| 1. |
- Ahlm, Clas, 1956-, et al.
(författare)
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Central nervous system and ophthalmic involvement in nephropathia epidemica (European type of haemorrhagic fever with renal syndrome)
- 1998
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Ingår i: Journal of Infection. - 0163-4453 .- 1532-2742. ; 36:2, s. 149-155
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Tidskriftsartikel (refereegranskat)abstract
- Central nervous system (CNS) - related symptoms occur in haemorrhagic fever with renal syndrome (HFRS). To study the CNS and ophthalmic involvement in nephropathia epidemica (NE), the European type of HFRS, we included 26 patients in a prospective study. Most common CNS-related symptoms were headache (96%), insomnia (83%), vertigo (79%), nausea (79%), and vomiting (71%). Ophthalmic symptoms were reported by 82% of patients; 41% had photophobia and 50% had impaired vision. A transient loss of vision was recorded in one patient, who also had a generalized seizure. Minor white matter lesions were found in about half of the patients investigated with brain magnetic resonance imaging (MRI). Electroencephalography (EEG) showed severe alterations in only one patient, and slight and reversible patterns in another two patients. Neopterin, interleukin-6 and interferon-gamma levels in the cerebrospinal fluid (CSF) were elevated, which may indicate immune activation. However, we found no evidence of intrathecal NE virus replication. We conclude that CNS-related symptoms are common in NE, and transient ophthalmic involvement can be demonstrated in about half of the patients.
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| 2. |
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| 3. |
- Ahlm, Clas, 1956-
(författare)
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Distribution of puumala virus in Sweden
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Puumala virus, belonging to the genus hantavirus, is the causative agent of nephropathia epidemica (NE), a relatively mild form of hemorrhagic fever with renal syndrome. Puumala virus occurs endemically in Central and Northern Europe and Western Russia. In Sweden, NE is reported from the northern and central parts but virtually not at all from the southern part of the country. The bank vole (Clethrionomys glareolus) is the main reservoir of Puumala virus and humans are infected by inhalation of aerosolized animal secreta. In northern Sweden, the density of the bank vole population varies cyclically in intervals of 3-4 years and the incidence of NE shows a covariation.The prevalence of serum antibodies to hantaviruses in northern Sweden was studied in a stratified and randomly selected adult population sample comprising 1538 subjects. As expected, the prevalence increased with age. There was no difference between men and women, which was unexpected based on a male:female ratio of > 2:1 in clinical reports. By use of an immunofiuorescent assay, a seroprevalence of 5.4% and by a newly developed enzyme-linked immunosorbent assay (ELISA) with recombinant Puumala virus nucleocapsid protein as antigen, a prevalence of 8.9% was recorded. This is about or more than ten times higher than what would be calculated from clinical reports.By use of the ELISA, an occupational risk of acquisition of Puumala virus infection was demonstrated. Serum samples from 910 farmers and 663 referent subjects living in various rural parts of Sweden were tested. Among farmers from the Puumala virus-endemic northern and central parts of the country, the seroprevalence (12.9%) was higher (p=0.01) than in referents (6.8%). In the southern part of Sweden, only 2/459 persons had antibodies. Only a limited number of children with NE had been previously reported. In a separate study, 32 children with Puumala virus infection were identified and the clinical picture of NE in children was found to be similar to that of adult cases.Variations in the prevalence of Puumala virus in the bank vole population within an endemic region are not well known. Here, a higher mean rodent density and a higher prevalence of Puumala virus-specific serum antibodies were recorded in the vicinity of households afflicted with NE than in rural control areas. The data indicated that the risk of exposure locally within an endemic region may vary widely and tentatively suggested that a threshold density of bank voles might be necessary to achieve before effective spread of Puumala virus within the rodent population may occur.There is no firm evidence of the occurrence of Puumala virus among wild living animals other than rodents. A study of Swedish moose, an animal which is ecologically well characterized, was performed. Convincing evidence of past Puumala virus infection was found in 5/260 moose originating from Puumala virus-endemic areas but in none of 167 animals from nonendemic areas. Based on the low seroprevalence recorded, moose seemed to serve as endstage hosts rather than being active parts of the enzootic circle of transmission.In conclusion, the present investigations confirmed that the exposure to Puumala virus is geographically well restricted in Sweden. Seroprevalence studies indicated that only a minor proportion of individuals infected with Puumala virus are clinically reported, with a bias in favour of men. NE was confirmed to occur in children, with a clinical picture similar to that of adults. An occupational risk was defined for acquisition of Puumala virus infection. Studies in rodents suggested that there may be wide local variations within a limited area in the risk of exposure to Puumala virus. The studies validated the usefulness of a newly developed ELISA based on recombinant nucleocapsid peptides of hantaviruses and finally, methodological progress was reached when Puumala virus was, for the first time, successfully isolated from a Scandinavian patient.
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| 4. |
- Ahlm, Clas, 1956-, et al.
(författare)
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High prevalence of hantavirus antibodies in bank voles (Clethrionomys glareolus) captured in the vicinity of households afflicted with nephropathia epidemica.
- 1997
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Ingår i: American Journal of Tropical Medicine and Hygiene. - 0002-9637 .- 1476-1645. ; 56:6, s. 674-8
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Tidskriftsartikel (refereegranskat)abstract
- Puumala virus, the causative agent of nephropathia epidemica (NE), occurs endemically in Europe and is spread mainly by the bank vole (Clethrionomys glareolus). In the vicinity of each of four households afflicted with NE, we studied rodents with regard to population density and prevalence of Puumala virus-specific antibodies. For each case area, a control area was randomly selected 10 km away, without regard to the presence of human settlement. During 6,000 trap nights, 328 rodents were caught, of which 299 were C. glareolus. The mean rodent densities of case and control areas were 6.6 and 3.7 animals per 100 trap nights (P < 0.001). The prevalence of serum antibodies was 15.9% in case areas compared with 5.6% in control areas (P < 0.05). In three of the case areas, where NE had occurred 3-10 weeks before trapping, the rodent density and seroprevalence were much higher than in the fourth area, where NE occurred 38 weeks before trapping. In conclusion, C. glareolus seropositive for Puumala virus occurred more frequently near households afflicted with NE than in control areas 10 km away.
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| 5. |
- Ahlm, Clas, 1956-, et al.
(författare)
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Prevalence of antibodies specific to Puumala virus among farmers in Sweden
- 1998
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 24:2, s. 104-108
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Tidskriftsartikel (refereegranskat)abstract
- Serological evidence confirmed that the exposure of humans to Puumala virus is firmly restricted to the northern and central parts of Sweden. In addition the evidence indicated that, in this region, farming is associated with an increased risk of contracting hantavirus infection.
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| 6. |
- Ahlm, Clas, 1956-, et al.
(författare)
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Prevalence of serum antibodies to hantaviruses in northern Sweden as measured by recombinant nucleocapsid proteins.
- 1997
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 29:4, s. 349-54
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Tidskriftsartikel (refereegranskat)abstract
- An enzyme-linked immunosorbent assay (ELISA) based on recombinant nucleocapsid protein (rN delta) (aa 1-117) of Hantaan, Seoul, Dobrava, Sin Nombre and Puumala hantaviruses was used to determine the prevalence of antibodies among randomized and stratified individuals from northern Sweden. In total, 137/1533 individuals (8.9%) had specific serum IgG antibodies to Puumala virus, the only hantavirus known to occur in the region. The prevalence of antibodies to Puumala virus (8.9%) was determined to be higher than previously reported (5.4%) in the same serum material, by use of immunofluorescence assay. As expected, sera reactive to Puumala virus rN delta did frequently cross-react with Sin Nombre virus protein. Unexpectedly, 21/1533 (1.4%) individuals recognized the Sin Nombre virus rN delta exclusively. Another 8 subjects showed reactivity in the ELISA to Hantaan, Seoul, or Dobrava virus-derived rN delta but not Puumala virus or Sin Nombre virus rN delta. The present demonstration in some individuals of antibodies specifically recognizing the Sin Nombre, Dobrava, Hantaan and Seoul virus protein justifies an awareness of the possibility that hantaviruses antigenically different from Puumala virus might occur in the region.
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| 7. |
- Alexeyev, O A, et al.
(författare)
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Hantavirus antigen detection using human serum immunoglobulin M as the capturing antibody in an enzyme-linked immunosorbent assay.
- 1996
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Ingår i: American Journal of Tropical Medicine and Hygiene. - 0002-9637 .- 1476-1645. ; 54:4, s. 367-71
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Tidskriftsartikel (refereegranskat)abstract
- An enzyme-linked immunosorbent assay (ELISA) was developed to detect different hantavirus antigens in cell culture; i.e. Puumala (PUU), Hantaan (HTN), and Dobrava (DOB) viruses. The assay was based on binding human serum immunoglobulin M (IgM) antibodies to the solid phase by use of goat anti-IgM antibodies. The captured IgM antibodies were present in the acute phase serum from two patients: one infected in Sweden and the other in Bosnia. Antigens being bound to the solid phase by the human anti-PUU and anti-DOB/HTN IgM antibodies were detected by a broadly reacting polyclonal rabbit anti PUU-recombinant nucleocapsid protein antiserum. The IgM isotype was proven to be at least five times more efficient than IgG when used as the capturing antibody. The sensitivity of the PUU antigen ELISA was approximately 0.5 ng/ml, as measured by titration with a PUU recombinant nucleoprotein antigen. Cell-associated PUU antigen in tissue culture was seen after 48 hr by the PUU-ELISA and after 96 hr by immunofluorescent assay. When tested for capacity to discriminate between PUU, DOB, and HTN viruses, significant differences were found: the Swedish serum detected PUU antigen at high titers, whereas no reactivity was found against DOB and HTN; the Bosnian serum detected both DOB and HTN at high titers but had a low reactivity to PUU. The method was also tested for its usefulness in detecting PUU antigen in bank vole (clethrionomys glareolus) lungs. Of 59 animals captured from the surroundings of patients with nephropathia epidemica, three became positive with a high activity in the PUU-ELISA, but with low reactivity in the DOB/HTN-ELISA. It is concluded that a sensitive ELISA has been developed to detect different hantaviruses in cell culture and lungs of bank voles.
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| 8. |
- Juto, Per, et al.
(författare)
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The first human isolate of Puumala virus in Scandinavia as cultured from phytohemagglutinin stimulated leucocytes.
- 1997
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Ingår i: Journal of Medical Virology. - 0146-6615 .- 1096-9071. ; 53:2, s. 150-6
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Tidskriftsartikel (refereegranskat)abstract
- A virus isolate was recovered from blood leucocytes of a patient with nephropathia epidemica (NE). Leucocytes were isolated from EDTA-blood by dextran sedimentation and cultured on monolayers of Vero E6 cells in the presence of phytohemagglutinin (PHA) in roller tubes during the first 72 hours of incubation followed by rolling culture for three weeks in total. Thereafter the first subculture was done in a plastic flask and afterward at at least 6 week intervals. Antigen was first detected after 6 months and 2 weeks of culture. When tested by monoclonal antibodies and patient sera the isolate had the characteristics of a PUU virus. PCR amplification using PUU-specific primers and subsequent partial sequencing of the S and M segments revealed that the Umeå/305/human/95 virus differs from the Finnish PUU Sotkamo rodent prototype virus and is similar but not identical to rodent strains of PUU virus acquired from the same region as the patient isolate. It is we concluded that the first human isolate of the etiologic agent of NE in Scandinavia was recovered from blood leucocytes stimulated with PHA by long-term culture in Vero E6 cells. The isolate belongs to the PUU serotype of hantaviruses as shown by its serologic profile and partial sequencing data.
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| 9. |
- Linderholm, Mats, et al.
(författare)
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Elevated plasma levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptors, interleukin (IL)-6, and IL-10 in patients with hemorrhagic fever with renal syndrome.
- 1996
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Ingår i: Journal of Infectious Diseases. - 0022-1899 .- 1537-6613. ; 173:1, s. 38-43
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Tidskriftsartikel (refereegranskat)abstract
- Plasma levels of cytokines were measured by EIA in 15 subjects hospitalized with nephropathia epidemica, a European form of hantavirus-induced hemorrhagic fever with renal syndrome. Concentrations of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were increased in all patients at admission, and the concentration of IL-10 was increased in most. TNF-alpha concentrations were still increased 1 week after onset of disease; levels of IL-6 and IL-10 were normalized. TNF-alpha was undetectable by the WEHI cell assay in serum samples obtained throughout the acute phase of disease. Serum levels of the two soluble TNF receptors p55 and p75 correlated with levels of the cytokine, indicating that receptor binding may be the reason for lack of bioactivity in vitro. TNF-alpha is known to induce pathophysiologic and clinical changes similar to those seen in nephropathia epidemica and in diseases caused by other hantaviruses.
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| 10. |
- Settergren, Bo, et al.
(författare)
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Pathogenetic and clinical aspects of the renal involvement in hemorrhagic fever with renal syndrome.
- 1997
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Ingår i: Renal failure. - : Informa UK Limited. - 0886-022X .- 1525-6049. ; 19:1, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Hemorrhagic fever with renal syndrome is the most common clinical manifestation of hantavirus infection. The main target organ is the kidney, resulting in an interstitial hemorrhagic nephritis and sometimes acute tubular necrosis. The pathogenesis is still largely unknown, but several recent studies indicate an important role for immune mechanisms including increased expression of cytokines, for example, tumor necrosis factor. Immunohistochemical studies of kidney biopsies have revealed deposits of IgG, IgM, and C3, but deposits were significantly less numerous than in chronic immune complex disease. Since hantaviruses are not cytolytic, a direct detrimental effect of the infecting virus is less likely. The long-term prognosis of hemorrhagic fever with renal syndrome seems to be favorable, but there are reports that previous hantavirus infection is associated with an increased risk of hypertensive renal disease. Prospective longitudinal studies addressing this issue are underway.
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