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Stöven, Svenja
Publications (10 of 16) Show all publications
Kinsman, J., Stöven, S., Elgh, F., Murillo, P. & Sulzner, M. (2018). Good practices and challenges in addressing poliomyelitis and measles in the European Union. European Journal of Public Health, 28(4), 730-734
Open this publication in new window or tab >>Good practices and challenges in addressing poliomyelitis and measles in the European Union
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2018 (English)In: European Journal of Public Health, ISSN 1101-1262, E-ISSN 1464-360X, Vol. 28, no 4, p. 730-734Article in journal (Refereed) Published
Abstract [en]

Background: All European Union (EU) and European Economic Area (EEA) Member States have pledged to ensure political commitment towards sustaining the region's poliomyelitis-free status and eliminating measles. However, there remain significant gaps between policy and practice in many countries. This article reports on an assessment conducted for the European Commission that aimed to support improvements in preparedness and response to poliomyelitis and measles in Europe.

Methods: A documentary review was complemented by qualitative interviews with professionals working in International and EU agencies, and in at-risk or recently affected EU/EEA Member States (six each for poliomyelitis and measles). Twenty-six interviews were conducted on poliomyelitis and 24 on measles; the data were subjected to thematic analysis. Preliminary findings were then discussed at a Consensus Workshop with 22 of the interviewees and eight other experts.

Results: Generic or disease-specific plans exist in the participating countries and cross-border communications during outbreaks were generally reported as satisfactory. However, surveillance systems are of uneven quality, and clinical expertise for the two diseases is limited by a lack of experience. Serious breaches of protocol have recently been reported from companies producing poliomyelitis vaccines, and vaccine coverage rates for both diseases were also sub-optimal. A set of suggested good practices to address these and other challenges is presented.

Conclusions: Poliomyelitis and measles should be brought fully onto the policy agendas of all EU/EEA Member States, and adequate resources provided to address them. Each country must abide by the relevant commitments that they have already made.

Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Public Health, Global Health, Social Medicine and Epidemiology Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-150590 (URN)10.1093/eurpub/cky056 (DOI)000440944400026 ()29659793 (PubMedID)
Available from: 2018-08-13 Created: 2018-08-13 Last updated: 2018-09-11Bibliographically approved
Plamboeck, A. H., Stöven, S., Davidson, R. D., Fykse, E.-M., Griffiths, M., Nieuwenhuizen, M., . . . van der Schans, M. (2016). Laboratory analysis of CBRN-substances: Stakeholder networks as clue to higher CBRN resilience in Europe. TrAC. Trends in analytical chemistry, 85(Part B), 2-9
Open this publication in new window or tab >>Laboratory analysis of CBRN-substances: Stakeholder networks as clue to higher CBRN resilience in Europe
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2016 (English)In: TrAC. Trends in analytical chemistry, ISSN 0165-9936, E-ISSN 1879-3142, Vol. 85, no Part B, p. 2-9Article in journal (Refereed) Published
Abstract [en]

The threat of terrorists using CBRN agents continues to pose a risk of mass casualties and severe disruption of societal functions in Europe. Standardisation of crisis management activities is one important step towards effective national and international interoperability and increased resilience. Understanding which CBRN agents are involved in an incident is vital for appropriate response measures. We applied a system's view on the process of CBRN sample analysis and see three discrete applications; Immediate incident response, Forensics, Post incident monitoring. Together with laboratory experts and policy makers from across Europe we identified needs for quality assurance measures in these three areas. Here, we suggest various harmonisation activities that can facilitate interoperability between all stakeholders concerned with CBRN sample analysis. Foremost, we recommend purpose-oriented laboratory networks, but also minimum performance requirements for First Responders' detection and sampling capabilities, best practices for sample transport and documentation.

Keywords
Standardisation, Resilient society, Immediate incident response, Forensic investigations, Post incident monitoring, Sample analyses, Laboratory network, Hazardous substances
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:umu:diva-130462 (URN)10.1016/j.trac.2016.03.006 (DOI)000390495900002 ()
Available from: 2017-01-24 Created: 2017-01-20 Last updated: 2018-06-09Bibliographically approved
Stöven, S., Bäcklund, A. & Sahovic, D. (2013). Ethics Issues Management Workshop: PRACTICE project deliverable 1.3.
Open this publication in new window or tab >>Ethics Issues Management Workshop: PRACTICE project deliverable 1.3
2013 (English)Report (Other academic)
National Category
Other Social Sciences
Identifiers
urn:nbn:se:umu:diva-110683 (URN)
Projects
PRACTICE Preparedness and Resilience against CBRN Terrorism using Integrated Concepts and Equipment
Funder
EU, FP7, Seventh Framework Programme, 261728
Available from: 2015-10-26 Created: 2015-10-26 Last updated: 2018-06-07
Vonkavaara, M., Pavel, S. T., Hölzl, K., Nordfelth, R., Sjöstedt, A. & Stöven, S. (2013). Francisella is sensitive to insect antimicrobial peptides. Journal of Innate Immunity, 5(1), 50-59
Open this publication in new window or tab >>Francisella is sensitive to insect antimicrobial peptides
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2013 (English)In: Journal of Innate Immunity, ISSN 1662-811X, E-ISSN 1662-8128, Vol. 5, no 1, p. 50-59Article in journal (Refereed) Published
Abstract [en]

Francisella tularensis causes the zoonotic disease tularemia. Arthropod vectors are important transmission routes for the disease, although it is not known how Francisella survives the efficient arthropod immune response. Here, we used Drosophila melanogaster as a model host for Francisella infections and investigated whether the bacteria are resistant to insect humoral immune responses, in particular to the antimicrobial peptides (AMPs) secreted into the insect hemolymph. Moreover, we asked to which extent such resistance might depend on LPS structure and surface characteristics of the bacteria. We analyzed F. novicida mutant strains in genes, directly or indirectly involved in specific steps of LPS biosynthesis, for virulence in wildtype and Relish E20 immune deficient flies, and tested selected mutants for sensitivity to AMPs in vitro. We demonstrate that Francisella is sensitive to specific fly AMPs, i.e. Attacin, Cecropin, Drosocin and Drosomycin. Furthermore, six bacterial genes, kpsF, manB, lpxF, slt, tolA and pal, were found to be required for resistance to Relish-dependent immune responses, illustrating the importance of structural details of Francisella lipid A and Kdo core for interactions with AMPs. Interestingly, a more negative surface charge and lack of O-antigen did not render mutant bacteria more sensitive to cationic AMPs and attenuated virulence in flies.

Place, publisher, year, edition, pages
Basel: Karger, 2013
Keywords
Francisella tularensis, Drosophila melanogaster, Antimicrobial peptides, Lipopolysaccharide, Host-pathogen interactions
National Category
Microbiology in the medical area
Research subject
Clinical Bacteriology
Identifiers
urn:nbn:se:umu:diva-54412 (URN)10.1159/000342468 (DOI)000313541600006 ()23037919 (PubMedID)
Note

Originally published in thesis in manuscript form.

Available from: 2012-04-26 Created: 2012-04-26 Last updated: 2018-06-08Bibliographically approved
Eneslätt, K., Normark, M., Björk, R., Rietz, C., Zingmark, C., Wolfraim, L. A., . . . Sjöstedt, A. (2012). Signatures of T cells as correlates of immunity to Francisella tularensis. PLoS ONE, 7(3), e32367
Open this publication in new window or tab >>Signatures of T cells as correlates of immunity to Francisella tularensis
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2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 3, p. e32367-Article in journal (Refereed) Published
Abstract [en]

Tularemia or vaccination with the live vaccine strain (LVS) of Francisella tularensis confers long-lived cell-mediated immunity. We hypothesized that this immunity depends on polyfunctional memory T cells, i.e., CD4(+) and/or CD8(+) T cells with the capability to simultaneously express several functional markers. Multiparametric flow cytometry, measurement of secreted cytokines, and analysis of lymphocyte proliferation were used to characterize in vitro recall responses of peripheral blood mononuclear cells (PBMC) to killed F. tularensis antigens from the LVS or Schu S4 strains. PBMC responses were compared between individuals who had contracted tularemia, had been vaccinated, or had not been exposed to F. tularensis (naive). Significant differences were detected between either of the immune donor groups and naive individuals for secreted levels of IL-5, IL-6, IL-10, IL-12, IL-13, IFN-gamma, MCP-1, and MIP-1 beta. Expression of IFN-gamma, MIP-1 beta, and CD107a by CD4(+)CD45RO(+) or CD8(+) CD45RO(+) T cells correlated to antigen concentrations. In particular, IFN-gamma and MIP-1 beta strongly discriminated between immune and naive individuals. Only one cytokine, IL-6, discriminated between the two groups of immune individuals. Notably, IL-2- or TNF-alpha-secretion was low. Our results identify functional signatures of T cells that may serve as correlates of immunity and protection against F. tularensis.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-55370 (URN)10.1371/journal.pone.0032367 (DOI)000303021100015 ()22412866 (PubMedID)
Available from: 2012-05-30 Created: 2012-05-14 Last updated: 2018-06-08Bibliographically approved
Eneslätt, K., Rietz, C., Rydén, P., Stöven, S., House, R. V., Wolfraim, L. A., . . . Sjöstedt, A. (2011). Persistence of cell-mediated immunity three decades after vaccination with the live vaccine strain of Francisella tularensis. European Journal of Immunology, 41(4), 974-980
Open this publication in new window or tab >>Persistence of cell-mediated immunity three decades after vaccination with the live vaccine strain of Francisella tularensis
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2011 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 41, no 4, p. 974-980Article in journal (Refereed) Published
Abstract [en]

The efficacy of many vaccines against intracellular bacteria depends on the generation of cell-mediated immunity, but studies to determine the duration of immunity are usually confounded by re-exposure. The causative agent of tularemia, Francisella tularensis, is rare in most areas and, therefore, tularemia vaccination is an interesting model for studies of the longevity of vaccine-induced cell-mediated immunity. Here, lymphocyte proliferation and cytokine production in response to F. tularensis were assayed in two groups of 16 individuals, vaccinated 1-3 or 27-34 years previously. As compared to naïve individuals, vaccinees of both groups showed higher proliferative responses and, out of 17 cytokines assayed, higher levels of MIP-1β, IFN-γ, IL-10, and IL-5 in response to recall stimulation. The responses were very similar in the two groups of vaccinees. A statistical model was developed to predict the immune status of the individuals and by use of two parameters, proliferative responses and levels of IFN-γ, 91.1% of the individuals were correctly classified. Using flow cytometry analysis, we demonstrated that during recall stimulation, expression of IFN-γ by CD4(+) CCR7(+) , CD4(+) CD62L(+) , CD8(+) CCR7(+) , and CD8(+) CD62L(+) cells significantly increased in samples from vaccinated donors. In conclusion, cell-mediated immunity was found to persist three decades after tularemia vaccination without evidence of decline.

Place, publisher, year, edition, pages
Weinheim: Wiley-VCH Verlagsgesellschaft, 2011
Keywords
Cell-mediated immunity, Francisella tularensis, Persistence, Vaccination
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-50333 (URN)10.1002/eji.201040923 (DOI)000288821000011 ()21442618 (PubMedID)
Available from: 2011-12-06 Created: 2011-12-06 Last updated: 2018-06-08Bibliographically approved
Åhlund, M. K., Rydén, P., Sjöstedt, A. & Stöven, S. (2010). Directed screen of Francisella novicida virulence determinants using Drosophila melanogaster. Infection and Immunity, 78(7), 3118-3128
Open this publication in new window or tab >>Directed screen of Francisella novicida virulence determinants using Drosophila melanogaster
2010 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 78, no 7, p. 3118-3128Article in journal (Refereed) Published
Abstract [en]

Francisella tularensis is a highly virulent, facultative intracellular human pathogen whose virulence mechanisms are not well understood. Occasional outbreaks of tularemia and the potential use of F. tularensis as a bioterrorist agent warrant better knowledge about the pathogenicity of this bacterium. Thus far, genome-wide in vivo screens for virulence factors have been performed in mice, all however restricted by the necessity to apply competition-based, negative-selection assays. We wanted to individually evaluate putative virulence determinants suggested by such assays and performed directed screening of 249 F. novicida transposon insertion mutants by using survival of infected fruit flies as a measure of bacterial virulence. Some 20% of the genes tested were required for normal virulence in flies; most of these had not previously been investigated in detail in vitro or in vivo. We further characterized their involvement in bacterial proliferation and pathogenicity in flies and in mouse macrophages. Hierarchical cluster analysis of mutant phenotypes indicated a functional linkage between clustered genes. One cluster grouped all but four genes of the Francisella pathogenicity island and other loci required for intracellular survival. We also identified genes involved in adaptation to oxidative stress and genes which might induce host energy wasting. Several genes related to type IV pilus formation demonstrated hypervirulent mutant phenotypes. Collectively, the data demonstrate that the bacteria in part use similar virulence mechanisms in mammals as in Drosophila melanogaster but that a considerable proportion of the virulence factors active in mammals are dispensable for pathogenicity in the insect model.

Place, publisher, year, edition, pages
ASM International, 2010
Keywords
tularensis subsp tularensis, disulfide bond formation, VI secretion, in vivo, schu S4, pathogenicity island, Escherichia coli, identification, mice, pathogenesis
National Category
Microbiology in the medical area Infectious Medicine Immunology in the medical area
Research subject
Microbiology
Identifiers
urn:nbn:se:umu:diva-38652 (URN)10.1128/IAI.00146-10 (DOI)000278830200025 ()20479082 (PubMedID)
Available from: 2010-12-20 Created: 2010-12-20 Last updated: 2018-06-08Bibliographically approved
Wiklund, M.-L., Steinert, S., Junell, A., Hultmark, D. & Stöven, S. (2009). The N-terminal half of the Drosophila Rel/NF-kappaB factor Relish, REL-68, constitutively activates transcription of specific Relish target genes. Developmental and Comparative Immunology, 33(5), 690-696
Open this publication in new window or tab >>The N-terminal half of the Drosophila Rel/NF-kappaB factor Relish, REL-68, constitutively activates transcription of specific Relish target genes
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2009 (English)In: Developmental and Comparative Immunology, ISSN 0145-305X, E-ISSN 1879-0089, Vol. 33, no 5, p. 690-696Article in journal (Refereed) Published
Abstract [en]

The Rel/NF-kappaB transcription factor Relish is a major regulator of the antimicrobial response in Drosophila. Upon immune challenge, Relish is cleaved to generate two fragments, the DNA-binding transcription factor REL-68 and the IkappaB-like REL-49. Using transgenic fly strains we show here that overexpression of REL-68 separately from REL-49 is sufficient to activate strong constitutive transcription of the Diptericin gene, but little constitutive or inducible transcription of Attacin and Cecropin, two other Relish target genes. Their transcription may therefore require additional modifications of Relish. However, phosphorylation of the conserved serine residue S431 is not involved in such modifications. This is unlike p65 and Dorsal, which are modulated by phosphorylation at their homologous site. In contrast to other IkappaB proteins, overexpression of REL-49 had no inhibitory effect on Relish-dependent transcription. Instead, we propose that the C-terminal IkappaB-like domain executes a scaffolding and recruiting function for full activation of Relish.

Place, publisher, year, edition, pages
New York: Pergamon Press, 2009
Identifiers
urn:nbn:se:umu:diva-35109 (URN)10.1016/j.dci.2008.12.002 (DOI)19135474 (PubMedID)
Available from: 2010-07-12 Created: 2010-07-12 Last updated: 2018-06-08
Ertürk-Hasdemir, D., Broemer, M., Leulier, F., Lane, W. S., Paquette, N., Hwang, D., . . . Silverman, N. (2009). Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes. Proceedings of the National Academy of Sciences of the United States of America, 106(24), 9779-9784
Open this publication in new window or tab >>Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes
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2009 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 24, p. 9779-9784Article in journal (Refereed) Published
Abstract [en]

The Drosophila NF-kappa B transcription factor Relish is an essential regulator of antimicrobial peptide gene induction after Gram-negative bacterial infection. Relish is a bipartite NF-kappa B precursor protein, with an N-terminal Rel homology domain and a C-terminal I kappa B-like domain, similar to mammalian p100 and p105. Unlike these mammalian homologs, Relish is endoproteolytically cleaved after infection, allowing the N-terminal NF-kappa B module to translocate to the nucleus. Signal-dependent activation of Relish, including cleavage, requires both the Drosophila I kappa B kinase (IKK) and death-related ced-3/Nedd2-like protein (DREDD), the Drosophila caspase-8 like protease. In this report, we show that the IKK complex controls Relish by direct phosphorylation on serines 528 and 529. Surprisingly, these phosphorylation sites are not required for Relish cleavage, nuclear translocation, or DNA binding. Instead they are critical for recruitment of RNA polymerase II and antimicrobial peptide gene induction, whereas IKK functions noncatalytically to support Dredd-mediated cleavage of Relish.

Place, publisher, year, edition, pages
National Academy of Sciences, 2009
Keywords
Drosophila immunity, innate immunity, NF-kappa B, caspase
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-115994 (URN)10.1073/pnas.0812022106 (DOI)000267045500043 ()19497884 (PubMedID)
Available from: 2016-02-25 Created: 2016-02-08 Last updated: 2018-06-07Bibliographically approved
Vonkavaara, M., Telepnev, M. V., Rydén, P., Sjöstedt, A. & Stöven, S. (2008). Drosophila melanogaster as a model for elucidating the pathogenicity of Francisella tularensis. Cellular Microbiology, 10(6), 1327-1338
Open this publication in new window or tab >>Drosophila melanogaster as a model for elucidating the pathogenicity of Francisella tularensis
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2008 (English)In: Cellular Microbiology, ISSN 1462-5814, E-ISSN 1462-5822, Vol. 10, no 6, p. 1327-1338Article in journal (Refereed) Published
Abstract [en]

Drosophila melanogaster is a widely used model organism for research on innate immunity and serves as an experimental model for infectious diseases. The aetiological agent of the zoonotic disease tularaemia, Francisella tularensis, can be transmitted by ticks and mosquitoes and Drosophila might be a useful, genetically amenable model host to elucidate the interactions between the bacterium and its arthropod vectors. We found that the live vaccine strain of F. tularensis was phagocytosed by Drosophila and multiplied in fly haemocytes in vitro and in vivo. Bacteria injected into flies resided both inside haemocytes and extracellularly in the open circulatory system. A continuous activation of the humoral immune response, i.e. production of antimicrobial peptides under control of the imd/Relish signalling pathway, was observed and it may have contributed to the relative resistance to F. tularensis as flies defective in the imd/Relish pathway died rapidly. Importantly, bacterial strains deficient for genes of the F. tularensis intracellular growth locus or the macrophage growth locus were attenuated in D. melanogaster. Our results demonstrate that D. melanogaster is a suitable model for the analysis of interactions between F. tularensis and its arthropod hosts and that it can also be used to identify F. tularensis virulence factors relevant for mammalian hosts.

National Category
Microbiology in the medical area
Research subject
Clinical Bacteriology
Identifiers
urn:nbn:se:umu:diva-9517 (URN)10.1111/j.1462-5822.2008.01129.x (DOI)18248629 [PubMed - as supplied by publisher] (PubMedID)
Available from: 2008-04-14 Created: 2008-04-14 Last updated: 2018-06-09
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