{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:50:56Z","timestamp":1789019456757,"version":"build-2803163510"},"update-to":[{"DOI":"10.3310\/nihropenres.13432.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T00:00:00Z","timestamp":1733184000000}}],"reference-count":27,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T00:00:00Z","timestamp":1733184000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/open-government-licence\/version\/3\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["NIHR200125"],"award-info":[{"award-number":["NIHR200125"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["openresearch.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["NIHR Open Res"],"abstract":"<ns3:p>\n                    Background Cutaneous leishmaniasis (CL) is a skin neglected tropical disease, with an estimated 40,000 new cases each year in Ethiopia. CL causes ulcers, nodules, and plaques on the skin, and in some instances the destruction of the nasopharyngeal mucosa and cartilage. Some CL lesions may heal spontaneously, whilst other lesions may require therapies which are associated with discomfort, adverse effects, prolonged treatment, and a frequent lack of a complete response. Scarring, a sequela of CL, causes permanent disfigurement and is associated with stigma linked with a reduction in health-related quality of life. The choice of treatment for CL is based upon factors including the causative species; the number, extent, size, and location of lesions; and the availability of treatments. The development of robust evidence for CL treatment is hindered by a lack of validated and appropriate outcome measures and few data to support hypothesis-generation and trial design. There is a paucity of prospective data with well-defined treatment outcomes for CL caused by\n                    <ns3:italic>L. aethiopica<\/ns3:italic>\n                    . Aim The overall aim of this study is to improve the understanding of the health and economic burden of CL. Methods We have designed an observational, multi-centre cohort study to examine treatment outcomes for CL in Ethiopia which includes clinical outcomes, laboratory outcomes, patient reported outcome measures, scar assessments and cost effectiveness. We aim to recruit up to 750 participants across two hospital sites. We present here the protocol for this cohort study with a 12-month follow up period for each participant. Conclusions These data will inform the design of randomized controlled trials to evaluate new treatment strategies, with appropriate economic evaluations. This will help improve evidence-based guidelines and support evidence-led policy decisions, not only in Ethiopia but also globally.\n                  <\/ns3:p>","DOI":"10.3310\/nihropenres.13432.2","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T08:50:08Z","timestamp":1733215808000},"page":"49","update-policy":"https:\/\/doi.org\/10.3310\/nihropenres.crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Protocol for a prospective observational cohort study of cutaneous leishmaniasis in Ethiopia"],"prefix":"10.3310","volume":"3","author":[{"given":"Amel Beshir","family":"Mohammed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fewzia Shikur","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feleke 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Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-49\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-49\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-49\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T05:10:10Z","timestamp":1737090610000},"score":1,"resource":{"primary":{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-49\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,3]]},"references-count":27,"URL":"https:\/\/doi.org\/10.3310\/nihropenres.13432.2","relation":{"has-version":[{"id-type":"doi","id":"10.3310\/nihropenres.13432.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.3310\/nihropenres.15037.r34052","asserted-by":"subject"},{"id-type":"doi","id":"10.3310\/nihropenres.15037.r33926","asserted-by":"subject"},{"id-type":"doi","id":"10.3310\/nihropenres.15037.r33926","asserted-by":"object"},{"id-type":"doi","id":"10.3310\/nihropenres.15037.r34052","asserted-by":"object"}]},"ISSN":["2633-4402"],"issn-type":[{"value":"2633-4402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,3]]},"assertion":[{"value":"Indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-49\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.3310\/nihropenres.15037.r33926, Najia Ahmed, Bahria University of Health Sciences, Karachi, 11 Jan 2025, version 2, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-49\/v2#referee-response-33926","order":0,"name":"referee-response-33926","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.14569.r30757, Talal Alharazi, Taiz University, Taiz, 23 Nov 2023, version 1, 2 approved with reservations","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-49\/v1#referee-response-30757","order":1,"name":"referee-response-30757","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Saba Lambert<\/b>; \n<i>Posted: 01 Dec 2024<\/i>; Dear Dr Alharazi,  We are grateful for your careful review of our protocol paper and your comments are important in helping us to improve it. We are addressing these one by one here.  \n<b>Introduction<\/b>  Shorten the background\/introduction to be more concise for a quantitative study  \n<b>It is mixed method research. <\/b> \n<b>This introduction reflects what is known about CL in Ethiopia and what data is available so far, bringing to the fore questions that need to be addressed. In view of the complex multi-disciplinary issues being addressed, and to address CL In Ethiopia holistically, we believe the introduction is as concise and inclusive as possible.<\/b>  \n<b>Methods<\/b>  Expand on the inclusion\/exclusion criteria, especially related to prior treatments  \n<b>Thank you, we have elaborated these criteria as follows:<\/b>  \n<b>\u201cAll adults and children diagnosed with CL and initiated on CL treatment at both study centers are eligible to be recruited in this study. Each participant will be followed for 360 days.<\/b> \n<b>Inclusion criteria: <\/b>  \n<b>Individuals with parasitologically confirmed CL using microscopy or culture <\/b> \n<b>Individuals receiving treatment at the study centers<\/b>   \n<b>Exclusion criteria: <\/b>  \n<b>Participants who have previously been treated with systemic anti-leishmania therapy<\/b> \n<b>Participants who do not or are unable to give informed consent<\/b> \n<b>to participate in the study\u201d<\/b>  &nbsp;  Specify which cytokines\/biomarkers will be analyzed in the immunology studies  \n<b>We have amended the text to: <\/b>  \n<b>\u201cTo interrogate the dynamics of immune responses in different clinical phenotypes of CL, blood and skin lesion samples will be collected at three time points. Participants will have blood samples and a skin biopsy (stored in RNAlater\u2122) taken to evaluate subsets of the innate and adaptive immunity; pro-inflammatory (IFN-\u03b3 and TNF-\u03b1) and anti-inflammatory (IL-6, IL-27, IL-10, IL-4, IL-13, TGF-\u03b2, and hsp18) cytokines and interleukins (IL)-12, IL-2, IL-1, IL-18, IL-15, IL-8, IL-17A, and IL-22) using Luminex multiplex assay. (ii) The change in mRNA (Ribonucleic acid) expression level of Toll-like receptors (TLRs) and pro-inflammatory (IFN-\u03b3, IL-12, IL-1\u03b2, IL-17A, and IL-12p70) and anti-inflammatory (IL-5, IL-6, IL-10, IL-4, TGF-\u03b2, and hsp18) cytokines will also be assessed before treatment (at day 0), during treatment (day 28) and after completion of treatment (day 90) using quantitative PCR (Real-time Polymerase Chain Reaction). In addition, the levels of chemokines (such as CXCL8, CXCL10, CCL5, CCL4, CCL3, and CCL2) will be determined in supernatants from the whole blood stimulation assays for the Luminex multiplex assay. HLA typing will be performed to assess if there is an association between HLA types (targeting probes for HLA-A, B, C, DR, DQ, and DP loci) and the clinical phenotypes of CL seen in our cohort.\u201d<\/b> &nbsp;  Elaborate on the sample size calculations and precision expected \n<b>&nbsp;Table 2 details the sample sizes required for different cure rates.<\/b>  &nbsp;  State which statistical tests and analysis software will be used  \n<b>This has now been under in each section of the Data Analysis paragraph<\/b>  \n<b>Analysis Plan<\/b>  Specify proposed statistical tests and significance levels for objectives  \n<b>This has now been under in each section of the Data Analysis paragraph<\/b>  \n<b>Discussion<\/b>  Reduce repetition of content covered elsewhere  \n<b>We feel the brief discussion summarizes the important points presented previously.<\/b> \n<b>References<\/b>  Update older references, over 5 years old unless seminal works  \n<b>CL is a NTD and research in Ethiopia is limited. We believe we have provided a thorough literature review. There are a few more recent articles, but these were not available at the date of our protocol development. These will be reviewed when results are presented.<\/b> &nbsp;  Overall, add more methodological specifics in line with quantitative reporting guidelines to facilitate reproducibility and interpretation.  \n<b>We believe our paper contains detailed methodological description<\/b>  Thank you for helping us improve our paper","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-49\/v2#referee-comment-3393","order":2,"name":"referee-comment-3393","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.15037.r34052, Sara M. Robledo, Universidad de Antioquia, Medell\u00edn, 17 Jan 2025, version 2, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/3-49\/v2#referee-response-34052","order":3,"name":"referee-response-34052","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This project is funded by the National Institute for Health Research (NIHR) under its Research and Innovation for Global Health Transformation (RIGHT) Programme (Grant Reference Number NIHR200125). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This open access work is licensed under the Open Government Licence v3.0.","order":0,"name":"copyright-info","label":"Copyright"}]}}