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Jukka Mustonen - One of the best experts on this subject based on the ideXlab platform.
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The pathogenesis of Nephropathia Epidemica: new knowledge and unanswered questions.
Antiviral research, 2013Co-Authors: Jukka Mustonen, Satu Mäkelä, Tuula K. Outinen, Outi Laine, Juulia Jylhävä, Petteri Arstila, Mikko Hurme, Antti VaheriAbstract: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: interleukin-6, pentraxin-3, C-reactive protein, indoleamine 2,3-dioxygenase, cell-free DNA, soluble urokinase-type plasminogen activator, GATA-3 and Mac-2 binding protein. The role of cytokines, vascular endothelial growth hormone, complement, bradykinin, cellular immune response and other mechanisms in the pathogenesis of NE as well as host genetic factors will be discussed. Finally therapeutic aspects and directions for further research will be handled.
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The degree of leukocytosis and urine GATA-3 mRNA levels are risk factors for severe acute kidney injury in Puumala virus Nephropathia Epidemica.
PloS one, 2012Co-Authors: Daniel H. Libraty, Satu Mäkelä, Antti Vaheri, Francis A. Ennis, Mikko Hurme, Jennifer Vlk, Jukka MustonenAbstract: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. Serial daily blood and urine samples were collected throughout acute illness and at 2 week and 6 month convalescent visits. By univariate analyses, the maximum white blood cell count during acute illness was a risk factor for severe AKI. There were no significant associations between PUUV-induced AKI severity and platelet counts, C-reactive protein, or alanine aminotransferase levels. Maximum plasma interleukin (IL)-6, urine IL-6, and urine IL-8 concentrations were positively associated with PUUV-induced AKI. Finally, the maximum urinary sediment GATA-3 mRNA level was positively correlated with the peak fold-change in serum creatinine, regardless of AKI severity classification. By multivariate analyses, we found that the maximum levels of leukocytes and urinary sediment GATA-3 mRNA during acute illness were independent risk factors for severe PUUV-induced AKI. We have identified novel acute illness risk factors for severe PUUV-induced AKI.
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Pulmonary high-resolution computed tomography findings in Nephropathia Epidemica
European journal of radiology, 2011Co-Authors: Antti Paakkala, Heini Huhtala, Satu Mäkelä, Ritva Järvenpää, Jukka MustonenAbstract:Abstract 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 chest radiography. Atelectasis, pleural effusion, intralobular and interlobular septal thickening were the most common HRCT findings. Ground-glass opacification (GGO) was seen in 4 and hilar and mediastinal lymphadenopathy in 3 patients. Atelectasis and pleural effusion were also mostly seen in chest radiographs, other findings only in HRCT. Conclusion Almost every NE patient showed lung parenchymal abnormalities in HRCT. The most common findings of lung involvement in NE can be defined as accumulation of pleural fluid and atelectasis and intralobular and interlobular septal thickening, most profusely in the lower parts of the lung. As a novel finding, lymphadenopathy was seen in a minority, probably related to capillary leakage and overall fluid overload. Pleural effusion is not the prominent feature in other viral pneumonias, whereas intralobular and interlobular septal thickening are characteristic of other viral pulmonary infections as well. Lung parenchymal findings in HRCT can thus be taken not to be disease-specific in NE and HRCT is useful only for scientific purposes.
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The severity of Puumala hantavirus induced Nephropathia Epidemica can be better evaluated using plasma interleukin-6 than C-reactive protein determinations
BMC infectious diseases, 2010Co-Authors: Tuula K. Outinen, Antti Paakkala, Satu Mäkelä, Ilpo Ala-houhala, Mikko Hurme, Heini Sa Huhtala, Ilkka Pörsti, Jaana Syrjänen, Jukka MustonenAbstract:Background 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.
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Association of chest radiography findings with host-related genetic factors in patients with Nephropathia Epidemica.
Scandinavian journal of infectious diseases, 2007Co-Authors: Antti Paakkala, Heini Huhtala, Satu Mäkelä, Jukka Partanen, Mikko Hurme, Jukka MustonenAbstract:Different host genetic factors causes imbalance in the immune response. The purpose of this study was to establish whether pathological findings in chest radiography are related to the various host-related immunological factors in Nephropathia Epidemica (NE). Chest radiography findings, human leukocyte antigen (HLA) alleles B8, DR3, B27, genotypes of the genes of tumour necrosis factor alpha (TNFα), interleukin −1α (IL-1α), IL1β and IL-1 receptor antagonist (IL1RA) were analysed in 114 patients with serologically confirmed acute NE. Both the presence and severity of abnormal NE-related chest radiography findings associated with the B8, DR3 and TNF2 alleles are known to form a frequent extended HLA haplotype in European populations. Pleural effusion showed the strongest association with these genetic factors. Pathological findings in chest radiography are related to host genetic factors in NE. Pleural effusion is a sign of increased capillary permeability, an important feature in NE. Host genetic factors m...
Antti Vaheri - One of the best experts on this subject based on the ideXlab platform.
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The pathogenesis of Nephropathia Epidemica: new knowledge and unanswered questions.
Antiviral research, 2013Co-Authors: Jukka Mustonen, Satu Mäkelä, Tuula K. Outinen, Outi Laine, Juulia Jylhävä, Petteri Arstila, Mikko Hurme, Antti VaheriAbstract: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: interleukin-6, pentraxin-3, C-reactive protein, indoleamine 2,3-dioxygenase, cell-free DNA, soluble urokinase-type plasminogen activator, GATA-3 and Mac-2 binding protein. The role of cytokines, vascular endothelial growth hormone, complement, bradykinin, cellular immune response and other mechanisms in the pathogenesis of NE as well as host genetic factors will be discussed. Finally therapeutic aspects and directions for further research will be handled.
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The degree of leukocytosis and urine GATA-3 mRNA levels are risk factors for severe acute kidney injury in Puumala virus Nephropathia Epidemica.
PloS one, 2012Co-Authors: Daniel H. Libraty, Satu Mäkelä, Antti Vaheri, Francis A. Ennis, Mikko Hurme, Jennifer Vlk, Jukka MustonenAbstract: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. Serial daily blood and urine samples were collected throughout acute illness and at 2 week and 6 month convalescent visits. By univariate analyses, the maximum white blood cell count during acute illness was a risk factor for severe AKI. There were no significant associations between PUUV-induced AKI severity and platelet counts, C-reactive protein, or alanine aminotransferase levels. Maximum plasma interleukin (IL)-6, urine IL-6, and urine IL-8 concentrations were positively associated with PUUV-induced AKI. Finally, the maximum urinary sediment GATA-3 mRNA level was positively correlated with the peak fold-change in serum creatinine, regardless of AKI severity classification. By multivariate analyses, we found that the maximum levels of leukocytes and urinary sediment GATA-3 mRNA during acute illness were independent risk factors for severe PUUV-induced AKI. We have identified novel acute illness risk factors for severe PUUV-induced AKI.
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Anti-endothelial cell antibodies in Nephropathia Epidemica and other viral diseases.
Clinical and experimental immunology, 2008Co-Authors: A. G. Wangel, M. Brummer-korvenkontio, Mari Temonen, Antti VaheriAbstract:Increased capillary permeability is a central feature of the severe forms of haemorrhagic fever with renal syndrome (HFRS) and occurs also, though less frequently, in Nephropathia Epidemica (NE), one of the milder forms of this syndrome, caused by Puumala virus. We therefore searched for antiendothelial cell antibodies (AECA) in patients with NE and in those with other presumed or serologically proven acute viral illnesses. By enzyme immunoassay, using human umbilical vein endothelial cells (HUVEC) as the substrate, IgG class AECA were detected significantly more frequently in patients with NE and with influenza A than in Red Cross blood donors. A lesser degree of reactivity could be shown with a human alveolar cell carcinoma line and with human and mouse embryonic fibroblasts. Pretreatment of HUVEC with interferon-gamma (IFN-gamma), but not with IL-1 or tumour necrosis factor-alpha (TNF-alpha), increased their ability to bind IgG of sera from patients with NE and acute febrile illnesses. We conclude that, although AECA can be demonstrated in NE, they occur also in other acute viral illnesses and, unless cytopathic by a mechanism not shared by the AECA of these other illnesses, are unlikely to be casually related to the capillary leak in HFRS.
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Immune responses to Puumala virus infection and the pathogenesis of Nephropathia Epidemica
Microbes and infection, 2004Co-Authors: Masanori Terajima, Olli Vapalahti, Heather L. Van Epps, Antti Vaheri, Francis A. EnnisAbstract:Puumala virus, causative agent of a mild form of hemorrhagic fever with renal syndrome, also known as Nephropathia Epidemica, induces long-lasting humoral and cellular immunity in patients. The virus itself is not cytopathic, and the immune responses to the virus may be involved in the pathogenesis of the disease.
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High-producer allele of tumour necrosis factor-alpha is part of the susceptibility MHC haplotype in severe puumala virus-induced Nephropathia Epidemica
Scandinavian journal of infectious diseases, 1998Co-Authors: Mari Kanerva, Jukka Mustonen, Antti Vaheri, Jukka PartanenAbstract:The biallelic polymorphisms in the tumour necrosis factor-alpha (TNF-alpha) gene promoter region were studied in patients with Nephropathia Epidemica (NE). The rarer TNF2 allele, associated with a high TNF-alpha producer phenotype, was more frequently found in hospitalized NE patients (42%) than in healthy controls (15%; p=0.0064). The putative role of TNF2 as an independent risk factor for NE is discussed.
Satu Mäkelä - One of the best experts on this subject based on the ideXlab platform.
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The pathogenesis of Nephropathia Epidemica: new knowledge and unanswered questions.
Antiviral research, 2013Co-Authors: Jukka Mustonen, Satu Mäkelä, Tuula K. Outinen, Outi Laine, Juulia Jylhävä, Petteri Arstila, Mikko Hurme, Antti VaheriAbstract: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: interleukin-6, pentraxin-3, C-reactive protein, indoleamine 2,3-dioxygenase, cell-free DNA, soluble urokinase-type plasminogen activator, GATA-3 and Mac-2 binding protein. The role of cytokines, vascular endothelial growth hormone, complement, bradykinin, cellular immune response and other mechanisms in the pathogenesis of NE as well as host genetic factors will be discussed. Finally therapeutic aspects and directions for further research will be handled.
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The degree of leukocytosis and urine GATA-3 mRNA levels are risk factors for severe acute kidney injury in Puumala virus Nephropathia Epidemica.
PloS one, 2012Co-Authors: Daniel H. Libraty, Satu Mäkelä, Antti Vaheri, Francis A. Ennis, Mikko Hurme, Jennifer Vlk, Jukka MustonenAbstract: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. Serial daily blood and urine samples were collected throughout acute illness and at 2 week and 6 month convalescent visits. By univariate analyses, the maximum white blood cell count during acute illness was a risk factor for severe AKI. There were no significant associations between PUUV-induced AKI severity and platelet counts, C-reactive protein, or alanine aminotransferase levels. Maximum plasma interleukin (IL)-6, urine IL-6, and urine IL-8 concentrations were positively associated with PUUV-induced AKI. Finally, the maximum urinary sediment GATA-3 mRNA level was positively correlated with the peak fold-change in serum creatinine, regardless of AKI severity classification. By multivariate analyses, we found that the maximum levels of leukocytes and urinary sediment GATA-3 mRNA during acute illness were independent risk factors for severe PUUV-induced AKI. We have identified novel acute illness risk factors for severe PUUV-induced AKI.
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Pulmonary high-resolution computed tomography findings in Nephropathia Epidemica
European journal of radiology, 2011Co-Authors: Antti Paakkala, Heini Huhtala, Satu Mäkelä, Ritva Järvenpää, Jukka MustonenAbstract:Abstract 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 chest radiography. Atelectasis, pleural effusion, intralobular and interlobular septal thickening were the most common HRCT findings. Ground-glass opacification (GGO) was seen in 4 and hilar and mediastinal lymphadenopathy in 3 patients. Atelectasis and pleural effusion were also mostly seen in chest radiographs, other findings only in HRCT. Conclusion Almost every NE patient showed lung parenchymal abnormalities in HRCT. The most common findings of lung involvement in NE can be defined as accumulation of pleural fluid and atelectasis and intralobular and interlobular septal thickening, most profusely in the lower parts of the lung. As a novel finding, lymphadenopathy was seen in a minority, probably related to capillary leakage and overall fluid overload. Pleural effusion is not the prominent feature in other viral pneumonias, whereas intralobular and interlobular septal thickening are characteristic of other viral pulmonary infections as well. Lung parenchymal findings in HRCT can thus be taken not to be disease-specific in NE and HRCT is useful only for scientific purposes.
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The severity of Puumala hantavirus induced Nephropathia Epidemica can be better evaluated using plasma interleukin-6 than C-reactive protein determinations
BMC infectious diseases, 2010Co-Authors: Tuula K. Outinen, Antti Paakkala, Satu Mäkelä, Ilpo Ala-houhala, Mikko Hurme, Heini Sa Huhtala, Ilkka Pörsti, Jaana Syrjänen, Jukka MustonenAbstract:Background 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.
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Association of chest radiography findings with host-related genetic factors in patients with Nephropathia Epidemica.
Scandinavian journal of infectious diseases, 2007Co-Authors: Antti Paakkala, Heini Huhtala, Satu Mäkelä, Jukka Partanen, Mikko Hurme, Jukka MustonenAbstract:Different host genetic factors causes imbalance in the immune response. The purpose of this study was to establish whether pathological findings in chest radiography are related to the various host-related immunological factors in Nephropathia Epidemica (NE). Chest radiography findings, human leukocyte antigen (HLA) alleles B8, DR3, B27, genotypes of the genes of tumour necrosis factor alpha (TNFα), interleukin −1α (IL-1α), IL1β and IL-1 receptor antagonist (IL1RA) were analysed in 114 patients with serologically confirmed acute NE. Both the presence and severity of abnormal NE-related chest radiography findings associated with the B8, DR3 and TNF2 alleles are known to form a frequent extended HLA haplotype in European populations. Pleural effusion showed the strongest association with these genetic factors. Pathological findings in chest radiography are related to host genetic factors in NE. Pleural effusion is a sign of increased capillary permeability, an important feature in NE. Host genetic factors m...
Bo Settergren - One of the best experts on this subject based on the ideXlab platform.
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Clinical aspects of Nephropathia Epidemica (Puumala virus infection) in Europe: a review.
Scandinavian journal of infectious diseases, 2000Co-Authors: Bo SettergrenAbstract:Nephropathia Epidemica (NE) is a prevalent zoonosis throughout Europe and is caused by the Puumala type of hantavirus. The incidence of NE varies in a cyclic fashion, with peaks occurring every 3rd to 4th year, coinciding with peaks in vole populations. The clinical course of NE is generally milder than haemorrhagic fever with renal syndrome caused by hantaviruses in other parts of the world. Typically, NE has a sudden onset with fever, headache, backpain and gastrointestinal symptoms. However, severe complications, e.g. gastrointestinal haemorrhage, occur and fatal cases have been reported. Renal involvement is prominent and manifests as initial oliguria and later as marked polyuria. Tests of renal function show pronounced glomerular and tubular involvement. Vaccine against Puumala virus infection as well as specific treatment for NE are still lacking.
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Nephropathia Epidemica (hemorrhagic fever with renal syndrome) in children: clinical characteristics.
The Pediatric infectious disease journal, 1994Co-Authors: Clas Ahlm, Bo Settergren, Leif Gothefors, Per JutoAbstract:The clinical characteristics of serologically verified Nephropathia Epidemica, the Scandinavian form of hemorrhagic fever with renal syndrome, were studied in Swedish children who were < 15 years of age. In 1990 to 1992, 14 cases were prospectively followed. A retrospective survey during 1984 to 1990 disclosed another 18 cases. Among the 32 cases (20 boys, 12 girls, 3 to 15 years of age; median age, 11 years), the most common symptoms were fever (100%), headache (100%), abdominal pain (93%), vomiting (91%) and back pain (76%). Laboratory findings included elevated serum creatinine concentration (19 of 28) and thrombocytopenia (7 of 22). Urinalysis showed proteinuria (31 of 31 patients) and hematuria (24 of 30). Six children had mild hemorrhagic manifestations (epistaxis, metrorrhagia, and petechiae). No severe complications occurred. The clinical symptoms of children with Nephropathia Epidemica seem to be similar to those found among adult Nephropathia Epidemica cases.
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Local Host Response in the Lower Respiratory Tract in Nephropathia Epidemica
Scandinavian journal of infectious diseases, 1993Co-Authors: Mats Linderholm, Per Juto, Bo Settergren, Leif Bjermer, Göran Roos, Thomas Sandström, Arne TärnvikAbstract:Various lines of evidence suggest a respiratory route of transmission of Nephropathia Epidemica (NE). To study the response of the respiratory tract in NE, fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) was performed in 5 patients in the acute phase of the disease. Compared to a reference group of 15 healthy individuals, BAL fluid of NE patients contained significantly higher total numbers of cells (p < 0.05) and significantly higher numbers of lysozyme-positive macrophages (p < 0.01), CD8+ T cells (p < 0.01), and natural killer (NK) cells (p < 0.01). There was no significant difference in numbers of CD4+ T cells, B cells, or neutrophils. When blood samples of 16 patients were examined at various intervals after onset of NE, a significant decrease in the number of NK cells (p < 0.01) was found in the acute phase of the disease. The findings are compatible with the presence of a local host response in the lower respiratory tract to NE virus infection.
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Pulmonary involvement in Nephropathia Epidemica as demonstrated by computed tomography
Infection, 1992Co-Authors: Mats Linderholm, Arne Tärnvik, Bo Settergren, Å. BillströmAbstract:In a prospective study 19 adult patients with Nephropathia Epidemica were examined in the acute phase of disease with computed tomography (CT) of the lungs and conventional chest radiography. Infiltrates and/or pleural effusions were seen in ten of 19 patients. In two of the patients, abnormalities were disclosed only by CT. Patients with pathologic radiography findings had a more pronounced inflammatory response, as measured by C-reactive protein and leukocyte count, than did those with normal radiography findings. It is concluded that radiological evidence of pulmonary involvement is a common finding early in the course of Nephropathia Epidemica. The possibility that the lung may be a site of viral replication merits further investigation. Neunzehn erwachsene Patienten in der akuten Phase von Nephropathia Epidemica wurden mit computertomographischem (CT) und konventionellem Thoraxröntgen untersucht. Infiltrate und/oder Pleuraergüsse wurden bei 10/19 der Patienten beobachtet. Bei zwei Patienten konnten pathologische Befunde nur mit Hilfe der CT erhoben werden. Patienten mit pathologischen Radiogrammen wiesen, verglichen mit normalen radiographischen Befunden, eine ausgeprägtere Entzündungsreaktion gemessen durch C-reaktives Protein und Leukozytenzahlen auf. Unsere Resultate zeigen, daß in der Frühphase der Nephropathia Epidemica röntgenologisch häufig eine Lungenbeteiligung nachgewiesen werden kann. Die Möglichkeit, der Lunge als eine Lokalisation der viralen Replikation sollte weiter untersucht werden.
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Detection of Nephropathia Epidemica Virus RNA in Patient Samples Using a Nested Primer-Based Polymerase Chain Reaction
The Journal of infectious diseases, 1992Co-Authors: Olof Grankvist, Mats Linderholm, Arne Tärnvik, Per Juto, Bo Settergren, Clas Ahlm, Leif Bjermer, Göran WadellAbstract:A nested primer-based polymerase chain reaction was constructed for the detection of Puumala virus RNA in patient samples. Puumala virus RNA was detected in cells from the urinary and the respiratory tracts and in peripheral blood mononuclear cells of patients with Nephropathia Epidemica. After inoculation with Nephropathia Epidemica patient material on Vero E6 cells and propagation for nine passages (4 months), Puumala virus RNA was detected at every passage. Hybridization under high-stringency conditions revealed that the overall nucleotide homology between the different patient isolates and the prototype strain (Puumala) is high. Using cDNA from Hallnas B1 strain as a probe, hybridization occurred only under low-stringency conditions.
Per Juto - One of the best experts on this subject based on the ideXlab platform.
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Development of humoral cross-reactivity to the nucleocapsid protein of heterologous hantaviruses in Nephropathia Epidemica
FEMS immunology and medical microbiology, 1998Co-Authors: Fredrik Elgh, Mats Linderholm, Göran Wadell, Arne Tärnvik, Per JutoAbstract:A hantavirus infection is followed by a prominent antibody response to the viral nucleocapsid protein. Antibodies from patients infected with one hantavirus cross-react to varying degrees with the nucleocapsid protein of other viruses of the genus. We studied the cross-reactivity in serially obtained blood samples from 17 patients with Nephropathia Epidemica, a European form of hemorrhagic fever with renal syndrome caused by Puumala virus. Recombinant truncated nucleocapsid protein (aa 1–117) of Puumala virus and four other hantaviruses, Hantaan, Seoul, Dobrava and Sin Nombre viruses, were used as antigens in an indirect ELISA. In most patients, an IgG response to the Puumala virus derived recombinant protein was detected within 2–8 days of onset of disease, remained high for 2–5 months, and declined gradually within 2–3 years. All patients had IgG antibodies cross-reacting with the nucleocapsid protein of Sin Nombre virus. The ratio of the ELISA values obtained with Sin Nombre vs. Puumala virus protein as antigen increased with time after onset of disease. To a lesser extent, cross-reacting IgG antibodies also occurred to Hantaan, Seoul, and Dobrava virus antigens. In the acute phase of the disease, two patients showed IgG antibodies to one or more of these viruses whereas 2–5 months later, 11 of 16 patients had IgG antibodies to all three viruses. IgM and IgA responses to the nucleocapsid protein of Puumala virus were transitory and cross-reactivities were weak. In conclusion, after onset of Nephropathia Epidemica the IgG response to the Puumala virus nucleocapsid protein was associated with a gradually increasing cross-reactivity to the nucleocapsid protein of heterologous hantavirus. Our findings have implications for the interpretation of serological data, both in the diagnostics of Nephropathia Epidemica and in seroprevalence studies.
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Evaluation of serological methods for diagnosis of Puumala hantavirus infection (Nephropathia Epidemica).
Journal of clinical microbiology, 1997Co-Authors: Katarina Brus Sjölander, Fredrik Elgh, Per Juto, Olli Vapalahti, Bo Niklasson, A. Vaheri, Hannimari Kallio-kokko, M Hägglund, V Palmcrantz, Åke LundkvistAbstract:Nephropathia Epidemica (NE), Puumala (PUU) virus infection, is a febrile disease which is commonly associated with acute renal impairment. To differentiate NE from other acute febrile illnesses, a rapid and reliable serological diagnosis is important, and a number of different protocols have recently been introduced. In the present report we describe a comparative evaluation of six PUU virus immunoglobulin M (IgM) and seven IgG enzyme-linked immunosorbent assay (ELISA) protocols based on native, Escherichia coli-expressed, or baculovirus-expressed nucleocapsid protein (N). Neutralization and immunofluorescence assays were included for comparison. Equally high sensitivities and specificities were obtained with three mu-capture-based IgM ELISAs using native, baculovirus-expressed, and E. coli-expressed N antigens, respectively, and by an ELISA based on purified E. coli-expressed full-length N adsorbed to solid phase. The assays based on truncated amino-terminal N proteins, including a commercially available PUU virus IgM ELISA, all showed lower sensitivities. For detection of PUU virus-specific IgG, ELISAs based on monoclonal antibody-captured native or baculovirus-expressed N antigens showed optimal sensitivities and specificities, while the assays based on E. coli-expressed N did not detect all PUU virus IgG-positive serum samples. A commercially available PUU virus IgG ELISA based on E. coli-expressed amino-terminal N showed a significantly lower sensitivity than those of all other IgG assays.
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Nephropathia Epidemica (hemorrhagic fever with renal syndrome) in children: clinical characteristics.
The Pediatric infectious disease journal, 1994Co-Authors: Clas Ahlm, Bo Settergren, Leif Gothefors, Per JutoAbstract:The clinical characteristics of serologically verified Nephropathia Epidemica, the Scandinavian form of hemorrhagic fever with renal syndrome, were studied in Swedish children who were < 15 years of age. In 1990 to 1992, 14 cases were prospectively followed. A retrospective survey during 1984 to 1990 disclosed another 18 cases. Among the 32 cases (20 boys, 12 girls, 3 to 15 years of age; median age, 11 years), the most common symptoms were fever (100%), headache (100%), abdominal pain (93%), vomiting (91%) and back pain (76%). Laboratory findings included elevated serum creatinine concentration (19 of 28) and thrombocytopenia (7 of 22). Urinalysis showed proteinuria (31 of 31 patients) and hematuria (24 of 30). Six children had mild hemorrhagic manifestations (epistaxis, metrorrhagia, and petechiae). No severe complications occurred. The clinical symptoms of children with Nephropathia Epidemica seem to be similar to those found among adult Nephropathia Epidemica cases.
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Local Host Response in the Lower Respiratory Tract in Nephropathia Epidemica
Scandinavian journal of infectious diseases, 1993Co-Authors: Mats Linderholm, Per Juto, Bo Settergren, Leif Bjermer, Göran Roos, Thomas Sandström, Arne TärnvikAbstract:Various lines of evidence suggest a respiratory route of transmission of Nephropathia Epidemica (NE). To study the response of the respiratory tract in NE, fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) was performed in 5 patients in the acute phase of the disease. Compared to a reference group of 15 healthy individuals, BAL fluid of NE patients contained significantly higher total numbers of cells (p < 0.05) and significantly higher numbers of lysozyme-positive macrophages (p < 0.01), CD8+ T cells (p < 0.01), and natural killer (NK) cells (p < 0.01). There was no significant difference in numbers of CD4+ T cells, B cells, or neutrophils. When blood samples of 16 patients were examined at various intervals after onset of NE, a significant decrease in the number of NK cells (p < 0.01) was found in the acute phase of the disease. The findings are compatible with the presence of a local host response in the lower respiratory tract to NE virus infection.
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Detection of serum IgM antibodies to glomerular basement membrane in two cases of Nephropathia Epidemica.
Journal of internal medicine, 1992Co-Authors: Jan Billheden, Bo Settergren, Bernd Stegmayr, Per JutoAbstract:We report two serologically verified cases of Nephropathia Epidemica (NE) who developed high serum levels of non-Goodpasture IgM antibodies against glomerular basement membrane (anti GBM) in the acute phase of the disease. Moreover, in one of the patients a renal biopsy showed granular deposits of complement factor 3 along the glomerular capillary walls. The possible pathogenic significance of these findings is discussed.