Bacterial aetiology, antimicrobial susceptibility patterns, and factors associated with urinary tract infection among under-five children at primary health facility, North-Western Tanzania

Roza Ernest; Nsiande Lema; Sued Yassin; Agricola Joachim; Mtebe Majigo

doi:10.1371/journal.pone.0303369

Peer Review History

Original SubmissionOctober 12, 2023
14 Nov 2023 Decision Letter - Mengistu Hailemariam Zenebe, Editor PONE-D-23-32229Etiologic Profile, Antimicrobial Susceptibility Patterns, and Factors Associated with Urinary Tract Infection among Under-five Children at Primary Health Facility, North-Western TanzaniaPLOS ONE Dear Dr. Ernest, 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 Dec 29 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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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 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: Thank you for inviting me to review a manuscript entitled “Etiologic Profile, Antimicrobial Susceptibility Patterns, and Factors Associated with Urinary Tract Infection among Under-five Children at Primary Health Facility, North-3Western Tanzania” Primarily, authors tried to determine culture confirmed UTI among febrile children at health care setting. They clearly presented justification to conduct the present study and they also discussed relevant literatures in similar topic both in the introduction and discussion section of the manuscript. To complement the manuscript, I listed my comments below Major comments 1. I am not sure how UTI often leads to septicemia, dehydration. Sometimes from kidney infection bacteria may have chance to enter blood stream and cause bacteremia. Line #47-48 “Urinary tract infection (UTI) is common in under-five children presenting with fever with significant consequences leading to septicemia, dehydration, kidney scarring…” 2. I suggest authors to describe the source and study population including Eligibility criteria for selection of the study participants. In this study it was mentioned that under five children with fever who visited the health care setting. Fever can indicate server condition (Acute febrile illness). Were there any additional criteria to select? What other laboratory tests were performed? Were infant included? 3. Was there multiple infections? 4. The description of AST in the manuscript may need revision example ‘highly susceptible’ as far as I know interpretation of AST result is Resistant, Intermediate or susceptible based on cut point. “E. coli were highly susceptible to cefepime” 5. Was the tool (questionnaire) used in the study validate? Briefly describe 6. It was indicated that the urine specimens were stored at 4oC until they tested. For how long were they stored? How far regional lab is from the hospital where study participants were recruited. The integrity of the specimen is key for recovery of bacteria. 7. Describe how antibiotics used in the study were selected 8. Did authors use only CLED for identification of Gram-positive and Gram-negative bacteria? How S. aureus and Micrococcus was differentiated? Overall the types of culture media used for AST were not indicated. 9. As the definition of multi-drug resistance may vary it advisable to include operational definition for Multi-drug resistance. 10. The sample size for was not indicted in the main method section. 11. Consider including 95% CI for culture confirmed UTI. 12. Figure 1, Y-axis is not labeled. Also include frequency and % on the top of each bar 13. It is difficult to understand the results presented in Table 3. Consider including R, I, and S Minor comments 1. Line# 135 “…..Identify…..’ the first letter should not be capital 2. ‘Gram-positive’ and ‘gram-positive’ is interchangeably used. It is good to stick to one. ‘Gram’ or ‘gram’ Reviewer #2: Look at the comments on the sticky note on the PDF. Modify all the comments and justify for not accepted comments. I hope the manuscript would improve a lot if the comments addressed properly. The manuscript has some important data but also miss leads the readers unless otherwise properly reviewed and edited. ****** 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: Yes: Tsegeye Alemayehu ******** [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. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. Attachments Attachment Submitted filename: UTI-commented.pdf https://doi.org/10.1371/journal.pone.0303369.r001
Revision 1
17 Jan 2024 Author Response Editor’s comments When submitting your revision, we need you to address these additional requirements. 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 Response: We have tried our best to write the manuscript following PLOS ONE’s style 2. We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can help you do this, you may wish to consider employing a professional scientific editing service. Whilst you may use any professional scientific editing service of your choice, PLOS has partnered with both American Journal Experts (AJE) and Editage to provide discounted services to PLOS authors. Both organizations have experience helping authors meet PLOS guidelines and can provide language editing, translation, manuscript formatting, and figure formatting to ensure your manuscript meets our submission guidelines. To take advantage of our partnership with AJE, visit the AJE website (http://learn.aje.com/plos/) for a 15% discount off AJE services. To take advantage of our partnership with Editage, visit the Editage website (www.editage.com) and enter referral code PLOSEDIT for a 15% discount off Editage services. If the PLOS editorial team finds any language issues in text that either AJE or Editage has edited, the service provider will re-edit the text for free. Upon resubmission, please provide the following: The name of the colleague or the details of the professional service that edited your manuscript. A copy of your manuscript showing your changes by either highlighting them or using track changes (uploaded as a supporting information file). A clean copy of the edited manuscript (uploaded as the new manuscript file)” Response: The manuscript has been thoroughly checked for language usage, spelling and grammar using Grammarly Premium 3. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability. Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized. Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access. We will update your Data Availability statement to reflect the information you provide in your cover letter. Response: The study’s minimal underlying data set has been uploaded as a Supporting Information files 4. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. Response: The study’s minimal underlying data set has been uploaded as a Supporting Information files 5. Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well. Response: The study obtained ethical clearance number MUHAS-REC-12-2022-1484 from the Muhimbili University of Health and Allied Sciences Senate Research and Publication Committee. This has been addressed in lines 228 to 230. Comments from reviewer 1 1.I am not sure how UTI often leads to septicemia, dehydration. Sometimes from kidney infection bacteria may have chance to enter blood stream and cause bacteremia. Line #47-48 “Urinary tract infection (UTI) is common in under-five children presenting with fever with significant consequences leading to septicemia, dehydration, kidney scarring” Response: The sentence has been revised in line 55 of the introduction section. 2. I suggest authors to describe the source and study population including Eligibility criteria for selection of the study participants. In this study it was mentioned that under five children with fever who visited the health care setting. Fever can indicate server condition (Acute febrile illness). Were there any additional criteria to select? What other laboratory tests were performed? Were infant included? Response: We involved children aged 2 months and above who met the inclusion criteria. We have to revise and write: We recruited children with fever who the attending clinician suspected to have UTI based on signs and symptoms such as fever of 38oC or above, pain or burning when urinating, frequency urination, discoloured urine, lower abdominal pain, or vomiting.. The eligibility criteria have been added; line 106 to 111 3. Was there multiple infections? Response: No multiple infection was obtained with significant growth of bacteria counts of �10⁵ CFU/ml. We have rephrased the result section to reflect this finding line 275 to 276. 4. The description of AST in the manuscript may need revision example ‘highly susceptible’ as far as I know interpretation of AST result is Resistant, Intermediate or susceptible based on cut point. “E. coli were highly susceptible to cefepime” Response: This has been addressed in table 4 of the manuscript, interpretation of AST which includes resistant, intermediate and sensitive were added in the table. 5. Was the tool (questionnaire) used in the study validate? Briefly describe Response: Yes, the questionnaire used for data collection was validated, and this is explained in the data collection section, line 124. 6. It was indicated that the urine specimens were stored at 4oC until they tested. For how long were they stored? How far regional lab is from the hospital where study participants were recruited. The integrity of the specimen is key for recovery of bacteria. Response: Samples were stored in the refrigerator for not more than 12 hours; we have indicated this in the sample collection section line 141. 7. Describe how antibiotics used in the study were selected Response: Descriptions on how antibiotics used in the study were selected has been added in line 174 to 175. 8. Did authors use only CLED for identification of Gram-positive and Gram-negative bacteria? How S. aureus and Micrococcus was differentiated? Overall, the types of culture media used for AST were not indicated. Response: We differentiated Staphylococcus aureus from Micrococcus species by observing colony characteristics and performing a gram stain. The type of culture used for AST has been indicated in lines 175-177 9. As the definition of multi-drug resistance may vary it advisable to include operational definition for multi-drug resistance. Response: We have added in the materials and methods a subsection of the definition of terms. The definition of multi-drug resistance has been included in lines 143-153 10. The sample size for was not indicted in the main method section. Response: The sample has been indicated in methodology line 114 11. Consider including 95% CI for culture confirmed UTI. Response: 95% CI has been added to the culture confirmed UTI in the abstract, results and discussion sections 12. Figure 1, Y-axis is not labelled. Also include frequency and % on the top of each bar Response: Figure one was changed to a table 2 which indicates frequency and percentage 13. It is difficult to understand the results presented in Table 3. Consider including R, I, and S Response: Table 3 has been revised for clarity and changed to table 4 since we added another table Minor comments 1. Line# 135 “…..Identify…..’ the first letter should not be capital 2. ‘Gram-positive’ and ‘gram-positive’ is interchangeably used. It is good to stick to one. ‘Gram’ or ‘gram’ Response: The first letter of "identify" has been written in lowercase. "Gram positive" and "gram positive" have been revised to "gram positive." However, when starting a sentence, "Gram" is written with a capital letter Comments from Review 2 Comments for Reviewer #2 were on the sticky note on the PDF file. We have addressed all comments and modified the manuscripts In title you said etiological profile, is it include fungi? Response: The title has been revised to reflect the bacterial etiology; line 1 Abstrct background:Where UTI is common infection?. Avoid use of short form in abstract. Better to be consistence as per title or should modify the title accordingly. Foristance febrile underfive,antibiotic vs antimicrobial,proportion of UTI vs etiology profile Response: We rephrased the sentences for clarity and to ensure consistency, and short-form words were omitted; lines 17-23 Abstract methodology: Why only febrile? Is fever the only criteria to be suspected as UTI for under five? Operationalize this. The method is not written well, rewrite again Response: The materials and methods subsection in the abstract has been rewritten for clarity; Lines 25-32 Abstract results : rewrite the result very well. Like of all 28.8% had Lab, confirmed means? do you mean culture confirmed? write the organism name in italic. Is circumcision a common practice for both male and female or for only for male? is those for female taken as nor not applicable? Rewrite bacteria in italic. Is suceptibility pattern for overall? or E.. coli & S. aurues Response: The result subsection of the abstract has been rewritten for clarity. Bacteria have been written in italics; the susceptibility patterns are for E.coli and S. aureus; Lines 34-43 Introduction Add One paragraph for common cause of UTI from different literature. Response: A paragraph detailing the common causes of UTI has been included; Line 62-69 what does the renal functions of the kidney mean? Response: The sentence has been revised to reflex that, Early diagnosis is essential to preserve and maintain the proper functioning of the kidneys and prevent any further decline in their function. Line 56-57 uncircumcision in male? Response: Yes uncircumcission in male, The sentence has been paraphrased; Line 43&73 The prevalence of UTI among under-five children ranges from 7.4 % to 43.6% where this studies conducted Response: The reported prevalence was indicated from Nigeria and Tanzania; Line 59-60 The risk factors for acquiring UTI in under-five children are multiple and differ with geographical locations, settings, and seasons. Add reference Response: Reference number 9 has been added; Line 71 Antimicrobial resistance (AMR) has become significant concern worldwide.add reference Response: Reference number 14 was added; Line 77 Can you generalize with your specific hospital data about the treatment? or can leads you to change treatment guidelines? Response: The sentence has been ommited, since the same information were discussed in line 89-94 Materials and methods Line 91, Can you clarify on primary health care and district hospital? in your title it says primary health care whereas the study is conducted in district hospital? Besides this your study area description don't indicate as whether it is urban or rural but in reasoning or gab analysis your said that rural community lacks attention? Response: Yes, in Tanzania, a district hospital is considered a primary healthcare facility. The Magu district, where our research was conducted, is situated in the rural parts of the region. However, when classifying the demographic data, we categorized urban as individuals from the town area of Magu, and rural as those from other areas outside the town; Line 103 why only children with fever? Response: Fever is a common symptom of various illnesses, the aim of recruiting children with fever ensured that,study participants have a higher likelihood of having the targeted condition; Line 106-109 The total sample size should be indicated here. Response: The total sample size was indicated; Line 114 In Data collection your sociodemographic is limited why? Response: The scope and objectives of this study prioritized these sociodemographic variables; Line 121 Is Sekou Toure Regional Referral Hospital different from above hospital? Response: Yes, the study was conducted at Magu District Hospital. However, the samples were analyzed at Sekou Toure Regional Referral Hospital since the District hospital lacked the capacity to process culture samples Line 131- 132, write more how do you handle in case of mixed growth Response: Handling of mixed growth of bacteria has been indicated; Line 161-162 Line 135, Identify should start with small letter Response: The word Identify written starting with small letter Line 165 is this the only biochemical test? how do you identify like P. aerigenosa & Acitenobacter spp Response: Oxidase test used to identify P. aerigenosa & Acitenobacter spp has been added Line 168-169 Antimicrobial susceptibility testing: Can we report erthromycin for organisms from UTI? this shows you haven't followed the CLSI properly. Response: Erthromycin disk has been removed from this manuscript Extended-Spectrum Beta-Lactamase Detection: Is this for the three or for one? if for one you have write cefotaxime or cftriaxone or ceftazidime. is the increase of zone of inhibition towards CAZ or CXT or both? Response: The sentence has been rephrased Line 192-193, 199-201 Quality assurance: As indicated in the quideline, on which guidelines? Response: The sentence” as indicated in the quideline was ommited since checking expiration date and assess reagents does not need any guideline. Data analysis: ≤ 0.2, this cut of value most of the time is 0.25. Do you have some justification for it? Response: The choice of a cut-off value in data analysis can depend on the specific field of study, the nature of the data, and the research question being addressed, This Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0303369.r002
21 Feb 2024 Decision Letter - Mengistu Hailemariam Zenebe, Editor PONE-D-23-32229R1Bacterial etiologic Profile, Antimicrobial Susceptibility Patterns, and Factors Associated with Urinary Tract Infection among Under-five Children at Primary Health Facility, North-Western TanzaniaPLOS ONE Dear Dr. Ernest, 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. ==============================Dear Author, I have seen that you have made a major correction and your reviewers have some more correction on it. could you adjust it as needed? ============================== Please submit your revised manuscript by Apr 05 2024 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. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Mengistu Hailemariam Zenebe, PhD Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [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 Reviewer #2: 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 Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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: Yes Reviewer #2: Yes ****** 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 Reviewer #2: 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: Thank you for addressing most of my comments. Comment 8 was not fully addressed I don’t think morphology and gram staining is sufficient to differentiate Staphylococcus aureus from Micrococcus you may indicate this in limitations. Reviewer #2: Hi, dear authors! You did a very good job of responding to the comments, and the response is fascinating. However, the manuscript still requires work in a few areas, primarily related to the discussion. Please refer to the sticky note in the PDF file that is attached. I do have a concern about some variables and associated factors, and before making a decision, these things should be resolved. ****** 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: Musa Ali Reviewer #2: Yes: Tsegaye Alemayehu ******** [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. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. Attachments Attachment Submitted filename: UTI second comment.pdf https://doi.org/10.1371/journal.pone.0303369.r003
Revision 2
10 Apr 2024 Author Response POINT TO POINT RESPONSE TO EDITOR AND REVIEWERS’ COMMENTS Editor’s comments Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Response: All references have been reviewed and errors corrected Comments from Reviewer #1 Thank you for addressing most of my comments. Comment 8 was not fully addressed I don’t think morphology and gram staining is sufficient to differentiate Staphylococcus aureus from Micrococcus you may indicate this in limitations. Response: Thank you for the comment. We have rephrased the paragraph related to previous comment 8 to indicate that We differentiated S. aureus from other Staphylococcus and Micrococcus species by coagulase tests. Line 164-165 Comments from Review # 2 Comments from Reviewer #2 were on the sticky note on the PDF file. We have extracted the comments from the PDF file and addressed all of them as follows: 1. Materials and methods in the abstract: i. Method only; remove material ii. Bring “District Hospital in Mwanza Region, North-Western Tanzania, between March and April 2023 to the objective to make it SMART and remove from the material and methods. iii. Still, the statistical analysis is not clearly written. OR, and CI, cut of a p-value. Response: We have addressed the comments related to the materials and methods in the abstract section as suggested. Line 23-30 2. Results in the abstract: i. Make the urinary tract infections culture-confirmed ii. Multidrug resistance was observed in 33.0% of isolates, Methicillin Staphylococcus aureus in 23.1% of Staphylococcus aureus, and extended-spectrum beta-lactamases in 25% of gram-negative bacteria. Make this in separate sentences as they are different, and the sentence does not make sense. Response: we have revised to indicate culture-confirmed urinary tract infection and separated the sentences as indicated for clarity. line 33-40 iii. Urinary tract infection was associated with vomiting, age, dysuria, abdominal pain, nappy use, and uncircumcision in males. Should be indicated which category associated with UTI, age, for instance, which range?, vomiting presence or absence, abdominal pain presence or absence similarly in conclusion. Response: We have revised the sentence in the abstract result section to clearly indicate the categories associated with UTI. Line 39-40 3. Conclusion in abstract what are commonly prescibed antibioitcs? Is your recomendation only the suspetibitly pattern? What about prevention and control based on your findings from associated factors? Response: The conclusion has been revised to include the list of common antibiotics and recommendations regarding associated factors. Line 41-45 4. Keywords: Add some words like ethiology agent, associated factros. Response: We have added the words aetiologic agent and associated factors to the list of keywords. Line 49 5. Use a square bracket for all references. Response: We have used square brackets for all references 6. Studies conducted in Nigeria and Tanzania have reported the prevalence of UTI in under-five children ranging from 7.4% to 43.6% (1,4,5). Better use some national data or meta-analysis data from Africa or WHO report. why you focused on Nigeria and Tanzania? Response: We have included reference # 4 with a systematic review and meta-analysis data. Line 57 7. First time, write long and short forms and use short forms throughout the document. Response: The comment has been accepted and addressed in the entire manuscript 8. In the study design, setting, and population, the study involved under-five children with a fever seeking healthcare services. Do you think all UTI patients presented with fever? What is the standard for under-five children to be suspected of UTI? Unless otherwise, this leads to a selection bias. Response: We have revised the paragraph for clarity. Line 101 - 104 9. We recruited children with fever who the attending clinician suspected to have UTI based on signs and symptoms such as fever of 38 degrees Celsius or above, pain or burning when urinating, frequent urination, discoloured urine, lower abdominal pain, or vomiting. this contradict with the above sentence. Response: As per the response to comment # 8 above, we have revised the paragraph for clarity and to avoid contraction. Line 101-104 10. The study did not include children who used catheters within 72 hours because catheter insertion may directly inoculate microorganisms into the urinary bladder. reference is needed which stanard recomend this? Response: We have added reference # 23 which indicates the effect of catheterization on UTI. Line 106 11. Risk factors: do you think nappy use works for all? Response: Nappy use as a risk factor for UTI may not work for all but has been indicated as a factor in other study 12. Definition of terms: Make in bullect with bold for the title. also include for UTI. Response: We have written the sentence in the definition of terms as suggested and included the definition of UTI. Line 137-147 13. Do you collect all the specimens with midstream? What about for catheters? Response: For the purpose of this study, we instructed parents and guardians to collect midstream urine. We did not use a catheter for urine collection. 14. In Table 1: Frequency and percentage of participants calculated as number within the variable category divided by the total sample size of the variable, * proportion of patients within the variable category with no Urinary Tract Infection calculated as number of divided by the total number of individuals in the variable category. *** proportion of patients within the variable category with Urinary Tract Infection calculated as number of cases divided by the total number of individuals in the variable category. I don't think this is important, remove from table to . Response: The table legend has been removed as suggested. Line 260 15. In Table 4, Morganella spp. You said M. morgannii in the above makes it uniform. Response: We have changed to M. morganii for uniformity. Line 312 16. In table 4: Give the title keynote: NIT= Nutrofurantion; it is better to use NIT-Nutrofurantion. Response: The Table 4 legend has been corrected as suggested. Line 313-315 17. Discussion: use the figure and country; double referencing is not important. similarly correct for others. all prevalence figures from another study should be included in all the discussion. Unless otherwise it is difficult to now whether higher, lower or inline. Response: The discussion section has been re-worked to address the comment accordingly Attachments Attachment Submitted filename: Response to Reviewers Comments.docx* https://doi.org/10.1371/journal.pone.0303369.r004
12 Apr 2024 Decision Letter - Mengistu Hailemariam Zenebe, Editor Bacterial aetiology, Antimicrobial Susceptibility Patterns, and Factors Associated with Urinary Tract Infection among Under-five Children at Primary Health Facility, North-Western Tanzania PONE-D-23-32229R2 Dear Dr. Ernest, 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. If you have any questions relating to publication charges, 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, Mengistu Hailemariam Zenebe, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0303369.r005

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