Background Hand, foot, and mouth disease (HFMD) is a globalinfectious disease; particularly, it has ahigh disease burden in China. This study was aimed to explore the temporal and spatial dis.tribution of the disease by analyzing its epidemiological characteristics, and to calculate theearly warning signals of HFMD by using a logistic differential equation (LDE) model. Methods This study included datasets of HFMD cases reported in seven regions in Mainland China.The early warning time (week) was calculated using the LDE model with the key parametersestimated by fitting with the data. Two key time points, ‘epidemic acceleration week (EAW)and ‘recommended warning week (RWW)’, were calculated to show the early warning time Results The mean annualincidence of HFMD cases per 100,000 per year was 218, 360, 223, 124and 359 in Hunan Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, YunxiaoCounty across the southern regions, respectively and 60 and 34 in Jilin Province and Longde County across the northern regions, respectively. The LDE model fitted well with thereported data (R’ > 0.65, P< 0.001). Distinct temporal patterns were found across geo-graphical regions: two early warning signals emerged in spring and autumn every yearacross southern regions while one early warning signals in summer every year across northern regions. Conclusions The disease burden of HFMD in China is still high, with more cases occurring in the southernregions. The early warning of HFMD across the seven regions is heterogeneous. In thenorthern regions, it has a high incidence during summer and peaks in June every year; inthe southern regions, it has two waves every year with the first wave during spring spreadingfaster than the second wave during autumn. Our findings can help predict and prepare foractive periods of HFMD
