{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:58:12Z","timestamp":1790517492684,"version":"4.1.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["106680\/B\/14\/Z"],"award-info":[{"award-number":["106680\/B\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Hand, Foot and Mouth Disease (HFMD) is a major public health concern in the Asia-Pacific region. Most recent HFMD outbreaks have been caused by enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), CVA10, and CVA6. There has been no report regarding the epidemiology and genetic diversity of CVA16 in Vietnam. Such knowledge is critical to inform the development of intervention strategies.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Materials and Methods:<\/jats:bold>\n                    From 2011 to 2017, clinical samples were collected from in- and outpatients enrolled in a HFMD research program conducted at three referral hospitals in Ho Chi Minh City (HCMC), Vietnam. Throat or rectal swabs positive for CVA16 with sufficient viral load were selected for whole genome sequencing and evolutionary analysis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Throughout the study period, 320 CVA16 positive samples were collected from 2808 HFMD patients (11.4%). 59.4% of patients were male. The median age was 20.8 months (IQR, 14.96\u201331.41). Patients resided in HCMC (55.3%), Mekong Delta (22.2%), and South East Vietnam (22.5%). 10% of CVA16 infected patients had moderately severe or severe HFMD. CVA16 positive samples from 153 patients were selected for whole genome sequencing, and 66 complete genomes were obtained. Phylogenetic analysis demonstrated that Vietnamese CVA16 strains belong to a single genogroup B1a that clusters together with isolates from China, Japan, Thailand, Malaysia, France and Australia. The CVA16 strains of the present study were circulating in Vietnam some 4 years prior to its detection in HFMD cases.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    We report for the first time on the molecular epidemiology of CVA16 in Vietnam. Unlike EV-A71, which showed frequent replacement between subgenogroups B5 and C4 every 2\u20133 years in Vietnam, CVA16 displays a less pronounced genetic alternation with only subgenogroup B1a circulating in Vietnam since 2011. Our collective findings emphasize the importance of active surveillance for viral circulation in HFMD endemic countries, critical to informing outbreak response and vaccine development.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2021.689658","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T11:26:23Z","timestamp":1624533983000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Coxsackievirus A16 in Southern Vietnam"],"prefix":"10.3389","volume":"12","author":[{"given":"Le Nguyen Truc","family":"Nhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Nguyen Thanh","family":"Nhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen To","family":"Anh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi Thu","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoang Minh Tu","family":"Van","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tran Tan","family":"Thanh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vu Thi Ty","family":"Hang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do Duong Kim","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi Han","family":"Ny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lam Anh","family":"Nguyet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du Tuan","family":"Quy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phan Tu","family":"Qui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Truong Huu","family":"Khanh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thanh","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha Manh","family":"Tuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Van Vinh","family":"Chau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Thwaites","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Rogier van","family":"Doorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Van","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/microorganisms8121856","article-title":"Epidemiology and sequence-based evolutionary analysis of circulating non-polio enteroviruses.","volume":"8","author":"Brown","year":"2020","journal-title":"Microorganisms"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-019-3878-6","article-title":"Clinical characteristics and managements of severe hand, foot and mouth disease caused by enterovirus A71 and coxsackievirus A16 in Shanghai.","volume":"19","author":"Cai","year":"2019","journal-title":"China. BMC Infect. Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1007\/s00705-018-4112-3","article-title":"Molecular surveillance of coxsackievirus A16 reveals the emergence of a new clade in mainland China.","volume":"164","author":"Chen","year":"2019","journal-title":"Arch. Virol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1017\/dmp.2018.155","article-title":"Profiles of human enteroviruses associated with hand, foot, and mouth disease in nanjing, China.","volume":"13","author":"Chen","year":"2019","journal-title":"Disaster Med. Public Health Prep."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2148-7-214","article-title":"BEAST: bayesian evolutionary analysis by sampling trees.","volume":"7","author":"Drummond","year":"2007","journal-title":"BMC Evol. Biol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s10096-018-3206-x","article-title":"Hand, foot and mouth disease: Current knowledge on clinical manifestations, epidemiology, aetiology and prevention.","volume":"37","author":"Esposito","year":"2018","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"8871","DOI":"10.1128\/jvi.00706-15","article-title":"Phylodynamics of enterovirus A71-associated hand, foot, and mouth disease in viet nam.","volume":"89","author":"Geoghegan","year":"2015","journal-title":"J. Virol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ve\/veaa084","article-title":"Genomic epidemiology of coxsackievirus A16 in mainland of China, 2000\u201318.","volume":"6","author":"Han","year":"2020","journal-title":"Virus Evol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1007\/bf02101990","article-title":"A new method for calculating evolutionary substitution rates.","volume":"20","author":"Lanave","year":"1984","journal-title":"J. Mol. Evol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2018.23.46.1800590","article-title":"Severe enterovirus A71 associated hand, foot and mouth disease. Vietnam, 2018: preliminary report of an impending outbreak.","volume":"23","author":"Le","year":"2018","journal-title":"Eurosurveillance"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0008544","article-title":"Clinical, etiological and epidemiological investigations of hand, foot and mouth disease in Southern Vietnam during 2015 \u2013 2018.","volume":"14","author":"Le","year":"2020","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/vev003","article-title":"RDP4: detection and analysis of recombination patterns in virus genomes.","volume":"1","author":"Martin","year":"2015","journal-title":"Virus Evol."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0008885","article-title":"An epidemiological surveillance of hand foot and mouth disease in paediatric patients and in community: a singapore retrospective cohort study, 2013\u20132018.","volume":"15","author":"Min","year":"2021","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1093\/molbev\/msu300","article-title":"IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies.","volume":"32","author":"Nguyen","year":"2015","journal-title":"Mol. Biol. Evol."},{"key":"B15","first-page":"17","article-title":"Emerging coxsackievirus A6 causing hand. foot and mouth disease, vietnam.","volume":"24","author":"Nguyen","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/s12985-016-0580-9","article-title":"Development and evaluation of a non-ribosomal random PCR and next-generation sequencing based assay for detection and sequencing of hand, foot and mouth disease pathogens.","volume":"13","author":"Nguyen","year":"2016","journal-title":"Virol. J."},{"key":"B17","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.ijid.2018.12.020","article-title":"Longitudinal study on enterovirus A71 and coxsackievirus A16 genotype\/subgenotype replacements in hand, foot and mouth disease patients in Thailand, 2000\u20132017.","volume":"80","author":"Noisumdaeng","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41426-018-0215-x","article-title":"Complete genome analysis demonstrates multiple introductions of enterovirus 71 and coxsackievirus A16 recombinant strains into Thailand during the past decade.","volume":"7","author":"Noisumdaeng","year":"2018","journal-title":"Emerg. Microbes Infect."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1007\/s00705-006-0934-5","article-title":"Molecular phylogeny of modern coxsackievirus A16.","volume":"152","author":"Perera","year":"2007","journal-title":"Arch. Virol."},{"key":"B20","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.3201\/eid1311.070632","article-title":"Epidemiologic and virologic investigation of hand, foot, and mouth disease, southern Vietnam, 2005.","volume":"13","author":"Phan","year":"2007","journal-title":"Emerg. Infect. Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1093\/sysbio\/syy032","article-title":"Posterior summarization in bayesian phylogenetics using tracer 1.7.","volume":"67","author":"Rambaut","year":"2018","journal-title":"Syst. Biol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/vew007","article-title":"Exploring the temporal structure of heterochronous sequences using tempEst (formerly Path-O-Gen).","volume":"2","author":"Rambaut","year":"2016","journal-title":"Virus Evol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/S0168-1702(00)00162-3","article-title":"Genetic analysis of enterovirus 71 isolated from fatal and non-fatal cases of hand, foot and mouth disease during an epidemic in Taiwan, 1998.","volume":"68","author":"Shih","year":"2000","journal-title":"Virus Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1128\/jvi.80.1.483-493.2006","article-title":"Frequency and dynamics of recombination within different species of human enteroviruses.","volume":"80","author":"Simmonds","year":"2006","journal-title":"J. Virol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1111\/j.1348-0421.2002.tb02767.x","article-title":"Complete sequence analyses of enterovirus 71 strains from fatal and non-fatal cases of the hand, foot and mouth disease outbreak in Singapore (2000).","volume":"46","author":"Singh","year":"2002","journal-title":"Microbiol. Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/oxfordjournals.molbev.a040023","article-title":"Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees.","volume":"10","author":"Tamura","year":"1993","journal-title":"Mol. Biol. Evol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3339","DOI":"10.1128\/JVI.01019-09","article-title":"Evolutionary genetics of human enterovirus 71: origin, population dynamics, natural selection, and seasonal periodicity of the VP1 gene.","volume":"84","author":"Tee","year":"2010","journal-title":"J. Virol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"788","DOI":"10.3201\/eid2504.181367","article-title":"Enterovirus A71 phenotypes causing hand, foot and mouth disease. Vietnam.","volume":"25","author":"Van Hoang","year":"","journal-title":"Emerg. Infect. Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijid.2018.12.004","article-title":"Clinical and aetiological study of hand, foot and mouth disease in southern Vietnam, 2013\u20132015: inpatients and outpatients.","volume":"80","author":"Van Hoang","year":"","journal-title":"Int. J. Infect. Dis."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.689658\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T11:26:29Z","timestamp":1624533989000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.689658\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,24]]},"references-count":29,"alternative-id":["10.3389\/fmicb.2021.689658"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2021.689658","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,24]]},"article-number":"689658"}}