Enterovirus 71 seroepidemiology in Taiwan in 2017 and comparison of those rates in 1997, 1999 and 2007

Jian-Te Lee; Ting-Yu Yen; Wei-Liang Shih; Chun-Yi Lu; Ding-Ping Liu; Yi-Chuan Huang; Luan-Yin Chang; Li-Min Huang; Tzou-Yien Lin

doi:10.1371/journal.pone.0224110

Peer Review History

Original SubmissionAugust 13, 2019
10 Sep 2019 Decision Letter - Dong-Yan Jin, Editor [EXSCINDED] PONE-D-19-22806 Enterovirus 71 Seroepidemiology in Taiwan in 2017 and comparison of those rates in 1997, 1999 and 2007 PLOS ONE Dear Prof. Chang, Thank you for submitting your manuscript to PLOS ONE. Your manuscript has been reviewed by two experts in the field and their comments follow. While both are supportive, they have also raised concerns that you should address in a revised manuscript. After careful consideration, we feel that your paper has merit and we invite you to submit a revised version of the manuscript. We would appreciate receiving your revised manuscript by Oct 25 2019 11:59PM. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. 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Additionally, please address the following: - whether a prior sample size calculation was carried out for this study - the rationale for the lack of multiple test correction in your statistical analysis - ensure you include details concerning the pretesting of your questionnaire included in this study and also a copy of it Additional Editor Comments: Please respond to reviewers' comments and provide the requested information if available. [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: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: 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: 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: The manuscript “Enterovirus 71 Seroepidemiology in Taiwan in 2017 and comparison of those rates in 1997, 1999 and 2007” provided an updated serostatus of EV71 in different region of Taiwan. This is a timely study as the threat of enterovirus infection continuously posing significant concern worldwide. Below are my comments for improvement. 1) Is there any patient data co-relating with the seropositive specimen? For example, successful rate of detecting viral RNAs/antigens in specimens of seropositive patients; the history of seropositive patients with enterovirus-related syndromes. 2) The authors suggested that female gender could be a risk factor of EV71 seropositivity. The comparison appears to be based on the absolute number of seropositivity in between male and female. The comparison may be subjected to the biases due to disproportion of male:female ratio within the community. The authors may need to consider this point and perform normalization accordingly. 3) The number of tested specimen (n) needs to be indicated in table 3. 4) The authors suggested the lower EV71 seropositivity detected in specimen of 2007 and 2017 could be due to the absence of disease outbreak. Does the high seropositivity detected in other countries, for example, Cambodia (Table 3), correlate to an EV71 outbreak? 5) Figure 2 showed similar but delayed trend of EV71 seropositivity between specimens obtained from 1997 and 1999 to 2007 and 2017. For example, an age 1 EV71 seropositive specimen detected in 1999 will become an age 8 EV71 seropositive specimen detected in 2007. In other words, the delay could be an indication of effective infectious disease control. The authors should discuss what infectious disease control policy may have been implemented during this period of time. When comparing with data from other countries, which ways do Taiwan do better or worse? Reviewer #2: Comments to the Author The manuscript aims to explore the EV71 serostatus in Taiwan. The authors made efforts to test the EV71 neutralizing antibody with serum samples and compared EV71 serostatus among 1997, 1999, 2007 and 2017. They illustrated that the EV71 seropositive rates in children were significantly lower in 2017, compared with the rates in 1997, 1999 and 2008. These results prompt the necessity of continuous surveillance for the prevention and control of the disease infected with EV71. The main limitations of the manuscript are listed below. 1. Did the questionnaire include the subjects' vaccination history? 2. As the authors indicated that the male-to-femal ratio of symptomatic and/or severe enterovirus infections shifted toward males in the discussion section. While the female gender was the risk factors associated with EV71 seropositivity in this study, and this conclusion was based the analysis of in preschool children in 2017. The risk factors could be analyzed including other ages. ****** 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. 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Revision 1
3 Oct 2019 Author Response Reviewers' comments: Comments to the Author Reviewer #1: The manuscript “Enterovirus 71 Seroepidemiology in Taiwan in 2017 and comparison of those rates in 1997, 1999 and 2007” provided an updated serostatus of EV71 in different region of Taiwan. This is a timely study as the threat of enterovirus infection continuously posing significant concern worldwide. Response: thank you very much for your comment and appreciation. Below are my comments for improvement. 1) Is there any patient data co-relating with the seropositive specimen? For example, successful rate of detecting viral RNAs/antigens in specimens of seropositive patients; the history of seropositive patients with enterovirus-related syndromes. Response: we did not have any data of detecting viral RNAs/antigens in specimens of seropositive patients, but we did have data on enterovirus-related ( HFMD or herpangina) history of seropositive children in Table 2. For example, 34% of seropositive preschool children had history of HFMD and 24% had history of herpangina (Table 2). 2) The authors suggested that female gender could be a risk factor of EV71 seropositivity. The comparison appears to be based on the absolute number of seropositivity in between male and female. The comparison may be subjected to the biases due to disproportion of male:female ratio within the community. The authors may need to consider this point and perform normalization accordingly. Response: we agree with this comment, so normalization was done for Figure 1 accordingly to minimize any disproportion of male:female ratio within the community. 3) The number of tested specimen (n) needs to be indicated in table 3. Response: Thank you very much for your suggestion and we added the numbers of seropositive and tested specimen in Table 3. However, only those numbers are not available in Cambodia and we can not add them. 4) The authors suggested the lower EV71 seropositivity detected in specimen of 2007 and 2017 could be due to the absence of disease outbreak. Does the high seropositivity detected in other countries, for example, Cambodia (Table 3), correlate to an EV71 outbreak? Response: We agree with your comment that the high seropositivity detected in other countries correlate to an EV71 outbreak. We mentioned it in the Discussion: Severe EV71 cases occurred more frequently in countries, such as China and Cambodia which had greater seropositive rates [7, 23, 31-33] and it indicates greater disease burden in these countries. EV71 outbreak occurred in Cambodia in 2012, it characterized by severe encephalitis with cardiovascular collapse and pulmonary edema seized international headlines and resulted in the death of at least 54 children [31], and more than 2 thousands of laboratory-confirmed EV71 cases died in China from 2008 to 2015 [7]. 5) Figure 2 showed similar but delayed trend of EV71 seropositivity between specimens obtained from 1997 and 1999 to 2007 and 2017. For example, an age 1 EV71 seropositive specimen detected in 1999 will become an age 8 EV71 seropositive specimen detected in 2007. In other words, the delay could be an indication of effective infectious disease control. The authors should discuss what infectious disease control policy may have been implemented during this period of time. When comparing with data from other countries, which ways do Taiwan do better or worse? Response: Thank you very much for your detailed review and suggestion. We described more infectious disease control policy in the Discussion to share our experience, which may be helpful to other countries. Reviewer #2: Comments to the Author The manuscript aims to explore the EV71 serostatus in Taiwan. The authors made efforts to test the EV71 neutralizing antibody with serum samples and compared EV71 serostatus among 1997, 1999, 2007 and 2017. They illustrated that the EV71 seropositive rates in children were significantly lower in 2017, compared with the rates in 1997, 1999 and 2008. These results prompt the necessity of continuous surveillance for the prevention and control of the disease infected with EV71. The main limitations of the manuscript are listed below. 1. Did the questionnaire include the subjects' vaccination history? Response: The questionnaire include the subjects' vaccination history. We deposited the questionnaires as supplementary files with Chinese-English parallel texts. We did not show it in the original manuscript since EV71 vaccine is not commercially available now in Taiwan and the current vaccination did not affect EV71 serostatus. We added it in the revised manuscript since you and the readers may be curious about it. 2. As the authors indicated that the male-to-female ratio of symptomatic and/or severe enterovirus infections shifted toward males in the discussion section. While the female gender was the risk factors associated with EV71 seropositivity in this study, and this conclusion was based the analysis of in preschool children in 2017. The risk factors could be analyzed including other ages. Response: Thank you very much for your suggestion. We analyzed the risk factors in the other age groups, which are shown in the text: For the 6 to 15 year-old children, no significant risk factors were found except older age. For 16-50-year-old people, the significant risk factor associated with EV71 seropositivity was having children in addition to older age: 61% of seropositive 16-50-year-old people had children in their families but only 27% of seronegative 16-50-year-old people had children in their families (p<0.001). Therefore, we did not find gender difference in the other age groups. Attachments Attachment Submitted filename: Response to Reviewers comment.docx https://doi.org/10.1371/journal.pone.0224110.r002
7 Oct 2019 Decision Letter - Dong-Yan Jin, Editor Enterovirus 71 Seroepidemiology in Taiwan in 2017 and comparison of those rates in 1997, 1999 and 2007 PONE-D-19-22806R1 Dear Dr. Chang, Thank you for submitting your revised manuscript. I have read it through carefully together with your response to reviewers' comments. I am fully satisfied with the modifications you made. We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication. Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. 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 enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and 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. With kind regards, Dong-Yan Jin Academic Editor PLOS ONE Reviewers' comments: https://doi.org/10.1371/journal.pone.0224110.r003
Formally Accepted
9 Oct 2019 Acceptance Letter - Dong-Yan Jin, Editor PONE-D-19-22806R1 Enterovirus 71 Seroepidemiology in Taiwan in 2017 and comparison of those rates in 1997, 1999 and 2007 Dear Dr. Chang: I am 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 notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, 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. For any other questions or concerns, please email plosone@plos.org. Thank you for submitting your work to PLOS ONE. With kind regards, PLOS ONE Editorial Office Staff on behalf of Prof. Dong-Yan Jin Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0224110.r004

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