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in search for factors that drive hantavirus epidemics.in europe, hantaviruses (bunyaviridae) are small mammal-associated zoonotic and emerging pathogens that can cause hemorrhagic fever with renal syndrome (hfrs). puumala virus, the main etiological agent carried by the bank vole myodes glareolus is responsible for a mild form of hfrs while dobrava virus induces less frequent but more severe cases of hfrs. since 2000 in europe, more than 3000 cases of hfrs have been recorded, in average, each year, which is nearly double compared to the previous de ...201222934002
antiviral therapy and prevention against hantavirus infections.hantaviruses are emerging zoonoses hosted by small mammals. in humans, they cause two diseases. hemorrhagic fever with renal syndrome is mainly caused by dobrava-belgrade virus, puumala virus, seoul virus and hantaan virus in asia and europe. on the other hand, the most important causes of hantavirus cardiopulmonary syndrome are sin nombre virus and andes virus in americas. ribavirin yet remains the only licensed drug against the hantavirus infections, but its sufficient antiviral activity remai ...201728105849
development of an immunochromatography strip test based on truncated nucleocapsid antigens of three representative hantaviruses.hantaviruses are causative agents of hemorrhagic fever with renal syndrome (hfrs) and nephropathia epidemica (ne) in the old world and hantavirus pulmonary syndrome (hps) in the new world. there is a need for time-saving diagnostic methods. in the present study, recombinant n antigens were used as antigens in an immunochromatography strip (icg) test to detect specific igg antibodies.201424885901
simultaneous detection of igg antibodies associated with viral hemorrhagic fever by a multiplexed luminex-based immunoassay.viral hemorrhagic fevers (vhfs) are worldwide diseases caused by several kinds of viruses. with the emergence of new viruses, advanced diagnostic methods are urgently needed for identification of vhfs. based on luminex xmap technology, a rapid, sensitive, multi-pathogen and high-throughput method which could simultaneously detect hemorrhagic fever viruses (hfvs) specific igg antibodies was developed. recombinant antigens of nine hfvs including hantaan virus (htnv), seoul virus (seov), puumala vi ...201424631566
a novel sin nombre virus dna vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (hps) and hemorrhagic fever with renal syndrome (hfrs).sin nombre virus (snv; family bunyaviridae, genus hantavirus) causes a hemorrhagic fever known as hantavirus pulmonary syndrome (hps) in north america. there have been approximately 200 fatal cases of hps in the united states since 1993, predominantly in healthy working-age males (case fatality rate 35%). there are no fda-approved vaccines or drugs to prevent or treat hps. previously, we reported that hantavirus vaccines based on the full-length m gene segment of andes virus (andv) for hps in so ...201323892100
construction and nonclinical testing of a puumala virus synthetic m gene-based dna vaccine.puumala virus (puuv) is a causative agent of hemorrhagic fever with renal syndrome (hfrs). although puuv-associated hfrs does not result in high case-fatality rates, the social and economic impact is considerable. there is no licensed vaccine or specific therapeutic to prevent or treat hfrs. here we report the synthesis of a codon-optimized, full-length m segment open reading frame and its cloning into a dna vaccine vector to produce the plasmid pwrg/puu-m(s2). pwrg/puu-m(s2) delivered by gene g ...201323239797
hantavirus infections by puumala or dobrava-belgrade virus in pregnant women.hantavirus infection in humans usually occurs via inhalation of infectious aerosolized excreta of rodents. horizontal human-to-human transmission was reported only for the highly virulent andes virus. the likelihood of vertical transmission and the clinical outcome of hantavirus infections in pregnancy is still unpredictable.201222877560
relating land cover and spatial distribution of nephropathia epidemica and lyme borreliosis in belgium.lyme borreliosis (lb) and nephropathia epidemica (ne) are zoonoses resulting from two different transmission mechanisms and the action of two different pathogens: the bacterium borrelia burgdorferi and the puumala virus, respectively. the landscape configuration is known to influence the spatial spread of both diseases by affecting vector demography and human exposure to infection. yet, the connections between landscape and disease have rarely been quantified, thereby hampering the exploitation ...201322894742
clinical aspects of hantavirus infections in bulgaria.hantaviruses cause two distinct human diseases: hemorrhagic fever with renal syndrome (hfrs) in asia and europe and hantavirus pulmonary syndrome (hps) in america. in europe, mainly puumala, dobrava and seoul viruses cause hfrs. a total of 23 cases of hfrs were detected in bulgaria over a 2‑year period 2013-2014. the aim of the study was to present epidemiology, clinical manifestations and laboratory findings of these patients.201728229289
[human hantavirus diseases - still neglected zoonoses?].hantavirus disease is the most common rodent-borne viral infection in the czech republic, with a mean annual incidence of 0.02 cases per 100 000 population and specific antibodies detected in 1% of the human population. four hantaviruses (puumala, dobrava-belgrade, tula, and seewis) circulate in this country, of which puumala virus (responsible for a mild form of hemorrhagic fever with renal syndrome called nephropathia epidemica) and dobrava-belgrade virus (causing haemorrhagic fever with renal ...201526795222
does proficiency testing improve the quality of hantavirus serodiagnostics? experiences with instand eqa schemes.hantavirus infections in germany appear periodically with peak numbers every 2-3 years. the reported cases in the years 2007, 2010 and 2012 exceeded many times over those in the years in-between. in order to reveal faults of certain in vitro diagnostic assays (ivds), to harmonize the performances of the individual assays and to improve the users' competence in interpreting the results, the national consiliary laboratory for hantaviruses and instand e.v. (society for promoting quality assurance i ...201526342877
surveillance of hantaviruses in poland: a study of animal reservoirs and human hantavirus disease in subcarpathia.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 an ...201424902039
high infection rate of bank voles (myodes glareolus) with puumala virus is associated with a winter outbreak of haemorrhagic fever with renal syndrome in croatia.an outbreak of haemorrhagic fever with renal syndrome (hfrs) started on medvednica mountain near zagreb in january 2012. in order to detect the aetiological agent of the disease in small rodents and to make the link with the human outbreak, rodents were trapped at four different altitudes. using nested rt-pcr, puumala virus (puuv) rna was detected in 41/53 (77·4%) bank voles (myodes glareolus) and dobrava virus (dobv) rna was found in 6/61 (9·8%) yellow-necked mice (apodemus flavicollis). sequen ...201424800636
hantavirus infections.over the past few decades understanding and recognition of hantavirus infection has greatly improved worldwide, but both the amplitude and the magnitude of hantavirus outbreaks have been increasing. several novel hantaviruses with unknown pathogenic potential have been identified in a variety of insectivore hosts. with the new hosts, new geographical distributions of hantaviruses have also been discovered and several new species were found in africa. hantavirus infection in humans can result in ...201524750436
identification of hantavirus infection by western blot assay and taqman pcr in patients hospitalized with acute kidney injury.hantaviruses, one of the causative agents of viral hemorrhagic fevers, represent a considerable healthcare threat. in hungary, dobrava-belgrade virus (dobv) and puumala virus (puuv) are the main circulating hantavirus species, responsible for the clinical picture known as hemorrhagic fever with renal syndrome, a disease that may be accompanied by acute kidney injury (aki), requiring hospitalization with occasionally prolonged recovery phase. a total of 20 patient sera were collected over a 2-yea ...201424703877
[hantaviruses in germany: threat for zoo, pet, companion and farm animals?].hantaviruses are so-called "emerging" and "re-emerging" viruses because of the new and sudden nature of their appearance. human infections can lead to two distinct disease patterns, the haemorrhagic fever with renal syndrome and the hantavirus cardiopulmonary syndrome. all known human pathogenic hantaviruses are transmitted through rodent hosts. there are three rodent-associated hantaviruses in germany. the bank vole-associated puumala virus (puuv) is responsible for most of the human hantavirus ...201424511827
phylogeographic diversity of pathogenic and non-pathogenic hantaviruses in slovenia.slovenia is a very diverse country from a natural geography point of view, with many different habitats within a relatively small area, in addition to major geological and climatic differences. it is therefore not surprising that several small mammal species have been confirmed to harbour hantaviruses: a. flavicollis (dobrava virus), a. agrarius (dobrava virus-kurkino), m. glareolus (puumala virus), s. areanus (seewis virus),m. agrestis, m. arvalis and m. subterraneus (tula virus). three of the ...201324335778
[actual problems of hemorrhagic fever with renal syndrome].from 2000 to 2011 85 600 cases of hemorrhagic fever with renal syndrome (hfrs) were registered in russian federation. epidemically active foci of hfrs infection are located generally in temperate latitudes of the european part and the far east. in the far east regions whose fraction of all the hfrs disease cases in russia is around 2%, the causative agents of the infection are hantaan, amur, seoul hantaviruses, the natural reservoir for those are striped field mouse, korean field mouse and brown ...201323805652
hemorrhagic fever with renal syndrome and crimean-congo hemorrhagic fever as causes of acute undifferentiated febrile illness in bulgaria.hemorrhagic fever with renal syndrome (hfrs) and crimean-congo hemorrhagic fever (cchf) are the 2 widespread viral hemorrhagic fevers occurring in europe. hfrs is distributed throughout europe, and cchf has been reported mainly on the balkan peninsula and russia. both hemorrhagic fevers are endemic in bulgaria. we investigated to what extent acute undifferentiated febrile illness in bulgaria could be due to hantaviruses or to cchf virus. using enzyme-linked immunosorbent assays (elisas), we test ...201323421884
human puumala and dobrava hantavirus infections in the black sea region of turkey: a cross-sectional study.this study was carried out to better understand the epidemiology of hantaviruses in a province of turkey (giresun) where human hantavirus disease has recently been detected. in this cross-sectional study, a total of 626 blood samples from healthy people aged 15 and 84 years old were collected both in urban and rural areas in 2009. the sera were tested by enzyme-linked immunosorbent assay (elisa), immunoblotting assay, and the focus reduction neutralization test (frnt). we screened the samples by ...201323289396
clinical and laboratory findings in patients with oliguric and non-oliguric hantavirus haemorrhagic fever with renal syndrome: an analysis of 128 patients.patients with haemorrhagic fever with renal syndrome (hfrs) may present without significant oliguria. we compared different initial clinical symptoms and laboratory findings in patients who developed oliguric acute renal failure (arf) with those in patients who did not develop oliguric arf. overall, 128 patients with serologically confirmed hfrs were hospitalized at the university hospital for infectious disease, zagreb, croatia between january 1999 and december 2010. clinical signs and laborato ...201322963396
genetic characterization of seoul hantavirus originated from norway rats (rattus norvegicus) captured in belgium.hantaviruses (genus hantavirus, family bunyaviridae) cause hemorrhagic fever with renal syndrome (hfrs) in eurasia and hantavirus (cardio)pulmonary syndrome (hcps) in the americas. so far, in europe, four pathogenic hantaviruses have been found, often in co-circulation: puumala virus (puuv), dobrava virus (dobv), saaremaa virus (saav), and seoul virus (seov). of those, only puuv was found in belgium. recently, in our search for hantaviruses in the flanders region of belgium we collected genetic ...201222711359
immunogenicity of a multi-epitope dna vaccine against hantavirus.hemorrhagic fever with renal syndrome (hfrs) is a severe epidemic disease caused by hantaviruses including hantaan virus (htnv), seoul virus (seov), dobrava virus (dobv) and puumala virus. three of the four hfrs hantaviruses, htnv, seov, and puuv are found in china. currently, there is no effective strategy available to reduce infection risk. in this study, we constructed a multi-epitope chimeric dna vaccine that encodes expressing 25 glycoprotein epitopes from seov, htnv and puuv (designated as ...201222426376
vaccinia virus-free rescue of fluorescent replication-defective vesicular stomatitis virus and pseudotyping with puumala virus glycoproteins for use in neutralization tests.puumala virus (puuv) grows slowly in cell culture. to study antigenic properties of puuv, an amenable method for their expression would be beneficial. to achieve this, a replication-defective recombinant vesicular stomatitis virus, rvsvδg*egfp, was rescued using bsrt7/5 and encephalomyocarditis virus (emcv) internal ribosomal entry site (ires)-enabled rescue plasmids. using these particles, pseudotypes bearing puuv sotkamo strain glycoproteins were produced, with titres in the range 105-108, and ...201626916544
production and biomedical applications of virus-like particles derived from polyomaviruses.virus-like particles (vlps), aggregates of capsid proteins devoid of viral genetic material, show great promise in the fields of vaccine development and gene therapy. these particles spontaneously self-assemble after heterologous expression of viral structural proteins. this review will focus on the use of virus-like particles derived from polyomavirus capsid proteins. since their first recombinant production 27 years ago these particles have been investigated for a myriad of biomedical applicat ...201323999392
the use of chimeric virus-like particles harbouring a segment of hantavirus gc glycoprotein to generate a broadly-reactive hantavirus-specific monoclonal antibody.monoclonal antibodies (mabs) against viral glycoproteins have important diagnostic and therapeutic applications. in most cases, the mabs specific to viral glycoproteins are raised against intact virus particles. the biosynthesis of viral glycoproteins in heterologous expression systems such as bacteria, yeast, insect or mammalian cells is often problematic due to their low expression level, improper folding and limited stability. to generate mabs against hantavirus glycoprotein gc, we have used ...201424513568
insufficient efficacy and safety of intravenous ribavirin in treatment of haemorrhagic fever with renal syndrome caused by puumala virus.intravenous ribavirin has been reported to be an effective treatment for haemorrhagic fever with renal syndrome (hfrs) caused by hantaan virus in asia. however, its therapeutic benefits for hfrs caused by puumala virus (puuv) in europe are still unknown.201728276794
concomitant leptospirosis-hantavirus co-infection in acute patients hospitalized in sri lanka: implications for a potentially worldwide underestimated problem.two global (re-)emerging zoonoses, leptospirosis and hantavirus infections, are clinically indistinguishable. thirty-one patients, hospitalized in sri lanka for acute severe leptospirosis, were after exclusion of other potentially involved pathogens, prospectively screened with igm elisa for both pathogens. of these, nine (29·0%) were positive for leptospirosis only, one (3·2%) for hantavirus only, seven (22·5%) for both pathogens concomitantly, whereas 13 (41·9%) remained negative for both. mor ...201525582980
a phase 1 clinical trial of hantaan virus and puumala virus m-segment dna vaccines for haemorrhagic fever with renal syndrome delivered by intramuscular electroporation.haemorrhagic fever with renal syndrome (hfrs) is endemic in asia, europe and scandinavia, and is caused by infection with the hantaviruses hantaan (htnv), seoul (seov), puumala (puuv), or dobrava (dobv) viruses. we developed candidate dna vaccines for hfrs expressing the gn and gc genes of htnv or puuv and evaluated them in an open-label, single-centre phase 1 study. three groups of nine participants each were vaccinated on days 0, 28 and 56 with the dna vaccines for htnv, puuv, or a mixture of ...201424447183
dna vaccines for hfrs: laboratory and clinical studies.dna vaccines can be constructed to produce specific immunogens while avoiding the risks associated with propagating infectious viruses. plasmid dna vaccines have well established manufacturing procedures and are safe in that they are replication defective, cannot revert to virulence and cannot be transmitted from person-to-person or into the environment. in addition, dna vaccines can be combined to form multivalent formulations and can be delivered by a variety of methods. because of these numer ...201424370868
role of nucleocapsid protein of hantaviruses in intracellular traffic of viral glycoproteins.to understand the role of nucleocapsid protein (np) of hantaviruses in viral assembly, the effect of np on intracellular traffic of viral glycoproteins gn and gc was investigated. double staining of viral and host proteins in hantaan virus (htnv)-infected vero e6 cells showed that gn and gc were localized to cis-golgi, in which virus particles are thought to be formed. when htnv gn and gc were expressed by a plasmid encoding glycoprotein precursor (gpc), which is posttranslationally cleaved into ...201324070985
isolation of hokkaido virus, genus hantavirus, using a newly established cell line derived from the kidney of the grey red-backed vole (myodes rufocanus bedfordiae).hantaviruses belong to the family bunyaviridae and are maintained in wild rodents. although vero e6 cells, which originate from african green monkey kidney, are used widely in hantavirus research, isolation of hantaviruses from this cell line is difficult. to develop an efficient method of propagation and isolation of hantaviruses we established a novel cell line, mrk101, derived from the kidney of the grey red-backed vole (myodes rufocanus bedfordiae), the natural host of hokkaido virus (hokv). ...201222791608
landscape features and helminth co-infection shape bank vole immunoheterogeneity, with consequences for puumala virus epidemiology.heterogeneity in environmental conditions helps to maintain genetic and phenotypic diversity in ecosystems. as such, it may explain why the capacity of animals to mount immune responses is highly variable. the quality of habitat patches, in terms of resources, parasitism, predation and habitat fragmentation may, for example, trigger trade-offs ultimately affecting the investment of individuals in various immunological pathways. we described spatial immunoheterogeneity in bank vole populations wi ...201424149655
surface-activated microtiter-plate microarray for simultaneous crp quantification and viral antibody detection.microarrays are widely used in high-throughput dna and rna hybridization tests and recently adopted to protein and small molecule interaction studies in basic research and diagnostics. parallel detection of serum antibodies and antigens has several potential applications in epidemiologic research, vaccine development, and in the diagnosis of allergies, autoimmunity, and infectious diseases. this study demonstrates an immobilization method for immunoassay-based microarray in conventional 96-well ...201323219230
islet autoantibodies present in association with ljungan virus infection in bank voles (myodes glareolus) in northern sweden.bank voles are known reservoirs for puumala hantavirus and probably also for ljungan virus (lv), a suggested candidate parechovirus in type 1 diabetes etiology and pathogenesis. the aim of this study was to determine whether wild bank voles had been exposed to lv and if exposure associated to autoantibodies against insulin (iaa), glutamic acid decarboxylase 65 (gada), or islet autoantigen-2 (ia-2a). serum samples from bank voles (myodes glareolus) captured in early summer or early winter of 1997 ...201727283793
lymphocytic choriomeningitis, ljungan and orthopoxvirus seroconversions in patients hospitalized due to acute puumala hantavirus infection.the emergence and re-emergence of zoonotic and vector-borne diseases are increasing in europe. prominent rodent-borne zoonotic viruses include puumala hantavirus (puuv; the causative agent of nephropathia epidemica, ne), lymphocytic choriomeningitis virus (lcmv), and orthopoxviruses (opv). in addition, ljungan virus (lv) is considered a potentially zoonotic virus.201627721109
serological survey in the finnish human population implies human-to-human transmission of ljungan virus or antigenically related viruses.ljungan virus (lv) is a picornavirus related to human parechoviruses (hpev). the virus has been found in bank voles (myodes glareolus) and several other rodent species, and suggested to have zoonotic potential. thus far, seroepidemiological data on lv infections in humans are scarce. in this study, we aimed to characterize the demographic and geographical distribution of lv-reactive antibodies in finland, and to investigate its occurrence in patients suspected of having a rodent-borne disease, n ...201626489898
hokkaido genotype of puumala virus in the grey red-backed vole (myodes rufocanus) and northern red-backed vole (myodes rutilus) in siberia.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 ...201526003760
muju virus, harbored by myodes regulus in korea, might represent a genetic variant of puumala virus, the prototype arvicolid rodent-borne hantavirus.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 a ...201424736214
leptospira spp. in small mammals from areas with low and high human hantavirus incidences in south-west germany.leptospirosis is caused by leptospira spp. and is considered the most widespread zoonotic disease worldwide. it mimics nephropathia epidemica in humans, a disease mainly caused by puumala hantavirus (puuv). small mammals are reservoirs for leptospira spp. and puuv. seewis virus (swsv) is a shrew-borne hantavirus with unknown pathogenicity. the objective of this study was to estimate the prevalence for leptospira spp. and the frequency of leptospira-hantavirus co-infections in small mammals colle ...201728332927
glomerular proteinuria predicts the severity of acute kidney injury in puumala hantavirus-induced tubulointerstitial nephritis.puumala virus (puuv)-induced hemorrhagic fever with renal syndrome is common in many european countries. the typical renal histologic lesion is acute tubulointerstitial nephritis. we examined the type and kinetics of urine protein excretion and prognostic significance of proteinuria for the severity of acute kidney injury (aki) in acute puuv infection.201728319945
expansion of spatial and host range of puumala virus in sweden: an increasing threat for humans?hantaviruses are globally distributed and cause severe human disease. puumala hantavirus (puuv) is the most common species in northern europe, and the only hantavirus confirmed to circulate in sweden, restricted to the northern regions of the country. in this study, we aimed to further add to the natural ecology of puuv in sweden by investigating prevalence, and spatial and host species infection patterns. specifically, we wanted to ascertain whether puuv was present in the natural reservoir, th ...201728249631
puumala hantavirus infections in bank vole populations: host and virus dynamics in central europe.in europe, bank voles (myodes glareolus) are widely distributed and can transmit puumala virus (puuv) to humans, which causes a mild to moderate form of haemorrhagic fever with renal syndrome, called nephropathia epidemica. uncovering the link between host and virus dynamics can help to prevent human puuv infections in the future. bank voles were live trapped three times a year in 2010-2013 in three woodland plots in each of four regions in germany. bank vole population density was estimated and ...201728245831
high prevalence of tula hantavirus in common voles in the netherlands.tula virus (tulv) is a zoonotic hantavirus. knowledge about tulv in the netherlands is very scarce. therefore in 2014, 49 common voles (microtus arvalis) from a region in the south of the netherlands, and in 2015, 241 common voles from regions in the north of the netherlands were tested with the tulv quantitative rt-pcr. in the southern region, prevalence of tulv was 41% (20/49). in the northern regions, prevalence ranged from 12% (4/34) to 45% (17/38). phylogenetic analysis of the obtained sequ ...201728112627
a highly divergent puumala virus lineage in southern poland.puumala virus (puuv) represents one of the most important hantaviruses in central europe. phylogenetic analyses of puuv strains indicate a strong genetic structuring of this hantavirus. recently, puuv sequences were identified in the natural reservoir, the bank vole (myodes glareolus), collected in the northern part of poland. the objective of this study was to evaluate the presence of puuv in bank voles from southern poland. a total of 72 bank voles were trapped in 2009 at six sites in this par ...201728093611
indoleamine 2,3-dioxygenase activity is associated with regulatory t cell response in acute puumala hantavirus infection.high indoleamine 2,3-dioxygenase (ido) activity is associated with clinically severe acute infection caused by puumala hantavirus. the immunoregulatory effects of ido can be mediated either through metabolic control of effector t cells, caused by depletion of the essential amino acid tryptophan, or intercellular signaling and activation of regulatory t cell responses. here, we have studied 24 patients with acute puumala hantavirus infection to distinguish between these possibilities. maximum ido ...201728057727
kidney disease in puumala hantavirus infection.acute kidney injury (aki) remains a predominant clinical expression of nephropathia epidemica (ne). its pathogenesis is not yet fully understood. here, we describe the tissue injury comprehensively and present new data aimed to characterize the injury and explain its pathophysiology. when compared to tubulointerstitial nephritis of a wide variety of other aetiologies, a high degree of proteinuria is a distinguished trait of ne, a finding that is also helpful in the clinical suspicion of the dise ...201728049381
elevated thrombopoietin and platelet indices confirm active thrombopoiesis but fail to predict clinical severity of puumala hantavirus infection.we evaluated the mechanisms of thrombocytopenia and procoagulant changes in relation with clinical variables in a cohort of patients with acute hantavirus disease.blood samples of 33 prospectively recruited, consecutive, hospitalized patients with acute puumala virus-induced hemorrhagic fever with renal syndrome (hfrs) were collected acutely and at the recovery visit (control). serum thrombopoietin (tpo) and activity of plasma microparticles (mps) from various cell sources were measured with enz ...201628033261
puumala virus in bank voles, lithuania.little is known about the presence of human pathogenic puumala virus (puuv) in lithuania. we detected this virus in bank voles (myodes glareolus) in a region of this country in which previously puuv-seropositive humans were identified. our results are consistent with heterogeneous distributions of puuv in other countries in europe.201727983939
host-associated absence of human puumala virus infections in northern and eastern germany.human hantavirus disease cases, caused by puumala virus (puuv), are mainly recorded in western and southern areas of germany. this bank vole reservoir survey confirmed puuv presence in these regions but its absence in northern and eastern regions. puuv occurrence is associated with the presence of the western bank vole phylogroup.201727983499
microevolution of bank voles (myodes glareolus) at neutral and immune-related genes during multiannual dynamic cycles: consequences for puumala hantavirus epidemiology.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 popula ...201727956196
reservoir-driven heterogeneous distribution of recorded human puumala virus cases in south-west germany.endemic regions for puumala virus (puuv) are located in the most affected federal state baden-wuerttemberg, south-west germany, where high numbers of notified human hantavirus disease cases have been occurring for a long time. the distribution of human cases in baden-wuerttemberg is, however, heterogeneous, with a high number of cases recorded during 2012 in four districts (h districts) but a low number or even no cases recorded in four other districts (l districts). bank vole monitoring during ...201627918151
autoimmune polyendocrinopathy and hypophysitis after puumala hantavirus infection.puumala hantavirus (puuv) infection causes nephropathia epidemica (ne), a relatively mild form of haemorrhagic fever with renal syndrome (hfrs). hypophyseal haemorrhage and hypopituitarism have been described in case reports on patients with acute ne. chronic hypopituitarism diagnosed months or years after the acute illness has also been reported, without any signs of a haemorrhagic aetiology. the mechanisms leading to the late-onset hormonal defects remain unknown. here, we present a case of ne ...201627857837
validation of the puumala virus rapid field test for bank voles in germany.puumala virus (puuv) causes many human infections in large parts of europe and can lead to mild to moderate disease. the bank vole (myodes glareolus) is the only reservoir of puuv in central europe. a commercial puuv rapid field test for rodents was validated for bank-vole blood samples collected in two puuv-endemic regions in germany (north rhine-westphalia and baden-württemberg). a comparison of the results of the rapid field test and standard elisas indicated a test efficacy of 93-95%, largel ...201727806736
human puumala hantavirus infection in northern sweden; increased seroprevalence and association to risk and health factors.the rodent borne puumala hantavirus (puuv) causes haemorrhagic fever with renal syndrome in central and northern europe. the number of cases has increased and northern sweden has experienced large outbreaks in 1998 and 2006-2007 which raised questions regarding the level of immunity in the human population.201627737653
hantavirus cardiopulmonary syndrome due to puumala virus in germany.in germany puumala virus (puuv), known to cause mild forms of hemorrhagic fever with renal syndrome (hfrs), is the predominating endemic hantavirus. we herein describe an unusually severe case of a puuv infection that occurred in summer 2015 in south eastern germany in a region known to be endemic for puuv since over ten years. a 54-year-old female gardener was admitted to hospital with fever, cough and dyspnea. within 48hours the patient developed a rapid progressive adult respiratory distress ...201627721108
declining ecosystem health and the dilution effect.the "dilution effect" implies that where species vary in susceptibility to infection by a pathogen, higher diversity often leads to lower infection prevalence in hosts. for directly transmitted pathogens, non-host species may "dilute" infection directly (1) and indirectly (2). competitors and predators may (1) alter host behavior to reduce pathogen transmission or (2) reduce host density. in a well-studied system, we tested the dilution of the zoonotic puumala hantavirus (puuv) in bank voles (my ...201627499001
smoking is a risk factor for severe acute kidney injury in hantavirus-induced nephropathia epidemica.hantaviruses are zoonotic pathogens causing emerging diseases worldwide. patients typically present with fever, acute kidney injury (aki) and thrombocytopenia. puumala virus (puuv) that causes nephropathia epidemica (ne) is common in germany. recently, a study from finland revealed an association between nicotine consumption and the severity of aki in ne. differences between individuals in finland and germany might modulate the effect; therefore, the aim of our study was to prove that smoking is ...201627388481
thrombocytopenia associates with the severity of inflammation and variables reflecting capillary leakage in puumala hantavirus infection, an analysis of 546 finnish patients.hantaviruses cause hemorrhagic fever with renal syndrome (hfrs) and hantavirus cardiopulmonary syndrome (hcps) in humans. hantavirus infections are characterized by thrombocytopenia. our objective was to assess the association of thrombocytopenia with disease severity in hfrs induced by puumala hantavirus (puuv).201627299174
electrocardiographic abnormalities and relative bradycardia in patients with hantavirus-induced nephropathia epidemica.nephropathia epidemica (ne), caused by puumala virus (puuv), is characterized by acute kidney injury (aki) and thrombocytopenia. cardiac involvement with electrocardiographic (ecg) abnormalities has been previously reported in ne; however, its prognostic value is unknown. relative bradycardia is an important clinical sign in various infectious diseases, and previous smaller studies have described pulse-temperature deficit in patients with puuv infection.201627296590
hantavirus in new geographic regions, sweden.in sweden, human cases of puumala hantavirus (puuv) infections are reported from the northern endemic regions. we found hantavirus-specific antibodies in yellow-necked mice (apodemus flavicollis) trapped in human dwellings in the surroundings of the cities of uppsala and stockholm, which are situated far south from the traditional endemic areas of puuv. because the yellow-necked mouse is the most common rodent in human dwellings, hantaviruses in this rodent species may be important for the publi ...201627258208
a molecular-level account of the antigenic hantaviral surface.hantaviruses, a geographically diverse group of zoonotic pathogens, initiate cell infection through the concerted action of gn and gc viral surface glycoproteins. here, we describe the high-resolution crystal structure of the antigenic ectodomain of gn from puumala hantavirus (puuv), a causative agent of hemorrhagic fever with renal syndrome. fitting of puuv gn into an electron cryomicroscopy reconstruction of intact gn-gc spike complexes from the closely related but non-pathogenic tula hantavir ...201627117403
regional differences in long-term cycles and seasonality of puumala virus infections, finland, 1995-2014.puumala hantavirus (puuv) causes haemorrhagic fever with renal syndrome in humans, an endemic disease in finland. we aimed to study recent trends in puuv infections in finland, to evaluate whether there are regional differences in seasonality and long-term cycles and whether the patterns have changed over time. we analysed serologically confirmed acute puuv infections reported to the national infectious disease register from 1 april 1995 to 31 march 2014. a total of 30 942 cases of puuv infectio ...201627113030
characterization of puumala hantavirus in bank voles from two regions in the netherlands where human cases occurred.puumala hantavirus (puuv) is the most common and widespread hantavirus in europe and is associated with a mild form of haemorrhagic fever with renal syndrome in humans, called nephropathia epidemica. this study presents the molecular characterization of puuv circulating in bank voles in two regions of the netherlands. most human cases of hantavirus infection are from these two regions. phylogenetic analysis of the (partial) s, m and l-segments indicated that the dutch strains belong to the ce li ...201627075118
erratum: temporal dynamics of puumala hantavirus infection in cyclic populations of bank voles. 201627072747
spatial and temporal epidemiology of nephropathia epidemica incidence and hantavirus seroprevalence in rodent hosts: identification of the main environmental factors in europe.in europe, the increasing number of nephropathia epidemica (ne) infections in humans, caused by puumala virus carried by bank voles (myodes glareolus), has triggered studies of environmental factors driving these infections. ne infections have been shown to occur in specific geographical areas characterized by environmental factors that influence the distribution and dynamics of host populations and virus persistence in the soil. here, we review the influence of environmental conditions (includi ...201626996739
[seoul hantavirus infection-associated hemorrhagic fever with renal syndrome in france: a case report].rodents are hantavirus hosts. in europe, hantaviruses are responsible for human infections resulting in hemorrhagic fever with renal syndrome. thousands of puumala virus infections are reported annually in europe, whereas human seoul virus infections are rarely detected.201626971198
temporal dynamics of puumala hantavirus infection in cyclic populations of bank voles.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 ...201626887639
selective predation on hantavirus-infected voles by owls and confounding effects from landscape properties.it has been suggested that predators may protect human health through reducing disease-host densities or selectively preying on infected individuals from the population. however, this has not been tested empirically. we hypothesized that tengmalm's owl (aegolius funereus) selectively preys on hantavirus-infected individuals of its staple prey, the bank vole (myodes glareolus). bank voles are hosts of puumala hantavirus, which causes a form of hemorrhagic fever in humans. selective predation by o ...201626873607
cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection.hantavirus infections may cause severe and sometime life-threatening lung failure. the pathogenesis is not fully known and there is an urgent need for effective treatment. we aimed to investigate the association between pulmonary viral load and immune responses, and their relation to disease severity. bronchoscopy with sampling of bronchoalveolar lavage (bal) fluid was performed in 17 patients with acute puumala hantavirus infection and 16 healthy volunteers acting as controls. lymphocyte subset ...201626873376
two clinical cases of renal syndrome caused by dobrava/saaremaa hantaviruses imported to the netherlands from poland and belarus, 2012-2014.we report the rare event of two imported cases in the netherlands presenting with renal syndrome caused by dobrava (dobv)/saaremaa (saav) hantaviruses. dobv/saav hantaviruses are not circulating in the netherlands and their clinical manifestation is typically more severe than that of the endemic puumala virus (puuv). this report aims to increase awareness among healthcare professionals and diagnostic laboratories to consider different hantaviruses as a cause of renal failure.201626818411
detection of puumala virus in the tissue of infected naturally rodent hosts in the area of central dinarides.hantaviruses are the causative agents of haemorrhagic fever with renal syndrome (hfrs) in euroasia and of hantavirus cardiopulmonary syndrome (hcps) in the north, central and south america. hfrs is endemic in the balkan peninsula, where sporadic cases or outbreaks have been reported. puumala virus (puuv) is the causative agent of nephropathia epidemica (ne), a mild form of hfrs. puuv is carried by the bank voles (myodes glareolus). in this study, we investigated viral rna from 76 tissues samples ...201626800777
three vole species and one (?) novel arvicolid hantavirus pathogen: tula virus revisited. 201626794642
interferons induce stat1-dependent expression of tissue plasminogen activator, a pathogenicity factor in puumala hantavirus disease.hantaviruses are zoonotic viruses that show various degrees of vasculopathy in humans. in this study, we analyzed the regulation of 2 fibrinolytic parameters, tissue plasminogen activator (tpa) and its physiological inhibitor, plasminogen activator inhibitor 1 (pai-1), in puumala hantavirus (puuv)-infected patients and in human microvascular endothelial cells. we detected strong upregulation of tpa in the acute phase of illness and in puuv-infected macaques and found the tpa level to positively ...201626704613
puumala hantavirus-induced hemorrhagic fever with renal syndrome must be considered across the borders of nephrology to avoid unnecessary diagnostic procedures.nephropathia epidemica (ne), a milder form of hemorrhagic fever with renal syndrome, is caused by puumala virus and is characterized by acute kidney injury and thrombocytopenia.201526650941
endothelial nitric oxide synthase g894t polymorphism associates with disease severity in puumala hantavirus infection.hantavirus infections are characterized by both activation and dysfunction of the endothelial cells. the underlying mechanisms of the disease pathogenesis are not fully understood. here we tested the hypothesis whether the polymorphisms of endothelial nitric oxide synthase, enos g894t, and inducible nitric oxide synthase, inos g2087a, are associated with the severity of acute puumala hantavirus (puuv) infection.201526561052
complete genome and phylogeny of puumala hantavirus isolates circulating in france.puumala virus (puuv) is the agent of nephropathia epidemica (ne), a mild form of hemorrhagic fever with renal syndrome (hfrs) in europe. ne incidence presents a high spatial variation throughout france, while the geographical distribution of the wild reservoir of puuv, the bank vole, is rather continuous. a missing piece of the puzzle is the current distribution and the genetic variation of puuv in france, which has been overlooked until now and remains poorly understood. during a population sur ...201526506370
urinary neutrophil gelatinase-associated lipocalin (ngal) and proteinuria predict severity of acute kidney injury in puumala virus infection.nephropathia epidemica (ne) is a mild form of hemorrhagic fever with renal syndrome (hfrs) that is caused by the puumala virus. periodic outbreaks have been described in endemic areas, with a substantial number of previously healthy individuals developing acute kidney injury (aki). there is a considerable diversity in the clinical course of the disease, and few patients require renal replacement therapy.201526503619
hantavirus infection-induced thrombocytopenia triggers increased production but associates with impaired aggregation of platelets except for collagen.we evaluated the mechanisms of thrombocytopenia encountered in hantavirus disease by studying platelet production together with platelet aggregation and deposition to collagen surface.201526462407
[acute angle-closure glaucoma triggered by epidemic nephropathy].epidemic nephropathy, i.e. nephropatia epidemica is a febrile illness caused by the puumala virus and involving a transient impairment in kidney function. additional commonly experienced symptoms include headache, backache and limb pain, as well as drowsiness or restlessness and nausea. visual disturbances appear in approx. one third of those affected with the disease. blurring of vision is the most common problem. we describe a patient case in which a previously healthy woman contracted epidemi ...201526237920
beech fructification and bank vole population dynamics--combined analyses of promoters of human puumala virus infections in germany.the transmission of wildlife zoonoses to humans depends, amongst others, on complex interactions of host population ecology and pathogen dynamics within host populations. in europe, the puumala virus (puuv) causes nephropathia epidemica in humans. in this study we investigated complex interrelations within the epidemic system of puuv and its rodent host, the bank vole (myodes glareolus). we suggest that beech fructification and bank vole abundance are both decisive factors affecting human puuv i ...201526214509
factors predicting kidney damage in puumala virus infected patients in southern denmark.in europe, infections with puumala hantavirus cause nephropathia epidemica. presently the risk factors predicting severe kidney damage after puumala virus infection are not well known. the objective of the study was to investigate environmental and individual factors predicting severe kidney damage caused by serologically established puumala infections. in a nationwide cohort study we investigated all serologically established puumala infections in southern denmark from 1996 to 2012. a total of ...201526205664
evaluation of lipase levels in patients with nephropathia epidemica--no evidence for acute pancreatitis.the most common causative agent for hemorrhagic fever with renal syndrome in germany is puumala virus (puuv) and a high percentage of patients with puuv infection have gastrointestinal (gi) symptoms. the aim of the present study was to determine the prevalence of increased lipase levels and acute pancreatitis during nephropathia epidemica (ne) in 166 patients from germany.201526204892
long-term hormonal follow-up after human puumala hantavirus infection.nephropathia epidemica (ne) is a haemorrhagic fever with renal syndrome (hfrs) caused by puumala hantavirus (puuv). pituitary haemorrhage and hypopituitarism may complicate recovery from acute ne.201626202013
environmental conditions in favour of a hantavirus outbreak in 2015 in germany?bank voles can harbour puumala virus (puuv) and vole populations usually peak in years after beech mast. a beech mast occurred in 2014 and a predictive model indicates high vole abundance in 2015. this pattern is similar to the years 2009/2011 when beech mast occurred, bank voles multiplied and human puuv infections increased a year later. given similar environmental conditions in 2014/2015, increased risk of human puuv infections in 2015 is likely. risk management measures are recommended.201626177110
smoking is associated with aggravated kidney injury in puumala hantavirus-induced haemorrhagic fever with renal syndrome.previous studies indicate that smoking affects the outcome of some infections and is a risk factor for puumala virus (puuv) infection. the aim of this study was to assess the effect of smoking on the clinical severity of puuv infection and the prevalence of smoking in patients with puuv infection.201526150428
community acquired severe acute kidney injury caused by hantavirus-induced hemorrhagic fever with renal syndrome has a favorable outcome.puumala hantavirus (puuv) induces an acute tubulointerstitial nephritis and acute kidney injury (aki). our aim was to evaluate the prognosis of severe aki associated with puuv infection.201526139246
spatiotemporal dynamics of puumala hantavirus associated with its rodent host, myodes glareolus.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. ...201526136821
risk factors and potential preventive measures for nephropatia epidemica in sweden 2011-2012: a case-control study.nephropatia epidemica (ne), a relatively mild form of hemorrhagic fever with renal syndrome caused by the puumala virus (puuv), is endemic in northern sweden. we aim to study the risk factors associated with ne in this region.201526134289
physiological condition of bank voles (myodes glareolus) during the increase and decline phases of the population cycle.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 ex ...201526006298
acalculous cholecystitis associated with hemorrhagic fever with renal syndrome.hantaviruses are responsible for various types of hemorrhagic fevers depending on the involved subtype. in europe, puumala virus is responsible for an epidemic nephropathy. this infection can be complicated by severe abdominal pain. a rarely reported cause of this presenting symptom is acalculous cholecystitis, which must be integrated in the clinicobiological spectrum and should not lead to a surgical sanction. its presence seems to be correlated with the severity of the disease, whose main pat ...201525982259
competitive homogeneous immunoassay for rapid serodiagnosis of hantavirus disease.in this study, we describe a competitive homogeneous immunoassay that makes use of förster resonance energy transfer (fret) in rapid detection of pathogen-specific antibodies. the assay principle is based on competition between a monoclonal antibody (mab) and serum antibodies to a given antigen. in the assay, named competitive fret immunoassay (cfret-ia), the fret signal is induced if mab carrying a donor label binds to an acceptor-labeled antigen. specific antibodies in serum compete for antige ...201525972427
age-related effects of chronic hantavirus infection on female host fecundity.1. pathogens often cause detrimental effects to their hosts and, consequently, may influence host population dynamics that may, in turn, feed back to pathogen transmission dynamics. understanding fitness effects of pathogens upon animal host populations can help to predict the risks that zoonotic pathogens pose to humans. 2. here we determine whether chronic infection by puumala hantavirus (puuv) affects important fitness-related traits, namely the probability of breeding, reproductive effort an ...201525965086
association of low serum tgf-β level in hantavirus infected patients with severe disease.hantaviruses are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome, an immune-mediated pathogenesis is discussed. the aim of the present study was to investigate the role of tgf-β expression in acute hantavirus infection.201525888018
landscape and regional environmental analysis of the spatial distribution of hantavirus human cases in europe.in europe, the most prevalent hantavirus, puumala virus, is transmitted by bank voles and causes nephropathia epidemica in human. the european spatial distribution of nephropathia epidemica is investigated here for the first time with a rich set of environmental variables.201525874194
[puumala hantavirus infection in isère: geographic extension of this zoonosis in france]. 201525840563
a multi-head intradermal electroporation device allows for tailored and increased dose dna vaccine delivery to the skin.the identification of an effective and tolerable delivery method is a necessity for the success of dna vaccines in the clinic. this article describes the development and validation of a multi-headed intradermal electroporation device which would be applicable for delivering multiple dna vaccine plasmids simultaneously but spatially separated. reporter gene plasmids expressing green and red fluorescent proteins were used to demonstrate the impact of spatial separation on dna delivery to increase ...201525839221
serological survey of seewis virus antibodies in patients suspected for hantavirus infection in finland; a cross-reaction between puumala virus antiserum with seewis virus n protein?puumala virus (puuv, carried by myodes glareolus) co-circulates with seewis virus (swsv, carried by sorex araneus) in finland. while puuv causes 1000-3000 nephropathia epidemica (ne) cases annually, the pathogenicity of swsv to man is unknown. to study the prevalence of swsv antibodies in hantavirus fever-like patients' sera, we used recombinant swsv nucleocapsid (n) protein as the antigen in elisa, immunofluorescence assay (ifa) and immunoblotting. while characterizing the recombinant swsv n pr ...201525787939
endothelial activation and repair during hantavirus infection: association with disease outcome.endothelial activation and dysfunction play a central role in the pathogenesis of sepsis and viral hemorrhagic fevers. hantaviral disease is a viral hemorrhagic fever and is characterized by capillary dysfunction, although the underlying mechanisms for hantaviral disease are not fully elucidated.201425734100
life-long shedding of puumala hantavirus in wild bank voles (myodes glareolus).the knowledge of viral shedding patterns and viraemia in the reservoir host species is a key factor in assessing the human risk of zoonotic viruses. the shedding of hantaviruses (family bunyaviridae) by their host rodents has widely been studied experimentally, but rarely in natural settings. here we present the dynamics of puumala hantavirus (puuv) shedding and viraemia in naturally infected wild bank voles (myodes glareolus). in a monthly capture-mark-recapture study, we analysed 18 bank voles ...201525701819
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