Uncertainties, work conditions and testing biases: Potential pathways to misdiagnosis in point-of-care rapid HIV testing in Zimbabwe

Morten Skovdal; Nadine Beckmann; Rufurwokuda Maswera; Constance Nyamukapa; Simon Gregson

doi:10.1371/journal.pone.0237239

Peer Review History

Original SubmissionJanuary 31, 2020
22 Jun 2020 Decision Letter - Julie AE Nelson, Editor PONE-D-20-02895 Uncertainties, work conditions and testing biases: Potential pathways to misdiagnosis in point-of-care rapid HIV testing in Zimbabwe PLOS ONE Dear Dr. Skovdal, 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 address all of the concerns of the reviewer. Please submit your revised manuscript by Aug 06 2020 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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[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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A ****** 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 ****** 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 ****** 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: With the availability of point – of – care diagnostic technology, globally, HIV testing coverage has been significantly improved through task shifting and decentralization of the service. While this facilitate access to HIV testing, greater attention to quality assurance is required and quality management system need to be in placed to ensure the quality of HIV testing. This qualitative study provided very important and practical perspectives on HIV misdiagnosis in Zimbabwe. The potential factors that may lead to misdiagnosis were classified in three thematic topics: uncertainties, work condition and testing bias. Such information would be very useful for Zimbabwe (and may be other country that have similar context) in terms of policy development or actions to be taken to ensure HIV testing quality. Overall, the manuscript was very well written. I have several minor comments for the authors to consider: - Page 7, age of the researchers is still missing “x to x”. However, I don’t think it is necessary to report researchers’ age. - Figure 1. Need to have descriptive caption. In the text, it said Figure 1 I national testing algorithm. However, from what I see in the Figure, this is national testing strategy not testing algorithm. - Table caption should be placed above the tables - Study participants: The Table 1 indicated 18 hospitals involved in the study. While the number of HIV counsellors and nurses interviewed were 17 and 10 respectively, only one lab technician participated in the study. The author said two or three rapid HIV testers were recruited from each facility (from 11 health facilities) who met the inclusion criteria. However, it is unclear if each facility had more than two (or three) testers who were eligible for participation in the study, how the interviewees were selected. The authors may need to provide further details. - External quality assessment (EQA) is a critical component for quality assurance system. It would be good if the authors can discuss whether EQA was available in Zimbabwe or not. The authors reported testers received some training but whether there was a certification system (for the testers and for the testing sites) in the country? - Reference: WHO handbook on “Improving the quality of HIV -related point-of-care testing: ensuring the reliability and accuracy of test results” could be a relevant reference for this manuscript. ****** 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: Yes: Dr Van Thi Thuy nguyen [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/. 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Revision 1
1 Jul 2020 Author Response - Page 7, age of the researchers is still missing “x to x”. However, I don’t think it is necessary to report researchers’ age. That was an error, thank you. We agree that age is not relevant and have removed the reference to their age. - Figure 1. Need to have descriptive caption. In the text, it said Figure 1 I national testing algorithm. However, from what I see in the Figure, this is national testing strategy not testing algorithm. We have added a descriptive caption to Figure 1. We have also amended the text to specify that it is a strategy. Because we anonymized the tests, the reviewer helpfully pointed out that it is no longer a populated algorithm, but a strategy. We also now explain this to the reader. - Table caption should be placed above the tables Done - Study participants: The Table 1 indicated 18 hospitals involved in the study. While the number of HIV counsellors and nurses interviewed were 17 and 10 respectively, only one lab technician participated in the study. The author said two or three rapid HIV testers were recruited from each facility (from 11 health facilities) who met the inclusion criteria. However, it is unclear if each facility had more than two (or three) testers who were eligible for participation in the study, how the interviewees were selected. The authors may need to provide further details. Thank you for this comment. We have added a sentence in the methodology to clarify this point: “As more than two or three HIV testers were eligible for participation at many of the health facilities, we invited the local Matron or Sister in charge to select the participants based on their experience and availability to participate in an interview on the day of our visit.” - External quality assessment (EQA) is a critical component for quality assurance system. It would be good if the authors can discuss whether EQA was available in Zimbabwe or not. The authors reported testers received some training but whether there was a certification system (for the testers and for the testing sites) in the country? In the discussion we now explain: “External quality assessment (EQA), as recommended by the WHO [9], was being rolled out in Zimbabwe in 2017/18 and reported as being present in 25% of cases at the time of our surveillance [20]. Although EQA coverage might have been higher at the time of the qualitative data collection, it did not feature in our findings.” We have also added a note on the absence of a certification system to the discussion: “There is also need for further training of HIV testers, accompanied with a certification system (this is currently under consideration in Zimbabwe).” - Reference: WHO handbook on “Improving the quality of HIV -related point-of-care testing: ensuring the reliability and accuracy of test results” could be a relevant reference for this manuscript. We have incorporated the handbook into our introduction (in relation to WHO recommendations) and into the discussion (to talk about EQA). https://doi.org/10.1371/journal.pone.0237239.r002
23 Jul 2020 Decision Letter - Julie AE Nelson, Editor Uncertainties, work conditions and testing biases: Potential pathways to misdiagnosis in point-of-care rapid HIV testing in Zimbabwe PONE-D-20-02895R1 Dear Dr. Skovdal, 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, Julie AE Nelson, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): There are grammatical errors that must be corrected before publication. See the list below. Throughout, “test-kits” does not need to be hyphenated, but if it is, it must be consistent, including in Table 2. Line 32: add comma after “facilities” Line 66: change to “the recent” Line 70: move comma to before “as” Line 89: Add “Zimbabwe” as follows: “to the current Zimbabwe national” Figure 1: also add “Zimbabwe” as follows: “The Zimbabwe National HIV” Line 92: delete “illustrated in figure 1” as redundant to previous sentence Line 110: remove “either” and add comma after “engineer” Line 112: change “HIV tests and the standard operating procedures and testing algorithms” to “HIV tests, SOPs, and testing algorithms” Line 115: fix misspelling of “assess” Line 119: add comma after “materials” Lines 123-126: change all verbs to past tense Lines 134-145: move this paragraph to the introduction; make the last part of the introduction about why you have done this study and include the information in this paragraph. Line 147: Change first word to “This” Lines 147-152: change all verbs to past tense Line 183: add comma after “test-kits” Line 195: change “as well as” to “and” Line 197: add comma after “pharmacy” Line 224: change “is” to “was” Line 229: change “standard operating procedures” to “SOPs” Line 243: add comma after “2B” Line 247: remove comma after “hospital” Line 277: Add period after “positive” Line 304: change dashes to parentheses Line 331: remove comma after “few” Line 340: change “, whether it relates to” to “from” Line 342: add “s” to “introduce” Line 382: change “standard operating procedures” to “SOPs” Line 388: add period after “wait” Line 409: add period after “results” Lines 432-435: this is the same quote as used in Lines 314-317. Do not use this quote twice; either use a different quote in one of the locations or refer to the earlier quote here without repeating it. Line 534: change “standard operating procedures” to “SOPs” Line 536: add comma after “confrontation” Line 549: change “standard operating procedures” to “SOPs” Line 556: change “et al” to “et al.” 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. 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A ****** 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: No ****** 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 ****** 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: The authors have sufficiently addressed all the recommendations. It can be considered for publication. ****** 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: Yes:** Van Thi Thuy Nguyen https://doi.org/10.1371/journal.pone.0237239.r003
Formally Accepted
4 Aug 2020 Acceptance Letter - Julie AE Nelson, Editor PONE-D-20-02895R1 Uncertainties, work conditions and testing biases: Potential pathways to misdiagnosis in point-of-care rapid HIV testing in Zimbabwe Dear Dr. Skovdal: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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 plosone@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. Julie AE Nelson Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0237239.r004

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