Time series analysis of reported cases of hand, foot, and mouth disease from 2010 to 2013 in Wuhan, China

Abstract

Background: Hand, foot, and mouth disease (HFMD) is an infectious disease caused by a group of enteroviruses, including Coxsackievirus A16 (CVA16) and Enterovirus A71 (EV-A71). In recent decades, Asian countries have experienced frequent and widespread HFMD outbreaks, with deaths predominantly among children. In several Asian countries, epidemics usually peak in the late spring/early summer, with a second small peak in late autumn/early winter. We investigated the possible underlying association between the seasonality of HFMD epidemics and meteorological variables, which could improve our ability to predict HFMD epidemics.

Methods: We used a time series analysis composed of a spectral analysis based on the maximum entropy method (MEM) in the frequency domain and the nonlinear least squares method in the time domain. The time series analysis was applied to three kinds of monthly time series data collected in Wuhan, China, where high-quality surveillance data for HFMD have been collected: (i) reported cases of HFMD, (ii) reported cases of EV-A71 and CVA16 detected in HFMD patients, and (iii) meteorological variables.

Results: In the power spectral densities for HFMD and EV-A71, the dominant spectral lines were observed at frequency positions corresponding to 1-year and 6-month cycles. The optimum least squares fitting (LSF) curves calculated for the 1-year and 6-month cycles reproduced the bimodal cycles that were clearly observed in the HFMD and EV-A71 data. The peak months on the LSF curves for the HFMD data were consistent with those for the EV-A71 data. The risk of infection was relatively high at 10 °C ≤ t < 15 °C (t, temperature [°C]) and 15 °C ≤ t < 20 °C, and peaked at 20 °C ≤ t < 25 °C.

Conclusion: In this study, the HFMD infections occurring in Wuhan showed two seasonal peaks, in summer (June) and winter (November or December). The results obtained with a time series analysis suggest that the bimodal seasonal peaks in HFMD epidemics are attributable to EV-A71 epidemics. Our results suggest that controlling the spread of EV-A71 infections when the temperature is approximately 20-25 °C should be considered to prevent HFMD infections in Wuhan, China.

Fig. 1

Location of Wuhan in China. Source: revised from “Chinese latitude and longitude map” (http://www.baidu.com)

Fig. 2

Dependence of the occurrence of EV-A71 infection and average temperature (N _T{A},E) on temperature interval (ΔT). Dashed line, ΔT = 1 °C; dotted line, ΔT = 3 °C; solid line, ΔT = 5 °C

Fig. 3

Age distribution of the reported HFMD cases at hospitals in the whole of Wuhan

Fig. 4

Monthly time series data for reported cases of HFMD, their pathogens, and meteorological variables. a HFMD, b EV-A71, c CVA16, d T{A}, T{M}, and T{m}, e RH, f RF, and g WV

Fig. 5

Power spectral densities of the monthly time series data. a HFMD, b EV-A71, c CVA16, d T{A}, T{M}, and T{m}, e RH, f RF, and g WV

Fig. 6

Contributions of periodic modes to the LSF curve of HFMD data

Fig. 7

Comparison of the LSF curves calculated for the fundamental modes with the original data. LSF curve, solid line; original data, dashed line. a HFMD, b EV-A71, c CVA16, d T{A}, T{M}, and T{m}, e RH, f RF, and g WV

Fig. 8

Comparison of the optimum LSF curve for the HFMD data in the prediction range. LSF curve, solid line; original data, dashed line; gray lines, 95 % confidence

Fig. 9

Normalized LSF curves. a The curves for HFMD (solid line) and EV-A71 (dashed line) calculated with the 1-year and 6-month cycles, and (b) the curves for HFMD (solid line) and CVA16 (dashed line) calculated with the 6-month cycle

Fig. 10

Occurrence of EV-A71 and CVA16 infections and meteorological variables. a–d Average EV-A71 infection occurrence (N _T{A},E, N _T{M},E, N _T{m},E, and N _RF,E) was defined as the average number of EV-A71 infections observed during a 1-month period for a given domain of T{A}, T{M}, T{m}, and RF. e The average CVA16 infection occurrence (N _RH,C) was defined as the average number of CVA16 infections observed during a 1-month period for a given domain of RH