Risk factors associated with scrub typhus infection: A case-control study from Luhe, China

Background: Globally, Scrub typhus (ST) is a serious public health issues in the rural of Asia-Pacific area. This study aimed to determine the risk factors associated with ST infection in Luhe District, China. Methods: The case-control study was conducted which involved (N=116) cases consisted of a patient who diagnosed with scrub typhus, and nearest neighbours control (N=232) subjects were selected by matching for occupation, place of residence and age (within 5-years) and lacked a history of scrub typhus. Statistical analysis was performed using SPSS version 25.0 for Windows. Results: The mean age of confirmed cases was 58.1(10.15) years, while that of control subjects were 56.14 (11.57). The ratio of farmers in cases and controls subjects was 90 (77.6%) and 187 (80.6%) respectively. There are no significant differences in the demographic characteristics of the study population (P>0.05). small and weed presence of mouse activities in house 3.88, P<0.054) significant associated with developing of ST infection. The logistic regression analysis showed that Two out of five general exposure factors were identified which include morning exercise in the park (AOR=3.848, 95% CI=1.018-4.544, P=0.047), and working as labourers in vegetable fields (AOR =1.792, 95% CI=1.12-2.87, P=0.016) a significant association with ST infection. ST infection. The findings derived from this study provide an information in the control and prevention of ST in Luhe, China.


Introduction
Globally, scrub typhus (ST) remains one of the major public health problems. Every year millions of people are infected with ST [1].
It was estimated approximately 55% of the world's population lives in areas where ST is endemic [2]. Epidemiological data shows that in areas where ST is an endemic, the risk of infection is mainly associated with farming and outdoor activities, particularly in rural areas [3]. Previously published studies report that the risk of ST outbreak are presented in bundling or moving waste straw, living in the edge of the village, living in a house near to grassland. In addition, individuals working in vegetable fields and hilly areas, ditches, rice fields, and stacking waste straw indoors are also highly affected [3][4][5]. In China, the disease is mainly prevalent in tropical and subtropical regions [5,6]. Recently conducted studies reported an increase of ST in China [7,8]. Therefore, this present study was undertaken to explore risk factors associated with ST infection in Luhe District, Nanjing, China.

Study area
The study was conducted in Luhe district (figure 1), with a population of more than 927,400 (2014), in the Northern part of Nanjing (longitude, 118°~119°E; latitude, 32°11' ~32°27' N). The district covers an area of 485.50 km 2 . This region has been considered as the main endemic area of ST in Nanjing. Luhe has a subtropical monsoon climate, with an estimated average annual temperature of 16°C to 36.4°C in July, with the lowest temperature being -8.2°C in December. Average annual precipitation ranges between 821mm to 938 mm, while the average annual sunshine is 1,722 hours and the average annual evaporation stands at about 1253. 8  obtained the socio-demographic information (age, gender, occupation, and educational level) of case and control subjects, factors associated with living environment (residential site, house type, house yard with cement, raising animals, piling weeds in the yard and around the house). Others such as case-control behaviours during the outdoor activities (bundling straw, morning exercise, grazing animals, having travelling history, and types of work in the agricultural field) within the previous month were all recorded during the season of ST reported cases using unified format, was applied to documented cases and control demographic information.

Statistical analysis
Data was entered using Epidata 3.1 (Jens M. Lauritsen, Odense, and Syddanmark, Denmark), and statistical analysis was performed using SPSS version 25.0 for Windows (IBM SPSS, Chicago, IL, USA). Continuous data were expressed as the mean (SD). Categorical data were expressed as the frequency or proportion between the case and control by using the Chi-square test (χ2) or Fisher exact test, where appropriate to detect the statistical difference in case and control group.
Furthermore, multivariate logistic regression model was used for assessing the association between cases and control variables. The two-sided p-value of less than 0.05 was considered statistically significant.

Ethical consideration
The study was conducted after obtaining approval from an Institutional Review

Results
In the period between 2015 and 2017, a total of 116 cases and 232 control were recruited in this study. Among all cases, 55 (47.4%) were male, and 61(52.6%) were females. The mean age was 58.1(10.15) years in cases and 56.14 (11.57) in control groups. The age group 41-60 had the predominant number of cases proportion at 61 (52.6%) in the case and 118 (50.9%) in the control group. Occupation-wise, 90 (77.6%) cases and 187 (80.6%) controls were farmers. Out of the total, 73 (62.9 %) of cases and 145 (62.5%) of control were in primary school level. There were no significant differences in age, gender, education level, house type, and occupational between the two groups (P >0.05), as shown in Table 1.
The association between ST outcome and risk factors of the living environment is shown in Table 2.  Table 4.

Discussion
Scrub typhus is known to be an endemic disease in China. 8 The number of cases has been reported in many parts of China [6,8,[10][11][12][13].
To identify the risk factors associated with ST in the district, we conducted a casecontrol study. In this case-control study, we found that most of the ST infected cases, 90 (77.6%) and 187 (80.6%) controls were farmers, which suggested that the disease endemicity is associated with agricultural activities and raising animals and livestock. Further, outdoor activities and less use of protection measures are significant factors associated with ST infection.
Factors that may contribute to the increase of ST included outdoor activities, changes in ecological environment, living in an endemic area might be the reason for increasing the chances of being bitten by chigger mites [14].These findings indicated significant differences between the two groups living in the environment. This is consistent with other findings [9].The results suggest that age above 40 years is closely associated with risk of ST infection [9]. Similarly, primary school level education is the most risk groups; which is in line with other studies [15]. to their frequent contact with disturbed habitats in their surroundings. Another element is that ST infection in Luhe district is more common in female than male. It may be because most women generally spend more time on the farm and engaged in outdoor activities [11].A study conducted in Korea reported that females are more likely to be at risk of ST infection than males [16]. Moreover, the rise of farming

Availability of data and materials
The datasets used in current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate
The study was conducted after obtaining approval from an Institutional Review

Consent for publication
Not applicable.

Competing interests
The authors declare that they have no competing interests.    * Only the significant factors in Table 3 were selected for this analysis. Map of study area (Luhe district, Jiangsu Province, China). Note: The designations employed