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Authors: Hsiao, Victor
Advisors: Grenfell, Bryan
Department: Ecology and Evolutionary Biology
Class Year: 2015
Abstract: Background: Hand-foot-and-mouth disease (HFMD) has been an increasing concern in China since HFMD outbreaks began there in 2008. HFMD became a national notifiable disease in China in 2008 and up to 2012, there were 7.2 million cases of probable HFMD cases reported to the China CDC. A number of public health guidelines including school closures have been implemented to minimize HFMD transmission and incidence in China. However, there is little evidence-based consensus about whether these school closures have effectively reduced HFMD incidence. A proposed, and potentially more effective, public health intervention is an HFMD vaccine. Different enterovirus serotypes have been shown to cause HFMD, with Enterovirus 71 (EV71) and Coxsackievirus 16 (CA16) being the predominant ones in China. Recent phase 3 clinical trials showed that inactivated monovalent EV71 vaccines effectively reduced EV71-related HFMD incidence. We use mathematical models to compare the impact of school closures and vaccination in reducing HFMD incidence in the cities of Beijing, Chongqing, Shanghai, and Tianjin, and thereby better inform future HFMD-related public health policy. Methods: We used the time-series susceptible-infected-recovered (TSIR) model to estimate average weekly seasonal transmission rates as well as the basic and effective reproductive number (R0 and RE) for HFMD in China from 2008 to 2012. These seasonal transmission rate estimates were used to fit the TSIR model to China’s HFMD epidemic time-series data. School closures were modeled by lowering the transmission rates at different times during the year. Vaccination campaigns were modeled by reducing the effective number of susceptible individuals entering the population. Lastly, the invasion of an HFMD-causing pathogen was simulated by increasing the proportion of the population susceptible to the pathogen. Results: RE peaked above 1 twice in southern cities and only once in northern cities, thus matching the number of peaks of HFMD incidence per year observed between 2008 and 2012. There was a minimal decrease in the seasonal transmission rates corresponding to the summer holidays, with this decrease being more pronounced in cities located in southern China. Single-week school closures at the calculated week of onset of the HFMD epidemic caused short-term decreases in incidence but had insignificant effects on long-term, annual HFMD incidence. Single-week school closures only caused the epidemic to slow down with the overall seasonality staying the same. Multiple-week school closures caused greater reductions in annual HFMD incidence as the number of weeks of school closure increased. However, even when schools were closed for the whole year, reductions in annual HFMD incidence did not drop below 94% relative to the noclosure annual HFMD incidence scenario. In comparison, with vaccination, HFMD incidence decreased as the proportion of newborns vaccinated increased and as the length of vaccination campaigns increased. Even at low vaccination coverage rates of 50%, incidence was reduced to below 90% in all cities that were studied. At 90% vaccination coverage, incidence was reduced to below 20% in all selected cities. Vaccination-related reductions in incidence were also less pronounced in southern cities. HFMD epidemic seasonality increased when invasion occurred during the winter months or when there was a lower proportion of the population that was susceptible to the given pathogen. Meanwhile, seasonality decreased when invasion occurred nearer to the summer months or when there was a higher proportion of the population that was susceptible to the given pathogen. Discussion: The possibility of the invasion of a new HFMD-causing virus strain is concerning, especially if a large proportion of the population is susceptible to the pathogen and if the invasion occurs during the summer months. School closures, however, are relatively ineffective for reducing annual HFMD incidence. As such, other public health interventions should be explored. Vaccination is a promising solution to dramatically reducing HFMD incidence especially because an EV71 vaccine is expected to be released in China this year.
Extent: 97 pages
Type of Material: Princeton University Senior Theses
Language: en_US
Appears in Collections:Ecology and Evolutionary Biology, 1992-2016

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