{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T13:21:28Z","timestamp":1783516888504,"version":"3.55.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T00:00:00Z","timestamp":1649462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Fever of unknown origin (FUO) investigations yield a substantial number of patients with infectious diseases. This systematic review and meta-analysis aimed to quantify more common FUO infectious diseases etiologies and to underscore geographic variation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Four databases (PubMed, Embase, Scopus, and Web of Science) were searched for prospective studies reporting FUO rates among adult patients from 1 January 1997 to 31 March 2021. The pooled proportion for infectious diseases etiology was estimated using the random-effects meta-analysis model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Nineteen prospective studies were included with 2667 total cases. No studies were available for Africa or the Americas. Overall, 37.0% (95.0% confidence interval [CI], 30.0%\u201344.0%) of FUO patients had an infectious disease etiology. Infections were more likely from Southeastern Asia (pooled proportion, 0.49 [95% CI, .43\u2013.55]) than from Europe (pooled proportion, 0.31 [95% CI, .22\u2013.41]). Among specifically reported infectious diseases (n\u2005=\u2005832), Mycobacterium tuberculosis complex predominated across all geographic regions (n\u2005=\u2005285 [34.3%]), followed by brucellosis (n\u2005=\u200581 [9.7%]), endocarditis (n\u2005=\u200562 [7.5%]), abscesses (n\u2005=\u200561 [7.3%]), herpesvirus (eg, cytomegalovirus and Epstein-Barr virus) infections (n\u2005=\u200560 [7.2%]), pneumonia (n\u2005=\u200554 [6.5%]), urinary tract infections (n\u2005=\u200554 [6.5%]), and enteric fever (n\u2005=\u200540 [4.8%]).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>FUO patients from Southeastern Asia were more likely to have an infectious diseases etiology when compared to other regions. The predominant factor for this finding appears to be differences in disease prevalence among various geographical locations or other factors such as access to timely care and diagnosis. Noting epidemiological disease factors in FUO investigations could improve diagnostic yields and clinical outcomes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofac151","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T18:13:13Z","timestamp":1649527993000},"source":"Crossref","is-referenced-by-count":27,"title":["Geographic Variation of Infectious Disease Diagnoses Among Patients With Fever of Unknown Origin: A Systematic Review and Meta-analysis"],"prefix":"10.1093","volume":"9","author":[{"given":"William F","family":"Wright","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1482-5612","authenticated-orcid":false,"given":"Gayane","family":"Yenokyan","sequence":"additional","affiliation":[{"name":"Johns Hopkins Biostatistics Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia J","family":"Simner","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"},{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen C","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G","family":"Auwaerter","sequence":"additional","affiliation":[{"name":"The Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,4,9]]},"reference":[{"key":"2022041913105741600_CIT0001","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1186\/s12879-019-4285-8","article-title":"Fever of unknown origin (FUO): which are the factors influencing the final diagnosis? A 2005-2015 systematic review.","volume":"19","author":"Fusco","year":"2019","journal-title":"BMC Infect Dis"},{"key":"2022041913105741600_CIT0002","doi-asserted-by":"crossref","first-page":"e032059","DOI":"10.1136\/bmjopen-2019-032059","article-title":"Key diagnostic characteristics of fever of unknown origin in Japanese patients: a prospective multicentre study.","volume":"9","author":"Naito","year":"2019","journal-title":"BMJ Open"},{"key":"2022041913105741600_CIT0003","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1093\/qjmed\/hcx158","article-title":"Referral of patients with fever of unknown origin to an expertise center has high diagnostic and therapeutic value.","volume":"110","author":"Mulders-Manders","year":"2017","journal-title":"QJM"},{"key":"2022041913105741600_CIT0004","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1001\/jama.1930.02710450001001","article-title":"Fever of unknown origin.","volume":"94","author":"Alt","year":"1930","journal-title":"JAMA"},{"key":"2022041913105741600_CIT0005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/00005792-196102000-00001","article-title":"Fever of unexplained origin: report on 100 cases.","volume":"40","author":"Petersdorf","year":"1961","journal-title":"Medicine (Baltimore)"},{"key":"2022041913105741600_CIT0006","first-page":"35","article-title":"Fever of unknown origin\u2014reexamined and redefined.","volume":"11","author":"Durack","year":"1991","journal-title":"Curr Clin Top Infect Dis"},{"key":"2022041913105741600_CIT0007","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1097\/00005792-199711000-00002","article-title":"Fever of unknown origin (FUO). I. A prospective multicenter study of 167 patients with FUO, using fixed epidemiologic entry criteria. The Netherlands FUO Study Group.","volume":"76","author":"de Kleijn","year":"1997","journal-title":"Medicine"},{"key":"2022041913105741600_CIT0008","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1097\/00005792-199711000-00003","article-title":"Fever of unknown origin (FUO). II. Diagnostic procedures in a prospective multicenter study of 167 patients. The Netherlands FUO Study Group.","volume":"76","author":"de Kleijn","year":"1997","journal-title":"Medicine"},{"key":"2022041913105741600_CIT0009","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1097\/MD.0b013e31802fe858","article-title":"A prospective multicenter study on fever of unknown origin: the yield of a structured diagnostic protocol.","volume":"86","author":"Bleeker-Rovers","year":"2007","journal-title":"Medicine"},{"key":"2022041913105741600_CIT0010","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1001\/jama.1896.02430730001001","article-title":"The study of the fevers of the South.","volume":"26","author":"Osler","year":"1896","journal-title":"JAMA"},{"key":"2022041913105741600_CIT0011","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.amjmed.2021.07.038","article-title":"Fever of unknown origin (FUO)\u2014a call for new research standards and updated clinical management.","volume":"135","author":"Wright","year":"2021","journal-title":"Am J Med"},{"key":"2022041913105741600_CIT0012","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0300-2977(96)00086-1","article-title":"Inquiry into the diagnostic workup of patients with fever of unknown origin.","volume":"50","author":"de Kleijn","year":"1997","journal-title":"Neth J Med"},{"key":"2022041913105741600_CIT0013","first-page":"44","article-title":"FUO revisited.","volume":"94","author":"Petersdorf","year":"1983","journal-title":"Trans Am Clin Climatol Assoc"},{"key":"2022041913105741600_CIT0014","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1056\/NEJMp1212725","article-title":"Fever of unknown origin or fever of too many origins?","volume":"368","author":"Horowitz","year":"2013","journal-title":"N Engl J Med"},{"key":"2022041913105741600_CIT0015","doi-asserted-by":"crossref","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.","volume":"6","author":"Moher","year":"2009","journal-title":"PLoS Med"},{"key":"2022041913105741600_CIT0016","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/2049-3258-72-39","article-title":"Metaprop: a STATA command to perform meta-analysis of binomial data.","volume":"72","author":"Nyaga","year":"2014","journal-title":"Arch Public Health"},{"key":"2022041913105741600_CIT0017","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1080\/713933774","article-title":"Fever of unknown origin in uremic patients: a controlled prospective study.","volume":"33","author":"Altiparmak","year":"2001","journal-title":"Scand J Infect Dis"},{"key":"2022041913105741600_CIT0018","first-page":"104","article-title":"Pyrexia of unknown origin: a prospective study of 100 cases.","volume":"47","author":"Kejariwal","year":"2001","journal-title":"J Postgrad Med"},{"key":"2022041913105741600_CIT0019","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0953-6205(03)00075-X","article-title":"Fever of unknown origin-predictors of outcome. A prospective multicenter study on 164 patients.","volume":"14","author":"Baicus","year":"2003","journal-title":"Eur J Intern Med"},{"key":"2022041913105741600_CIT0020","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1001\/archinte.163.9.1033","article-title":"From prolonged febrile illness to fever of unknown origin: the challenge continues.","volume":"163","author":"Vanderschueren","year":"2003","journal-title":"Arch Intern Med"},{"key":"2022041913105741600_CIT0021","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jinf.2003.08.006","article-title":"Fever of unknown origin in Turkey: evaluation of 87 cases during a nine-year-period of study.","volume":"48","author":"Saltoglu","year":"2004","journal-title":"J Infect"},{"key":"2022041913105741600_CIT0022","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jinf.2004.06.007","article-title":"Revised definition of \u201cfever of unknown origin\u201d: limitations and opportunities.","volume":"50","author":"Erg\u00f6n\u00fcl","year":"2005","journal-title":"J Infect"},{"key":"2022041913105741600_CIT0023","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ijid.2007.04.013","article-title":"The spectrum of diseases causing fever of unknown origin in Turkey: a multicenter study.","volume":"12","author":"Kucukardali","year":"2008","journal-title":"Int J Infect Dis"},{"key":"2022041913105741600_CIT0024","doi-asserted-by":"crossref","first-page":"26","DOI":"10.33899\/mmed.2010.8927","article-title":"Fever of unknown origin: a prospective study in northern Iraq.","volume":"36","author":"Adil Khalil","year":"2010","journal-title":"Ann Coll Med Mosul"},{"key":"2022041913105741600_CIT0025","first-page":"379","article-title":"Clinical spectrum of fever of unknown origin among adult Egyptian patients admitted to Ain Shams University Hospitals: a hospital based study.","volume":"41","author":"Ali-Eldin","year":"2011","journal-title":"J Egypt Soc 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for acute infection: true or false?","volume":"23","author":"Landry","year":"2016","journal-title":"Clin Vaccine Immunol"},{"key":"2022041913105741600_CIT0036","article-title":"Brucella.","volume-title":"Manual of Clinical Microbiology, 12th ed","author":"Araj","year":"2019"},{"key":"2022041913105741600_CIT0037","doi-asserted-by":"crossref","first-page":"135","DOI":"10.31729\/jnma.229","article-title":"Bone marrow culture vs blood culture in FUO.","volume":"48","author":"Jha","year":"2009","journal-title":"J Nepal Med Assoc"},{"key":"2022041913105741600_CIT0038","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1186\/s12879-015-1248-6","article-title":"Evaluation of sensitivity and specificity of ELISA against Widal test for typhoid diagnosis in endemic population of Kathmandu.","volume":"15","author":"Adhikari","year":"2015","journal-title":"BMC Infect 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