Hepatitis C virus seroprevalence, testing, and treatment capacity in public health facilities in Ghana, 2016–2021; A multi-centre cross-sectional study

Yvonne Ayerki Nartey; Rafiq Okine; Atsu Seake-Kwawu; Georgia Ghartey; Yaw Karikari Asamoah; Ampem Darko Jnr Siaw; Kafui Senya; Amoako Duah; Alex Owusu-Ofori; Opei Adarkwa; Seth Agyeman; Sally Afua Bampoh; Lindsey Hiebert; Henry Njuguna; Neil Gupta; John W. Ward; Lewis Rowland Roberts; Ansumana Sandy Bockarie; Yaw Asante Awuku; Dorcas Obiri-Yeboah

doi:10.1371/journal.pone.0287580

Peer Review History

Original SubmissionApril 9, 2023
5 May 2023 Decision Letter - Olatunji Matthew Kolawole, Editor PONE-D-23-08352Hepatitis C virus seroprevalence, testing, and treatment capacity in public health facilities in Ghana, 2016 – 2021; A multi-centre cross-sectional study.PLOS ONE Dear Dr. Nartey, 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 19 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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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 ****** 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 ****** 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: 1. The rapid test kits used in this sero-prevalence study of hepatitis C need to have an evidence of post market verification using a serological test gold standard such enzyme immuno assay or multiplex beads assay as a gold standard. 2. Are remnants of the donors samples archived in these blood banks in order to provide answers to some of these questions? If yes, is recommended that you compare the serologically positive samples with the nucleic acid testing or at least EIA results. The sensitivity, specificity, positive predictive vale and the negative predictive value from the evaluation/ post market verification of these rapid test kits are quite essential to the reliability of this sero-prevalence data. 3. Does the record in the blood banks indicate the route of transmission of hepatitis C among the positive donors? This will help in prevention of Hepatitis C infection in Ghana. Reviewer #2: As a Medical Laboratory Scientist , I enjoyed every bit of the article. The research methodology and data analysis was brilliant. But I beg different will that 17% data available would not be able to give a good representation of the prevalence of HCV infection in Northern Ghana. It is a brilliant idea, I hope this findings from this research is submitted to relevant stakeholders to help formulate policies that build a good disease surveillance for JCV infection in Ghana ****** 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. 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Attachments Attachment Submitted filename: PONE-D-23-08352.pdf https://doi.org/10.1371/journal.pone.0287580.r001
Revision 1
24 May 2023 Author Response Reviewer #1: 1. The rapid test kits used in this sero-prevalence study of hepatitis C need to have an evidence of post market verification using a serological test gold standard such enzyme immuno assay or multiplex beads assay as a gold standard. a. We agree with the reviewer. There was variability in test kits used by study sites over the testing period studied, therefore we could not obtain information on test kit performance/verification. The pitfalls of failure to use WHO prequalified kits is discussed on page 17 line 358-360 and in the limitations on page 19 line 410-412 2. Are remnants of the donors samples archived in these blood banks in order to provide answers to some of these questions? If yes, is recommended that you compare the serologically positive samples with the nucleic acid testing or at least EIA results. The sensitivity, specificity, positive predictive vale and the negative predictive value from the evaluation/ post market verification of these rapid test kits are quite essential to the reliability of this sero-prevalence data. a. Thank you for your suggestion. This will be a good next step for this study; therefore, a new proposal will be written for ethical approval to undertake such a study. For the current paper, we are unfortunately unable to perform this analysis as we do not have permission to obtain any archived samples from 2016-2021. 3. Does the record in the blood banks indicate the route of transmission of hepatitis C among the positive donors? This will help in prevention of Hepatitis C infection in Ghana. a. The records in the blood-bank made available to us did not contain routes of transmission among positive donors. We are currently conducting a study to investigate the risk factors associated with HCV seropositivity in Ghana. Reviewer #2: 1. As a Medical Laboratory Scientist , I enjoyed every bit of the article. The research methodology and data analysis was brilliant. But I beg different will that 17% data available would not be able to give a good representation of the prevalence of HCV infection in Northern Ghana. It is a brilliant idea, I hope this findings from this research is submitted to relevant stakeholders to help formulate policies that build a good disease surveillance for JCV infection in Ghana a. Thank you for your review and contribution. Reviewer #3: 1. It will be of great benefit to the manuscript/audience if the authors could provide information on any HCV-related intervention or policies the Ghana health services have introduced during the study period. With an elimination target in view, I believe every country would have initiated some action/intervention. The data presented suggest an increase in HCV infections – this could result from no intervention being conducted or interventions not doing what they are intended to. We can only arrive at such a conclusion if we have an idea of what interventions have been put in place. a. Thank you for your suggestion. The authors are not aware of a specific HCV intervention undertaken during the study period. Information regarding a 2023 HCV-specific intervention by the Ghana Health Service has been included on page 18 lines 389-394. 2. To estimate prevalence, the authors rely on serological data. However, the authors also mentioned access to molecular data although on a small scale at 1-2 health facilities. Was this molecular data included in estimating the seroprevalence or most of these individuals with molecular test results were initially tested with a serological test? The authors should provide information on how the molecular test results were processed. a. We stated that “PCR testing for HCV RNA was only available in two centres visited, with one of these outsourcing to a private laboratory.” In both centers, this test had only become available a few months before the data collection period and even then, availability was dependent on whether there were cartridges to run the sample. There were only a handful of results available, which were too few to use for data analysis (fewer than 10 at the time of data collection). We therefore opted to use only seroprevalence data for this study. For individuals with molecular tests, it could not be ascertained whether the serological test was conducted within the same facility or upon request from a referral facility. 3. The study authors need to revise and standardize some minor aspects of the manuscript. For example, Materials and Method section (abstract) On page 5 line 108 the authors mentioned that the study was conducted in public health institutions (that could be interpreted as government-run facilities) but on page 6 lines 113 – 118, the private and faith-based health facilities were included in the review. a. The following institutions were stated: “Ghana Health Service hospitals, teaching hospitals, public health reference labs and faith-based institutions”. These facilities visited all fell under the public health space and not the private sector. No private institution was visited for data collection. Furthermore, were the 16 admin regions grouped into 3 zones (northern, middle, and southern) from which the health facilities were selected. If yes, could the authors rephrase this section to better highlight what was done? Could the authors also provide information on the final number of facilities reviewed per zone? a. We have rephrased the section as suggested (page 6 lines 115-120). The information on final number per zone has been updated in the results section on page 8 lines 164-165 In the Method section (~ 6 per zone = 18 but in the results section, the authors mentioned 23 health facilities. What of the blood banks) a. A purposive sampling approach was used to select at least 2 two regional hospitals, 2 district hospitals, 1 faith-based hospital and 1 public health reference laboratory, - this makes up 6 per zone totaling 18 sites. Additionally, we gathered data from, “...all teaching hospitals located within each zone”. There are 5 teaching hospitals in the country, making up 23 health facilities as stated in the results. Out of the 23 sites approached, laboratory data was available for 17 institutions and 13 blood banks. The section has been updated for clarity (page 6 lines 115-120) Interestingly, in the result sections the zones are not mentioned. So why did the authors adopt a zoning approach that was eventually not used? I will suggest the zoning aspect be deleted. It is of no significance. a. Zoning was purposively done to ensure that a range of public health facilities in each part of the country were included in data collection in order to have a dataset that spanned all areas of Ghana. b. Additionally, zoning helped to illustrate that the administrative regions in northern Ghana appeared to have a higher seroprevalence compared to the other two zones. Wording has been updated to reflect this on page 9, lines 192, 196, 287, 289. The discussion has previously discussed potential reasons for the difference in seroprevalence in Northern Ghana on page 14 lines 290-300. 4. As a study limitation, does the use of seroprevalence data overestimate the prevalence of HCV? Lines 73-78 as indicate a lower disease burden when viraemic data is considered. Seroprevalence data could reflect three possible scenarios 1) active infection 2) a resolved past infection and 3) a false positive. I will suggest the authors highlight this shortcoming in their analysis. a. This is well noted. The following has been added to the study limitations on page 19 lines 408-410 “Additionally, the use of seroprevalence data may overestimate the HCV prevalence, since anti-HCV positivity comprises those with active infection, resolved infection or a false positive test result.” 5. What is the added value of figure 3 that highlights cases < 18 years of age? The data presented by the authors suggest a higher burden as age increases. If a more granular analysis was required, the focus should have been on the elderly group. What do the authors wish to highlight in the <18 group that is more important for this group? a. We wish to highlight the HCV prevalence in the under 18 age-group since the WHO treatment guidelines were recently updated to include guidance on treating children with HCV infection. 6. Minor language corrections Introduction Line 78 page 4: modify “high burden of viremia.” to “high burden of viraemic persons” ; Introduction Line 91 page 5: modify “The challenges to HCV response” to “The challenges of achieving the HCV elimination targets” Methods section: Line 117 page 13 correct “refence” to “reference” laboratory Include a reference for the Agyeman and colleagues study mentioned in line 255. All the suggested modifications and corrections have been effected, thank you. 7. Discussion section: The statement of HCV knowledge among healthcare workers is at best speculative. If not supported by a reference. The statement should either be referenced or deleted if no reference is available. Lines 296-298 a. The following sentence has been deleted: “If the same is true, and HCV knowledge among healthcare workers in Ghana is insufficient, this may mean that healthcare workers may be less likely to screen, treat, or link HCV patients to appropriate care.” Attachments Attachment Submitted filename: Response to reviewers PLOS HCV 230523.docx https://doi.org/10.1371/journal.pone.0287580.r002
8 Jun 2023 Decision Letter - Olatunji Matthew Kolawole, Editor Hepatitis C virus seroprevalence, testing, and treatment capacity in public health facilities in Ghana, 2016 – 2021; A multi-centre cross-sectional study. PONE-D-23-08352R1 Dear Dr. Nartey, 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, Olatunji Matthew Kolawole, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0287580.r003
Formally Accepted
15 Jun 2023 Acceptance Letter - Olatunji Matthew Kolawole, Editor PONE-D-23-08352R1 Hepatitis C virus seroprevalence, testing, and treatment capacity in public health facilities in Ghana, 2016 – 2021; A multi-centre cross-sectional study. Dear Dr. Nartey: 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. Olatunji Matthew Kolawole Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0287580.r004

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