spraying on Aedes-borne viruses in Merida, MexicoPLOS ONE Dear Dr. Vazquez-Prokopec, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. The title is quite self-explanatory: "The TIRS trial: enrollment procedures and baseline characterization of a pediatric cohort to quantify the epidemiological impact of targeted indoor residual spraying on Aedes-borne viruses in Merida, Mexico", is a well-written manuscript that aims to describe the selection criteria and profile of participants, being studied for a Targeted Indoor Residual Spraying (TRIS) program, whose objective is to reduce the transmission of arboviruses (DENV, CHIKV and ZIKV) in Mérida. Small changes were suggested by the reviewers and once followed, I believe that the work will improve and will be ready to be published. Please submit your revised manuscript by Sep 05 2024 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. 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Additional Editor Comments: The title is quite self-explanatory: "The TIRS trial: enrollment procedures and baseline characterization of a pediatric cohort to quantify the epidemiological impact of targeted indoor residual spraying on Aedes-borne viruses in Merida, Mexico", is a well-written manuscript that aims to describe the selection criteria and profile of participants, being studied for a Targeted Indoor Residual Spraying (TRIS) program, whose objective is to reduce the transmission of arboviruses (DENV, CHIKV and ZIKV) in Mérida. As a sequential activity of the project, we await the results in new publications. [Note: HTML markup is below. Please do not edit.] 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 Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 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 Reviewer #2: Yes Reviewer #3: Yes ****** 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 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: This manuscript describes baseline finding for a large cRCT for a clinical trial evaluating Targeted Indoor Residual Spraying to reduce Aedes Borne Virus disease in Merida, Mexico. The objectives of the manuscript appear to have three objectives: 1) clearly describe the trial methodology so it can be cited in future publications (I support this approach), 2) demonstrate that clusters are well balanced on a large variety of relevant factors between treatment and control clusters prior to deployment of the intervention, and 3) provides additional insight about a trial that had to adjust in “real time” to the COVID-19 pandemic. Full disclosure, I reviewed an earlier version of this manuscript when submitted to PLOS NTD and can say the authors clearly considered my previous suggestions and concerns made at the time. Overall, I think this manuscript adds value to the literature on vector control trials for Aedes borne Viruses, demonstrating a very rigorous study design and approach. One could argue that this information should be included in a publication of the trial results, but I see value in this detailed presentation at the outset. It also provides some insight on ABV seroprevalence across Merida. I think this would be of interest to PLOS ONE readers and merits publication. Below are a few general and specific comments that the authors might consider. General Comments: Blinding. I understand why the authors have stratified their results into A and B to not reveal the treatment or control assignments which is appropriate. Some trialists (purists) might object to this, I personally do not, but I suggest the authors describe any blinding they are doing (this is some text already in the methods), but maybe a stronger statement in the discussion about the NEED and PRACTICALITY of blinding. So follow up questions associated with this are: 1) Why are seroprevalence results not presented for A and B arms. This is the most critical variable where you need to show balance and if not balance, rates would need to be age adjusted in the final primary outcome analyses. (This is Table 3 and Figure 3). Maybe this was an oversight but strange that this is the only data category not stratified. 2) Suggested Figure would be Age-seroprevalence curves (much in the text and Table 3, but this would be a contribution to the field). Data Availability: I do not see any statement but imagine that the authors would be restricted from posting data at this stage. I’m not concerned but was a question posed by the journal. Specific comments. Make sure you check throughout Aedes aegypti or Ae. aegypti there are many places were Aegypti is capitalized. Reviewer #2: The study design, statistical analysis are very rigorous. Results are clearly and completely presented and has only minor issues for revision: "Ae Aegypti" Should be "Ae. aegypti" Figure 3: quality is low, wich does not allow to understand it. Figure 5: Mortality (%) Reviewer #3: This is a well-written manuscript, which describes the recruitment and baseline characteristics of study participants for a Targeted Indoor Residual Spraying (TRIS) program, the goal of which is to reduce arbovirus (DENV, CHIKV, and ZIKV) transmission in Merida, Mexico. Baseline seroprevalence data and demographic information are provided. As a side note, the authors should be commended for keeping the study on track, despite the challenges faced due to the COVID-19 pandemic. Line 46 (and elsewhere): replace “dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) virus” with “dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV)” Line 47: delete “ongoing”. It implies that the COVID-19 pandemic is still ongoing at this very moment in time, which isn’t really the case Line 56: replace “seropositive for antibodies against one or more flaviviruses” with “seropositive for one or more flaviviruses”. Similar changes need to be made elsewhere. The word “antibodies” is redundant because “seropositive” means that antibodies were detected Abstract: perhaps I’m being a bit picky with this one, but it would be helpful if it was explicitly stated in the abstract that indoor spraying has not yet commenced Lines 83-84: it would be better to say “among the leading causes” because the global number of JEV or YFV cases may exceed that of ZIKV or CHIKV Line 146: add a space between “(ICTRP)(see” Lines 252-253: avoid using the word “genus” or replace “flavivirus” with “orthoflavivirus” throughout the manuscript. The genus Flavivirus has been renamed to Orthoflavivirus. Line 264: is 72 h enough time for all dengue virus serotypes? Check that the wrong number hasn’t been added Line 268: replace “mouse monoclonal” with mouse flavivirus-reactive monoclonal” or something similar Tables 1 & 3: it would be helpful if the title of the table was above (rather than below) the table Line 388: replace “IgG antibodies” with “IgG”. We all know that IgG is a type of antibody so it is redundant to include the word “antibodies” Line 390: it says that seroprevalence is similar between both arms. It also says that the ratio of male and female participants is similar between both arms. The authors explain that this info is provided in Table 3. However, I don’t see “arm data” in the table, only “overall data”. Reword the text or clearly show the Arm A vs B data as done in Tables 1 and 2. Table 4: arm data are not provided (only overall data) ****** 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. 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 Reviewer #2: No Reviewer #3: 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. 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Revision 1
15 Aug 2024 Author Response Response to Reviewers’ Comments Reviewer #1: This manuscript describes baseline finding for a large cRCT for a clinical trial evaluating Targeted Indoor Residual Spraying to reduce Aedes Borne Virus disease in Merida, Mexico. The objectives of the manuscript appear to have three objectives: 1) clearly describe the trial methodology so it can be cited in future publications (I support this approach), 2) demonstrate that clusters are well balanced on a large variety of relevant factors between treatment and control clusters prior to deployment of the intervention, and 3) provides additional insight about a trial that had to adjust in “real time” to the COVID-19 pandemic. Full disclosure, I reviewed an earlier version of this manuscript when submitted to PLOS NTD and can say the authors clearly considered my previous suggestions and concerns made at the time. Overall, I think this manuscript adds value to the literature on vector control trials for Aedes borne Viruses, demonstrating a very rigorous study design and approach. One could argue that this information should be included in a publication of the trial results, but I see value in this detailed presentation at the outset. It also provides some insight on ABV seroprevalence across Merida. I think this would be of interest to PLOS ONE readers and merits publication. Below are a few general and specific comments that the authors might consider. We thank the reviewer for all of their effort in improving our manuscript as well as their kind words written here. General Comments: Blinding. I understand why the authors have stratified their results into A and B to not reveal the treatment or control assignments which is appropriate. Some trialists (purists) might object to this, I personally do not, but I suggest the authors describe any blinding they are doing (this is some text already in the methods), but maybe a stronger statement in the discussion about the NEED and PRACTICALITY of blinding. We added the following statement to the discussion “Per protocol, only the statistical analysis team was unblinded to the identity of each trial arm. Once the trial is open for analysis, blinding will be lifted. For the purposes of this manuscript, the use of blinded trial arms allows depicting the aspects of the trial that were involvement in participant enrollment and baseline information while respecting the blinding.” (lines 516-520) So follow up questions associated with this are: 1) Why are seroprevalence results not presented for A and B arms. This is the most critical variable where you need to show balance and if not balance, rates would need to be age adjusted in the final primary outcome analyses. (This is Table 3 and Figure 3). Maybe this was an oversight but strange that this is the only data category not stratified. We have added arm data to table 3 and we respectfully argue that figure 3 (now fig 4) contains so much information that adding arm information would be confusing to readers (we have already addressed complaints that the data is hard to read in it’s current format).Similar to how the arms are balanced in terms of age, sex, and seroprevalence we did not observe any significant difference in FRNT titers between the arms. 2) Suggested Figure would be Age-seroprevalence curves (much in the text and Table 3, but this would be a contribution to the field). This figure is now Fig 3 in the manuscript Data Availability: I do not see any statement but imagine that the authors would be restricted from posting data at this stage. I’m not concerned but was a question posed by the journal. Correct, the data has been uploaded to Mendeley and will be released upon acceptance (see lines 317-319) Specific comments. Make sure you check throughout Aedes aegypti or Ae. aegypti there are many places were Aegypti is capitalized. These mistakes have been corrected Reviewer #2: The study design, statistical analysis are very rigorous. Results are clearly and completely presented and has only minor issues for revision: We thank the reviewer for their kind words "Ae Aegypti" Should be "Ae. aegypti" These mistakes have been corrected Figure 3: quality is low, wich does not allow to understand it. We are not sure why this is the case, but it is an issue with the compiled version of the manuscript and not our submitted TIFF. Hopefully a more clear version will be included in this submission Figure 5: Mortality (%) I apologize, but it is unclear to me what this means. If there is a correction needed, please clarify. Reviewer #3: This is a well-written manuscript, which describes the recruitment and baseline characteristics of study participants for a Targeted Indoor Residual Spraying (TRIS) program, the goal of which is to reduce arbovirus (DENV, CHIKV, and ZIKV) transmission in Merida, Mexico. Baseline seroprevalence data and demographic information are provided. As a side note, the authors should be commended for keeping the study on track, despite the challenges faced due to the COVID-19 pandemic. We thank this reviewer for their work and kind words here. Line 46 (and elsewhere): replace “dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) virus” with “dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV)” This has been corrected as suggested (lines 46-47) Line 47: delete “ongoing”. It implies that the COVID-19 pandemic is still ongoing at this very moment in time, which isn’t really the case This has been corrected as requested (line 49) Line 56: replace “seropositive for antibodies against one or more flaviviruses” with “seropositive for one or more flaviviruses”. Similar changes need to be made elsewhere. The word “antibodies” is redundant because “seropositive” means that antibodies were detected This change has been included (line 59) Abstract: perhaps I’m being a bit picky with this one, but it would be helpful if it was explicitly stated in the abstract that indoor spraying has not yet commenced We agree that this is important to include in the abstract, we have made revisions to the abstract to reflect that TIRS spraying has not yet occurred (lines 54-56) Lines 83-84: it would be better to say “among the leading causes” because the global number of JEV or YFV cases may exceed that of ZIKV or CHIKV This statement has been changed as requested (line 87) Line 146: add a space between “(ICTRP)(see” Fixed (line 149) Lines 252-253: avoid using the word “genus” or replace “flavivirus” with “orthoflavivirus” throughout the manuscript. The genus Flavivirus has been renamed to Orthoflavivirus. Thank you for pointing this out, we have changed the word to “orthoflavivirus” (line 257) Line 264: is 72 h enough time for all dengue virus serotypes? Check that the wrong number hasn’t been added In our hands, this assay works at 72h for the virus serotypes we used, though we are aware that different viruses require different incubation times. Line 268: replace “mouse monoclonal” with mouse flavivirus-reactive monoclonal” or something similar We have changed the wording to “mouse monoclonal antibody that is cross-reactive to multiple orthoflaviviruses” (line 274) Tables 1 & 3: it would be helpful if the title of the table was above (rather than below) the table We have changed the location of the table titles to above the tables per your suggestion and editorial guidelines Line 388: replace “IgG antibodies” with “IgG”. We all know that IgG is a type of antibody so it is redundant to include the word “antibodies” This change has been included (line 400) Line 390: it says that seroprevalence is similar between both arms. It also says that the ratio of male and female participants is similar between both arms. The authors explain that this info is provided in Table 3. However, I don’t see “arm data” in the table, only “overall data”. Reword the text or clearly show the Arm A vs B data as done in Tables 1 and 2. We have added arm information to a new version of table 3 Table 4: arm data are not provided (only overall data) The table shows the result of a GLMM model comparing Arm A (baseline) with B. So, the betas and Pvalue are indicative of whether Arm B differed from Arm A. Here, ‘Arm’ is the treatment variable not an individual arm. Attachments Attachment Submitted filename: 080924 Response to Reviewer Comments.docx https://doi.org/10.1371/journal.pone.0310480.r003
2 Sep 2024 Decision Letter - André Ricardo Ribas Freitas, Editor The TIRS trial: enrollment procedures and baseline characterization of a pediatric cohort to quantify the epidemiologic impact of targeted indoor residual spraying on Aedes-borne viruses in Merida, Mexico PONE-D-24-00764R1 Dear Dr. Vazquez-Prokopec, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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, André Ricardo Ribas Freitas Academic Editor PLOS ONE Additional Editor Comments (optional): I hope this message finds you well. I am pleased to inform you that your manuscript titled "The TIRS trial: enrollment procedures and baseline characterization of a pediatric cohort to quantify the epidemiologic impact of targeted indoor residual spraying on Aedes-borne viruses in Merida, Mexico" has been accepted for publication in PLOS ONE. We appreciate the thorough and thoughtful revisions you made in response to the reviewers' comments. The reviewers acknowledged the significant improvements, and we are confident that your article now meets the high standards required by our journal. Your attention to addressing the reviewers' feedback, including the discussion on blinding, the addition of data in the tables, and the correction of technical details, has not only enhanced the clarity of your manuscript but also strengthened the presentation and interpretation of your findings. Your work makes a valuable contribution to the literature on vector control and epidemiological studies, particularly given the additional challenges posed by the COVID-19 pandemic. You will soon receive further instructions regarding the next steps for the publication of your article. If you have any questions or need additional assistance, please do not hesitate to reach out. Congratulations on the acceptance of your manuscript, and thank you for choosing PLOS ONE to share your important work. Best regards, André Ribas Freitas https://doi.org/10.1371/journal.pone.0310480.r004
Formally Accepted
6 Sep 2024 Acceptance Letter - André Ricardo Ribas Freitas, Editor PONE-D-24-00764R1 PLOS ONE Dear Dr. Vazquez-Prokopec, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. André Ricardo Ribas Freitas Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0310480.r005

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