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- Hantavirus–bank vole system
- Mathematical model of the bank vole–hantavirus system
The long-term spread and persistence of viral diseases are generally believed to depend essentially on the number and type of contacts between hosts and thus the number of transmission opportunities (Swinton 1998). Most host–parasite systems that have been studied are characterized by continuous, uninterrupted interactions between individuals over time. Recently, attention has focused on spatial heterogeneity of disease transmission (Grenfell & Harwood 1997) but little consideration has been given to the influence of cyclic host population growth on virus persistence, except about the susceptible part of a constant population (Grenfell & Bolker 1994). In the most extreme cases, the susceptible host population may disappear entirely (Berthier et al. 2000 in a feral cat (Felis catus) population). Several small mammal populations are subject to regular, often abrupt, seasonal or yearly population size variability. The success of viruses facing such disturbance depends on their ability to avoid extinction in the host population.
Within the Bunyaviridae family, the hantavirus genus provides a good example of interaction between viruses and fluctuating host populations. Hantaviruses fall into the emerging or re-emerging disease category since the first human infection was detected in France in 1982 and the first epidemic spread of American hantavirus pulmonary syndrome (HPS) occurred in 1993 (Schmaljohn & Hjelle 1997). In Eurasia, these hantaviruses are responsible for haemorrhagic fever with renal syndrome (HFRS), a zoonotic disease of varying severity (see McCaughey & Hart 2000 for a recent review). In Western Europe, the aetiological agent of HFRS is the Puumala virus. The main hosts of hantaviruses are rodents or insectivores, but each strain of virus is specific to a host species (Monroe et al. 1999). The bank vole is the host of the Puumala virus strain and vector of the mildest form of HFRS, nephropathia epidemica (NE).
Two strategies whereby a virus could persist in rodent populations during low-density periods have been discussed previously (Begon et al. 1999; Abbot, Ksiazek & Mills 1999). The first strategy relates to the chronic feature of the infection: infection of a long-lived class of individuals provides a reservoir of infected hosts which sustains the virus during the period of low host density. Such a persistence mode is possible because there is no associated host mortality and the virus is shed chronically by infected rodents (Verhagen et al. 1986; Bernshtein et al. 1999). An example is the American hantavirus ‘Sin Nombre’ that infects dominant individuals, the most long-lived class, of deer mice Peromyscus maniculatus (Abbot et al. 1999). Infection occurs via a bite from an infected individual and a correlation between wounds and seropositivity to Sin Nombre has been found (Abbot et al. 1999). Such a correlation has never been reported in the bank vole because aggressive encounters are much less frequent than in deer mice (Mironov 1990). The environment of bank voles in Eastern France is much less heterogeneous than in the Western American desert and dominance status does not result in markedly different survival rates among social classes. This chronic strategy cannot explain the long-term persistence of the Puumala virus in the fluctuating bank vole population.
The second strategy is to survive in stable, or at least asynchronous, populations of a reservoir host living in sympatry with the primary host (Begon et al. 1999). Such a dual host tropism allows the virus to persist for extended periods of time. Bank voles could then become infected from these reservoir hosts when bank vole density increases (Mills et al. 1999; Escutenaire et al. 2000). Such host switches have been documented in the evolutionary history of rodent–hantavirus systems (Vapalahti et al. 1997, 1999; Scharninghausen et al. 1999) while a viral adaptation to different species has been observed over a short time scale (Monroe et al. 1999). The wood mouse Apodemus sylvaticus has been recently detected PUU antibody-positive by ELISA (Escutenaire et al. 2000) but this technique presents a lack of virus strain specificity (Heyman et al. 1999). However, positive wood mice were found only during the peak of vole density (Escutenaire et al. 2000). Thus this appears to be a spillover situation rather than a secondary reservoir situation.
A third strategy for persistence during low-density periods consists of viral survival outside its host and has been overlooked until now. Human contamination by hantaviruses occurs mainly through inhalation of dust contaminated by rodent secretas (Ahlm et al. 1997; Chaturvedi et al. 2000; Ijaz, Suchmann & Hjelle 2000). Also, the presence of infected bank voles in low-density phases is related to humid environments (Verhagen et al. 1986; Ahlm et al. 1997). Thus the focal high prevalence of PUU in bank voles (Heyman et al. 2001) could be explained by survival of the virus in the soil litter, depending on microclimatic or chemical parameters. This suggests that the virus remains active outside the host. Viral survival in the damp ground could permit transmission of the virus to a susceptible bank vole without the physical presence of the infectious rodent. Some viruses are known to have adopted such a strategy, e.g. the parvovirus infection in the domestic cat F. catus (Berthier et al. 2000).
Here, we investigate the importance of this potential indirect mode of transmission in virus persistence in fluctuating bank vole populations using a mathematical modelling approach. We begin by reviewing the available data on bank voles and hantaviruses, in order to identify the important epidemiological, biological and clinical features of the infection epidemic. Then, we describe the structure of the mathematical models, including and excluding indirect transmission. Next, we present results of numerical simulations. Finally, we discuss our findings in relation to the key features of virus persistence, concentrating especially on data required to test the predictions of the model.
- Top of page
- Hantavirus–bank vole system
- Mathematical model of the bank vole–hantavirus system
Escutenaire et al. (2000) have described bank vole–Puumala dynamics in Belgium near the French border. The pattern was closed to our own observations in France (unpublished data), but revealed a slightly higher seroprevalence. In autumn 1996, the prevalence recorded was 20·1% and decreased to 14·3% in spring 1997. In autumn 1997, the prevalence was 6·6% and it remained about 6·5% in 1998 despite the vole density increase. The seroprevalence increased greatly and rapidly in 1999 to reach a mean of 47·7% in the capture plots (for a range from 10% to 67% for the four plots studied). The main features of this pattern are caught well by the model: 2 years of low seroprevalence and a rapid increase the peak year of the 3-year host demographic cycle. Moreover, adults are infected more often than juveniles, as expected due to the accumulation of cases with age. Escutenaire et al. (2000) reported periods of virus non-detection in each of their four plots studied: one season for two of them, 1 year for one and 15 months in the last plot.
The originality of the bank vole–hantavirus system over other well-studied cyclic systems such as the fox-rabies (Suppo et al. 2000) or human–measles system (Grenfell & Bolker 1994) lies in the fact that fluctuations in the susceptible host population are not caused by the virus. Mathematical modelling of the hantavirus–bank vole system, taking into account indirect transmission, captures accurately many features of observed epidemic dynamics. We found that the risk of extinction of the hantavirus was decreased when indirect transmission was incorporated. Indirect transmission leads to a high prevalence at high host density, which was not obtained with biologically realistic parameters of direct transmission. Indirect transmission also decreased the length of time the virus was almost absent and thus the probability of infection extinction by stochastic events. All these observations support the indirect transmission hypothesis.
By survival outside the host, we consider survival in the forest litter environment and not in the air. Hantavirus is excreted preferentially in urine and bank voles are territorial during the breeding season. A territory is delimited by the owner through urine deposit. Each urine release mixes with soil water that spreads the virus over a small volume of litter. Conditions are optimal for conservation of the virus virulence: it remains in a hydrosolution and is protected from sunlight and heat by forest cover and soil litter (e.g. Edwards 2000 for the swine fever virus). The contaminated surfaces constitute areas where new infections of voles can occur without the physical presence of infectious rodents. Because territorial mammals mark the borders of their territory daily (Rozenfeld et al. 1987), a high proportion of this border area can be permanently infectious, even if the survival of the virus is only few days. Scent marks are attractive to territorial mammals, increasing the probability for a foraging rodent to explore the marked area at the border of its territory compared to other interior areas. This mechanism could greatly enhance the spread of infection, despite the temporal avoidance behaviour of voles. Infection could occur through direct investigation of scent marks of an infectious neighbour or through removal of contaminated dust from the pelage that was acquired while foraging in a contaminated area. Thus, even if an infectious vole dies, the next owner of the territory could be infected several days after disappearance of the infectious vole.
The elasticity analysis indicated that the demographic parameters that control the supply of susceptible hosts (sexual maturation, adult mortality and adult capacity), and to a lesser extent the direct contact rate, are the most important parameters driving the system. Note that elasticities do not necessarily reflect the actual impact of a parameter in a population since some parameters may be more variable than others, and therefore the assumption of the same relative change in the various parameters made for calculating elasticities may not be valid in practice. A precise measure of these parameters in field studies is thus required. Simulations suggested that indirect transmission acts as a reservoir which supplies the host population with a few infected individuals but in sufficient numbers to permit the virus to spread rapidly to the whole population through direct transmission.
Infection acquisition from contaminated ground to healthy individuals could be a much more general strategy used by viruses to persist than recognized until now. Ground transmission could explain the high, unexpected number of new infections in a study of bank voles by Begon et al. (1999). In this study of interspecific transmission of cowpox, there were more newly infected bank voles than expected through direct transmission either from infectious conspecifics or infectious wood mice. The unknown source of infection could be due to ground contamination. In addition, the indirect transmission hypothesis could explain the pattern of infection from northern European countries to France. First, it is compatible with Verhagen et al.'s (1986) observation of different prevalences associated with different environmental humidities. The humidity factor could explain the persistence of the virus in a given area. Secondly, differences in climatic conditions and in bank vole demography among western European areas could result in differences in survival of the virus in the ground, and can modulate the importance of direct and indirect transmission for virus persistence. Several studies have reported the coexistence of different genotypes of the same hantavirus in a same area, even in the Puumala hantavirus strain (Escutenaire et al. 2001), and genetic reassortment among those viruses (see Henderson et al. 1995; Rowe et al. 1995; Rodriguez et al. 1998, for the Sin Nombre virus case). A further important issue in persistence is the survival rate of the virus according to soil conditions (e.g. pH and humidity because hantaviruses are susceptible to acid and dry conditions) and the proportion of the territory contaminated by the infectious owner.
The relative importance of direct and indirect transmission in the spread of hantavirus infection will need further investigation according to the physical and chemical properties of the soil. There are currently insufficient data to definitely reject the autonomous or the secondary reservoir hypothesis. Contradictory data exist concerning the secondary host species: hantavirus phylogeny analysis shows a strong coevolution between a virus and its main hosts (Schmaljohn & Hjelle 1997; Monroe et al. 1999) but cases exist where two host species are infected or have been infected by the same virus (Vapalahti et al. 1997, 1999; Scharninghausen et al. 1999). There is clearly a need for a better theoretical analysis of these different features of the bank vole–hantavirus system and their implication for the persistence of infection. Moreover, the social structure of bank voles and the dynamics of excretion of the virus in the saliva and in the urine change with the time of year. In particular, males have larger territories during the breeding season and are less aggressive than females (Ishibashi et al. 1998; Kapusta & Marchiewska-Koj 1998) and survival differs between sexes by season (Verhagen et al. 2000). Males could then have a greater influence on infection propagation than suspected until now (Bernshtein et al. 1999). The presence of clusters of bank voles during winter (De Jonge 1983; Karlsson & Ås 1987; Bujalska 1990) may increase social contact between voles, in shared burrows, during the period of high virus secretion in saliva (Verhagen et al. 1986). A final comment about social features and spread of infection is the differential pattern of urine marks deposited by dominant and subordinate male voles (Rozenfeld et al. 1987). Thus, individual behaviour can be crucial to understanding the persistence of the Puumala virus, especially at low density. Such features must be incorporated in future individual-based models to analyse their respective impact in virus propagation and persistence.
The main result is that transmission by the contaminated ground may matter and should therefore be properly assessed in the field.