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Decline in Chinese HFMD epidemic projected under new vaccination scheme


Broad vaccination with newly available monovalent hand, foot, and mouth disease (HFMD) vaccines will decrease HFMD incidence in China, according to predictions from an epidemiologic model published this week in PLOS Medicine. The study, conducted by Saki Takahashi and Bryan T. Grenfell at Princeton University, New Jersey, USA, Hongjie Yu at the Chinese Center for Disease Control and Prevention, Beijing, China, and colleagues, further suggests that serotype replacement (spread of viruses that differ from those in a vaccine, replacing viruses to which the vaccine confers immunity) will not significantly deplete the benefits of a HFMD vaccination campaign.

China reported 9 million cases of HFMD between 2008 and 2013. In clinical trials, inactivated monovalent vaccines against enterovirus serotype EV-A71-associated HFMD were highly efficacious against infection with EV-A71 but did not cross-protect against serotype CV-A16-associated HFMD. To estimate the effects of broad vaccination, Takahashi and colleagues used HFMD incidence data collected in 31 Chinese provinces between 2009 and 2013 to develop a two-serotype time series susceptible-infected-recovered epidemic model. According to model outcomes, cross-protection following infection with EV-A71 or CV-A16 lasts 6.77 weeks on average (95% confidence interval: 2.50, 10.03), resulting in cross-serotype protection. Based on this and the estimated basic reproduction number (which represents the average number of people who will become infected by each individual infected person) for both serotypes (26.63 for EV-A71 (interquartile range [IQR]: 23.14, 30.40) and 27.13 for CV-A16 (IQR: 23.15, 31.34)), Takahashi and colleagues predicted that EV-A71 vaccination will decrease EV-A71-associated HFMD incidence and leave CV-A16 incidence relatively unchanged, and that coverage above 96% will achieve population-level immunity.

The accuracy of these findings depends on the assumptions included in the model and the quality of the data. However, the modeling is conservative and tested within the study for its ability to replicate observed epidemic cycles. The authors state, "a mass EV-A71 vaccination program of infants and young children should provide significant benefits in terms of a reduction in overall HFMD burden."


Research Article


This work is supported by the National Science Fund for Distinguished Young Scholars (No. 81525023) (HY), the National Natural Science Foundation of China (No. 81473031) (HY), the Li Ka Shing Oxford Global Health Programme (No. B9RST00-B900.57) (HY), the Science and Technology Directorate, Department of Homeland Security contract HSHQDC-12-C-00058 (TPVB, CJEM, BTG), the Fulbright Program (TPVB), the Bill & Melinda Gates Foundation (OPP1094793) (CJEM, BTG), the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security and the Fogarty International Center, National Institutes of Health (CJEM, BTG), the Harvard Center for Communicable Disease Dynamics from the National Institute of General Medical Sciences (grant no. U54 GM088558) (JTW, BJC, GML), a commissioned grant from the Health and Medical Research Fund from the Government of the Hong Kong Special Administrative Region (JTW, BJC, GML), the Wellcome Trust (JJF), the Li Ka Shing Oxford Global Health Programme (JJF), and the Wellcome Trust Programme Grant 089276/Z/09/Z (HRvD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests:

The views expressed in this study are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of General Medical Sciences, the National Institutes of Health, or the Chinese Center for Disease Control and Prevention. BJC has received research funding from MedImmune Inc. and Sanofi Pasteur, and consults for Crucell NV. MedImmune Inc, Sanofi Pasteur, and Crucell NV do not market HFMD vaccines. The other authors have declared that no competing interests exist.


Takahashi S, Liao Q, Van Boeckel TP, Xing W, Sun J, Hsiao VY, et al. (2016) Hand, Foot, and Mouth Disease in China: Modeling Epidemic Dynamics of Enterovirus Serotypes and Implications for Vaccination. PLoS Med 13(2): e1001958. doi:10.1371/journal.pmed.1001958

Author Affiliations:

Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America

Division of Infectious Disease, Key Laboratory of Surveillance and Early Warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China

Woodrow Wilson School of Public and International Affairs, Princeton University, Princeton, New Jersey, United States of America

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China

Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam

Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom

Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America



Bryan Grenfell
Princeton University
Dept Ecology and Evolutionary Biology
Woodrow Wilson School of Public and International Affairs
211 Eno Hall
[email protected]

Hongjie Yu
Chinese Center for Disease Control and Prevention
Division of Infectious Disease
155# ChangBai Road
Changping District
Beijing, 102206
86 10 58900548FAX: 86 10 58900548
[email protected]

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