Hand, foot and mouth disease (HFMD) is a highly contagious infectious disease that primarily affects children under the age of five years [1
]. It is caused by a spectrum of pathogens in the enterovirus (EV) family [2
] and is transmitted via the oral–fecal route and by contact with contaminated fluids and respiratory droplets; the infection may result in neurological complications and death. From January 2008 to July 2012, at least 6.5 million children were reported with HFMD infections, and more than 2200 died in China [3
]. HFMD ranked first among the notifiable infectious diseases in 2015 [4
], and nationwide HFMD epidemics have become a significant public health concern in China [5
HFMD transmission demonstrates seasonal variation. In mainland China in 2008–2009, HFMD cases peaked in April [5
], while in Hong Kong and Japan, the seasonal peak was during the summer months [6
]. This suggests that local meteorological variables might have an important influence on the temporal risk of this disease.
The association between HFMD and climatic factors has been studied in many regions [8
]; the main factors are temperature, precipitation and relative humidity. A higher HFMD incidence occurs in China when temperatures are in the range of 70 °F to 80 °F, and when there is higher relative humidity, lower wind speed, and greater precipitation [2
]. In addition, the HFMD rate shows a similar trajectory of geometric center to temperature across 47 weeks in China [11
]. Similarly, mean temperature and precipitation are significantly associated with the HFMD incidence rate in Singapore [12
]. In Japan, temperature and relative humidity are significantly linked to increased HFMD occurrence [7
In addition to seasonal variation, HFMD also features spatial heterogeneity. Some studies have shown that a high risk of HFMD is closely correlated to high population density [2
]. Cheng et al. found that the number of urban HFMD cases was much greater than that of rural ones, with an urban-to-rural ratio of 2.2:1, and the incidence rate of HFMD in urban areas was 3.6 times higher than in rural areas [16
]. Also, rural-to-urban migrant-worker parents were found to be the major risk factor associated with HFMD in children [3
The Beijing–Tianjin–Hebei region is one of the three major urban agglomerations in China, with a population of 107 million and covering an area of 210,000 km2. It is located in a temperate monsoon climate zone with high climatic variation. Economic development is imbalanced; around the most prosperous cities, such as Beijing and Tianjin, there are large numbers of underdeveloped regions. Many migrant rural workers are found in the cities and neighboring regions. In recent years, the incidence of HFMD has been increasing in this region. The present study aimed to analyze the epidemiological features of HFMD and locate the areas having higher risk to reveal the spatial and time patterns of the disease and quantify the association between HFMD and socioeconomic and meteorological risk factors to explore the determinant power of these factors.
HFMD remains a major public health concern in China. The Beijing–Tianjin–Hebei region, one of the largest urban agglomerations in north China, has had a notably high incidence of HFMD in recent years [1
]. This study explored the epidemiological characteristics of the disease, and detected the high-risk areas. The associations between HFMD and meteorological variables, as well as socioeconomic factors, were examined. The results indicated that the highest risk is mainly found in urban and suburban areas with high population densities. In addition, meteorological factors have a significant effect on the transmission rate of HFMD.
An exploration of the epidemiologic characteristics of children with HFMD under the age of five years showed that boys outnumbered girls, and those aged one to two years accounted for the majority of complicated cases, which is consistent with the results of the study by Zeng et al. [3
]. This may be because boys are more active than girls, and would therefore have more opportunity to be exposed to environments that contain the HFMD virus. Furthermore, studies have shown that breastfeeding has protective effects against HFMD [32
], which may be why infants under one year of age have a lower incidence than children aged one to two years. In China, maternity leave is only four months, so children over the age of one year receive less protection via breast milk.
The incidence of HFMD changes with the seasons throughout the year in the study area. This seasonal variation in incidence is associated with meteorological risk factors, which are considered key environmental factors that influence the incubation and survival of HFMD. We found that high temperature and greater precipitation were positively associated with the incidence of HFMD, possibly because under such climatic conditions HFMD viruses become more active. Similar to our findings, temperature and cumulative rainfall have been found to be significantly associated with HFMD incidence in Singapore [12
]. In an analysis using an S-BME spatiotemporal model, the number of HFMD cases showed a close relationship to monthly precipitation in mainland China [2
]. In Hong Kong, temperature and precipitation were also found to play important roles based on a regression model [9
]. A study in Jinan of northern China also found that average temperature and average relative humidity were positive associated with HFMD, while precipitation and sunshine hours were negatively associated [17
]. In South Korea, the risk of HFMD has been shown to increase with the rise of temperature and relative humidity [20
The results of the SaTScan showed that the most likely spatial clusters were mainly located in urban Beijing and its neighboring areas, with an RR value of 3.04 (p < 0.01). In this area, the population density is very high, and the results were consistent with the findings of the influencing-factor analysis using GeoDetector, in which urban areas with high population density and high per capita GDP had higher rates of HFMD.
This study found that the proportion of primary industry was negatively associated with HFMD transmission, while the proportion of tertiary industry had a positive relationship. This indicates that urban and suburban areas have a higher risk compared to rural regions.
Previous studies indicated that kindergarten/daycare center attendance is an important risk factor for HFMD infection [3
]. Most children in the developed areas of mainland China are sent to daycare centers or kindergartens, whereas children in undeveloped areas usually stay at home and have few opportunities to gather with other children, thus reducing the opportunities for contact with HFMD-infected children. Furthermore, migrant workers mainly live in suburban areas and usually have less education, poorer economic statuses, limited knowledge about disease prevention, and less appropriate health care for the diagnosis and treatment of disease.
This study found that GDP and population density play important roles in the transmission of HFMD, as the regions with high GDP and high population density had a higher rate of HFMD. This is consistent with a previous study by Zhu et al., which found that economically developed areas, such as Beijing, Tianjin, Shanghai, and Zhejiang, had a higher disease incidence than underdeveloped areas [5
]. Similarly, Huang et al. found that tertiary industry and population density had the most important influence in their selected factors, explaining 42% of the HFMD transmission [19
]. Zeng et al. found that children of rural-to-urban migrant workers in China are at a higher risk of contracting severe HFMD [3
]. Finally, Hu et al. indicated that population density is an important factor across China [13
]. In China, developed areas with a high GDP also have higher population densities. One important reason for the high disease incidence in those areas is that people are in contact with each other more frequently, which is conducive to the spread of HFMD. This indicates that developed regions should pay more attention to public health resource allocations.
In order to analyze the epidemiological features of HFMD, reveal spatial clusters, and detect risk factors, a group of statistical methods were used in the study. SaTScan was carried out to detect spatial clusters of HFMD, GeoDetector was used to identify potential risk factors and assess their determinant power, and the spatial paneled model was used to quantify the elastic coefficient between HFMD and the risk factors, considering spatial autocorrelation and heterogeneity. The results have clear statistical meanings. However, some epidemiological parameters cannot be obtained only from a limited number of models, so more models with other perspectives, such as SIR(Susceptible-Infected-Recovered) type dynamic model [34
], would be a beneficial supplement for future studies.
HFMD is also significantly influenced by micro-environments, such as community and home environments, parental educational levels, and hygiene customs. The spatial scale used in this study was at the county level, which may obscure some factors via the ecological fallacy effect [35
]. Meanwhile, some confounders may influence the results of the study. For example, during the summer holidays in China there are large numbers of tourists from home and abroad, and the large crowds along with higher temperatures, lead to more opportunities for disease transmission, and thus the influence of temperature may be overestimated. The above-mentioned factors could introduce some uncertainties in the study.