{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T23:52:46Z","timestamp":1784332366226,"version":"3.55.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["216427\/Z\/19\/Z"],"award-info":[{"award-number":["216427\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009187","name":"Medical Research Foundation","doi-asserted-by":"publisher","award":["MR\/R015600\/1"],"award-info":[{"award-number":["MR\/R015600\/1"]}],"id":[{"id":"10.13039\/501100009187","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["ISSF204826\/Z\/16\/Z"],"award-info":[{"award-number":["ISSF204826\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Enterovirus A71 (EV-A71) and coxsackievirus A6 (CVA6) primarily cause hand, foot and mouth disease and have emerged to cause potential fatal neurological and systemic manifestations. However, limited surveillance data collected through passive surveillance systems hampers characterization of their epidemiological dynamics. We fit a series of catalytic models to age-stratified seroprevalence data for EV-A71 and CVA6 collected in England at three time points (2006, 2011 and 2017) to estimate the force of infection (FOI) over time and assess possible changes in transmission. For both serotypes, model comparison does not support the occurrence of important changes in transmission over the study period, and we find that a declining risk of infection with age and \/ or seroreversion are needed to explain the seroprevalence data. Furthermore, we provide evidence that the increased number of reports of CVA6 during 2006\u20132017 is unlikely to be explained by changes in surveillance. Therefore, we hypothesize that the increased number of CVA6 cases observed since 2011 must be explained by increased virus pathogenicity. Further studies of seroprevalence data from other countries would allow to confirm this. Our results underscore the value of seroprevalence data to unravel changes in the circulation dynamics of pathogens with weak surveillance systems and large number of asymptomatic infections.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012703","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T18:23:28Z","timestamp":1732127008000},"page":"e1012703","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Enterovirus A71 and coxsackievirus A6 circulation in England, UK, 2006\u20132017: A mathematical modelling study using cross-sectional seroprevalence data"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4285-2255","authenticated-orcid":true,"given":"Everlyn","family":"Kamau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Celma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Beard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heli","family":"Harvala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Simmonds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C.","family":"Grassly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Pons-Salort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"issue":"3","key":"ppat.1012703.ref001","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/S1473-3099(20)30452-7","article-title":"Protecting the most vulnerable from hand, foot, and mouth disease","volume":"21","author":"YW Tan","year":"2021","journal-title":"Lancet Infect Dis"},{"issue":"10","key":"ppat.1012703.ref002","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1099\/jgv.0.000911","article-title":"ICTV Virus Taxonomy Profile: Picornaviridae","volume":"98","author":"R Zell","year":"2017","journal-title":"J Gen Virol"},{"issue":"6","key":"ppat.1012703.ref003","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.4269\/ajtmh.18-0099","article-title":"The Effect of School Closure on Hand, Foot, and Mouth Disease Transmission in Singapore: A Modeling Approach","volume":"99","author":"Y Chen","year":"2018","journal-title":"Am J Trop Med Hyg"},{"issue":"9","key":"ppat.1012703.ref004","doi-asserted-by":"crossref","first-page":"e0184266","DOI":"10.1371\/journal.pone.0184266","article-title":"Economic costs and health-related quality of life for hand, foot and mouth disease (HFMD) patients in China.","volume":"12","author":"Y Zheng","year":"2017","journal-title":"PLoS One"},{"issue":"12","key":"ppat.1012703.ref005","doi-asserted-by":"crossref","first-page":"3078","DOI":"10.1073\/pnas.1721159115","article-title":"The seasonality of nonpolio enteroviruses in the United States: Patterns and drivers","volume":"115","author":"M Pons-Salort","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"ppat.1012703.ref006","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/S1473-3099(13)70342-6","article-title":"Hand, foot, and mouth disease in China, 2008\u201312: an epidemiological study","volume":"14","author":"W Xing","year":"2014","journal-title":"Lancet Infect Dis"},{"key":"ppat.1012703.ref007","unstructured":"singapore. [Available from: https:\/\/www.ncid.sg\/Health-Professionals\/Pages\/Weekly-Infectious-Diseases-Bulletin.aspx."},{"issue":"6404","key":"ppat.1012703.ref008","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1126\/science.aat6777","article-title":"Serotype-specific immunity explains the incidence of diseases caused by human enteroviruses","volume":"361","author":"M Pons-Salort","year":"2018","journal-title":"Science"},{"issue":"3","key":"ppat.1012703.ref009","doi-asserted-by":"crossref","first-page":"e0004562","DOI":"10.1371\/journal.pntd.0004562","article-title":"Cyclical Patterns of Hand, Foot and Mouth Disease Caused by Enterovirus A71 in Malaysia.","volume":"10","author":"N NikNadia","year":"2016","journal-title":"PLoS Negl Trop Dis."},{"issue":"5","key":"ppat.1012703.ref010","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1080\/21645515.2019.1581539","article-title":"Enterovirus A71 vaccine effectiveness in preventing enterovirus A71 infection among medically-attended hand, foot, and mouth disease cases, Beijing, China.","volume":"15","author":"X Wang","year":"2019","journal-title":"Hum Vaccin Immunother."},{"issue":"9183","key":"ppat.1012703.ref011","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S0140-6736(98)11032-2","article-title":"Isolation of subgenus B adenovirus during a fatal outbreak of enterovirus 71-associated hand, foot, and mouth disease in Sibu","volume":"354","author":"MJ Cardosa","year":"1999","journal-title":"Sarawak. Lancet"},{"issue":"13","key":"ppat.1012703.ref012","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1056\/NEJM199909233411301","article-title":"An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group","volume":"341","author":"M Ho","year":"1999","journal-title":"N Engl J Med"},{"issue":"7","key":"ppat.1012703.ref013","doi-asserted-by":"crossref","DOI":"10.2807\/1560-7917.ES.2019.24.7.1800089","article-title":"Molecular epidemiology of an enterovirus A71 outbreak associated with severe neurological disease, Spain, 2016.","volume":"24","author":"R Gonzalez-Sanz","year":"2019","journal-title":"Euro Surveill."},{"issue":"39","key":"ppat.1012703.ref014","doi-asserted-by":"crossref","DOI":"10.2807\/1560-7917.ES.2019.24.39.1900556","article-title":"The Laboratory Network For Enterovirus Diagnostic La NED. Increased detection of enterovirus A71 infections, Germany, 2019","volume":"24","author":"S Bottcher","year":"2019","journal-title":"Euro Surveill."},{"issue":"2","key":"ppat.1012703.ref015","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S1473-3099(19)30632-2","article-title":"Clinical characteristics of enterovirus A71 neurological disease during an outbreak in children in Colorado, USA, in 2018: an observational cohort study","volume":"20","author":"K Messacar","year":"2020","journal-title":"Lancet Infect Dis"},{"issue":"1","key":"ppat.1012703.ref016","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jinf.2018.08.007","article-title":"Emergence of Coxsackie A6 hand-foot-and-mouth disease and comparative severity of Coxsackie B vs. echovirus infections, 2014\u20132016, UK","volume":"78","author":"KW Teo","year":"2019","journal-title":"J Infect"},{"issue":"4","key":"ppat.1012703.ref017","doi-asserted-by":"crossref","first-page":"654","DOI":"10.3201\/eid2404.171298","article-title":"Emerging Coxsackievirus A6 Causing Hand, Foot and Mouth Disease, Vietnam","volume":"24","author":"NT Anh","year":"2018","journal-title":"Emerg Infect Dis"},{"issue":"3","key":"ppat.1012703.ref018","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.jinf.2014.04.001","article-title":"Epidemic characteristics of hand, foot, and mouth disease in southern China, 2013: coxsackievirus A6 has emerged as the predominant causative agent.","volume":"69","author":"JL Li","year":"2014","journal-title":"J Infect"},{"issue":"1","key":"ppat.1012703.ref019","doi-asserted-by":"crossref","first-page":"5491","DOI":"10.1038\/s41598-017-05618-0","article-title":"Persistent circulation of Coxsackievirus A6 of genotype D3 in mainland of China between 2008 and 2015.","volume":"7","author":"Y Song","year":"2017","journal-title":"Sci Rep."},{"issue":"9","key":"ppat.1012703.ref020","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1586\/14787210.2015.1058156","article-title":"Coxsackievirus A6: a new emerging pathogen causing hand, foot and mouth disease outbreaks worldwide.","volume":"13","author":"L Bian","year":"2015","journal-title":"Expert Rev Anti Infect Ther"},{"issue":"12","key":"ppat.1012703.ref021","doi-asserted-by":"crossref","first-page":"20745","DOI":"10.2807\/1560-7917.ES2014.19.12.20745","article-title":"Atypical hand, foot, and mouth disease associated with coxsackievirus A6 infection, Edinburgh, United Kingdom, January to February 2014.","volume":"19","author":"C Sinclair","year":"2014","journal-title":"Euro Surveill."},{"key":"ppat.1012703.ref022","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jcv.2018.11.003","article-title":"Severe atypical hand-foot-and-mouth disease in adults due to coxsackievirus A6: Clinical presentation and phylogenesis of CV-A6 strains.","volume":"110","author":"F Broccolo","year":"2019","journal-title":"J Clin Virol"},{"issue":"10","key":"ppat.1012703.ref023","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1093\/cid\/ciu624","article-title":"Severe hand, foot, and mouth disease and coxsackievirus A6-Shenzhen, China","volume":"59","author":"F Yang","year":"2014","journal-title":"Clin Infect Dis"},{"issue":"1","key":"ppat.1012703.ref024","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jcv.2010.02.002","article-title":"Co-circulation of coxsackieviruses A6 and A10 in hand, foot and mouth disease outbreak in Finland.","volume":"48","author":"S Blomqvist","year":"2010","journal-title":"J Clin Virol"},{"issue":"4","key":"ppat.1012703.ref025","doi-asserted-by":"crossref","DOI":"10.3201\/eid1904.121589","article-title":"Hand, foot, and mouth disease outbreak and coxsackievirus A6, northern Spain, 2011","volume":"19","author":"M Montes","year":"2013","journal-title":"Emerg Infect Dis"},{"issue":"1","key":"ppat.1012703.ref026","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S1473-3099(13)70264-0","article-title":"Jr., Bennett N, Modlin JF. Atypical hand, foot, and mouth disease: a vesiculobullous eruption caused by Coxsackie virus A6","volume":"14","author":"HM Feder","year":"2014","journal-title":"Lancet Infect Dis"},{"issue":"3","key":"ppat.1012703.ref027","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/S1473-3099(19)30566-3","article-title":"Circulation of non-polio enteroviruses in 24 EU and EEA countries between 2015 and 2017: a retrospective surveillance study.","volume":"20","author":"L Bubba","year":"2020","journal-title":"Enterovirus study c.Lancet Infect Dis."},{"issue":"1","key":"ppat.1012703.ref028","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s12889-020-8284-x","article-title":"Non-polio enteroviruses among healthy children in the Philippines.","volume":"20","author":"MMA Jiao","year":"2020","journal-title":"BMC Public Health"},{"issue":"7","key":"ppat.1012703.ref029","doi-asserted-by":"crossref","first-page":"e0181234","DOI":"10.1371\/journal.pone.0181234","article-title":"Prevalence of enteroviruses in healthy populations and excretion of pathogens in patients with hand, foot, and mouth disease in a highly endemic area of southwest China.","volume":"12","author":"Q Wu","year":"2017","journal-title":"PLoS One."},{"issue":"4","key":"ppat.1012703.ref030","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1093\/infdis\/jiv470","article-title":"Reconstruction of 60 Years of Chikungunya Epidemiology in the Philippines Demonstrates Episodic and Focal Transmission","volume":"213","author":"H Salje","year":"2016","journal-title":"J Infect Dis"},{"issue":"9","key":"ppat.1012703.ref031","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.3201\/eid2709.204915","article-title":"Seroprevalence and Virologic Surveillance of Enterovirus 71 and Coxsackievirus A6, United Kingdom, 2006\u20132017","volume":"27","author":"E Kamau","year":"2021","journal-title":"Emerg Infect Dis"},{"issue":"10","key":"ppat.1012703.ref032","doi-asserted-by":"crossref","first-page":"3192","DOI":"10.1128\/JCM.00628-08","article-title":"Molecular epidemiology of human enterovirus 71 in the United Kingdom from 1998 to 2006","volume":"46","author":"JM Bible","year":"2008","journal-title":"J Clin Microbiol"},{"issue":"12","key":"ppat.1012703.ref033","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1111\/1469-0691.12753","article-title":"Enterovirus infections in England and Wales, 2000\u20132011: the impact of increased molecular diagnostics","volume":"20","author":"S Kadambari","year":"2014","journal-title":"Clin Microbiol Infect"},{"issue":"6","key":"ppat.1012703.ref034","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1017\/S0950268809990781","article-title":"Seventy-five years of estimating the force of infection from current status data","volume":"138","author":"N Hens","year":"2010","journal-title":"Epidemiol Infect"},{"issue":"4","key":"ppat.1012703.ref035","doi-asserted-by":"crossref","first-page":"e0003719","DOI":"10.1371\/journal.pntd.0003719","article-title":"Estimating dengue transmission intensity from sero-prevalence surveys in multiple countries.","volume":"9","author":"N Imai","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1012703.ref036","unstructured":"RStan. [Available from: https:\/\/mc-stan.org\/users\/interfaces\/rstan."},{"issue":"5","key":"ppat.1012703.ref037","doi-asserted-by":"crossref","first-page":"e64","DOI":"10.1016\/S1473-3099(15)00543-5","article-title":"Global emergence of enterovirus D68: a systematic review","volume":"16","author":"CC Holm-Hansen","year":"2016","journal-title":"Lancet Infect Dis"},{"issue":"1","key":"ppat.1012703.ref038","doi-asserted-by":"crossref","first-page":"92","DOI":"10.3201\/eid2201.151323","article-title":"Seroepidemiology of Human Enterovirus 71 Infection among Children, Cambodia","volume":"22","author":"PF Horwood","year":"2016","journal-title":"Emerg Infect Dis"},{"issue":"5","key":"ppat.1012703.ref039","doi-asserted-by":"crossref","first-page":"e0127999","DOI":"10.1371\/journal.pone.0127999","article-title":"Seroepidemiology of Coxsackievirus A6, Coxsackievirus A16, and Enterovirus 71 Infections among Children and Adolescents in Singapore, 2008\u20132010.","volume":"10","author":"LW Ang","year":"2015","journal-title":"PLoS One."},{"issue":"34","key":"ppat.1012703.ref040","doi-asserted-by":"crossref","first-page":"30005","DOI":"10.2807\/1560-7917.ES.2015.20.34.30005","article-title":"Transmission patterns of human enterovirus 71 to, from and among European countries, 2003 to 2013.","volume":"20","author":"C Hassel","year":"2015","journal-title":"Euro Surveill"},{"issue":"3","key":"ppat.1012703.ref041","doi-asserted-by":"crossref","first-page":"432","DOI":"10.3201\/eid2403.171303","article-title":"Epidemiology of Recurrent Hand, Foot and Mouth Disease, China, 2008\u20132015","volume":"24","author":"J Huang","year":"2018","journal-title":"Emerg Infect Dis"},{"issue":"2","key":"ppat.1012703.ref042","doi-asserted-by":"crossref","first-page":"280","DOI":"10.4049\/jimmunol.2200143","article-title":"Comparison of Neutralizing Antibody Response Kinetics in Patients with Hand, Foot, and Mouth Disease Caused by Coxsackievirus A16 or Enterovirus A71: A Longitudinal Cohort Study of Chinese Children, 2017\u20132019","volume":"209","author":"Y Zhou","year":"2022","journal-title":"J Immunol"},{"issue":"10","key":"ppat.1012703.ref043","doi-asserted-by":"crossref","first-page":"5686","DOI":"10.1128\/JVI.00020-12","article-title":"Human SCARB2-dependent infection by coxsackievirus A7, A14, and A16 and enterovirus 71","volume":"86","author":"S Yamayoshi","year":"2012","journal-title":"J Virol"},{"issue":"1","key":"ppat.1012703.ref044","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12929-021-00708-8","article-title":"Antivirals blocking entry of enteroviruses and therapeutic potential","volume":"28","author":"MI Anasir","year":"2021","journal-title":"J Biomed Sci"},{"issue":"3","key":"ppat.1012703.ref045","doi-asserted-by":"crossref","first-page":"e0118529","DOI":"10.1371\/journal.pone.0118529","article-title":"Epidemic 2014 enterovirus D68 cross-reacts with human rhinovirus on a respiratory molecular diagnostic platform.","volume":"10","author":"SC McAllister","year":"2015","journal-title":"PLoS One."}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012703","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T18:23:46Z","timestamp":1732127026000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012703"}},"subtitle":[],"editor":[{"given":"Hannah E.","family":"Clapham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":45,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1012703","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]}}}