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Identifying factors that drive infection dynamics in reservoir host populations is essential in understanding human risk from wildlife-originated zoonoses. We studied zoonotic Puumala orthohantavirus (PUUV) in the host, the bank vole (Myodes glareolus), populations in relation to the host population, rodent and predator community and environment-related factors and whether these processes are translated into human infection incidence. We used 5-year rodent trapping and bank vole PUUV serology data collected from 30 sites located in 24 municipalities in Finland. We found that PUUV seroprevalence in the host was negatively associated with the abundance of red foxes, but this process did not translate into human disease incidence, which showed no association with PUUV seroprevalence. The abundance of weasels, the proportion of juvenile bank voles in the host populations and rodent species diversity were negatively associated with the abundance index of PUUV positive bank voles, which, in turn, showed a positive association with human disease incidence. Our results suggest certain predators, a high proportion of young bank vole individuals, and a diverse rodent community, may reduce PUUV risk for humans through their negative impacts on the abundance of infected bank voles. [ABSTRACT FROM AUTHOR]

In northern Europe, rodent populations display cyclic density fluctuations that can be correlated with the human incidence of zoonotic diseases they spread. During density peaks, field voles ( Microtus agrestis) become one of the most abundant rodent species in northern Europe, yet little is known of the viruses they host. We screened 709 field voles, trapped from 14 sites over 3 years, for antibodies against four rodent-borne, potentially zoonotic viruses or virus groups-hantaviruses, lymphocytic choriomeningitis virus (LCMV), Ljungan virus (LV), and orthopoxviruses (OPV). Antibodies against all four viruses were detected. However, seroprevalence of hantaviruses, LV, and LCMV was low. OPV antibodies (most likely cowpox) were more common but restricted geographically to southeastern Finland. Within these sites, antibody prevalence showed delayed density dependence in spring and direct density dependence in fall. Higher seroprevalence was found in spring than fall. These results substantially increase knowledge of the presence and distribution of viruses of field voles in Finland, as well as CPXV infection dynamics. [ABSTRACT FROM AUTHOR]

Intensive management of Fennoscandian forests has led to a mosaic of woodlands in different stages of maturity. The main rodent host of the zoonotic Puumala hantavirus (PUUV) is the bank vole (Myodes glareolus), a species that can be found in all woodlands and especially mature forests. We investigated the influence of forest age structure on PUUV infection dynamics in bank voles. Over four years, we trapped small mammals twice a year in a forest network of different succession stages in Northern Finland. Our study sites represented four forest age classes from young (4 to 30 years) to mature (over 100 years) forests. We show that PUUV-infected bank voles occurred commonly in all forest age classes, but peaked in mature forests. The probability of an individual bank vole to be PUUV infected was positively related to concurrent host population density. However, when population density was controlled for, a relatively higher infection rate was observed in voles trapped in younger forests. Furthermore, we found evidence of a ''dilution effect'' in that the infection probability was negatively associated with the simultaneous density of other small mammals during the breeding season. Our results suggest that younger forests created by intensive management can reduce hantaviral load in the environment, but PUUV is common in woodlands of all ages. As such, the Fennoscandian forest landscape represents a significant reservoir and source of hantaviral infection in humans. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background In collaboration with six European public health agencies as part of the PANDEM-2 consortium, we have developed and validated a self-assessment tool that captures the workforce capacities and capabilities needed at the institutional level within National Public Health Institutes (NPHIs) to deal with public health emergencies. Methods The work carried out in this study included (i) a review of existing tools for workforce assessment, (ii) focus group discussions and interviews to map the experiences and needs of NPHI's, (iii) the development of a tool for NPHI's to assess their workforce capacity and capabilities in public health emergency preparedness (PHEP) and (iv) refinement of the assessment tool via a Delphi study. Results Capacity markers were identified to assess the workforce required for PHEP functions and the availability of surge capacity during a public health emergency. The tool also enables NPHIs to analyze gaps in PHEP staff competencies. The assessment scores can assist NPHI pandemic preparedness by identifying and prioritizing training and recruitment needs. Conclusions In line with EU Regulation 2022/2371 on serious cross-border threats to health, article 11 Training of healthcare staff and public health staff, Member States (MS) are tasked with assessing current workforce capacity and capability gaps. The PANDEM-2 workforce self-assessment tool aligns with this requirement and will support effective planning and development to strengthen the public health workforce capacity in EU MS. [ABSTRACT FROM AUTHOR]

Hantaviruses are emerging viruses carried by rodents, soricomorphs (shrews and moles) and bats. In Finland, Puumala virus (PUUV) was for years the only hantavirus detected. In 2009, however, Seewis virus (SWSV) was reported from archival common shrew ( Sorex araneus ) samples collected in 1982 in Finland. To elucidate the diversity of hantaviruses in soricomorphs in Finland, 180 individuals were screened, representing seven species captured from 2001 to 2012: hantavirus RNA was screened using RT-PCR, and hantaviral antigen using immunoblotting with polyclonal antibodies raised against truncated SWSV nucleocapsid protein. The overall hantavirus RNA prevalence was 14% (26/180), antigen could be demonstrated in 9 of 20 SWSV RT-PCR positive common shrews. Genetic analyses revealed that four soricomorph-borne hantaviruses circulate in Finland, including Boginia virus (BOGV) in water shrew ( Neomys fodiens ) and Asikkala virus (ASIV) in pygmy shrew ( Sorex minutus ). Interestingly, on two study sites, common shrews harbored strains of two different hantaviruses: Seewis virus and a new distinct, genetically distant (identity 57% at amino acid level) virus (Altai-like virus) which clusters together with viruses in the basal phylogroup I of hantaviruses with 62–67% identity at amino acid level. This is the first evidence of coexistence of two clearly distinct hantavirus species circulating simultaneously in one host species population. The findings suggest an ancient host-switching event from a yet unknown host to S. araneus . In addition, phylogenetic analyses of partial S and M segment sequences showed that SWSV in Finland represents a unique genotype in Europe. [ABSTRACT FROM AUTHOR]

Tick-borne encephalitis virus (TBEV) infects bank voles (Myodes glareolus) in nature, but the relevance of rodents for TBEV transmission and maintenance is unclear. We infected colonized bank voles subcutaneously to study and compare the infection kinetics, acute infection, and potential viral persistence of the three known TBEV subtypes: European (TBEV-Eur), Siberian (TBEV-Sib) and Far Eastern (TBEV-FE). All strains representing the three subtypes were infective and highly neurotropic. They induced (meningo)encephalitis in some of the animals, however most of the cases did not present with apparent clinical symptoms. TBEV-RNA was cleared significantly slower from the brain as compared to other organs studied. Supporting our earlier findings in natural rodent populations, TBEV-RNA could be detected in the brain for up to 168 days post infection, but we could not demonstrate infectivity by cell culture isolation. Throughout all time points post infection, RNA of the TBEV-FE was detected significantly more often than RNA of the other two strains in all organs studied. TBEV-FE also induced prolonged viremia, indicating distinctive kinetics in rodents in comparison to the other two subtypes. This study shows that bank voles can develop a neuroinvasive TBEV infection with persistence of viral RNA in brain, and mount an anti-TBEV IgG response. The findings also provide further evidence that bank voles can serve as sentinels for TBEV endemicity. [ABSTRACT FROM AUTHOR]

Despite the increasing numbers of travel-acquired dengue, few studies have assessed virologic markers of the disease in non-endemic populations. We examined the kinetics of diagnostic markers and their associations with clinical parameters in 93 patients with travel-acquired dengue fever. Kinetics analyses suggested a longer average duration for viremia (9 days, CI95%: 8–10) and non-structural protein 1 (NS1) antigenemia (15 days, CI95%: 12–20) than reported in endemic populations. While none of the tests sufficed alone, the best diagnostic coverage was achieved by combining antibody detection with RNA or NS1 testing. Studied by regression models, early relative levels of viremia and NS1 antigenemia proved to be significantly associated with several clinical parameters: high viremia predicted greater likelihood and increased length of hospitalization, the degree of NS1 antigenemia correlated positively with hematocrit and liver transaminases, and both viremia and NS1 antigenemia levels negatively with platelet counts in follow-up. Levels of viremia and NS1 antigenemia may serve as predictors of the clinical manifestations in travel-acquired dengue. [ABSTRACT FROM AUTHOR]

Hantaviruses have co-existed with their hosts for millions of years. Seewis virus (SWSV), a soricomorph-borne hantavirus, is widespread in Eurasia, ranging from Central Siberia to Western Europe. To gain insight into the phylogeography and evolutionary history of SWSV in Finland, lung tissue samples of 225 common shrews ( Sorex araneus ) trapped from different parts of Finland were screened for the presence of SWSV RNA. Forty-two of the samples were positive. Partial small (S), medium (M) and large (L) segments of the virus were sequenced, and analyzed together with all SWSV sequences available in Genbank. The phylogenetic analysis of the partial S-segment sequences suggested that all Finnish SWSV strains shared their most recent common ancestor with the Eastern European strains, while the L-segment suggested multiple introductions. The difference between the L- and S-segment phylogenies implied that reassortment events play a role in the evolution of SWSV. Of the Finnish strains, variants from Eastern Finland occupied the root position in the phylogeny, and had the highest genetic diversity, supporting the hypothesis that SWSV reached Finland first form the east. During the spread in Finland, the virus has formed three separate lineages, identified here by correlation analysis of genetic versus geographic distance combined with median-joining network analysis. These results support the hypothesis that Finnish SWSV recolonized Finland with its host, the common shrew, from east after the last ice age 12,000–8000 years ago, and then subsequently spread along emerging land bridges towards west or north with the migration and population expansion of its host. [ABSTRACT FROM AUTHOR]

Yersinia enterocolitica and Yersinia pseudotuberculosis are important zoonotic bacteria causing human enteric yersiniosis commonly reported in Europe. All Y. pseudotuberculosis strains are considered pathogenic, while Y. enterocolitica include both pathogenic and nonpathogenic strains which can be divided into six biotypes (1A, 1B, and 2-5) and about 30 serotypes. The most common types causing yersiniosis in Europe are Y. enterocolitica bioserotypes 4/O:3 and 2/O:9. Strains belonging to biotype 1A are considered as nonpathogenic because they are missing important virulence genes like the attachment-invasion-locus ( ail) gene in the chromosome and the virulence plasmid. The role of wild small mammals as a reservoir of enteropathogenic Yersinia spp. is still obscure. In this study, the presence of Yersinia spp. was examined from 1840 wild small mammals, including voles, mice, and shrews, trapped in Finland during a 7-year period. We isolated seven Yersinia species. Y. enterocolitica was the most common species, isolated from 8% of the animals; while most of these isolates represented nonpathogenic biotype 1A, human pathogenic bioserotype 2/O:9 was also isolated from a field vole. Y. pseudotuberculosis of bioserotype 1/O:2 was isolated from two shrews. The ail gene, which is typically only found in the isolates of biotypes 1B and 2-5 associated with yersiniosis, was frequently (23%) detected in the nonpathogenic isolates of biotype 1A and sporadically (6%) in Yersinia kristensenii isolates. Our results suggest that wild small mammals, especially voles, may serve as carriers for ail-positive Y. enterocolitica 1A and Y. kristensenii. We also demonstrate that voles and shrews sporadically excrete pYV-positive Y. enterocolitica 2/O:9 and Y. pseudotuberculosis 1/O:2, respectively, in their feces and, thus, can serve as a contamination source for vegetables by contaminating the soil. [ABSTRACT FROM AUTHOR]

Understanding how host dynamics, including variations of population size and dispersal, may affect the epidemiology of infectious diseases through ecological and evolutionary processes is an active research area. Here we focus on a bank vole ( Myodes glareolus ) metapopulation surveyed in Finland between 2005 and 2009. Bank vole is the reservoir of Puumala hantavirus (PUUV), the agent of nephropathia epidemica (NE, a mild form of hemorrhagic fever with renal symptom) in humans. M . glareolus populations experience multiannual density fluctuations that may influence the level of genetic diversity maintained in bank voles, PUUV prevalence and NE occurrence. We examine bank vole metapopulation genetics at presumably neutral markers and immune-related genes involved in susceptibility to PUUV ( Tnf -promoter, Tlr4 , Tlr7 and Mx2 gene) to investigate the links between population dynamics, microevolutionary processes and PUUV epidemiology. We show that genetic drift slightly and transiently affects neutral and adaptive genetic variability within the metapopulation. Gene flow seems to counterbalance its effects during the multiannual density fluctuations. The low abundance phase may therefore be too short to impact genetic variation in the host, and consequently viral genetic diversity. Environmental heterogeneity does not seem to affect vole gene flow, which might explain the absence of spatial structure previously detected in PUUV in this area. Besides, our results suggest the role of vole dispersal on PUUV circulation through sex-specific and density-dependent movements. We find little evidence of selection acting on immune-related genes within this metapopulation. Footprint of positive selection is detected at Tlr - 4 gene in 2008 only. We observe marginally significant associations between Mx2 genotype and PUUV genogroups. These results show that neutral processes seem to be the main factors affecting the evolution of these immune-related genes at a contemporary scale, although the relative effects of neutral and adaptive forces could vary temporally with density fluctuations. Immune related gene polymorphism may in turn partly influence PUUV epidemiology in this metapopulation. [ABSTRACT FROM AUTHOR]

The dynamics of animal populations are greatly influenced by interactions with their natural enemies and food resources. However, quantifying the relative effects of these factors on demographic rates remains a perpetual challenge for animal population ecology. Food scarcity is assumed to limit the growth and to initiate the decline of cyclic herbivore populations, but this has not been verified with physiological health indices. We hypothesized that individuals in declining populations would exhibit signs of malnutrition-induced deterioration of physiological condition. We evaluated the association of body condition with population cycle phase in bank voles ( Myodes glareolus ) during the increase and decline phases of a population cycle. The bank voles had lower body masses, condition indices and absolute masses of particular organs during the decline. Simultaneously, they had lower femoral masses, mineral contents and densities. Hemoglobin and hematocrit values and several parameters known to respond to food deprivation were unaffected by the population phase. There were no signs of lymphopenia, eosinophilia, granulocytosis or monocytosis. Erythrocyte counts were higher and plasma total protein levels and tissue proportions of essential polyunsaturated fatty acids lower in the population decline. Ectoparasite load was lower and adrenal gland masses or catecholamine concentrations did not suggest higher stress levels. Food availability seems to limit the size of voles during the decline but they can adapt to the prevailing conditions without clear deleterious health effects. This highlights the importance of quantifying individual health state when evaluating the effects of complex trophic interactions on the dynamics of wild animal populations. [ABSTRACT FROM AUTHOR]

In the Mekong Delta in southern Vietnam, rats are commonly traded in wet markets and sold live for food consumption. We investigated seroprevalence to selected groups of rodent-borne viruses among human populations with high levels of animal exposure and among co-located rodent populations. The indirect fluorescence antibody test (IFAT) was used to determine seropositivity to representative reference strains of hantaviruses (Dobrava virus [DOBV], Seoul virus [SEOV]), cowpox virus, arenaviruses (lymphocytic choriomeningitis virus [LCMV]), flaviviruses (tick-borne encephalitis virus [TBEV]), and rodent parechoviruses (Ljungan virus), using sera from 245 humans living in Dong Thap Province and 275 rodents representing the five common rodent species sold in wet markets and present in peridomestic and farm settings. Combined seropositivity to DOBV and SEOV among the rodents and humans was 6.9% (19/275) and 3.7% (9/245), respectively; 1.1% (3/275) and 4.5% (11/245) to cowpox virus; 5.4% (15/275) and 47.3% (116/245) for TBEV; and exposure to Ljungan virus was 18.8% (46/245) in humans, but 0% in rodents. Very little seroreactivity was observed to LCMV in either rodents (1/275, 0.4%) or humans (2/245, 0.8%). Molecular screening of rodent liver tissues using consensus primers for flaviviruses did not yield any amplicons, whereas molecular screening of rodent lung tissues for hantavirus yielded one hantavirus sequence (SEOV). In summary, these results indicate low to moderate levels of endemic hantavirus circulation, possible circulation of a flavivirus in rodent reservoirs, and the first available data on human exposures to parechoviruses in Vietnam. Although the current evidence suggests only limited exposure of humans to known rodent-borne diseases, further research is warranted to assess public health implications of the rodent trade. [ABSTRACT FROM AUTHOR]

Background: Puumala virus, the agent of nephropathia epidemica (NE), is the most prevalent hantavirus in Europe. The risk for human infection seems to be strongly correlated with the prevalence of Puumala virus (PUUV) in populations of its reservoir host species, the bank vole Myodes glareolus. In humans, the infection risks of major viral diseases are affected by the presence of helminth infections. We therefore proposed to analyse the influence of both helminth community and landscape on the prevalence of PUUV among bank vole populations in the Ardennes, a PUUV endemic area in France. Results: Among the 313 voles analysed, 37 had anti-PUUV antibodies. Twelve gastro-intestinal helminth species were recorded among all voles sampled. We showed that PUUV seroprevalence strongly increased with age or sexual maturity, especially in the northern forests (massif des Ardennes). The helminth community structure significantly differed between this part and the woods or hedgerows of the southern cretes pre-ardennaises. Using PUUV RNA quantification, we identified significant coinfections between PUUV and gastro-intestinal helminths in the northern forests only. More specifically, PUUV infection was positively associated with the presence of Heligmosomum mixtum, and in a lesser extent, Aonchotheca muris-sylvatici. The viral load of PUUV infected individuals tended to be higher in voles coinfected with H. mixtum. It was significantly lower in voles coinfected with A. muris-sylvatici, reflecting the influence of age on these latter infections. Conclusions: This is the first study to emphasize hantavirus - helminth coinfections in natural populations. It also highlights the importance to consider landscape when searching for such associations. We have shown that landscape characteristics strongly influence helminth community structure as well as PUUV distribution. False associations might therefore be evidenced if geographic patterns of helminths or PUUV repartition are not previously identified. Moreover, our work revealed that interactions between helminths and landscape enhance/ deplete the occurrence of coinfections between PUUV and H. mixtum or A. muris-sylvatici. Further experimental analyses and long-term individual surveys are now required to confirm these correlative results, and to ascertain the causal links between helminth and PUUV infection risks. [ABSTRACT FROM AUTHOR]

Rodents might maintain tick-borne encephalitis virus (TBEV) in nature through latent persistent infections. During 2 subsequent winters, 2008 and 2009, in Finland, we detected RNA of European and Siberian subtypes of TBEV in Microtus agrestis and Myodes glareolus voles, respectively. Persistence in rodent reservoirs may contribute to virus overwintering. [ABSTRACT FROM AUTHOR]

Abstract: The tumor necrosis factor-alpha (TNF-α) influences the ability to limit parasite infection but its over-production might result in inflammatory disorders. The level of Tnf-α gene expression could thus mediate a balance of tolerance/resistance to infections. This study focused on Puumala hantavirus (PUUV) infection in its rodent host, the bank vole (Myodes glareolus). In humans, PUUV is responsible of a mild form of hemorrhagic fever with renal syndrome, nephropathia epidemica (NE). The severity of NE is associated with an over-production of TNF-α. By contrast, PUUV infection in bank vole is chronic and asymptomatic. It is likely that different coevolutionary histories between PUUV and its hosts could lead to different balances of resistance/tolerance to PUUV infection, at least partly mediated by variable production levels of TNF-α. We investigated the hypothesis that bank voles from PUUV endemic areas should exhibit higher levels of tolerance, i.e. lower levels of TNF-α production, than bank voles from areas where PUUV prevalence is low. For this purpose, we analysed variations of Tnf-α gene expression and promoter sequences among European populations of bank voles. Our results revealed an absence of up-regulation of Tnf-α gene expression in PUUV infected bank voles and significant differences in Tnf-α gene expression level with regard to PUUV endemicity. These results corroborated the hypothesis of different balances of tolerance/resistance to PUUV. Two single-nucleotide polymorphism genotypes within the Tnf-α promoter (−302 GG/GG and −296 A/A) were associated with higher Tnf-α gene expression and were more frequent in non-endemic areas. This study emphasized the potential influence of selection acting on TNF-α production and mediating a tolerance/resistance balance to PUUV in bank voles. Further investigations, including the role of phenotypic plasticity and parasite communities on Tnf-α expression levels, should provide important keys to understand the prevalence of PUUV over Europe. [Copyright &y& Elsevier]

We determined the prevalence of infection with lymphocytic choriomeningitis virus (LCMV) among small mammals in northern Italy and analyzed long-term dynamics of LCMV in a rodent population in the province of Trento. LCMV is circulating among the most widespread and common wild rodent species in this area (Apodemus flavicollis, Myodes glareolus, and Microtus arvalis); overall prevalence is 6.8%. During 2000-2006, intensive monitoring of LCMV in a population of yellow-necked mice (A. flavicollis) showed a positive correlation between prevalence of infection and rodent density. At the individual level, weight and sex appeared to correlate with antibody prevalence, which suggests that horizontal transmission of LCMV occurs principally among heavier, older males and occurs during fighting. Isolation and genetic characterization of this virus will be the crucial next steps for a better understanding of its ecology. [ABSTRACT FROM AUTHOR]

We determined the prevalence of infection with lymphocytic choriomeningitis virus (LCMV) among small mammals in northern Italy and analyzed long-term dynamics of LCMV in a rodent population in the province of Trento. LCMV is circulating among the most widespread and common wild rodent species in this area (Apodemus flavicollis, Myodes glareolus, and Microtus arvalis); overall prevalence is 6.8%. During 2000-2006, intensive monitoring of LCMV in a population of yellow-necked mice (A. flavicollis) showed a positive correlation between prevalence of infection and rodent density. At the individual level, weight and sex appeared to correlate with antibody prevalence, which suggests that horizontal transmission of LCMV occurs principally among heavier, older males and occurs during fighting. Isolation and genetic characterization of this virus will be the crucial next steps for a better understanding of its ecology. [ABSTRACT FROM AUTHOR]

Abstract: Puumala virus (PUUV) is a hantavirus specifically harboured by the bank vole, Myodes (earlier Clethrionomys) glareolus. It causes a mild form of hemorrhagic fever with renal syndrome (HFRS) in humans, called Nephropathia epidemica (NE). The clinical severity of NE is variable among patients and depends on their major histocompatibility complex (MHC) genetic background. In this study we investigated the potential role of class II MHC gene polymorphism in the susceptibility/resistance to PUUV in the wild reservoir M. glareolus. We performed an association study between the exon 2 of the DQA gene and PUUV antibodies considering a natural population of bank voles. Because immune gene polymorphism is likely to be driven by multiple parasites in the wild, we also screened bank voles for other potential viral and parasitic infections. We used multivariate analyses to explore DQA polymorphism/PUUV associations while considering the potential antagonist and/or synergistic effects of the whole parasite community. Our study suggests links between class II MHC characteristics and viral infections including PUUV and Cowpox virus. Several alleles are likely to be involved in the susceptibility or in the resistance of bank voles to these infections. Alternatively, heterozygosity does not seem to be associated with PUUV or any other parasite infections. This result thus provides no evidence in favour of the hypothesis of selection through overdominance. Finally this multivariate approach reveals a strong antagonism between ectoparasitic mites and PUUV, suggesting direct or indirect immunogenetic links between infections by these parasites. Other datasets are now required to confirm these results and to test whether the associations vary in space and/or time. [Copyright &y& Elsevier]

A letter to the editor is presented related to transmission of Hantaviruses to humans from rodents of the families Cricetidae and Muridae causing hemorrhagic fever with renal syndrome.