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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
hantavirus infections by puumala or dobrava-belgrade virus in pregnant women.hantavirus infection in humans usually occurs via inhalation of infectious aerosolized excreta of rodents. horizontal human-to-human transmission was reported only for the highly virulent andes virus. the likelihood of vertical transmission and the clinical outcome of hantavirus infections in pregnancy is still unpredictable.201222877560
relating land cover and spatial distribution of nephropathia epidemica and lyme borreliosis in belgium.lyme borreliosis (lb) and nephropathia epidemica (ne) are zoonoses resulting from two different transmission mechanisms and the action of two different pathogens: the bacterium borrelia burgdorferi and the puumala virus, respectively. the landscape configuration is known to influence the spatial spread of both diseases by affecting vector demography and human exposure to infection. yet, the connections between landscape and disease have rarely been quantified, thereby hampering the exploitation ...201322894742
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
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
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
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
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
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
[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
[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
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
model-based prediction of nephropathia epidemica outbreaks based on climatological and vegetation data and bank vole population dynamics.wildlife-originated zoonotic diseases in general are a major contributor to emerging infectious diseases. hantaviruses more specifically cause thousands of human disease cases annually worldwide, while understanding and predicting human hantavirus epidemics pose numerous unsolved challenges. nephropathia epidemica (ne) is a human infection caused by puumala virus, which is naturally carried and shed by bank voles (myodes glareolus). the objective of this study was to develop a method that allows ...201323176630
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
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
construction and nonclinical testing of a puumala virus synthetic m gene-based dna vaccine.puumala virus (puuv) is a causative agent of hemorrhagic fever with renal syndrome (hfrs). although puuv-associated hfrs does not result in high case-fatality rates, the social and economic impact is considerable. there is no licensed vaccine or specific therapeutic to prevent or treat hfrs. here we report the synthesis of a codon-optimized, full-length m segment open reading frame and its cloning into a dna vaccine vector to produce the plasmid pwrg/puu-m(s2). pwrg/puu-m(s2) delivered by gene g ...201323239797
puumala virus infections associated with cardiovascular causes of death.we studied the causes of death of patients in sweden with diagnoses of hemorrhagic fever with renal syndrome (hfrs) during 1997-2009. cardiovascular disorders were a common cause of death during acute-phase hfrs and were the cause of death for >50% of those who died during the first year after hfrs.201323260342
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
development and evaluation of a broad reacting sybr-green based quantitative real-time pcr for the detection of different hantaviruses.hantaviruses are endemic in most parts of the world and cause hundreds of thousand human cases of hemorrhagic fever with renal syndrome (hfrs) and hantavirus cardiopulmonary syndrome (hcps) annually throughout eurasia and the americas. they are zoonotic viruses, most commonly transmitted to humans by aerosolized rodent excreta. new hantaviruses are frequently discovered in previously unknown reservoir species and geographic areas. consequently, there is a need to improve hantavirus diagnostics.201323290388
a severe case of puumala hantavirus infection successfully treated with bradykinin receptor antagonist icatibant.a patient with severe capillary leakage syndrome caused by a puumala hantavirus infection was treated with a single dose of icatibant, a bradykinin receptor antagonist, with a dramatic positive response. we suggest that this drug should be tested in a larger number of patients with severe hantavirus infection.201323294035
ecological niche modelling of bank voles in western europe.the bank vole (myodes glareolus) is the natural host of puumala virus (puuv) in vast areas of europe. puuv is one of the hantaviruses which are transmitted to humans by infected rodents. puuv causes a general mild form of hemorrhagic fever with renal syndrome (hfrs) called nephropathia epidemica (ne). vector-borne and zoonotic diseases generally display clear spatial patterns due to different space-dependent factors. land cover influences disease transmission by controlling both the spatial dist ...201323358234
[what the practising veterinarian should know about puumala virus]. 201323367591
puumala virus outbreak in western thuringia, germany, 2010: epidemiology and strain identification.in 2010, the highest annual number of human puumala virus (puuv) infections was reported in germany since hantavirus surveillance started in 2001. the increase in annual case numbers was especially marked in western thuringia. we combined results of case-based hantavirus surveillance in humans and serological and molecular investigations in the rodent reservoir to describe the epidemiological situation and to identify the putative outbreak strain. a 5-fold increase in notified hantavirus cases c ...201323398736
hemorrhagic fever with renal syndrome and crimean-congo hemorrhagic fever as causes of acute undifferentiated febrile illness in bulgaria.hemorrhagic fever with renal syndrome (hfrs) and crimean-congo hemorrhagic fever (cchf) are the 2 widespread viral hemorrhagic fevers occurring in europe. hfrs is distributed throughout europe, and cchf has been reported mainly on the balkan peninsula and russia. both hemorrhagic fevers are endemic in bulgaria. we investigated to what extent acute undifferentiated febrile illness in bulgaria could be due to hantaviruses or to cchf virus. using enzyme-linked immunosorbent assays (elisas), we test ...201323421884
another case of "european hantavirus pulmonary syndrome" with severe lung, prior to kidney, involvement, and diagnosed by viral inclusions in lung macrophages.puumala virus (puuv) is considered a classic old world etiologic agent of nephropathia epidemica (ne), or hemorrhagic fever with renal syndrome (hfrs). hfrs is considered to be distinct from hantavirus (cardio-)pulmonary syndrome (hps or hcps), described in the new world. here, we report a severe case, which fulfilled most, if not all, centers for disease control and prevention (cdc) criteria for hps, needing non-invasive ventilation and subsequent acute hemodialysis. however, the etiological ag ...201323670277
microevolution of puumala hantavirus during a complete population cycle of its host, the bank vole (myodes glareolus).microevolution of puumala hantavirus (puuv) was studied throughout a population cycle of its host, the bank vole (myodes glareolus). we monitored puuv variants circulating in the host population in central finland over a five-year period that included two peak-phases and two population declines. of 1369 bank voles examined, 360 (26.3%) were found infected with puuv. partial sequences of each of the three genome segments were recovered (approx. 12% of puuv genome) from 356 bank voles. analyses of ...201323717616
[acalculous cholecystitis in hantavirus infections].three men, aged 32, 56 and 41 years, respectively, were hospitalized within two weeks because of flu-like symptoms, limb pain and abdominal pain. being in a febrile, impaired general condition, pressure pains in the upper abdomen and flank pains were particularly noteworthy.201323720184
[en route in switzerland - tick-borne and hantavirus infections].tick-borne infections are endemic in switzerland with borreliosis being the most frequent one, followed by the vaccine-preventable tick-borne encephalitis and more rarely by anaplasmosis, rickettsioses and babesiosis. short characteristics of these infections are presented. the main preventive measures for stays in endemic regions include not leaving forest tracks and wearing closely fitted clothes and shoes, impregnated with an insecticide. following at-risk activities, clothes as well as the b ...201323732453
viral load and humoral immune response in association with disease severity in puumala hantavirus-infected patients--implications for treatment.hantaviruses are the causative agents of haemorrhagic fever with renal syndrome (hfrs) in eurasia and of hantavirus cardiopulmonary syndrome (hcps) in the americas. the case fatality rate varies between different hantaviruses and can be up to 40%. at present, there is no specific treatment available. the hantavirus pathogenesis is not well understood, but most likely, both virus-mediated and host-mediated mechanisms are involved. the aim of the present study was to investigate the association am ...201423742660
[development of elisa on the basis of monoclonal antibodies for detecting specific activity of the vaccine against hemorrhagic fever with renal syndrome].the monoclonal antibodies to puumala, dobrava, hantaan, and seoul hantaviruses were obtained using mice. the viruses were known to cause hfrs, and two variants of elisa were designed. first, hanta-puu variant, was constructed using monoclonal antibodies to puumala virus envelope glycoprotein (g(n):g(c)) for detecting only puumala virus antigen. the second, hanta-n variant, was constructed using monoclonal antibodies to dobrava and puumala nucleocapsid proteins for detecting four above mentioned ...201623785761
[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
a novel sin nombre virus dna vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (hps) and hemorrhagic fever with renal syndrome (hfrs).sin nombre virus (snv; family bunyaviridae, genus hantavirus) causes a hemorrhagic fever known as hantavirus pulmonary syndrome (hps) in north america. there have been approximately 200 fatal cases of hps in the united states since 1993, predominantly in healthy working-age males (case fatality rate 35%). there are no fda-approved vaccines or drugs to prevent or treat hps. previously, we reported that hantavirus vaccines based on the full-length m gene segment of andes virus (andv) for hps in so ...201323892100
hantaviruses as zoonotic pathogens in germany.hantavirus disease is a zoonosis of increasing clinical importance. a new incidence peak was reached in germany in 2012, with more than 2800 reported cases. these viruses are transmitted from small mammals to human beings. the disease begins with high fever and non-pathognomonic manifestations that can end in shock and organ failure.201323964302
elevated cerebrospinal fluid neopterin concentration is associated with disease severity in acute puumala hantavirus infection.nephropathia epidemica (ne) caused by puumala hantavirus (puuv) is the most common hemorrhagic fever with renal syndrome (hfrs) in europe. the infection activates immunological mechanisms that contribute to the pathogenesis and characteristics of the illness. in this study we measured cerebrospinal fluid (csf) neopterin concentration from 23 acute-phase ne patients. we collected data on kidney function, markers of tissue permeability, haemodynamic properties, blood cell count, length of hospital ...201323983770
plasma levels of soluble urokinase-type plasminogen activator receptor associate with the clinical severity of acute puumala hantavirus infection.urokinase-type plasminogen activator receptor is a multifunctional glycoprotein, the expression of which is increased during inflammation. it is known to bind to β3-integrins, which are elementary for the cellular entry of hantaviruses. plasma soluble form of the receptor (supar) levels were evaluated as a predictor of severe puumala hantavirus (puuv) infection and as a possible factor involved in the pathogenesis of the disease.201323990945
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
no gender-related differences in the severity of nephropathia epidemica, germany.the number of cases of hantavirus disease caused by puumala virus is increasing enormously in germany within the last years. men are overrepresented in hantavirus disease and differences in course and symptoms in relation to gender were reported from several countries. this study was conducted to define possible gender-specific risk factors and aspects of severity in hantavirus infections occurring in germany.201324090247
the pathogenesis of nephropathia epidemica: new knowledge and unanswered questions.puumala virus (puuv) causes an acute hemorrhagic fever with renal syndrome (hfrs), a zoonosis also called nephropathia epidemica (ne). the reservoir host of puuv is the bank vole (myodes glareolus). herein we review the main clinical manifestations of ne, acute kidney injury, increased vascular permeability, coagulation abnormalities as well as pulmonary, cardiac, central nervous system and ocular manifestations of the disease. several biomarkers of disease severity have recently been discovered ...201324126075
clinical presentation of puumala virus infections in southern austria in the peak year 2012.in 2012, an extraordinary rise in puumala infections causing nephropathia epidemica (ne) was observed in southern austria. we investigated differences in epidemiology, clinical presentation, laboratory results, treatment parameters, and outcome between patients in 2012 and previous years (2007-2011). all patients diagnosed with puumala virus infections between 2007 and 2012 using a point of care puumala igm test at the microbiology laboratory, department of internal medicine, medical university ...201424136061
landscape features and helminth co-infection shape bank vole immunoheterogeneity, with consequences for puumala virus epidemiology.heterogeneity in environmental conditions helps to maintain genetic and phenotypic diversity in ecosystems. as such, it may explain why the capacity of animals to mount immune responses is highly variable. the quality of habitat patches, in terms of resources, parasitism, predation and habitat fragmentation may, for example, trigger trade-offs ultimately affecting the investment of individuals in various immunological pathways. we described spatial immunoheterogeneity in bank vole populations wi ...201424149655
mobilization of circulating endothelial progenitor cells correlates with the clinical course of hantavirus disease.infections with hemorrhagic fever viruses are characterized by increased permeability leading to capillary leakage. hantavirus infection is associated with endothelial dysfunction, and the clinical course is related to the degree of vascular injury. circulating endothelial progenitor cells (cepcs) play a pivotal role in the repair of the damaged endothelium. therefore, we analyzed the number of cepcs and their mobilizing growth factors in patients suffering from hantavirus disease induced by inf ...201424155401
cardiopulmonary involvement in puumala hantavirus infection.hantavirus infections cause potentially life-threatening disease in humans world-wide. infections with american hantaviruses may lead to hantavirus pulmonary syndrome characterised by severe cardiopulmonary distress with high mortality. pulmonary involvement in european puumala hantavirus (puuv) infection has been reported, whereas knowledge of potential cardiac manifestations is limited. we aimed to comprehensively investigate cardiopulmonary involvement in patients with puuv-infection.201324160911
regulatory t cell response correlates with the severity of human hantavirus infection.hantaviruses are an important group of emerging zoonotic pathogens, with significant mortality rates. immunopathology is thought to be important in hantaviral disease, but the balance between protective and harmful responses is unknown. we studied puumala hantavirus (puuv) infection, which causes hemorrhagic fever with renal syndrome (hfrs) with a generally mild but highly variable clinical course.201424269676
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
maternal antibodies contribute to sex-based difference in hantavirus transmission dynamics.individuals often differ in their ability to transmit disease and identifying key individuals for transmission is a major issue in epidemiology. male hosts are often thought to be more important than females for parasite transmission and persistence. however, the role of infectious females, particularly the transient immunity provided to offspring through maternal antibodies (matabs), has been neglected in discussions about sex-biased infection transmission. we examined the effect of host sex up ...201324352416
dna vaccines for hfrs: laboratory and clinical studies.dna vaccines can be constructed to produce specific immunogens while avoiding the risks associated with propagating infectious viruses. plasmid dna vaccines have well established manufacturing procedures and are safe in that they are replication defective, cannot revert to virulence and cannot be transmitted from person-to-person or into the environment. in addition, dna vaccines can be combined to form multivalent formulations and can be delivered by a variety of methods. because of these numer ...201424370868
plasma b-type natriuretic peptide (bnp) in acute puumala hantavirus infection.nephropathia epidemica (ne) is a haemorrhagic fever with renal syndrome (hfrs) caused by puumala hantavirus (puuv). acute infection causes transient kidney injury, permeability disorder, and fluid retention, for example.201424393073
puumala hantavirus outbreak among u.s. military health care beneficiaries, stuttgart, germany--2012.hantaviruses are viruses of the family bunyaviridae that are transmitted to humans via inhalation of the aerosolized excrement of rodents. the geographic distribution of hantavirus includes the americas, asia, and europe. an outbreak of puumala hantavirus infections among u.s. military health care beneficiaries was identified by the u.s. army public health command region-europe at u.s. army installations in stuttgart, germany, during 2012. overall, five cases (one probable and four confirmed) we ...201324428538
hemorrhagic fever with renal syndrome in the new, and hantavirus pulmonary syndrome in the old world: paradi(se)gm lost or regained?since the first clinical description in 1994 of the so-called "hantavirus pulmonary syndrome" (hps) as a "newly recognized disease", hantavirus infections have always been characterized as presenting in two distinct syndromes, the so-called "hemorrhagic fever with renal syndrome" (hfrs) in the old world, with the kidney as main target organ, in contrast to hps in the new world, with the lung as main target organ. however, european literature mentions already since 1934 a mostly milder local hfrs ...201424440318
a phase 1 clinical trial of hantaan virus and puumala virus m-segment dna vaccines for haemorrhagic fever with renal syndrome delivered by intramuscular electroporation.haemorrhagic fever with renal syndrome (hfrs) is endemic in asia, europe and scandinavia, and is caused by infection with the hantaviruses hantaan (htnv), seoul (seov), puumala (puuv), or dobrava (dobv) viruses. we developed candidate dna vaccines for hfrs expressing the gn and gc genes of htnv or puuv and evaluated them in an open-label, single-centre phase 1 study. three groups of nine participants each were vaccinated on days 0, 28 and 56 with the dna vaccines for htnv, puuv, or a mixture of ...201424447183
first molecular evidence for puumala hantavirus in poland.puumala virus (puuv) causes mild to moderate cases of haemorrhagic fever with renal syndrome (hfrs), and is responsible for the majority of hantavirus infections of humans in fennoscandia, central and western europe. although there are relatively many puuv sequences available from different european countries, little is known about the presence of this virus in poland. during population studies in 2009 a total of 45 bank voles were trapped at three sites in north-eastern poland, namely islands o ...201424452006
[hantaviruses in germany: threat for zoo, pet, companion and farm animals?].hantaviruses are so-called "emerging" and "re-emerging" viruses because of the new and sudden nature of their appearance. human infections can lead to two distinct disease patterns, the haemorrhagic fever with renal syndrome and the hantavirus cardiopulmonary syndrome. all known human pathogenic hantaviruses are transmitted through rodent hosts. there are three rodent-associated hantaviruses in germany. the bank vole-associated puumala virus (puuv) is responsible for most of the human hantavirus ...201424511827
the use of chimeric virus-like particles harbouring a segment of hantavirus gc glycoprotein to generate a broadly-reactive hantavirus-specific monoclonal antibody.monoclonal antibodies (mabs) against viral glycoproteins have important diagnostic and therapeutic applications. in most cases, the mabs specific to viral glycoproteins are raised against intact virus particles. the biosynthesis of viral glycoproteins in heterologous expression systems such as bacteria, yeast, insect or mammalian cells is often problematic due to their low expression level, improper folding and limited stability. to generate mabs against hantavirus glycoprotein gc, we have used ...201424513568
simultaneous detection of igg antibodies associated with viral hemorrhagic fever by a multiplexed luminex-based immunoassay.viral hemorrhagic fevers (vhfs) are worldwide diseases caused by several kinds of viruses. with the emergence of new viruses, advanced diagnostic methods are urgently needed for identification of vhfs. based on luminex xmap technology, a rapid, sensitive, multi-pathogen and high-throughput method which could simultaneously detect hemorrhagic fever viruses (hfvs) specific igg antibodies was developed. recombinant antigens of nine hfvs including hantaan virus (htnv), seoul virus (seov), puumala vi ...201424631566
identification of hantavirus infection by western blot assay and taqman pcr in patients hospitalized with acute kidney injury.hantaviruses, one of the causative agents of viral hemorrhagic fevers, represent a considerable healthcare threat. in hungary, dobrava-belgrade virus (dobv) and puumala virus (puuv) are the main circulating hantavirus species, responsible for the clinical picture known as hemorrhagic fever with renal syndrome, a disease that may be accompanied by acute kidney injury (aki), requiring hospitalization with occasionally prolonged recovery phase. a total of 20 patient sera were collected over a 2-yea ...201424703877
comparison of two automated immunoassays for the determination of puumalavirus igm and igg.puumala virus (puuv), a member of the genus hantavirus, can cause nephropathia epidemica, a mild form of haemorrhagic fever with renal syndrome. the method of choice for the serodiagnosis of hantavirus infections are enzyme-linked immunosorbent assays (elisas).201424713176
urine soluble urokinase-type plasminogen activator receptor levels correlate with proteinuria in puumala hantavirus infection.urokinase-type plasminogen activator receptor (upar) is upregulated during inflammation and known to bind to β3 -integrins, receptors used by pathogenic hantaviruses to enter endothelial cells. it has been proposed that soluble upar (supar) is a circulating factor that causes focal segmental glomerulosclerosis and proteinuria by activating β3 -integrin in kidney podocytes. proteinuria is also a characteristic feature of hantavirus infections. the aim of this study was to evaluate the relation be ...201424717117
muju virus, harbored by myodes regulus in korea, might represent a genetic variant of puumala virus, the prototype arvicolid rodent-borne hantavirus.the genome of muju virus (mujv), identified originally in the royal vole (myodes regulus) in korea, was fully sequenced to ascertain its genetic and phylogenetic relationship with puumala virus (puuv), harbored by the bank vole (my. glareolus), and a puuv-like virus, named hokkaido virus (hokv), in the grey red-backed vole (my. rufocanus) in japan. whole genome sequence analysis of the 6544-nucleotide large (l), 3652-nucleotide medium (m) and 1831-nucleotide small (s) segments of mujv, as well a ...201424736214
hantavirus infections.over the past few decades understanding and recognition of hantavirus infection has greatly improved worldwide, but both the amplitude and the magnitude of hantavirus outbreaks have been increasing. several novel hantaviruses with unknown pathogenic potential have been identified in a variety of insectivore hosts. with the new hosts, new geographical distributions of hantaviruses have also been discovered and several new species were found in africa. hantavirus infection in humans can result in ...201524750436
plasma pentraxin-3 and coagulation and fibrinolysis variables during acute puumala hantavirus infection and associated thrombocytopenia.thrombocytopenia and altered coagulation characterize all hantavirus infections. to further assess the newly discovered predictive biomarkers of disease severity during acute puumala virus (puuv) infection, we studied the associations between them and the variables reflecting coagulation, fibrinolysis and endothelial activation. nineteen hospital-treated patients with serologically confirmed acute puuv infection were included. acutely, plasma levels of pentraxin-3 (ptx3), cell-free dna (cf-dna), ...201424751477
high infection rate of bank voles (myodes glareolus) with puumala virus is associated with a winter outbreak of haemorrhagic fever with renal syndrome in croatia.an outbreak of haemorrhagic fever with renal syndrome (hfrs) started on medvednica mountain near zagreb in january 2012. in order to detect the aetiological agent of the disease in small rodents and to make the link with the human outbreak, rodents were trapped at four different altitudes. using nested rt-pcr, puumala virus (puuv) rna was detected in 41/53 (77·4%) bank voles (myodes glareolus) and dobrava virus (dobv) rna was found in 6/61 (9·8%) yellow-necked mice (apodemus flavicollis). sequen ...201424800636
detection of puumala hantavirus antigen in human intestine during acute hantavirus infection.puumala virus (puuv) is the most important hantavirus species in central europe. nephropathia epidemica (ne), caused by puuv, is characterized by acute renal injury (aki) with thrombocytopenia and frequently gastrointestinal symptoms.201424857988
survey for hantaviruses, tick-borne encephalitis virus, and rickettsia spp. in small rodents in croatia.in croatia, several rodent- and vector-borne agents are endemic and of medical importance. in this study, we investigated hantaviruses and, for the first time, tick-borne encephalitis virus (tbev) and rickettsia spp. in small wild rodents from two different sites (mountainous and lowland region) in croatia. in total, 194 transudate and tissue samples from 170 rodents (a. flavicollis, n=115; a. agrarius, n=2; myodes glareolus, n=53) were tested for antibodies by indirect immunofluorescence assays ...201424866325
development of an immunochromatography strip test based on truncated nucleocapsid antigens of three representative hantaviruses.hantaviruses are causative agents of hemorrhagic fever with renal syndrome (hfrs) and nephropathia epidemica (ne) in the old world and hantavirus pulmonary syndrome (hps) in the new world. there is a need for time-saving diagnostic methods. in the present study, recombinant n antigens were used as antigens in an immunochromatography strip (icg) test to detect specific igg antibodies.201424885901
quantifying the past and future impact of climate on outbreak patterns of bank voles (myodes glareolus).central european outbreak populations of the bank vole (myodes glareolus schreber) are known to cause damage in forestry and to transmit the most common type of hantavirus (puumala virus, puuv) to humans. a sound estimation of potential effects of future climate scenarios on population dynamics is a prerequisite for long-term management strategies. historic abundance time series were used to identify the key weather conditions associated with bank vole abundance, and were extrapolated to future ...201524889216
surveillance of hantaviruses in poland: a study of animal reservoirs and human hantavirus disease in subcarpathia.the first cluster of hemorrhagic fever with renal syndrome (hfrs) in poland was identified in 2007 in the subcarpathian region. the natural environment of this area is a key habitat for hantavirus vectors. the animal reservoir of existing human hfrs clusters was studied to assess the occurrence of viruses (including tula virus, puumala virus, and dobrava-belgrade virus) among rodents. we examined 70 suspected human cases with symptoms corresponding to the clinical picture of hfrs. serological an ...201424902039
multiple infections of rodents with zoonotic pathogens in austria.rodents are important reservoirs for a large number of zoonotic pathogens. we examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, leptospira spp., borrelia spp., rickettsia spp., bartonella spp., coxiella burnetii, and toxoplasma gondii. in 2008, 110 rodents of four species (40 clethrionomys glareolus, 29 apodemus flavicollis, 26 apodemus sylvaticus, and ...201424915446
increased risk for lymphoma following hemorrhagic fever with renal syndrome.hemorrhagic fever with renal syndrome (hfrs) is a severe acute disease. although long-term consequences to public health have been reported, no association with cancer is known. we examined the risk of cancer development after hfrs in the swedish population between 1997 and 2011 (n = 6582) and report a 73% increased risk for lymphoma.201424965350
[epidemic nephropathy due to puumala virus: a case report]. 201424969100
hantaviruses in finnish soricomorphs: evidence for two distinct hantaviruses carried by sorex araneus suggesting ancient host-switch.hantaviruses are emerging viruses carried by rodents, soricomorphs (shrews and moles) and bats. in finland, puumala virus (puuv) was for years the only hantavirus detected. in 2009, however, seewis virus (swsv) was reported from archival common shrew (sorex araneus) samples collected in 1982 in finland. to elucidate the diversity of hantaviruses in soricomorphs in finland, 180 individuals were screened, representing seven species captured from 2001 to 2012: hantavirus rna was screened using rt-p ...201424997334
spleen enlargement is a common finding in acute puumala hantavirus infection and it does not associate with thrombocytopenia.the pathogenesis of thrombocytopenia in puumala hantavirus (puuv) infection is probably multifactorial. we aimed to evaluate the possible spleen enlargement during acute puuv infection, and to determine its association with thrombocytopenia and disease severity. magnetic resonance imaging (mri) of the spleen was performed in 20 patients with acute puuv infection. mri was repeated 5-8 months later. the change in spleen length was compared with markers describing the severity of the disease. in al ...201425119440
the hanta hunting study: underdiagnosis of puumala hantavirus infections in symptomatic non-travelling leptospirosis-suspected patients in the netherlands, in 2010 and april to november 2011.leptospirosis and haemorrhagic fever with renal syndrome (hfrs) are hard to distinguish clinically since these two important rodent-borne zoonoses share hallmark symptoms such as renal failure and haemorrhage. leptospirosis is caused by infection with a spirochete while hfrs is the result of an infection with certain hantaviruses. both diseases are relatively rare in the netherlands. increased incidence of hfrs has been observed since 2007 in countries that border the netherlands. since a simila ...201425139076
pathophysiology of a severe case of puumala hantavirus infection successfully treated with bradykinin receptor antagonist icatibant.we recently described a patient with very severe puumala hantavirus infection manifested by capillary leakage syndrome and shock. he was successfully treated with the bradykinin receptor antagonist, icatibant (antonen et al., 2013). here we report analysis of the pathophysiology which indicated pronounced complement activation, prolonged leukocytosis, extensive fibrinolysis, circulating histones, and defects in liver function. the patient had an uncommon hla-phenotype, which may have contributed ...201425194993
puumala hantavirus infection alters the odour attractiveness of its reservoir host.the random-mixing assumptions of many parasite-transmission models are challenged if healthy individuals can alter their behaviour to reduce their risk of infection. some pathogens reduce the attractiveness of their hosts' excretions, for example, potentially altering contact rates and thus the predicted force of infection for pathogens transmissible by contact with excretions. for bank voles (myodes glareolus), contact with contaminated urine is an important route of transmission for puumala ha ...201425209840
acute kidney injury and tools for risk-stratification in 456 patients with hantavirus-induced nephropathia epidemica.puumala virus (puuv) is the most common species of hantavirus in central europe. nephropathia epidemica (ne), caused by puuv, is characterized by acute kidney injury (aki) and thrombocytopenia. the major goals of this study were to provide a clear clinical phenotyping of aki in patients with ne and to develop an easy prediction rule to identify patients, who are at lower risk to develop severe aki.201525313168
inflammatory cytokines kinetics define the severity and phase of nephropathia epidemica.nephropathia epidemica (ne) is a form of hemorrhagic fever with renal syndrome associated with the puumala virus species of hantavirus. the pathogenesis of ne is not well understood; therefore, investigating the inflammatory cytokine response to infection may provide useful knowledge in deciphering the pathophysiology of ne.201525313675
identification of factors influencing the puumala virus seroprevalence within its reservoir in amontane forest environment.puumala virus (puuv) is a major cause of mild to moderate haemorrhagic fever with renal syndrome and is transmitted by the bank vole (myodes glareolus). there has been a high cumulative incidence of recorded human cases in south-eastern germany since 2004 when the region was first recognized as being endemic for puuv. as the area is well known for outdoor recreation and the bavarian forest national park (bfnp) is located in the region, the increasing numbers of recorded cases are of concern. to ...201425341661
severe thrombocytopenia in hantavirus-induced nephropathia epidemica.nephropathia epidemica is a milder form of hemorrhagic fever with renal syndrome, caused by puumala virus. the clinical picture is characterized by a rapid loss of renal function (acute kidney injury) and thrombocytopenia. the purpose of the current analysis was to compare the clinical course of patients presenting with or without severe thrombocytopenia. in 47 out of 456 patients with acute nephropathia epidemica, the nadir count of thrombocytes was available for the acute course of the disease ...201525380569
the importance of bank vole density and rainy winters in predicting nephropathia epidemica incidence in northern sweden.pathogenic hantaviruses (family bunyaviridae, genus hantavirus) are rodent-borne viruses causing hemorrhagic fever with renal syndrome (hfrs) in eurasia. in europe, there are more than 10,000 yearly cases of nephropathia epidemica (ne), a mild form of hfrs caused by puumala virus (puuv). the common and widely distributed bank vole (myodes glareolus) is the host of puuv. in this study, we aim to explain and predict ne incidence in boreal sweden using bank vole densities. we tested whether the num ...201425391132
nk cell activation in human hantavirus infection explained by virus-induced il-15/il15rα expression.clinical infection with hantaviruses cause two severe acute diseases, hemorrhagic fever with renal syndrome (hfrs) and hantavirus pulmonary syndrome (hps). these diseases are characterized by strong immune activation, increased vascular permeability, and up to 50% case-fatality rates. one prominent feature observed in clinical hantavirus infection is rapid expansion of natural killer (nk) cells in peripheral blood of affected individuals. we here describe an unusually high state of activation of ...201425412359
[nephropathy due to puumala hantavirus].hemorrhagic fever with renal syndrome (hfrs) is due to an infection by the virus of the hantavirus genus. rodent hosts of hantavirus are present in restricted areas in france; consequently, there are ecological niches and microepidemics of human hantavirus infections. a hfrs case was diagnosed in the paris region. the 11-year-old child had an acute debut fever-persistent despite antipyretic medication-asthenia, headache, abdominal pain, myalgia, thrombocytopenia, as well as renal failure with pr ...201425449445
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 manuscript 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 increa ...201425483486
severe puumala virus infection in a patient with a lymphoproliferative disease treated with icatibant.early identification of patients at risk of a severe course of hantaviral disease and lack of effective medication represent a global challenge in the treatment of this emerging infection. we describe a 67-year-old female patient with a history of chronic lymphoproliferative disease involving the spleen and an extremely severe acute puumala hantavirus infection. she was treated with the bradykinin receptor antagonist icatibant and recovered. she is the second patient with a spleen abnormality an ...201525496418
rapid homogeneous immunoassay based on time-resolved förster resonance energy transfer for serodiagnosis of acute hantavirus infection.we recently introduced a homogeneous immunoassay based on time-resolved förster resonance energy transfer (tr-fret) elicited by fluorophore-labeled antigen and fluorophore-labeled protein l, bound by an immunoglobulin. as the first clinical application, we employ this approach (lfret) in serodiagnosis of puumala hantavirus (puuv) infection. a reference panel containing serum from individuals with acute (n = 21) or past (n = 17) puuv infection and from puuv-seronegative individuals (n = 20) was u ...201525520445
polyuria in hantavirus infection reflects disease severity and is associated with prolonged hospital stay: a systematic analysis of 335 patients from southern germany.background/aims: puumala virus (puuv) infection leads to nephropathia epidemica (ne), especially in endemic areas in central europe. the clinical course of ne is characterized by acute kidney injury (aki) with thrombocytopenia followed by polyuria to a different degree. the prevalence of polyuria and its associated risk factors have not been reported in a large cohort of ne patients. methods: clinical and laboratory data during the acute phase of the disease were obtained from the medical report ...201425531933
clinical course and long-term outcome of hantavirus-associated nephropathia epidemica, germany.human infection with puumala virus (puuv), the most common hantavirus in central europe, causes nephropathia epidemica (ne), a disease characterized by acute kidney injury and thrombocytopenia. to determine the clinical phenotype of hantavirus-infected patients and their long-term outcome and humoral immunity to puuv, we conducted a cross-sectional prospective survey of 456 patients in germany with clinically and serologically confirmed hantavirus-associated ne during 2001-2012. prominent clinic ...201525533268
complete genome of a puumala virus strain from central europe.puumala virus (puuv) is one of the predominant hantavirus species in europe causing mild to moderate cases of haemorrhagic fever with renal syndrome. parts of lower saxony in north-western germany are endemic for puuv infections. in this study, the complete puuv genome sequence of a bank vole-derived tissue sample from the 2007 outbreak was determined by a combined primer-walking and rna ligation strategy. the s, m and l genome segments were 1,828, 3,680 and 6,550 nucleotides in length, respecti ...201525543297
[variants of the immunoreactivity and infectious process in bank vole (myodes glareolus) experimentally infected with the hantavirus puumala (puuv)].as a result of a longitudinal study of the puumala hantavirus (puuv) in the experimentally infected bank voles (myodes glareolus), we revealed three groups of the voles differing in the immunoreactivity and viral antigen concentration in the organs. the close correlation between these parameters suggested the existence of various mechanisms of the hantavirus persistence in the host.201625549467
climate variability and the occurrence of human puumala hantavirus infections in europe: a systematic review.hantaviruses are distributed worldwide and are transmitted by rodents. in europe, the infection usually manifests as a mild form of haemorrhagic fever with renal syndrome (hfrs) known as nephropathia epidemica (ne), which is triggered by the virus species puumala. its host is the bank vole (myodes glareolus). in the context of climate change, interest in the role of climatic factors for the disease has increased. a systematic review was conducted to investigate the association between climate va ...201525557350
concomitant leptospirosis-hantavirus co-infection in acute patients hospitalized in sri lanka: implications for a potentially worldwide underestimated problem.two global (re-)emerging zoonoses, leptospirosis and hantavirus infections, are clinically indistinguishable. thirty-one patients, hospitalized in sri lanka for acute severe leptospirosis, were after exclusion of other potentially involved pathogens, prospectively screened with igm elisa for both pathogens. of these, nine (29·0%) were positive for leptospirosis only, one (3·2%) for hantavirus only, seven (22·5%) for both pathogens concomitantly, whereas 13 (41·9%) remained negative for both. mor ...201525582980
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
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
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
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
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
[puumala hantavirus infection in isère: geographic extension of this zoonosis in france]. 201525840563
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
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
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
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