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population-based seroprevalence of puumala hantavirus in finland: smoking as a risk factor.puumala hantavirus (puuv) causes hemorrhagic fever with renal syndrome in humans, that is an endemic disease in finland. we estimated the seroprevalence of puuv in finland and explored risk factors and disease associations by using unique survey data with health register linkage. a total of 2000 sera from a nationwide health survey from 2011, representative of the adult population, were screened for puuv igg by immunofluorescence assay. we performed statistical analysis adjusting for stratified ...201829310747
delayed ifn type 1-induced antiviral state is a potential factor for hfrs severity.hantaviruses cause hemorrhagic fever with renal syndrome (hfrs) in europe and asia. interferon (ifn) responses play an important role in hfrs pathogenesis and it is known that the early ifnβ response is delayed by pathogenic hantaviruses. the clinical severity of hfrs caused by dobrava virus (dobv) and puumala virus (puuv) varies greatly and the aim of our study was to determine whether differences in early activation of the ifn type 1-induced antiviral state influence hfrs severity. peripheral ...201729281106
fatal puumala hantavirus disease: involvement of complement activation and vascular leakage in the pathobiology.the case-fatality rate of hantavirus disease depends strongly on the causative hantavirus, ranging from 0.1% to 40%. however, the pathogenesis is not fully understood, and at present no licensed therapies exist. we describe fatal cases caused by puumala hantavirus indicating involvement of complement activation and vascular leakage.201729255728
risk of venous thromboembolism following hemorrhagic fever with renal syndrome: a self-controlled case series study.bleeding is associated with viral hemorrhagic fevers; however, thromboembolic complications have received less attention. hemorrhagic fever with renal syndrome (hfrs) is a mild viral hemorrhagic fever caused by puumala hantavirus. we previously identified hfrs as a risk factor for myocardial infarction and stroke, but the risk for venous thromboembolism (vte), including deep vein thrombosis (dvt) and pulmonary embolism (pe), is unknown.201829020303
acute hantavirus infection presenting as haemolytic-uraemic syndrome (hus): the importance of early clinical diagnosis.the european prototype of hantavirus, puumala virus (puuv), isolated from a common wild rodent, the bank vole (myodes glareolus), causes nephropathia epidemica (ne). ne can perfectly mimic haemolytic-uraemic syndrome (hus), progressing from an aspecific flu-like syndrome to acute kidney injury with thrombocytopaenia, and presenting with some signs of haemolytic anaemia and/or coagulopathy. moreover, both ne and hus can occur in local outbreaks. we report an isolated case of ne, initially referre ...201828986730
diminished coagulation capacity assessed by calibrated automated thrombography during acute puumala hantavirus infection.: coagulation abnormalities are associated with puumala-virus-induced hemorrhagic fever with renal syndrome (puuv-hfrs). we evaluated the coagulation capacity of plasma during acute puuv-hfrs by measuring thrombin generation using calibrated automated thrombography (cat). the study cohort comprised 27 prospectively collected, consecutive, hospital-treated patients with acute puuv infection. blood samples were drawn in the acute phase and at the control visit approximately 5 weeks later. to evalu ...201828968301
serological survey of hantavirus and flavivirus among wild rodents in central italy.hantaviruses are a group of zoonotic viruses carried by rodents. puumala virus (puuv) and dobrava virus (dobv) are the causative agents of human hantavirus infections in europe. knowledge about hantavirus circulation in italy is very scarce. west nile virus (wnv) and usutu virus (usuv) are emerging neuropathogenic flaviviruses, both endemic in most part of the italian territories. to monitor the circulation of puuv, dobv, wnv, and usuv in natural environment in central italy, we carried out sero ...201728953448
gastrointestinal tract as entry route for hantavirus infection.background: hantaviruses are zoonotic agents that cause hemorrhagic fevers and are thought to be transmitted to humans by exposure to aerosolized excreta of infected rodents. puumala virus (puuv) is the predominant endemic hantavirus in europe. a large proportion of puuv-infected patients suffer from gastrointestinal symptoms of unclear origin. in this study we demonstrate that puuv infection can occur via the alimentary tract. methods: we investigated susceptibility of the human small intestina ...201728943870
bank vole immunoheterogeneity may limit nephropatia epidemica emergence in a french non-endemic region.ecoevolutionary processes affecting hosts, vectors and pathogens are important drivers of zoonotic disease emergence. in this study, we focused on nephropathia epidemica (ne), which is caused by puumala hantavirus (puuv) whose natural reservoir is the bank vole, myodes glareolus. we questioned the possibility of ne emergence in a french region that is considered to be ne-free but that is adjacent to a ne-endemic region. we first confirmed the epidemiology of these two regions and we demonstrated ...201728931451
structural transitions of the conserved and metastable hantaviral glycoprotein envelope.hantaviruses are zoonotic pathogens with a near-global distribution that can cause severe hemorrhagic fever and pulmonary syndrome. the outer membrane of the hantavirus envelope displays a lattice of two glycoproteins, gn and gc, which orchestrate host cell recognition and entry. here, we describe the crystal structure of the gn glycoprotein ectodomain from the asiatic hantaan virus (htnv), the most prevalent pathogenic hantavirus. structural overlay analysis reveals that the htnv gn fold is hig ...201728835498
serogrouping and seroepidemiology of north european hantaviruses using a novel broadly targeted synthetic nucleoprotein antigen array.introduction: hantaviruses are globally distributed zoonotic pathogens. great diversity and high antigenic cross-reactivity makes diagnosis by traditional methods cumbersome. materials and methods: 'megapeptides', 119-120-mers from the amino terminus of the nucleoprotein of 16 hantaviruses, representing the four major branches of the hantavirus phylogenetic tree, were utilized in a novel igg-based hantavirus suspension multiplex immunoassay (hsmia) for detection of past hantavirus infections in ...201728815001
dampening of population cycles in voles affects small mammal community structure, decreases diversity, and increases prevalence of a zoonotic disease.long-term decline and depression of density in cyclic small rodents is a recent widespread phenomenon. these observed changes at the population level might have cascading effects at the ecosystem level. here, we assessed relationships between changing boreal landscapes and biodiversity changes of small mammal communities. we also inferred potential effects of observed community changes for increased transmission risk of puumala virus (puuv) spread, causing the zoonotic disease nephropatica epide ...201728770071
haematuria is a marker for the severity of acute kidney injury but does not associate with thrombocytopenia in acute puumala hantavirus infection.puumala hantavirus (puuv) causes haemorrhagic fever with renal syndrome characterized by thrombocytopenia, capillary leakage and acute kidney injury (aki) with proteinuria and haematuria. although the typical histologic lesion is acute tubulointerstitial nephritis, the amount of glomerular proteinuria predicts the severity of upcoming aki. here, we studied the associations of haematuria and proteinuria with the severity of emerging aki, thrombocytopenia and markers of coagulation and fibrinolysi ...201728762841
spatial prediction and validation of zoonotic hazard through micro-habitat properties: where does puumala hantavirus hole - up?to predict the risk of infectious diseases originating in wildlife, it is important to identify habitats that allow the co-occurrence of pathogens and their hosts. puumala hantavirus (puuv) is a directly-transmitted rna virus that causes hemorrhagic fever in humans, and is carried and transmitted by the bank vole (myodes glareolus). in northern sweden, bank voles undergo 3-4 year population cycles, during which their spatial distribution varies greatly.201728747170
deregulation of levels of angiopoietin-1 and angiopoietin-2 is associated with severe courses of hantavirus infection.hantavirus disease is characterized by endothelial dysfunction. angiopoietin-1 (ang-1) and its antagonist angiopoietin-2 (ang-2) play a key role in the control of capillary permeability. ang-1 is responsible for maintenance of cell-to-cell contacts whereas ang-2 destabilizes monolayers. an imbalance of ang-1 and ang-2 levels results in enhanced permeability and capillary leakage.201728734140
phylogenetic analysis of puumala virus strains from central europe highlights the need for a full-genome perspective on hantavirus evolution.puumala virus (puuv), carried by bank voles (myodes glareolus), is the medically most important hantavirus in central and western europe. in this study, a total of 523 bank voles (408 from germany, 72 from slovakia, and 43 from czech republic) collected between the years 2007-2012 were analyzed for the presence of hantavirus rna. partial puuv genome segment sequences were obtained from 51 voles. phylogenetic analyses of all three genome segments showed that the newfound strains cluster with othe ...201728664467
human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways.hantaviruses infect humans via inhalation of virus-contaminated rodent excreta. infection can cause severe disease with up to 40% mortality depending on the viral strain. the virus primarily targets the vascular endothelium without direct cytopathic effects. instead, exaggerated immune responses may inadvertently contribute to disease development. mononuclear phagocytes (mnps), including monocytes and dendritic cells (dcs), orchestrate the adaptive immune responses. since hantaviruses are transm ...201728640917
circulation and diagnostics of puumala virus in norway: nephropatia epidemica incidence and rodent population dynamics.hantaviruses pose a public health concern worldwide causing haemorrhagic fever with renal syndrome (hfrs) and hantavirus pulmonary syndrome (hps). puumala virus (puuv) is the most prevalent hantavirus in central and northern europe, and causes a mild form of hfrs, also known as nephropathia epidemica (ne). in nature, the main host of puuv is the bank vole (myodes glareolus), and transmission to humans occurs through inhalation of aerosols from rodent excreta. nephropathia epidemica is particular ...201728585306
modelling human puumala hantavirus infection in relation to bank vole abundance and masting intensity in the netherlands.this paper deals with modelling the relationship between human puumala hantavirus (puuv) infection, the abundance and prevalence of infection of the host (the bank vole), mast, and temperature. these data were used to build and parametrise generalised regression models, and parametrise them using datasets on these factors pertaining to the netherlands. the performance of the models was assessed by considering their predictive power. models including mast and monthly temperature performed well, a ...201728567209
country-wide seroprevalence studies on crimean-congo hemorrhagic fever and hantavirus infections in general population of bulgaria.crimean-congo hemorrhagic fever (cchf) and hantavirus infections are the two viral hemorrhagic fevers spread in europe. to test actual circulation of cchf virus (cchfv) and hantaviruses in bulgaria, we conducted country-wide seroepidemiological studies. serum samples were collected prospectively from 1500 residents of all 28 districts in bulgaria. cchfv seroprevalence of 3.7% was revealed. anamnesis for tick bites, contact with livestock, age over 40 years and residency in haskovo district were ...201728561377
experimental infections of wild bank voles (myodes glareolus) from nephropatia epidemica endemic and non-endemic regions revealed slight differences in puumala virological course and immunological responses.in europe, the occurrence of nephropathia epidemica (ne), a human disease caused by puumala virus (puuv), exhibits considerable geographical heterogeneity despite the continuous distribution of its reservoir, the bank vole myodes glareolus. to better understand the causes of this heterogeneity, wild voles sampled in two adjacent ne endemic and non-endemic regions of france were infected experimentally with puuv. the responses of bank voles to puuv infection, based on the levels of anti-puuv igg ...201728396283
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
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
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
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
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
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
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
clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (hfrs) caused by hantaviruses puumala and dobrava-belgrade genotype sochi.hantavirus disease belongs to the emerging infections. the clinical picture and severity of infections differ between hantavirus species and may even vary between hantavirus genotypes. the mechanisms that lead to the broad variance of severity in infected patients are not completely understood. host- and virus-specific factors are considered.201627842513
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
crystal structure of glycoprotein c from a hantavirus in the post-fusion conformation.hantaviruses are important emerging human pathogens and are the causative agents of serious diseases in humans with high mortality rates. like other members in the bunyaviridae family their m segment encodes two glycoproteins, gn and gc, which are responsible for the early events of infection. hantaviruses deliver their tripartite genome into the cytoplasm by fusion of the viral and endosomal membranes in response to the reduced ph of the endosome. unlike phleboviruses (e.g. rift valley fever vi ...201627783673
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
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
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
inhibition of the hantavirus fusion process by predicted domain iii and stem peptides from glycoprotein gc.hantaviruses can cause hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome in humans. to enter cells, hantaviruses fuse their envelope membrane with host cell membranes. previously, we have shown that the gc envelope glycoprotein is the viral fusion protein sharing characteristics with class ii fusion proteins. the ectodomain of class ii fusion proteins is composed of three domains connected by a stem region to a transmembrane anchor in the viral envelope. these fusion protein ...201627414047
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
hmgb1 is a potential biomarker for severe viral hemorrhagic fevers.hemorrhagic fever with renal syndrome (hfrs) and crimean-congo hemorrhagic fever (cchf) are common representatives of viral hemorrhagic fevers still often neglected in some parts of the world. infection with dobrava or puumala virus (hfrs) and crimean-congo hemorrhagic fever virus (cchfv) can result in a mild, nonspecific febrile illness or as a severe disease with hemorrhaging and high fatality rate. an important factor in optimizing survival rate in patients with vhf is instant recognition of ...201627348219
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
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
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
acute human inkoo and chatanga virus infections, finland.inkoo virus (inkv) and chatanga virus (chatv), which are circulating in finland, are mosquitoborne california serogroup orthobunyaviruses that have a high seroprevalence among humans. worldwide, inkv infection has been poorly described, and chatv infection has been unknown. using serum samples collected in finland from 7,961 patients suspected of having viral neurologic disease or puumala virus infection during the summers of 2001-2013, we analyzed the samples to detect california serogroup infe ...201627088268
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
molecular diagnosis of hemorrhagic fever with renal syndrome caused by puumala virus.rodent-borne hantaviruses cause two severe acute diseases: hemorrhagic fever with renal syndrome (hfrs) in eurasia, and hantavirus pulmonary syndrome (hps; also called hantavirus cardiopulmonary syndrome [hcps]) in the americas. puumala virus (puuv) is the most common causative agent of hfrs in europe. current routine diagnostic methods are based on serological analyses and can yield inconclusive results. hantavirus-infected patients are viremic during the early phase of disease; therefore, dete ...201626962084
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
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
[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
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
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
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
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
[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
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
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
effect of puumala hantavirus infection on human umbilical vein endothelial cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release.puumala virus (puuv) infection causes over 5000 cases of hemorrhagic fever in europe annually and can influence the hemostatic balance extensively. infection might lead to hemorrhage, while a recent study showed an increased risk of myocardial infarction during or shortly after puuv infection. the mechanism by which this hantavirus influences the coagulation system remains unknown. therefore we aimed to elucidate mechanisms explaining alterations seen in primary and secondary hemostasis during p ...201525852676
[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
determination of procalcitonin levels in patients with nephropathia epidemica - a useful tool or an unnecessary diagnostic procedure?puumala virus causes nephropathia epidemica (ne), a milder form of hemorrhagic fever with renal syndrome that occurs in central and northern europe. several studies have sought to identify risk factors for severe ne. however, elevated procalcitonin (pct) levels have not previously been investigated as a predictive marker for a severe course of ne.201525662000
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