{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:27:19Z","timestamp":1779150439597,"version":"3.51.4"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Hand, foot, and mouth disease (HFMD) is a common illness in young children. A monovalent vaccine has been developed in China protecting against enterovirus-71, bivalent vaccines preventing HFMD caused by two viruses are under development.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>To predict and compare the incidence of HFMD under different vaccination scenarios in China.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We developed a compartmental model to capture enterovirus transmission and the natural history of HFMD in children aged 0\u20135, and calibrated to reported cases in the same age-group from 2015 to 2018. We compared the following vaccination scenarios: different combinations of monovalent and bivalent vaccine; a program of constant vaccination to that of pulse vaccination prior to seasonal outbreaks.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We estimate 1,982,819, 2,258,846, 1,948,522 and 2,398,566 cases from 2015 to 2018. Increased coverage of monovalent vaccine from 0 to 80% is predicted to decrease the cases by 797,262 (49.1%). Use of bivalent vaccine at an 80% coverage level would decrease the cases by 828,560. Use of a 2.0\u00d7 pulse vaccination for the bivalent vaccine in addition to 80% coverage would reduce cases by over one million. The estimated <jats:italic>R<\/jats:italic><jats:sub><jats:italic>0<\/jats:italic><\/jats:sub> for HFMD in 2015\u20132018 was 1.08, 1.10, 1.35 and 1.17.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our results point to the benefit of bivalent vaccine and using a pulse vaccination in specific months over routine vaccination. Other ways to control HFMD include isolation of patients in the early stage of dissemination, more frequent hand-washing and ventilation, and better treatment options for patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12879-021-06157-w","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T13:02:45Z","timestamp":1625490165000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The burden of hand, foot, and mouth disease among children under different vaccination scenarios in China: a dynamic modelling study"],"prefix":"10.1186","volume":"21","author":[{"given":"Zhixi","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Liu-Helmersson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharmistha","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abram L.","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weibing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"6157_CR1","unstructured":"China Statistical Yearbook Database. http:\/\/www.stats.gov.cn\/tjsj\/ndsj\/. Accessed 4 Apr 2019."},{"key":"6157_CR2","unstructured":"Online Direct Reporting of Official Infectious Diseases. http:\/\/www.nhc.gov.cn\/jkj\/new_index.shtml. Accessed 4 Apr 2019."},{"issue":"4","key":"6157_CR3","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/S1473-3099(13)70342-6","volume":"14","author":"W Xing","year":"2014","unstructured":"Xing W, Liao Q, Viboud C, Zhang J, Sun J, Wu JT, et al. Hand, foot, and mouth disease in China, 2008-12: an epidemiological study. Lancet Infect Dis. 2014;14(4):308\u201318. https:\/\/doi.org\/10.1016\/S1473-3099(13)70342-6.","journal-title":"Lancet Infect Dis"},{"issue":"2","key":"6157_CR4","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/rmv.1827","volume":"25","author":"SL Liu","year":"2015","unstructured":"Liu SL, Pan H, Liu P, Amer S, Chan TC, Zhan J, et al. Comparative epidemiology and virology of fatal and nonfatal cases of hand, foot and mouth disease in mainland China from 2008 to 2014. Rev Med Virol. 2015;25(2):115\u201328. https:\/\/doi.org\/10.1002\/rmv.1827.","journal-title":"Rev Med Virol"},{"issue":"12","key":"6157_CR5","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1056\/NEJMoa065954","volume":"356","author":"LY Chang","year":"2007","unstructured":"Chang LY, Huang LM, Gau SS, Wu YY, Hsia SH, Fan TY, et al. Neurodevelopment and cognition in children after enterovirus 71 infection. N Engl J Med. 2007;356(12):1226\u201334. https:\/\/doi.org\/10.1056\/NEJMoa065954.","journal-title":"N Engl J Med"},{"issue":"6","key":"6157_CR6","doi-asserted-by":"publisher","first-page":"e1785","DOI":"10.1542\/peds.2006-1547","volume":"118","author":"MC Huang","year":"2006","unstructured":"Huang MC, Wang SM, Hsu YW, Lin HC, Chi CY, Liu CC. Long-term cognitive and motor deficits after enterovirus 71 brainstem encephalitis in children. Pediatrics. 2006;118(6):e1785\u20138. https:\/\/doi.org\/10.1542\/peds.2006-1547.","journal-title":"Pediatrics"},{"issue":"5","key":"6157_CR7","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1586\/14760584.2016.1138862","volume":"15","author":"QY Mao","year":"2016","unstructured":"Mao QY, Wang Y, Bian L, Xu M, Liang Z. EV71 vaccine, a new tool to control outbreaks of hand, foot and mouth disease (HFMD). Expert Rev Vaccines. 2016;15(5):599\u2013606. https:\/\/doi.org\/10.1586\/14760584.2016.1138862.","journal-title":"Expert Rev Vaccines"},{"key":"6157_CR8","doi-asserted-by":"crossref","unstructured":"Chuo F, Tiing S, Labadin J: A simple deterministic model for the spread of hand, foot and mouth disease (HFMD) in Sarawak. In: 2008 Second Asia International Conference on Modelling & Simulation (AMS): 2008: IEEE; 2008: 947\u2013952.","DOI":"10.1109\/AMS.2008.139"},{"issue":"1\u20132","key":"6157_CR9","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s12190-012-0597-1","volume":"41","author":"J-Y Yang","year":"2013","unstructured":"Yang J-Y, Chen Y, Zhang F-Q. Stability analysis and optimal control of a hand-foot-mouth disease (HFMD) model. J Appl Math Comput. 2013;41(1\u20132):99\u2013117. https:\/\/doi.org\/10.1007\/s12190-012-0597-1.","journal-title":"J Appl Math Comput"},{"issue":"1\u20132","key":"6157_CR10","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/s11071-010-9848-6","volume":"64","author":"JL Liu","year":"2011","unstructured":"Liu JL. Threshold dynamics for a HFMD epidemic model with periodic transmission rate. Nonlinear Dynam. 2011;64(1\u20132):89\u201395. https:\/\/doi.org\/10.1007\/s11071-010-9848-6.","journal-title":"Nonlinear Dynam"},{"issue":"12","key":"6157_CR11","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.1128\/CVI.00491-13","volume":"20","author":"YM Hu","year":"2013","unstructured":"Hu YM, Wang X, Wang JZ, Wang L, Zhang YJ, Chang L, et al. Immunogenicity, safety, and lot consistency of a novel inactivated enterovirus 71 vaccine in Chinese children aged 6 to 59 months. Clin Vaccine Immunol. 2013;20(12):1805\u201311. https:\/\/doi.org\/10.1128\/CVI.00491-13.","journal-title":"Clin Vaccine Immunol"},{"issue":"9","key":"6157_CR12","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1056\/NEJMoa1303224","volume":"370","author":"R Li","year":"2014","unstructured":"Li R, Liu L, Mo Z, Wang X, Xia J, Liang Z, et al. An inactivated enterovirus 71 vaccine in healthy children. N Engl J Med. 2014;370(9):829\u201337. https:\/\/doi.org\/10.1056\/NEJMoa1303224.","journal-title":"N Engl J Med"},{"issue":"9","key":"6157_CR13","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1056\/NEJMoa1304923","volume":"370","author":"F Zhu","year":"2014","unstructured":"Zhu F, Xu W, Xia J, Liang Z, Liu Y, Zhang X, et al. Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China. N Engl J Med. 2014;370(9):818\u201328. https:\/\/doi.org\/10.1056\/NEJMoa1304923.","journal-title":"N Engl J Med"},{"issue":"9","key":"6157_CR14","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1016\/j.vaccine.2014.10.081","volume":"33","author":"L Li","year":"2015","unstructured":"Li L, Yin H, An Z, Feng Z. Considerations for developing an immunization strategy with enterovirus 71 vaccine. Vaccine. 2015;33(9):1107\u201312. https:\/\/doi.org\/10.1016\/j.vaccine.2014.10.081.","journal-title":"Vaccine"},{"issue":"21","key":"6157_CR15","doi-asserted-by":"publisher","first-page":"2406","DOI":"10.1016\/j.vaccine.2014.03.012","volume":"32","author":"C Yicun","year":"2014","unstructured":"Yicun C, Zhiqiang K, Qingwei L, Qibin L, Zhong HJV. A combination vaccine comprising of inactivated enterovirus 71 and coxsackievirus A16 elicits balanced protective immunity against both viruses. Vaccine. 2014;32(21):2406\u201312.","journal-title":"Vaccine"},{"issue":"3","key":"6157_CR16","doi-asserted-by":"publisher","first-page":"695","DOI":"10.3934\/mbe.2017039","volume":"14","author":"S Liu","year":"2017","unstructured":"Liu S, Li Y, Bi Y, Huang Q. Mixed vaccination strategy for the control of tuberculosis: a case study in China. Math Biosci Eng. 2017;14(3):695\u2013708. https:\/\/doi.org\/10.3934\/mbe.2017039.","journal-title":"Math Biosci Eng"},{"issue":"12","key":"6157_CR17","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1089\/cmb.2009.0003","volume":"17","author":"X Zhang","year":"2010","unstructured":"Zhang X, Zhao Y, Neumann AU. Partial immunity and vaccination for influenza. J Comput Biol. 2010;17(12):1689\u201396. https:\/\/doi.org\/10.1089\/cmb.2009.0003.","journal-title":"J Comput Biol"},{"issue":"1","key":"6157_CR18","first-page":"1","volume":"7","author":"J Li","year":"2018","unstructured":"Li J, Pan H, Wang X, Zhu Q, Ge Y, Cai J, et al. Epidemiological surveillance of hand, foot and mouth disease in Shanghai in 2014\u20132016, prior to the introduction of the enterovirus 71 vaccine. Emerg Microbes Infect. 2018;7(1):1\u20137.","journal-title":"Emerg Microbes Infect"},{"issue":"4","key":"6157_CR19","first-page":"458l464","volume":"22","author":"ZJ An","year":"2016","unstructured":"An ZJ, Liu Y, Liao QH, Zhang Y, Li KL, Yue CY, et al. Technical guide for the use of enterovirus type 71 inactivated vaccine. Chin J Vaccines Immun. 2016;22(4):458l464.","journal-title":"Chin J Vaccines Immun"},{"issue":"3\u20134","key":"6157_CR20","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/S0895-7177(03)90088-4","volume":"38","author":"YC Zhou","year":"2003","unstructured":"Zhou YC, Liu HW. Stability of periodic solutions for an SIS model with pulse vaccination. Math Comput Model. 2003;38(3\u20134):299\u2013308. https:\/\/doi.org\/10.1016\/S0895-7177(03)90088-4.","journal-title":"Math Comput Model"},{"issue":"3","key":"6157_CR21","doi-asserted-by":"publisher","first-page":"3108","DOI":"10.3390\/ijerph110303108","volume":"11","author":"Y Li","year":"2014","unstructured":"Li Y, Zhang J, Zhang X. Modeling and preventive measures of hand, foot and mouth disease (HFMD) in China. Int J Environ Res Public Health. 2014;11(3):3108\u201317. https:\/\/doi.org\/10.3390\/ijerph110303108.","journal-title":"Int J Environ Res Public Health"},{"issue":"3","key":"6157_CR22","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s10884-008-9111-8","volume":"20","author":"WD Wang","year":"2008","unstructured":"Wang WD, Zhao XQ. Threshold dynamics for compartmental epidemic models in periodic environments. J Dyn Differ Equ. 2008;20(3):699\u2013717. https:\/\/doi.org\/10.1007\/s10884-008-9111-8.","journal-title":"J Dyn Differ Equ"},{"issue":"1\u20132","key":"6157_CR23","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0025-5564(02)00108-6","volume":"180","author":"P van den Driessche","year":"2002","unstructured":"van den Driessche P, Watmough J. Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission. Math Biosci. 2002;180(1\u20132):29\u201348. https:\/\/doi.org\/10.1016\/S0025-5564(02)00108-6.","journal-title":"Math Biosci"},{"issue":"7","key":"6157_CR24","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1017\/S0950268815002630","volume":"144","author":"CC Lai","year":"2016","unstructured":"Lai CC, Jiang DS, Wu HM, Chen HH. A dynamic model for the outbreaks of hand, foot, and mouth disease in Taiwan. Epidemiol Infect. 2016;144(7):1500\u201311. https:\/\/doi.org\/10.1017\/S0950268815002630.","journal-title":"Epidemiol Infect"},{"key":"6157_CR25","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.amc.2015.11.035","volume":"274","author":"J Wang","year":"2016","unstructured":"Wang J, Xiao Y, Peng Z. Modelling seasonal HFMD infections with the effects of contaminated environments in mainland China. Appl Math Comput. 2016;274:615\u201327. https:\/\/doi.org\/10.1016\/j.amc.2015.11.035.","journal-title":"Appl Math Comput"},{"key":"6157_CR26","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.amc.2015.11.090","volume":"276","author":"Y Li","year":"2016","unstructured":"Li Y, Wang L, Pang L, Liu S. The data fitting and optimal control of a hand, foot and mouth disease (HFMD) model with stage structure. Appl Math Comput. 2016;276:61\u201374. https:\/\/doi.org\/10.1016\/j.amc.2015.11.090.","journal-title":"Appl Math Comput"},{"key":"6157_CR27","doi-asserted-by":"crossref","unstructured":"Wang J, Cao Z, Zeng DD, Wang Q, Wang X: Assessment for spatial driving forces of HFMD prevalence in Beijing, China. In: Proceedings of the Second ACM SIGSPATIALInternational Workshop on the Use of GIS in Emergency Management: 2016: ACM; 2016: 6.","DOI":"10.1145\/3017611.3017617"},{"issue":"10","key":"6157_CR28","doi-asserted-by":"publisher","first-page":"2885","DOI":"10.4161\/hv.29823","volume":"10","author":"S Shiyang","year":"2014","unstructured":"Shiyang S, Liping J, Zhenglun L, Qunying M, Weiheng S, Huafei Z, et al. Evaluation of monovalent and bivalent vaccines against lethal Enterovirus 71 and Coxsackievirus A16 infection in newborn mice. Vaccine. 2014;10(10):2885\u201395.","journal-title":"Vaccine"},{"issue":"3","key":"6157_CR29","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1016\/j.chaos.2006.05.054","volume":"35","author":"S Gakkhar","year":"2008","unstructured":"Gakkhar S, Negi K. Pulse vaccination in SIRS epidemic model with non-monotonic incidence rate. Chaos Soliton Fract. 2008;35(3):626\u201338. https:\/\/doi.org\/10.1016\/j.chaos.2006.05.054.","journal-title":"Chaos Soliton Fract"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-021-06157-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12879-021-06157-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-021-06157-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T13:04:12Z","timestamp":1625490252000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-021-06157-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,5]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["6157"],"URL":"https:\/\/doi.org\/10.1186\/s12879-021-06157-w","relation":{},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,5]]},"assertion":[{"value":"13 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"650"}}