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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
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
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
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
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
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
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
Co-circulation of two Puumala hantavirus lineages in Latvia: A russian lineage described previously and a novel Latvian lineage.Puumala hantavirus (PUUV) causes a mild form of haemorrhagic fever with renal syndrome in Europe. Seven genetic lineages of PUUV have thus far been recorded, which exhibit geographic structure within the distribution of its natural host, the bank vole (Myodes glareolus). This study presents evidence for two distinct PUUV lineages co-circulating in Latvia: one previously described from Russia and a novel one that appears to be endemic. The Latvian lineage (LAT) is considerably divergent and sever ...201222170553
Immunogenic epitopes of Hantaviruses' N protein are restricted to conserved regions.The Bunyaviridae virus family is composed by five genera, of which the Hantavirus genus is one of the most important representatives. Occasionally, these viruses can be transmitted to humans, giving rise to severe diseases that present high mortality rates. We analyzed the amino acid sequences of the nucleocapsid (N) proteins of 34 different hantaviruses to investigate the potential mechanisms involved in immunogenicity against hantaviruses. Immunogenic epitopes described in the literature throu ...201222201821
a phase 1 clinical trial of hantaan virus and puumala virus m-segment dna vaccines for hemorrhagic fever with renal syndrome.candidate dna vaccines for hemorrhagic fever with renal syndrome expressing the envelope glycoprotein genes of hantaan (htnv) or puumala (puuv) viruses were evaluated in an open-label, single-center phase 1 study consisting of three vaccination groups of nine volunteers. the volunteers were vaccinated by particle-mediated epidermal delivery (pmed) three times at four-week intervals with the htnv dna vaccine, the puuv dna vaccine or both vaccines. at each dosing, the volunteers received 8μg dna/4 ...201222248821
impact of puumala virus infection on maturation and survival in bank voles: a capture-mark-recapture analysis.many zoonotic diseases are caused by rodent-borne viruses. major fluctuations in the transmission of these viruses have been related to large changes in reservoir host population numbers due to external factors. however, the impact of the pathogen itself on the demography of its reservoir host is often overlooked. we investigated the impact of puumala virus (puuv) on survival and reproductive maturation probability of its reservoir host, the bank vole (myodes glareolus). three years (2004-06) of ...201222247383
occurrence of immunoglobulin m antibodies against several bacterial and viral pathogens in acute hantavirus infection.elevated levels of immunoglobulin m antibodies against various pathogens, most frequently epstein-barr-virus and coxiella burnetii, were detected by immunoassay in 15 of 48 patients (31.3%) with acute puumala virus infections. although the mechanisms leading to this igm response are not clear yet, polyspecific immunoglobulin m antibodies have to be taken into account to avoid misinterpretation of serological results in acute hantavirus infection.201222787199
atypical severe puumala hantavirus infection and virus sequence analysis of the patient and regional reservoir host.nephropathia epidemica (ne) caused by puumala hantavirus (puuv) is a mild variant of haemorrhagic fever with renal syndrome, which is endemic in germany. we describe the case of a 67-year-old man initially presenting with acute bilateral angle-closure glaucoma, an atypical clinical presentation of puuv infection. subsequently, the patient developed a severe course of disease additionally complicated by profound hepatitis and interstitial nephritis, both phenomena which are rarely described in as ...201222958255
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
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
gene expression of estrogen receptors in pbmc from patients with puumala-virus infection.abstract: the influence of estrogen signaling on infectious diseases is not fully known. males seem to be more susceptible to infections than females. this has also been noted for the scandinavian form of hemorrhagic fever with renal syndrome (hfrs) caused by puumala hantavirus (puuv). to investigate the differences in estrogen receptors in relation to sex and clinical severity, 20 patients (10 males, 10 females) with confirmed puuv infection was studied. real-time pcr was performed for analyzin ...201222266976
spatiotemporal dynamics of puumala hantavirus in suburban reservoir rodent populations.the transmission of pathogens to susceptible hosts is dependent on the vector population dynamics. in europe, bank voles (myodes glareolus) carry puumala hantavirus, which causes nephropathia epidemica (ne) in humans. fluctuations in bank vole populations and epidemics in humans are correlated but the main factors influencing this relationship remain unclear. in belgium, more ne cases are reported in spring than in autumn. there is also a higher incidence of human infections during years of larg ...201223181849
[renal failure in a couple caused by puumala hantavirus].in scandinavia puumala hantavirus causes nephropathia epidemica (ne), characterised by an acute debut of fever, headache, increasing back and abdominal pain, thrombocytopenia, increasing azotemia parameters, as well as microscopic haematuria and mild proteinuria. in some cases transitory myopia can be found. the diagnosis is made with a relevant clinical history and serology, and in most cases a kidney biopsy is not necessary. there is a risk of missing cases of ne as in this case, where a coupl ...201223121909
[hantavirus infection as the cause of haemorrhagic fever with renal syndrome].hantavirus is an rna virus that can cause potentially fatal pulmonary and renal diseases in humans. infections with hantaviruses occur through inhalation of aerosol from rodent faeces, urine or saliva. the predominant virus type in denmark is the puumala virus, which causes the mildest form of haemorrhagic fever with renal syndrome, the so-called nephropathia epidemica (ne) with good prognosis (mortality 0.1-0.4%). the incidence of hantavirus-infection in denmark is about ten cases a year. the d ...201223121908
modelling zoonotic diseases in humans: comparison of methods for hantavirus in sweden.because their distribution usually depends on the presence of more than one species, modelling zoonotic diseases in humans differs from modelling individual species distribution even though the data are similar in nature. three approaches can be used to model spatial distributions recorded by points: based on presence/absence, presence/available or presence data. here, we compared one or two of several existing methods for each of these approaches. human cases of hantavirus infection reported by ...201222984887
multiple synchronous outbreaks of puumala virus, germany, 2010.to investigate 2,017 cases of hantavirus disease in germany, we compared 38 new patient-derived puumala virus rna sequences identified in 2010 with bank vole-derived small segment rna sequences. the epidemic process was driven by outbreaks of 6 puumala virus clades comprising strains of human and vole origin. each clade corresponded to a different outbreak region.201222932394
blurred vision and myopic shift in puumala virus infections are independent of disease severity.puumala virus infection causes epidemic nephropathia (ne), a certain type of haemorrhagic fever with renal syndrome (hfrs). myopic shift is considered a pathognomonic sign of ne and hfrs but rates of ocular involvement vary. the aim of the study was to evaluate whether clinical and laboratory findings are associated with ophthalmic involvement in ne in austria. we found that blurred vision and myopic shift are frequent in puumala virus infections in austria but are independent of disease severit ...201222909300
signs of general inflammation and kidney function are associated with the ocular features of acute puumala hantavirus infection.puumala hantavirus (puuv) causes nephropathia epidemica (ne), a type of viral haemorrhagic fever with renal syndrome (hfrs). this febrile infection may affect the kidneys, central nervous system (cns), and the eye. acute illness is associated with increased tissue permeability and tissue oedema, and many patients experience reduced vision. the aim of this study was to explore the physiological events associated with the ocular features of acute ne.201222830303
resequencing of the puumala virus strain sotkamo from the who arbovirus collection.rna viruses exhibit a high mutation rate as the rna-dependent rna polymerase lacks proofreading and repair capabilities. it is known that serial passaging on cell culture leads to virus adaptation. puumala virus (puuv) strain sotkamo is the prototype virus for the low-pathogenic hantavirus puumala, family bunyaviridae. a full-length sequence of the strain sotkamos tripartite genome was made available more than 15 years ago, after at least 15 passages on vero e6 cells. a distinct sample from the ...201222798055
the degree of leukocytosis and urine gata-3 mrna levels are risk factors for severe acute kidney injury in puumala virus nephropathia epidemica.puumala hantavirus (puuv) infection, also known as nephropathia epidemica, is the most common cause of hemorrhagic fever with renal syndrome (hfrs) in europe. the pathogenesis of puuv nephropathia epidemica is complex and multifactorial, and the risk factors for severe acute kidney injury (aki) during acute puuv infection are not well defined. we conducted a prospective study of hospitalized patients with puuv infection in tampere, finland to identify acute illness risk factors for hfrs severity ...201222523590
hyperintense lesion in the corpus callosum associated with puumala hantavirus infection. 201222349863
plasma cell-free dna levels are elevated in acute puumala hantavirus infection.puumala hantavirus (puuv) causes a hemorrhagic fever with renal syndrome called nephropathia epidemica (ne). the aim of the present study was to evaluate plasma cell-free dna (cf-dna) levels and urinary cf-dna excretion in acute ne as well as their associations with the severity of the disease.201222347483
[from mice to men - insights from the hantavirus epidemic in 2010].with 2017 notified cases the largest hantavirus epidemic in germany has occurred in 2010. we report on two interesting cases illustrating the wide range of the individual clinical course and the diagnostic problems in hantavirus disease. the first patient was a seriously ill 44-year-old man who needed dialysis after an onset of flu-like symptoms with oliguria. an initially negative result of a hantavirus serology focused attention on rapidly progressive glomerulonephritis. the second patient, a ...201222318843
analysis of complete puumala virus genome, finland.puumala virus causes nephropathia epidemica, a rodent-borne zoonosis that is endemic to europe. we sequenced the complete puumala virus genome that was directly recovered from a person who died and compared it with those of viruses from local bank voles. the virus strain involved was neither a unique nor rare genetic variant.201223171600
environmental change and disease dynamics: effects of intensive forest management on puumala hantavirus infection in boreal bank vole populations.intensive management of fennoscandian forests has led to a mosaic of woodlands in different stages of maturity. the main rodent host of the zoonotic puumala hantavirus (puuv) is the bank vole (myodes glareolus), a species that can be found in all woodlands and especially mature forests. we investigated the influence of forest age structure on puuv infection dynamics in bank voles. over four years, we trapped small mammals twice a year in a forest network of different succession stages in norther ...201222745755
cross-sectional survey of the seroprevalence of puumala hantavirus in austria.the prevalence of puumala hantavirus infections in austria and the occupational exposure of military personnel to this virus were assessed in 2009 in an exploratory nationwide cross-sectional seroprevalence survey in 526 healthy individuals, of which 222 were soldiers and 304 were civilians. in addition, information on possible risk factors for hantavirus exposure, including previous foreign military assignments, residential area, occupational animal contact, and regular outdoor activities, was ...201222607075
a multi-structured epidemic problem with direct and indirect transmission in heterogeneous environments.in this work, we analyse a deterministic epidemic mathematical model motivated by the propagation of a hantavirus (puumala hantavirus) within a bank vole population (clethrionomys glareolus). the host population is split into juvenile and adult individuals. a heterogeneous spatial chronological age and infection age structure is considered, and also indirect transmission via the environment. maturation rates for juvenile individuals are adult density-dependent. for the reaction-diffusion systems ...201122873589
procalcitonin in hantavirus infections.in hantavirus infections levels of serum leukocytes or c-reactive protein are usually elevated to levels found in serious bacterial infections. however, procalcitonin in patients infected with hantavirus has not yet been discussed in the literature. a total of 29 adult patients with hantavirus infection, 30 with sepsis, and 19 with tick-borne encephalitis were included in this observational retrospective study. the median procalcitonin level in patients with hantavirus infection was 0.53 µg/l (r ...201121344982
phylogenetic analysis of puumala virus subtype bavaria, characterization and diagnostic use of its recombinant nucleocapsid protein.puumala virus (puuv) is the predominant hantavirus species in germany causing large numbers of mild to moderate cases of haemorrhagic fever with renal syndrome (hfrs). during an outbreak in south-east germany in 2004 a novel puuv subtype designated bavaria was identified as the causative agent of hfrs in humans [1]. here we present a molecular characterization of this puuv strain by investigating novel partial and almost entire nucleocapsid (n) protein-encoding small (s-) segment sequences and p ...201121598005
an unusual cause of a usual presentation. hantavirus infection. 201121868815
A five-year perspective on the situation of haemorrhagic fever with renal syndrome and status of the hantavirus reservoirs in Europe, 2005-2010.Hantavirus infections are reported from many countries in Europe and with highly variable annual case numbers. In 2010, more than 2,000 human cases were reported in Germany, and numbers above the baseline have also been registered in other European countries. Depending on the virus type human infections are characterised by mild to severe forms of haemorrhagic fever with renal syndrome. The member laboratories of the European Network for diagnostics of Imported Viral Diseases present here an ove ...201121924118
a model system for in vitro studies of bank vole borne viruses.the bank vole (myodes glareolus) is a common small mammal in europe and a natural host for several important emerging zoonotic viruses, e.g. puumala hantavirus (puuv) that causes hemorrhagic fever with renal syndrome (hfrs). hantaviruses are known to interfere with several signaling pathways in infected human cells, and hfrs is considered an immune-mediated disease. there is no in vitro-model available for infectious experiments in bank vole cells, nor tools for analyses of bank vole immune acti ...201122194969
efficient production of hantaan and puumala pseudovirions for viral tropism and neutralization studies.puumala (puuv) and hantaan (htnv) viruses are hantaviruses within the family bunyaviridae and associated with hemorrhagic fever with renal syndrome (hfrs) in humans. little is known about how these viruses interact with host cells, though pathogenic hantaviruses interact with α(v)β(3) integrin. to study host cell interactions and rapidly test the ability of antibodies to prevent infection, we produced htnv and puuv pseudovirions on a vesicular stomatitis virus (vsv) core. similar to replication- ...201122209230
detection of puumala and rift valley fever virus by quantitative rt-pcr and virus viability tests in samples of blood dried and stored on filter paper.haemorrhagic fever viruses cause emerging infections worldwide, and blood or serum is the main sample used for diagnosis. however, storage and transportation of such samples from remote areas to regional laboratories may be complicated and expensive. in this study, a novel approach was evaluated for the detection of puumala hantavirus (puuv) rna and rift valley fever virus (rvfv) rna. whole-blood samples spiked with viable virus particles were tested in parallel with clinical samples from patien ...201121946288
cytokine expression during early and late phase of acute puumala hantavirus infection.abstract: background: hantaviruses of the family bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (hfrs) in the old world and hantavirus pulmonary syndrome (hps) in the new world. an immune-mediated pathogenesis is discussed for both syndromes. the aim of our study was to investigate cytokine expression during the course of acute puumala hantavirus infection. results: we retrospectively studied 64 patients hospitalised with acute puumala hantavirus ...201122085404
specific humoral reaction of hemorrhagic fever with renal syndrome (hfrs) patients in china to recombinant nucleocapsid proteins from european hantaviruses.hemorrhagic fever with renal syndrome (hfrs) is endemic in east asia and europe. this study was initiated to investigate the reactivity of antibodies in sera of chinese hfrs patients with the recombinant nucleocapsid proteins (rnps) of hantaan virus (htnv), dobrava-belgrade virus (dobv), and puumala virus (puuv), which are the prevalent hantavirus strains in europe. forty-eight pairs of acute and convalescent sera were collected from hfrs patients in hubei, china (1985-2002) and tested by indire ...201121222012
time to revise the paradigm of hantavirus syndromes? hantavirus pulmonary syndrome caused by european hantavirus.hantaviruses have previously been recognised to cause two separate syndromes: hemorrhagic fever with renal syndrome in eurasia, and hantavirus pulmonary syndrome (hps) in the americas. however, increasing evidence suggests that this dichotomy is no longer fruitful when recognising human hantavirus disease and understanding the pathogenesis. herein are presented three cases of severe european puumala hantavirus infection that meet the hps case definition. the clinical and pathological findings we ...201121234633
concomitant influence of helminth infection and landscape on the distribution of puumala hantavirus in its reservoir, myodes glareolus.puumala virus, the agent of nephropathia epidemica (ne), is the most prevalent hantavirus in europe. the risk for human infection seems to be strongly correlated with the prevalence of puumala virus (puuv) in populations of its reservoir host species, the bank vole myodes glareolus. in humans, the infection risks of major viral diseases are affected by the presence of helminth infections. we therefore proposed to analyse the influence of both helminth community and landscape on the prevalence of ...201121303497
[bilateral acute angle-closure glaucoma due to an infection with hantavirus].a poor general condition of patients with hemorrhagic fever and elevated creatinine should raise suspicion of a systemic infection with hantavirus. this can often also cause ocular changes. above all, changes of intraocular pressure, in our case bilateral acute angle-closure glaucoma, due to edema and hemorrhage in the ciliary body result in anterolateral rotation of the iris-lens diaphragm with closure of the chamber angle. it can also cause a transient myopia, and intraretinal hemorrhages can ...201121327947
high activity of indoleamine 2,3-dioxygenase is associated with renal insufficiency in puumala hantavirus induced nephropathia epidemica.nephropathia epidemica (ne) is a hemorrhagic fever with renal syndrome caused by puumala hantavirus. the severity of ne varies greatly. the aim of the present study was to evaluate whether serum indoleamine 2,3-dioxygenase (ido) activity is associated with the severity of ne. a prospectively collected cohort of 102 consecutive patients with acute serologically confirmed ne was examined. serum kynurenine, tryptophan, creatinine, crp, and blood cell count were measured for up to 5 consecutive days ...201121328391
hantavirus-specific iga in saliva and viral antigen in the parotid gland in patients with hemorrhagic fever with renal syndrome.the hantavirus genus comprises rodent borne, zoonotic viruses of the bunyaviridae family that cause hemorrhagic fever with renal syndrome (hfrs) in eurasia and hantavirus cardiopulmonary syndrome (hcps) in the americas. rodent saliva contains infectious hantavirus and evidence suggests that hantavirus is also shed in human saliva, but person-to-person transmission is rare. in saliva, immunoglobulin (ig) a is the predominant immunoglobulin class. secretory iga serves as an important first line of ...201121360546
seroepidemiological survey of hantavirus infection in healthy people in vallès occidental, barcelona.hantaviruses are the etiological agents of hemorrhagic fever with renal syndrome in europe and asia, and hantavirus pulmonary syndrome in america. approximately 150,000 cases are reported annually worldwide. in spain, some hantavirus infection cases have been described. besides, rodents that have been described as hantavirus reservoirs are present. the aim of the present study was to determinate the seroprevalence of hantavirus in humans in the northeast of spain.201121417923
presence of activated airway t lymphocytes in human puumala hantavirus disease.hantaviruses cause two clinical syndromes: hemorrhagic fever with renal syndrome (hfrs) and hantavirus pulmonary syndrome (hps). the clinical spectrum in hfrs also often involves respiratory symptoms. as information about the pulmonary pathogenesis in hfrs is limited, we aimed to further study the local airway immune response in the lower airways.201121436245
complement activation in puumala hantavirus infection correlates with disease severity.abstract introduction. hantaviruses are important human pathogens that cause clinical diseases characterized by renal and cardiopulmonary manifestations. their pathogenesis is currently poorly understood. we have studied the role of the complement system in the pathogenesis of puumala (puuv) hantavirus infection. material and methods. we studied the activation of complement by measuring the terminal complement complex sc5b-9 and complement component c3 and c4 levels in patients with acute puuv i ...201121495786
platelet ligands and adamts13 during puumala hantavirus infection and associated thrombocytopenia.we aimed here to elucidate the role of adhesive platelet ligands and endothelial involvement during the acute phase of puumala hantavirus (puuv) infection. nineteen hospital-treated patients with serologically confirmed diagnosis of acute puuv infection were included. patient charts were reviewed for clinical and basic laboratory data. plasma levels of von willebrand factor antigen (vwf: ag), ristocetin cofactor (vwf: rco), factor viii (fviii: c) and a disintegrin and metalloproteinase with a th ...201121508829
seroprevalence study in forestry workers of a non-endemic region in eastern germany reveals infections by tula and dobrava-belgrade hantaviruses.highly endemic and outbreak regions for human hantavirus infections are located in the southern, southeastern, and western parts of germany. the dominant hantavirus is the bank vole transmitted puumala virus (puuv). in the eastern part of germany, previous investigations revealed tula virus (tulv) and dobrava-belgrade virus (dobv) infections in the respective rodent reservoirs. here, we describe a seroprevalence study in forestry workers from brandenburg, eastern germany, using igg elisa and imm ...201121611907
glomerulonephritis emerging shortly after puumala hantavirus infection: a report on 7 patients.aims: nephropathia epidemica (ne) is mild type of hemorrhagic fever caused by puumala (puu) hantavirus. renal biopsy typically shows acute tubulointerstitial nephritis and complete recovery is the usual outcome. we previously described 5 patients with membranoproliferative glomerulonephritis (mpgn) after acute ne. we now report on 7 more patients who developed biopsy-confirmed glomerulonephritis (gn) during the convalescent phase of ne. material and methods: we present case histories of 7 patien ...201121612760
puumala virus infection in syrian hamsters (mesocricetus auratus) resembling hantavirus infection in natural rodent hosts.the mechanism of hantavirus persistent infection in natural hosts is poorly understood due to a lack of laboratory animal models. herein, we report that syrian hamsters (mesocricetus auratus) infected with puumala virus (puuv) at 4weeks old show persistent infection without clinical symptoms for more than 2months. igg and igm antibodies against the viral nucleocapsid protein and neutralizing antibody were first detectable at 14days postinoculation (dpi) and maintained through 70dpi. viral rna wa ...201121672562
the cytoplasmic tail of hantavirus gn glycoprotein interacts with rna.we recently characterized the interaction between the intraviral domains of envelope glycoproteins (gn and gc) and ribonucleoprotein (rnp) of puumala and tula hantaviruses (genus hantavirus, family bunyaviridae). herein we report a direct interaction between spike-forming glycoprotein and nucleic acid. we show that the envelope glycoprotein gn of hantaviruses binds genomic rna through its cytoplasmic tail (ct). the nucleic acid binding of gn-ct is unspecific, as demonstrated by interactions with ...201121807393
longitudinal analysis of the human t cell response during acute hantavirus infection.longitudinal studies of t cell immune responses during viral infections in humans are essential for our understanding of how effector t cell responses develop, clear infection, and provide long-lasting immunity. here, following an outbreak of a puumala hantavirus infection in the human population, we longitudinally analyzed the primary cd8 t cell response in infected individuals from the first onset of clinical symptoms until viral clearance. a vigorous cd8 t cell response was observed early fol ...201121795350
hla associated hemorrhagic fever with renal syndrom disease progression in slovenian patients.mhc class i and class ii genes regulate the balance between appropriate aggressive responses and invading pathogens while minimising the destruction of host tissue. several studies have shown that in hfrs patients the disease outcome is determined by a complex interaction between the virus, immunopathologic and human genetic factors. in slovenia the severity of the disease caused by puuv is significantly lower than that of hfrs due to dobv. we have determined 23 different hla-b and 12 different ...201121775516
landscape genetics highlights the role of bank vole metapopulation dynamics in the epidemiology of puumala hantavirus.rodent host dynamics and dispersal are thought to be critical for hantavirus epidemiology as they determine pathogen persistence and transmission within and between host populations. we used landscape genetics to investigate how the population dynamics of the bank vole myodes glareolus, the host of puumala hantavirus (puuv), vary with forest fragmentation and influence puuv epidemiology. we sampled vole populations within the ardennes, a french puuv endemic area. we inferred demographic features ...201121819469
young male patients are at elevated risk of developing serious central nervous system complications during acute puumala hantavirus infection.abstract:201121838931
hantavirus outbreak in western europe: reservoir host infection dynamics related to human disease patterns.within europe, puumala virus (puuv) is the causal agent of nephropathia epidemica (ne) in humans, a zoonotic disease with increasing significance in recent years. in a region of belgium with a historically high incidence of ne, bank voles (the puuv reservoir hosts), were monitored for puuv igg antibody prevalence in nine study sites before, during, and after the highest ne outbreak recorded in belgium in 2005. we found that the highest numbers of puuv igg-positive voles coincided with the peak o ...201120450527
non-human primates in outdoor enclosures: risk for infection with rodent-borne hantaviruses.different species of non-human primates have been exploited as animal disease models for human hantavirus infections. to study the potential risk of natural hantavirus infection of non-human primates, we investigated serum samples from non-human primates of three species living in outdoor enclosures of the german primate center (gpc), göttingen, located in a hantavirus endemic region of central germany. for that purpose we used serological assays based on recombinant antigens of the bank vole (m ...201120727685
puumala virus infection: radiologic findings.a 33-year-old male patient was admitted to our nephrology department with rapidly deteriorating general health, fever, respiratory difficulties, and acute renal failure. computed tomography of the thorax revealed interstitial edema with thickening of the interlobular septa, peribronchial cuffing, ground-glass opacities, and small pleural and pericardial effusions. polymerase chain reaction tests verified puumala virus infection. the patient recovered with supportive treatment. hantavirus infecti ...201120736852
prospective study on ocular findings in acute puumala hantavirus infection in hospitalised patients.to appraise the ocular manifestations of puumala hantavirus evoked haemorrhagic fever with renal syndrome nephropathia epidemica (ne) and to clarify the mechanisms of ocular changes in the largest series of patients examined to date.201120679079
environmental risk factors for haemorrhagic fever with renal syndrome in a french new epidemic area.summaryin france, haemorrhagic fever with renal syndrome (hfrs) is endemic along the belgian border. however, this rodent-borne zoonosis caused by the puumala virus has recently spread south to the franche-comté region. we investigated the space-time distribution of hfrs and evaluated the influence of environmental factors that drive the hantavirus reservoir abundance and/or the disease transmission in this area. a scan test clearly indicated space-time clustering, highlighting a single-year (20 ...201120822577
systematic literature review of symptoms, signs and severity of serologically confirmed nephropathia epidemica in paediatric and adult patients.the clinical picture of nephropathia epidemica (ne), a rodent-mediated puumala virus (puuv) zoonosis, appears to be different in paediatric and adult patients, since severe complications are seen only in adults. to confirm this clinical impression, we made a systematic literature review to determine whether the severity of ne is similar in children and adults. we searched pubmed for articles dealing with the clinical symptoms, physical signs and outcomes of patients with ne, published in english ...201121341977
[transient myopia.]although transient myopia is an extremely rare symptom, systemic diseases which can also lead to a life-threatening condition should also be considered in cases of sudden deterioration of vision. therefore, the initial diagnosis in an ophthalmological clinic or practice plays a decisive role.201121590350
pulmonary high-resolution computed tomography findings in nephropathia epidemica.purpose: to evaluate lung high-resolution computed tomography (hrct) findings in patients with puumala hantavirus-induced nephropathia epidemica (ne), and to determine if these findings correspond to chest radiograph findings. materials and methods: hrct findings and clinical course were studied in 13 hospital-treated ne patients. chest radiograph findings were studied in 12 of them. results: twelve patients (92%) showed lung parenchymal abnormalities in hrct, while only 8 had changes in their c ...201121600717
a new permanent cell line derived from the bank vole (myodes glareolus) as cell culture model for zoonotic viruses.abstract:201121729307
polymorphisms of pai-1 and platelet gp ia may associate with impairment of renal function and thrombocytopenia in puumala hantavirus infection.introduction: puumala virus (puuv) infection is a viral hemorrhagic fever with renal syndrome (hfrs) characterized by thrombocytopenia and acute impairment of renal function. we aimed to assess whether genetic polymorphisms of platelet antigens together with those of von willebrand factor (vwf) and plasminogen activator inhibitor (pai-1) correlate with disease severity. patients and methods 172 consecutive hospital-treated patients with serologically confirmed acute puuv infection were included. ...201122133274
High pentraxin-3 plasma levels associate with thrombocytopenia in acute Puumala hantavirus-induced nephropathia epidemica.Our aim was to investigate whether plasma levels of the long pentraxin-3 (PTX3) associate with the severity of Puumala hantavirus-induced nephropathia epidemica (NE). Sixty-one prospectively identified consecutively hospitalized NE patients were examined. Plasma PTX3, interleukin (IL)-6, terminal complement complex SC5b-9, complement component C3, C-reactive protein (CRP), creatinine, sodium, kynurenine, and tryptophan levels, as well as the blood cell count, were determined for up to five conse ...201121901638
case-control study on puumala virus infection: smoking is a risk factor.puumala hantavirus (puuv) is apparently transmitted to humans by inhalation of aerosolized secretions of carrier rodents (bank voles). the means of transmission and the associated risk factors are poorly defined. an epidemiological study during the peak of an epidemic season in finland was conducted based on 282 acute clinical puuv infections and 204 controls without puuv infection or immunity. the main risk factors adjusted by age, sex and living environment were cigarette smoking [odds ratio ( ...201019781114
hantavirus nephropathy as a pseudo-import pathology from ecuador.we report a case of hantavirus infection (nephropathia epidemica) diagnosed in a belgian backpacker returning from a trekking expedition in ecuador, after likely heavy exposure to rodents. because of epidemiological inconsistency, molecular investigation was performed and revealed a puumala infection acquired during very limited exposure in belgium upon return.201019821128
disease burden of puumala virus infections, 1995-2008.puumala virus (puuv) causes mild haemorrhagic fever with renal syndrome, a rodent-borne zoonosis. to evaluate the disease burden of puuv infections in finland, we analysed data reported by laboratories to the national infectious disease registry during 1995-2008 and compared these with data from other national registries (death, 1998-2007; hospital discharge, 1996-2007; occupational diseases, 1995-2006). a total of 22,681 cases were reported (average annual incidence 31/100,000 population); 85% ...201020109263
headache and low platelets in a patient with acute leukemia. 201020308016
nephropathia epidemica (puumala virus infection) in austrian children.from 2000 to 2007, 19 austrian children (aged 6-18 years) had serologically verified nephropathia epidemica. common clinical features were abdominal/flank/back pain, fever, nausea, vomiting, headache, and transient visual disturbances. acute renal failure was present in 18 (95%) patients. all patients recovered completely. childhood nephropathia epidemica in austria takes a similar course to those reported for northern european puumala virus strains.201020400926
associations between mhc genes and puumala virus infection in myodes glareolus are detected in wild populations, but not from experimental infection data.we analysed the influence of mhc class ii dqa and drb genes on puumala virus (puuv) infection in bank voles (myodes glareolus). we considered voles sampled in five european localities or derived from a previous experiment that showed variable infection success of puuv. the genetic variation observed in the dqa and drb genes was assessed by using single-strand conformation polymorphism and pyrosequencing methods, respectively. patterns were compared with those obtained from 13 microsatellites. we ...201020573856
[nephropathia epidemica: data on voles indicate new, extensive outbreak]. 201020812561
mortality rate patterns for hemorrhagic fever with renal syndrome caused by puumala virus.to investigate nephropathia epidemica in sweden during 1997-2007, we determined case-fatality rates for 5,282 patients with this disease. overall, 0.4% died of acute nephropathia epidemica ≤3 months after diagnosis. case-fatality rates increased with age. only women showed an increased case-fatality rate during the first year after diagnosis.201020875284
tnf-α expression and promoter sequences reflect the balance of tolerance/resistance to puumala hantavirus infection in european bank vole populations.the tumor necrosis factor-alpha (tnf-α) influences the ability to limit parasite infection but its over-production might result in inflammatory disorders. the level of tnf-α gene expression could thus mediate a balance of tolerance/resistance to infections. this study focused on puumala hantavirus (puuv) infection in its rodent host, the bank vole (myodes glareolus). in humans, puuv is responsible of a mild form of hemorrhagic fever with renal syndrome, nephropathia epidemica (ne). the severity ...201020691810
hantaviruses and their hosts in europe: reservoirs here and there, but not everywhere?five hantaviruses are known to circulate among rodents in europe, and at least two among insectivores. four (dobrava, saaremaa, seoul, and puumala [puuv] viruses) are clearly associated with hemorrhagic fever with renal syndrome (hfrs). puuv, the most common etiological agent of hfrs in europe, is carried by the bank vole (myodes glareolus), one of the most widespread and abundant mammal species in europe. this host-virus system is among hantaviruses also the most studied one in europe. however, ...201020795916
characterization of a natural focus of puumala hantavirus infection in the czech republic.hantaviruses are rna viruses of the bunyaviridae family, represented in the czech republic by three genospecies: dobrava-belgrade, puumala and tula. they persist in natural foci of infection. in 2004 to 2009, a local outbreak with 18 reported cases of nephropathia epidemica caused by puumala hantavirus occurred in the sumava mountains and foothills and was spacially associated with another outbreak in lower bavaria, germany. in the jeleni locality in the sumava mountains at 880 m above sea level ...201020939264
pathogenic landscapes: interactions between land, people, disease vectors, and their animal hosts.landscape attributes influence spatial variations in disease risk or incidence. we present a review of the key findings from eight case studies that we conducted in europe and west africa on the impact of land changes on emerging or re-emerging vector-borne diseases and/or zoonoses. the case studies concern west nile virus transmission in senegal, tick-borne encephalitis incidence in latvia, sandfly abundance in the french pyrenees, rift valley fever in the ferlo (senegal), west nile fever and t ...201020979609
hantavirus infection: a neglected diagnosis in thrombocytopenia and fever?thrombocytopenia, fever, and acute renal failure are characteristic features of nephropathia epidemica, the predominant hantavirus infection in europe. however, clinical presentation and blood cell counts may point to other disorders, such as a hematologic disease, particularly when impairment of renal function is not evident. this differential diagnosis often results in further extensive and unnecessary testing. we describe 3 patients with hantavirus infection with no renal failure, in whom a h ...201021037045
characterization of two substrains of puumala virus that show phenotypes that are different from each other and from the original strain.hantaviruses, the causative agents of two emerging diseases, are negative-stranded rna viruses with a tripartite genome. we isolated two substrains from a parental strain of puumala hantavirus (puuv-pa), puuv-small (puuv-sm) and puuv-large (puuv-la), named after their focus size when titrated. the two isolates were sequenced; this revealed differences at two positions in the nucleocapsid protein and two positions in the rna-dependent rna polymerase, but the glycoproteins were identical. we also ...201021106742
[nephropathia epidemica caused by puumala hantavirus infection: a case report from the outpatient sector].a 42-year-old man without pre-existing health problems presented to his family practitioner in baden-württemberg with fever (up to 39˚ c for two days), headache, abdominal pain, back pain and aching limbs. ten days before, he had done heavy gardening work. he felt diffuse pain on abdominal palpation. the physical examination of the skin, lymph nodes, the heart, the lungs and the oral mucosa was unremarkable.201021140328
temporal variation in individual factors associated with hantavirus infection in bank voles during an epizootic: implications for puumala virus transmission dynamics.abstract puumala virus (puuv), the causal agent of nephropathia epidemica in humans, is one of the many hantaviruses included in the list of emerging pathogens. hantavirus infection is not distributed evenly among puuv reservoir hosts (i.e., bank voles [myodes glareolus]). besides environmental factors and local population features, individual characteristics play an important role in vole puuv infection risk. identifying the relative importance of these individual characteristics can provide cr ...201021142469
characterization of monoclonal antibodies against hantavirus nucleocapsid protein and their use for immunohistochemistry on rodent and human samples.monoclonal antibodies are important tools for various applications in hantavirus diagnostics. recently, we generated puumala virus (puuv)-reactive monoclonal antibodies (mabs) by immunisation of mice with chimeric polyomavirus-derived virus-like particles (vlps) harbouring the 120-amino-acid-long amino-terminal region of the puuv nucleocapsid (n) protein. here, we describe the generation of two mabs by co-immunisation of mice with hexahistidine-tagged full-length n proteins of sin nombre virus ( ...201021161552
an efficient in vivo method for the isolation of puumala virus in syrian hamsters and the characterization of the isolates from russia.puumala virus (puuv) and other arvicolinae-borne hantaviruses are difficult to cultivate in cell culture. to isolate these hantaviruses efficiently, hantavirus nucleocapsid protein (np)-positive but seronegative wild rodents were selected by np-detection elisa. three of 68 myodes glareolus captured in samara, russia, were np-positive and seronegative. syrian hamsters were inoculated with lung homogenates from np-positive rodents for virus propagation. virus isolation in vitro was carried out by ...201021192975
comparison of the effects of puumala and dobrava viruses on early and long-term renal outcomes in patients with haemorrhagic fever with renal syndrome.the clinical course and outcome of patients with haemorrhagic fever with renal syndrome (hfrs) caused by puumala (puuv) and dobrava viruses (dobv) were analyzed and whether it left long-term consequences on kidney function after 10 years was evaluated.201020470304
the severity of puumala hantavirus induced nephropathia epidemica can be better evaluated using plasma interleukin-6 than c-reactive protein determinations.nephropathia epidemica (ne) is a scandinavian type of hemorrhagic fever with renal syndrome caused by puumala hantavirus. the clinical course of the disease varies greatly in severity. the aim of the present study was to evaluate whether plasma c-reactive protein (crp) and interleukin (il)-6 levels associate with the severity of ne.201020500875
the severity of acute puumala hantavirus infection does not predict the long-term outcome of patients.we have found greater urinary protein excretion and higher glomerular filtration rate (gfr) and blood pressure in patients 6 years after acute nephropathia epidemica (ne) compared with seronegative controls. the present aim was to establish whether the long-term outcome is determined by the severity of acute illness.201020502044
steep rise in notified hantavirus infections in germany, april 2010.from january to april 2010, 396 hantavirus infections were notified in germany, a considerable increase compared with previous years (mean: 83 for january-april 2004-2009) including the record-setting year, 2007 (n=232 january-april). most patients are residents of known puumala virus endemic areas in southern germany. the recent increase in notified hantavirus infections is probably due to an increased population density of the main animal reservoir, the bank vole (myodes glareolus).201020504391
generation and characterization of genetic reassortants between puumala and prospect hill hantavirus in vitro.hantaviruses belong to the family bunyaviridae characterized by tri-segmented rna genomes. depending on the hantavirus species, infection can lead to hantavirus cardiopulmonary or haemorrhagic fever with renal syndrome. in vitro studies suggest that pathogenic hantaviruses evade induction of innate antiviral responses, and this ability might determine the virulence in humans. since reverse genetic systems are not available, in vitro reassortment is currently the only way to culture defined hanta ...201020505009
central nervous system-related symptoms and findings are common in acute puumala hantavirus infection.puumala hantavirus (puuv) causes a hemorrhagic fever with renal syndrome (hfrs) also called nephropathia epidemica (ne). recent case reports and retrospective studies suggest that ne may damage the pituitary gland. based on these observations, our goal was to explore the nature of this complication prospectively.201020545485
characterization and outcome following puumala virus infection: a retrospective analysis of 75 cases.infection with the puumala virus (puuv), which belongs to the hantavirus family, is a common but often neglected cause of acute kidney injury (aki) in endemic areas of europe. the objective of the present study was to systematically analyse clinical presentation and renal outcomes following puuv infection.201020223893
hormonal deficiencies during and after puumala hantavirus infection.previous reports have described panhypopituitarism associated with severe cases of hemorrhagic fever with renal syndrome (hfrs), but the prevalence of hormonal deficiencies after nephropathia epidemica (ne), a milder form of hfrs, has not been studied. this study was conducted in order to determine the prevalence of hormonal defects in patients with acute ne and during long-term follow-up. fifty-four patients with serologically confirmed acute ne were examined by serum hormonal measurements duri ...201020397036
cytoplasmic tails of hantavirus glycoproteins interact with the nucleocapsid protein.here we characterize the interaction between the glycoproteins (gn and gc) and the ribonucleoprotein (rnp) of puumala virus (puuv; genus hantavirus, family bunyaviridae). the interaction was initially established with native proteins by co-immunoprecipitating puuv nucleocapsid (n) protein with the glycoprotein complex. mapping of the interaction sites revealed that the n protein has multiple binding sites in the cytoplasmic tail (ct) of gn and is also able to bind to the predicted ct of gc. the ...201020444994
enhanced thrombin formation and fibrinolysis during acute puumala hantavirus infection.nephropathia epidemica (ne) is a viral hemorrhagic fever with renal syndrome associated with thrombocytopenia and mild bleeding. we assessed activation of coagulation and fibrinolysis during the acute phase of ne.201020579693
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