{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:09:22Z","timestamp":1788998962919,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T00:00:00Z","timestamp":1728691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2022YFC2305305"],"award-info":[{"award-number":["2022YFC2305305"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["INV-016826"],"award-info":[{"award-number":["INV-016826"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bill &amp; Melinda Gates Foundation","award":["2022YFC2305305"],"award-info":[{"award-number":["2022YFC2305305"]}]},{"name":"Bill &amp; Melinda Gates Foundation","award":["INV-016826"],"award-info":[{"award-number":["INV-016826"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Objective: To investigate the effect of Enterovirus A71 (EV71) vaccination on the transmissibility of different enterovirus serotypes of hand, foot, and mouth disease (HFMD) in Zhejiang, China. Methods: Daily surveillance data of HFMD and EV71 vaccination from August 2016 to December 2019 were collected. Epidemic periods for each HFMD type were defined, and the time-varying effective reproduction number (Rt) was estimated, which could provide more direct evidence of disease epidemics than case number. General additive models (GAMs) were employed to analyze associations between EV71 vaccination quantity and rate and HFMD transmissibility. The epidemic prevention threshold, represented by required vaccination numbers and rates, was also estimated. Results: Vaccinating every 100,000 children \u2264 5 years could lead to a decrease in the Rt of EV71-associated HFMD by 14.44% (95%CI: 6.76%, 21.42%). Additionally, a positive correlation was observed between vaccinations among children \u2264 5 years old (per 100,000) and the increased transmissibility of other HFMD types (caused by enteroviruses other than EV71 and CA16) at 1.82% (95%CI: 0.80%, 2.84%). It was estimated that an additional 362,381 vaccinations, corresponding to increased vaccine coverage to 54.51% among children \u2264 5 years could effectively prevent EV71 epidemics in Zhejiang. Conclusions: Our findings highlight the importance of enhancing EV71 vaccine coverage for controlling the epidemic of EV71-HFMD and assisting government officials in developing strategies to prevent HFMD.<\/jats:p>","DOI":"10.3390\/vaccines12101166","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T04:02:58Z","timestamp":1728878578000},"page":"1166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effect of EV71 Vaccination on Transmission Dynamics of Hand, Foot, and Mouth Disease and Its Epidemic Prevention Threshold"],"prefix":"10.3390","volume":"12","author":[{"given":"Dashan","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingzhi","family":"Shen","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqi","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zitong","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha E.","family":"Qian","sequence":"additional","affiliation":[{"name":"College of Arts and Sciences, Saint Louis University, Saint Louis, MO 63108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Ling","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1037-620X","authenticated-orcid":false,"given":"Ziping","family":"Miao","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Medical University, 169 Changle West Road, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0558-8731","authenticated-orcid":false,"given":"Stephen Edward","family":"McMillin","sequence":"additional","affiliation":[{"name":"School of Social Work, Saint Louis University, Saint Louis, MO 63103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9010-5991","authenticated-orcid":false,"given":"Sabel","family":"Bass","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, College for Public Health and Social Justice, Saint Louis University, Saint Louis, MO 63104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimin","family":"Sun","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hualiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Medical University, 169 Changle West Road, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16-00824","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":"Eurosurveillance"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1128\/JCM.01801-16","article-title":"Universal PCR Primers Are Critical for Direct Sequencing-Based Enterovirus Genotyping","volume":"55","author":"Liu","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/s41390-023-02930-6","article-title":"Laboratory diagnosis of CNS infections in children due to emerging and re-emerging neurotropic viruses","volume":"95","author":"Liu","year":"2024","journal-title":"Pediatr. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bsheal.2019.02.005","article-title":"Surveillance, epidemiology, and pathogen spectrum of hand, foot, and mouth disease in mainland of China from 2008 to 2017","volume":"1","author":"Ji","year":"2019","journal-title":"Biosaf. Health"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gonzalez, G., Carr, M.J., Kobayashi, M., Hanaoka, N., and Fujimoto, T. (2019). Enterovirus-Associated Hand-Foot and Mouth Disease and Neurological Complications in Japan and the Rest of the World. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20205201"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1056\/NEJMoa1304923","article-title":"Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China","volume":"370","author":"Zhu","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1056\/NEJMoa1303224","article-title":"An inactivated enterovirus 71 vaccine in healthy children","volume":"370","author":"Li","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1093\/cid\/ciz1188","article-title":"Early Evidence of Inactivated Enterovirus 71 Vaccine Impact Against Hand, Foot, and Mouth Disease in a Major Center of Ongoing Transmission in China, 2011\u20132018: A Longitudinal Surveillance Study","volume":"71","author":"Head","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S2352-4642(19)30185-3","article-title":"Effectiveness of EV-A71 vaccination in prevention of paediatric hand, foot, and mouth disease associated with EV-A71 virus infection requiring hospitalisation in Henan, China, 2017\u20132018: A test-negative case-control study","volume":"3","author":"Li","year":"2019","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yang, B., Lau, E.H., Wu, P., and Cowling, B.J. (2016). Transmission of Hand, Foot and Mouth Disease and Its Potential Driving Factors in Hong Kong. Sci. Rep., 6.","DOI":"10.1038\/srep27500"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.jiph.2023.03.029","article-title":"Association of public health and social measures on the hand-foot-mouth epidemic in South Korea","volume":"16","author":"Ryu","year":"2023","journal-title":"J. Infect. Public Health"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wu, H., Xue, M., Wu, C., Lu, Q., Ding, Z., Wang, X., Fu, T., Yang, K., and Lin, J. (2022). Trend of hand, foot, and mouth disease from 2010 to 2021 and estimation of the reduction in enterovirus 71 infection after vaccine use in Zhejiang Province, China. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0274421"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lu, Q., Ding, Z., Wu, C., Wu, H., and Lin, J. (2019). Analysis of Epidemiological Characteristics of Notifiable Diseases Reported in Children Aged 0\u201314 Years from 2008 to 2017 in Zhejiang Province, China. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16020168"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1080\/22221751.2022.2125346","article-title":"Molecular epidemiology and clinical features of hand, foot and mouth disease requiring hospitalization after the use of enterovirus A71 inactivated vaccine in chengdu, China, 2017\u20132022: A descriptive study","volume":"11","author":"Duan","year":"2022","journal-title":"Emerg. Microbes Infect."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/s12985-023-02169-x","article-title":"Molecular epidemiology and clinical characteristics of enteroviruses associated HFMD in Chengdu, China, 2013\u20132022","volume":"20","author":"Yang","year":"2023","journal-title":"Virol. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4934","DOI":"10.1002\/jmv.27906","article-title":"Epidemiological characteristics of hand, foot, and mouth disease clusters during 2016-2020 in Beijing, China","volume":"94","author":"Cui","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.jinf.2022.06.020","article-title":"The impact of enterovirus A71 vaccination program on hand, foot, and mouth disease in Guangdong, China: A longitudinal surveillance study","volume":"85","author":"Xiao","year":"2022","journal-title":"J. Infect."},{"key":"ref_18","unstructured":"(2016, June 08). Technical Guidelines for the Use of Inactivated Enterovirus Type 71 Vaccines. Available online: https:\/\/www.chinacdc.cn\/zxdt\/201606\/t20160608_131032.html."},{"key":"ref_19","first-page":"1088","article-title":"The impact of EV71 vaccination program on hand, foot and mouth disease in Zhejiang Province, China: A negative control study","volume":"8","author":"Zheng","year":"2023","journal-title":"Infect. Dis. Model."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"113082","DOI":"10.1016\/j.ecoenv.2021.113082","article-title":"Ambient sulfur dioxide and hospital expenditures and length of hospital stay for respiratory diseases: A multicity study in China","volume":"229","author":"Cao","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Fraser, C. (2007). Estimating individual and household reproduction numbers in an emerging epidemic. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000758"},{"key":"ref_22","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":"ref_23","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1001\/jama.291.2.222","article-title":"Transmission and clinical features of enterovirus 71 infections in household contacts in Taiwan","volume":"291","author":"Chang","year":"2004","journal-title":"JAMA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1093\/aje\/kwh255","article-title":"Different epidemic curves for severe acute respiratory syndrome reveal similar impacts of control measures","volume":"160","author":"Wallinga","year":"2004","journal-title":"Am. J. Epidemiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3201\/eid1201.050593","article-title":"Real-time estimates in early detection of SARS","volume":"12","author":"Cauchemez","year":"2006","journal-title":"Emerg. Infect. Dis."},{"key":"ref_26","first-page":"779","article-title":"Associations of Ambient NO(2) with Daily Hospitalization, Hospitalization Expenditure and Length of Hospital Stay of Cause-Specific Respiratory Diseases\u2014Shanxi, China, 2017\u20132019","volume":"4","author":"Zheng","year":"2022","journal-title":"China CDC Wkly."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4917","DOI":"10.1016\/j.vaccine.2020.05.001","article-title":"WHO working group meeting to develop WHO Recommendations to assure the quality, safety and efficacy of enterovirus 71 vaccines","volume":"38","author":"Lei","year":"2020","journal-title":"Vaccine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1093\/cid\/ciz1114","article-title":"Effectiveness and Safety of an Inactivated Enterovirus 71 Vaccine in Children Aged 6-71 Months in a Phase IV Study","volume":"71","author":"Guan","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Cheng, L., Zhong, S., Xu, X., Li, J., Xie, F., Lin, Y., and Zhang, D. (2024). Chinese parents\u2019 intention to vaccinate their 0\u20135-year-old children with the EV-71 vaccine against hand, foot, and mouth disease and willingness-to-pay. Front. Public Health, 12.","DOI":"10.3389\/fpubh.2024.1336687"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Jiang, L., Jiang, H., Tian, X., Xia, X., and Huang, T. (2021). Epidemiological characteristics of hand, foot, and mouth disease in Yunnan Province, China, 2008\u20132019. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06462-4"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Takahashi, S., Liao, Q., Van Boeckel, T.P., Xing, W., Sun, J., Hsiao, V.Y., Metcalf, C.J., Chang, Z., Liu, F., and Zhang, J. (2016). Hand, Foot, and Mouth Disease in China: Modeling Epidemic Dynamics of Enterovirus Serotypes and Implications for Vaccination. PLoS Med., 13.","DOI":"10.1371\/journal.pmed.1001958"},{"key":"ref_32","first-page":"373","article-title":"The non-stationary and spatially varying associations between hand, foot and mouth disease and multiple environmental factors: A Bayesian spatiotemporal mapping model study","volume":"9","author":"Shen","year":"2024","journal-title":"Infect. Dis. Model."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Meng, D., Xu, J., and Zhao, J. (2021). Analysis and prediction of hand, foot and mouth disease incidence in China using Random Forest and XGBoost. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0261629"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"He, X., Dong, S., Li, L., Liu, X., Wu, Y., Zhang, Z., and Mei, S. (2020). Using a Bayesian spatiotemporal model to identify the influencing factors and high-risk areas of hand, foot and mouth disease (HFMD) in Shenzhen. PLoS Neglected Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008085"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s40249-023-01145-5","article-title":"Immunization coverage, knowledge, satisfaction, and associated factors of non-National Immunization Program vaccines among migrant and left-behind families in China: Evidence from Zhejiang and Henan provinces","volume":"12","author":"Zhou","year":"2023","journal-title":"Infect. Dis. Poverty"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/12\/10\/1166\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:12:17Z","timestamp":1760112737000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/12\/10\/1166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,12]]},"references-count":35,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["vaccines12101166"],"URL":"https:\/\/doi.org\/10.3390\/vaccines12101166","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,12]]}}}