The acceptability of minimally invasive tissue sampling for cause of death determination in rural South Africa: A qualitative analysis

Laura-Lynne Brandt; Gift Mathebula; Zokwane Lucky Mondlane; Sara Jewett; Kathleen Kahn; Ryan Gregory Wagner; Jessica Price

doi:10.1371/journal.pone.0345107

Peer Review History

Original SubmissionDecember 10, 2024
2 May 2025 Decision Letter - Jayeshkumar Kanani, Editor -->PONE-D-24-56472-->-->The acceptability of Minimally Invasive Tissue Sampling for cause of death determination in rural South Africa: a qualitative analysis-->-->PLOS ONE Dear Dr. Brandt, 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. Please submit your revised manuscript by Jun 14 2025 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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The funding was awarded to the PI, KK, and team. The MRC/Wits Rural Public Health and Health Transitions Research Unit and Agincourt Health and Socio-Demographic Surveillance System, a node of the South African Population Research Infrastructure Network (SAPRIN), is supported by the Department of Science, Technology and Innovation, the University of the Witwatersrand, and the Medical Research Council, South Africa, and previously the Wellcome Trust, UK (grants 058893/Z/99/A; 069683/Z/02/Z; 085477/Z/08/Z; 085477/B/08/Z) Bill and Melinda Gates Foundation: https://www.gatesfoundation.org/ MITS Alliance: https://mitsalliance.org/ Department of Science, Technology and Innovation: https://www.dsti.gov.za/ The University of the Witwatersrand: https://www.wits.ac.za/ Medical Research Council, South Africa: https://www.samrc.ac.za/ Wellcome Trust, UK: https://wellcome.org/]. Please state what role the funders took in the study. 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Additional Editor Comments: Dear author, please address the reviewers' suggestions. [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: Partly 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.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 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: Following clarification needed. For a scientific study which will be helpful to the community, why so remote area is selected? The study is based only on the basis of question and answer by interview or any follow up study. Line 28-29 experience of death in family, How it will help in study? does this include the experience of cause of death investigation and any disgusting feeling by them during that procedure. Does inform consent was in camera? there is no clarification. There is no clarification about the type of tissue and from which site of body samples will be collected. Who will collect the samples and who will process them? What will be the cost effectiveness of such investigations? If the community agree on the study, does author has proceeded for sampling and if yes what was the results? Is the technique is applicable only to nature undiagnosed deaths or it can be used for unnatural deaths to know cause of death? Have author conducted any such study by taking minimum tissues? If yes what was the result? What is the total population of study area? Is the tissue sampling is under sonography or CT guided? If yes then whether these facilities are available there? or the investigator have to transport the samples to other center. Reviewer #2: The authors address the issue of acceptability of MITS for determining the cause of death in rural South Africa The paper is well written and clear. Recommendations: Accept My Comments: Introduction: Line 53 “ a useable” – can be replaced with a better word Methodology: No change Results: 197 Table 3. Summary of FGD participants – Table incomplete? Conclusions: No change Reviewer #3: It is an very interesting paper, that fulfill and regard many aspects in the autopsy procedure acceptance, even complete or minimally invasive, in low-income settings. The writing was very clear and sound, with a right lenght of text. The methods are good, and suitable with the strenghts and limitations discussion. ****** -->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 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? 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Revision 1
1 Dec 2025 Author Response Dear Editors and Reviewers, We wish to thank the reviewers and editors for their valuable feedback regarding the manuscript titled “The acceptability of minimally invasive tissue sampling for cause of death determination in rural South Africa: a qualitative analysis”. We greatly value the feedback provided and will summarise our response in this comment. Please see the documents titled, "Cover letter" and "Response to reviewers" for more detailed clarifications. Reviewer 1: For a scientific study which will be helpful to the community, why so remote area is selected? - This study was purposefully set in a rural community as their are more gaps in cause of death data in these low-resource settings. Minimally invasive tissue sampling (MITS) could be a potentially be useful for filling these gaps. This study specifically aims to identify cultural and structural barriers to the implementation of MITS in these settings. The study is based only on the basis of question and answer by interview or any follow up study. - This study relies purely on in-depth interviews and focus group discussions as a source of data. A follow-up study is underway, however, the results of this study is not yet available. Line 28-29 experience of death in family, How it will help in study? does this include the experience of cause of death investigation and any disgusting feeling by them during that procedure. - Participant that have recently experienced a death would have more insight into the emotional distress and the ritual practices surrounding deaths in this setting. These participants would be better equipped to share their personal experiences and how amenable grieving families would be to participating in a MITS study. The vast majority of residents in this setting have no experience with autopsies, so this was not part of our inclusion criteria. We provided demonstrations on how the MITS procedure is performed to ensure their responses were well informed. Does inform consent was in camera? there is no clarification. - We recorded the interviews with audio recorders, not cameras. We apologise for not clarifying this in the initial manuscript. The updated manuscript includes which recording modalities was used and how consent was obtained. There is no clarification about the type of tissue and from which site of body samples will be collected. - We apologise for the lack of clarity. This study is a formative study performed prior to the start of the MITS intervention study, in order to better understand whether the intervention would be acceptable and to inform the design of the MITS intervention study. We included a section in the manuscript detailing the procedures undertaken during the MITS process, included what tissues will be sampled. Please see the "Response to reviewers" document and the updated manuscript for more details. Who will collect the samples and who will process them? - We did not include this level of detail regarding the methodology of the MITS intervention study, as this manuscript is not about the MITS intervention study. This was a qualitative study undertaken to assisting with the planning of the MITS intervention study to optimize implementation efforts. This paper specifically discusses the acceptability of MITS and explore cultural and structural barriers to its implementation. What will be the cost effectiveness of such investigations? - Unfortunately, no studies to date have investigated the cost-effectiveness of MITS and it is also beyond the scope of this study. If the community agree on the study, does author has proceeded for sampling and if yes what was the results? - The MITs intervention study has commenced (after ethical clearance and permission from the relevant authorities). This study is still ongoing and the result of this study will be published in a separate paper. Is the technique is applicable only to nature undiagnosed deaths or it can be used for unnatural deaths to know cause of death? Have author conducted any such study by taking minimum tissues? If yes what was the result? - The MITS technique is relatively novel and its application to unnatural deaths has not been investigated. This study is part of formative work conducted prior to the MITS intervention study and will only discuss the acceptability of the procedure. The MITS study is still ongoing at the result will be discussed in a different paper. What is the total population of study area? - The latest estimates included about 117 000 residents within the Agincourt Health and socioDemographic Surveillance system platform. Is the tissue sampling is under sonography or CT guided? If yes then whether these facilities are available there? or the investigator have to transport the samples to other center. - The research team is not utilizing any imaging modalities to guide the MITS process. The team is working on a protocol to incorporate portable ultrasound-guided sampling into the procedure. Reviewer 2: Introduction: Line 53 “ a useable” – can be replaced with a better word - Replaced “a useable” with “an informative” Methodology: No change Results: 197 Table 3. Summary of FGD participants – Table incomplete? - Our apologies if there was an error in uploading table 3. We have double checked that the table is not missing any information and have uploaded a new copy. Conclusions: No change Reviewer 3: - No changes noted. Below we will comment on the feedback for the editors regarding issues with our initial submission. 1. Financial disclosure revised. Please find the updated statement with the added statement regarding the Role of Funders below. “This project has been funded by the MITS Surveillance Alliance through funding from the Gates Foundation (INV-034017). The funding was awarded to the principal investigator, KK, and team. The SAMRC/Wits Rural Public Health and Health Transitions Research Unit and Agincourt Health and socio-Demographic Surveillance System, a node of the South African Population Research Infrastructure Network (SAPRIN), is supported by the Department of Science, Technology and Innovation, the University of the Witwatersrand, and the Medical Research Council, South Africa, and previously the Wellcome Trust, UK (grants 058893/Z/99/A; 069683/Z/02/Z; 085477/Z/08/Z; 085477/B/08/Z) Gates Foundation: https://www.gatesfoundation.org/ MITS Surveillance Alliance: https://mitsalliance.org/ Department of Science, Technology and Innovation: https://www.dsti.gov.za/ The University of the Witwatersrand: https://www.wits.ac.za/ South African Medical Research Council, South Africa: https://www.samrc.ac.za/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” 2. Funding information section on the submission form has been updated to match financial disclosure as above. 3. Regarding data availability. We do, however, have concerns regarding making our dataset available to the public. We recognise that data sharing is important for transparency and replicability in research, however we are concerned that even a de-identified set of interview transcripts would risk breaking confidentiality with the participants included in this study. The interviews were conducted in a small community, easily identified because of its institutional base and research history. and Participants shared deeply personal and unique experiences, recounting events that led to deaths which would be recognised by other members of the community. To remove these elements from the transcripts in an attempt to de-identify the transcripts would remove core content which forms the basis of the thematic analysis included in this paper and would defeat the purpose of sharing the raw data. We hope that given this special circumstance we may be exempted from this data-sharing policy. We are happy to share the transcripts elements of the data with individual researchers on request, where data protection and privacy conditions can be assured. We would also be happy to upload our code book to the data repository if this would be helpful. This concludes our comments on the responses from the editors and reviewers. We would like to thank them again for their valuable input. Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0345107.r002
9 Dec 2025 Decision Letter - Jayeshkumar Kanani, Editor -->PONE-D-24-56472R1-->-->The acceptability of Minimally Invasive Tissue Sampling for cause of death determination in rural South Africa: a qualitative analysis-->-->PLOS One Dear Dr. Brandt, 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. Please submit your revised manuscript by Jan 23 2026 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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Additional Editor Comments: Reviewer 1: Still the point is not clear to me, why the author chose to study on the interview basis? Why general public was involved in a study which require authorization from higher authorities? The author has not discussed about cost effectiveness of the test because if it is free burdone to goventment and if chargeble then people have to know the cost per test. [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 #1: All comments have been addressed ******** -->2. 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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.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 ****** -->5. Is the manuscript presented in an intelligible fashion and written in standard English? 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25 Feb 2026 Author Response Dear Reviewers, RE: MANUSCRIPT NO: PONE-D-24-56472.Title: “The acceptability of minimally invasive tissue sampling for cause of death determination in rural South Africa: a qualitative analysis” We would like to thank the reviewers for considering our updated manuscript titled “The acceptability of minimally invasive tissue sampling for cause of death determination in rural South Africa: a qualitative analysis”. We understand that there are still some points that you found to be unclear and we are happy to provide further explanation. The responses to the reviewer comments are as follows: Still the point is not clear to me, why the author chose to study on the interview basis? Previous studies exploring the acceptability of MITS also utilised interviews to collect their data. Our rationale for using interviews and focus group discussions to explore this topic was to get a detailed account of factors affecting the acceptability of MITS and to explore other practical aspects around the implementation of MITS in the Agincourt HDSS area. Quantitative methods would not have allowed us to get the depth of information we needed to inform the implementation of MITS in this setting. I have included references to other studies that have explored the acceptability of MITS using qualitative interviews below. These studies have also been cited in the manuscript. Why general public was involved in a study which require authorization from higher authorities? This study was approved by the University of the Witwatersrand Human Research Ethics Committee (Medical) and from the Mpumalanga Provincial Health Research and Ethics Committee as these were the local ethics committees responsible for enforcing ethical standards in research in the area. This was not a national project, but a research study conducted only within the Agincourt HDSS area. The author has not discussed about cost effectiveness of the test because if it is free burdone to goventment and if chargeble then people have to know the cost per test. This study is purely for research purposes, and all the costs of the project are covered by research grants. This is not a service that is provided by the South African government currently nor a service that is available to the general community on request at their own cost. For this study there is no cost to the consumer or to the government. A cost effectiveness analysis can be conducted at a later stage once full costing implications are better understood. The research presented in this manuscript was a qualitative investigation into the acceptability of MITS in a rural community and so costings were not reflective of the MITS procedure itself. List of article investigating the acceptability of MITS: 1. Magaço A, Alonso Y, Maixenchs M, Ambrosio C, Sitoe A, Vitorino P, et al. A Qualitative Assessment of Community Acceptability and Its Determinants in the Implementation of Minimally Invasive Tissue Sampling in Children in Quelimane City, Mozambique. Am J Trop Med Hyg. 2023 Apr 10;tpmd220343. 2. Ngwenya N, Coplan D, Nzenze S, Myburgh N, Madhi S. Community acceptability of minimally invasive autopsy (MIA) in children under five years of age in Soweto, South Africa. Anthropol South Afr. 2017 June 2;40(2):108–21. 3. O’Mara Sage E, Munguambe KR, Blevins J, Guilaze R, Kosia B, Maixenchs M, et al. Investigating the Feasibility of Child Mortality Surveillance With Postmortem Tissue Sampling: Generating Constructs and Variables to Strengthen Validity and Reliability in Qualitative Research. Clin Infect Dis Off Publ Infect Dis Soc Am. 2019 Oct 9;69(Suppl 4):S291–301. 4. Das MK, Arora NK, Kaur G, Malik P, Kumari M, Joshi S, et al. Perceptions of family, community and religious leaders and acceptability for minimal invasive tissue sampling to identify the cause of death in under-five deaths and stillbirths in North India: a qualitative study. Reprod Health. 2021 Aug 4;18(1):168. 5. Feroz A, Ibrahim MN, McClure EM, Ali AS, Tikmani SS, Reza S, et al. Perceptions of parents and religious leaders regarding minimal invasive tissue sampling to identify the cause of death in stillbirths and neonates: Results from a qualitative study. Reprod Health [Internet]. 2019;16(1). Available from: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85065569015&doi=10.1186%2fs12978-019-0730-9&partnerID=40&md5=330380b6971fd968805251084a64f4ed 6. Lawrence S, Namusanya D, Hamuza A, Huwa C, Chasweka D, Kelley M, et al. Hypothetical acceptability of hospital-based post-mortem pediatric minimally invasive tissue sampling in Malawi: The role of complex social relationships. PloS One. 2021;16(2):e0246369. 7. Rugwizangoga B, Niyibizi JB, Ndayisaba MC, Musoni E, Manirakiza F, Uwineza A, et al. Exploring Perceptions and Acceptance of Minimally Invasive Tissue Sampling among Bereaved Relatives and Health-Care Professionals in Rwanda. J Multidiscip Healthc. 2021 Dec 15;14:3421–7. 8. Ahsan N, Malik FA, Mughis W, Jabeen R, Mehboob S, Allana R, et al. Postmortem minimally invasive tissue sampling in communities: exploring perceptions of families, funeral workers, religious and community leaders and healthcare providers from Pakistan. BMC Health Serv Res. 2023 Dec 13;23(1):1402. Thank you for considering this manuscript and giving me the opportunity to respond to your queries. I look forward to your response. Kind regards, Laura-Lynne Brandt Attachments Attachment Submitted filename: Response_to_reviewers_auresp_2.docx https://doi.org/10.1371/journal.pone.0345107.r004
2 Mar 2026 Decision Letter - Jayeshkumar Kanani, Editor The acceptability of Minimally Invasive Tissue Sampling for cause of death determination in rural South Africa: a qualitative analysis PONE-D-24-56472R2 Dear Dr. Brandt, 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. For questions related to billing, please contact and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support.. 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, Jayeshkumar Kanani Guest Editor PLOS One Additional Editor Comments (optional): The authors have carefully considered all reviewer comments and have provided appropriate revisions and clarifications throughout the manuscript. The revised version demonstrates significant improvement in structure, scientific rigor, and overall presentation. The concerns raised during the initial review have been satisfactorily resolved. Therefore, I believe the manuscript is now suitable and acceptable for publication. Reviewers' comments: https://doi.org/10.1371/journal.pone.0345107.r005
Formally Accepted
Acceptance Letter - Jayeshkumar Kanani, Editor PONE-D-24-56472R2 PLOS One Dear Dr. Brandt, 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 You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. 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. Jayeshkumar Kanani Guest Editor PLOS One https://doi.org/10.1371/journal.pone.0345107.r006

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