Epidemiological Characteristics and Associated Factors of Imported Respiratory Infectious Diseases in China , 2014-2018

Jinlong Wang (  jinlongrunner@163.com ) National Institute for Viral Disease Control and Prevention https://orcid.org/0000-0002-3847-3298 Tao Chen National Institute for Viral Disease Control and Prevention Lele Deng National Institute for Viral Disease Control and Prevention Yajun Han National Institute for Viral Disease Control and Prevention Dayan Wang National Institute for Viral Disease Control and Prevention Liping Wang Chinese Center for Disease Control and Prevention Guangxue He National Institute for Viral Disease Control and Prevention

reached 1.4 billion which are more than 10% Chinese citizens [3]. Meanwhile, the speed and volume of cross-border spread of infectious diseases increase with population mobility increasing [1]. The 1918 in uenza pandemic spreading to the world mainly by sea and land transportation, at that time international spread speed slower compared with the cross-border spread of infectious diseases today which can traverse the globe within one day [4][5][6]. Therefore, the surveillance, early warning, prevention and control of the cross-border spread of infectious diseases should be paid more attention.
In the past century, EIDs especially severe acute respiratory infectious diseases (RIDs), constantly occur worldwide, which have an enormous impact on human health and social development [2]. The rapid development of human society, convenient transportation, and frequent international exchanges have accelerated the cross-border spread of RIDs, which poses a signi cant challenge to the prevention and control. The Middle East Respiratory Syndrome (MERS) was rst reported in Saudi Arabia in 2012, and continued to spread to other countries as a result of travel of MERS cases. As of 26 April 2016, a total of 1,728 laboratory-con rmed MERS cases have been reported in 27 countries around the world [7]. In 2015, Guangdong Province reported the rst imported MERS case from South Korea, and rapid response and control were implemented quickly, avoiding the potential risk of onward spread and outbreaks [8,9].
Over the past decades, several international studies reported the relation between population mobility and infectious diseases spread [10][11][12]. Two previous studies had investigated the travel-related infections based on long-term surveillance data analysis, and reported the epidemiology of imported infections [13][14][15]. However, for imported RIDs, the detailed epidemiological characteristics and relative factors have not been further explored and analyzed. So that, we investigate the epidemiological characteristics and relative factors of imported RIDs for using high-tech and wisdom methods to early nd and stop the The imported RIDs information in our study were from the EESNC and NNDRS, and which is routine surveillance, and all cases information was anonymized.

Case de nition
The imported RIDs cases information was extracted and integrated from both EESNC and NNDRS. According to the Rules for the Implementation of Frontier Health and Quarantine Law of the People's Republic of China, all inbound passengers underwent routine infectious diseases screening when they passed through customs, which were reported through EESNC [19]. Symptomatic passengers were searched by fever screening and medical inspections, and other possible cases were found through selfdeclaration, on-board staff reports, and other methods. Suspector/suspected cases were transferred to epidemiological investigation and laboratory testing. For post-travel cases, medical staff identi ed the imported illness based on the diagnostic criteria of different infectious diseases and the travel history, which were reported through NNDRS [14].
Data management and quality control A uni ed criteria and de nition was made for using the data, and data management was performed by two staff accordingly. The imported RIDs information was obtained by linking the two EESNC and NNDRS databases, and the duplicate individual information was removed. Although imported RIDs came from 143 countries, only 24 countries' travel volume to China was obtained from the China Statistical Yearbook. Due to the in uenza accounted for over 90% of imported RIDs, we focused on analyzing imported in uenza situation to explore the relationship between the number of imported RIDs and the epidemiology in original regions. Scatter plots by continents were mapped using the imported in uenza data and annual in uenza surveillance report data from source countries.

Statistical analysis
Incidence per 100,000 travels were estimated as the number of imported cases divided by the number of inbound travelers. Seasonal index, which was used to describe the seasonality of imported respiratory infectious cases, was calculated by dividing each month number of imported RIDs by the respective yearly average number. The seasonal index was greater than 1, indicating the amount of that month is higher than the monthly average. A radar chart of the monthly seasonal indices of imported RIDs was plotted to clearly show the seasonal distribution characteristics. Continuous variables were summarized as median and range, and categorical variables were summarized as numbers and percentages. Pearson correlation coe cients were assessed to examine associations between independent variables and imported infections. Data analysis and visualization were conducted with R (version 4.0.5).  Fig. 1).

Temporal distribution
During 2014 to 2017, RIDs cases were mainly imported in July, with seasonal indices ranging from 2.95 to 10.10. In 2018, imported respiratory infectious cases were mainly concentrated in January-March, which was different from the previous importation peak in 2014-2017 (Fig. 3) .

Correlation analysis
The Pearson correlation coe cient between number of imported cases and inbound travel volume was 0.874 (95% con dence interval [CI]: 0.727 to 0.945). A linear relationship was observed from the scatter plot, and a best-tting line was calculated using the least squares method. The simple linear regression showed that the estimated coe cient for the slope of the line was 0.458, which indicated that, for every 10 thousand of inbound foreigners, the imported foreign respiratory infectious cases increased, on average, by 0.458 case. The results of the regression showed that the model explained 75.37% of the variance (adjusted R 2 = 0.7537) and that the model was signi cant, F(1,22) = 71.37, p < 0.001 (Fig. 4).
It can be observed that the number of imported in uenza cases increased with the increase of in uenza reports from the source countries, but countries from different continents showed various imported epidemiological characteristics. Compared with other continents, the number of in uenza cases imported to China from Asia countries was high, but the number of in uenza cases reported by Asian countries is relatively small. Clear linear relationships were observed from countries in Americas and Oceania (Fig. 5).

Discussion
The RIDs have huge impacts on people's health globally, and with the progress of globalization, the social, economic, cultural, and population exchanges of countries around the world have become more frequent, which poses a challenge to the prevention and control of cross-border transmission of RIDs [20,21]. This study described the epidemiological characteristics of imported RIDs in China during 2014-2018, and reported the correlation on the number of imported RIDs cases with inbound population volume, and the number of in uenza cases in the source countries. In uenza accounted for the majority of imported RIDs with obvious seasonality. The spatial distribution of imported RIDs was different between Chinese and foreigners. Among inbound foreigners, the incidence of imported RIDs was comparable high in male, 0-14 years old group, and Oceania. With the increase of inbound travel volume and number of in uenza cases in source countries, the number of imported RIDs cases increased. We hope the ndings can help to improve the surveillance and early warning of imported RIDs, promote the construction of joint prevention and control of infectious diseases among countries with high burden of RIDs, and protecting the health and safety of people around the world.
There are differences in the incidence of travel-related infectious diseases in different genders and age groups [22,23]. The differences are relative to the type of infectious disease, the population, and the destination of travel [23]. In this study, males and the 0-14 age group have a higher risk of importation of RIDs, which is consistent with previous studies [24][25][26][27]. Males, accounting for the major of travelers, may be more susceptible to RIDs infection due to some risk behaviors and habits during the travel. Children may be more susceptible to respiratory infections due to the lack of proper protection against infectious diseases and lower immunity compared with adults [24][25][26][27]. Most children have been infected with at least one in uenza virus by the age of 6 years old [29,30]. Children infected with in uenza during travel will increase the risk of infection to their parents and other relatives, which can be reduced by vaccination before travel [30].
The seasonal uctuation of imported RIDs are observed in our study, which may be affected by several factors, e.g. international travel on holidays, and seasonality of RIDs in original areas [31].The number of population traveling abroad increase during holidays, such as Chinese traditional spring festival from January to February and summer vacation for Chinese students from July to August, which promote the cross-border spread of RIDs. In addition, the seasonality of the in uenza imported to China was similar to in uenza in Asian countries, which accounted for the majority of imported RIDs. The import peak in January-March 2018 was different from that in 2014-2017, which might be mainly affected by the 2018 spring in uenza pandemic in northern hemisphere countries [32].
Travel volume is an important factor in uencing the number of RIDs cases imported [33,34]. Passengers who contracted infectious diseases before or during travel spread the infectious diseases to another country by cross-border travel. Generally, the risk of imported infectious diseases increases with the increase of passenger volume. A previous study on the cross-border transmission of H1N1 revealed that the risk of importing H1N1 into countries that received more than 1,400 passengers from the endemic countries has increased signi cantly [35]. Travel volumes, especially the air travel data, are often used as an important variable for estimating the risk of cases importation at certain conditions [36]. Therefore, when emerging and reemerging infectious diseases outbreak, the cross-border spread of infectious diseases can be constrained effectively by scienti c travel restriction, which has been proved in the practice of prevention and control of RIDs in recent years [37][38][39][40].
The number of imported cases is associated with the number of reported cases in source countries, which may be affected by prevalence of the disease and population of that country [41]. In general, the higher prevalence of infectious diseases in the source country, the higher risk of importation into neighboring countries. However, to estimate the risk of imported cases, the source countries' RIDs prevalence needs to be analyzed comprehensively with some other factors, such as travel restriction, cultural customs, social environment, travel distance, travel transportation and purpose. This study found that the average number of in uenza case reports in the source countries of Asia is smaller than that in the Americas and European countries, but the number of importation cases from Asia countries is the highest. The travel volume variable can explain part of that variation, but other signi cant variables in uencing on the importation of infectious diseases should be further explored.
In order to assess and predict the risk of importation, previous studies have developed some statistical models based on the data related to importation, such as international ights information, the epidemiology of selected diseases and demographic information of the source countries [42,43]. Given the prerequisites of these models, it is often assumed that all residents have the same chance of infection, and all infected persons have the same chance of boarding the ights abroad. However, this assumption is di cult to come real, which is also the main reason for the difference between the predicted results of the model and the true results. Therefore, some other factors that can affect imported infectious diseases should be further studied and included in the analysis of the predictive models.
By the way, we think that there are additional factors that affect the epidemiological characteristics of imported RIDs, which need to be further explored. Vaccination status is one of the factors that in uence imported RIDs. Also, environmental changes, e.g. temperature, humidity, air pollution, and sun exposure may also in uence the RIDs spread [44]. Travel duration is often considered as another important factor of imported RIDs. Besides, due to the data mainly from EESNC and NNIDRS, it is possible to lose some information in our study, and might lead to inexactly calculated incidence of imported RIDs.

Conclusions
The trend of imported RIDs incidence increased from 2014 to 2018. The gender, age, continent, inbound passenger volume and number of reported cases in original countries associated relatively with the incidence of imported RIDs. With the annual increase of international travel, the potential risk of RIDs spread to China rises accordingly. Therefore, it is urgent to strengthen the surveillance at customs for inbound population, and establish the wisdom surveillance and warning systems for imported RIDs to early nd and stop the RIDs spreading to China. Furthermore, if the infectious diseases were controlled and eradicated at the original countries, the health and safety of people around the world will be protected effectively. So, it is very important for international community to support the important RIDs prevention and control for countries with limited resources. Figure 1 Caption not available with this version of the manuscript.

Figure 2
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Figure 5
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