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  • 201.
    Näslund, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lagerqvist, Nina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Habjan, Matthias
    Department of Virology, University of Freiburg, D-79008 Freiburg, Germany.
    Lundkvist, Ake
    Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Weber, Friedemann
    Department of Virology, University of Freiburg, D-79008 Freiburg, Germany.
    Bucht, Göran
    Swedish Defence Research Agency, Department of CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    Vaccination with virus-like particles protects mice from lethal infection of Rift Valley fever virus2009In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 385, no 2, p. 409-415Article in journal (Refereed)
    Abstract [en]

    Rift Valley Fever virus (RVFV) regularly accounts for severe and often lethal outbreaks among livestock and humans in Africa. Safe and effective veterinarian and human vaccines are highly needed. We present evidence that administration of RVF virus-like particles (VLPs) induces protective immunity in mice. In an accompanying paper, (Habjan, M., Penski, N., Wagner, V., Spiegel, M., Overby, A.K., Kochs, G., Huiskonen, J., Weber, F., 2009. Efficient production of Rift Valley fever virus-like particles: the antiviral protein MxA can inhibit primary transcription of Bunyaviruses. Virology 385, 400-408) we report the production of these VLPs in mammalian cells. After three subsequent immunizations with 1x10(6) VLPs/dose, high titers of virus-neutralizing antibodies were detected; 11 out of 12 mice were protected from challenge and only 1 out of 12 mice survived infection in the control groups. VLP vaccination efficiently suppressed replication of the challenge virus, whereas in the control animals high RNA levels and increasing antibody titers against the nucleocapsid protein indicated extensive viral replication. Our study demonstrates that the RVF VLPs are highly immunogenic and confer protection against RVFV infection in mice. In the test groups, the vaccinated mice did not exhibit any side effects, and the lack of anti-nucleocapsid protein antibodies serologically distinguished vaccinated animals from experimentally infected animals.

  • 202.
    Olfat, Farzad
    Umeå University, Faculty of Medicine, Odontology.
    Helicobacter pylori: bacterial adhesion and host response2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The gastric pathogen Helicobacter pylori infects more than half of the population worldwide. H. pylori manage to establish persistent infection, which would be life-long if not treated. In order to establish such an infection, this pathogen has to deal with the host immune system. H. pylori has certain characteristics which make the bacteria less announced to the host immune system. Additionally, for remaining in the harsh and acidic environment of the stomach with peristaltic movements and a high frequency of turnover of epithelial cells, H. pylori has developed different binding modes to structures present both in the mucus and on the surface of gastric cells and also to extracellular matrix proteins. Evidently, adhesion has a determinant role for a successful colonization by H. pylori. It has been shown that a small fraction of the H. pylori infection is in intimate contact and attached to the host epithelium. Despite its small proportion, this group maintains the persistency of infection. As there is no suitable in vitro system to mimic the human stomach for studies of H. pylori infection, we have developed the In Vitro Explant Culture technique (IVEC). By using this model we could show that H. pylori use the Lewis b blood group antigen to bind to the host gastric mucosa, during experimental conditions most similar to the in vivo situation. Furthermore, we could show that the host tissue responses to the bacterial attachment by expression of Interleukin 8 (IL- ), which will guide the inflammatory processes. Interestingly, by inhibition of bacterial adhesion through receptor competition i.e., by use of soluble Lewis b antigen, IL-8 production was hampered in the IVEC system, which further validates the presence of a tight relation between bacterial adhesion and induction of host immune responses. One of the inflammation signaling cursors in vivo is the upregulated sialylated Lewis x (sLex) antigen, an inflammation associated carbohydrate structure well established as a binding site for the selectin family of adhesion molecules. We could show that during chronic gastric inflammation, which is actually caused by the persistent H. pylori infection, the bacterial cells adapt their binding mode, and preferentially bind to sLex, which will provide an even more intimate contact with the host cells. This interaction is mediated by SabA, the H. pylori adhesin for sialylated oligosaccharides/glycoconjugates. By employing red blood cells as a model we could further demonstrate that SabA is identical to the “established” H. pylori hemagglutinin. We could also show that SabA binds to sialylated glycolipids (gangliosides) rather than glycoproteins on cell surfaces. Our result also revealed that SabA also binds to and activates human neutrophils. Such effect was unrelated to BabA and the H. pylori Neutrophil Activating Protein (HP- AP), which were not directly involved in the activation of neutrophils. Furthermore, phagocytosis of bacteria by neutrophils was demonstrated to be mainly dependent on presence of SabA. Interestingly, HP-NAP showed a possible role in guiding the bacterial adhesion during conditions of limited sialylation, i.e. equivalent to mild gastritis, when the tissue would be less inflamed and sialylated. In conclusion, H. pylori adhesion causes host tissue inflammation, then the bacteria will adapt to the new condition and bind to epithelial cells in a tighter mode by synergistic activities of BabA and SabA. Additionally, SabA bind to and activate human neutrophils, which will exacerbate inflammation responses and cause damage to host tissue. Thus, BabA and SabA are potential candidates to be targeted for therapeutic strategies against H. pylori and gastric disease.

  • 203.
    Olsson, Gert E
    et al.
    Institutionen för vilt, fisk och miljö, Sveriges lantbruksuniversitet, Umeå.
    Hjertqvist, Marika
    Epidemiologiska avdelningen, Smittskyddsinstitutet, Solna.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Hörnfeldt, Birger
    Institutionen för vilt, fisk och miljö, Sveriges lantbruksuniversitet, Umeå.
    Sorkfeberprognos: sorkdata pekar på nytt, stort utbrott2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 29-31, p. 1769-1770Article in journal (Other academic)
  • 204.
    Olsson, Gert E
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    White, Neil
    Department of Primary Industries and Fisheries, Toowoomba, Australia.
    Hjältén, Joakim
    Department of Animal Ecology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Habitat factors associated with bank voles (Clethrionomys glareolus) and concomitant hantavirus in northern Sweden2005In: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 5, no 4, p. 315-323Article in journal (Refereed)
    Abstract [en]

    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.

  • 205.
    Olsson, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Bergh Drott, Johanna
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Laurantzon, Lovisa
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Laurantzon, Oscar
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Chronic prostatic infection and inflammation by propionibacterium acnes in a rat prostate infection model2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 12, p. e51434-Article in journal (Refereed)
    Abstract [en]

    Chronic inflammation in the prostate, seen as infiltration of inflammatory cells into the prostate gland in histological samples, affects approximately half the male population without indication of prostate disease, and is almost ubiquitous in patients diagnosed with benign prostate hyperplasia and cancer. Several studies have demonstrated the Gram-positive bacterium Propionibacterium acnes to be frequently present in prostate tissue from men suffering from prostate disease. P. acnes has been shown to be associated with histological inflammation in human prostatectomy specimens, and also to induce strong inflammatory response in prostate-derived tissue culture models. The present paper describes a rat model for assessment of the pathogenic potential of P. acnes in prostate. Prostate glands of Sprague Dawley rats (n = 98) were exposed via an abdominal incision and live P. acnes or, in control rats, saline were injected into the ventral and dorso-lateral lobes. Rats were sacrificed 5 days, 3 weeks, 3 months and 6 months post infection, and prostate tissue was analyzed for bacterial content and histological inflammation. Rat sera were assessed for levels of CRP and anti-P. acnes IgG. Live P. acnes could be recovered from the dorso-lateral lobes up to 3 months post infection, while the ventral lobes were cleared from bacteria at that time. In samples up to 3 months post infection, the dorso-lateral lobes exhibited intense focal inflammation. CRP and IgG levels were elevated throughout the span of the experiment, and reached maximum levels 3 weeks and 3 months post infection, respectively. We show that P. acnes have the potential to cause chronic infection in previously healthy prostate, and that the infection has potential to cause chronic histological inflammation in the infected tissue. The high prevalence of P. acnes in human prostate tissue calls for resolution of pathogenic details. The present rat model suggests that complications such as chronic inflammation may be induced by P. acnes infection.

  • 206.
    Olsson, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Johansson, Jörgen
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Laboratory Medicine, Clinical Microbiology, Umeå University Hospital, Umeå, Sweden.
    Honkala, Emma
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Blomqvist, Bert
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Laboratory Medicine, Clinical Microbiology, Umeå University Hospital, Umeå, Sweden.
    Kok, Eloise
    Weidung, Bodil
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Urea dilution of serum for reproducible anti-HSV1 IgG avidity index2019In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 19, article id 164Article in journal (Refereed)
    Abstract [en]

    Herpes simplex virus type 1 (HSV1), establishes life-long latency and can cause symptoms during both first-time infection and later reactivation. The aim of the present study was to describe a protocol to generate a reliable and discriminative avidity index (AI) for anti-HSV1 IgG content in human sera. Human serum from two distinct cohorts; one a biobank collection (Betula) (n = 28), and one from a clinical diagnostics laboratory at Northern Sweden University Hospital (NUS) (n = 18), were assessed for presence of IgG antibodies against HSV1 by a commercially available ELISA-kit. Addition of urea at the incubation step reduces effective binding, and the ratio between urea treated sample and non-treated sample was used to express an avidity index (AI) for individual samples. AI score ranged between 43.2 and 73.4% among anti-HSV1 positive biobank sera. Clinical samples ranged between 36.3 and 74.9%. Reproducibility expressed as an intraclass correlation coefficient (ICC) was estimated at 0.948 (95% CI: 0.900-0.979) and 0.989 (95% CI 0.969-0.996) in the biobank and clinical samples, respectively. The method allows for AI scoring of anti-HSV1 IgG from individual human sera with a single measurement. The least significant change between two measurements at the p < 0.05 level was estimated at 5.4 and 3.2 points, respectively, for the two assessed cohorts.

  • 207.
    Olsson, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kok, Eloise
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Herpes virus seroepidemiology in the adult Swedish population2017In: Immunity & Ageing, ISSN 1742-4933, E-ISSN 1742-4933, Vol. 14, article id 10Article in journal (Refereed)
    Abstract [en]

    Background: Herpes viruses establish a life-long latency and can cause symptoms during both first-time infection and later reactivation. The aim of the present study was to describe the seroepidemiology of Herpes simplex type 1 (HSV1), Herpes simplex type 2 (HSV2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV) and Human herpes virus type 6 (HHV6) in an adult Swedish population (35-95 years of age). Methods: Presence of antibodies against the respective viruses in serum from individuals in the Betula study was determined with an enzyme-linked immunosorbent assay (ELISA). Singular samples from 535 persons (53.9% women, mean age at inclusion 62.7 +/- 14.4 years) collected 2003-2005 were analyzed for the five HHVs mentioned above. In addition, samples including follow-up samples collected 1988-2010 from 3,444 persons were analyzed for HSV. Results: Prevalence of HSV1 was 79.4%, HSV2 12.9%, CMV 83.2%, VZV 97.9%, and HHV6 97.5%. Herpes virus infections were more common among women (p = 0.010) and a lower age-adjusted HSV seroprevalence was found in later birth cohorts (p < 0.001). The yearly incidence of HSV infection was estimated at 14.0/1000. Conclusion: Women are more often seropositive for HHV, especially HSV2. Age-adjusted seroprevalence for HSV was lower in later birth cohorts indicating a decreasing childhood and adolescent risk of infection.

  • 208. O'Reilly, Kathleen M.
    et al.
    Lowe, Rachel
    Edmunds, W. John
    Mayaud, Philippe
    Kucharski, Adam
    Eggo, Rosalind M.
    Funk, Sebastian
    Bhatia, Deepit
    Khan, Kamran
    Kraemer, Moritz U. G.
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Department of Disease Control, London School of Hygiene & Tropical Medicine, London, UK; Institute of Public Health, University of Heidelberg, Heidelberg, Germany.
    Rodrigues, Laura C.
    Brasil, Patricia
    Massad, Eduardo
    Jaenisch, Thomas
    Cauchemez, Simon
    Brady, Oliver J.
    Yakob, Laith
    Projecting the end of the Zika virus epidemic in Latin America: a modelling analysis2018In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 16, article id 180Article in journal (Refereed)
    Abstract [en]

    Background: Zika virus (ZIKV) emerged in Latin America and the Caribbean (LAC) region in 2013, with serious implications for population health in the region. In 2016, the World Health Organization declared the ZIKV outbreak a Public Health Emergency of International Concern following a cluster of associated neurological disorders and neonatal malformations. In 2017, Zika cases declined, but future incidence in LAC remains uncertain due to gaps in our understanding, considerable variation in surveillance and the lack of a comprehensive collation of data from affected countries.

    Methods: Our analysis combines information on confirmed and suspected Zika cases across LAC countries and a spatio-temporal dynamic transmission model for ZIKV infection to determine key transmission parameters and projected incidence in 90 major cities within 35 countries. Seasonality was determined by spatio-temporal estimates of Aedes aegypti vectorial capacity. We used country and state-level data from 2015 to mid-2017 to infer key model parameters, country-specific disease reporting rates, and the 2018 projected incidence. A 10-fold cross-validation approach was used to validate parameter estimates to out-of-sample epidemic trajectories.

    Results: There was limited transmission in 2015, but in 2016 and 2017 there was sufficient opportunity for wide-spread ZIKV transmission in most cities, resulting in the depletion of susceptible individuals. We predict that the highest number of cases in 2018 would present within some Brazilian States (Sao Paulo and Rio de Janeiro), Colombia and French Guiana, but the estimated number of cases were no more than a few hundred. Model estimates of the timing of the peak in incidence were correlated (p < 0.05) with the reported peak in incidence. The reporting rate varied across countries, with lower reporting rates for those with only confirmed cases compared to those who reported both confirmed and suspected cases.

    Conclusions: The findings suggest that the ZIKV epidemic is by and large over within LAC, with incidence projected to be low in most cities in 2018. Local low levels of transmission are probable, but the estimated rate of infection suggests that most cities have a population with high levels of herd immunity.

  • 209. Orikiiriza, Judy
    et al.
    Surowiec, Izabella
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lindquist, Elisabeth
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Bonde, Mari
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Magambo, Jimmy
    Muhinda, Charles
    Bergström, Sven
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Normark, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Lipid response patterns in acute phase paediatric Plasmodium falciparum malaria2017In: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 13, no 4, article id 41Article in journal (Refereed)
    Abstract [en]

    Introduction: Several studies have observed serum lipid changes during malaria infection in humans. All of them were focused at analysis of lipoproteins, not specific lipid molecules. The aim of our study was to identify novel patterns of lipid species in malaria infected patients using lipidomics profiling, to enhance diagnosis of malaria and to evaluate biochemical pathways activated during parasite infection.

    Methods: Using a multivariate characterization approach, 60 samples were representatively selected, 20 from each category (mild, severe and controls) of the 690 study participants between age of 0.5–6 years. Lipids from patient’s plasma were extracted with chloroform/methanol mixture and subjected to lipid profiling with application of the LCMS-QTOF method.

    Results: We observed a structured plasma lipid response among the malaria-infected patients as compared to healthy controls, demonstrated by higher levels of a majority of plasma lipids with the exception of even-chain length lysophosphatidylcholines and triglycerides with lower mass and higher saturation of the fatty acid chains. An inverse lipid profile relationship was observed when plasma lipids were correlated to parasitaemia.

    Conclusions: This study demonstrates how mapping the full physiological lipid response in plasma from malaria-infected individuals can be used to understand biochemical processes during infection. It also gives insights to how the levels of these molecules relate to acute immune responses.

  • 210. Orsborne, James
    et al.
    DeRaedt Banks, Sarah
    Hendy, Adam
    Gezan, Salvador A.
    Kaur, Harparkash
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
    Lindsay, Steve W.
    Logan, James G.
    Personal Protection of Permethrin-Treated Clothing against Aedes aegypti, the Vector of Dengue and Zika Virus, in the Laboratory2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, article id e0152805Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The dengue and Zika viruses are primarily transmitted by Aedes aegypti mosquitoes, which are most active during day light hours and feed both in and outside of the household. Personal protection technologies such as insecticide-treated clothing could provide individual protection. Here we assessed the efficacy of permethrin-treated clothing on personal protection in the laboratory.

    METHODS: The effect of washing on treated clothing, skin coverage and protection against resistant and susceptible Ae. aegypti was assessed using modified WHO arm-in-cage assays. Coverage was further assessed using free-flight room tests to investigate the protective efficacy of unwashed factory-dipped permethrin-treated clothing. Clothing was worn as full coverage (long sleeves and trousers) and partial coverage (short sleeves and shorts). Residual permethrin on the skin and its effect on mosquitoes was measured using modified WHO cone assays and quantified using high-pressure liquid chromatography (HPLC) analysis.

    RESULTS: In the arm-in-cage assays, unwashed clothing reduced landing by 58.9% (95% CI 49.2-66.9) and biting by 28.5% (95% CI 22.5-34.0), but reduced to 18.5% (95% CI 14.7-22.3) and 11.1% (95% CI 8.5-13.8) respectively after 10 washes. Landing and biting for resistant and susceptible strains was not significantly different (p<0.05). In free-flight room tests, full coverage treated clothing reduced landing by 24.3% (95% CI 17.4-31.7) and biting by 91% (95% CI 82.2-95.9) with partial coverage reducing landing and biting by 26.4% (95% CI 20.3-31.2) and 49.3% (95% CI 42.1-59.1) respectively with coverage type having no significant difference on landing (p<0.05). Residual permethrin was present on the skin in low amounts (0.0041mg/cm2), but still produced a KD of >80% one hour after wearing treated clothing.

    CONCLUSION: Whilst partially covering the body with permethrin-treated clothing provided some protection against biting, wearing treated clothing with long sleeves and trousers provided the highest form of protection. Washing treated clothing dramatically reduced protection provided. Permethrin-treated clothing could provide protection to individuals from Ae. aegypti that show permethrin resistance. Additionally, it could continue to provide protection even after the clothing has been worn. Field trials are urgently needed to determine whether clothing can protect against dengue and Zika.

  • 211. Paixao, Enny S.
    et al.
    Leong, Wei-Yee
    Rodrigues, Laura C.
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Asymptomatic Prenatal Zika Virus Infection and Congenital Zika Syndrome2018In: Open Forum Infectious Diseases, ISSN 2328-8957, Vol. 5, no 4Article in journal (Refereed)
    Abstract [en]

    To investigate to what extent asymptomatic vs symptomatic prenatal Zika virus infections contribute to birth defects, we identified 3 prospective and 8 retrospective studies. The ratio varied greatly in the retrospective studies, most likely due to recruitment and recall bias. The prospective studies revealed a ratio of 1: 1 for asymptomatic vs symptomatic maternal Zika infections resulting in adverse fetal outcomes.

  • 212.
    Palmgren, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Importance of wild birds in the spread of Salmonella2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Salmonella is one of the most important enteropathogenic bacteria. It is responsible for about 5000 reported cases of human gastroenteritis each year in Sweden. Salmonellosis is a zoonotic disease, and the bacterium has the ability to infect a variety of both domestic and wild animal species.

    In studies of Swedish wild bird populations, we found that Black-headed gull may be the main reservoir for Salmonella in birds, and that Salmonella infection is expressed as carriage with no obvious disease manifestations. Black-headed gull is a migratory bird and can transport strains of Salmonella with virulence traits like antibiotic resistance, from sources outside Sweden. Genetic molecular methods, PFGE and IS200, also demonstrate that Black-headed gull play a role in the transmission chain of Salmonella in Sweden.

    In a study of the Swedish Peregrine Falcon population, Salmonella amager and Campylobacter jejuni were found. There were indications, based on serotyping of Salmonella and genetical typing by PFGE of Campylobacter that these isolates were transmitsted to the falcons from a human or domestic animal source. This bird of prey has sparse contact with humans but may be infected by Salmonella of human origin by feeding on other birds, like gull.

    Salmonella was found in penguins, albatrosses and mainly in seals in a study in Antarctica. Several features of the Salmonella serotypes found indicate a human source for Salmonella infection in these animals, and also a spread of Salmonella within and between animal species in Antarctica.

  • 213.
    Palmgren, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Meningococcal disease and climate2009In: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 2Article in journal (Refereed)
  • 214.
    Palmgren, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Aspán, A.
    Department of Bacteriology, National Veterinary Institute, SE-750 07 Uppsala, Sweden.
    Bengtsson, K.
    Broman, Tina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Blomquist, L.
    Bergström, Sven
    Umeå University, Faculty of Medicine, Microbiology.
    Sellin, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Wollin, R.
    Department of Bacteriology, Swedish Institute for Infectious Disease Control, Solna, Sweden.
    Olsen, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Salmonella carriage in European Black headed gulls (Larus ridibundus) in SwedenManuscript (preprint) (Other academic)
  • 215.
    Palmgren, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Broman, Tina
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Waldenström, Jonas
    Research Institute for Zoonotic Ecology and Epidemiology, Färjestaden, Sweden and Department of Animal Ecology, Ecology Building, Lund University, Lund, Sweden .
    Lindberg, Peter
    Department of Zoology, University of Göteborg, Göteborg, Sweden .
    Aspán, Anna
    Department of Bacteriology, National Veterinary Institute, Uppsala, Sweden .
    Olsen, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Research Institute for Zoonotic Ecology and Epidemiology, Färjestaden, Sweden.
    Salmonella Amager, Campylobacter jejuni, and urease-positive thermophilic Campylobacter found in free-flying peregrine falcons (Falco peregrinus) in Sweden2004In: Journal of Wildlife Diseases, ISSN 0090-3558, E-ISSN 1943-3700, Vol. 40, no 3, p. 583-587Article in journal (Refereed)
    Abstract [en]

    Rare species with small population sizes are vulnerable to perturbations such as disease, inbreeding, or random events. The threat arising from microbial pathogens could be large and other species could act as reservoirs for pathogens. We report finding three enteric bacterial species, Salmonella Amager, Campylobacter jejuni, and urease-positive thermophilic Campylobacter, in nestling free-flying peregrine falcons (Falco peregrinus) in Sweden in 2000. Campylobacter jejuni isolates exhibited marked genetic similarities to an isolate from a human, providing a possible association between a human-associated strain of this bacterium and peregrine falcons.

  • 216.
    Palmgren, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    McCafferty, D.
    British Antarctic SurŠey, National EnŠironment Research Council, Cambridge, UK.
    Aspán, A.
    Department of Bacteriology, National Veterinary Institute, Uppsala, Sweden.
    Broman, Tina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Sellin, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Wollin, R.
    Department of Bacteriology, Swedish Institute for Infectious Disease Control, Solna, Sweden.
    Bergström, Sven
    Umeå University, Faculty of Medicine, Microbiology.
    Olsen, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Department of Infectious Diseases, Kalmar County Hospital, S-381 95 Kalmar, Sweden.
    Salmonella in sub-Antarctica: low heterogeneity in salmonella serotypes in South Georgian seals and birds2000In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 125, no 2, p. 257-262Article in journal (Refereed)
    Abstract [en]

    The number of human visitors to Antarctica is increasing rapidly, and with it a risk of introducing infectious organisms to native animals. To study the occurrence of salmonella serotypes in sub- Antarctic wildlife, faecal samples were collected from gentoo penguins, macaroni penguins, gray-headed albatrosses, black-browed albatrosses and Antarctic fur seals on Bird Island in the South Georgian archipelago during the austral summer of 1996 and 1998. In 1996, S. havana, S. typhimurium and S. enteritidis were isolated from 7% of gentoo penguins and 4% of fur seals. In 1998, however, 22% of fur seals were found to be infected with S. havana, S. enteritidis and S. newport. All isolates, except one, showed identical pulsed-field gel electrophoresis-patterns within each serotype, irrespective of sampling year and animal reservoir. No significant antibiotic resistance was found. The very low heterogeneity in the salmonella isolates found could either indicate a high genetic adaptation of the bacteria to the environment or a recent introduction of salmonella into the area.

  • 217.
    Palmgren, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Sellin, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Bergström, Sven
    Umeå University, Faculty of Medicine, Microbiology.
    Olsen, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Enteropathogenic Bacteria in Migrating Birds Arriving in Sweden1997In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 29, no 6, p. 565-568Article in journal (Refereed)
    Abstract [en]

    Birds have been thought to play a role in transmitting infectious agents like influenza, Borrelia and Salmonella. To investigate the role of migrating birds in the dispersal of enteropathogenic bacteria, stool samples from 151 wild birds (50 gulls and 101 passerines) just entering Sweden from their winter grounds were analysed for Salmonella spp., Campylobacter spp. and EHEC O157:H7. The thermophilic isolated enteropathogens found were further analysed by antibiograms. Among the 50 gulls examined, we found 2 isolates of Salmonella typhimurium with multiple antibiotic resistance. Three isolates of C. jejuni were found in the 101 stool samples from passerines. We did not isolate EHEC O157:H7 in any of the bird stools examined.

  • 218.
    Palmquist, Eva
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Claeson, Anna-Sara
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Neely, Gregory
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Stenberg, Berndt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Nordin, Steven
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Overlap in prevalence between various types of environmental intolerance2014In: International journal of hygiene and environmental health (Print), ISSN 1438-4639, E-ISSN 1618-131X, Vol. 217, no 4-5, p. 427-434Article in journal (Refereed)
    Abstract [en]

    Environmental intolerance (EI) is characterized by attribution of several, multisystem symptoms to specific environmental exposures, such as exposure to odorous/pungent chemicals, certain buildings, electromagnetic fields (EMFs) and everyday sounds. The symptoms are medically unexplained, non-specific and the symptoms overlap between different types of EI. To approach the issue of underlying mechanisms the matter of overlap in prevalence between intolerances can provide valuable information. The aim of the study was to examine if the overlap between intolerance to odorous/pungent chemicals, certain buildings, EMFs and sounds is larger than the expected overlap if no association would exist between them. The study was using cross-sectional data from the Västerbotten Environmental Health Study in Sweden; a large questionnaire-based survey. 8520 adults (18-79 years) were randomly selected after stratification for age and sex, of whom 3406 (40%) participated. Individuals with the four types of intolerance were identified either through self-report, or by having been physician-diagnosed with a specific EI. The overlaps between the four EIs were greater than predictions based on coincidence for both self-reported and diagnosed cases (except for the overlap between diagnosed intolerance to sounds and EMFs). The results raise the question whether different types of EI share similar underlying mechanisms, or at least that the sufferers of EI share some predisposition to acquire the conditions.

  • 219. Parkinson, Alan
    et al.
    Koch, Anders
    Evengård, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Infectious disease in the Arctic: a panorama in transition2015In: The new Arctic / [ed] Birgitta Evengård, Joan Nymand Larsen, Øyvind Paasche, Cham: Springer, 2015, p. 239-257Chapter in book (Refereed)
    Abstract [en]

    Many interconnected factors are responsible for the continuing and growing importance of infectious diseases in the Arctic. Many of these factors not only contribute to the risk of infectious diseases but also are broad determinants of the populations overall health. In the last part of the nineteenth and first part of the twentieth centuries, infectious diseases were major causes of mortality in Arctic communities. However the health of indigenous peoples of the circumpolar region has improved over the last 50 years. Despite these improvements, rates of viral hepatitis, tuberculosis, respiratory tract infections, invasive bacterial infections, sexually transmitted diseases, infections caused by Helicobacter pylori, and certain zoonotic and parasitic infections are higher in the Arctic indigenous peoples when compared to their respective national population rates. More recently the climate and ecosystem driven emergence of climate sensitive infectious diseases and disease patterns in the Arctic region presents an emerging challenge to those living in the Arctic. As in other parts of the world, a key component of prevention and control of infectious diseases is surveillance. The use of circumpolar health networks, together with effective coordinated surveillance can facilitate timely control of infectious disease outbreaks, inform public health officials’ decisions on resource allocation, provide data to adjust prevention and control strategies to maximize their effects, and inform future research needs.

  • 220. Pecl, Gretta T.
    et al.
    Araujo, Miguel B.
    Bell, Johann D.
    Blanchard, Julia
    Bonebrake, Timothy C.
    Chen, I-Ching
    Clark, Timothy D.
    Colwell, Robert K.
    Danielsen, Finn
    Evengård, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Falconi, Lorena
    Ferrier, Simon
    Frusher, Stewart
    Garcia, Raquel A.
    Griffis, Roger B.
    Hobday, Alistair J.
    Janion-Scheepers, Charlene
    Jarzyna, Marta A.
    Jennings, Sarah
    Lenoir, Jonathan
    Linnetved, Hlif I.
    Martin, Victoria Y.
    McCormack, Phillipa C.
    McDonald, Jan
    Mitchell, Nicola J.
    Mustonen, Tero
    Pandolfi, John M.
    Pettorelli, Nathalie
    Popova, Ekaterina
    Robinson, Sharon A.
    Scheffers, Brett R.
    Shaw, Justine D.
    Sorte, Cascade J. B.
    Strugnell, Jan M.
    Sunday, Jennifer M.
    Tuanmu, Mao-Ning
    Verges, Adriana
    Villanueva, Cecilia
    Wernberg, Thomas
    Wapstra, Erik
    Williams, Stephen E.
    Biodiversity redistribution under climate change: Impacts on ecosystems and human well-being2017In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 355, no 6332, article id eaai9214Article, review/survey (Refereed)
    Abstract [en]

    Distributions of Earth's species are changing at accelerating rates, increasingly driven by human-mediated climate change. Such changes are already altering the composition of ecological communities, but beyond conservation of natural systems, how and why does this matter? We review evidence that climate-driven species redistribution at regional to global scales affects ecosystem functioning, human well-being, and the dynamics of climate change itself. Production of natural resources required for food security, patterns of disease transmission, and processes of carbon sequestration are all altered by changes in species distribution. Consideration of these effects of biodiversity redistribution is critical yet lacking in most mitigation and adaptation strategies, including the United Nation's Sustainable Development Goals.

  • 221.
    Pettersson, Lisa
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Rasmuson, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Andersson, Charlotta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Hantavirus-specific IgA in saliva and viral antigen in the parotid gland in patients with hemorrhagic fever with renal syndrome2011In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 83, no 5, p. 864-870Article in journal (Refereed)
    Abstract [en]

    The Hantavirus genus comprises rodent borne, zoonotic viruses of the Bunyaviridae family that cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. Rodent saliva contains infectious hantavirus and evidence suggests that hantavirus is also shed in human saliva, but person-to-person transmission is rare. In saliva, immunoglobulin (Ig) A is the predominant immunoglobulin class. Secretory IgA serves as an important first line of defence on epithelial surfaces and the binding of secretory IgA to pathogens can inhibit adherence of microorganisms to mucosal cells and neutralize viruses. This study investigated the presence and importance of salivary IgA in relation to viral antigen in the saliva by testing Puumala hantavirus (PUUV) specific IgA, and RNA in saliva in acutely ill patients with HFRS. In saliva samples, PUUV specific IgA was detected in 12 of 33 (36%) patients with HFRS and 20 (61%) were PUUV RNA positive. There was a statistically significant inverse association between the presence of salivary IgA antibodies and PUUV RNA in the saliva. PUUV-specific IgA in saliva was not found in a long-term follow-up, while PUUV IgA in serum was detected in three patients, 28-32 months after the initial study. Notably, both PUUV RNA and PUUV nucleocapsid antigen were detected in endothelial cells within the parotid gland of a deceased patient with HFRS. J. Med. Virol. 83:864-870, 2011. © 2011 Wiley-Liss, Inc.

  • 222.
    Pettersson, Lisa
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Thunberg, Therese
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Klingström, Jonas
    Department of medicine, Center for Infectious Medicine, Karolinska institutet, Stockholm.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Viral load and humoral immune response in association with disease severity in Puumala hantavirus-infected patients-implications for treatment2014In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 20, no 3, p. 235-241Article in journal (Refereed)
    Abstract [en]

    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 among Puumala hantavirus (PUUV) viral RNA load, humoral immune response and disease severity in patients with HFRS. We performed a study of 105 PUUV-infected patients that were followed during the acute phase of disease and for up to 1-3 months later. Fifteen of the 105 patients (14%) were classified as having moderate/severe disease. A low PUUV-specific IgG response (p <0.05) and also a higher white blood cell count (p <0.001) were significantly associated with more severe disease. The PUUV RNA was detected in a majority of patient plasma samples up to 9 days after disease onset; however, PUUV RNA load or longevity of viraemia were not significantly associated with disease severity. We conclude that a low specific IgG response was associated with disease severity in patients with HFRS, whereas PUUV RNA load did not seem to affect the severity of HFRS. Our results raise the possibility of passive immunotherapy as a useful treatment for hantavirus-infected patients.

  • 223. Pilo, Paola
    et al.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Frey, Joachim
    Identification of Francisella tularensis cluster in Central and Western Europe2009In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 15, no 12, p. 2049-2051Article in journal (Refereed)
    Abstract [en]

    We conducted a molecular analysis of Francisella Marensis strains isolated in Switzerland and identified a specific subpopulation belonging to a cluster of F tularensis subsp. holarctica that is widely dispersed in central and western continental Europe. This subpopulation was present before the tularemia epidemics on the Iberian Peninsula.

  • 224. Povey, Michael
    et al.
    Henry, Ouzama
    Bergsaker, Marianne A. Riise
    Chlibek, Roman
    Esposito, Susanna
    Flodmark, Carl-Erik
    Gothefors, Leif
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. The Public Health Agency of Sweden.
    Man, Sorin
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Štéfkovičová, Mária
    Usonis, Vytautas
    Wysocki, Jacek
    Gillard, Paul
    Prymula, Roman
    Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine or one dose of monovalent varicella vaccine: 10-year follow-up of a phase 3 multicentre, observer-blind, randomised, controlled trial2019In: Lancet. Infectious diseases (Print), ISSN 1473-3099, E-ISSN 1474-4457, Vol. 19, no 3, p. 287-297Article in journal (Refereed)
    Abstract [en]

    Background: The duration of protection provided by varicella vaccines is unclear. We assessed the 10-year vaccine efficacy of two doses of a combined measles-mumps-rubella-varicella vaccine (MMRV), one live attenuated varicella vaccine (V) dose given after one measles-mumps-rubella vaccine (MMR) dose (MMR + V), versus two MMR doses (control vaccine) for the prevention of confirmed varicella.

    Methods: This was a phase 3b follow-up of an observer-blinded, randomised, controlled trial. In phase a, children aged 12-22 months (at first vaccination) from Czech Republic (Czechia), Greece, Italy, Lithuania, Norway, Poland, Romania, Russia, Slovakia, and Sweden were randomly assigned by computer-generated randomisation list (3: 3: 1) to receive two doses of MMRV, one dose of MMR and one dose of varicella vaccine, or two doses of MMR, 42 days apart. Varicella cases were confirmed by detection of viral DNA, or epidemiological link and clinical assessment, by an independent data monitoring committee; disease severity was based on a modified Vazquez scale. Hazard ratios for MMRV and MMR + V versus MMR estimated in the per-protocol cohort using a Cox proportional hazards regression model were used to calculate vaccine efficacy and 95% CI. Serious adverse events were recorded throughout the study in all vaccinated children. Study objectives were secondary and descriptive. The trial is registered at ClinicalTrials.gov, number NCT00226499.

    Findings: Between Sept 1, 2005, and May 10, 2006, 5803 children (mean age 14.2 months, SD 2.5) were vaccinated. The per-protocol cohort included 2279 children from the MMRV group, 2266 from the MMR + V group, and 744 from the MMR group. From baseline to a median follow-up of 9.8 years, 76 (3%) children in the MMRV group, 469 (21%) in the MMR + V group, and 352 (47%) in the MMR group had varicella. Vaccine efficacy against all varicella was 95.4% (95% CI 94.0-96.4) for MMRV and 67.2% (62.3-71.5) for MMR + V; vaccine efficacy against moderate or severe varicella was 99.1% (97.9-99.6) for MMRV and 89.5% (86.1-92.1) for MMR + V. During phase b, serious adverse events were reported by 290 (15%) of 1961 children in the MMRV group, 317 (16%) of 1978 in the MMR + V group, and 93 (15%) of 641 in the MMR group. There were no treatment-related deaths.

    Interpretation: The 10-years vaccine efficacy observed, suggests that a two-dose schedule of varicella vaccine provided optimum long-term protection for the prevention of varicella by offering individual protection against all severities of disease and leading to a potential reduction in transmission, as observed in the US experience with universal mass vaccination.

  • 225. Prymula, Roman
    et al.
    Szenborn, Leszek
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Wysocki, Jacek
    Albrecht, Piotr
    Traskine, Magali
    Gardev, Asparuh
    Song, Yue
    Borys, Dorota
    Safety, reactogenicity and immunogenicity of two investigational pneumococcal protein-based vaccines: results from a randomized phase II study in infants2017In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 35, no 35B, p. 4603-4611Article in journal (Refereed)
    Abstract [en]

    Introduction: Vaccination with formulations containing pneumococcal protein antigens such as pneumolysin toxoid (dPly) and histidine-triad protein D (PhtD) may extend serotype-related protection of pneumococcal conjugate vaccines (PCVs) against Streptococcus pneumoniae.

    Methods: This phase II, multi-center, observer-blind trial conducted in Europe (NCT01204658) assessed 2 investigational vaccines containing 10 serotype-specific polysaccharide conjugates of PHiD-CV and either 10 or 30 mu g of dPly and PhtD each. Infants randomized 1:1:1:1 received 4 doses of PHiD-CV/dPly/PhtD-10, PHiD-CV/c1Ply/PhtD-30, PHiD-CV, or 13-valent PCV (PCV13), co-administered with DTPa-HBV-IPV/Flib, at ages 2, 3, 4 and 12-15 months. Occurrences of fever >40.0 degrees C following primary vaccination with PHiD-CV/dPly/PhtD vaccines compared to PHiD-CV (non-inferiority objective), dose superiority, safety and immunogenicity were assessed.

    Results: 575 children received primary vaccination, and 564 booster vaccination. The non-inferiority objective was met; no fever >40.0 degrees C causally related to vaccination was reported during primary vaccination. Incidence of adverse events appeared similar between the 3 PHiD-CV groups. Serious adverse events were reported in 13, 9, 21 (1 related to vaccination), and 17 children in the PHiD-CV/c1Ply/PhtD-10, PHiD-CV/dPly/PhtD-30, PHiD-CV, and PCV13 groups, respectively. PHiD-CV/dPly/PhtD-30 was superior to PHiD-CV/c1Ply/PhtD-10 in terms of post-dose 3 anti-Ply and Anti-PhtD antibody levels. Anti-Ply and anti-PhtD antibody levels were higher in both PHiD-CV/dPly/PhtD groups than in controls and increased from post-primary to post-booster timepoint. Post-primary and booster vaccination, for each PHiD-CV serotype, >= 98.5% of participants in PHiD-CV/dPly/PhtD groups had antibody concentrations >= 0.2 mu g/mL, except for 6B (>= 72.3%) and 23 F (>= 82.7%) post-primary vaccination. Similar results were observed in the PHiD-CV group. Immune responses to protein D and DTPa-HBV-IPV/Hib were within similar ranges for the 3 PHiD-CV groups.

    Conclusion: Both PHiD-CV/dPly/PhtD formulations co-administered with DTPa-HBV-IPV/Hib in infants were well-tolerated and immunogenic for dPly and PhtD antigens, while immune responses to serotype-specific, protein D and co-administered antigens did not appear altered in comparison to PHiD-CV group. 

  • 226.
    Rasmuson, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Cardiopulmonary involvement in Puumala hantavirus infection2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome in Europe. After inhalation of virus shed by bank voles, the virus systemically targets the vascular endothelium leading to vascular dysfunction and leakage. Many patients with PUUV infection experience cardiopulmonary manifestations but the underlying mechanisms have not been determined.

    The aims of the studies presented were to describe cardiopulmonary manifestations, investigate pathogenetic mechanisms including presence of virus in the lungs and the local immune response in PUUV infection.

    The results showed cardiopulmonary involvement of varying severity in almost all studied patients. High-resolution computed tomography frequently revealed vascular leakage into the lungs or pleural cavities. Pulmonary function tests generally showed reduced gas diffusing capacity, evidenced in patients as dyspnea, poor oxygenation and frequent need of oxygen treatment. Among patients who were not fully recovered at 3 months follow-up, remaining decreased gas diffusing capacity was highly common.

    Echocardiography revealed mainly right heart dysfunction which was related to manifestations within the lungs, in terms of increased estimated pulmonary vascular resistance, mild to moderate pulmonary hypertension, and reduced right ventricular systolic function in patients with more pronounced lung involvement, as indicated by need of oxygen treatment.

    Analyses on bronchoalveolar lavage (BAL) and bronchial biopsies revealed a highly activated cytotoxic T cell (CTL) response in the lungs. The CTL response was not balanced by the expansion of regulatory T cells and high numbers of CTLs were associated with more severe disease. PUUV RNA was detected in almost all patients’ BAL samples and the viral load was inversely correlated to the number of CTLs.

    Three patients presenting with severe and fatal cardiopulmonary distress were also described. Autopsies revealed PUUV protein in vascular endothelium in all investigated organs, including the heart and lungs, along with a massive CTL response mainly in the lungs.

    In conclusion, cardiopulmonary involvement of varying severity was present in almost all patients with PUUV infection. Cytotoxic immune responses could contribute to disease development but also help in clearing the infection. Long lasting fatigue after hantavirus infection may be explained by remaining manifestations within the lungs. 

  • 227.
    Rasmuson, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Andersson, Charlotta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Norrman, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Time to revise the paradigm of hantavirus syndromes? Hantavirus pulmonary syndrome caused by European hantavirus2011In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 30, no 5, p. 685-690Article in journal (Refereed)
    Abstract [en]

    Hantaviruses have previously been recognised to cause two separate syndromes: hemorrhagic fever with renal syndrome in Eurasia, and hantavirus pulmonary syndrome (HPS) in the Americas. However, increasing evidence suggests that this dichotomy is no longer fruitful when recognising human hantavirus disease and understanding the pathogenesis. Herein are presented three cases of severe European Puumala hantavirus infection that meet the HPS case definition. The clinical and pathological findings were similar to those found in American hantavirus patients. Consequently, hantavirus infection should be considered as a cause of acute respiratory distress in all endemic areas worldwide.

  • 228.
    Rasmuson, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Sörensen, Karen
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Hedström, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Cardiopulmonary involvement in Puumala hantavirus infection2013In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 13, no 1, p. 501-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: 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.

    METHODS: Twenty-seven hospitalised patients with PUUV-infection were examined with lung function tests, chest high-resolution CT (HRCT), echocardiography including speckle tracking strain rate analysis, ECG and measurements of cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-ProBNP) and troponin T. Patients were re-evaluated after 3 months. Twenty-five age and sex-matched volunteers acted as controls for echocardiography data.

    RESULTS: Two-thirds of the patients experienced respiratory symptoms as dry cough or dyspnoea. Gas diffusing capacity was impaired in most patients, significantly improving at follow-up but still subnormal in 38%. HRCT showed thoracic effusions or pulmonary oedema in 46% of the patients. Compared to controls, the main echocardiographic findings in patients during the acute phase were significantly higher pulmonary vascular resistance, higher systolic pulmonary artery pressure, lower left ventricular ejection fraction and impaired left atrial myocardial motion. Pathological ECG, atrial fibrillation or T-wave changes, was demonstrated in 26% of patients. NT-ProBNP concentrations were markedly increased and were inversely associated with gas diffusing capacity but positively correlated to pulmonary vascular resistance. Furthermore, patients experiencing impaired general condition at follow-up had significantly lower gas diffusing capacity and higher pulmonary vascular resistance, compared to those feeling fully recovered.

    CONCLUSIONS: In a majority of patients with PUUV-infection, both cardiac and pulmonary involvement was demonstrated with implications on patients' recovery. The results demonstrate vascular leakage in the lungs that most likely is responsible for impaired gas diffusing capacity and increased pulmonary vascular resistance with secondary pulmonary hypertension and right heart distress. Interestingly, NT-ProBNP was markedly elevated even in the absence of overt ventricular heart failure. The method of simultaneous investigations of important cardiac and respiratory measurements improves the interpretation of the underlying pathophysiologic mechanisms.

  • 229.
    Rasmuson, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Linderholm, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Presence of activated airway T lymphocytes in human puumala hantavirus disease2011In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 140, no 3, p. 715-722Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hantaviruses cause two clinical syndromes; hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The clinical spectrum in HFRS also often involves respiratory symptoms. As information of the pulmonary pathogenesis in HFRS is limited, we aimed to further study the local airway immune response in the lower airways.

    METHODS: In 15 hospitalized HFRS patients, bronchoscopy was performed with sampling of endobronchial mucosal biopsies and bronchoalveolar lavage (BAL) fluid. Biopsies were stained for leukocytes, lymphocyte subsets and vascular endothelial adhesion molecules. BAL fluid and blood lymphocyte subsets were determined using flow cytometry. Fourteen healthy volunteers acted as control group.

    RESULTS: Compared to controls, endobronchial mucosal biopsies from HFRS patients revealed increased numbers of CD8(+) T cells in both epithelium and submucosa (p≤0.001), along with an increase in submucosal CD4(+) T cells (p=0.001). In contrast, patients' submucosal neutrophil and eosinophil numbers were reduced (p<0.001). The expression of vascular cell adhesion molecule-1 (VCAM-1) was enhanced in HFRS patients (p<0.001). In HFRS patients, analyses of T cell subsets in BAL fluid showed higher proportions of CD3(+) and CD8(+) T cells (p=0.011 and p=0.025), NK cells (p<0.001) together with an increased expression of activation markers HLA-DR and CD25 on T cells (p<0.001 and p<0.001).

    CONCLUSIONS: The present findings indicate a local immune response in terms of activated T lymphocytes in the lungs of patients with HFRS. The elevated expression of activation markers and VCAM-1 further implies the importance of cytotoxic lymphocytes in the pathogenesis of pulmonary involvement in HFRS.

  • 230.
    Rasmuson, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mohamed, Nahla
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Lejon, Kristina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection2016In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, no 4, p. 713-721Article in journal (Refereed)
    Abstract [en]

    Hantavirus infections may cause severe and sometime life-threatening lung failure. The pathogenesis is not fully known and there is an urgent need for effective treatment. We aimed to investigate the association between pulmonary viral load and immune responses, and their relation to disease severity. Bronchoscopy with sampling of bronchoalveolar lavage (BAL) fluid was performed in 17 patients with acute Puumala hantavirus infection and 16 healthy volunteers acting as controls. Lymphocyte subsets, granzyme concentrations, and viral load were determined by flow cytometry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. Analyses of BAL fluid revealed significantly higher numbers of activated CD8+ T cells and natural killer (NK) cells, as well as higher concentrations of the cytotoxins granzymes A and B in hantavirus-infected patients, compared to controls. In patients, Puumala hantavirus RNA was detected in 88 % of BAL cell samples and correlated inversely to the T cell response. The magnitude of the pulmonary cytotoxic lymphocyte response correlated to the severity of disease and systemic organ dysfunction, in terms of need for supplemental oxygen treatment, hypotension, and laboratory data indicating renal failure, cardiac dysfunction, vascular leakage, and cell damage. Regulatory T cell numbers were significantly lower in patients compared to controls, and may reflect inadequate immune regulation during hantavirus infection. Hantavirus infection elicits a pronounced cytotoxic lymphocyte response in the lungs. The magnitude of the immune response was associated with disease severity. These results give insights into the pathogenesis and possibilities for new treatments.

  • 231. Rehn, Moa
    et al.
    Wallensten, Anders
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Lilja, Mikael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Grunewald, Maria
    Stenmark, Stephan
    Kark, Malin
    Lindh, Johan
    Post-infection symptoms following two large waterborne outbreaks of Cryptosporidium hominis in Northern Sweden, 2010-20112015In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 15, article id 529Article in journal (Refereed)
    Abstract [en]

    Background: In 2010-2011, two large waterborne outbreaks caused by Cryptosporidium hominis affected two cities in Sweden, Ostersund and Skelleftea. We investigated potential post-infection health consequences in people who had reported symptoms compatible with cryptosporidiosis during the outbreaks using questionnaires. Methods: We compared cases linked to these outbreaks with non-cases in terms of symptoms present up to eleven months after the initial infection. We examined if cases were more likely to report a list of symptoms at follow-up than non-cases, calculating odds ratios (OR) and 95 % confidence intervals (CI) obtained through logistic regression. Results: A total of 872 (310 cases) and 743 (149 cases) individuals responded to the follow-up questionnaires in Ostersund and Skelleftea respectively. Outbreak cases were more likely to report diarrhea (Ostersund OR: 3.3, CI: 2.0-5.3. Skelleftea OR: 3.6, CI: 2.0-6.6), watery diarrhea (Ostersund OR: 3.4, CI: 1.9-6.3. Skelleftea OR: 2.8, CI: 1.5-5.1) abdominal pain (Ostersund OR: 2.1, CI: 1.4-3.3, Skelleftea OR: 2.7, CI: 1.5-4.6) and joint pain (Ostersund OR: 2.0, CI: 1.2-3.3, Skelleftea OR: 2.0, CI: 1.1-3.6) at follow-up compared to non-cases. Conclusions: Our findings suggest that gastrointestinal-and joint symptoms can persist several months after the initial infection with Cryptosporidium and should be regarded as a potential cause of unexplained symptoms in people who have suffered from the infection.

  • 232. Reuterswärd, Philippa
    et al.
    Bergström, Sofia
    Orikiiriza, Judy
    Lindquist, Elisabeth
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Bergström, Sven
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Svahn, Helene Andersson
    Ayoglu, Burcu
    Uhlén, Mathias
    Wahlgren, Mats
    Normark, Johan
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ribacke, Ulf
    Nilsson, Peter
    Levels of human proteins in plasma associated with acute paediatric malaria2018In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 17, article id 426Article in journal (Refereed)
    Abstract [en]

    Background: The intimate interaction between the pathophysiology of the human host and the biology of the Plasmodium falciparum parasite results in a wide spectrum of disease outcomes in malaria. Development of severe disease is associated with a progressively augmented imbalance in pro- and anti-inflammatory responses to high parasite loads and sequestration of parasitized erythrocytes. Although these phenomena collectively constitute common denominators for the wide variety of discrete severe malaria manifestations, the mechanistic rationales behind discrepancies in outcome are poorly understood. Exploration of the human pathophysiological response by variations in protein profiles in plasma presents an excellent opportunity to increase the understanding. This is ultimately required for better prediction, prevention and treatment of malaria, which is essential for ongoing elimination and eradication efforts.

    Results: An affinity proteomics approach was used to analyse 541 paediatric plasma samples collected from community controls and patients with mild or severe malaria in Rwanda. Protein profiles were generated with an antibody-based suspension bead array containing 255 antibodies targetting 115 human proteins. Here, 57 proteins were identified with significantly altered levels (adjusted p-values < 0.001) in patients with malaria compared to controls. From these, the 27 most significant proteins (adjusted p-values < 10−14) were selected for a stringent analysis approach. Here, 24 proteins showed elevated levels in malaria patients and included proteins involved in acute inflammatory response as well as cell adhesion. The remaining three proteins, also implicated in immune regulation and cellular adhesivity, displayed lower abundance in malaria patients. In addition, 37 proteins (adjusted p-values < 0.05) were identified with increased levels in patients with severe compared to mild malaria. This set includes, proteins involved in tissue remodelling and erythrocyte membrane proteins. Collectively, this approach has been successfully used to identify proteins both with known and unknown association with different stages of malaria.

    Conclusion: In this study, a high-throughput affinity proteomics approach was used to find protein profiles in plasma linked to P. falciparum infection and malaria disease progression. The proteins presented herein are mainly involved in inflammatory response, cellular adhesion and as constituents of erythrocyte membrane. These findings have a great potential to provide increased conceptual understanding of host-parasite interaction and malaria pathogenesis.

  • 233.
    Rocklöv, Joacim
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Tozan, Yesim
    Ramadona, Aditya Lia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sewe, Maquins Odhiambo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Sudre, Bertrand
    Garrido, Jon
    de Saint Lary, Chiara Bellegarde
    Lohr, Wolfgang
    Semenza, Jan C.
    Using Big Data to Monitor the Introduction and Spread of Chikungunya, Europe, 20172019In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 25, no 6, p. 1041-1049Article in journal (Refereed)
    Abstract [en]

    With regard to fully harvesting the potential of big data, public health lags behind other fields. To determine this potential, we applied big data (air passenger volume from international areas with active chikungunya transmission, Twitter data, and vectorial capacity estimates of Aedes albopictus mosquitoes) to the 2017 chikungunya outbreaks in Europe to assess the risks for virus transmission, virus importation, and short-range dispersion from the outbreak foci. We found that indicators based on voluminous and velocious data can help identify virus dispersion from outbreak foci and that vector abundance and vectorial capacity estimates can provide information on local climate suitability for mosquitoborne outbreaks. In contrast, more established indicators based on Wikipedia and Google Trends search strings were less timely. We found that a combination of novel and disparate datasets can be used in real time to prevent and control emerging and reemerging infectious diseases.

  • 234. Rohmer, Laurence
    et al.
    Fong, Christine
    Abmayr, Simone
    Wasnick, Michael
    Larson Freeman, Theodore J
    Radey, Matthew
    Guina, Tina
    Svensson, Kerstin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Hayden, Hillary S
    Jacobs, Michael
    Gallagher, Larry A
    Manoil, Colin
    Ernst, Robert K
    Drees, Becky
    Buckley, Danielle
    Haugen, Eric
    Bovee, Donald
    Zhou, Yang
    Chang, Jean
    Levy, Ruth
    Lim, Regina
    Gillett, Will
    Guenthener, Don
    Kang, Allison
    Shaffer, Scott A
    Taylor, Greg
    Chen, Jinzhi
    Gallis, Byron
    D'Argenio, David A
    Forsman, Mats
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Olson, Maynard V
    Goodlett, David R
    Kaul, Rajinder
    Miller, Samuel I
    Brittnacher, Mitchell J
    Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains2007In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 8, no 6, article id R102Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Francisella tularensis subspecies tularensis and holarctica are pathogenic to humans, whereas the two other subspecies, novicida and mediasiatica, rarely cause disease. To uncover the factors that allow subspecies tularensis and holarctica to be pathogenic to humans, we compared their genome sequences with the genome sequence of Francisella tularensis subspecies novicida U112, which is nonpathogenic to humans. RESULTS: Comparison of the genomes of human pathogenic Francisella strains with the genome of U112 identifies genes specific to the human pathogenic strains and reveals pseudogenes that previously were unidentified. In addition, this analysis provides a coarse chronology of the evolutionary events that took place during the emergence of the human pathogenic strains. Genomic rearrangements at the level of insertion sequences (IS elements), point mutations, and small indels took place in the human pathogenic strains during and after differentiation from the nonpathogenic strain, resulting in gene inactivation. CONCLUSION: The chronology of events suggests a substantial role for genetic drift in the formation of pseudogenes in Francisella genomes. Mutations that occurred early in the evolution, however, might have been fixed in the population either because of evolutionary bottlenecks or because they were pathoadaptive (beneficial in the context of infection). Because the structure of Francisella genomes is similar to that of the genomes of other emerging or highly pathogenic bacteria, this evolutionary scenario may be shared by pathogens from other species.

  • 235. Roos, K.
    et al.
    Simark-Mattsson, C.
    Grahn Håkansson, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Larsson, L.
    Sandberg, T.
    Ahren, C.
    Can probiotic lactobacilli eradicate persistent carriage of meticillin-resistant Staphylococcus aureus?2011In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 78, no 1, p. 77-78Article in journal (Refereed)
  • 236. Rosjo, Egil
    et al.
    Lossius, Andreas
    Abdelmagid, Nada
    Lindstrom, Jonas C.
    Kampman, Margitta T.
    Jorgensen, Lone
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Olsson, Tomas
    Steffensen, Linn H.
    Torkildsen, Oivind
    Holmoy, Trygve
    Effect of high-dose vitamin D-3 supplementation on antibody responses against Epstein-Barr virus in relapsing-remitting multiple sclerosis2017In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, no 3, p. 395-402Article in journal (Refereed)
    Abstract [en]

    Background: Elevated antibody levels against Epstein–Barr virus (EBV) and a poor vitamin D status are environmental factors that may interact in relapsing-remitting multiple sclerosis (RRMS) aetiology.

    Objectives: To examine effects of high-dose oral vitamin D3 supplementation on antibody levels against EBV nuclear antigen 1 (EBNA1) in RRMS.

    Methods: Serum 25-hydroxyvitamin D3 (25(OH)D) and immunoglobulin G antibody levels against EBNA1 (whole protein and amino acid 385–420 fragment), EBV viral capsid antigen (VCA), cytomegalovirus (CMV) and varicella zoster virus (VZV) were measured in 68 RRMS patients enrolled in a 96-week randomised double-blinded placebo-controlled clinical trial of oral vitamin D3 supplementation (20,000 IU/week) (NCT00785473).

    Results: The mean 25(OH)D level more than doubled in the vitamin D group and was significantly higher than in the placebo group at study conclusion (123.2 versus 61.8 nmol/L, p < 0.001). Compared to the placebo group, both anti-EBNA1 protein and fragment antibody levels decreased in the vitamin D group from baseline to week 48 (p = 0.038 and p = 0.004, respectively), but not from baseline to week 96. Vitamin D3 supplementation did not affect antibodies against VCA, CMV or VZV.

    Conclusion: The results indicate that high-dose oral vitamin D3 supplementation can affect humoral immune responses against the latent EBV antigen EBNA1 in RRMS.

  • 237. Ruzek, Daniel
    et al.
    Zupanc, Tatjana Avsic
    Borde, Johannes
    Chrdle, Ales
    Eyer, Ludek
    Karganova, Galina
    Kholodilov, Ivan
    Knap, Natasa
    Kozlovskaya, Liubov
    Matveev, Andrey
    Miller, Andrew D.
    Osolodkin, Dmitry I.
    Överby, Anna K.
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Tikunova, Nina
    Tkachev, Sergey
    Zajkowska, Joanna
    Tick-borne encephalitis in Europe and Russia: review of pathogenesis, clinical features, therapy, and vaccines2019In: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, Vol. 164, p. 23-51Article, review/survey (Refereed)
    Abstract [en]

    Tick-borne encephalitis (TBE) is an illness caused by tick-borne encephalitis virus (TBEV) infection which is often limited to a febrile illness, but may lead to very aggressive downstream neurological manifestations. The disease is prevalent in forested areas of Europe and northeastern Asia, and is typically caused by infection involving one of three TBEV subtypes, namely the European (TBEV-Eu), the Siberian (TBEV-Sib), or the Far Eastern (TBEV-FE) subtypes. In addition to the three main TBEV subtypes, two other subtypes; i.e., the Baikalian (TBEV-Bkl) and the Himalayan subtype (TBEV-Him), have been described recently. In Europe, TBEV-Eu infection usually results in only mild TBE associated with a mortality rate of < 2%. TBEV-Sib infection also results in a generally mild TBE associated with a non-paralytic febrile form of encephalitis, although there is a tendency towards persistent TBE caused by chronic viral infection. TBE-FE infection is considered to induce the most severe forms of TBE. Importantly though, viral subtype is not the sole determinant of TBE severity; both mild and severe cases of TBE are in fact associated with infection by any of the subtypes. In keeping with this observation, the overall TBE mortality rate in Russia is similar to 2%, in spite of the fact that TBEV-Sib and TBEV-FE subtypes appear to be inducers of more severe TBE than TBEV-Eu. On the other hand, TBEV-Sib and TBEV-FE subtype infections in Russia are associated with essentially unique forms of TBE rarely seen elsewhere if at all, such as the hemorrhagic and chronic (progressive) forms of the disease. For post-exposure prophylaxis and TBE treatment in Russia and Kazakhstan, a specific anti-TBEV immunoglobulin is currently used with well-documented efficacy, but the use of specific TBEV immunoglobulins has been discontinued in Europe due to concerns regarding antibody-enhanced disease in naive individuals. Therefore, new treatments are essential. This review summarizes available data on the pathogenesis and clinical features of TBE, plus different vaccine preparations available in Europe and Russia. In addition, new treatment possibilities, including small molecule drugs and experimental immunotherapies are reviewed. The authors caution that their descriptions of approved or experimental therapies should not be considered to be recommendations for patient care.

  • 238.
    Rydén, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Björk, Rafael
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Schäfer, Martina L
    Lundström, Jan O
    Petersén, Bodil
    Lindblom, Anders
    Forsman, Mats
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Outbreaks of tularemia in a boreal forest region depends on mosquito prevalence2012In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 205, no 2, p. 297-304Article in journal (Refereed)
    Abstract [en]

    Background. We aimed to evaluate the potential association of mosquito prevalence in a boreal forest area with transmission of the bacterial disease tularemia to humans, and model the annual variation of disease using local weather data.

    Methods. A prediction model for mosquito abundance was built using weather and mosquito catch data. Then a negative binomial regression model based on the predicted mosquito abundance and local weather data was built to predict annual numbers of humans contracting tularemia in Dalarna County, Sweden.

    Results. Three hundred seventy humans were diagnosed with tularemia between 1981 and 2007, 94% of them during 7 summer outbreaks. Disease transmission was concentrated along rivers in the area. The predicted mosquito abundance was correlated (0.41, P < .05) with the annual number of human cases. The predicted mosquito peaks consistently preceded the median onset time of human tularemia (temporal correlation, 0.76; P < .05). Our final predictive model included 5 environmental variables and identified 6 of the 7 outbreaks.

    Conclusions. This work suggests that a high prevalence of mosquitoes in late summer is a prerequisite for outbreaks of tularemia in a tularemia-endemic boreal forest area of Sweden and that environmental variables can be used as risk indicators.

  • 239.
    Röhm, Marc
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Grimm, Melissa J.
    D'Auria, Anthony C.
    Almyroudis, Nikolaos G.
    Segal, Brahm H.
    Urban, Constantin F.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    NADPH Oxidase Promotes Neutrophil Extracellular Trap Formation in Pulmonary Aspergillosis2014In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 82, no 5, p. 1766-1777Article in journal (Refereed)
    Abstract [en]

    NADPH oxidase is a crucial enzyme in antimicrobial host defense and in regulating inflammation. Chronic granulomatous disease (CGD) is an inherited disorder of NADPH oxidase in which phagocytes are defective in generation of reactive oxidant intermediates. Aspergillus species are ubiquitous, filamentous fungi, which can cause invasive aspergillosis, a major cause of morbidity and mortality in CGD, reflecting the critical role for NADPH oxidase in antifungal host defense. Activation of NADPH oxidase in neutrophils can be coupled to the release of proteins and chromatin that comingle in neutrophil extracellular traps (NETs), which can augment extracellular antimicrobial host defense. NETosis can be driven by NADPH oxidase-dependent and -independent pathways. We therefore undertook an analysis of whether NADPH oxidase was required for NETosis in Aspergillus fumigatus pneumonia. Oropharyngeal instillation of live Aspergillus hyphae induced neutrophilic pneumonitis in both wildtype and NADPH oxidase-deficient (p47(phox-/-)) mice which had resolved in wild-type mice by day 5 but progressed in p47(phox-/-) mice. NETs, identified by immunostaining, were observed in lungs of wild-type mice but were absent in p47(phox-/-) mice. Using bona fide NETs and nuclear chromatin decondensation as an early NETosis marker, we found that NETosis required a functional NADPH oxidase in vivo and ex vivo. In addition, NADPH oxidase increased the proportion of apoptotic neutrophils. Together, our results show that NADPH oxidase is required for pulmonary clearance of Aspergillus hyphae and generation of NETs in vivo. We speculate that dual modulation of NETosis and apoptosis by NADPH oxidase enhances antifungal host defense and promotes resolution of inflammation upon infection clearance.

  • 240. Saffari, Fereshteh
    et al.
    Monsen, Tor
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Karmostaji, Afsaneh
    Azimabad, Fahimeh Bahadori
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Significant spread of extensively drug-resistant Acinetobacter baumannii genotypes of clonal complex 92 among intensive care unit patients in a university hospital in southern Iran2017In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 66, no 11, p. 1656-1662Article in journal (Refereed)
    Abstract [en]

    Purpose: Infections associated with Acinetobacter baumannii represent an increasing threat in healthcare settings. Therefore, we investigated the epidemiological relationship between clinical isolates of A. baumannii obtained from patients in a university hospital in Bandar Abbas in southern Iran.

    Methodology: Sixty-four consecutive non-duplicate clinical isolates collected during 2014–2015 were subjected to susceptibility testing, clonal relationship analysis using PFGE, multilocus variable-number tandem-repeat analysis (MLVA) and multilocus sequence typing (MLST), and examined for the presence of carbapenemases and integrons.

    Results: Almost all A. baumannii isolates were extensively drug-resistant (XDR; 98 %) and carried an OXA carbapenemase gene (bla OXA-23-like; 98 %) and class 1 integrons (48 %). PFGE and MLST analysis identified three major genotypes, all belonging to clonal complex 92 (CC92): sequence type 848 (ST848) (n=23), ST451 (n=16) and ST195 (n=8). CC92 has previously been documented in the hospital setting in northern Iran, and ST195 has been reported in Arab States of the Persian Gulf. These data suggest national and global transmission of A. baumannii CC92.

    Conclusion: This report demonstrates the occurrence and potential spread of closely related XDR genotypes of A. baumannii CC92 within a university hospital in southern Iran. These genotypes were found in the majority of the investigated isolates, showed high prevalence of blaOXA-23 and integron class 1, and were associated with stay in the intensive care unit. Very few treatment options remain for healthcare-adapted XDR A. baumannii, and hence effective measures are desperately needed to reduce the spread of these strains and resultant infections in the healthcare setting.

  • 241. Saffari, Fereshteh
    et al.
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Gurram, Bharat Kumar
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Edebro, Helen
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Hojabri, Zoya
    Monsen, Tor
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Molecular and Phenotypic Characterization of Multidrug-Resistant Clones of Staphylococcus epidermidis in Iranian Hospitals: Clonal Relatedness to Healthcare-Associated Methicillin-Resistant Isolates in Northern Europe2016In: Microbial Drug Resistance, ISSN 1076-6294, E-ISSN 1931-8448, Vol. 22, no 7, p. 570-577Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to investigate the molecular epidemiology of Staphylococcus epidermidis in Iranian hospitals and to compare the genotypes with a previously characterized collection of >1,300 S. epidermidis isolates of nosocomial and community origin from Northern Europe, Australia, and USA. In total, 82 clinical S. epidermidis isolates from three Iranian hospitals were examined by multilocus sequence typing, pulsed-field gel electrophoresis (PFGE) and staphylococcal cassette chromosome mec (SCCmec) typing. In addition, antimicrobial susceptibility, the presence of the ica operon, and the predilection to biofilm formation were assessed. Three predominant PFGE clones were found. The PFGE patterns of the most common sequence type (PFGE type 040-ST2) showed 80% similarity to multidrug-resistant S. epidermidis (MDRSE) clinical isolates from eight hospitals in Northern Europe. The second most common (PFGE 024-ST22) showed an unique PFGE pattern, whereas the third most predominant genotype (PFGE 011-ST5) proved indistinguishable to the PFGE Co-ST5 identified in five hospitals in Northern Europe. In conclusion, the study documented the dissemination of three MDRSE clones within and between hospitals in Iran and revealed an intercontinental spread of two clonal multidrug-resistant lineages (ST2 and ST5) in the hospital environment. Isolates of the predominant clones were significantly more frequently associated with multidrug-resistance and biofilm formation compared to nonclonal isolates. Further studies are needed to explore and characterize the genetic traits that enable these successful MDRSE clones to persist and disseminate worldwide in the healthcare settings.

  • 242. Sahdo, Berolla
    et al.
    Särndahl, Eva
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Söderquist, Bo
    Propionibacterium acnes activates caspase-1 in human neutrophils2013In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 7, p. 652-663Article in journal (Refereed)
    Abstract [en]

    Propionibacterium acnes is a Gram-positive, slow-growing, anaerobic bacillus, predominantly found as a commensal on the skin and mucous membranes of adults. It is, however, also considered an opportunistic pathogen; mostly associated with acne vulgaris, but rarely also with severe infections such as infective endocarditis, prosthetic joint infections, and deep sternal wound infections following cardiothoracic surgery. In addition, P. acnes has recently been found in high frequency in prostate tissue from patients with prostatitis and prostate cancer. The NOD-like receptors (NLR) act as intracellular sensors of microbial components, and a number of various bacteria have been found to induce assembling and activation of NLR-inflammasomes; leading to a pro-inflammatory response. The inflammasome-mediated formation of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18 involves the auto-proteolytic maturation of caspase-1. This study investigated if P. acnes activates inflammasomes. Propionibacterium acnes isolates (n = 29) with diverse origin were used as stimuli for peripheral leukocytes obtained from blood donors (BDs). The activity of inflammasomes was determined by measuring caspase-1 by flow cytometry and cytokine production by ELISA. A significant amount of caspase-1 was found in neutrophils upon P. acnes stimulation, whereas only a modest activation was seen in monocytes. The activation was mainly produced by components of the bacterial cell and no exo-products, because heat-killed and live bacteria caused high activation of caspase-1 as well as cytokine production, whereas the bacterial supernatant elicited minor effect. The response among different BDs varied significantly, almost fivefold. In addition, P. acnes of various origins showed considerable variation, however, the commensal isolates showed a stronger response compared with the invasive. In conclusion, although regarded as a harmless commensal of the skin, P. acnes strongly activates the inflammasome of human peripheral neutrophils.

  • 243. Sang, Rosemary
    et al.
    Arum, Samwel
    Chepkorir, Edith
    Mosomtai, Gladys
    Tigoi, Caroline
    Sigei, Faith
    Lwande, Olivia Wesula
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Landmann, Tobias
    Affognon, Hippolyte
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evander, Magnus
    Distribution and abundance of key vectors of Rift Valley fever and other arboviruses in two ecologically distinct counties in Kenya2017In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, no 2, article id e0005341Article in journal (Refereed)
    Abstract [en]

    Background Rift Valley fever (RVF) is a mosquito-borne viral zoonosis of ruminants and humans that causes outbreaks in Africa and the Arabian Peninsula with significant public health and economic consequences. Humans become infected through mosquito bites and contact with infected livestock. The virus is maintained between outbreaks through vertically infected eggs of the primary vectors of Aedes species which emerge following rains with extensive flooding. Infected female mosquitoes initiate transmission among nearby animals, which amplifies virus, thereby infecting more mosquitoes and moving the virus beyond the initial point of emergence. With each successive outbreak, RVF has been found to expand its geographic distribution to new areas, possibly driven by available vectors. The aim of the present study was to determine if RVF virus (RVFV) transmission risk in two different ecological zones in Kenya could be assessed by looking at the species composition, abundance and distribution of key primary and secondary vector species and the level of virus activity. Methodology Mosquitoes were trapped during short and long rainy seasons in 2014 and 2015 using CO2 baited CDC light traps in two counties which differ in RVF epidemic risk levels(high risk Tana-River and low risk Isiolo), cryo-preserved in liquid nitrogen, transported to the laboratory, and identified to species. Mosquito pools were analyzed for virus infection using cell culture screening and molecular analysis. Findings Over 69,000 mosquitoes were sampled and identified as 40 different species belonging to 6 genera (Aedes, Anopheles, Mansonia, Culex, Aedeomyia, Coquillettidia). The presence and abundance of Aedes mcintoshi and Aedes ochraceus, the primary mosquito vectors associated with RVFV transmission in outbreaks, varied significantly between Tana-River and Isiolo. Ae. mcintoshi was abundant in Tana-River and Isiolo but notably, Aedes ochraceus found in relatively high numbers in Tana-River (n = 1,290), was totally absent in all Isiolo sites. Fourteen virus isolates including Sindbis, Bunyamwera, and West Nile fever viruses were isolated mostly from Ae. mcintoshi sampled in Tana-River. RVFV was not detected in any of the mosquitoes. Conclusion This study presents the geographic distribution and abundance of arbovirus vectors in two Kenyan counties, which may assist with risk assessment for mosquito borne diseases.

  • 244.
    Schliamser, Silvia E.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Neurotoxicity of β-lactam antibiotics: experimental kinetic and neurophysiological studies1988Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The neurotoxic potential of intravenous administered benzylpenicillin (BPC) was studied in rabbits with intact blood-CNS barriers and rabbits with experimental E. coli meningitis. At onset of epileptogenic EEG activity or seizures, serum, CSF and brain tissue were collected for assay of BPC. Based on the fact that, in tissues, BPC seems to remain extracellularly, brain concentrations of BPC were expressed as brain tissue fluid (BTF) levels, calculated as lOx the concentration in whole brain tissue. Neurotoxicity could be precipitated in all rabbits. In normal rabbits BTF levels of BPC were considerably higher than those in CSF indicating a better penetration across the blood-brain barrier (BBB). BPC penetrated better to CSF and BTF in meningitic rabbits than in normal controls, suggesting some degree of damage of the BBB concomitant with meningeal inflammation. E. coli meningitis did not increase the neurotoxicity of BPC. In control rabbits the intracistemal injection of saline resulted in some degree of pleocytosis. Unmanipulated animals are therefore preferable as controls. Epileptogenic EEG-changes was the most precise of the two variables used for demonstration of neurotoxicity. EEG-changes were therefore used as neurotoxicity criterion in the following rabbit experiments. To evaluate the effect of uraemia alone and uraemia plus meningitis on the neurotoxity of BPC in rabbits, cephaloridine was used to induce uraemia. Meningitis was induced by intracistemal inoculation of a cephalosporinresistant strain of E. cloacae. Untreated  rabbits were used as controls. Uraemia resulted in increased BTF penetration of BPC, possibly explained by permeability changes in the BBB and/or decreased binding of BPC to albumin. Uraemia did not result in increased penetration of BPC into the CSF of non-meningitic rabbits. Uraemic non-meningitic rabbits had the highest BTF levels of BPC at the criterion, indicating that cephaloridine-induced renal failure increased the epileptogenic threshold in these rabbits. The combination of uraemia and meningitis increased the neurotoxicity of BPC since the criterion was reached at considerably lower BTF levels of BPC. Meningitis, either alone or together with uraemia, did not increase the neurotoxicity in comparison to control rabbits. Higher BTF levels of BPC were found in meningitic rabbits than in controls with intact blood-CNS barriers at onset of EEG-changes. In all groups of rabbits there was a pronounced variability of BPC levels in the CSF while the intra-group variations in BTF levels were much smaller. Thus, BTF and not CSF levels were decisive for the neurotoxicity of BPC. Using   the same EEG-model, the neurotoxic potential of imipenem/cilastatin (I) and a new penem derivative, FCE 22101 were compared in a cross-over study. Both I and FCE 22101 were significantly more neurotoxic than BPC. While BTF levels of the three antibiotics could be detected in all tested rabbits, detectable CSF levels were only found in one of twelve rabbits treated with I or FCE 22101, indicating that BTF concentrations rather than CSF ones are decisive for neurotoxicity of ß-lactam antibiotics. The EEG-model used was found to be a suitable model for cross-over studies of intravenously administered antibiotics. Using the "silent-second" as EEG-threshold, a CNS interaction between intraperitoneally administered BPC and intravenous thiopental was demonstrated in rats. The most probably site for this interaction is the organic acid transport system out of the CNS. Thiopental distribution in the rat brain seemed to depend not only on its lipid solubility.

  • 245. Semenza, Jan C.
    et al.
    Lindgren, Elisabet
    Balkanyi, Laszlo
    Espinosa, Laura
    Almqvist, My S.
    Penttinen, Pasi
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Determinants and Drivers of Infectious Disease Threat Events in Europe2016In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 22, no 4, p. 581-589Article in journal (Refereed)
    Abstract [en]

    Infectious disease threat events (IDTEs) are increasing in frequency worldwide. We analyzed underlying drivers of 116 IDTEs detected in Europe during 2008-2013 by epidemic intelligence at the European Centre of Disease Prevention and Control. Seventeen drivers were identified and categorized into 3 groups: globalization and environment, sociodemographic, and public health systems. A combination of >= 2 drivers was responsible for most IDTEs. The driver category globalization and environment contributed to 61% of individual IDTEs, and the top 5 individual drivers of all IDTEs were travel and tourism, food and water quality, natural environment, global trade, and climate. Hierarchical cluster analysis of all drivers identified travel and tourism as a distinctly separate driver. Monitoring and modeling such disease drivers can help anticipate future IDTEs and strengthen control measures. More important, intervening directly on these underlying drivers can diminish the likelihood of the occurrence of an IDTE and reduce the associated human and economic costs.

  • 246. Semenza, Jan C.
    et al.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Penttinen, Pasi
    Lindgren, Elisabet
    Observed and projected drivers of emerging infectious diseases in Europe2016In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1382, p. 73-83Article in journal (Refereed)
    Abstract [en]

    Emerging infectious diseases are of international concern because of the potential for, and impact of, pandemics; however, they are difficult to predict. To identify the drivers of disease emergence, we analyzed infectious disease threat events (IDTEs) detected through epidemic intelligence collected at the European Centre for Disease Prevention and Control (ECDC) between 2008 and 2013, and compared the observed results with a 2008 ECDC foresight study of projected drivers of future IDTEs in Europe. Among 10 categories of IDTEs, foodborne and waterborne IDTEs were the most common, vaccine-preventable IDTEs caused the highest number of cases, and airborne IDTEs caused the most deaths. Observed drivers for each IDTE were sorted into three main groups: globalization and environmental drivers contributed to 61% of all IDTEs, public health system drivers contributed to 21%, and social and demographic drivers to 18%. A multiple logistic regression analysis showed that four of the top five drivers for observed IDTEs were in the globalization and environment group. In the observational study, the globalization and environment group was related to all IDTE categories, but only to five of eight categories in the foresight study. Directly targeting these drivers with public health interventions may diminish the chances of IDTE occurrence from the outset.

  • 247. Sendi, P
    et al.
    Christensson, B
    Uçkay, I
    Trampuz, A
    Achermann, Y
    Boggian, K
    Svensson, D
    Widerström, Micael
    Department of Infectious Diseases, Östersund Hospital, Östersund, Sweden.
    Zimmerli, W
    Group B streptococcus in prosthetic hip and knee joint-associated infections2011In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 79, no 1, p. 64-69Article in journal (Refereed)
    Abstract [en]

    The incidence of invasive group B streptococcus (GBS) infections in non-pregnant adults is increasing. Little is known about GBS in periprosthetic joint infections (PJIs). We aimed to analyse the clinical presentation of GBS PJI and its treatment in association with the outcome. The characteristics of 36 GBS PJIs collected from 10 centres were investigated. In 34 episodes, follow-up examination of ≥ 2 years was available, allowing treatment and outcome analysis. Most infections (75%) occurred ≥ 3 months after implantation. Most patients (91%) had at least one comorbidity; 69% presented with acute symptoms and 83% with damaged periprosthetic soft tissue. In 20 of 34 episodes debridement and retention of implant was attempted, but in five of these the prosthesis was ultimately removed. Hence, in 19 (56%) episodes, the implant was removed, including 14 immediate removals. In four episodes the removal was permanent. Penicillin derivatives and clindamycin were the most common antimicrobials administered (68%). In 94% the infection was cured, and in 82% functional mobility preserved. Debridement with implant retention was successful if the duration of symptoms was short, the prosthesis stable, and the tissue damage minor (10/10 vs 3/10 episodes, P = 0.003). Surgery that complied with a published algorithm was associated with a favourable outcome (P = 0.049).

  • 248.
    Silver, Jim
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Islam, Bakhtiar
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Mei, Ya-Fang
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Replication-competent adenovirus 11p GFP vector (RCAd11pGFP) enhances CEACAM6 expression in colon cancer cellsManuscript (preprint) (Other academic)
  • 249. Sironen, Tarja
    et al.
    Sane, Jussi
    Lokki, Marja-Liisa
    Meri, Seppo
    Andersson, Leif C.
    Hautala, Timo
    Kauma, Heikki
    Vuorinen, Sakari
    Rasmuson, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Vaheri, Antti
    Fatal Puumala Hantavirus Disease: Involvement of Complement Activation and Vascular Leakage in the Pathobiology2017In: Open Forum Infectious Diseases, ISSN 2328-8957, Vol. 4, no 4, article id ofx229Article in journal (Refereed)
    Abstract [en]

    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.

  • 250. Sjöwall, J
    et al.
    Carlsson, A
    Vaarala, O
    Bergström, Sven
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Ernerudh, J
    Forsberg, P
    Ekerfelt, C
    Innate immune responses in Lyme borreliosis: enhanced tumour necrosis factor-alpha and interleukin-12 in asymptomatic individuals in response to live spirochetes2005In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 141, no 1, p. 89-98Article in journal (Refereed)
    Abstract [en]

    Innate immunity is important for early defence against borrelia spirochetes and should play a role in the clinical outcome of the infection. In order to study early cytokine responses, in vitro differentiated dendritic cells (DCs) and whole blood cells from 21 patients with different clinical outcomes of Lyme neuroborreliosis were stimulated with live borrelia spirochetes. The borrelia-induced secretion of interleukin (IL)-4, IL-10, IL-12p70, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in DCs and IL-1 beta, IL-6, IL-8, IL-10, IL-12p70, TNF-alpha, regulated upon activation normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta and eotaxin in whole blood cells was measured by enzyme-linked immunospot (ELISPOT) and multiplex arrays, respectively. We found increased numbers of TNF-alpha-secreting DCs (P = 0.018) in asymptomatic seropositive individuals compared to patients with subacute neuroborreliosis and seronegative controls. Asymptomatic individuals were also found to have elevated levels of IL-12p70 (P = 0.031) in whole blood cell supernatants compared to seronegative controls. These results are in line with previous experiments using cells of the adaptive immune response, indicating that strong T helper type 1 (Th1) proinflammatory responses might be associated with a successful resolution of Lyme disease.

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