Background
Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by hantaviruses. Each hantavirus tends to be specific to a different rodent or insectivore host [
1,
2]. Two dominant hantaviruses, Seoul virus (SEOV) and Hantaan virus (HTNV), carried by
Rattus norvegicus and
Apodemus agrarius, respectively, cause HFRS in China [
3]. China is one of the countries most affected by hantaviruses (mainly HTNV and SEOV). The reported cases in China account for 90% of the total global burden of the HFRS [
4‐
6]. HFRS has become an important public health problem in Asia. The mortality rates have reached 12% in some outbreaks [
7]. In recent years, the incidence of HFRS has significantly decreased. However, 30,000–60,000 cases are reported annually in China [
8]. Hunan Province is one of the most seriously affected areas in mainland China [
2,
6,
9]. Since HFRS was first detected in Hunan Province in 1963, more than 90% of the cities in the province have reported cases [
4,
10,
11]. Hunan Province has reported several hantavirus strains, predominantly SEOV, and various species of rodent host, including
A. agrarius,
R. norvegicus,
Mus musculus, and
Rattus flavipectus [
12,
13]. All of these species can carry hantaviruses [
14] and were found to carry and transmit hantavirus frequently in recent years [
15].
Rodent population densities, virus prevalence in rodents, diversity of rodents, rodent community composition, and species distributions have important influences on HFRS transmission [
16‐
22]. Different rodent species thrive in different habitats. For example,
A. agrarius prefers humid and food-rich environments, and is found predominantly in forested regions and fields.
R. norvegicus is abundant in residential areas, and is the main vector for zoonotic diseases in rural and urban populations [
4]. The main routes of transmission to humans are inhalation of aerosolized urine or feces, contact with the saliva of infected rodents, or via contaminated food, all of which require humans and rodent hosts to share the same space [
4,
23]. Previous studies revealed that land use influences HFRS transmission through the effect on the reservoir, host, and environmental conditions [
6,
24]. To date, few studies have examined the relationships among landscape, rodent community composition and HFRS occurrence. In 2006–2008, the rodent density in different habitats and the prevalence of major rodent-borne diseases (including HFRS) in Nanchang City in Jiangxi Province were investigated and the risks of the rodent-borne diseases were assessed [
25]; The spatial as well as temporal variation in the occurrence of HFRS is linked to geographic differences in the population dynamics of the reservoir rodents in different biomes of Europe [
26]. These studies showed that studying the relationships among landscape, rodent community composition and HFRS occurrence are beneficial works to promote the progress of the understanding of HFRS epidemiology.
The first case in Shaoyang, one of the prefecture-level cities most seriously affected by HFRS in Hunan Province, was reported in 1965 [
27]. In 2006, 135 cases were reported in Shaoyang, accounting for 24.1% of the total cases in Hunan Province. There were more than 1000 cases, in total, from 1980 to 1999, but the incidence decreased for unknown reasons by 54.3% during this time period. In prefecture-level city of Loudi, after the first case emerged in the 1970s, the incidence of HFRS increased substantially in the 1990s. Despite a decline in incidence in Loudi that began in the early 2000s, there was still one area with high incidence. The annual incidence in Loudi increased to 3.7 cases per 100,000 people in 2007, and was the highest in Hunan Province.
The aims of this study were to: 1) investigate how the community composition of the hosts influences the risk of HFRS among different landscapes; 2) to identify dominant rodent species in different environments; and 3) to investigate the spatiotemporal distribution of hantavirus infection risk at small spatial scales.
Discussion
This study investigated the relationships among HFRS occurrence, land use type, and rodent community composition. The results indicated that different rodent species influenced the HFRS occurrence for different land use types.
Overall, the highest probability of HFRS was on cultivated land, followed by urban areas, forests, and grasslands. Relatively few cases of HFRS were identified in water covered areas in both Shaoyang and Loudi. For the same land use type, the probability of HFRS occurrence varied between cities. The high probability of HFRS on cultivated land may be due to the humid environment with adequate food for rodents to survive. Farmers working on cultivated land increase the potential for contact between rodents and humans, thereby increasing the risk of HFRS transmission. In 2012, relatively high HFRS risk was predicted in urban areas in Shaoyang, but in 2013, the predicted HFRS risk was lower. This might have resulted from increases in
R. norvegicus and
A. agrarius in 2012 and 2013.
R. norvegicus was positively associated with HFRS in urban land while
A. agrarius was negatively associated with the HFRS in urban land. The negative correlation was stronger than the positive correlation (Fig.
2b). Therefore, the increase in
A. agrarius had a greater influence on HFRS in urban land in Shaoyang. An increase in intensive human activities, such as farming, leading to agricultural encroachment on forests, grassland areas, and water covered areas, and large human populations in urban areas changing the geographical landscape [
20], has an important impact on the spread of viruses. A previous study, focused on HFRS cases caused by HTNV in rural areas, found that agricultural land use and cultivated soil were related to high risk for HFRS [
6]. We found the risks among different land use types varied in relation to rodent community composition.
Hantaviruses are transmitted to humans by infected rodents. Different land uses lead to different rodent community composition and distribution [
31,
32]. Moreover, each land use type has a predominant rodent species. In the current study, the risks of hantavirus infection in cultivated land were associated with different rodent species in Loudi and Shaoyang. The risks of HFRS occurrence in other land use types varied for different rodent species. In Loudi,
A. agrarius was the most predominant species (Figs.
3 and
4a). However, the highest risk of hantavirus infection was on cultivated land, and mainly correlated with
R. norvegicus (Fig.
2a)
. This suggests Loudi city may be a mixed-type epidemic area. In Shaoyang,
R. norvegicus was the predominant species (Figs.
5 and
4b). Cultivated and urban areas had higher risk of HFRS and HFRS in these areas was predominantly associated with
A. agrarius and
M. musculus, respectively (Fig.
2b), indicating that Shaoyang may be a mixed-type epidemic area. It can be concluded that both of the cities are mixed-type HFRS epidemic areas with various reservoir rodents. The corresponding risks of potential contact between humans and rodents in different landscapes may also change over time with varied rodent community composition.
Different rodent population dynamics have disparate influences on HFRS occurrence.
A. agrarius and
R. norvegicus were the predominant species in Loudi and Shaoyang, respectively. According to monitoring data from the last 20 years in China, the highest virus-carrying indexes among host animals in wild and residential areas are for
A. agrarius and
R. norvegicus, respectively [
33‐
35]. Different rodents have their own preferred habitats and different abilities to carry and transmit pathogenic viruses.
A. agrarius are more active outdoors and
M. musculus,
R. norvegicus, and
R. flavipectus are active both outdoors and indoors [
13]. We found different rodent species in both Loudi and Shaoyang, so the occurrences of HFRS cases in both outdoor (cultivated land, forest, grass, and water) and indoor (urban land) environments are consistent with prior knowledge. The coefficient matrix of Loudi indicated that
R. norvegicus was the dominant species affecting HFRS risk on cultivated land. HFRS occurrence and the related dominant rodent host varied for each environment. This suggests that rodent community composition has a significant influence on the epidemic pattern and transmissions of hantaviruses.
Based on these findings, preventative measures can be developed for different land use types, in different cities and epidemic areas. HFRS is related to the number of rodents in different environments. Therefore, we can effectively identify the dominant rodent species in different areas and enact preventative measures to reduce the risk of hantavirus transmission. Cultivated land was a high-risk area for HFRS in our study. The dominant rodent species in this environment has an important impact on the HFRS risk. Therefore, more attention should be spent reducing rodent numbers in these environments. This is consistent with a previous study that found that HFRS cases commonly occur in rural areas [
36].
R. norvegicus was the main vector for hantavirus in Loudi and the main vectors in Shaoyang were primarily
A. agrarius,
R. flavipectus, and
M. musculus. Differences in rodent community composition may result in different epidemic characteristics, infection risks, and even control measures. For example, when
A. agrarius is the predominant species in the rodent population, as in Loudi, the main risk of HFRS is from cultivated land, so the prevention of HFRS should focus more on the farmlands. In contrast, when
R. norvegius is the predominant species in the rodent population, such as in Shaoyang, the main risk of HFRS is from cultivated land, forest, and urban land, which indicates that more attention should be paid to all these types of land. Our study indicates that rodent community composition and land use types are associated with the epidemiology of HFRS. This information can be used to develop species-specific control measures to reduce the risk of potential contact between hantavirus and humans in different environments.
Several limitations for this study should be noted. First, it only considered the influence of rodents on HFRS. Hantavirus transmission results from a combination of environment, climate change, change in biotope, hantavirus species, and social factors [
13,
31,
37]. Second, more detailed information about both rodents and humans needs to be considered, including rodent density, virus-carrying index, and population density. In the absence of the virus-carrying and population density data, we cannot investigate the actual role of rodent species in viral transmission from rodents to humans. Third, change in land use was not considered in our model because these data were not available. Finally, we used the postal addresses of patients to represent the sites of contact, which might have induced measurement error. The accuracy of address resolution was also limited. Further studies are needed to determine the effect of rodent community composition, density, distribution and virus-carrying index on the risks of HFRS transmission. Additionally, potential seasonal variation in prevalence is critical and should be considered when studying contact rate. It is therefore prevalence, seasonal variations of prevalence, and other environmental factors should also be considered in future studies.