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[cloning and expression of the nucleoprotein gene of puumala-like virus].in order to detect hokkaido virus (hokv), a recombinant baculovirus containing the nucleoprotein (np) gene of hokv was constructed, and then the np was expressed in insect cell.200919565881
the first established focus of hantavirus infection in poland, 2007.the first hantavirus infection outbreak in poland (with different seroetiology) was identified between august-december 2007. thirteen cases were reported in southeast poland: 12 cases in the carpathians bordering with northeast slovakia, mainly in the forested areas of the bieszczady mountains, and one case approximately 100-120 kilometres north from the others, in the adjacent sub-carpathian region. four additional cases of past infection were identified retrospectively, based on the presence o ...200919572481
hantaviruses and climate change.most hantaviruses are rodent-borne emerging viruses. they cause two significant human diseases, haemorrhagic fever with renal syndrome in asia and europe, and hantavirus cardiopulmonary syndrome in the americas. very recently, several novel hantaviruses with unknown pathogenic potential have been identified in africa and in a variety of insectivores (shrews and a mole). because there is very limited information available on the possible impact of climate change on all of these highly dangerous p ...200919604276
risk factors for human infection with puumala virus, southwestern germany.puumala virus, which causes nephropathia epidemica (ne), is the most prevalent hantavirus in germany; bank voles serve as the main reservoir. during 2001-2007, most ne cases reported from germany occurred in the southwestern state of baden-württemberg. we investigated the influence of bank vole habitats (beech forest, seed plants), vole food supply (beechnut mast), climate factors (winter and spring temperatures), and human population density on spatial and temporal occurrence of ne cases in bad ...200919624917
[serological characteristics of hantaviruses from clinical specimens analyzed in 1998-2008 in the department of virology, public health institute, ostrava].in 1998 - 2008, serum samples from 464 patients, predominantly residents of the moravia-silesian region, were examined in the department of virology, public health institute in ostrava, using enzyme-linked immunosorbent assay (elisa) for the detection of specific anti-hantavirus antibodies. seropositivity was ascertained in 41 persons (8.8%). more patients tested seropositive against hantaan virus (24, i.e. 58.5%) than against puumala virus (13, i.e. 31.7%). four persons were reactive against bo ...200919750821
inhibition of tnf-alpha-induced activation of nf-kappab by hantavirus nucleocapsid proteins.hantaviruses cause two human diseases thought to be immune-mediated: hemorrhagic fever with renal syndrome (hfrs) and hantavirus pulmonary syndrome (hps). we recently reported that the nucleocapsid (n) protein of hfrs-causing hantaan virus (htnv) inhibits tumor necrosis factor-alpha (tnf-alpha) activation of nuclear factor-kappab (nf-kappab). here we measured the ability of other hantaviral n proteins to similarly interfere with the inflammatory process of tnf-alpha. we found that like htnv n, t ...200919751407
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
molecular diagnostics of hemorrhagic fever with renal syndrome during a dobrava virus infection outbreak in the european part of russia.a large outbreak of hemorrhagic fever with renal syndrome (hfrs) occurred in the winter of 2006-2007 in a region southeast of moscow in central european russia. of the 422 patients with hfrs investigated in this study, 58 patients were found to be infected by puumala virus, whereas as many as 364 were infected by dobrava-belgrade virus (dobv). early serum samples from 10 dobv-infected patients were used for nucleic acid amplification, which was successful for 5 patients. molecular analyses demon ...200919828747
co-circulation of three pathogenic hantaviruses: puumala, dobrava, and saaremaa in hungary.hantaviruses (bunyaviridae) cause hemorrhagic fever with renal syndrome (hfrs) in eurasia and hantavirus (cardio)pulmonary syndrome (hcps) in the americas. hfrs is caused by hantaan virus (htnv), seoul virus (seov), dobrava virus (dobv), saaremaa virus (saav), and puumala virus (puuv). of those, only htnv is not present in europe. in recent years, hantaviruses, described in other parts of europe, were also detected at various locations in hungary. to study the genetic properties of hungarian han ...200919856478
defective particles can lead to underestimated antibody titers in virus neutralization tests.stocks of rna viruses often contain divergent mixtures of infectious and defective particles (dps). since the surface of both particles share the same immunoreactivity, differing ratios of these particles in stocks used for virus neutralization tests might alter the results. here the impact of such off-target effects were measured.200919864921
puumala virus reference strain for hantavirus serodiagnosis in france. 201019885688
epidemiological study of hantavirus infection in the samara region of european russia.european russia is a highly endemic area of hemorrhagic fever with renal syndrome (hfrs), a rodent-borne zoonotic disease, caused by hantaviruses. in total, 145 small mammals of four species (myodes glareolus, apodemus flavicollis, a. agrarius, and a. uralensis) were trapped in the samara region of european russia in august 2005 and examined for the presence of hantavirus (hv). anti-hv antibodies were found in six of 68 (8.8%) m. glareolus and in one of 19 (5.3%) a. flavicollis by indirect immun ...200920046023
milder winters in northern scandinavia may contribute to larger outbreaks of haemorrhagic fever virus.the spread of zoonotic infectious diseases may increase due to climate factors such as temperature, humidity and precipitation. this is also true for hantaviruses, which are globally spread haemorrhagic fever viruses carried by rodents. hantaviruses are frequently transmitted to humans all over the world and regarded as emerging viral diseases. climate variations affect the rodent reservoir populations and rodent population peaks coincide with increased number of human cases of hantavirus infect ...200920052429
puumala hantavirus and myodes glareolus in northern europe: no evidence of co-divergence between genetic lineages of virus and host.the genus hantavirus (family bunyaviridae) includes negative-strand rna viruses that are carried by persistently infected rodent and insectivore species. puumala virus (puuv), carried by bank voles (myodes glareolus), is a pathogenic hantavirus that causes outbreaks of mild haemorrhagic fever with renal syndrome across europe. in northern europe, puuv is represented by several genetic lineages that are maintained by distinct phylogroups of bank voles. the present study describes sequences of new ...201020107019
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
different cross-reactivity of human and rodent sera to tula virus and puumala virus.tula virus (tulv) and puumala virus (puuv) are hantaviruses carried by the bank vole (myodes glareolus) and european common vole (microtus arvalis), respectively. puuv is a causative agent of hemorrhagic fever with renal syndrome (hfrs), while tulv is thought to be apathogenic to humans. the n-terminal regions of the n proteins from tulv and puuv were expressed and applied as enzyme-linked immunosorbent assay (elisa) antigens. colonized japanese grass voles (microtus montebelli) and balb/c mice ...201020116854
the occurrence of hemorrhagic fever with renal syndrome in southern parts of bosnia and herzegovina.bosnia and herzegovina (b&h) has been known as an endemic region for hemorrhagic fever with renal syndrome (hfrs) for over 50 years. multiple epidemics of this disease have been registered so far, especially in endemic parts of central and northeastern bosnia, as well as the sarajevo region. seroepidemiological investigations demonstrate naturalization of hantaviruses and their wide spread in b&h. however, there are no studies from the southern areas of b&h, and endemic foci of this disease are ...200920120399
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
headache and low platelets in a patient with acute leukemia. 201020308016
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
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
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
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
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
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
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
hantavirus infections in fluctuating host populations: the role of maternal antibodies.infected females may transfer maternal antibodies (matabs) to their offspring, which may then be transiently protected against infections the mother has encountered. however, the role of maternal protection in infectious disease dynamics in wildlife has largely been neglected. here, we investigate the effects of puumala hantavirus (puuv)-specific matabs on puuv dynamics, using 7 years' data from a cyclic bank vole population in finland. for the first time to our knowledge, we partition seroposit ...201020591866
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
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
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
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
[nephropathia epidemica: data on voles indicate new, extensive outbreak]. 201020812561
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
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
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
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
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
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
cyclic hantavirus epidemics in humans--predicted by rodent host dynamics.wildlife-originated zoonotic diseases are a major contributor to emerging infectious diseases. hantaviruses cause thousands of human disease cases annually worldwide, and understanding and predicting human hantavirus epidemics still poses unsolved challenges. here we studied the three-level relationships between the human disease nephropathia epidemica (ne), its etiological agent puumala hantavirus (puuv) and the rodent host of the virus, the bank vole (myodes glareolus). a large and long-term d ...200921352757
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
[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
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
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
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
transient hypopituitarism in a patient with nephropathia epidemica.involvement of the pituitary gland is only rarely observed in hantavirus infection. this report describes the case of a patient who had transient hypopituitarism requiring hormonal replacement therapy due to hypophysitis as a result of puumala virus infection. mri studies revealed oedematous swelling of the gland as a morphological correlate. this report provides new evidence that hypopituitarism can be a serious complication in puumala virus infection and highlights the clinical implications of ...200921691389
a new permanent cell line derived from the bank vole (myodes glareolus) as cell culture model for zoonotic viruses.abstract:201121729307
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
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
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
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
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
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
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
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
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
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
acute human inkoo and chatanga virus infections, finland.inkoo virus (inkv) and chatanga virus (chatv), which are circulating in finland, are mosquitoborne california serogroup orthobunyaviruses that have a high seroprevalence among humans. worldwide, inkv infection has been poorly described, and chatv infection has been unknown. using serum samples collected in finland from 7,961 patients suspected of having viral neurologic disease or puumala virus infection during the summers of 2001-2013, we analyzed the samples to detect california serogroup infe ...201627088268
inhibition of the hantavirus fusion process by predicted domain iii and stem peptides from glycoprotein gc.hantaviruses can cause hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome in humans. to enter cells, hantaviruses fuse their envelope membrane with host cell membranes. previously, we have shown that the gc envelope glycoprotein is the viral fusion protein sharing characteristics with class ii fusion proteins. the ectodomain of class ii fusion proteins is composed of three domains connected by a stem region to a transmembrane anchor in the viral envelope. these fusion protein ...201627414047
crystal structure of glycoprotein c from a hantavirus in the post-fusion conformation.hantaviruses are important emerging human pathogens and are the causative agents of serious diseases in humans with high mortality rates. like other members in the bunyaviridae family their m segment encodes two glycoproteins, gn and gc, which are responsible for the early events of infection. hantaviruses deliver their tripartite genome into the cytoplasm by fusion of the viral and endosomal membranes in response to the reduced ph of the endosome. unlike phleboviruses (e.g. rift valley fever vi ...201627783673
molecular diagnosis of hemorrhagic fever with renal syndrome caused by puumala virus.rodent-borne hantaviruses cause two severe acute diseases: hemorrhagic fever with renal syndrome (hfrs) in eurasia, and hantavirus pulmonary syndrome (hps; also called hantavirus cardiopulmonary syndrome [hcps]) in the americas. puumala virus (puuv) is the most common causative agent of hfrs in europe. current routine diagnostic methods are based on serological analyses and can yield inconclusive results. hantavirus-infected patients are viremic during the early phase of disease; therefore, dete ...201626962084
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
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
clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (hfrs) caused by hantaviruses puumala and dobrava-belgrade genotype sochi.hantavirus disease belongs to the emerging infections. the clinical picture and severity of infections differ between hantavirus species and may even vary between hantavirus genotypes. the mechanisms that lead to the broad variance of severity in infected patients are not completely understood. host- and virus-specific factors are considered.201627842513
hmgb1 is a potential biomarker for severe viral hemorrhagic fevers.hemorrhagic fever with renal syndrome (hfrs) and crimean-congo hemorrhagic fever (cchf) are common representatives of viral hemorrhagic fevers still often neglected in some parts of the world. infection with dobrava or puumala virus (hfrs) and crimean-congo hemorrhagic fever virus (cchfv) can result in a mild, nonspecific febrile illness or as a severe disease with hemorrhaging and high fatality rate. an important factor in optimizing survival rate in patients with vhf is instant recognition of ...201627348219
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
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