The capability of rodent-borne viruses to survive outside the host is critical for the transmission dynamics within rodent populations and to humans. The transmission of Puumala virus (PUUV) in colonized bank voles (Clethrionomys glareolus) was investigated and additional longevity studies in cell culture with PUUV and Tula (TULV) hantaviruses were performed. Wild-type PUUV excreted by experimentally infected donor bank voles was shown to be transmitted indirectly between rodents through contaminated beddings, and maintained its infectivity to recipient voles at room temperature for 12-15 days. In cell culture supernatants, PUUV and TULV remained infectious for 5-11 days at room temperature and up to 18 days at 4 6C, but were inactivated after 24 h at 37 6C. Interestingly, a fraction of dried virus was still infectious after 1 h at 56 6C. These results demonstrated that hantavirus transmission does not require direct contact between rodents, or between rodents and humans, and that the indirect transmission of PUUV through contaminated environment takes place among the rodents for a prolonged period of time. The results also have implications for safety recommendations for work with hantaviruses and for preventive measures. INTRODUCTIONThe survival of pathogens outside the host is important for the epidemiological dynamics of several disease agents. The persistence in the environment is highly important for the circulation of Hepatitis A virus (Crance et al., 1998), Footand-mouth disease virus (Thomson et al., 2003, parvovirus (Barker & Parrish, 2001), as well as for infectious canine hepatitis virus (Woods, 2001) and avian influenza viruses (Stallknecht et al., 1990). However, only limited data are available concerning the potential of rodent-borne viruses, transmitted without an intermediate vector, to remain infectious outside their natural hosts.Many rodent populations undergo strong density fluctuations. The temporal low host-population density is critical for long-term persistence of rodent-borne viruses. The capability of viruses to avoid extinction depends on the host-population dynamics and on the specific characteristics of the host-virus interaction. Recently, Sauvage et al. (2003) highlighted the importance of potential survival of Puumala hantavirus (PUUV) outside the rodent host for its persistence and transmission dynamics. Mathematical modelling suggested that an indirect mode of transmission via the natural environment and prolonged survival outside the host was required to generate an epidemic pattern compatible with the one observed (Sauvage et al., 2003). Prolonged contagiousness outside the host may facilitate the persistence of viruses during a temporal loss of the infection in the host population. Such persistence in the Botten et al., 2002;Gavrilovskaya et al., 1990; Kariwa et al., 1998;Lee et al., 1981;Nuzum et al., 1988;Yanagihara et al., 1985), the relative importance of the different modes of transmission is not known. The resistance of hantaviruses against environmental conditions ...

A key aim in epidemiology is to understand how pathogens spread within their host populations. Central to this is an elucidation of a pathogen's transmission dynamics. Mathematical models have generally assumed that either contact rate between hosts is linearly related to host density (density-dependent) or that contact rate is independent of density (frequency-dependent), but attempts to confirm either these or alternative transmission functions have been rare. Here, we fit infection equations to 6 years of data on cowpox virus infection (a zoonotic pathogen) for 4 natural populations to investigate which of these transmission functions is best supported by the data. We utilize a simple reformulation of the traditional transmission equations that greatly aids the estimation of the relationship between density and host contact rate. Our results provide support for an infection rate that is a saturating function of host density. Moreover, we find strong support for seasonality in both the transmission coefficient and the relationship between host contact rate and host density, probably reflecting seasonal variations in social behavior and/or host susceptibility to infection. We find, too, that the identification of an appropriate loss term is a key component in inferring the transmission mechanism. Our study illustrates how time series data of the hostpathogen dynamics, especially of the number of susceptible individuals, can greatly facilitate the fitting of mechanistic disease models.cowpox ͉ disease ͉ population cycles ͉ Markov chain Monte Carlo T he seminal studies of Anderson and May (1, 2) introduced a framework for modeling the dynamics of pathogens and their hosts that has since underpinned most predictive models of host-pathogen dynamics. It has been standard practice when modeling the dynamics of host-microparasite interactions (viral and bacterial infections) to represent the rate of change of infected hosts I(t) at time t by dI͑t͒ dt ϭ transmission rate ͑infection͒ Ϫ loss rate ͑death ϩ recovery͒.[1]However, empirically based identification of appropriate functional forms for the ''transmission rate'' and ''loss rate'' terms has not generally been possible for systems with host dynamics because of a lack of sufficient data (although refs. 3 and 4 have recently done this for infectious diseases of human populations).To date, most studies have used transmission rate terms that are either density-dependent or frequency-dependent (5, 6). The underlying difference between these is the assumption about how host contact rate c, varies with host density [(N(t))/A], where N(t) is host abundance and A, the area occupied by the population, is usually assumed constant and omitted from the equations (6). For density-dependent transmission, host contact rate varies linearly with density [typically adopted for directly transmitted diseases such as measles (7) and foot and mouth disease (8)], whereas for frequencydependent transmission it is constant [typically adopted for sexually transmitted diseases such as HIV in ...

Wildlife-originated zoonotic diseases are a major contributor to emerging infectious diseases. Hantaviruses cause thousands of human disease cases annually worldwide, and understanding and predicting human hantavirus epidemics still poses unsolved challenges. Here we studied the three-level relationships between the human disease nephropathia epidemica (NE), its etiological agent Puumala hantavirus (PUUV) and the rodent host of the virus, the bank vole (Myodes glareolus). A large and long-term data set (14 years, 2583 human NE cases and 4751 trapped bank voles) indicates that the number of human infections shows both seasonal and multi-annual fluctuations, is influenced by the phase of vole cycle and time of the year, and follows vole abundance with a lag of a few months. Our results suggest that although human hantavirus epidemics are preceded by high sero prevalence in the host population, they may be accurately predicted solely by the population dynamics of the carrier species, even without any knowledge about hantavirus dynamics in the host populations.

The influence of pathogens on host fitness is one of the key questions in infection ecology. Hantaviruses have coevolved with their hosts and are generally thought to have little or no effect on host survival or reproduction. We examined the effect of Puumala virus (PUUV) infection on the winter survival of bank voles (Myodes glareolus), the host of this virus. The data were collected by monitoring 22 islands over three consecutive winters (a total of 55 island populations) in an endemic area of central Finland. We show that PUUV infected bank voles had a significantly lower overwinter survival probability than antibody negative bank voles. Antibody negative female bank voles from low-density populations living on large islands had the highest survival. The results were similar at the population level as the spring population size and density were negatively correlated with PUUV prevalence in the autumn. Our results provide the first evidence for a significant effect of PUUV on host survival suggesting that hantaviruses, and endemic pathogens in general, deserve even more attention in studies of host population dynamics.

Cowpox with a severe, generalized eruption was diagnosed in an atopic 4-year-old girl by electron microscopy, virus isolation, polymerase chain reaction, and immunoglobulin (Ig) M and low-avidity IgG antibodies. The hemagglutinin gene of the isolate clustered with a Russian cowpox virus strain, and more distantly, with other cowpox and vaccinia virus strains. The patient’s dog had orthopoxvirus-specific antibodies, indicating a possible transmission route.

The transfer of maternal antibodies from mother to progeny is a well-known phenomenon in avian and mammalian species. Optimally, they protect the newborn against the pathogens in the environment. The effect of maternal antibodies on microparasite transmission dynamics may have important consequences for both the fitness of the host and the epizootic processes of the pathogens. However, there is a scarcity of studies examining these effects in free-living wild species. We studied the influence of maternal antibodies against the zoonotic Puumala hantavirus (PUUV) on the fitness of bank voles (Clethrionomys glareolus) and on PUUV transmission by exposing young maternal antibody-positive (MatAbC) and negative (MatAbK) bank voles (nZ160) to PUUV in experimental populations. PUUV-specific maternal antibodies delayed the timing of infection. Females were more susceptible to PUUV infection than males. Interestingly, both the females and the males with maternal antibodies matured earlier than the other individuals in the population. Our results highlight the significance of maternal antibodies in the transmission of a pathogen and in the breeding success of the carriers.

This article reviews research on the evolutionary mechanisms leading to different transmission modes. Such modes are often under genetic control of the host or the pathogen, and often in conflict with each other via trade-offs. Transmission modes may vary among pathogen strains and among host populations. Evolutionary changes in transmission mode have been inferred through experimental and phylogenetic studies, including changes in transmission associated with host shifts and with evolution of the unusually complex life cycles of many parasites. Understanding the forces that determine the evolution of particular transmission modes presents a fascinating medley of problems for which there is a lack of good data and often a lack of conceptual understanding or appropriate methodologies. Our best information comes from studies that have been focused on the vertical versus horizontal transmission dichotomy. With other kinds of transitions, theoretical approaches combining epidemiology and population genetics are providing guidelines for determining when and how rapidly new transmission modes may evolve, but these are still in need of empirical investigation and application to particular cases. Obtaining such knowledge is a matter of urgency in relation to extant disease threats.This article is part of the themed issue ‘Opening the black box: re-examining the ecology and evolution of parasite transmission’.

Infected females may transfer maternal antibodies (MatAbs) to their offspring, which may then be transiently protected against infections the mother has encountered. However, the role of maternal protection in infectious disease dynamics in wildlife has largely been neglected. Here, we investigate the effects of Puumala hantavirus (PUUV)-specific MatAbs on PUUV dynamics, using 7 years' data from a cyclic bank vole population in Finland. For the first time to our knowledge, we partition seropositivity data from a natural population into separate dynamic patterns for MatAbs and infection. The likelihood of young of the year carrying PUUV-specific MatAbs during the breeding season correlated positively with infection prevalence in the overwintered parent population in the preceding spring. The probability of PUUV infection varied between seasons (highest in spring, lowest in late summer) and depended on population structure, but was also, in late autumn, notably, negatively related to summer MatAb prevalence, as well as to infection prevalence earlier in the breeding season. Hence, our results suggest that high infection prevalence in the early breeding season leads to a high proportion of transiently immune young individuals, which causes delays in transmission. This suggests, in turn, that MatAb protection has the potential to affect infection dynamics in natural populations.