| 1. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 2. |
- Evander, Magnus, et al.
(författare)
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Puumala hantavirus viremia diagnosed by real-time reverse transcriptase PCR using samples from patients with hemorrhagic fever and renal syndrome
- 2007
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Ingår i: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 45:8, s. 2491-2497
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Tidskriftsartikel (refereegranskat)abstract
- Puumala virus (PUUV) is the endemic hantavirus in northern Sweden and causes nephropathia epidemica (NE), a milder form of hemorrhagic fever with renal syndrome. There is a need for fast and reliable diagnostics to differentiate the disease from other infections. By aligning virus RNA sequences isolated from 11 different bank voles and one human patient, we designed a real-time reverse transcriptase (RT) PCR method for detection of PUUV RNA. The real-time RT-PCR assay showed linearity from 20 to 2 x 10(6) virus copies with a correlation coefficient above 0.98 to 0.99 for all experiments. The detection threshold for PUUV cDNA was two copies per reaction. A two-step qualitative RT-PCR to detect PUUV RNA showed 100% concordance with the real-time RT-PCR assay. PUUV RNA viremia was detected in 33 of 34 PUUV immunoglobulin M (IgM)-positive patients with typical clinical NE disease from the region of endemicity. One PUUV IgM-negative sample had PUUV RNA, and 4 days later, the patient was IgM positive. Of samples with indeterminate IgM, 43% were PUUV RNA positive. The kinetics of antibody titers and PUUV viremia were studied, and five of six NE patients displayed a decrease in PUUV viremia a few days after disease outbreak coupled with an increase in PUUV IgM and IgG. In one patient with continuously high PUUV RNA levels but low IgM and no IgG response, the infection was lethal. These findings demonstrated that real-time RT-PCR is a useful method for diagnosis of PUUV viremia and for detecting PUUV RNA at early time points, before the appearance of IgM antibodies.
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| 3. |
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| 4. |
- Johansson, Patrik, et al.
(författare)
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Puumala hantavirus genetic variability in an endemic region (Northern Sweden)
- 2008
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Ingår i: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-1348 .- 1567-7257. ; 8:3, s. 286-296
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Tidskriftsartikel (refereegranskat)abstract
- Puumala hantavirus (PUUV), naturally harboured and shed by bank voles (Myodes [Clethrionomys] glareolus), is the etiological agent to nephropathia epidemica (NE), a mild haemorrhagic fever with renal syndrome. Both host and virus are found throughout much of the European continent and in northern Sweden NE is the second most prevalent serious febrile viral infection after influenza. The reliability of diagnostics by PCR depends on genetic variability for the detection of viral nucleic acids in unknown samples. In the present study we evaluated the genetic variability of PUUV isolated from bank voles in an area of northern Sweden highly endemic for NE. Genetic variability among bank voles was also investigated to evaluate co-evolutionary patterns. We found that the viral sequence appeared stable across the 80 km study region, with the exception of the southernmost sampling site, which differed from its nearest neighbour by 7%, despite a geographical separation of only 10 km. The southernmost sampling site demonstrated a higher degree of genetic similarity to PUUV previously isolated 100 km south thereof; two locations appear to constitute a separate PUUV phylogenetic branch. In contrast to the viral genome, no phylogenetic variance was observed in the bank vole mtDNA in this study. Previous studies have shown that as a result of terrestrial mammals' postglacial re-colonization routes, bank voles and associated PUUV of a southern and a northern lineage established a dichotomous contact zone across the Scandinavian peninsula approximately 100-150km south of the present study sites. Our observations reveal evolutionary divergence of PUUV that has led to dissimilarities within the restricted geographical scale of the northern host re-colonization route as well. These results suggest either a static situation in which PUUV strains are regionally well adapted, or an ongoing process in which strains of PUUV circulate on a geographical scale not yet reliably described. (c) 2008 Elsevier B.V. All rights reserved.
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| 5. |
- Olsson, Gert E, et al.
(författare)
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Demographic factors associated with hantavirus infection in bank voles (Clethrionomys glareolus)
- 2002
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Ingår i: Emerging Infectious Diseases. - 1080-6040 .- 1080-6059. ; 8:9, s. 924-929
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Tidskriftsartikel (refereegranskat)abstract
- The bank vole (Clethrionomys glareolus) is the natural reservoir of Puumala virus (PUUV), a species in the genus Hantavirus. PUUV is the etiologic agent of nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome. Factors that influence hantavirus transmission within host populations are not well understood. We evaluated a number of factors influencing on the association of increased PUUV infection in bank voles captured in a region in northern Sweden endemic for the virus. Logistic regression showed four factors that together correctly predicted 80% of the model outcome: age, body mass index, population phase during sampling (increase, peak, or decline/low), and gender. This analysis highlights the importance of population demography in the successful circulation of hantavirus. The chance of infection was greatest during the peak of the population cycle, implying that the likelihood of exposure to hantavirus increases with increasing population density.
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| 6. |
- Olsson, Gert E, et al.
(författare)
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Habitat factors associated with bank voles (Clethrionomys glareolus) and concomitant hantavirus in northern Sweden
- 2005
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Ingår i: Vector Borne and Zoonotic Diseases. - : Mary Ann Liebert Inc. - 1530-3667 .- 1557-7759. ; 5:4, s. 315-323
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Tidskriftsartikel (refereegranskat)abstract
- Puumala virus (PUUV), genus hantavirus, causes nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome in humans. In this study, bank voles, the natural reservoir of PUUV, were captured at locations of previous human PUUV exposure and paired controls within a region of high incidence in northern Sweden. The aim of the study was to evaluate the influence of environmental factors on the abundance of bank voles and the occurrence of PUUV. The total number of voles and the number of PUUV-infected voles did not differ between locations of previous human PUUV exposure and paired controls. The number of bank voles expressing antibodies to PUUV infection increased linearly with total bank vole abundance implying density independent transmission. Using principal component and partial correlation analysis, we found that particular environmental characteristics associated with old-growth moist forests (i.e., those dominated by Alectoria spp., Picea abies, fallen wood, and Vaccinium myrtillus) were also associated with increased abundance of bank vole and hence the number of PUUV-infected bank voles, whereas there were no correlations with factors associated with dry environments (i.e., Pinus sylvestris and V. vitis-idea). This suggests that circulation and persistence of PUUV within bank vole populations was influenced by habitat factors. Future modeling of risk of exposure to hantavirus and transmission of PUUV within vole populations should include the influence of these factors.
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| 7. |
- Olsson, Gert E, et al.
(författare)
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Hantavirus antibody occurrence in bank voles (Clethrionomys glareolus) during a vole population cycle
- 2003
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Ingår i: Journal of Wildlife Diseases. - : Wildlife Disease Association. - 0090-3558 .- 1943-3700. ; 39:2, s. 299-305
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Tidskriftsartikel (refereegranskat)abstract
- Puumala virus, genus Hantavirus, is the etiologic agent of nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome. The bank vole (Clethrionomys glareolus) is the natural reservoir species of this hantavirus. We initiated sampling of bank voles at sites of recently identified human nephropathia epidemica cases and paired control sites in the fall of 1995 in coastal areas of northern Sweden. Sites were trapped annually in spring and fall until 1999. Prevalence of antibody to Puumala virus was similar among local bank vole populations in the two types of sites over time. During peak years, however, the absolute number of bank voles was higher in case sites than control sites. Consequently, the likelihood of Puumala virus exposure was increased at case sites during population highs. This would imply that the risk of Puumala virus exposure to conspecifics and humans is habitat and site dependent with a temporal component.
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| 8. |
- Pfirrmann, Markus, et al.
(författare)
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The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in chronic myeloid leukemia
- 2020
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Ingår i: Leukemia. - : NATURE PUBLISHING GROUP. - 0887-6924 .- 1476-5551. ; 34:8, s. 2138-2149
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Tidskriftsartikel (refereegranskat)abstract
- Prognostic scores support clinicians in selecting risk-adjusted treatments and in comparatively assessing different results. For patients with chronic-phase chronic myeloid leukemia (CML), four baseline prognostic scores are commonly used. Our aim was to compare the prognostic performance of the scores and to arrive at an evidence-based score recommendation. In 2949 patients not involved in any score development, higher hazard ratios and concordance indices in any comparison demonstrated the best discrimination of long-term survival with the ELTS score. In a second step, of 5154 patients analyzed to investigate risk group classification differences, 23% (n = 1197) were allocated to high-risk by the Sokal score. Of the 1197 Sokal high-risk patients, 56% were non-high-risk according to the ELTS score and had a significantly more favorable long-term survival prognosis than the 526 high-risk patients according to both scores. The Sokal score identified too many patients as high-risk and relatively few (40%) as low-risk (versus 60% with the ELTS score). Inappropriate risk classification jeopardizes optimal treatment selection. The ELTS score outperformed the Sokal score, the Euro, and the EUTOS score regarding risk group discrimination. The recent recommendation of the European LeukemiaNet for preferred use of the ELTS score was supported with significant statistical evidence.
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| 9. |
- Warvsten, Anna, et al.
(författare)
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Islet autoantibodies present in association with Ljungan virus infection in bank voles (Myodes glareolus) in northern Sweden
- 2017
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Ingår i: Journal of Medical Virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 89:1, s. 24-31
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Tidskriftsartikel (refereegranskat)abstract
- Bank voles are known reservoirs for Puumala hantavirus and probably also for Ljungan virus (LV), a suggested candidate parechovirus in type 1 diabetes etiology and pathogenesis. The aim of this study was to determine whether wild bank voles had been exposed to LV and if exposure associated to autoantibodies against insulin (IAA), glutamic acid decarboxylase 65 (GADA), or islet autoantigen-2 (IA-2A). Serum samples from bank voles (Myodes glareolus) captured in early summer or early winter of 1997 and 1998, respectively, were analyzed in radio binding assays for antibodies against Ljungan virus (LVA) and Puumala virus (PUUVA) as well as for IAA, GADA, and IA-2A. LVA was found in 25% (189/752), IAA in 2.5% (18/723), GADA in 2.6% (15/615), and IA-2A in 2.5% (11/461) of available bank vole samples. LVA correlated with both IAA (P = 0.007) and GADA (P < 0.001), but not with IA-2A (P = 0.999). There were no correlations with PUUVA, detected in 17% of the bank voles. Compared to LVA negative bank voles, LVA positive animals had higher levels of both IAA (P = 0.002) and GADA (P < 0.001), but not of IA-2A (P = 0.205). Levels of LVA as well as IAA and GADA were higher in samples from bank voles captured in early summer. In conclusion, LVA was detected in bank voles and correlated with both IAA and GADA but not with IA-2A. These observations suggest that exposure to LV may be associated with islet autoimmunity. It remains to be determined if islet autoantibody positive bank voles may develop diabetes in the wild. J. Med. Virol. 89:24-31, 2017. © 2016 Wiley Periodicals, Inc.
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