The ecological dynamics of hantavirus diseases: From environmental variability to disease prevention largely based on data from China

Abstract

Hantaviruses can cause hantavirus pulmonary syndrome (HPS) in the Americas and hemorrhagic fever with renal syndrome (HFRS) in Eurasia. In recent decades, repeated outbreaks of hantavirus disease have led to public concern and have created a global public health burden. Hantavirus spillover from natural hosts into human populations could be considered an ecological process, in which environmental forces, behavioral determinants of exposure, and dynamics at the human-animal interface affect human susceptibility and the epidemiology of the disease. In this review, we summarize the progress made in understanding hantavirus epidemiology and rodent reservoir population biology. We mainly focus on three species of rodent hosts with longitudinal studies of sufficient scale: the striped field mouse (Apodemus agrarius, the main reservoir host for Hantaan virus [HTNV], which causes HFRS) in Asia, the deer mouse (Peromyscus maniculatus, the main reservoir host for Sin Nombre virus [SNV], which causes HPS) in North America, and the bank vole (Myodes glareolus, the main reservoir host for Puumala virus [PUUV], which causes HFRS) in Europe. Moreover, we discuss the influence of ecological factors on human hantavirus disease outbreaks and provide an overview of research perspectives.

Fig 1. Map of Old World and New World hantavirus genotypes reported to be pathogenic for humans.

Hantaviruses that have been shown to cause HFRS are shown in red, and those that cause HPS are shown in green. PUUV, which causes a milder form of HFRS (NE), is found in Europe. The described African hantavirus, Sangassou virus, was found in Guinea in 2016. In recent studies, THAIV is considered to act as an additional causative agent of HFRS. It should be noted that SEOV is harbored by Rattus norvegicus (brown rat) worldwide, but only those locations where reports of human infections with SEOV are shown. The map was created specifically for this manuscript and was generated by ArcGIS 9.2 (ESRI, Redlands, CA, USA) based on World Countries (http://www.arcgis.com/home/item.html?id=d974d9c6bc924ae0a2ffea0a46d71e3d). HFRS, hemorrhagic fever with renal syndrome; HPS, hantavirus pulmonary syndrome; NE, nephropathia epidemica; PUUV, Puumala virus; SEOV, Seoul virus; THAIV, Thailand virus.

Fig 2. An overview of the ecological dynamics of HFRS caused by HTNV infection.

Arrows represent connections affected by environment: the green line represents rainfall, and the orange line represents temperature. The solid line indicates available data, used in models linking the ENSO (Nino3.4 index) with local climate (rainfall and temperature), rodent population density (capture rate), and human HTNV infections. The rectangles delimit the seasonal, interannual, and zoonotic cycles of HTNV. Source: Adapted from [46]. ENSO, El Niño Southern Oscillation; HFRS, hemmorrhagic fever with renal syndrome; HTNV, Hantaan virus.

Fig 3. Environmental factors associated with hantavirus disease outbreaks.

(A) Relationship between summer temperature, summer rainfall, and HFRS cases in Weihe Plain, North China, 1960 to 2013. Circle size is proportionate to the number of HFRS cases [46]. (B) Contribution of the environmental variables to the explained variance of hantavirus-antibody–positive in rodents using a multivariate principal component analysis in Hunan Province, South China, 2007 to 2010. Dimensions 1 and 2 are the spaces where variables are expressed. The length (angle) of the arrows represents the magnitude (direction) of the correlation coefficient between the variable and the principal components. The contributions of the variables to the hantavirus-antibody–positive in rodents are ranked with colors ranging from green to red, respectively (reproduced from Xiao 2016 with permission of the publisher [127]). Dim, dimension; HFRS, hemorrhagic fever with renal syndrome; NDVI, normalized difference vegetation index.

Fig 4. Urbanization, immigration, and hantavirus disease epidemics in an endemic area of south China.

(A) Urbanization and HFRS incidence in Hunan Province. A biphasic inverted U-shaped relationship was found between hantavirus disease epidemics and urbanization. (B) The number of immigrants and HFRS incidence. This result indicates that the effect of urbanization on HFRS epidemics changed, whereas the effect of immigration remained constant. Source: Adapted from [114]. HFRS, hemorrhagic fever with renal syndrome.