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
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
[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
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
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
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
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
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
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
[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
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
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
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
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
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
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
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
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
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
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
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
[epidemic nephropathy due to puumala virus: a case report]. 201424969100
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
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
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
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
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
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
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
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
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
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
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
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
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
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
clinical presentation of puumala virus infections in southern austria in the peak year 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
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
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
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
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
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
[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
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
[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
[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
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
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
puumala virus outbreak in western thuringia, germany, 2010: epidemiology and strain 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
[what the practising veterinarian should know about puumala virus]. 201323367591
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
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
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
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
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
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
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
[renal failure in a couple caused by puumala hantavirus].in scandinavia puumala hantavirus causes nephropathia epidemica (ne), characterised by an acute debut of fever, headache, increasing back and abdominal pain, thrombocytopenia, increasing azotemia parameters, as well as microscopic haematuria and mild proteinuria. in some cases transitory myopia can be found. the diagnosis is made with a relevant clinical history and serology, and in most cases a kidney biopsy is not necessary. there is a risk of missing cases of ne as in this case, where a coupl ...201223121909
[hantavirus infection as the cause of haemorrhagic fever with renal syndrome].hantavirus is an rna virus that can cause potentially fatal pulmonary and renal diseases in humans. infections with hantaviruses occur through inhalation of aerosol from rodent faeces, urine or saliva. the predominant virus type in denmark is the puumala virus, which causes the mildest form of haemorrhagic fever with renal syndrome, the so-called nephropathia epidemica (ne) with good prognosis (mortality 0.1-0.4%). the incidence of hantavirus-infection in denmark is about ten cases a year. the d ...201223121908
modelling zoonotic diseases in humans: comparison of methods for hantavirus in sweden.because their distribution usually depends on the presence of more than one species, modelling zoonotic diseases in humans differs from modelling individual species distribution even though the data are similar in nature. three approaches can be used to model spatial distributions recorded by points: based on presence/absence, presence/available or presence data. here, we compared one or two of several existing methods for each of these approaches. human cases of hantavirus infection reported by ...201222984887
multiple synchronous outbreaks of puumala virus, germany, investigate 2,017 cases of hantavirus disease in germany, we compared 38 new patient-derived puumala virus rna sequences identified in 2010 with bank vole-derived small segment rna sequences. the epidemic process was driven by outbreaks of 6 puumala virus clades comprising strains of human and vole origin. each clade corresponded to a different outbreak region.201222932394
blurred vision and myopic shift in puumala virus infections are independent of disease severity.puumala virus infection causes epidemic nephropathia (ne), a certain type of haemorrhagic fever with renal syndrome (hfrs). myopic shift is considered a pathognomonic sign of ne and hfrs but rates of ocular involvement vary. the aim of the study was to evaluate whether clinical and laboratory findings are associated with ophthalmic involvement in ne in austria. we found that blurred vision and myopic shift are frequent in puumala virus infections in austria but are independent of disease severit ...201222909300
signs of general inflammation and kidney function are associated with the ocular features of acute puumala hantavirus infection.puumala hantavirus (puuv) causes nephropathia epidemica (ne), a type of viral haemorrhagic fever with renal syndrome (hfrs). this febrile infection may affect the kidneys, central nervous system (cns), and the eye. acute illness is associated with increased tissue permeability and tissue oedema, and many patients experience reduced vision. the aim of this study was to explore the physiological events associated with the ocular features of acute ne.201222830303
resequencing of the puumala virus strain sotkamo from the who arbovirus collection.rna viruses exhibit a high mutation rate as the rna-dependent rna polymerase lacks proofreading and repair capabilities. it is known that serial passaging on cell culture leads to virus adaptation. puumala virus (puuv) strain sotkamo is the prototype virus for the low-pathogenic hantavirus puumala, family bunyaviridae. a full-length sequence of the strain sotkamos tripartite genome was made available more than 15 years ago, after at least 15 passages on vero e6 cells. a distinct sample from the ...201222798055
environmental change and disease dynamics: effects of intensive forest management on puumala hantavirus infection in boreal bank vole populations.intensive management of fennoscandian forests has led to a mosaic of woodlands in different stages of maturity. the main rodent host of the zoonotic puumala hantavirus (puuv) is the bank vole (myodes glareolus), a species that can be found in all woodlands and especially mature forests. we investigated the influence of forest age structure on puuv infection dynamics in bank voles. over four years, we trapped small mammals twice a year in a forest network of different succession stages in norther ...201222745755
cross-sectional survey of the seroprevalence of puumala hantavirus in austria.the prevalence of puumala hantavirus infections in austria and the occupational exposure of military personnel to this virus were assessed in 2009 in an exploratory nationwide cross-sectional seroprevalence survey in 526 healthy individuals, of which 222 were soldiers and 304 were civilians. in addition, information on possible risk factors for hantavirus exposure, including previous foreign military assignments, residential area, occupational animal contact, and regular outdoor activities, was ...201222607075
the degree of leukocytosis and urine gata-3 mrna levels are risk factors for severe acute kidney injury in puumala virus nephropathia epidemica.puumala hantavirus (puuv) infection, also known as nephropathia epidemica, is the most common cause of hemorrhagic fever with renal syndrome (hfrs) in europe. the pathogenesis of puuv nephropathia epidemica is complex and multifactorial, and the risk factors for severe acute kidney injury (aki) during acute puuv infection are not well defined. we conducted a prospective study of hospitalized patients with puuv infection in tampere, finland to identify acute illness risk factors for hfrs severity ...201222523590
hyperintense lesion in the corpus callosum associated with puumala hantavirus infection. 201222349863
plasma cell-free dna levels are elevated in acute puumala hantavirus infection.puumala hantavirus (puuv) causes a hemorrhagic fever with renal syndrome called nephropathia epidemica (ne). the aim of the present study was to evaluate plasma cell-free dna (cf-dna) levels and urinary cf-dna excretion in acute ne as well as their associations with the severity of the disease.201222347483
[from mice to men - insights from the hantavirus epidemic in 2010].with 2017 notified cases the largest hantavirus epidemic in germany has occurred in 2010. we report on two interesting cases illustrating the wide range of the individual clinical course and the diagnostic problems in hantavirus disease. the first patient was a seriously ill 44-year-old man who needed dialysis after an onset of flu-like symptoms with oliguria. an initially negative result of a hantavirus serology focused attention on rapidly progressive glomerulonephritis. the second patient, a ...201222318843
serogrouping and seroepidemiology of north european hantaviruses using a novel broadly targeted synthetic nucleoprotein antigen array.introduction: hantaviruses are globally distributed zoonotic pathogens. great diversity and high antigenic cross-reactivity makes diagnosis by traditional methods cumbersome. materials and methods: 'megapeptides', 119-120-mers from the amino terminus of the nucleoprotein of 16 hantaviruses, representing the four major branches of the hantavirus phylogenetic tree, were utilized in a novel igg-based hantavirus suspension multiplex immunoassay (hsmia) for detection of past hantavirus infections in ...201728815001
deregulation of levels of angiopoietin-1 and angiopoietin-2 is associated with severe courses of hantavirus infection.hantavirus disease is characterized by endothelial dysfunction. angiopoietin-1 (ang-1) and its antagonist angiopoietin-2 (ang-2) play a key role in the control of capillary permeability. ang-1 is responsible for maintenance of cell-to-cell contacts whereas ang-2 destabilizes monolayers. an imbalance of ang-1 and ang-2 levels results in enhanced permeability and capillary leakage.201728734140
country-wide seroprevalence studies on crimean-congo hemorrhagic fever and hantavirus infections in general population of bulgaria.crimean-congo hemorrhagic fever (cchf) and hantavirus infections are the two viral hemorrhagic fevers spread in europe. to test actual circulation of cchf virus (cchfv) and hantaviruses in bulgaria, we conducted country-wide seroepidemiological studies. serum samples were collected prospectively from 1500 residents of all 28 districts in bulgaria. cchfv seroprevalence of 3.7% was revealed. anamnesis for tick bites, contact with livestock, age over 40 years and residency in haskovo district were ...201728561377
structural transitions of the conserved and metastable hantaviral glycoprotein envelope.hantaviruses are zoonotic pathogens with a near-global distribution that can cause severe hemorrhagic fever and pulmonary syndrome. the outer membrane of the hantavirus envelope displays a lattice of two glycoproteins, gn and gc, which orchestrate host cell recognition and entry. here, we describe the crystal structure of the gn glycoprotein ectodomain from the asiatic hantaan virus (htnv), the most prevalent pathogenic hantavirus. structural overlay analysis reveals that the htnv gn fold is hig ...201728835498
dampening of population cycles in voles affects small mammal community structure, decreases diversity, and increases prevalence of a zoonotic disease.long-term decline and depression of density in cyclic small rodents is a recent widespread phenomenon. these observed changes at the population level might have cascading effects at the ecosystem level. here, we assessed relationships between changing boreal landscapes and biodiversity changes of small mammal communities. we also inferred potential effects of observed community changes for increased transmission risk of puumala virus (puuv) spread, causing the zoonotic disease nephropatica epide ...201728770071
haematuria is a marker for the severity of acute kidney injury but does not associate with thrombocytopenia in acute puumala hantavirus infection.puumala hantavirus (puuv) causes haemorrhagic fever with renal syndrome characterized by thrombocytopenia, capillary leakage and acute kidney injury (aki) with proteinuria and haematuria. although the typical histologic lesion is acute tubulointerstitial nephritis, the amount of glomerular proteinuria predicts the severity of upcoming aki. here, we studied the associations of haematuria and proteinuria with the severity of emerging aki, thrombocytopenia and markers of coagulation and fibrinolysi ...201728762841
spatial prediction and validation of zoonotic hazard through micro-habitat properties: where does puumala hantavirus hole - up?to predict the risk of infectious diseases originating in wildlife, it is important to identify habitats that allow the co-occurrence of pathogens and their hosts. puumala hantavirus (puuv) is a directly-transmitted rna virus that causes hemorrhagic fever in humans, and is carried and transmitted by the bank vole (myodes glareolus). in northern sweden, bank voles undergo 3-4 year population cycles, during which their spatial distribution varies greatly.201728747170
phylogenetic analysis of puumala virus strains from central europe highlights the need for a full-genome perspective on hantavirus evolution.puumala virus (puuv), carried by bank voles (myodes glareolus), is the medically most important hantavirus in central and western europe. in this study, a total of 523 bank voles (408 from germany, 72 from slovakia, and 43 from czech republic) collected between the years 2007-2012 were analyzed for the presence of hantavirus rna. partial puuv genome segment sequences were obtained from 51 voles. phylogenetic analyses of all three genome segments showed that the newfound strains cluster with othe ...201728664467
human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways.hantaviruses infect humans via inhalation of virus-contaminated rodent excreta. infection can cause severe disease with up to 40% mortality depending on the viral strain. the virus primarily targets the vascular endothelium without direct cytopathic effects. instead, exaggerated immune responses may inadvertently contribute to disease development. mononuclear phagocytes (mnps), including monocytes and dendritic cells (dcs), orchestrate the adaptive immune responses. since hantaviruses are transm ...201728640917
circulation and diagnostics of puumala virus in norway: nephropatia epidemica incidence and rodent population dynamics.hantaviruses pose a public health concern worldwide causing haemorrhagic fever with renal syndrome (hfrs) and hantavirus pulmonary syndrome (hps). puumala virus (puuv) is the most prevalent hantavirus in central and northern europe, and causes a mild form of hfrs, also known as nephropathia epidemica (ne). in nature, the main host of puuv is the bank vole (myodes glareolus), and transmission to humans occurs through inhalation of aerosols from rodent excreta. nephropathia epidemica is particular ...201728585306
modelling human puumala hantavirus infection in relation to bank vole abundance and masting intensity in the netherlands.this paper deals with modelling the relationship between human puumala hantavirus (puuv) infection, the abundance and prevalence of infection of the host (the bank vole), mast, and temperature. these data were used to build and parametrise generalised regression models, and parametrise them using datasets on these factors pertaining to the netherlands. the performance of the models was assessed by considering their predictive power. models including mast and monthly temperature performed well, a ...201728567209
experimental infections of wild bank voles (myodes glareolus) from nephropatia epidemica endemic and non-endemic regions revealed slight differences in puumala virological course and immunological europe, the occurrence of nephropathia epidemica (ne), a human disease caused by puumala virus (puuv), exhibits considerable geographical heterogeneity despite the continuous distribution of its reservoir, the bank vole myodes glareolus. to better understand the causes of this heterogeneity, wild voles sampled in two adjacent ne endemic and non-endemic regions of france were infected experimentally with puuv. the responses of bank voles to puuv infection, based on the levels of anti-puuv igg ...201728396283
gastrointestinal tract as entry route for hantavirus infection.background: hantaviruses are zoonotic agents that cause hemorrhagic fevers and are thought to be transmitted to humans by exposure to aerosolized excreta of infected rodents. puumala virus (puuv) is the predominant endemic hantavirus in europe. a large proportion of puuv-infected patients suffer from gastrointestinal symptoms of unclear origin. in this study we demonstrate that puuv infection can occur via the alimentary tract. methods: we investigated susceptibility of the human small intestina ...201728943870
delayed ifn type 1-induced antiviral state is a potential factor for hfrs severity.hantaviruses cause hemorrhagic fever with renal syndrome (hfrs) in europe and asia. interferon (ifn) responses play an important role in hfrs pathogenesis and it is known that the early ifnβ response is delayed by pathogenic hantaviruses. the clinical severity of hfrs caused by dobrava virus (dobv) and puumala virus (puuv) varies greatly and the aim of our study was to determine whether differences in early activation of the ifn type 1-induced antiviral state influence hfrs severity. peripheral ...201729281106
serological survey of hantavirus and flavivirus among wild rodents in central italy.hantaviruses are a group of zoonotic viruses carried by rodents. puumala virus (puuv) and dobrava virus (dobv) are the causative agents of human hantavirus infections in europe. knowledge about hantavirus circulation in italy is very scarce. west nile virus (wnv) and usutu virus (usuv) are emerging neuropathogenic flaviviruses, both endemic in most part of the italian territories. to monitor the circulation of puuv, dobv, wnv, and usuv in natural environment in central italy, we carried out sero ...201728953448
population-based seroprevalence of puumala hantavirus in finland: smoking as a risk factor.puumala hantavirus (puuv) causes hemorrhagic fever with renal syndrome in humans, that is an endemic disease in finland. we estimated the seroprevalence of puuv in finland and explored risk factors and disease associations by using unique survey data with health register linkage. a total of 2000 sera from a nationwide health survey from 2011, representative of the adult population, were screened for puuv igg by immunofluorescence assay. we performed statistical analysis adjusting for stratified ...201829310747
fatal puumala hantavirus disease: involvement of complement activation and vascular leakage in the pathobiology.the case-fatality rate of hantavirus disease depends strongly on the causative hantavirus, ranging from 0.1% to 40%. however, the pathogenesis is not fully understood, and at present no licensed therapies exist. we describe fatal cases caused by puumala hantavirus indicating involvement of complement activation and vascular leakage.201729255728
risk of venous thromboembolism following hemorrhagic fever with renal syndrome: a self-controlled case series study.bleeding is associated with viral hemorrhagic fevers; however, thromboembolic complications have received less attention. hemorrhagic fever with renal syndrome (hfrs) is a mild viral hemorrhagic fever caused by puumala hantavirus. we previously identified hfrs as a risk factor for myocardial infarction and stroke, but the risk for venous thromboembolism (vte), including deep vein thrombosis (dvt) and pulmonary embolism (pe), is unknown.201829020303
acute hantavirus infection presenting as haemolytic-uraemic syndrome (hus): the importance of early clinical diagnosis.the european prototype of hantavirus, puumala virus (puuv), isolated from a common wild rodent, the bank vole (myodes glareolus), causes nephropathia epidemica (ne). ne can perfectly mimic haemolytic-uraemic syndrome (hus), progressing from an aspecific flu-like syndrome to acute kidney injury with thrombocytopaenia, and presenting with some signs of haemolytic anaemia and/or coagulopathy. moreover, both ne and hus can occur in local outbreaks. we report an isolated case of ne, initially referre ...201828986730
diminished coagulation capacity assessed by calibrated automated thrombography during acute puumala hantavirus infection.: coagulation abnormalities are associated with puumala-virus-induced hemorrhagic fever with renal syndrome (puuv-hfrs). we evaluated the coagulation capacity of plasma during acute puuv-hfrs by measuring thrombin generation using calibrated automated thrombography (cat). the study cohort comprised 27 prospectively collected, consecutive, hospital-treated patients with acute puuv infection. blood samples were drawn in the acute phase and at the control visit approximately 5 weeks later. to evalu ...201828968301
bank vole immunoheterogeneity may limit nephropatia epidemica emergence in a french non-endemic region.ecoevolutionary processes affecting hosts, vectors and pathogens are important drivers of zoonotic disease emergence. in this study, we focused on nephropathia epidemica (ne), which is caused by puumala hantavirus (puuv) whose natural reservoir is the bank vole, myodes glareolus. we questioned the possibility of ne emergence in a french region that is considered to be ne-free but that is adjacent to a ne-endemic region. we first confirmed the epidemiology of these two regions and we demonstrated ...201728931451
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