In this study, a novel BSTHM was used to explore spatial-temporal patterns of HFMD and its association with meteorological factors in Ningxia province, which is semi-arid region in northwest China. Previous studies showed that HFMD mostly concentrate in densely populated areas with humid or temperate climates. However sparely populated areas with arid/semi-arid climate should not be overlooked as it will provide evidence on HFMD distribution in different climate conditions and act as a reference.
In areas with arid/semi-arid climate conditions, the response of HFMD incidence with respect to climate change differs. The results in this paper showed that with a 1 °C increase in temperature, HFMD incidence increased by 9.21%. While in Gansu province with similar climate conditions, a 1 °C increase in temperature resulted in HFMD increase of only 1.8% . This discrepancy indicates that other factors, regardless of climate or socioeconomic, may have played a part in determining the final outcome of HFMD incidence.
The positive correlation between temperature increase and HFMD incidence are corroborated by other studies conducted in areas with different climate conditions. Study conducted in Shanxi province (located in central China) with temperate climate, in Jiangsu province, and Guangzhou city (both are located in south China) also demonstrated similar pattern [13, 31, 32].
However, the positive relation does not hold universally, it is only valid for limited temperature range. For example, a study conducted in Wuhan, the capital city of Hubei province located in south China showed that temperature ranging from 20 to 25 °C prevent HFMD infections in Wuhan . Other climate conditions may also have a threshold effect. A study conducted in mainland China, showed that relative humidity between 80.59 and 82.55% would lead to a higher risk of HFMD .
The temporal trends of HFMD in Ningxia varied for different counties. As presented in Table 1, the temporal trend in one (Helan) of five hot spot counties (20%) showed a rapidly increasing trend compared to the overall trend, indicating that Helan county will likely to continue experience a greater RR in the future. As a result, more attention should be paid to prevent the potential HFMD from happening in Helan county. In contrast, one (Yuanzhou) of five hot spot counties (20%) showed a slowly increasing trend in comparison with the overall trend, denoting that HFMD cases will not likely to increase for Yuanzhou district in the future. However, this is not to say that Yuanzhou district is immune from HFMD. On the contrary, because of the large number of HFMD cases in Yuanzhou district, even HFMD cases in Yuanzhou district showed a slowly increasing trend, attention should still be paid to prevent large outbreaks. Finally, the temporal trends in three (Xixia, Xingqing and Yongning) of five hot spot counties (60%) were consistent with the overall trend.
Regarding cold spot counties, three (Longde, Jingyuan, Haiyuan) of five (60%) exhibited a faster increasing trend than the overall increasing trend, indicating that the countries will likely have a high risk of HFMD and even become hot spots in the future. Furthermore, one of the five cold spots counties (20%) showed a slower increasing trend than the overall trend, ndicating that the risk in the county will likely be lower than the overall risk in the future. Finally, the trend in one (Pengyang) of the five cold spot counties (20%) was consistent with the overall trend, indicating that the current risk level in these counties will stay the same in the future.
Of the 12 counties that were neither hot nor cold spots: Huinong, Shapotou and Hongsipu showed a faster local increasing trend than the overall increasing trend, indicating that these counties will likely become hot spots in the future. The public health department should focus its attention on these counties. In addition, three: Qingtongxia, Lingwu and Yanchi, of the 12 counties that were neither hot nor cold spots showed a slower increasing trend compared to the overall increasing trend. Therefore, the counties will probably have a lower RR than the overall risk of other counties in the future, although only by a small margin. Finally, the trend in six of the 12 counties (50%) that were neither hot nor cold spots was consistent with the overall trend.
The relation between climate factors and HFMD incidence is not a straight forward liner relationship, there exists many confounding variables that may potentially influence HFMD incidence. For example, in Ningxia, the spatial distribution of HFMD risk was non-homogeneous, areas with the highest incidence (hot spots) of the disease were mainly concentrated in the northern regions with more developed economy and are more densely populated. Developed economy and favorable living conditions drew large number of internal migrants from underdeveloped southern mountainous areas and their neighboring provinces, where the living conditions are less favorable and economy under-developed. These socioeconomic conditions contributed to the high risk of HFMD in northern part of Ningxia.
Relatively large number of population and more developed economic conditions also contributed to higher risk of HFMD in Yuanzhou county, which stood out as the most disease-prone region in southern Ningxia surrounded by neighboring low risk areas. Similar to Yinchuan, the capital city of Ningxia, Yuanzhou is the economic center in southern mountainous regions and has more favorable living conditions than the neighboring mountainous counties. Furthermore, it has been chosen as the destination of the ecological migrants for the surrounding mountainous areas. Similar studies also found that economically developed and densely populated areas generally have higher risk of HFMD. Wang et al. explored spatiotemporal cluster patterns of HFMD at the county level in mainland China and found that clustering of HFMD were mostly present in eastern and southern China where economy is more developed and population density is high . HFMD rate in urban areas were also found to be higher than in rural areas, corroborating the previous finding .
This fact signifies the importance of socioeconomic factors on the incidence of HFMD compared to climate factors. For example, in response to the national strategy of targeted poverty reduction and relocating the poor, large amount of people in underdeveloped mountainous regions have been migrated to areas where the economic and living conditions are better. Yuanzhou district is one of the largest allocation destinations of the ecological migration in mountainous areas. As a result, the incidence of HFMD in Yuanzhou had increased dramatically. This finding was consistent with that of previous studies that population density , child density , and changes in the size of the population at risk (children 0–14 years old) have influences on HFMD incidence, together with other risk factor such as GDP [37, 38]. However, the influences of these socioeconomic factors are sometimes difficult to quantify than climate factors. Previous study also demonstrated that the performance of health systems is also an important influencing factor of HFMD transmission. When the Health System Performance was low, HFMD transmission increased with the population density, when the Health System Performance was high, HFMD transmission was suppressed .
From 2009 to 2013 the incidence of HFMD in Ningxia was generally increasing with varying rate for different counties. However, the rate of change (stable, slower increase, faster increase) did not show a clustering pattern. They showed a scattered pattern across the entire region of Ningxia instead. Furthermore, the rate of change did not correspond with hot/cold spots. In other words, fast increasing trend did not correspond to hot spots while slow increasing trend did not correspond to cold spots. This finding indicated that incidence of HFMD in Ningxia was subject to spatial-temporal heterogeneity, which should be taken into account for the public health department when controlling HFMD in Ningxia.
It should also be noted that although the southern part of Ningxia generally belongs to cold spot regions, the relative risk of HFMD occurrence is increasing. Moreover, the trend of increasing also happened in the middle and northern part of Ningxia, signifying the importance of controlling the HFMD not only in currently high risk areas but also in currently low risk areas to prevent unexpected large outbreaks in the future.
In addition to being spatially non-homogeneous, the risk of HFMD exhibited apparent seasonal variation. The seasonality of HFMD risk also indicated that climate factors likely played an important role in the temporal variance of this disease, as many previous studies indicated [39,40,41] because temperature may influence the recombination of the pathogenic viruses and the survival of the viruses . In addition, temperatures may be associated with specific human behavioral patterns such as time spend going outside or school time, which could affect the transmission of HFMD . During the entire study period, the highest incidence occurred in fall (September, October and November) and the lowest incidence occurred in winter in Ningxia, which is different from various other studies [4, 8, 13], indicating the influence of climate on HFMD incidence exist difference in different geographic areas. The increased HFMD in fall in Ningxia may be contributed to the climate conditions. As the temperature rises in spring, the risk of HFMD was increasing and reached the secondary peak, but as the temperature continued to rise, the HFMD risk dropped, similar to the threshold effect reported in Wuhan . However, the exact conditions (range of temperature and humidity) that trigger this threshold effect are probably different as Wuhan is located in south China with humid climate.
Moreover, similar studies also found that there was also a secondary peak of HFMD occurrence around spring (April, May, and June). For example, in one of the largest population-based study to date of the epidemiology of HFMD, Xing et al. reported that in China, HFMD peaked annually in June in the North, whereas Southern China experienced semi-annual outbreaks in May, September, and October . Apart from climate factors, the secondary peak may also relate to the concentration of internal migrant workers. After the Chinese New Year, large number of internal migrant workers from rural areas begin to move to more economically developed cities in eastern and southern China in order to make more profit. Large number of migrants potentially increases the risk of HFMD occurrence. In Ningxia province, large amount of migrant workers moves from southern mountainous areas to northern areas in Ningxia and other provinces in China, which is organized by the local government of Ningxia as a remedy for alleviating the poor from underdeveloped mountainous regions. From 2017 to 2020, there is an expected amount of 120,000 such migrants. High concentration of migrant population during spring potentially aggravated HFMD transmission and caused the secondary peak.
Although climate, socioeconomic factors and policy were identified as potential risk factors for the HFMD incidence in Ningxia, the relative importance for each factor and their interaction were not performed, in part due to the difficulty in quantify the influence of policy, health systems and other similar socioeconomic factors. Future studies aiming to explore the influence on the HFMD influence could compare the number of HFMD incidence before and after the policy on promoting local workers working outside Ningxia was implemented. Although it appeared from the result that HFMD in Ningxia is more sensitive to temperature variation compared with other semi-arid, humid or temperate areas, we should be cautious to draw the conclusion as there are other possible confounding variables not controlled. Future studies should therefore try to identify the influence of different risk factors that can potentially influence the HFMD incidence, and to quantify the interactions between the risk factors.