{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T01:02:29Z","timestamp":1781830949958,"version":"3.54.5"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National Science and Technology Major Project of China","award":["2016ZX09101120-004"],"award-info":[{"award-number":["2016ZX09101120-004"]}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["16\/137\/109"],"award-info":[{"award-number":["16\/137\/109"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-003174"],"award-info":[{"award-number":["INV-003174"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Enterovirus 71 (EV-A71), coxsackievirus A16 (CV-A16), and coxsackievirus A6 (CV-A6) are common serotypes causing hand, foot, and mouth disease (HFMD). Analyses on the basic reproduction number (R0) of common pathogens causing HFMD are limited and there are no related studies using field data from outbreaks in mainland China.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We estimated the pathogen-specific basic reproduction number based on laboratory-confirmed HFMD outbreaks (clusters of \u226510 HFMD cases) reported to the national surveillance system between 2011 and 2018. The reproduction numbers were calculated using a mathematical model and the cumulative cases during the initial growth periods.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>This study included 539 outbreaks, of which 198 were caused by EV-A71, 316 by CV-A16, and 25 by CV-A6. All 10\u2005417 cases involved were children. Assuming the outbreaks occurred in closed systems and the incubation period is 5 days, the median (interquartile range [IQR]) R0 estimates of EV-A71, CV-A16, and CV-A6 were 5.06 (2.81, 10.20), 4.84 (3.00, 9.00), and 5.94 (3.27, 10.00). After adjusting for seroprevalences, the R0 (IQR) estimates for EV-A71, CV-A16 (optimistic and conservative scenarios), and CV-A6 were 12.60 (7.35, 25.40), 9.29 (6.01, 19.20), 15.50 (9.77, 30.40), and 25.80 (14.20, 43.50), respectively. We did not observe changes in the R0 of EV-A71 after vaccine licensure (P = .67).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>HFMD is highly transmissible when caused by the 3 most common serotypes. In mainland China, it primarily affects young children. Although a vaccine became available in 2016, we have not yet observed any related changes in the disease dynamics.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciaa1853","type":"journal-article","created":{"date-parts":[[2020,12,13]],"date-time":"2020-12-13T12:08:08Z","timestamp":1607861288000},"page":"e2552-e2559","source":"Crossref","is-referenced-by-count":30,"title":["Basic Reproduction Number of Enterovirus 71 and Coxsackievirus A16 and A6: Evidence From Outbreaks of Hand, Foot, and Mouth Disease in China Between 2011 and 2018"],"prefix":"10.1093","volume":"73","author":[{"given":"Zhong","family":"Zhang","sequence":"first","affiliation":[{"name":"Nanjing Municipal Center for Disease Control and Prevention, Nanjing, China"},{"name":"Chinese Field Epidemiology Training Program (CFETP), Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Centre for Mathematical Modelling of Infectious Diseases, Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Infectious disease, Key Laboratory of Surveillance and Early Warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minrui","family":"Ren","sequence":"additional","affiliation":[{"name":"Division of Infectious disease, Key Laboratory of Surveillance and Early Warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taoran","family":"Nie","sequence":"additional","affiliation":[{"name":"Division of Infectious disease, Key Laboratory of Surveillance and Early Warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhao","family":"Cui","sequence":"additional","affiliation":[{"name":"Division of Infectious disease, Key Laboratory of Surveillance and Early Warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaorui","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Infectious disease, Key Laboratory of Surveillance and Early Warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongjie","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Infectious disease, Key Laboratory of Surveillance and Early Warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"2021110300350587300_CIT0001","doi-asserted-by":"crossref","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":"2021110300350587300_CIT0002","doi-asserted-by":"crossref","first-page":"e285","DOI":"10.1097\/INF.0000000000001242","article-title":"The epidemiology of hand, foot and mouth disease in Asia: a systematic review and analysis","volume":"35","author":"Koh","year":"2016","journal-title":"Pediatr Infect Dis J"},{"key":"2021110300350587300_CIT0003","doi-asserted-by":"crossref","first-page":"16","DOI":"10.2807\/1560-7917.ES.2017.22.50.16-00824","article-title":"Epidemiology of hand, foot and mouth disease in China, 2008 to 2015 prior to the introduction of EV-A71 vaccine","volume":"22","author":"Yang","year":"2017","journal-title":"Euro Surveill"},{"key":"2021110300350587300_CIT0004","first-page":"554","article-title":"Prevalence and analyses of the changing etiology of hand, foot and mouth disease in China","volume":"31","author":"Zhao","year":"2015","journal-title":"Bing Du Xue Bao"},{"key":"2021110300350587300_CIT0005","doi-asserted-by":"crossref","first-page":"395","DOI":"10.3345\/kjp.2016.59.10.395","article-title":"Enterovirus 71 infection and neurological complications","volume":"59","author":"Lee","year":"2016","journal-title":"Korean J Pediatr"},{"key":"2021110300350587300_CIT0006","doi-asserted-by":"crossref","first-page":"e420","DOI":"10.1016\/S1473-3099(17)30307-9","article-title":"The basic reproduction number (R0) of measles: a systematic review","volume":"17","author":"Guerra","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"2021110300350587300_CIT0007","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1097\/EDE.0b013e318231d67a","article-title":"Hand, foot, and mouth disease in China: patterns of spread and transmissibility","volume":"22","author":"Wang","year":"2011","journal-title":"Epidemiology"},{"key":"2021110300350587300_CIT0008","doi-asserted-by":"crossref","first-page":"e1001958","DOI":"10.1371\/journal.pmed.1001958","article-title":"Hand, foot, and mouth disease in china: modeling epidemic dynamics of enterovirus serotypes and implications for vaccination","volume":"13","author":"Takahashi","year":"2016","journal-title":"PLoS Med"},{"key":"2021110300350587300_CIT0009","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1186\/s12879-019-4560-8","article-title":"Onychomadesis and potential association with HFMD outbreak in a kindergarten in Hubei province, China, 2017","volume":"19","author":"Li","year":"2019","journal-title":"BMC Infect Dis"},{"key":"2021110300350587300_CIT0010","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1186\/s12887-018-1253-1","article-title":"An outbreak of Coxsackievirus A6-associated hand, foot, and mouth disease in a kindergarten in Beijing in 2015","volume":"18","author":"Li","year":"2018","journal-title":"BMC Pediatr"},{"key":"2021110300350587300_CIT0011","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1097\/INF.0b013e3182116e95","article-title":"Estimation of the basic reproduction number of enterovirus 71 and coxsackievirus A16 in hand, foot, and mouth disease outbreaks","volume":"30","author":"Ma","year":"2011","journal-title":"Pediatr Infect Dis J"},{"key":"2021110300350587300_CIT0012","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1017\/S0950268815002137","article-title":"Basic reproduction number of coxsackievirus type A6 and A16 and enterovirus 71: estimates from outbreaks of hand, foot and mouth disease in Singapore, a tropical city-state","volume":"144","author":"Lim","year":"2016","journal-title":"Epidemiol Infect"},{"key":"2021110300350587300_CIT0013","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":"Xing","year":"2014","journal-title":"Lancet Infect Dis"},{"key":"2021110300350587300_CIT0014","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1136\/jech.57.10.831","article-title":"A simple approximate mathematical model to predict the number of severe acute respiratory syndrome cases and deaths","volume":"57","author":"Choi","year":"2003","journal-title":"J Epidemiol Community Health"},{"key":"2021110300350587300_CIT0015","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1097\/INF.0000000000000900","article-title":"Seroprevalence of enterovirus 71 antibody among children in China: a systematic review and meta-analysis","volume":"34","author":"Yang","year":"2015","journal-title":"Pediatr Infect Dis J"},{"key":"2021110300350587300_CIT0016","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41426-017-0011-z","article-title":"Epidemiological and serological surveillance of hand-foot-and-mouth disease in Shanghai, China, 2012\u20132016","volume":"7","author":"Wang","year":"2018","journal-title":"Emerg Microbes Infect"},{"key":"2021110300350587300_CIT0017","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.jinf.2016.08.008","article-title":"Seroepidemiology of Coxsackievirus A6, Coxsackievirus A16, and Enterovirus 71 infections in infants and children: a prospective cohort study in Jiangsu, China","volume":"73","author":"Gao","year":"2016","journal-title":"J Infect"},{"key":"2021110300350587300_CIT0018","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1186\/1743-422X-9-248","article-title":"Seroepidemiology of human enterovirus71 and coxsackievirusA16 in Jiangsu province, China","volume":"9","author":"Ji","year":"2012","journal-title":"Virol J"},{"key":"2021110300350587300_CIT0019","first-page":"e162373","article-title":"Seroprevalence of enterovirus A71 and Coxsackievirus A16 in healthy people in Shandong Province, China","volume":"11","author":"Wang","year":"2016","journal-title":"PLoS One"},{"key":"2021110300350587300_CIT0020","first-page":"599","article-title":"How generation intervals shape the relationship between growth rates and reproductive numbers","volume":"274","author":"Wallinga","year":"2007","journal-title":"Proc Biol Sci"},{"key":"2021110300350587300_CIT0021","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.1750-2659.2009.00106.x","article-title":"Estimation of the reproductive number and the serial interval in early phase of the 2009 influenza A\/H1N1 pandemic in the USA","volume":"3","author":"White","year":"2009","journal-title":"Influenza Other Respir Viruses"},{"key":"2021110300350587300_CIT0022","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1093\/aje\/kwt133","article-title":"A new framework and software to estimate time-varying reproduction numbers during epidemics","volume":"178","author":"Cori","year":"2013","journal-title":"Am J Epidemiol"},{"key":"2021110300350587300_CIT0023","volume-title":"R: a language and environment for statistical computing","author":"R Core Team"},{"key":"2021110300350587300_CIT0024","first-page":"e147532","article-title":"Spatiotemporal cluster patterns of hand, foot, and mouth disease at the county level in Mainland China, 2008\u20132012","volume":"11","author":"Wang","year":"2016","journal-title":"PLoS One"},{"key":"2021110300350587300_CIT0025","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.3201\/eid2410.171953","article-title":"Emerging enteroviruses causing hand, foot and mouth disease, China, 2010\u20132016","volume":"24","author":"Li","year":"2018","journal-title":"Emerg Infect Dis"},{"key":"2021110300350587300_CIT0026","volume-title":"The HFMD prevention and control handbook","author":"Liu","year":"2009","edition":"1"},{"key":"2021110300350587300_CIT0027","doi-asserted-by":"crossref","first-page":"285","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, China","volume":"19","author":"Cai","year":"2019","journal-title":"BMC Infect Dis"},{"key":"2021110300350587300_CIT0028","doi-asserted-by":"crossref","first-page":"e179623","DOI":"10.1371\/journal.pone.0179623","article-title":"Estimating the basic reproduction rate of HFMD using the time series SIR model in Guangdong, China","volume":"12","author":"Du","year":"2017","journal-title":"PLoS One"},{"key":"2021110300350587300_CIT0029","author":"Chinese Center for Disease Control and Prevention"},{"key":"2021110300350587300_CIT0030","first-page":"293","article-title":"Birth cohort analysis on inoculation rate of enterovirus 71 vaccine among children at ages of 0~5 years in Fujian Province, China from 2017 to 2018","volume":"33","author":"Pan","year":"2020","journal-title":"Chin J Biologicals"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciaa1853\/36246158\/ciaa1853.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/73\/9\/e2552\/41060755\/ciaa1853.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/73\/9\/e2552\/41060755\/ciaa1853.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:36:49Z","timestamp":1635899809000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/73\/9\/e2552\/6035193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,15]]},"references-count":30,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,12,15]]},"published-print":{"date-parts":[[2021,11,2]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciaa1853","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,11,1]]},"published":{"date-parts":[[2020,12,15]]}}}