{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T07:30:31Z","timestamp":1773732631213,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011509","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000}}],"reference-count":109,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foreign, Commonwealth and Development Office and Wellcome","award":["215091\/Z\/18\/Z"],"award-info":[{"award-number":["215091\/Z\/18\/Z"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Plague is a zoonotic disease that, despite affecting humans for more than 5000 years, has historically been the subject of limited drug development activity. Drugs that are currently recommended in treatment guidelines have been approved based on animal studies alone\u2013no pivotal clinical trials in humans have yet been completed. As a result of the sparse clinical research attention received, there are a number of methodological challenges that need to be addressed in order to facilitate the collection of clinical trial data that can meaningfully inform clinicians and policy-makers. One such challenge is the identification of clinically-relevant endpoints, which are informed by understanding the clinical characterisation of the disease\u2013how it presents and evolves over time, and important patient outcomes, and how these can be modified by treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology\/Principal findings<\/jats:title>\n                    <jats:p>This systematic review aims to summarise the clinical profile of 1343 patients with bubonic plague described in 87 publications, identified by searching bibliographic databases for studies that meet pre-defined eligibility criteria. The majority of studies were individual case reports. A diverse group of signs and symptoms were reported at baseline and post-baseline timepoints\u2013the most common of which was presence of a bubo, for which limited descriptive and longitudinal information was available. Death occurred in 15% of patients; although this varied from an average 10% in high-income countries to an average 17% in low- and middle-income countries. The median time to death was 1 day, ranging from 0 to 16 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions\/Significance<\/jats:title>\n                    <jats:p>This systematic review elucidates the restrictions that limited disease characterisation places on clinical trials for infectious diseases such as plague, which not only impacts the definition of trial endpoints but has the knock-on effect of challenging the interpretation of a trial\u2019s results. For this reason and despite interventional trials for plague having taken place, questions around optimal treatment for plague persist.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0011509","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T13:50:52Z","timestamp":1699537852000},"page":"e0011509","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["A systematic review of the clinical profile of patients with bubonic plague and the outcome measures used in research settings"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4687-8380","authenticated-orcid":true,"given":"Josephine","family":"Bourner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lovarivelo","family":"Andriamarohasina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Salam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nzelle Delphine","family":"Kayem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rindra","family":"Randremanana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piero","family":"Olliaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,11,9]]},"reference":[{"key":"pntd.0011509.ref001","author":"World Health Organisation","year":"2017","journal-title":"Plague"},{"key":"pntd.0011509.ref002","article-title":"U.S. Centers for Disease Control and Prevention.","year":"2021","journal-title":"Plague: Symptoms"},{"issue":"5","key":"pntd.0011509.ref003","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S1473-3099(18)30730-8","article-title":"Epidemiological characteristics of an urban plague epidemic in Madagascar, August-November, 2017: an outbreak report","volume":"19","author":"R Randremanana","year":"2019","journal-title":"Lancet Infect Dis"},{"issue":"5","key":"pntd.0011509.ref004","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1086\/500137","article-title":"Treatment of plague with gentamicin or doxycycline in a randomized clinical trial in Tanzania","volume":"42","author":"W Mwengee","year":"2006","journal-title":"Clin Infect Dis"},{"key":"pntd.0011509.ref005","volume-title":"Weekly Epidemiological Record: Plague around the world in 2019","author":"E. 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