{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:19:52Z","timestamp":1789604392151,"version":"build-2803163510"},"update-to":[{"DOI":"10.12688\/f1000research.150743.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000}},{"DOI":"10.12688\/f1000research.150743.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000}}],"reference-count":19,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/igo\/"}],"funder":[{"name":"The Special Programme for Research and Training in Tropical Diseases (TDR), Geneva, Switzerland","award":["HQTDR 2422924-4.1-72863."],"award-info":[{"award-number":["HQTDR 2422924-4.1-72863."]}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<jats:p>Background\nLassa fever (LF) is an endemic and immediately notifiable disease in Liberia, and one laboratory confirmed case constitutes an outbreak. We described the epidemiological characteristics and hospital outcomes of LF cases hospitalized during the 2022-2023 outbreak in Liberia.\n\nMethods\nA retrospective cohort study was conducted using routine LF surveillance data from the 2022-2023 outbreak in Liberia. Descriptive statistics were used to summarize the data and log binomial regression to assess the association between epidemiological characteristics and mortality.\n\nResults\nA total of 439 suspected LF cases were reported. The median age was 22 (interquartile range (IQR): 10-33) years and 233 (53%) were females. The median number of days between symptom onset and admission was 4 (IQR 2-7). Of the 439 cases, 416 (95%) were tested for LF and 138 were confirmed with 33% positivity rate. The majority, 95 (69%), of confirmed cases were &lt;30 years, 78 (57%) were females, and 81 (59%) were reported during the dry season (October \u2013 March). Contact with rodents, 95 (69%), was the commonest mode of exposure. Fever, 128 (93%), malaise, 121 (88%), headache, 114 (83%) and myalgia, 114 (83%) were the most common clinical presentations. There were 83 (19%) deaths among hospitalized suspected LF cases - 42 deaths (15%) among 278 individuals who tested negative and 41 among confirmed cases with 30% case fatality rate (CFR). Presenting CFR per age group, age 40-49 years accounted for 8\/12 (67%) and those aged\u226550 reported 5\/8 (63%) of the deaths among the confirmed cases. There was no significant association between epidemiological characteristics and LF mortality.\n\nConclusions\nThe outbreak highlighted a high disease burden of LF with young adults disproportionately infected, and mortality, even among those who tested negative for the virus. This underscores the urgent need for preventive measures like vaccines and health education campaigns.<\/jats:p>","DOI":"10.12688\/f1000research.150743.3","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T08:35:08Z","timestamp":1764146108000},"update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Epidemiological characteristics and hospital outcomes of hospitalized Lassa fever cases during the 2022-2023 outbreak in Liberia"],"prefix":"10.12688","author":[{"given":"Emmanuel","family":"Dwalu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2025]]},"reference":[{"key":"ref1","first-page":"1","article-title":"Lassa fever in West African sub-region: an overview.","volume":"44","author":"O Ogbu","year":"2007","journal-title":"J. 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Dis."},{"key":"ref5","first-page":"1-9","article-title":"Infection pattern, case fatality rate and spread of Lassa virus in Nigeria.","volume":"21","author":"C Yaro","year":"2021 citat 13 juliol 2023","journal-title":"BMC Infect. Dis. BMC."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"767-774","DOI":"10.1016\/j.ijid.2022.07.006","article-title":"Epidemiological characteristics of Lassa fever cases in Liberia: a retrospective analysis of surveillance data, 2019-2020.","volume":"122","author":"R Jetoh","journal-title":"Int. J. Infect. Dis."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"466-473","DOI":"10.4269\/ajtmh.20-0487","article-title":"Lassa Fever: an evolving emergency in West Africa.","volume":"104","author":"O Balogun","year":"2020","journal-title":"Am. J. Trop. Med. 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J."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1026-1027","DOI":"10.3201\/eid2505.181247","article-title":"Increase in lassa fever cases in Nigeria, January\u2013March 2018.","volume":"25","author":"E Ilori","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"262-264","DOI":"10.2105\/AJPH.2017.304186","article-title":"Mortality among confirmed Lassa Fever cases during the 2015\u20132016 outbreak in Nigeria.","volume":"108","author":"M Buba","year":"2018","journal-title":"Am. J. Public Health."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e2748","DOI":"10.1371\/journal.pntd.0002748","article-title":"Lassa Fever in Post-Conflict Sierra Leone.","volume":"8","author":"J Shaffer","year":"2014","journal-title":"Dis. PLoS Negl. Trop."},{"key":"ref23","article-title":"An R & D Blueprint for Action To Prevent Epidemics Funding & Coordination Models for.","year":"2016"}],"container-title":["F1000Research"],"original-title":[],"link":[{"URL":"https:\/\/f1000research.com\/articles\/13-661\/v3\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/13-661\/v3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/13-661\/v3\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T14:43:04Z","timestamp":1764600184000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/13-661\/v3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":19,"URL":"https:\/\/doi.org\/10.12688\/f1000research.150743.3","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.183459.r390704","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/13-661\/v3#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.183459.r390704, Davidson Hamer, Department of Global Health, Boston University School of Public Health, Boston, MA, 14 Jun 2025, version 3, indexed","URL":"https:\/\/f1000research.com\/articles\/13-661\/v3#referee-response-390704","order":0,"name":"referee-response-390704","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.165339.r296578, Elisabeth Fichet-Calvet, Bernhard Nocht Institute for Tropical Medicine, Hamburg, 09 Sep 2024, version 1, 2 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/13-661\/v1#referee-response-296578","order":1,"name":"referee-response-296578","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Emmanuel Dwalu<\/b>; \n<i>Posted: 21 Mar 2025<\/i>; \n<b>The Editor F1000 Peer Review Journal<\/b>  \n<b>Ref: Response to Peer Reviewers\u2019 Reports - F1000 Research Peer Review: Epidemiological characteristics and hospital outcomes of hospitalized Lassa fever cases during the 2022 \u2013 2023 outbreak in Liberia <\/b>  Dear F1000 Research Editorial Team, Thank you for facilitating the peer review process for our manuscript. We have carefully addressed all the reviewers\u2019 comments, and we believe that the revised manuscript now aligns with the journal\u2019s requirements. Below, we provide a line-by-line response to the reviewers\u2019 comments, with the original comments highlighted in bold. Sincerely, Emmanuel Dwalu  \n<b>Reviewer # 2:&nbsp; <\/b> \n<b>General comments: <\/b>  \n<b>The manuscript is full of percentages; I counted over 200 in the introduction, results, discussion, figures and tables. This is far too many, because in the end you don't know which ones to pick out. There is often redundancy in the figures presented in the text and in the tables. There is no point in repeating the same information twice in a scientific text. It is also important to always mention the denominator when quoting a percentage in the text.<\/b>  We appreciate the reviewer\u2019s observation. We have revised removing some percentages from the introduction section. However, we still think it is necessary to maintain the percentages in the manuscript's results section.   \n<b>Percentages are often compared using terms such as &quot;highest&quot;, &quot;lower&quot;, &quot;more&quot;, without any statistics to support the comparison. These formulations should be removed from the manuscript as they are not scientific. Only statistics can confirm that one figure is smaller or larger than another.<\/b>  Thanks to the reviewer for this comment. We have revised the manuscript accordingly. &nbsp;   \n<b>The abbreviations \u201cLF\u201d for Lassa fever and \u201cLASV\u201d for Lassa virus should be used once the term has been quoted in full for the first time. In addition, the lines should be numbered to facilitate the report of the reviewers.<\/b>  We have revised the manuscript accordingly.    \n<b>Specific comments:<\/b> \n<b>Introduction:<\/b>  \n<b>\u201c\u2026 disease is primarily transmitted\u2026\u201d should be \u201cLASV is primarily transmitted\u2026\u201d because a disease is never transmitted. It is the pathogen that is transmitted.<\/b>  We have revised the manuscript accordingly.   \n<b>Replace \u201cMastomys rats\u201d with \u201cthe Natal multimammate mice (Mastomys natalensis)\u201d. Use the term of \u201cmice\u201d instead of \u201crats\u201d throughout the manuscript.<\/b>  We agree and have revised the manuscript.   \n<b>Transmission of LASV by direct or indirect contact is a hypothesis. It has not been scientifically proven. Therefore, use the conditional tense in this sentence.<\/b>  We have revised the manuscript accordingly.   \n<b>Update the morbidity and mortality figures according to the recent publication done by Basinski,.et.al., 2021 (Ref 1)<\/b>  We appreciate the reviewer for this observation and recommendation. However, the figure presented in the recommended study (a systematic review), has different sources of data but our study (retrospective cohort study) has all the data coming from one surveillance system is Liberia. Therefore, the authors have seen it useful to maintain the figure used in our study.   \n<b>Some case fatality rates are presented; where do they come from? Country? Years?<\/b>  The authors have cited the reference in the manuscript to reflect \u201d The case fatality rate (CFR) among hospitalized patients is estimated to be between 15% and 20% [17] but could be more during epidemics [7,18,19][7].    \n<b>Methods:<\/b>  \n<b>Study design and study setting should be combined in one paragraph. The general setting is useless because the results do not use this information.<\/b>  Thanks to the reviewer for this comment. In the general setting, we provide an overview of the Liberian health system's structure, with an emphasis on the reference system, which is later linked to LF case definition and case detection in the specific setting. Therefore, we respectfully disagree with the reviewer\u2019s suggestion to combine the design section and remove the general setting.   \n<b>I think the authors did a case-control study, not a cohort study, because they did not analyze, the outcome variable (LF infection) over time. They compared different exposures or variables between cases (LASV positive) and controls (LASV negative).<\/b>  Thank you for your comment. We would like to clarify that this is a retrospective cohort study (we have now added the word retrospective) in which all suspected Lf cases were followed until diagnosis, and those confirmed with the infection were followed until discharge. The cases (LASV-positive) and controls (LASV-negative) were not selected based on their exposure status.   \n<b>Exposure to LASV: how do you know that patients touched contaminated utensils? What is a rodent-borne food? A rodent contaminated-food? It would be useful to have the questionnaire in a supplementary information in order to know how the authors evaluated\/quoted the exposure to rodents.<\/b>  We agree with the reviewer. There was no questionnaire for data collection, as it was clearly stated that the study obtained and utilized case-based records of routine national surveillance data of all suspected Lassa fever cases reported between January 2022 and December 2023 that were reported to the National Public Health Institute of Liberia and cross-checked. However, in our study methods (specific setting), we have revised the definition of exposure to Lassa virus as \u201cany contact with rodents, either directly (handling rodents or their food sources) or indirectly (through contact with contaminated utensils, feces, urine, or consumption of food contaminated with rodent feces or urine). However, the form had incomplete data which necessitated grouping of the responses into the categories that are reported in the manuscript.   \n<b>\u201cA confirmed case\u2026 laboratory confirmed case\u2026 or virus isolation)\u201d. This sentence should be removed as the authors only used the RT-PCR to confirm LF in this study. <\/b>  We have revised the manuscript as: A confirmed case&nbsp; was defined as a suspected or probable case with a confirmed \/positive laboratory test (positive IgM antibody, positive RT-PCR) or epidemiologically linked to a laboratory confirmed case [22].   \n<b>CSO and DSO: it is pointless to give abbreviation as this term is not used in the rest of the text.<\/b>  We agree and have revised the manuscript. \n<b>&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;&nbsp;<\/b>   \n<b>Study population: this sentence is redundant with the one in Study design<\/b>  We appreciate the reviewer and have revised the manuscript.   \n<b>Study data sources: also redundant with the information presented at the end of the Specific setting<\/b>  We appreciate the reviewer\u2019s comment. However, in the entire specific setting, the authors explained LF case detection, recording\/documentation and reporting as well as case definition (suspected, probable, and confirmed). &nbsp;At the end, the authors explained that data from the IDSR ledger and case alert and laboratory paper-based forms were regularly entered into an MS Excel dataset containing the line-list of LF surveillance data in each district, then submitted to the county level and onward to the National Public Health Institute of Liberia. &nbsp;Information on sources was explained in the succeeding paragraph (Study data sources, variables, and validation).   \n<b>Statistical analysis: please use the term of \u201cLASV prevalence\u201d instead of \u201cpositivity rate\u201d, and throughout the manuscript. Please specify variables as dependent or independent. <\/b>  We have revised the manuscript accordingly.   \n<b>Why did not you perform statistics (binomial regression) on LASV prevalence and other variables? You only did statistics on CFR.<\/b>  We thank the reviewer for the useful observation. However, the focus of our study was the characteristics and hospital outcomes of Lf patients. We had to indicate the total suspected, tested and positivity to inform our readers before delving into the characteristics of the confirmed and their outcomes. Therefore, the authors think that the analysis performed supports the study objectives' attainment.&nbsp; &nbsp;    \n<b>Results <\/b> \n<b>Section \u201cCharacteristics of the suspected Lassa fever cases\u201d:<\/b>  \n<b>change this title in \u201cDiagnosis, Ribavirin treatment and outcome\u201d<\/b>  We have revised the manuscript: The CFR for patients tested LASV negative is indicated in figure 2 (15%, 42\/278)) against the 30% (41\/138) CFR for confirmed cases.   \n<b>The numbers presented in this paragraph are redundant with Table 1. I would remove this part and focus only on LASV-positive patients.<\/b>  We appreciate the reviewer but the authors think this is relevant to be maintained.    \n<b>Section \u201cPositivity rate of Lassa fever cases\u201d: <\/b>  \n<b>see my comment above about the positivity rate.<\/b>  Please see response below response in addition to the succeeding comments.   \n<b>Use the term of \u201cLASV prevalence\u201d instead of \u201cpositivity rate\u201d throughout the text, figure and table.<\/b>  We appreciate the reviewer\u2019s detailed review and comments\/recommendations. However, our analysis focused on LASV positivity rather than prevalence. This is because prevalence looks at a specific number of people who have (or had) the disease during a specific time period, which would be the number of truly positive individuals out of the entire population\u2014not just who is tested. The positivity rate\u2014also referred to as \u201cpercent positive rate\u201d or \u201cpercent positive\u201d is the percentage of all Lf tests performed that are actually positive. Positivity rate is usually expressed as a percentage (Rogers &amp; John Hopkins School of Public Health, 2020).   \n<b>Again, there is a lot of redundancy between the text and the table.<\/b>  We have revised highlighting the key findings instead of reproducing the table in text.   \n<b>\u201chighest\u201d see my general comment<\/b>  We agreed and revised the manuscript accordingly.   \n<b>Why not to analyze the data to build a model?<\/b> The reviewer\u2019s comment is appreciated. However, the authors did not set to build a model in this study. This could be considered in subsequent studies.  \n<b>Section \u201cEpicurve\u201d:<\/b>  \n<b>look at the \u201cmore confirmed cases\u201d: statistics?<\/b>   We have revised the manuscript accordingly.  \n<b>Section \u201cType of exposure\u201d:<\/b>  \n<b>data redundant with table 3, and not well analyzed. If you wanted to analyze exposure to rodents, the question would be \u201care the LASV+ patients more exposed to rodents than the LASV- patients? To do this, you would need to build a model where the RT-PCR result as an outcome (0 or 1) is a function of rodent exposure (absence\/presence according to respondent?) + other variables. You did not answer this question in your article.<\/b> \n<b>I would be curious to know such a result, as I suspect that everyone was exposed to rodents in the area\u2026<\/b>   We appreciate the reviewer\u2019s comments. . However, our analysis was focused on describing the characteristics of the confirmed Lf cases and their outcomes. These characteristics included socio-demographics, clinical, and exposures (including rodent exposure, etc). We did not set out to deal with factors associated with LASV positivity among the patients.&nbsp;  \n<b>Section \u201cFactors associated\u201d:<\/b>  \n<b>this is the most interesting part of the article. However, factors such as \u201coccupation\u201d and \u201cduration of onset prior to admission\u201d are not presented. You could say that these two variables do not affect CFR when analyzed in a bivariate model. <\/b>   Occupation and duration of onset prior to admission, along with others were presented in the bivariate analysis but were not significant. That\u2019s why we did not present them in the multivariate analysis, but rather focused on those that were significant.  \n<b>Discussion:<\/b>  \n<b>Dry season as risk season: there is no data in this article to support this assumption.<\/b> \n<b>Furthermore, in another article (Dwalu et al. Trend of Lassa fever cases and factors associated with mortality in Liberia, 2016 - 2021: a secondary data analysis. Pan African Medical Journal. 2024;47(22). 10.11604\/pamj.2024.47.22.42156) you published data clearly showing Lassa cases throughout the year, in 6 consecutive years between 2016 and 2021. Only two years showed a peak in the dry season. So, I think it is wrong to claim a seasonal risk when your data shows the opposite in 4 out of 6 years.<\/b>   The reviewer\u2019s comment is appreciated. The two years indicated in the article mentioned above (2019 &amp; 2020) recorded the majority of the cases (54%) but the overall majority was reported during the dry season (79%) covering October to March. Over half of the cases (59%, 81\/138) clustered between epi-weeks 1-12 and 40-52, aligning with the dry season (October \u2013 March) (Figure 4).\u201d Based on this, the authors could safely say that dry season accounted for the majority of the cases, likewise the current study. \n<b>Rodent exposure: this is not analyzed in this paper (see my comment above).<\/b> Rodent exposure was analyzed in table 2 along with clinical characteristics and outcome and 68% of the confirmed cases were exposed to rodents. \n<b>High testing: what is that? <\/b> We appreciate the reviewer and have according revised this to high detection and positivity, instead of high testing and positivity rates. \n<b>\u201cyounger age group more affected\u201d: I have not seen this result. Where did you do the analysis?<\/b> We thank the reviewer for the observation. This analysis can be seen in tables 1 and 3 where 95 (69%) were less than 30 years.&nbsp; However, the authors have agreed to omit this finding from the discussion. \n<b>\u201cdirect or indirect contact with rodents\u201d: this is not analyzed, leading to over-interpretation.<\/b> Our data analyzed showed exposure to rodents but did not establish direct or indirect contact. This was provided in the discussion to mean that exposure to rodents could be either by direct or indirect contact to rodents. The majority of the confirmed cases reported exposure to rodents suggesting exposure (68%, 95\/138). We have revised the manuscript to remain with exposure to rodents. \n<b>CFR in other countries: give the raw data, and do not repeat this idea twice at the beginning and in the middle of the discussion.<\/b> \n<b>40% (xx\/xx?) in Liberia: what is the reference?<\/b> We agree and have revised the manuscript accordingly (40 \n<b>(41\/103)<\/b>\n<b>[6]<\/b>\n<b> <\/b>in Liberia. \n<b>Rodent-proofing measures need to be proposed with great caution. See our recent paper on rodent control strategies in Guinea (Marien, J., M. Sage, U. Bangura, A. Lame, M. Koropogui, T. Rieger, B. Soropogui, M. Douno, N. Magassouba and E. Fichet-Calvet (2024). &quot;Rodent control strategies and Lassa virus: some unexpected effects in Guinea, West Africa.&quot; Emerg Microbes Infect 13(1): 2341141).<\/b>&nbsp; We agree with the reviewer and have revised it accordingly\n<b>. <\/b> \n<b>As you published data from 2016-2021 surveillance in Dwalu et al. 2024, why don\u2019t you discuss the results presented here with those published previously?<\/b> \n<b>More generally, what is the novelty of this article when compared to Dwalu et al. 2024?<\/b> The reviewer\u2019s comment is highly appreciated. However, the previous study was focused on trend, though it also highlighted factors associated with mortality. In the current study, clinical and exposure characteristics are highlighted in addition to mortality, which were missing in the previous study.&nbsp; \n<b>Is the work clearly and accurately presented and does it cite the current literature?<\/b>  \n<b>Partly&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;&nbsp;<\/b>  \n<b>Is the study design appropriate and is the work technically sound?<\/b>  \n<b>Partly<\/b>  \n<b>Are sufficient details of methods and analysis provided to allow replication by others?<\/b>  \n<b>Partly<\/b>  \n<b>If applicable, is the statistical analysis and its interpretation appropriate?<\/b>  \n<b>No<\/b>  \n<b>Are all the source data underlying the results available to ensure full reproducibility?<\/b>  \n<b>Partly<\/b>  \n<b>Are the conclusions drawn adequately supported by the results?<\/b>  \n<b>Partly<\/b>  \n<b>References<\/b> \n<b>1. Basinski AJ, Fichet-Calvet E, Sjodin AR, Varrelman TJ, et al.: Bridging the gap: Using reservoir ecology and human serosurveys to estimate Lassa virus spillover in West Africa.PLoS Comput Biol. 2021; 17 (3): e1008811 PubMed Abstract | Publisher Full Text<\/b>  \n<b>Competing Interests<\/b> \n<b>No competing interests were disclosed.<\/b>  \n<b>Reviewer Expertise<\/b> \n<b>Lassa fever, Lassa virus evolution, phylogeography, rodent ecology, West Africa, eco-epidemiology<\/b> \n<b>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however, I have significant reservations, as outlined above.<\/b>","URL":"https:\/\/f1000research.com\/articles\/13-661\/v3#referee-comment-13600","order":2,"name":"referee-comment-13600","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.181955.r385516, Qudus Lawal, Irrua Specialist Teaching hospital, Irrua, 04 Jun 2025, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/13-661\/v2#referee-response-385516","order":3,"name":"referee-response-385516","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Emmanuel Dwalu<\/b>; \n<i>Posted: 08 Jun 2025<\/i>; \n<b>The Editor F1000 Peer Review Journal<\/b>  \n<b>Ref: Response to Peer Reviewers\u2019 Reports - F1000 Research Peer Review: Epidemiological characteristics and hospital outcomes of hospitalized Lassa fever cases during the 2022 \u2013 2023 outbreak in Liberia <\/b>  Dear F1000 Research Editorial Team, Thank you for facilitating the peer review process for our manuscript. We have carefully addressed all the reviewers\u2019 comments, and we believe that the revised manuscript now aligns with the journal\u2019s requirements. Below, we provide a line-by-line response to the reviewers\u2019 comments, with the original comments highlighted in bold. Sincerely, Emmanuel Dwalu &nbsp;  \n<b>Reviewer # 2:&nbsp; <\/b>  \n<b>General comments: <\/b> \n<b>The study is relevant and explores an important aspect of Lassa fever control and prevention. Understanding the epidemiology of Lassa will help improve policies and guidelines.<\/b> \n<b>The method of retrospective cohort using a national database helps give a reliable estimate.<\/b> \n<b>A supplementary document of the tool used for data collection will be helpful to improve replicability and understanding of what was done.<\/b>  Thanks to the reviewer for this comment. However, the data used for this study was a routinely collected LF surveillance data obtained from the National Public Health Institute of Liberia in an excel file (national line list of LF patients\u2019 records), it was not a primary data collected from the patients using questionnaire or specific data collection tool for the purpose of this study.   \n<b>However, the authors can improve the quality of the article by addressing the following:<\/b> \n<b>1) Fever, 128 (93%), malaise, 121 (88%), headache, 114 (83%) and myalgia, 114 (83%) were the most common clinical characteristics.<\/b> \n<b>Comment:&nbsp;&nbsp;&nbsp; it reads better as Fever, 128 (93%), malaise, 121 (88%), headache, 114 (83%), and myalgia, 114 (83%) were the most common clinical presentations.<\/b>  We have revised the manuscript accordingly.   \n<b>2) Age 40-49 years accounted for 8\/12 (67%), and those aged\u226550 reported 5\/8 (63%) of the deaths among the confirmed cases. <\/b> \n<b>Comment: If the author intends to present the CFR per age group, it should be clearly stated as such. <\/b>  The sentence has been revised in the manuscript.   \n<b>Introduction<\/b> \n<b>3) while a retrospective study in 2022 identified fever, fatigue, sore throat, loss of appetite, headache, vomiting, and myalgia as presenting symptoms among confirmed cases.<\/b> \n<b>Comment: The findings of the retrospective study didn't contrast with the SR; rather, it added some other findings, thus the use of 'while' is not appropriate. It will be more important to mention the percentage frequency quoted in these studies, given that it was mentioned for the index study in discussion. <\/b>  We appreciate the reviewer for this comment. However, the percentages were indicated in our previous version of the manuscript, but were recommended to be removed by the previous reviewer, pointing out that we had many percentages in the manuscript, especially in the introduction section. Reducing it, especially in the introduction section, could be okay. &nbsp; Therefore, the authors have revised the manuscript, changing the \u201cwhile\u201d to \u201cand\u201d as recommended by the reviewer, but maintained the clinical manifestations as they are without percentages.   \n<b>4) this study aimed to understand the 2022-2023 LF outbreak in Liberia by investigating characteristics of suspected <\/b> \n<b>comment. The characteristic of all suspected cases was not fully elucidated. A valuable characteristic will be the final diagnosis of the suspected cases. <\/b>  We thank the reviewer for these comments. These were the available variables for analysis, and the authors believe that the demographics provided here have given some understanding of the characteristics of the suspected cases in this study before delving more into the analysis for the confirmed cases. The final diagnosis for the suspected cases was indicated as LF positive, showing that 138 of the suspected cases tested were LF positive. The overall positivity rate was 33% (138\/416) (\n<b>Figure 1<\/b> &amp; \n<b>Table 1<\/b>).   \n<b>5) had a history of rodent contact were also considered suspected cases<\/b> \n<b>Comment: The author should share how this was determined, was it from historical record, was these captures in the tool used?<\/b>  As indicated supra, \u201cthe data used for this study was routinely collected LF surveillance data\u201d, \u201chad a history of rodent contact\u201d was from the historical record of the patients already collected, these were not captured in a specific tool used for primary data collection during the study.   \n<b>6) epidemiologically linked to a laboratory-confirmed case<\/b> \n<b>Comment: it will be important to know the proportion of diagnoses that were based on this case definition<\/b>  Thanks to the reviewer for this observation. Though the authors did not emphasize this finding, it was indicated in table 2 that 11 (8%) of the total confirmed cases had contact with a confirmed Lf case (epidemiologically linked to a laboratory-confirmed case). We have added this to the results. &nbsp;   \n<b>7) Individuals with negative results after a RT-PCR testing results were discontinued from ribavirin treatment and were discharged immediately<\/b> \n<b>Comment: Where were these patients discharged to? Home or hospital, how was their outcome captured<\/b>  We thank the reviewer for the comment. Individuals with negative results after a RT-PCR testing results were discontinued from ribavirin treatment and were discharged home immediately. We have revised the manuscript.   \n<b>8) We opted for four sites instead of all eight because these were the sites reporting majority of the cases and reviewing records from these sites would address the incomplete record issue or data quality issues in the existing data set used for the study.<\/b> \n<b>Comment: This justification is quite unclear. were the incomplete data from the smaller sites. Interestingly the table 1 account for all the sites. Kindly explain further.<\/b>  Thanks to the reviewer for this observation. The incompleteness in some variables was across the reporting counties, not unique to one specific reporting county or reporting site. Though our visit aimed to address the incomplete record issue or data quality issues in the existing data, the secondary nature of the routinely collected data could not allow us to further correct records that were already existing at the reporting sites, but could only validate available records with the national database for analysis.   \n<b>9) We performed all statistical analyses using Epi Info analysis software (version 7.2.5.0) and Stata v18.0 (open-source alternative is R: The R Project for Statistical Computing), version 4.3.2.<\/b> \n<b>Comment: It would be interesting to know why two statistical packages was used for analysis. Which analysis was done with each package<\/b>  Thanks to the reviewer for the comment. The Epi Info analysis software was used for all descriptive statistics, while Stata v18.0 (the open-source alternative is R: The R Project for Statistical Computing), was used to conduct the regression analysis. We have revised the manuscript.   \n<b>10A) Figure 1 will be improved if a brief description is given on<\/b> \n<b>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; reason for not testing<\/b> \n<b>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; reason for not treating in positive cases<\/b>  We thank the reviewer for these comments. The routinely collected LF surveillance data used for this study did not provide these reasons, which we cannot explain at this time. However, we pointed out that the incompleteness of some records highlights the need to strengthen data collection practices within healthcare facilities to ensure complete and accurate data for informed outbreak response efforts.  \n<b>&nbsp;&nbsp; <\/b> \n<b>10B) for the test negative ribavirin patients, what is the mean\/median duration of treatment<\/b> Thanks to the reviewer. This data was not available for analysis in the set of data used of the study.&nbsp;  \n<b>11) Nimba had the shortest median time, with a median of &lt;1 day (IQR &lt; 1-1.5).<\/b>  \n<b>comment: This presupposes that there is a trend to admit within a day of symptoms in this county; it will be important to know the method and unit of measure (minutes\/hours\/days) that was used to assess this construct. <\/b>  We thank the reviewer for this comment. The duration was calculated using the date of symptom onset and date of patient's admission (duration from symptom onset to the date of patient's admission) at the treatment facility, and the unit of measure used was days.   \n<b>12) Positivity rate of Lassa fever cases<\/b> \n<b>Comment: Positivity rate, as described in this study is a measure of sensitivity of physician suspicion of Lassa (number of suspected cases that tested positive) rather than the distribution of the disease. Using it as an estimate of distribution will be biased as it is more dependent on the physician's index of suspicion. <\/b>  Thanks to the reviewer for the comment. The sensitivity of physician suspicion of Lassa points to case detection using the suspected LF case definition at the reporting health facilities.&nbsp; Positivity as used in this study referred to the proportion of suspected LF cases positive among those tested using RT-PCR; not all suspected cases were tested.   \n<b>13) 68% (94\/138) among confirmed LF cases. For clinical characteristics, fever accounted for 93% (128\/138), followed by malaise (88%, 121\/138), headache (83%, 114\/138), and myalgia (83%, 114\/138).<\/b>  \n<b>Comment: follow a consistent format, percent (fraction)<\/b>  We have revised the manuscript accordingly.   \n<b>14) we found that LF patients \u226530 years were 1.9 times more likely to die<\/b> \n<b>Comment: It will be good to know what informed the choice of age 30 for categorisation in the bivariate analysis. This is particularly important because in the discussion section, the result categorization used to explain the result was elderly.<\/b>  Thanks to the reviewer for this very useful comment. Pointing out mortality as our outcome variable (alive or dead) in table 3, we found in our analysis that majority of the deaths among confirmed cases were recorded among patients aged &gt;=30 years, 44% CFR (19\/43), which was nearly twice the mortality among those &lt; 30 years, 23% (22\/95). We then decided to assess if there was an association between &gt;=30 years and LF mortality at both bivariate and multivariate levels. &nbsp;&nbsp; We have revised the phrase \u201celderly people\u201d to middle-aged and older adult population in the entire manuscript. &nbsp;  \n<b>&nbsp;&nbsp;<\/b>  \n<b>15) Nimba County were 2.0 times more likely to die (cRR=2.0, 95% CI=1.129-3.771, p=0.019) compared to those reported from other counties<\/b> \n<b>Comment: The comparison is to the ref, (Bongo). Although incidentally, Great Bassa has cRR of 1, which makes the interpretation given by the author accurate.<\/b> Thanks to the reviewer. We have revised the manuscript.  \n<b>16) Surprisingly, there was death (13%) observed among hospitalized individuals without LF, highlighting challenges in diagnosis and LF management.<\/b> \n<b>Comment: This is why it is important to highlight the diagnosis of those who tested negative. Could they be having a diagnosis equally lethal or worse than LF. <\/b>  We appreciate the reviewer for this comment. The diagnosis in the data used for this study was only for Lassa fever, as was suspected.&nbsp;   \n<b>17) The high CFR in Nimba could be due to the fact that the county is endemic to LF and sometimes misdiagnosed with malaria, which impacts early treatment among LF patients.<\/b> \n<b>Comment: This explanation isn't accurate given the study data; median presentation time is less than 1 day<\/b>  Thanks to the reviewer for this observation. We have revised the manuscript accordingly.   \n<b>18) Similar to other studies, the CFR was higher among elderly people, although the causes of high mortality are unknown, we suspect that factors such as comorbidities, waning immunity, etc may have likely contributed. <\/b> \n<b>Comment: This should be referenced.<\/b>  Thanks to the reviewer. We have revised the manuscript.","URL":"https:\/\/f1000research.com\/articles\/13-661\/v3#referee-comment-14034","order":4,"name":"referee-comment-14034","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.181955.r387846, Junki Maruyama, The University of Texas Medical Branch, Galveston, Texas, 14 Jun 2025, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/13-661\/v2#referee-response-387846","order":5,"name":"referee-response-387846","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This SORT IT Programme was funded by the Special Programme for Research and Training in Tropical Diseases (TDR), Geneva, Switzerland (Grant Number HQTDR 2422924-4.1-72863. The APC was also funded by TDR. TDR is able to conduct its work thanks to the commitment and support from a variety of funders. A full list of TDR donors is available at: https:\/\/tdr.who.int\/about-us\/our-donors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":6,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution IGO Licence.","order":0,"name":"copyright-info","label":"Copyright"}]}}