{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T14:18:27Z","timestamp":1760710707144,"version":"3.40.5"},"reference-count":69,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Programa Polos de Desarrollo Universitario from Comisi\u00f3n Coordinadora del Interior of the Universidad de la Rep\u00fablica, Uruguay","award":["PDU 2010"],"award-info":[{"award-number":["PDU 2010"]}]},{"name":"Agencia Nacional de Investigaci\u00f3n e Innovaci\u00f3n (ANII), Uruguay","award":["Sistema Nacional de Investigadores (SNI)"],"award-info":[{"award-number":["Sistema Nacional de Investigadores (SNI)"]}]},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Argentina","award":["Investigador CONICET"],"award-info":[{"award-number":["Investigador CONICET"]}]},{"name":"Comisi\u00f3n Acad\u00e9mica de Posgrado (CAP) and Programa de Desarrollo de las Ciencias B\u00e1sicas (PEDECIBA) of Universidad de la Rep\u00fablica, Uruguay","award":["PhD scholarship 2016\u20132019"],"award-info":[{"award-number":["PhD scholarship 2016\u20132019"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Human enteroviruses (EVs) comprise more than 100 types of coxsackievirus, echovirus, poliovirus and numbered enteroviruses, which are mainly transmitted by the faecal-oral route leading to diverse diseases such as aseptic meningitis, encephalitis, and acute flaccid paralysis, among others. Since enteroviruses are excreted in faeces, wastewater-based epidemiology approaches are useful to describe EV diversity in a community. In Uruguay, knowledge about enteroviruses is extremely limited. This study assessed the diversity of enteroviruses through Illumina next-generation sequencing of VP1-amplicons obtained by RT-PCR directly applied to viral concentrates of 84 wastewater samples collected in Uruguay during 2011\u20132012 and 2017\u20132018. Fifty out of the 84 samples were positive for enteroviruses. There were detected 27 different types belonging to <jats:italic>Enterovirus A<\/jats:italic> species (CVA2-A6, A10, A16, EV-A71, A90), <jats:italic>Enterovirus B<\/jats:italic> species (CVA9, B1-B5, E1, E6, E11, E14, E21, E30) and <jats:italic>Enterovirus C<\/jats:italic> species (CVA1, A13, A19, A22, A24, EV-C99). Enterovirus A71 (EV-A71) and echovirus 30 (E30) strains were studied more in depth through phylogenetic analysis, together with some strains previously detected by us in Argentina. Results unveiled that EV-A71 sub-genogroup C2 circulates in both countries at least since 2011\u20132012, and that the C1-like emerging variant recently entered in Argentina. We also confirmed the circulation of echovirus 30 genotypes E and F in Argentina, and reported the detection of genotype E in Uruguay. To the best of our knowledge this is the first report of the EV-A71 C1-like emerging variant in South-America, and the first report of EV-A71 and E30 in Uruguay.<\/jats:p>","DOI":"10.1371\/journal.pone.0255846","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T18:58:42Z","timestamp":1628794722000},"page":"e0255846","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["First evidence of enterovirus A71 and echovirus 30 in Uruguay and genetic relationship with strains circulating in the South American region"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8062-6916","authenticated-orcid":true,"given":"Andr\u00e9s","family":"Lizasoain","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiana","family":"Mir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mat\u00edas","family":"Salvo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviana","family":"Bortagaray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gisela","family":"Masachessi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adri\u00e1n","family":"Far\u00edas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N\u00e9lida","family":"Rodr\u00edguez-Osorio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Nates","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mat\u00edas","family":"Victoria","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodney","family":"Colina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"pone.0255846.ref001","first-page":"723","volume-title":"Enteroviruses: 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serotypes and provides new insight into enterovirus 5\u2019-untranslated region evolution","author":"T Smura","year":"2007","journal-title":"J Gen Virol"},{"key":"pone.0255846.ref007","article-title":"Coxsackievirus A6 and hand, foot, and mouth disease, Finland","author":"R Osterback","year":"2009","journal-title":"Emerg Infect Dis"},{"key":"pone.0255846.ref008","article-title":"A fatal central nervous system enterovirus 68 infection","author":"JD Kreuter","year":"2011","journal-title":"Arch Pathol Lab Med"},{"key":"pone.0255846.ref009","article-title":"Newly Identified Enterovirus C Genotypes, Identified in the Netherlands through Routine Sequencing of All Enteroviruses Detected in Clinical Materials from 2008 to 2015.","author":"CC Van Leer-Buter","year":"2016","journal-title":"J Clin Microbiol"},{"key":"pone.0255846.ref010","article-title":"Polio\u2014The old foe and new challenges: An update for clinicians.","author":"J Bao","year":"2020","journal-title":"J Paediatr Child Health."},{"key":"pone.0255846.ref011","article-title":"Non-polio Enterovirus detection with acute flaccid paralysis: A systematic review","author":"S Suresh","year":"2018","journal-title":"J Med Virol"},{"key":"pone.0255846.ref012","article-title":"Molecular epidemiology of enteroviruses associated with severe hand, foot and mouth disease in Shenzhen, China, 2014\u20132018","author":"L Chen","year":"2020","journal-title":"Arch Virol"},{"key":"pone.0255846.ref013","article-title":"Enterovirus infection and acute flaccid myelitis.","author":"P Uprety","year":"2020","journal-title":"Curr Opin Virol."},{"key":"pone.0255846.ref014","article-title":"Diseases caused by enterovirus 71 infection.","author":"TC Lee","year":"2009","journal-title":"Pediatr Infect Dis J."},{"key":"pone.0255846.ref015","article-title":"WHO working group meeting to develop WHO Recommendations to assure the quality, safety and efficacy of enterovirus 71 vaccines","author":"D Lei","year":"2020","journal-title":"Vaccine"},{"key":"pone.0255846.ref016","article-title":"Enterovirus A71 Vaccines.","author":"ML Li","year":"2021","journal-title":"Vaccines (Basel)."},{"key":"pone.0255846.ref017","article-title":"Identification and Phylogenetic Characterization of Human Enteroviruses Isolated from Cases of Aseptic Meningitis in Brazil, 2013\u20132017.","author":"E Ramalho","year":"2019","journal-title":"Viruses"},{"key":"pone.0255846.ref018","article-title":"Circulation of non-polio enteroviruses in 24 EU and EEA countries between 2015 and 2017: a retrospective surveillance study.","author":"Enterovirus study collaborators","year":"2020","journal-title":"Lancet Infect Dis."},{"key":"pone.0255846.ref019","article-title":"Transmission networks and population turnover of echovirus 30","author":"EC McWilliam Leitch","year":"2009","journal-title":"J Virol"},{"key":"pone.0255846.ref020","article-title":"Epidemiology and Sequence-Based Evolutionary Analysis of Circulating Non-Polio Enteroviruses.","author":"DM Brown","year":"2020","journal-title":"Microorganisms"},{"key":"pone.0255846.ref021","article-title":"Genetic diversity and molecular characterization of enteroviruses from sewage-polluted urban and rural rivers in the Philippines","author":"LN Apostol","year":"2012","journal-title":"Virus Genes"},{"key":"pone.0255846.ref022","article-title":"Environmental surveillance of poliovirus and non-polio enterovirus in urban sewage in Dakar, Senegal (2007\u20132013).","author":"AK Ndiaye","year":"2014","journal-title":"Pan Afr Med J."},{"key":"pone.0255846.ref023","article-title":"Poliovirus and non-polio-enterovirus environmental surveillance in Parma within the \"Global Polio Eradication Program\" (GPEI).","author":"R Zoni","year":"2019","journal-title":"Acta Biomed"},{"key":"pone.0255846.ref024","article-title":"Monitoring of enterovirus diversity in wastewater by ultra-deep sequencing: An effective complementary tool for clinical enterovirus surveillance","author":"M Bisseux","year":"2020","journal-title":"Water Res"},{"key":"pone.0255846.ref025","first-page":"91566","article-title":"Outbreak of paralytic poliomyelitis in Finland: widespread circulation of antigenically altered poliovirus type 3 in a vaccinated population","author":"T Hovi","year":"1986","journal-title":"Lancet"},{"key":"pone.0255846.ref026","article-title":"A large Finnish echovirus 30 outbreak was preceded by silent circulation of the same genotype","author":"C Savolainen-Kopra","year":"2011","journal-title":"Virus Genes"},{"key":"pone.0255846.ref027","article-title":"Molecular epidemiology and phylogenetics of human enteroviruses: Is there a forest behind the trees?","author":"AN Lukashev","year":"2018","journal-title":"Rev Med Virol."},{"key":"pone.0255846.ref028","article-title":"An Environmental Surveillance in Uruguay Reveals the Presence of Highly Divergent Types of Human Enterovirus Species C and a High Frequency of Species A and B 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Taiwan Enterovirus Epidemic Working Group","author":"M Ho","year":"1999","journal-title":"N Engl J Med"},{"key":"pone.0255846.ref042","article-title":"Hand, foot, and mouth disease in China: patterns of spread and transmissibility.","author":"Y Wang","year":"2011","journal-title":"Epidemiology"},{"key":"pone.0255846.ref043","article-title":"Enterovirus and Encephalitis.","author":"BS Chen","year":"2020","journal-title":"Front Microbiol"},{"key":"pone.0255846.ref044","article-title":"The Epidemiological and Clinical Characteristics of Hand, Foot, and Mouth Disease in Hangzhou, China, 2016 to 2018.","author":"J Wang","year":"2020","journal-title":"Clin Pediatr (Phila)."},{"key":"pone.0255846.ref045","article-title":"Coxsackievirus A10 causing hand-foot-and-mouth disease in Uruguay","author":"A Lizasoain","year":"2020","journal-title":"Int J Infect Dis"},{"key":"pone.0255846.ref046","article-title":"Hand-foot-and-mouth disease in uruguay: Coxsackievirus A6 identified as causative of an outbreak in a rural childcare center","author":"A Lizasoain","year":"2020","journal-title":"J Med Virol"},{"key":"pone.0255846.ref047","article-title":"Molecular epidemiology and evolution of enterovirus 71 strains isolated from 1970 to 1998.","author":"BA Brown","year":"1999","journal-title":"J Virol"},{"key":"pone.0255846.ref048","article-title":"Molecular and seroepidemiologic studies of Enterovirus 71 infection in the State of Para, Brazil.","author":"CM Castro","year":"2005","journal-title":"Rev Inst Med Trop Sao Paulo."},{"key":"pone.0255846.ref049","article-title":"Evidence of enterovirus 71 infections in Brazil.","author":"EE da Silva","year":"1990","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"pone.0255846.ref050","article-title":"Enterovirus-71 genotype C isolated in Peru between 2006 and 2009.","author":"JL Huaman","year":"2016","journal-title":"J Clin Virol."},{"key":"pone.0255846.ref051","article-title":"Molecular characterization and epidemiological aspects of non-polio enteroviruses isolated from acute flaccid paralysis in Brazil: a historical series (2005\u2013","author":"IP Sousa","year":"2017","journal-title":"Emerg Microbes Infect. 2020"},{"issue":"8","key":"pone.0255846.ref052","first-page":"1","article-title":"Enterovirus surveillance\u2014United States, 1970\u20132005.","volume":"55","author":"Centers for Disease Control and Prevention","year":"2006","journal-title":"MMWR Surveill Summ."},{"key":"pone.0255846.ref053","article-title":"Outbreak of neurologic enterovirus type 71 disease: a diagnostic challenge","author":"CM P\u00e9rez-V\u00e9lez","year":"2007","journal-title":"Clin Infect Dis"},{"key":"pone.0255846.ref054","article-title":"Recent advances in the molecular epidemiology and control of human enterovirus 71 infection.","author":"PC McMinn","year":"2012","journal-title":"Curr Opin Virol."},{"key":"pone.0255846.ref055","article-title":"Clinical characteristics of enterovirus A71 neurological disease during an outbreak in children in Colorado, USA, in 2018: an observational cohort study","author":"K Messacar","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"pone.0255846.ref056","article-title":"Coxsackievirus A6 and enterovirus 71 causing hand, foot and mouth disease in Cuba, 2011\u20132013","author":"MC Fonseca","year":"2014","journal-title":"Arch Virol"},{"journal-title":"Euro Surveill.","article-title":"Increased detection of enterovirus A71 infections, Germany, 2019.","author":"The Laboratory Network For Enterovirus Diagnostic LaNED.","key":"pone.0255846.ref057"},{"key":"pone.0255846.ref058","article-title":"Recombinant Enterovirus A71 Subgenogroup C1 Strains, Germany, 2015.","author":"Laboratory Network for Enterovirus Diagnostics.","year":"2016","journal-title":"Emerg Infect Dis"},{"key":"pone.0255846.ref059","article-title":"Co-circulation of multiple subtypes of enterovirus A71 (EV- A71) genotype C, including novel recombinants characterised by use of whole genome sequencing (WGS), Denmark 2016.","author":"SE Midgley","year":"2017","journal-title":"Euro Surveill."},{"key":"pone.0255846.ref060","article-title":"Molecular epidemiology of an enterovirus A71 outbreak associated with severe neurological disease, Spain, 2016.","author":"R Gonz\u00e1lez-Sanz","year":"2019","journal-title":"Euro Surveill."},{"key":"pone.0255846.ref061","article-title":"Multirecombinant Enterovirus A71 Subgenogroup C1 Isolates Associated with Neurologic Disease, France, 2016\u20132017","author":"ST Ngangas","year":"2019","journal-title":"Emerg Infect Dis"},{"key":"pone.0255846.ref062","article-title":"Molecular epidemiology of enteroviruses in Cyprus 2008\u20132017.","author":"J Richter","year":"2019","journal-title":"PLoS One."},{"key":"pone.0255846.ref063","article-title":"Emergence of a non vaccine-cognate enterovirus A71 genotype C1 in mainland China.","author":"H Zeng","year":"2021","journal-title":"J Infect."},{"key":"pone.0255846.ref064","article-title":"Long-term cognitive and motor deficits after enterovirus 71 brainstem encephalitis in children","author":"MC Huang","year":"2006","journal-title":"Pediatrics"},{"key":"pone.0255846.ref065","article-title":"Human enterovirus 71 epidemics: what\u2019s next?","author":"CC Yip","year":"2013","journal-title":"Emerg Health Threats J."},{"key":"pone.0255846.ref066","article-title":"Enterovirus A71 neurologic complications and long-term sequelae","author":"LY Chang","year":"2019","journal-title":"J Biomed Sci"},{"key":"pone.0255846.ref067","article-title":"Genetic diversity of Echovirus 30 involved in aseptic meningitis cases in Brazil (1998\u20132008).","author":"GP dos Santos","year":"2011","journal-title":"J Med Virol"},{"key":"pone.0255846.ref068","article-title":"Molecular identification of human enteroviruses in children with neurological infections from the central region of Argentina","author":"A Far\u00edas","year":"2011","journal-title":"Arch Virol"},{"key":"pone.0255846.ref069","article-title":"Molecular 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