Spatio-Temporal Dynamics of HFMD Serotypes

We used three sources of data in this analysis. First, weekly reports of HFMD incidence between 1 January 2009 and 31 December 2013 (a total of 262 wk) were obtained from a national surveillance system maintained by the Chinese Center for Disease Control and Prevention (China CDC) in Beijing, China. These reports were available at two spatial scales: the seven administrative regions and 31 provinces of China.
Second, we obtained time series of weekly laboratory-confirmed HFMD for a sub-sample of cases from each province, with virological test results classified as EV-A71, CV-A16, other non-EV-A71 and non-CV-A16 serotypes of enterovirus, or negative [15 (link)]. This information was aggregated to the regional scale on a monthly basis to reduce potential biases from the sampling scheme (S1 Fig). The proportions of each serotype were estimated, with all positive and negative tests included in the denominator. If there were no virological test data available for a given month, the proportions from the virological tests of the previous month were substituted. We applied these proportions to the reported case counts from the surveillance registry to estimate serotype-specific weekly incidence by province (Fig 1; S2 Dataset). Since infection with EV-A71 or CV-A16 accounted for the majority of total laboratory-confirmed HFMD cases between 2008 and 2013 (73%), we limited the scope of the main analysis to infection with either of these two serotypes. We used a time step of 1 wk: the incubation period of HFMD is 7 to 14 d and viral excretion persists for about 2 wk after symptom onset, so the generation time would be contained in this time frame. It has previously been shown that the estimation of seasonality is robust to the length of the chosen time step [43 (link)].
Third, we obtained yearly birth rates and population sizes between 2009 and 2013 by region and by province from the National Bureau of Statistics of China (S1 Dataset) [44 ]. Although reports of HFMD cases were available from 2008, the time frame of this analysis was limited to the period between 1 January 2009 and 31 December 2013 because of the sparsity of laboratory-confirmed cases during the first year of surveillance.