Early warning of hand, foot, and mouth disease transmission: A modeling study in mainland, China

Abstract

Background: Hand, foot, and mouth disease (HFMD) is a global infectious disease; particularly, it has a high disease burden in China. This study was aimed to explore the temporal and spatial distribution of the disease by analyzing its epidemiological characteristics, and to calculate the early 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 parameters estimated 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 annual incidence of HFMD cases per 100,000 per year was 218, 360, 223, 124, and 359 in Hunan Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County 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 the reported data (R2 > 0.65, P < 0.001). Distinct temporal patterns were found across geographical regions: two early warning signals emerged in spring and autumn every year across 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 southern regions. The early warning of HFMD across the seven regions is heterogeneous. In the northern regions, it has a high incidence during summer and peaks in June every year; in the southern regions, it has two waves every year with the first wave during spring spreading faster than the second wave during autumn. Our findings can help predict and prepare for active periods of HFMD.

Fig 1. Geographical distribution and incidence distribution in Hunan Province, Jilin Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County, and Longde County.

Fig 1A shows the locations and reported cases of in Hunan Province, Jilin Province, Shenzhen City, Xiamen City, Chuxiong Prefecture Yunxiao County, and Longde County in the map of mainland China. The dark grey regions include provinces with severe HFMD outbreaks every year. China can be roughly divided into two parts according to its humidity and temperature: the drier and colder part in the northwest and the more humid and warmer part in the southeast (Fig 1B). Five of the seven regions belong to the subtropical zone and two belongs to the mid-temperate zone. The southeast part includes tropical, subtropical and warm temperate zones; the northwest part includes middle temperate zone, the plateau zone and the middle and warm mixture zone. Fig 1C shows the time series of incidence in Hunan Province, Jilin Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County, and Longde County. The map depicted in this figure was taken from Wikimedia Commons https://commons.wikimedia.org/wiki/Atlas_of_the_People%27s_Republic_of_China#/media/File:China_Hunan.svg.

Fig 2. Diagram of method to determine early warning week of HFMD in epidemic cycle.

(S is the standard deviation; EAW is epidemic acceleration week; RWW is recommended warning week; WRW is warning removed week).

Fig 3. Distribution of Hand, Foot and Mouth Disease in Six Temperature Zones in China.

(A: Mixer Zone; B: Plateau Zone; C: Middle Temperature Zone; D: Warm Temperature Zone; E: Subtropical Zone; F: Tropical Zone).

Fig 4. The temporal and spatial distribution of HFMD in Hunan Province, Jilin Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County, and Longde County.

The map depicted in this figure was taken from Wikimedia Commons (http://commons.wikimedia.org/wiki/Main_Page). (A: Hunan Province; B: Xiamen City; C: Yunxiao County; D: Shenzhen City; E: Chuxiong Prefecture; F: Longde County; G: Jilin Province).

Fig 5. Epidemics of HFMD and LDE model fittings within Hunan Province and its 14 regions.

(A: Hunan Province; B: Changsha City; C: Zhuzhou City; D: Xiangtan City; E: Hengyang City; F: Shaoyang City; G: Yueyang City; H: Changde City; I: Zhangjiajie City; J: Yiyang City; K: Chenzhou City; L: Yongzhou City; M: Huaihua City; N: Loudi City; O: Xiangxi Prefecture).

Fig 6. Epidemics of HFMD and LDE model fittings within Jilin Province and its 9 regions.

(A: Jilin Province; B: Baicheng City; C: Baishan City; D: Jilin City; E: Liaoyuan City; F: Siping City; G: Songyuan City; H: Tonghua City; I: Yanbian City; J: Changchun City).

Fig 7. Epidemics of HFMD and LDE model fittings within ShenZhen City and its 6 districts.

(A: Shenzhen City; B: Baoan District; C: Futian District; D: Longgang District; E: Luohu District; F: Nanshan District; G: Yantian District).

Fig 8. Epidemics of HFMD and LDE model fittings within Xiamen City and its 6 districts.

(A: Xiamen City; B: Haicang District; C: Huli District; D: Jimei District; E: Simin District; F: Tongan District; G: Xiangan District).

Fig 9. Epidemics of HFMD and LDE model fittings within Chuxiong Prefecture.

Fig 10. Epidemics of HFMD and LDE model fittings within Yunxiao County.

Fig 11. Epidemics of HFMD and LDE model fittings within Longde County.

Fig 12. “EAW” and “RWW” of HFMD in spring and autumn in Hunan Province, Jilin Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County, and Longde County based on the weekly data.

(A: Hunan Province; B: Shenzhen City; C: Xiamen City; D: Chuxiong Prefecture; E: Yunxiao County; F: Jilin Province; G: Longde County).

Fig 13. Time and space warning map in Hunan Province, Jilin Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County, and Longde County.

The warning signals in this figure were median early warning week of each area. (A: Spring to Summer; B: Autumn to Winter; Red signals represent that the epidemic is in the accelerated period and indicate the beginning of early warning, and green signals represent that the epidemic is in the deceleration period, meaning that the early warning can be subsequently relieved.) The map depicted in this figure was taken from Wikimedia Commons https://commons.wikimedia.org/wiki/Atlas_of_the_People%27s_Republic_of_China#/media/File:China_Hunan.svg.