{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:34:40Z","timestamp":1794004480937,"version":"4.8.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T00:00:00Z","timestamp":1688428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>In Spain, the largest human West Nile virus (WNV) outbreak among humans was reported in 2020, constituting the second most important outbreak in Europe that season. Extremadura (southwestern Spain) was one of the affected areas, reporting six human cases. The first autochthonous human case in Spain was reported in Extremadura in 2004, and no other human cases were reported until 2020. In this work, we describe the first WNV human outbreak registered in Extremadura, focusing on the most important clinical aspects, diagnostic results, and control actions which followed. In 2020, from September to October, human WNV infections were diagnosed using a combination of molecular and serological methods (an in-house specific qRT-PCR and a commercial ELISA for anti-WNV IgM and IgG antibodies) and by analysing serum, urine, and\/or cerebrospinal fluid samples. Serological positive serum samples were further tested using commercial kits against related flaviviruses Usutu and Tick-borne encephalitis in order to analyse serological reactivity and to confirm the results by neutralisation assays. In total, six cases of WNV infection (five with neuroinvasive disease and one with fever) were identified. Clinical presentation and laboratory findings are described. No viral RNA was detected in any of the analysed samples, but serological cross-reactivity was detected against the other tested flaviviruses. Molecular and serological methods for WNV detection in various samples as well as differential diagnosis are recommended. The largest number of human cases of WNV infection ever registered in Extremadura, Spain, occurred in 2020 in areas where circulation of WNV and other flaviviruses has been previously reported in humans and animals. Therefore, it is necessary to enhance surveillance not only for the early detection and implementation of response measures for WNV but also for other emerging flaviviruses that could be endemic in this area.<\/jats:p>","DOI":"10.3389\/fcimb.2023.1155867","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T18:44:36Z","timestamp":1690569876000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["West Nile virus emergence in humans in Extremadura, Spain 2020"],"prefix":"10.3389","volume":"13","author":[{"given":"Alicia","family":"Macias","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Mart\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayte","family":"P\u00e9rez-Olmeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Fern\u00e1ndez-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"G\u00f3mez-Barroso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esperanza","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian Mauro","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Herrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saray","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Delgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paz","family":"S\u00e1nchez-Seco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Gal\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Jes\u00fas","family":"Corbacho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Jimenez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Montero-Pe\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Valle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"V\u00e1zquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens8040193","article-title":"Current understanding of West Nile virus clinical manifestations, immune responses, neuroinvasion, and immunotherapeutic implications","volume":"8","author":"Bai","year":"2019","journal-title":"Pathogens"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3411","DOI":"10.1128\/JCM.01328-14","article-title":"Isolation of West Nile virus from urine samples of patients with acute infection","volume":"52","author":"Barzon","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1586\/14787210.2015.1007044","article-title":"Latest developments and challenges in the diagnosis of human West Nile virus infection","volume":"13","author":"Barzon","year":"2015","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2021.109020","article-title":"West Nile and usutu virus infections in wild birds admitted to rehabilitation centres in extremadura, western Spain 2017\u20132019","volume":"255","author":"Bravo-Barriga","year":"2021","journal-title":"Vet. Microbiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1155\/2023\/6893677","article-title":"Identification of usutu virus Africa 3 lineage in a survey of mosquitoes and birds from urban areas of Western Spain","author":"Bravo-Barriga","year":"2023","journal-title":"Transbound Emerg. Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1086\/506939","article-title":"Long-term clinical and neuropsychological outcomes of West Nile virus infection","volume":"43","author":"Carson","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens12010083","article-title":"Risk factors for exposure of wild birds to West Nile virus in a gradient of wildlife-livestock interaction","volume":"12","author":"Casades-Mart\u00ed","year":"2023","journal-title":"Pathogens"},{"key":"B8","unstructured":"StockholmWest Nile Virus infection. annual epidemiological report for 20182019"},{"key":"B9","unstructured":"Epidemiological update: West Nile virus transmission season in Europe 20202020"},{"key":"B10","unstructured":"Epidemiological update: West Nile virus transmission season in Europe 20212022"},{"key":"B11","unstructured":"Weekly updates: 2022 West Nile virus transmission season2022"},{"key":"B12","unstructured":"Commission implementing decision (EU) 2018\/945 of 22 June 2018 on the communicable diseases and related special health issues to be covered by epidemiological surveillance as well as relevant case definitions2018"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2397","DOI":"10.3201\/eid1712.110651","article-title":"West Nile Fever outbreak in horses and humans, spai","volume":"17","author":"Garc\u00eda-Bocanegra","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1111\/tbed.12801","article-title":"Exposure to West Nile virus and tick-borne encephalitis virus in dogs in Spain","volume":"65","author":"Garc\u00eda-Bocanegra","year":"2018","journal-title":"Transbound Emerg. Dis."},{"key":"B15","doi-asserted-by":"publisher","first-page":"pii=2002010","DOI":"10.2807\/1560-7917.ES.2021.26.19.2002010","article-title":"Unprecedented increase of West Nile virus neuroinvasive disease, Spain, summer 2020","volume":"26","author":"Garc\u00eda San Miguel Rodr\u00edguez-Alarc\u00f3n","year":"2021","journal-title":"Eurosurveillance"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S59902","article-title":"A review of the epidemiological and clinical aspects of West Nile virus","volume":"7","author":"Gray","year":"2014","journal-title":"Int. J. Gen. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1111\/tbed.13810","article-title":"Serological evidence of co-circulation of West Nile and usutu viruses in equids from western Spain","volume":"68","author":"Guerrero-Carvajal","year":"2021","journal-title":"Transbound Emerg. Dis."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148898","article-title":"West Nile Virus retinopathy and associations with long term neurological and neurocognitive sequelae","volume":"11","author":"Hasbun","year":"2016","journal-title":"PloS One"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1086\/518281","article-title":"The long-term outcomes of human West Nile virus infection","volume":"44","author":"Hughes","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"B20","unstructured":"Fiebre del nilo occidental2021"},{"key":"B21","volume-title":"Informe epidemiol\u00f3gico sobre la situaci\u00f3n de la fiebre del nilo occidental en espa\u00f1a. a\u00f1os 2021 y 2022","year":"2022"},{"key":"B22","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1080\/00365540600740553","article-title":"West Nile Virus in Spain: report of the first diagnosed case (in Spain) in a human with aseptic meningitis","volume":"39","author":"Kaptoul","year":"2007","journal-title":"Scand. J. Infect. Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e20190065","DOI":"10.1590\/0037-8682-0065-2019","article-title":"West Nile Virus retinitis in a patient with neuroinvasive disease","volume":"52","author":"Konjevoda","year":"2019","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"B24","doi-asserted-by":"publisher","first-page":"179","DOI":"10.4269\/ajtmh.2012.12-0113","article-title":"Medical risk factors for severe West Nile virus disease, united states 2008\u20132010","volume":"87","author":"Lindsey","year":"2012","journal-title":"Am. J. Trop. Med. Hyg"},{"key":"B25","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1089\/vbz.2009.0232","article-title":"Incidence of West Nile virus in birds arriving in wildlife rehabilitation centers in southern Spain","volume":"11","author":"L\u00f3pez","year":"2011","journal-title":"Vector-Borne Zoonotic Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"pii=17-00261","DOI":"10.2807\/1560-7917.ES.2018.23.14.17-00261","article-title":"West Nile Virus outbreak in humans and epidemiological surveillance, west Andalusia, spai","volume":"23","author":"L\u00f3pez-Ruiz","year":"2018","journal-title":"Eurosurveillance"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02421","article-title":"Surveillance and diagnosis of West Nile virus in the face of flavivirus cross-reactivity","volume":"9","author":"Lustig","year":"2018","journal-title":"Front. Microbiol."},{"key":"B28","unstructured":"2023"},{"key":"B29","unstructured":"Actualizaci\u00f3n de la situaci\u00f3n epidemiol\u00f3gica de la fiebre del nilo occidental (West Nile fever)2023"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/v13122404","article-title":"Widespread circulation of flaviviruses in horses and birds in northeastern Spain (Catalonia) between 2010 and 2019","volume":"13","author":"Napp","year":"2021","journal-title":"Viruses"},{"key":"B31","unstructured":"MadridVirus del nilo occidental2021"},{"key":"B32","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.virol.2009.09.013","article-title":"Characterization of West Nile virus isolates from Spain: new insights into the distinct West Nile virus eco-epidemiology in the Western Mediterranean","volume":"395","author":"Sotelo","year":"2009","journal-title":"Virology"},{"key":"B33","unstructured":"Meningoencefalitis por el virus del nilo occidental en espa\u00f1a (2a actualizaci\u00f3n-cierre de temporada)2020"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2232","DOI":"10.1128\/JCM.38.6.2232-2239.2000","article-title":"Evaluation of immunoglobulin m (IgM) and IgG enzyme immunoassays in serologic diagnosis of West Nile virus infection","volume":"38","author":"Tardei","year":"2000","journal-title":"J. Clin. Microbiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1089\/vbz.2016.2042","article-title":"Circulation of zoonotic arboviruses in equine populations of mallorca island (Spain)","volume":"17","author":"Vanhomwegen","year":"2017","journal-title":"Vector Borne Zoonotic Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.jviromet.2016.07.026","article-title":"Real time PCR assay for detection of all known lineages of West Nile virus","volume":"236","author":"V\u00e1zquez","year":"2016","journal-title":"J. Virol. Methods"},{"key":"B37","doi-asserted-by":"publisher","first-page":"178","DOI":"10.4269\/ajtmh.2011.11-0042","article-title":"West Nile And usutu viruses in mosquitoes in Spain 2008-2009","volume":"85","author":"V\u00e1zquez","year":"2011","journal-title":"Am. J. Trop. Med. Hyg"},{"key":"B38","doi-asserted-by":"publisher","first-page":"549","DOI":"10.3201\/eid1603.091033","article-title":"Putative new lineage of West Nile virus, Spain","volume":"16","author":"V\u00e1zquez","year":"2010","journal-title":"Emerg. Infect. Dis."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/v12020156","article-title":"Imported human West Nile virus lineage 2 infection in Spain: neurological and gastrointestinal complications","volume":"12","author":"Velasco","year":"2020","journal-title":"Viruses"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1155867\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T18:44:42Z","timestamp":1690569882000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1155867\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,4]]},"references-count":39,"alternative-id":["10.3389\/fcimb.2023.1155867"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2023.1155867","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,4]]},"article-number":"1155867"}}