Predicting high risk for human hantavirus infections, Sweden.
ABSTRACT: An increased risk for hemorrhagic fever with renal syndrome caused by Puumala hantavirus was forecast for Sweden in 2007. The forecast was based on a predicted increase in the number of Myodes glareolus rodents (reservoir hosts). Despite raised awareness and preparedness, the number of human cases during July 2007-June 2008 was 1,483, a new high.
Project description:Natural reservoirs of zoonotic pathogens generally seem to be capable of tolerating infections. Tolerance and its underlying mechanisms remain difficult to assess using experiments or wildlife surveys. High-throughput sequencing technologies give the opportunity to investigate the genetic bases of tolerance, and the variability of its mechanisms in natural populations. In particular, population genomics may provide preliminary insights into the genes shaping tolerance and potentially influencing epidemiological dynamics. Here, we addressed these questions in the bank vole Myodes glareolus, the specific asymptomatic reservoir host of Puumala hantavirus (PUUV), which causes nephropathia epidemica (NE) in humans. Despite the continuous spatial distribution of M. glareolus in Sweden, NE is endemic to the northern part of the country. Northern bank vole populations in Sweden might exhibit tolerance strategies as a result of coadaptation with PUUV. This may favor the circulation and maintenance of PUUV and lead to high spatial risk of NE in northern Sweden. We performed a genome-scan study to detect signatures of selection potentially correlated with spatial variations in tolerance to PUUV. We analyzed six bank vole populations from Sweden, sampled from northern NE-endemic to southern NE-free areas. We combined candidate gene analyses (Tlr4, Tlr7, and Mx2 genes) and high-throughput sequencing of restriction site-associated DNA (RAD) markers. Outlier loci showed high levels of genetic differentiation and significant associations with environmental data including variations in the regional number of NE human cases. Among the 108 outliers that matched to mouse protein-coding genes, 14 corresponded to immune-related genes. The main biological pathways found to be significantly enriched corresponded to immune processes and responses to hantavirus, including the regulation of cytokine productions, TLR cascades, and IL-7, VEGF, and JAK-STAT signaling. In the future, genome-scan replicates and functional experimentations should enable to assess the role of these biological pathways in M. glareolus tolerance to PUUV.
Project description:The first cluster of hemorrhagic fever with renal syndrome (HFRS) in Poland was identified in 2007 in the Subcarpathian region. The natural environment of this area is a key habitat for hantavirus vectors. The animal reservoir of existing human HFRS clusters was studied to assess the occurrence of viruses (including Tula virus, Puumala virus, and Dobrava-Belgrade virus) among rodents. We examined 70 suspected human cases with symptoms corresponding to the clinical picture of HFRS. Serological analysis (indirect immunofluorescence assay and immunoblot) confirmed the presence of anti-hantavirus antibodies in 18 patients, which were surveyed with regard to developed symptoms and presumed rodent contact. Seroepidemiological analysis of newly confirmed human cases was performed, putative areas of human exposure were studied, and 194 rodents were subsequently captured from identified areas. Internal organs (lungs, heart, spleen, bladder, and kidneys) were collected from 64 Apodemus flavicollis, 55 Apodemus agrarius, 40 Myodes glareolus, 21 Mus musculus, and 14 Microtus arvalis and tested for the presence of hantavirus RNA by reverse transcription and subsequent real-time PCR. Positive samples were also tested by indirect immunofluorescence. Animal reservoir surveillance enabled the first detection of Puumala virus and Dobrava-Belgrade virus among animals in Poland. Furthermore, some places where rodents were captured correlated with areas of residence of laboratory-confirmed human cases and likely detected virus species. Moreover, three species of hantaviruses coexisting in a relatively small area were identified.
Project description:Three species of Myodes voles known to harbor hantaviruses include the bank vole (Myodes glareolus), which serves as the reservoir host of Puumala virus (PUUV), the prototype arvicolid rodent-borne hantavirus causing hemorrhagic fever with renal syndrome (HFRS) in Europe, and the grey red-backed vole (Myodes rufocanus) and royal vole (Myodes regulus) which carry two PUUV-like hantaviruses, designated Hokkaido virus (HOKV) and Muju virus (MUJV), respectively. To ascertain the hantavirus harbored by the northern red-backed vole (Myodes rutilus), we initially screened sera from 233 M. rutilus, as well as from 90 M. rufocanus and 110 M. glareolus, captured in western and eastern Siberia during June 2007 to October 2009, for anti-hantaviral antibodies. Thereafter, lung tissues from 44 seropositive voles were analyzed for hantavirus RNA by reverse transcription-polymerase chain reaction. Partial L-, M- and S-segment sequences, detected in M. rutilus and M. rufocanus, were closely related to HOKV, differing from previously published L-, M- and S-segment sequences of HOKV by 17.8-20.2%, 15.9-23.4% and 15.0-17.0% at the nucleotide level and 2.6-7.9%, 1.3-6.3% and 1.2-4.0% at the amino acid level, respectively. Alignment and comparison of hantavirus sequences from M. glareolus trapped in Tyumen Oblast showed very high sequence similarity to the Omsk lineage of PUUV. Phylogenetic analysis, using neighbor-joining, maximal likelihood and Bayesian methods, showed that HOKV strains shared a common ancestry with PUUV and exhibited geographic-specific clustering. This report provides the first molecular evidence that both M. rutilus and M. rufocanus harbor HOKV, which might represent a genetic variant of PUUV.
Project description:Acute-phase sera from >5 % of cases of haemorrhagic fever with renal syndrome occurring annually in Korea have been found to exhibit a fourfold or higher antibody titre to Puumala virus (PUUV) than to Hantaan virus (HTNV) by double-sandwich IgM ELISA, suggesting the existence of a PUUV-related hantavirus. Based on the phylogenetic relationships among arvicolid rodents, the royal vole (Myodes regulus) was targeted as a likely reservoir host of hantavirus. Using RT-PCR, a genetically distinct hantavirus, designated Muju virus (MUJV), was detected in lung tissue of royal voles, captured in widely separated geographical regions in Korea during 1996-2007. Pairwise analysis of the full-length S (1857 nt) and M (3634 nt) segments of MUJV indicated approximately 77 % sequence similarity with PUUV. At the amino acid level, MUJV differed from PUUV by 5.5-6.9 % (nucleocapsid) and 10.0-11.6 % (Gn and Gc envelope glycoproteins). Interstrain variation of MUJV sequences from royal voles captured in different regions suggested geographic-specific clustering. Neutralizing antibody titres against PUUV were two- to sixfold higher than to HTNV in sera of MUJV-infected Myodes regulus. Although virus isolation attempts were unsuccessful, the collective data indicate that MUJV is a distinct hantavirus species.
Project description:Hantavirus genome sequences were recovered from tissue samples of Myodes rufocanus, Microtus fortis and Microtus oeconomus captured in the Baikal area of Buryatia, Russian Federation. Genetic analysis of S- and M-segment sequences of Buryatian hantavirus strains showed that Myodes-associated strains belong to Hokkaido virus (HOKV) type while Microtus-associated strains belong to Vladivostok virus (VLAV) type. On phylogenetic trees Buryatian HOKV strains were clustered together with M. rufocanus- originated strains from Japan, China and Far-East Russia (Primorsky region). Buryatian Microtus- originated strains shared a common recent ancestor with M. fortis- originated VLAV strain from Far-East Russia (Vladivostok area). Our data (i) confirm that M. rufocanus carries a hantavirus which is similar to but distinct from both Puumala virus carried by M. glareolus and Muju virus associated with M. regulus, (ii) confirm that M. fortis is the natural host for VLAV, and (iii) suggest M. oeconomus as an alternative host for VLAV.
Project description:The genome of Muju virus (MUJV), identified originally in the royal vole (Myodes regulus) in Korea, was fully sequenced to ascertain its genetic and phylogenetic relationship with Puumala virus (PUUV), harbored by the bank vole (My. glareolus), and a PUUV-like virus, named Hokkaido virus (HOKV), in the grey red-backed vole (My. rufocanus) in Japan. Whole genome sequence analysis of the 6544-nucleotide large (L), 3652-nucleotide medium (M) and 1831-nucleotide small (S) segments of MUJV, as well as the amino acid sequences of their gene products, indicated that MUJV strains from different capture sites might represent genetic variants of PUUV, the prototype arvicolid rodent-borne hantavirus in Europe. Distinct geographic-specific clustering of MUJV was found in different provinces in Korea, and phylogenetic analyses revealed that MUJV and HOKV share a common ancestry with PUUV. A better understanding of the taxonomic classification and pathogenic potential of MUJV must await its isolation in cell culture.
Project description:Individuals often differ in their ability to transmit disease and identifying key individuals for transmission is a major issue in epidemiology. Male hosts are often thought to be more important than females for parasite transmission and persistence. However, the role of infectious females, particularly the transient immunity provided to offspring through maternal antibodies (MatAbs), has been neglected in discussions about sex-biased infection transmission. We examined the effect of host sex upon infection dynamics of zoonotic Puumala hantavirus (PUUV) in semi-natural, experimental populations of bank vole (Myodes glareolus). Populations were founded with either females or males that were infected with PUUV, whereas the other sex was immunized against PUUV infection. The likelihood of the next generation being infected was lower when the infected founders were females, underlying the putative importance of adult males in PUUV transmission and persistence in host populations. However, we show that this effect probably results from transient immunity that infected females provide to their offspring, rather than any sex-biased transmission efficiency per se. Our study proposes a potential contrasting nature of female and male hosts in the transmission dynamics of hantaviruses.
Project description:Background:Worldwide, the number of recorded human hantavirus infections as well as the number of affected countries is on the rise. In Europe, most human hantavirus infections are caused by the Puumala virus (PUUV), with bank voles (Myodes glareolus) as reservoir hosts. Generally, infection outbreaks have been related to environmental conditions, particularly climatic conditions, food supply for the reservoir species and land use. However, although attempts have been made, the insufficient availability of environmental data is often hampering accurate temporal and spatially explicit models of human hantavirus infections. Methods:In the present study, dynamics of human PUUV infections between 2001 and 2015 were explored using ArcGIS in order to identify spatio-temporal patterns. Results:Percentage cover of forest area was identified as an important factor for the spatial pattern, whereas beech mast was found explaining temporal patterns of human PUUV infections in Germany. High numbers of infections were recorded in 2007, 2010 and 2012 and areas with highest records were located in Baden-Wuerttemberg (southwest Germany) and North Rhine-Westphalia (western Germany). Conclusion:More reliable data on reservoir host distribution, pathogen verification as well as an increased awareness of physicians are some of the factors that should improve future human infection risk assessments in Germany.
Project description:Many viruses significantly impact human and animal health. Understanding the population dynamics of these viruses and their hosts can provide important insights for epidemiology and virus evolution. Puumala virus (PUUV) is a European hantavirus that may cause regional outbreaks of hemorrhagic fever with renal syndrome in humans. Here, we analyzed the spatiotemporal dynamics of PUUV circulating in local populations of its rodent reservoir host, the bank vole (Myodes glareolus) during eight years. Phylogenetic and population genetic analyses of all three genome segments of PUUV showed strong geographical structuring at a very local scale. There was a high temporal turnover of virus strains in the local bank vole populations, but several virus strains persisted through multiple years. Phylodynamic analyses showed no significant changes in the local effective population sizes of PUUV, although vole numbers and virus prevalence fluctuated widely. Microsatellite data demonstrated also a temporally persisting subdivision between local vole populations, but these groups did not correspond to the subdivision in the virus strains. We conclude that restricted transmission between vole populations and genetic drift play important roles in shaping the genetic structure and temporal dynamics of PUUV in its natural host which has several implications for zoonotic risks of the human population.
Project description:Understanding the dynamics of zoonotic pathogens in their reservoir host populations is a prerequisite for predicting and preventing human disease epidemics. The human infection risk of Puumala hantavirus (PUUV) is highest in northern Europe, where populations of the rodent host (bank vole, Myodes glareolus) undergo cyclic fluctuations. We conducted a 7-year capture-mark-recapture study to monitor seasonal and multiannual patterns of the PUUV infection rate in bank vole populations exhibiting a 3-year density cycle. Infected bank voles were most abundant in mid-winter months during years of increasing or peak host density. Prevalence of PUUV infection in bank voles exhibited a regular, seasonal pattern reflecting the annual population turnover and accumulation of infections within each year cohort. In autumn, the PUUV transmission rate tracked increasing host abundance, suggesting a density-dependent transmission. However, prevalence of PUUV infection was similar during the increase and peak years of the density cycle despite a twofold difference in host density. This may result from the high proportion of individuals carrying maternal antibodies constraining transmission during the cycle peak years. Our exceptionally intensive and long-term dataset provides a solid basis on which to develop models to predict the dynamic public health threat posed by PUUV in northern Europe.