Chronic inflammation was a major predictor and determinant factor of anemia in lactating women in Sidama zone southern Ethiopia: A cross-sectional study

Tafere Gebreegziabher; Taylor Roice; Barbara J. Stoecker

doi:10.1371/journal.pone.0240254

Peer Review History

Original SubmissionJune 26, 2020
1 Sep 2020 Decision Letter - Gary Kupfer, Editor PONE-D-20-19809 Chronic inflammation was a major predictor and determinant factor of anemia in lactating women in Sidama zone southern Ethiopia: a cross-sectional study PLOS ONE Dear Dr. Gegreegziabher, 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 September 29. 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 funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." We note that you received funding from a commercial source: Nestle. Please provide an amended Competing Interests Statement that explicitly states this commercial funder, along with any other relevant declarations relating to employment, consultancy, patents, products in development, marketed products, etc. Within this Competing Interests Statement, please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. 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Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests [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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes 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 main claims for this paper are that anemia in the geographic area of study is associated with AGP, a marker of chronic inflammation, and the authors propose that this chronic inflammation is from infection from malaria/parasites. The authors analyzed the data in such a way to suggest that chronic inflammation is a top factor in patients having anemia which seems to be the novel contribution of this manuscript. The authors suggest that interventions to decrease anemia might need to include treating infection before nutrition supplementation to decrease this chronic inflammation. - Previous literature (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767796/) has described the association between malaria with anemia and laboratory markers of inflammation, but this previous literature has not performed the type of analysis performed in this paper providing some possible ranking on the contribution of various factors to anemia in areas with high rates of malaria. The novel information provided by this paper seems to be that chronic inflammation plays a leading role in anemia in this geographic area with high rates of malaria. On one hand this could be practical/impactful information to guide policy on how to improve anemia in malaria infected areas by focusing first on treating the chronic inflammation by treating the malaria. On the other hand, there already is data to suggest that iron supplementation in endemic areas for malaria could prove harmful (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124144/#B116) which would seem to suggest that treating malaria should be done before supplementing with iron, which is the same policy message suggested by the authors of this paper. - The authors should consider placing their study results in the context of the literature describing the interplay between anemia and malaria and inflammation (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124144/#B116, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124144/#B116) to give more context of how their finding of inflammatory markers with chronic inflammation playing a large role in anemia fits in with the context of past data showing that supplementation with iron in malaria endemic areas could be harmful. - The authors do a good job of not overstating their claims based on their data analysis, by only mildly suggesting that infection should be treated before nutritional supplementation for anemia. - Can the authors provide specific data on the proportion of patients with anemia who also have markers of chronic inflammation? Reviewer #2: The manuscript by Gebreegziabher purports to analyze anemia in Ethiopian women and factors promoting the disease state. Focus was on lactating women in areas prone to infection, esp malaria. Surprisingly, the fraction of cases of anemia attributable to iron deficiency in isolation was small, and the authors ascribe a large percentage to chronic inflammation. The documentation and correlation of low fraction of iron def and high degree of chronic inflammation is interesting and helpful in the way public health authorities may think about health in underserved communities. The paper would be helped by a more careful English edit Are the authors able to report B12, folate? ****** 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 [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. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. 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Revision 1
14 Sep 2020 Author Response 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf - Formatted according to PLOS ONE style 2. In your Methods section, please provide additional information about the participant recruitment method and the demographic details of your participants. Please ensure you have provided sufficient details to replicate the analyses such as: a) the recruitment date range (month and year), b) a description of any inclusion/exclusion criteria that were applied to participant recruitment, c) a table of relevant demographic details, d) a statement as to whether your sample can be considered representative of a larger population, e) a description of how participants were recruited, and f) descriptions of where participants were recruited and where the research took place. Moreover, please clarify how the wealth index was calculated. a) The recruitment date range June to August, 2013 in line 98. b) Inclusion criteria were included in lines 99 – 101. Eligibility criteria were: the woman must be 18 years of age or older, must be lactating six months after delivery and must have no history of illness. c) Demographic characteristics (age, household size and number of children) are included to table 1. d) A statement included in line 101 – 102. Because all women agreed to join the study, we consider the study representative of the rural Sidama population. e) A description of where participants were recruited were given in line 97 – 98 and 102 – 103. We conducted a cross-sectional study of lactating Ethiopian women from eight randomly selected rural villages in Sidama zone, southern Ethiopia. Women came to their local community health post for the data collections. f) A description of where the research took place was given on line number 97 - 98. Please refer to ‘e’ above. - A statement on how wealth index was calculated was given on line number 120 – 121. Principal component analysis (PCA) was applied to compute wealth index, and the score was used to divide the participants into five quintiles. 3. Please correct your reference to "p=0.000" to "p<0.001" or as similarly appropriate, as p values cannot equal zero. - “p = 0.000 is changed to p < 0.001” 4. Thank you for stating the following in the Financial Disclosure section: "The research was funded by the USDA Multistate Project, W-3002 to BJS; Nestlé Foundation to TG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." We note that you received funding from a commercial source: Nestle. Please provide an amended Competing Interests Statement that explicitly states this commercial funder, along with any other relevant declarations relating to employment, consultancy, patents, products in development, marketed products, etc. Within this Competing Interests Statement, please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. Please include your amended Competing Interests Statement within your cover letter. We will change the online submission form on your behalf. Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests Thank you for the comment. Nestlé Foundation is not a commercial organization. Please see the link for Nestlé Foundation http://www.nestlefoundation.org/e/ The Nestle Foundation has a review board of esteemed scientists and has a history of supporting nutrition projects in developing countries. 5. Review Comments to the Author Reviewer #1: - The main claims for this paper are that anemia in the geographic area of study is associated with AGP, a marker of chronic inflammation, and the authors propose that this chronic inflammation is from infection from malaria/parasites. The authors analyzed the data in such a way to suggest that chronic inflammation is a top factor in patients having anemia which seems to be the novel contribution of this manuscript. The authors suggest that interventions to decrease anemia might need to include treating infection before nutrition supplementation to decrease this chronic inflammation. - Previous literature (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767796/) has described the association between malaria with anemia and laboratory markers of inflammation, but this previous literature has not performed the type of analysis performed in this paper providing some possible ranking on the contribution of various factors to anemia in areas with high rates of malaria. The novel information provided by this paper seems to be that chronic inflammation plays a leading role in anemia in this geographic area with high rates of malaria. On one hand this could be practical/impactful information to guide policy on how to improve anemia in malaria infected areas by focusing first on treating the chronic inflammation by treating the malaria. On the other hand, there already is data to suggest that iron supplementation in endemic areas for malaria could prove harmful (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124144/#B116) which would seem to suggest that treating malaria should be done before supplementing with iron, which is the same policy message suggested by the authors of this paper. - The authors should consider placing their study results in the context of the literature describing the interplay between anemia and malaria and inflammation (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124144/#B116, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124144/#B116) to give more context of how their finding of inflammatory markers with chronic inflammation playing a large role in anemia fits in with the context of past data showing that supplementation with iron in malaria endemic areas could be harmful. - Reference included (Reference no.38) - The authors do a good job of not overstating their claims based on their data analysis, by only mildly suggesting that infection should be treated before nutritional supplementation for anemia. - Thank you for the comment - Can the authors provide specific data on the proportion of patients with anemia who also have markers of chronic inflammation? - Based on your suggestion we have included the following sentence in the discussion line 276. ‘12 women who were anemic had high AGP or CRP. Reviewer #2: The manuscript by Gebreegziabher purports to analyze anemia in Ethiopian women and factors promoting the disease state. Focus was on lactating women in areas prone to infection, esp malaria. Surprisingly, the fraction of cases of anemia attributable to iron deficiency in isolation was small, and the authors ascribe a large percentage to chronic inflammation. The documentation and correlation of low fraction of iron def and high degree of chronic inflammation is interesting and helpful in the way public health authorities may think about health in underserved communities. The paper would be helped by a more careful English edit Are the authors able to report B12, folate? -The English has been carefully edited. -Thank you for the comment. We did not analyzed B12 and folate. Attachments Attachment Submitted filename: Answer to reviewers.docx https://doi.org/10.1371/journal.pone.0240254.r002
23 Sep 2020 Decision Letter - Gary Kupfer, Editor Chronic inflammation was a major predictor and determinant factor of anemia in lactating women in Sidama zone southern Ethiopia: a cross-sectional study PONE-D-20-19809R1 Dear Dr. Gebreegziabher, 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, Gary Kupfer Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0240254.r003
Formally Accepted
25 Sep 2020 Acceptance Letter - Gary Kupfer, Editor PONE-D-20-19809R1 Chronic inflammation was a major predictor and determinant factor of anemia in lactating women in Sidama zone southern Ethiopia: a cross-sectional study Dear Dr. Gebreegziabher: 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 Gary Kupfer Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0240254.r004

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