Katrien Tersago

Hantavirus disease (nephropathia epidemica) in Belgium : effects of tree seed production and climate

Recently, human cases of nephropathia epidemica (NE) due to Puumala virus infection in Europe have increased. Following the hypothesis that high reservoir host abundance induces higher transmission rates to humans, explanations for this altered epidemiology must be sought in factors that cause bank vole (Myodes glareolus) abundance peaks. In Western Europe, these abundance peaks are often related to high tree seed production, which is supposedly triggered by specific weather conditions. We evaluated the relationship between tree seed production, climate and NE incidence in Belgium and show that NE epidemics are indeed preceded by abundant tree seed production. Moreover, a direct link between climate and NE incidence is found. High summer and autumn temperatures, 2 years and 1 year respectively before NE occurrence, relate to high NE incidence. This enables early forecasting of NE outbreaks. Since future climate change scenarios predict higher temperatures in Europe, we should regard Puumala virus as an increasing health threat.

Determinants of the geographic distribution of Puumala virus and Lyme borreliosis infections in Belgium

BackgroundVector-borne and zoonotic diseases generally display clear spatial patterns due to different space-dependent factors. Land cover and land use influence disease transmission by controlling both the spatial distribution of vectors or hosts, and the probability of contact with susceptible human populations. The objective of this study was to combine environmental and socio-economic factors to explain the spatial distribution of two emerging human diseases in Belgium, Puumala virus (PUUV) and Lyme borreliosis. Municipalities were taken as units of analysis.ResultsNegative binomial regressions including a correction for spatial endogeneity show that the spatial distribution of PUUV and Lyme borreliosis infections are associated with a combination of factors linked to the vector and host populations, to human behaviours, and to landscape attributes. Both diseases are associated with the presence of forests, which are the preferred habitat for vector or host populations. The PUUV infection risk is higher in remote forest areas, where the level of urbanisation is low, and among low-income populations. The Lyme borreliosis transmission risk is higher in mixed landscapes with forests and spatially dispersed houses, mostly in wealthy peri-urban areas. The spatial dependence resulting from a combination of endogenous and exogenous processes could be accounted for in the model on PUUV but not for Lyme borreliosis.ConclusionA large part of the spatial variation in disease risk can be explained by environmental and socio-economic factors. The two diseases not only are most prevalent in different regions but also affect different groups of people. Combining these two criteria may increase the efficiency of information campaigns through appropriate targeting.

Population, environmental, and community effects on local bank vole (Myodes glareolus) Puumala virus infection in an area with low human incidence.

In this study, the distribution of Puumala hantavirus (PUUV) infection in local bank vole Myodes glareolus populations in an area with low human PUUV infection (nephropathia epidemica [NE]) incidence in northern Belgium was monitored for 2 consecutive years. Bank voles were trapped in preferred habitat and tested for anti-PUUV IgG. Infection data were related to individual bank vole features, population demography, and environmental variables. Rare occurrence of PUUV infection was found and PUUV prevalence was low compared with data from the high NE incidence area in southern Belgium. Small-scale climatic differences seemed to play a role in PUUV occurrence, vegetation index and deciduous forest patch size both influenced PUUV prevalence and number of infected voles in a positive way. The data suggested a density threshold in vole populations below which PUUV infection does not occur. This threshold may vary between years, but the abundance of bank voles does not seem to affect the degree of PUUV seroprevalence further. We found indications for a dilution effect on PUUV prevalence, dependent on the relative proportion of nonhost wood mice Apodemus sylvaticus in a study site. In conclusion, we regard the combination of a dilution effect, a possible threshold density that depends on local conditions, and a higher fragmentation of suitable bank vole habitat in our study area as plausible explanations for the sparse occurrence of PUUV infection and low prevalence detected. Thus, beside human activity patterns, local environmental conditions and rodent community structure are also likely to play a role in determining PUUV infection risk for humans.

Environmental conditions and Puumala virus transmission in Belgium.

BackgroundNon-vector-borne zoonoses such as Puumala hantavirus (PUUV) can be transmitted directly, by physical contact between infected and susceptible hosts, or indirectly, with the environment as an intermediate. The objective of this study is to better understand the causal link between environmental features and PUUV prevalence in bank vole population in Belgium, and hence with transmission risk to humans. Our hypothesis was that environmental conditions controlling the direct and indirect transmission paths differ, such that the risk of transmission to humans is not only determined by host abundance. We explored the relationship between, on one hand, environmental variables and, on the other hand, host abundance, PUUV prevalence in the host, and human cases of nephropathia epidemica (NE). Statistical analyses were carried out on 17 field sites situated in Belgian broadleaf forests.ResultsLinear regressions showed that landscape attributes, particularly landscape configuration, influence the abundance of hosts in broadleaf forests. Based on logistic regressions, we show that PUUV prevalence among bank voles is more linked to variables favouring the survival of the virus in the environment, and thus the indirect transmission: low winter temperatures are strongly linked to prevalence among bank voles, and high soil moisture is linked to the number of NE cases among humans. The transmission risk to humans therefore depends on the efficiency of the indirect transmission path. Human risk behaviours, such as the propensity for people to go in forest areas that best support the virus, also influence the number of human cases.ConclusionThe transmission risk to humans of non-vector-borne zoonoses such as PUUV depends on a combination of various environmental factors. To understand the complex causal pathways between the environment and disease risk, one should distinguish between environmental factors related to the abundance of hosts such as land-surface attributes, landscape configuration, and climate – i.e., host ecology, – and environmental factors related to PUUV prevalence, mainly winter temperatures and soil moisture – i.e., virus ecology. Beyond a threshold abundance of hosts, environmental factors favouring the indirect transmission path (soil and climate) can better predict the number of NE cases among humans than factors influencing the abundance of hosts.

Hantavirus outbreak in Western Europe: reservoir host infection dynamics related to human disease patterns.

Within Europe, Puumala virus (PUUV) is the causal agent of nephropathia epidemica (NE) in humans, a zoonotic disease with increasing significance in recent years. In a region of Belgium with a historically high incidence of NE, bank voles (the PUUV reservoir hosts), were monitored for PUUV IgG antibody prevalence in nine study sites before, during, and after the highest NE outbreak recorded in Belgium in 2005. We found that the highest numbers of PUUV IgG-positive voles coincided with the peak of NE cases at the regional level, indicating that a PUUV epizootic in bank voles directly led to the NE outbreak in humans. On a local scale, PUUV infection in voles was patchy and not correlated to NE incidence before the epizootic. However, during the epizootic period PUUV infection spread in the vole populations and was significantly correlated to local NE incidence. Initially, local bank-vole numbers were positively associated with local PUUV infection risk in voles, but this was no longer the case after the homogeneous spreading of PUUV during the PUUV outbreak.

Impact of Puumala virus infection on maturation and survival in bank voles: a capture-mark-recapture analysis.

Many zoonotic diseases are caused by rodent-borne viruses. Major fluctuations in the transmission of these viruses have been related to large changes in reservoir host population numbers due to external factors. However, the impact of the pathogen itself on the demography of its reservoir host is often overlooked. We investigated the impact of Puumala virus (PUUV) on survival and reproductive maturation probability of its reservoir host, the bank vole (Myodes glareolus). Three years (2004–06) of data from nine independent sites in southern Belgium were collected and analyzed with a capture-mark-recapture (CMR) method that includes statistical correction for the variation in capture probability of voles. A multistate model based on four states of reproductive activity and PUUV immunoglobulin G (IgG) antibody status was used to estimate survival and probability of transition from one reproductive or infection state to another. Although survival estimates for reproductively active voles were similar between infected and noninfected individuals, PUUV infection in reproductively inactive voles decreased mean monthly survival by 14%. PUUV infection was associated with a threefold increase in the probability of reproductive maturation in bank voles. Moreover, the probability of PUUV IgG seroconversion was three times higher for reproductively active voles compared to reproductively inactive voles. Our model indicates that PUUV infection may alter bank vole population dynamics by affecting both survival and maturation in its host. Additional studies, using CMR methodology with shorter time intervals between trapping sessions and possibly a longer duration, are needed to confirm these findings.

Temporal Variation in Individual Factors Associated with Hantavirus Infection in Bank Voles During an Epizootic: Implications for Puumala Virus Transmission Dynamics

Puumala virus (PUUV), the causal agent of nephropathia epidemica in humans, is one of the many hantaviruses included in the list of emerging pathogens. Hantavirus infection is not distributed evenly among PUUV reservoir hosts (i.e., bank voles [Myodes glareolus]). Besides environmental factors and local population features, individual characteristics play an important role in vole PUUV infection risk. Identifying the relative importance of these individual characteristics can provide crucial information on PUUV transmission processes. In the present study, bank voles were monitored during the nephropathia epidemica outbreak of 2005 in Belgium. Vole sera were tested for presence of immunoglobulin G against PUUV, and a logistic mixed model was built to investigate the temporal variation in individual characteristics and their relative importance to PUUV infection risk in bank voles. Relative risk calculations for individual vole characteristics related to PUUV infection in the reservoir host show that reproductive activity dominates infection risk. The gender effect is only found in reproductively active voles, where reproductively active males have the highest infection risk. Results also revealed a clear seasonal variation in the importance of reproductive activity linked to PUUV infection. In contrast to the main effect found in other trapping sessions, no difference in infection risk ratio was found between reproductively active and nonactive voles in the spring period. Combined with increased infection risk for the reproductively nonactive group at that time, these results indicate a shift in the transmission process due to changes in bank vole behavior, physiology, or climate conditions. Hence, our results suggest that mathematical models should take into account seasonal shifts in transmission mechanisms. When these results are combined with the seasonal changes in population structure during the epizootic period, we identify vole reproductive activity and length of the breeding season as potential drivers of PUUV epizootics in west-central European regions.