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  • 1.
    Albinsson, Bo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Laboratory of Clinical Microbiology, Uppsala University Hospital, Uppsala.
    Vene, Sirkka
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. The Public Health Agency of Sweden, Solna.
    Rombo, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Department of Infectious diseases, Eskilstuna.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lundkvist, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Rönnberg, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Laboratory of Clinical Microbiology, Uppsala University Hospital .
    Distinction between serological responses following tick-borne encephalitis virus (TBEV) infection vs vaccination, Sweden 20172018In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 23, no 3, p. 2-7, article id 17-00838Article in journal (Refereed)
    Abstract [en]

    Tick-borne encephalitis virus (TBEV) is an important European vaccine-preventable pathogen. Discrimination of vaccine-induced antibodies from those elicited by infection is important. We studied anti-TBEV IgM/IgG responses, including avidity and neutralisation, by multiplex serology in 50 TBEV patients and 50 TBEV vaccinees. Infection induced antibodies reactive to both whole virus (WV) and non-structural protein 1 (NS1) in 48 clinical cases, whereas 47 TBEV vaccinees had WV, but not NS1 antibodies, enabling efficient discrimination of infection/vaccination.

  • 2.
    Bartlett, S. R.
    et al.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Grebely, J.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Eltahla, A. A.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Reeves, J. D.
    Lab Corp Amer Holdings, Monogram Biosci, San Francisco, CA USA..
    Howe, A.
    St Pauls Hosp, BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada..
    Miller, V.
    Univ Calif Berkeley, Forum Collaborat HIV Res, Washington, DC USA..
    Bull, R. A.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Ceccherini-Silberstein, F.
    Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy..
    Douglas, M. W.
    Westmead Inst Med Res, Storr Liver Ctr, Sydney, NSW, Australia..
    Dore, G. J.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Harrington, P.
    US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA..
    Lloyd, A. R.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Jacka, B.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Matthews, G. V.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Wang, G. P.
    Univ Florida, Coll Med, Dept Med, Gainesville, FL USA..
    Pawlotsky, J. -M
    Feld, J. J.
    Univ Toronto, Univ Hlth Network, Toronto Western Hosp, Ctr Liver, Toronto, ON, Canada..
    Schinkel, J.
    Acad Med Ctr, Dept Med Microbiol, Amsterdam, Netherlands..
    Garcia, F.
    Complejo Hosp Univ Granada, Clin Microbiol Serv, Granada, Spain..
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Applegate, T. L.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Systematic review & expert guidance on methods for sequencing of hepatitis C virus for detection of direct-acting antiviral resistance2017In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 66, no 1, p. S323-S323Article in journal (Other academic)
  • 3.
    Baygan, Arjang
    et al.
    Translational Cell Therapy Research Group (TCR), Division of Therapeutic Immunology, Department of LabMed, Karolinska Institutet, Stockholm, Sweden.
    Aronsson-Kurttila, Wictor
    Translational Cell Therapy Research Group (TCR), Division of Therapeutic Immunology, Department of LabMed, Karolinska Institutet, Stockholm, Sweden.
    Moretti, Gianluca
    Translational Cell Therapy Research Group (TCR), Division of Therapeutic Immunology, Department of LabMed, Karolinska Institutet, Stockholm, Sweden.
    Tibert, Babylonia
    Translational Cell Therapy Research Group (TCR), Division of Therapeutic Immunology, Department of LabMed, Karolinska Institutet, Stockholm, Sweden.
    Dahllöf, Göran
    Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Klingspor, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology. Department of Microbiology, Uppsala University Hospital, Uppsala, Sweden.
    Gustafsson, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Khoein, Bita
    Translational Cell Therapy Research Group (TCR), Division of Therapeutic Immunology, Department of LabMed, Karolinska Institutet, Stockholm, Sweden.
    Moll, Guido
    Translational Cell Therapy Research Group (TCR), Division of Therapeutic Immunology, Department of LabMed, Karolinska Institutet, Stockholm, Sweden.
    Hausmann, Charlotta
    Center for Allogeneic Stem Cell Transplantation, Department of Pathology/Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Svahn, Britt-Marie
    Translational Cell Therapy Research Group (TCR), Division of Therapeutic Immunology, Department of LabMed, Karolinska Institutet, Stockholm, Sweden.
    Westgren, Magnus
    Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden.
    Remberger, Mats
    Center for Allogeneic Stem Cell Transplantation, Department of Pathology/Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Sadeghi, Behnam
    Translational Cell Therapy Research Group (TCR), Division of Therapeutic Immunology, Department of LabMed, Karolinska Institutet, Stockholm, Sweden.
    Ringden, Olle
    Translational Cell Therapy Research Group (TCR), Division of Therapeutic Immunology, Department of LabMed, Karolinska Institutet, Stockholm, Sweden.
    Safety and Side Effects of Using Placenta-Derived Decidual Stromal Cells for Graft-versus-Host Disease and Hemorrhagic Cystitis2017In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, article id 795Article in journal (Refereed)
    Abstract [en]

    Mesenchymal stromal cells (MSCs) are increasingly used in regenerate medicine. Placenta-derived decidual stromal cells (DSCs) are a novel therapy for acute graft-versus-host-disease (GVHD) and hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT). DSCs are more immunosuppressive than MSCs. We assessed adverse events and safety using DSCs among 44 treated patients and 40 controls. The median dose of infused cells was 1.5 (range 0.9–2.9) × 106 DSCs/kg. The patients were given 2 (1–5) doses, with a total of 82 infusions. Monitoring ended 3 months after the last DSC infusion. Three patients had transient reactions during DSC infusion. Laboratory values, hemorrhages, and transfusions were similar in the two groups. The frequency of leukemic relapse (2/2, DSC/controls) and invasive fungal infections (6/6) were the same in the two groups. Causes of death were those seen in HSCT patients: infections (5/3), respiratory failure (1/1), circulatory failure (3/1), thromboembolism (1/0), multiorgan failure (0/1), and GVHD and others (2/7). One-year survival for the DSC patients with GVHD was 67%, which was significantly better than achieved previously at our center. One-year survival was 90% in the DSC-treated HC group. DSC infusions appear safe. Randomized studies are required to prove efficacy.

  • 4.
    Bergqvist, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Loss of DNA-binding and new transcriptional trans-activation function in polyomavirus large T-antigen with mutation of zinc finger motif.1990In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962Article in journal (Refereed)
  • 5.
    Blomberg, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Gottfries, Carl-Gerhard
    Gottfries Clin AB, Molndal, Sweden..
    Elfaitouri, Amal
    Benghazi Univ, Fac Publ Hlth, Dept Infect Dis & Trop Med, Benghazi, Libya..
    Rizwan, Muhammad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Rosén, Anders
    Linkoping Univ, Div Cell Biol, Dept Clin & Expt Med, Linkoping, Sweden..
    Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model2018In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, article id 229Article in journal (Refereed)
    Abstract [en]

    Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of controversy and a considerable scientific literature, we think that a solid understanding of ME/CFS pathogenesis is emerging. In this study, we compiled recent findings and placed them in the context of the clinical picture and natural history of the disease. A pattern emerged, giving rise to an explanatory model. ME/CFS often starts after or during an infection. A logical explanation is that the infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism. According to our model for ME/CFS pathogenesis, patients with a genetic predisposition and dysbiosis experience a gradual development of B cell clones prone to autoreactivity. Under normal circumstances these B cell offsprings would have led to tolerance. Subsequent exogenous microbial exposition (triggering) can lead to comorbidities such as fibromyalgia, thyroid disorder, and orthostatic hypotension. A decisive infectious trigger may then lead to immunization against autoantigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing postexertional malaise and ME/CFS, affecting both muscle and brain. In principle, cloning and sequencing of immunoglobulin variable domains could reveal the evolution of pathogenic clones. Although evidence consistent with the model accumulated in recent years, there are several missing links in it. Hopefully, the hypothesis generates testable propositions that can augment the understanding of the pathogenesis of ME/CFS.

  • 6.
    Dahlberg, Jenny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Hadad, Ronza
    Elfving, Karin
    Larsson, Inger
    Isaksson, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Magnuson, Anders
    Fredlund, Hans
    Unemo, Magnus
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Ten years transmission of the new variant of Chlamydia trachomatis in Sweden: prevalence of infections and associated complications.2018In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 94, no 2, p. 100-104Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: (nvCT) was discovered in Sweden. It has a deletion in the plasmid resulting in failed detection by the single target systems from Abbott and Roche used at that time, whereas the third system used, from Becton Dickinson (BD), detects nvCT. The proportion of nvCT was initially up to 65% in counties using Abbott/Roche systems. This study analysed the proportion of nvCT from 2007 to 2015 in four selected counties and its impact on chlamydia-associated complications.

    METHODS: sequencing. Ectopic pregnancy and pelvic inflammatory disease records were extracted from the national registers.

    RESULTS: -positive samples were analysed. The nvCT proportion significantly decreased in the two counties using Roche systems, from 56% in 2007 to 6.5% in 2015 (p<0.001). In the two counties using BD systems, a decrease was also seen, from 19% in 2007 to 5.2% in 2015 (p<0.001). Fifteen nvCT cases from 2015 and 102 cases from 2006 to 2009 had identical MLST profiles. Counties using Roche/Abbott systems showed higher mean rates of ectopic pregnancy and pelvic inflammatory disease compared with counties using BD systems.

    CONCLUSIONS: The nvCT proportion has decreased in all counties and converged to a low prevalence irrespective of previous rates. Genotyping showed that nvCT is clonal and genetically stable. Failing detection only marginally affected complication rates.

  • 7.
    Gifford, Robert J.
    et al.
    Univ Glasgow, MRC, Ctr Virus Res, Glasgow, Lanark, Scotland.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Coffin, John M.
    Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
    Fan, Hung
    Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA;Univ Calif Irvine, Canc Res Inst, Irvine, CA 92697 USA.
    Heidmann, Thierry
    Inst Gustave Roussy, CNRS UMR 9196, Dept Mol Physiol & Pathol Infect & Endogenous Ret, F-94805 Villejuif, France.
    Mayer, Jens
    Univ Saarland, Med Fac, Dept Human Genet, Ctr Human & Mol Biol, Homburg, Germany.
    Stoye, Jonathan
    Francis Crick Inst, Mill Hill Lab, Mill Hill, London, England.
    Tristem, Michael
    Imperial Coll London, Silwood Pk Campus,Buckhurst Rd, Ascot SL5 7PY, Berks, England.
    Johnson, Welkin E.
    Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA.
    Nomenclature for endogenous retrovirus (ERV) loci2018In: Retrovirology, ISSN 1742-4690, E-ISSN 1742-4690, Vol. 15, article id 59Article, review/survey (Refereed)
    Abstract [en]

    Retroviral integration into germline DNA can result in the formation of a vertically inherited proviral sequence called an endogenous retrovirus (ERV). Over the course of their evolution, vertebrate genomes have accumulated many thousands of ERV loci. These sequences provide useful retrospective information about ancient retroviruses, and have also played an important role in shaping the evolution of vertebrate genomes. There is an immediate need for a unified system of nomenclature for ERV loci, not only to assist genome annotation, but also to facilitate research on ERVs and their impact on genome biology and evolution. In this review, we examine how ERV nomenclatures have developed, and consider the possibilities for the implementation of a systematic approach for naming ERV loci. We propose that such a nomenclature should not only provide unique identifiers for individual loci, but also denote orthologous relationships between ERVs in different species. In addition, we propose that-where possible-mnemonic links to previous, well-established names for ERV loci and groups should be retained. We show how this approach can be applied and integrated into existing taxonomic and nomenclature schemes for retroviruses, ERVs and transposable elements.

  • 8.
    Grandi, Nicole
    et al.
    Univ Cagliari, Dept Life & Environm Sci, Cagliari.
    Cadeddu, Marta
    Univ Cagliari, Dept Life & Environm Sci, Cagliari.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Mayer, Jens
    Univ Saarland, Inst Human Genet, Homburg.
    Tramontano, Enzo
    Univ Cagliari, Dept Life & Environm Sci, Cagliari; CNR, IRGB, Monserrato.
    HERV-W group evolutionary history in non-human primates: characterization of ERV-W orthologs in Catarrhini and related ERV groups in Platyrrhini2018In: BMC Evolutionary Biology, ISSN 1471-2148, E-ISSN 1471-2148, Vol. 18, article id 6Article in journal (Refereed)
    Abstract [en]

    Background: The genomes of all vertebrates harbor remnants of ancient retroviral infections, having affected the germ line cells during the last 100 million years. These sequences, named Endogenous Retroviruses (ERVs), have been transmitted to the offspring in a Mendelian way, being relatively stable components of the host genome even long after their exogenous counterparts went extinct. Among human ERVs (HERVs), the HERV-W group is of particular interest for our physiology and pathology. A HERV-W provirus in locus 7q21.2 has been coopted during evolution to exert an essential role in placenta, and the group expression has been tentatively linked to Multiple Sclerosis and other diseases. Following up on a detailed analysis of 213 HERV-W insertions in the human genome, we now investigated the ERV-W group genomic spread within primate lineages.

    Results: We analyzed HERV-W orthologous loci in the genome sequences of 12 non-human primate species belonging to Simiiformes (parvorders Catarrhini and Platyrrhini), Tarsiiformes and to the most primitive Prosimians. Analysis of HERV-W orthologous loci in non-human Catarrhini primates revealed species-specific insertions in the genomes of Chimpanzee (3), Gorilla (4), Orangutan (6), Gibbon (2) and especially Rhesus Macaque (66). Such sequences were acquired in a retroviral fashion and, in the majority of cases, by L1-mediated formation of processed pseudogenes. There were also a number of LTR-LTR homologous recombination events that occurred subsequent to separation of Catarrhini sub-lineages. Moreover, we retrieved 130 sequences in Marmoset and Squirrel Monkeys (family Cebidae, Platyrrhini parvorder), identified as ERV1–1_CJa based on RepBase annotations, which appear closely related to the ERV-W group. Such sequences were also identified in Atelidae and Pitheciidae, representative of the other Platyrrhini families. In contrast, no ERV-W-related sequences were found in genome sequence assemblies of Tarsiiformes and Prosimians.

    Conclusions: Overall, our analysis now provides a detailed picture of the ERV-W sequences colonization of the primate lineages genomes, revealing the exact dynamics of ERV-W locus formations as well as novel insights into the evolution and origin of the group.

  • 9.
    Grandi, Nicole
    et al.
    University of Cagliari, Cagliari, Italy.
    Cadeddu, Marta
    University of Cagliari, Cagliari, Italy.
    Pisano, Maria Paola
    University of Cagliari, Cagliari, Italy.
    Esposito, Francesca
    University of Cagliari, Cagliari, Italy.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Tramontano, Enzo
    University of Cagliari, Cagliari, Italy.
    Identification of a novel HERV-K(HML10): comprehensive characterization and comparative analysis in non-human primates provide insights about HML10 proviruses structure and diffusion2017In: Mobile DNA, ISSN 1759-8753, E-ISSN 1759-8753, Vol. 8, article id 15Article in journal (Refereed)
    Abstract [en]

    About half of the human genome is constituted of transposable elements, including human endogenous retroviruses (HERV). HERV sequences represent the 8% of our genetic material, deriving from exogenous infections occurred millions of years ago in the germ line cells and being inherited by the offspring in a Mendelian fashion. HERV-K elements (classified as HML1-10) are among the most studied HERV groups, especially due to their possible correlation with human diseases. In particular, the HML10 group was reported to be upregulated in persistent HIV-1 infected cells as well as in tumor cells and samples, and proposed to have a role in the control of host genes expression. An individual HERV-K(HML10) member within the major histocompatibility complex C4 gene has even been studied for its possible contribution to type 1 diabetes susceptibility. Following a first characterization of the HML10 group at the genomic level, performed with the innovative software RetroTector, we have characterized in detail the 8 previously identified HML10 sequences present in the human genome, and an additional HML10 partial provirus in chromosome 1p22.2 that is reported here for the first time. Using a combined approach based on RetroTector software and a traditional Genome Browser Blat search, we identified a novel HERV-K(HML10) sequence in addition to the eight previously reported in the human genome GRCh37/hg19 assembly. We fully characterized the nine HML10 sequences at the genomic level, including their classification in two types based on both structural and phylogenetic characteristics, a detailed analysis of each HML10 nucleotide sequence, the first description of the presence of an Env Rec domain in the type II HML10, the estimated time of integration of individual members and the comparative map of the HML10 proviruses in non-human primates. We performed an unambiguous and exhaustive analysis of the nine HML10 sequences present in GRCh37/hg19 assembly, useful to increase the knowledge of the group's contribution to the human genome and laying the foundation for a better understanding of the potential physiological effects and the tentative correlation of these sequences with human pathogenesis.

  • 10.
    Hambraeus, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Lytsy, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Infection Control and What to Wear in the Operating Room2018In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 67, no 1, p. 159-159Article in journal (Other academic)
  • 11.
    Howe, Anita
    et al.
    Univ Milan, Ctr Excellence HIV AIDS, Milan, Italy.
    Cento, Valeria
    Univ Milan, Microbiol & Virol, Milan, Italy.
    Knight, Nathaniel
    Ctr Excellence HIV AIDS, Res Lab, Frankfurt, Germany.
    Dietz, Julia
    Univ Hosp Frankfurt, Frankfurt, Germany.
    Di Maio, Velia Chiara
    Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy.
    De Salazar, Adolfo
    Hosp Univ San Cecilio, Jefe Serv Microbiol, Granada, Spain.
    Popping, Stephanie
    Erasmus MC, Dept Virosci, Rotterdam, Netherlands.
    Fourati, Slim
    Henri Mondor Univ Hosp, Virol, Creteil, France.
    Knops, Elena
    Univ Hosp Cologne, Inst Virol, Cologne, Germany.
    Kjellin, Midori
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Sayan, Murat
    Univ Res Ctr Expt Hlth Sci, Nicosia, Northern Cyprus, Cyprus.
    Mor, Orna
    Sheba Med Ctr, Cent Virol Lab, Ramat Gan, Israel.
    De Knegt, Robert J.
    Erasmus MC, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands.
    Mitchell, Robert
    Univ British Columbia, Vancouver, BC, Canada.
    Tam, Edward V.
    Lair Ctr, Vancouver, BC, Canada.
    Pai, Rohit
    Pereira, Oscar Octavio Cruz
    Royal Jubilee Hosp, Victoria, BC, Canada.
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Wang, Gary P.
    Univ Florida, Gainesville, FL 32611 USA.
    Wong, Alexander
    Univ Saskatchewan, Infect Dis, Saskatoon, SK, Canada.
    Parczewski, Milosz
    Pomeranian Med Univ, Dept Infect Trop Dis & Immune Deficiency, Szczecin, Poland.
    Applegate, Tanya
    Kirby Inst, Viral Hepatitis Clin Res Program, Kensington, NSW, Australia.
    Ramji, Alnoor
    Univ British Columbia, Div Gastroenterol, Vancouver, BC, Canada.
    Perno, Carlo Federico
    Univ Milan, Milan, Italy.
    Kaiser, Rolf
    7Univ Hosp Cologne, Virol, Cologne, Germany.
    Boucher, Charles A. B.
    Erasmus MC, Dept Virosci, Rotterdam, Netherlands.
    Feld, Jordan J.
    Univ Hlth Network, Toronto Ctr Liver Dis, Toronto, ON, Canada.
    Pawlotsky, Jean-Michel
    INSERM, Imrb U955, Team 18, Paris, France.
    Garcia, Federico
    Inst Invest Biosanitaria Ibs, Virol, Granada, Spain.
    Ceccherini-Silberstein, Francesca
    Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy.
    Sarrazin, Christoph
    Goethe Univ Hosp, Frankfurt, Germany.
    Harrigan, Richard
    Univ British Columbia, AIDS, Vancouver, BC, Canada.
    A Real World Resistance Profile of Virologic Failures Collected from an International Collaboration (SHARED)2018In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 68, p. 128A-128AArticle in journal (Other academic)
  • 12.
    Ianevski, Aleksandr
    et al.
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, N-7028 Trondheim, Norway.
    Zusinaite, Eva
    Univ Tartu, Inst Technol, EE-50090 Tartu, Estonia.
    Kuivanen, Suvi
    Univ Helsinki, Dept Virol, FIN-00014 Helsinki, Finland.
    Strand, Mårten
    Umea Univ, Dept Clin Microbiol, S-90185 Umea, Sweden.
    Lysvand, Hilde
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, N-7491 Trondheim, Norway.
    Teppor, Mona
    Univ Tartu, Inst Technol, EE-50090 Tartu, Estonia.
    Kakkola, Laura
    Univ Turku, Inst Biomed, FIN-20520 Turku, Finland.
    Paavilainen, Henrik
    Univ Turku, Inst Biomed, FIN-20520 Turku, Finland.
    Laajala, Mira
    Univ Jyvaskyla, Dept Biol & Environm Sci, Jyvaskyla 40500, Finland.
    Kallio-Kokko, Hannimari
    Univ Helsinki, Helsinki Univ Hosp, Dept Virol & Immunol, FIN-00014 Helsinki, Finland.
    Valkonen, Miia
    Helsinki Univ Hosp, Helsinki 00014, Finland.
    Kantele, Anu
    Helsinki Univ Hosp, Helsinki 00014, Finland.
    Telling, Kaidi
    Univ Tartu, Inst Med Microbiol, EE-50411 Tartu, Estonia.
    Lutsar, Irja
    Univ Tartu, Inst Med Microbiol, EE-50411 Tartu, Estonia.
    Letjuka, Pille
    Narva Haigla, EE-20104 Narva, Estonia.
    Metelitsa, Natalja
    Narva Haigla, EE-20104 Narva, Estonia.
    Oksenych, Valentyn
    Trondheim Reg & Univ Hosp, St Olays Hosp, Clin Med, N-7006 Trondheim, Norway.
    Bjorås, Magnar
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, N-7491 Trondheim, Norway.
    Nordbo, Svein Arne
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, N-7491 Trondheim, Norway;Trondheim Reg & Univ Hosp, St Olays Hosp, Dept Med Microbiol, N-7006 Trondheim, Norway.
    Dumpis, Uga
    Pouls Stradins Clin Univ Hosp, LV-1002 Riga, Latvia.
    Vitkauskiene, Astra
    Lithuanian Univ Hlth Sci, Dept Lab Med, LT-44307 Kaunas, Lithuania.
    Öhrmalm, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bergqvist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Aittokallio, Tero
    Univ Helsinki, Inst Mol Med Finland, FIMM, FIN-00290 Helsinki, Finland;Univ Turku, Dept Math & Stat, Turku 20014, Finland.
    Cox, Rebecca J.
    Univ Bergen, Influenza Ctr, Dept Clin Sci, N-5021 Bergen, Norway.
    Evander, Magnus
    Umea Univ, Dept Clin Microbiol, S-90185 Umea, Sweden.
    Hukkanen, Veijo
    Univ Turku, Inst Biomed, FIN-20520 Turku, Finland.
    Marjomaki, Varpu
    Univ Jyvaskyla, Dept Biol & Environm Sci, Jyvaskyla 40500, Finland.
    Julkunen, Ilkka
    Univ Turku, Inst Biomed, FIN-20520 Turku, Finland.
    Vapalahti, Olli
    Univ Helsinki, Dept Virol, FIN-00014 Helsinki, Finland;Helsinki Univ Hosp, Helsinki 00014, Finland;Univ Helsinki, Dept Vet Biosci, FIN-00014 Helsinki, Finland.
    Tenson, Tanel
    Univ Tartu, Inst Technol, EE-50090 Tartu, Estonia.
    Merits, Andres
    Univ Tartu, Inst Technol, EE-50090 Tartu, Estonia.
    Kainov, Denis
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, N-7028 Trondheim, Norway;Univ Tartu, Inst Technol, EE-50090 Tartu, Estonia.
    Novel activities of safe-in-human broad-spectrum antiviral agents2018In: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, Vol. 154, p. 174-182Article in journal (Refereed)
    Abstract [en]

    According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-inhuman antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley fever virus. Thus, the spectrum of antiviral activities of existing antiviral agents could be expanded towards other viral diseases.

  • 13.
    Isaksson, Jenny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Carlsson, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Airell, Asa
    Karolinska Univ Hosp Huddinge, Dept Clin Bacteriol, Stockholm, Sweden..
    Strömdahl, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bratt, Goran
    South Gen Hosp, Dept Infect Dis, Venhalsan, Stockholm, Sweden..
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Lymphogranuloma venereum rates increased and Chlamydia trachomatis genotypes changed among men who have sex with men in Sweden 2004-20162017In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 66, no 11, p. 1684-1687Article in journal (Refereed)
    Abstract [en]

    This study aimed to determine the incidence of lymphogranuloma venereum (LGV) in Sweden since 2004 and to study in detail a consecutive number of Chlamydia trachomatis cases in men who have sex with men (MSM) during a 10 month period (September 2014 to July 2015). LGV increased from sporadic import cases in 2004 to comprise a spread within Sweden in 2016. Initially, only the L2b ompA genotype was detected, but in 2015 half of the genotyped LGV cases were L2 genotype. The changing genotype distribution in Sweden is linked to increased LGV spread in Europe. High-resolution multilocus sequence typing of 168 C. trachomatis cases from MSM in 2015 resulted in 29 sequence types, of which 3 accounted for 49% of cases. The increased rates and different genotypes of LGV indicate that more concern for high-risk taking MSM is needed to avoid further spread of this invasive infection.

  • 14.
    Johansson, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Nilsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Rautelin, Hilpi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Campylobacter coli clade 3 isolates induce rapid cell death in vitroIn: Article in journal (Other academic)
  • 15.
    Kaden, Rene
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology. National Veterinary Institute, Uppsala, Sweden; Swedish Forum for Biopreparedness Diagnostics, Umeå, Uppsala and Solna, Sweden; Swedish Joint Laboratory for Food Safety and Biopreparedness, Uppsala, Sweden.
    Ferrari, Sevinc
    National Veterinary Institute, Uppsala, Sweden; Swedish Forum for Biopreparedness Diagnostics, Umeå, Uppsala and Solna, Sweden; Swedish Joint Laboratory for Food Safety and Biopreparedness, Uppsala, Sweden.
    Jinnerot, Tomas
    National Veterinary Institute, Uppsala, Sweden; Swedish Forum for Biopreparedness Diagnostics, Umeå, Uppsala and Solna, Sweden; Swedish Joint Laboratory for Food Safety and Biopreparedness, Uppsala, Sweden.
    Lindberg, Martina
    National Veterinary Institute, Uppsala, Sweden; Swedish Forum for Biopreparedness Diagnostics, Umeå, Uppsala and Solna, Sweden; Swedish Joint Laboratory for Food Safety and Biopreparedness, Uppsala, Sweden; National Food Agency, Uppsala, Sweden.
    Wahab, Tara
    Swedish Forum for Biopreparedness Diagnostics, Umeå, Uppsala and Solna, Sweden; Public Health Agency of Sweden Solna, Sweden..
    Lavander, Moa
    Swedish Forum for Biopreparedness Diagnostics, Umeå, Uppsala and Solna, Sweden; Swedish Joint Laboratory for Food Safety and Biopreparedness, Uppsala, Sweden; National Food Agency, Uppsala, Sweden..
    Brucella abortus: determination of survival times and evaluation of methods for detection in several matrices2018In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 18, article id 259Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Brucella abortus is a highly pathogenic zoonotic agent, tempting for the development of a rapid diagnostic method to enable adequate treatment and prevent further spread. Enrichment of the bacteria is often used as a first step in diagnostics to increase the bacterial number above the detection limit of the real-time PCR. The enrichment of Brucella spp. takes at least 3 days, which might be avoidable if sensitive PCR methods can be used. Since many matrices contain PCR inhibitors, the limit of detection (LOD) must be determined for each separate matrix. Another aim of this study was the determination of survival of Brucella abortus in the analyzed matrices. METHODS: The LOD for the detection of B. abortus in 14 matrices, relevant for human medicine, veterinary medicine and food and feed safety, was determined to evaluate the need of a pre-enrichment step prior to real-time PCR. The survival of B. abortus in the spiked matrices was tested by plate count in a 7-day interval for 132 days. RESULTS: The limit of detection for B. abortus in most matrices was in the range of 10(3)-10(4) CFU/g for cultivation and 10(4)-10(5) CFU/g for direct real-time PCR. The survival time of B. abortus was less than 21 days in apple puree and stomach content and 28 days in water while B. abortus remained viable at day 132 in milk, blood, spinach and minced meat. CONCLUSIONS: A direct PCR analysis without enrichment of bacteria saves at least 3 days. However, the limit of detection between direct PCR and plate count differs in a 10 fold range. We conclude that this lower sensitivity is acceptable in most cases especially if quick analysis are required.

  • 16.
    Kjellin, Midori
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Wesslén, Terése
    Uppsala Univ Hosp, Dept Med Sci, Sect Infect Dis, Uppsala, Sweden.
    Löfblad, Erik
    Uppsala Univ Hosp, Dept Med Sci, Sect Infect Dis, Uppsala, Sweden.
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Lannergård, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    The effect of the first-generation HCV-protease inhibitors boceprevir and telaprevir and the relation to baseline NS3 resistance mutations in genotype 1: experience from a small Swedish cohort2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 1, p. 50-56Article in journal (Refereed)
    Abstract [en]

    Background: The clinical experience with protease-inhibitor (PI) triple regimen appears disappointing regarding effect, side effects, high work load, and costs. This real-world study evaluates baseline and emerging resistance-associated substitutions (RASs) and their significance for treatment outcome.

    Method: Thirty-six genotype 1a/b patients treated according to Swedish recommendations during 2011-2013 with triple therapy including pegylated interferon and ribavirin in combination with a protease-inhibitor, either boceprevir (BOC) or telaprevir (TVR), were retrospectively evaluated. Frozen serum samples from the patients were tested for resistance with pan-genotypic population sequencing.

    Results: Overall, 56% (20/36) of the patients achieved sustained viral response (SVR). The SVR was comparable between BOC (64%; 9/14) and TVR (50%; 11/22) (p = 0.07), and the IL28B type non-CC (48%; 12/25) and CC (46%; 6/13) (p = 0.77). The SVR was higher in patients without cirrhosis (89.5%; 17/19) (p < 0.0005), in treatment-naive patients (70%; 14/20) (p = 0.02), and those with low viral load (<800,000 IU/mL) (66.7%; 8/12) (p < 0.0002), compared to those with cirrhosis (17.6%; 3/17), treatment-experienced (37.5%; 6/16), and high viral load (>800,000 IU/mL) (50%; 12/24).

    Conclusion: PI triple regimes were highly effective in treatment-naive patients without cirrhosis, but in this real-world cohort an inferior effect was evident in cirrhotic and treatment-experienced patients. Although tested on a limited sample, the baseline resistance testing seems to have no impact on prediction of therapy outcome. The reason could be that the baseline RASs T54S and V55A have relatively low resistance towards BOC and TVR. Emerging RASs, mainly R155K, with known high resistance to BOC and TVR were frequently found in non-responders.

  • 17.
    Klingspor, Lena
    et al.
    Karolinska Inst, Div Clin Microbiol, Dept Lab Med, Stockholm, Sweden.
    Ullberg, Mans
    Karolinska Inst, Div Clin Microbiol, Dept Lab Med, Stockholm, Sweden;Karolinska Univ Hosp, Dept Clin Microbiol, Stockholm, Sweden.
    Rydberg, Johan
    Dept Clin Microbiol, Div Lab Med, Lund, Sweden.
    Kondori, Nahid
    Univ Gothenburg, Sahlgrenska Acad, Dept Infect Dis, Gothenburg, Sweden.
    Serrander, Lena
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Swanberg, Jonas
    Ryhov Hosp, Dept Clin Microbiol, Jonkoping, Sweden.
    Nilsson, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Bengten, Cecilia Jendle
    Karlstad Cent Hosp, Dept Clin Microbiol, Karlstad, Sweden.
    Johansson, Marcus
    Kalmar Cty Hosp, Dept Clin Microbiol, Kalmar, Sweden.
    Granlund, Margareta
    Umea Univ, Dept Clin Microbiol, Umea, Sweden.
    Tornqvist, Eva
    Orebro Univ Hosp, Dept Lab Med Clin Microbiol, Orebro, Sweden.
    Nyberg, Anders
    Cty Hosp Sundsvall Harnosand, Lab Med Clin Microbiol, Sundsvall Harnosand, Sweden.
    Kindlund, Karin
    Hallands Hosp, Dept Clin Microbiol, Halmstad, Sweden.
    Ygge, Minna
    Sunderby Hosp, Lulea, Sweden.
    Kartout-Boukdir, Dalila
    Unilabs AB, Malarsjukhuset Hosp, Clin Microbiol, Eskilstuna, Sweden.
    Toepfer, Michael
    Unilabs AB, Skaraborg Hosp, Clin Microbiol, Eskilstuna, Sweden.
    Halldin, Eva
    Vasteras Hosp, Clin Microbiol, Vasteras, Sweden.
    Kahlmeter, Gunnar
    Cent Hosp Vaxjo, Dept Clin Microbiol, Vaxjo, Sweden.
    Ozenci, Volkan
    Karolinska Inst, Div Clin Microbiol, Dept Lab Med, Stockholm, Sweden;Karolinska Univ Hosp, Dept Clin Microbiol, Stockholm, Sweden.
    Epidemiology of fungaemia in Sweden: A nationwide retrospective observational survey2018In: Mycoses (Berlin), ISSN 0933-7407, E-ISSN 1439-0507, Vol. 61, no 10, p. 777-785Article in journal (Refereed)
    Abstract [en]

    ObjectivesTo identify the epidemiology and antifungal susceptibilities of Candida spp. among blood culture isolates to identify the epidemiology and antifungal susceptibilities of Candida spp. among blood culture isolates in Sweden. MethodsThe study was a retrospective, observational nationwide laboratory-based surveillance for fungaemia and fungal meningitis and was conducted from September 2015 to August 2016. ResultsIn total, 488 Candida blood culture isolates were obtained from 471 patients (58% males). Compared to our previous study, the incidence of candidaemia has increased from 4.2/100000 (2005-2006) to 4.7/100000 population/year (2015-2016). The three most common Candida spp. isolated from blood cultures were Candida albicans (54.7%), Candida glabrata (19.7%) and species in the Candida parapsilosis complex (9.4%). Candida resistance to fluconazole was 2% in C.albicans and between 0% and 100%, in non-albicans species other than C.glabrata and C.krusei. Resistance to voriconazole was rare, except for C.glabrata, C.krusei and C.tropicalis. Resistance to anidulafungin was 3.8% while no Candida isolate was resistant to amphotericin B. ConclusionsWe report an overall increase in candidaemia but a minor decrease of C.albicans while C.glabrata and C.parapsilosis remain constant over this 10-year period.

  • 18.
    Klingspor, Lena
    et al.
    Karolinska Inst, Stockholm, Sweden.
    Özenci, Volkan
    Karolinska Inst, Stockholm, Sweden.
    Ullberg, Måns
    Karolinska Inst, Stockholm, Sweden.
    Rydberg, Johan
    Univ Skåne, Malmö, Sweden.
    Kondori, Nahid
    Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.
    Serrander, Lena
    Linköping Univ Hosp, Linköping, Sweden.
    Swanberg, Jonas
    Ryhov Hosp, Jönköping, Sweden.
    Nilsson, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Bengten, Cecilia Jendle
    Karlstad Hosp, Karlstad, Sweden.
    Johansson, Marcus
    Kalmar Cty Hosp, Kalmar, Sweden.
    Sjöberg, B.
    Örebro Univ Hosp, Örebro, Sweden.
    Granlund, Margareta
    Umeå Univ Hosp, Umeå, Sweden.
    Törnqvist, E.
    Örebro Univ Hosp, Örebro, Sweden.
    Sjögren, Sjögren
    Örebro Univ Hosp, Örebro, Sweden.
    Sundqvist-Persson, Anna-Lena
    Sundsvall Härnösand Hosp, Sundsvall Härnösand, Sweden.
    Kindlund, Karin
    Halmstad Cty Hosp, Halmstad, Sweden.
    Ygge, Minna
    Sunderby Hosp, Luleå, Sweden.
    Kartoutboukir, Dalila
    Unilabs, Eskilstuna, Sweden.
    Toepfer, Michael
    Unilabs, Eskilstuna, Sweden.
    Halldin, Eva
    Västerås Hosp, Västerås, Sweden.
    Nyberg, Anders
    Sundsvall Härnösand Hosp, Sundsvall Härnösand, Sweden.
    Kahlmeter, Gunnar
    Växjö Hosp, Växjö, Sweden.
    Epidemiology of fungaemia and fungal meningitis in Sweden: a nationwide retrospective observational survey from sept 2015-aug 20162018In: Medical Mycology, ISSN 1369-3786, E-ISSN 1460-2709, Vol. 56, no Supplement: 2, p. S61-S61Article in journal (Other academic)
  • 19.
    Lindbäck, Heidi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Inadequate adherence to Swedish guidelines for uncomplicated lower urinary tract infections among adults in general practice2017In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 125, no 9, p. 816-821Article in journal (Refereed)
    Abstract [en]

    In a primary care study of urinary tract infections (UTIs) performed 2008 in Uppsala County, Sweden, 43% of the patients were culture negative. In order to investigate the background to the observed overdiagnosis of UTI, study invitations were sent to the previously included patients. A total of 256 patients (88% women) approved to participate. Patient charts and recorded laboratory data were reviewed. Two or more of the cardinal symptoms were reported in 53% of the women and in 19% of the men. A dipstick test was performed in 93% of the consultations. The highest positive predicted values in women had a positive nitrite test (95%, 95% CI 87; 99) and dysuria in combination with urgency (81%, 95% CI 72; 88). Seventy-one percent of the women who fulfilled the symptom criteria received an antibiotic prescription directly, 87% of these had a positive culture. The drug of choice was pivmecillinam for women (51%) and quinolones (50%) for men. The treatment duration was too long for the women; 68% were treated for 7 days. In conclusion, the adherence to national guidelines/recommendations was inadequate. To reduce the selection of multiresistant bacteria, an improvement of the use of diagnostic criteria/tools and antibiotic drugs in primary care is necessary.

  • 20.
    Madsen, Kim B.
    et al.
    Falu Hospital, Section of Opthalmology.
    Wallménius, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Fridman, Åke
    Falu Hospital, Section of Opthalmology.
    Påhlson, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Nilsson, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology. Falu Hospital, Centre of Clinical Research.
    Seroprevalence against Rickettsia and Borrelia Species in Patients with Uveiti: A Prospective Survey2017In: Journal of Ophthalmology, ISSN 2090-004X, E-ISSN 2090-0058, article id 9247465Article in journal (Refereed)
    Abstract [en]

    Vector-borne diseases such as Lyme borreliosis and rickettsioses have been associated with ocular inflammation. Our aim was to study patients with diagnosed uveitis to evaluate serological signs of infection or exposure to these tick-borne agents. Forty-eight patients were prospectively examined with serology together with medical records and a questionnaire concerning previous exposure, diseases, and treatments. Seven patients (14.6%) showed seroconversion to Rickettsia spp. between acute and convalescent phase sera, which provides support for a positive Rickettsia diagnosis according to guidelines. The specificity was confirmed by Western blot. Additional 28 patients had stationary titres of which eight (16.6%) had 1 : 256 or higher titre in the first serum, and another 13 patients were seronegative. No epidemiological risk factor or marker could be identified. For Borrelia, only three patients showed moderate IgG titres. A control group of 100 blood donors, 60 patients with rheumatic disease, and 56 patients seeking medical care were tested of which 2.0–7.1% showed low anti-Rickettsia titres and 3.0–8.3% anti-Borrelia titres. The findings are indicative for an association between infection or exposure to Rickettsia spp. and uveitis with a seropositivity among patients with recurrent uveitis in concordance with the spread of rickettsial exposure in a tick-exposed population.

  • 21.
    Nilsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Characterization of Campylobacter jejuni and Campylobacter coli water isolates2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Campylobacter jejuni and C. coli are together the most common cause of bacterial gastroenteritis in the European Union. Campylobacter can be transmitted to humans via contaminated water, but it is largely unknown how these bacteria survive in water.

    The aim of this thesis was to better understand the water survival strategies and pathogenic potential of Campylobacter water isolates. For this purpose, C. jejuni and C. coli, originally isolated from incoming water at surface water plants, were characterized using whole genome sequencing, phenotypical assays, water survival experiments and an in vitro infection model.

    C. jejuni water isolates included both common and uncommon sequence types for human pathogens, whereas C. coli isolates were assigned to clades 2 and 3, associated with environmental sources. For C. jejuni, comparative genomics revealed genes involved in oxidative and aerobic stress response. In C. coli, various carbon metabolism-related sequences were identified in clade 2 isolates and in clade 3 isolates, oxidative stress and putative virulence genes were detected. All water isolates were motile and the majority of C. jejuni isolates, but none of C. coli isolates, were able to form biofilm. C. jejuni survived better than C. coli in untreated well and lake water. Furthermore, in contrast to C. coli, a seasonal difference in survival was observed for C. jejuni with better survival in lake water collected during autumn than in spring. When tested in an in vitro infection model, all water isolates adhered to and induced IL-8 response in HT-29 cells indicating pathogenic potential. However, C. coli clade 3 isolates demonstrated a strong cytotoxic effect on human HT-29 cells leading to rapid cell death. This novel phenomenon was not observed for C. coli clade 2 or C. jejuni isolates.

    This is, to the best of our knowledge, the first study on Campylobacter water isolates characterized using genomic, phenotypical and in vitro infection analyses. These findings suggest that some Campylobacter isolates might survive better than others in water and water survival patterns shown here help us further understand the seasonality and predominance of water-related C. jejuni infections.

    List of papers
    1. Genomic and phenotypic characteristics of Swedish C. jejuni water isolates
    Open this publication in new window or tab >>Genomic and phenotypic characteristics of Swedish C. jejuni water isolates
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    2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 12, article id e0189222Article in journal (Refereed) Published
    Abstract [en]

    Campylobacter jejuni is the most common cause of bacterial gastroenteritis. Major reservoirs are warm-blooded animals, poultry in particular, but Campylobacter can also be transmitted via water. In this paper, we have taken a closer look at the biology and potential virulence of C. jejuni water isolates. Seven C. jejuni isolates from incoming surface water at water plants in Sweden were characterized with whole genome sequencing and phenotypical testing. Multi locus sequence typing analysis revealed that these isolates belonged to groups known to include both common (ST48CC) and uncommon (ST1275CC, ST683, ST793 and ST8853) human pathogens. Further genomic characterization revealed that these isolates had potential for arsenic resistance (due to presence of arsB gene in all isolates), an anaerobic dimethyl sulfoxide oxidoreductase (in three isolates) and lacked the MarR-type transcriptional regulator gene rrpB (in all but one isolate) earlier shown to be involved in better survival under oxidative and aerobic stress. As putative virulence factors were concerned, there were differences between the water isolates in the presence of genes coding for cytolethal distending toxin (cdtABC), Type VI secretion system and sialylated LOS, as well as in biofilm formation. However, all isolates were motile and could adhere to and invade the human HT-29 colon cancer cell line in vitro and induce IL-8 secretion suggesting potential to infect humans. This is, to the best of our knowledge, the first study where C. jejuni water isolates have been characterized using whole genome sequencing and phenotypical assays. We found differences and shared traits among the isolates but also potential to infect humans.

    National Category
    Microbiology in the medical area
    Identifiers
    urn:nbn:se:uu:diva-339657 (URN)10.1371/journal.pone.0189222 (DOI)000417337800098 ()29216271 (PubMedID)
    Funder
    Swedish Research Council Formas, 221-2012-1442
    Available from: 2018-01-22 Created: 2018-01-22 Last updated: 2018-03-08Bibliographically approved
    2. Characterization of Swedish Campylobacter coli clade 2 and clade 3 water isolates
    Open this publication in new window or tab >>Characterization of Swedish Campylobacter coli clade 2 and clade 3 water isolates
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    2018 (English)In: MicrobiologyOpen, ISSN 2045-8827, E-ISSN 2045-8827, Vol. 7, no 4, article id e00583Article in journal (Refereed) Published
    Abstract [en]

    Campylobacter jejuni and Campylobacter coli are important bacterial enteropathogens. Poultry is the best-known reservoir for Campylobacter infection but natural bodies of water have also been shown to be important pathways for transmission. Campylobacter can survive in cold water but most of the studies have focused on C. jejuni only. In this paper, we take a closer look at the biology and water survival strategies of C. coil. Eight C. coil isolates cultivated from raw (incoming) surface water at water plants in Sweden were characterized using whole-genome sequencing and phenotypical assays. Phylogenetic analysis assigned the Swedish water isolates to clades 2 and 3, known to include C. coil of environmental origin. In addition, 53 earlier published sequences of C. coil clade 2 and 3 from environmental waters were included for in silico analyses. Generally, clade 2 isolates had larger genomes, which included a functional tricarballylate utilization locus, while clade 3 isolates contained different genes involved in oxidative stress as well as putative virulence factors. The Swedish water isolates of clade 2 formed large, blurry bacterial colonies on agar, whereas clade 3 colonies were smaller. All Swedish isolates were motile, but clade 3 isolates formed larger motility zones on soft agar, and none of these isolates produced biofilm. Although water survival varied between the analyzed isolates, there were hardly any clade-specific significant differences. Our results highlight the diversity of C. coil in general, and show differences in metabolic capabilities and ways to handle oxidative stress between clade 2 and 3 water isolates.

    Keywords
    Campylobacter coli, phenotypic identification, waterborne pathogens, whole-genome sequencing
    National Category
    Microbiology in the medical area
    Identifiers
    urn:nbn:se:uu:diva-332076 (URN)10.1002/mbo3.583 (DOI)000440928500006 ()29424055 (PubMedID)
    Funder
    Swedish Research Council Formas, 221- 2012-1442Swedish Research Council, 521-2011-3527
    Available from: 2018-01-30 Created: 2018-01-30 Last updated: 2018-10-31Bibliographically approved
    3. Campylobacter coli clade 3 isolates induce rapid cell death in vitro
    Open this publication in new window or tab >>Campylobacter coli clade 3 isolates induce rapid cell death in vitro
    (English)In: Article in journal (Other academic) Submitted
    National Category
    Microbiology in the medical area
    Identifiers
    urn:nbn:se:uu:diva-332077 (URN)
    Funder
    Swedish Research Council Formas, 221-2012-1442
    Available from: 2018-01-30 Created: 2018-01-30 Last updated: 2018-02-05
    4. Survival of Campylobacter jejuni and C. coli water isolates in lake and well water
    Open this publication in new window or tab >>Survival of Campylobacter jejuni and C. coli water isolates in lake and well water
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    2018 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 9, p. 762-770Article in journal (Refereed) Published
    Abstract [en]

    The role of water for transmission of Campylobacter jejuni and C. coli to humans might be underestimated, as factors important for bacterial viability in water are largely unknown. We have studied water survival of seven C. jejuni and eight C. coli isolates originally isolated from Swedish waters, together with selected reference strains, over eight days at 4 °C in the dark in untreated water collected from a local lake and a private well. To study seasonality, lake water samples were collected during spring and autumn. Samples for culturable bacterial counts were taken on days 2, 4, 6, and 8 and compared to the start inoculum. For C. jejuni, a significantly better survival was observed in autumn than in spring lake water. Furthermore, C. jejuni had a significantly better survival than C. coli in autumn lake and well water samples; the rate of culturability loss was almost double for C. coli in autumn lake water. These findings contribute to a better understanding on the seasonality of waterborne Campylobacter infections and the general predominance of C. jejuni.

    Keywords
    C. jejuni, C. coli, water survival, seasonality
    National Category
    Microbiology in the medical area Microbiology
    Research subject
    Microbiology; Clinical Bacteriology
    Identifiers
    urn:nbn:se:uu:diva-332079 (URN)10.1111/apm.12879 (DOI)000443111200008 ()
    Funder
    Swedish Research Council Formas, 221-2012-1442
    Available from: 2018-01-30 Created: 2018-01-30 Last updated: 2018-11-06Bibliographically approved
  • 22.
    Nilsson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Johansson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Skarp, Astrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Kaden, Rene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Bertilsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
    Rautelin, Hilpi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Survival of Campylobacter jejuni and C. coli water isolates in lake and well water2018In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 9, p. 762-770Article in journal (Refereed)
    Abstract [en]

    The role of water for transmission of Campylobacter jejuni and C. coli to humans might be underestimated, as factors important for bacterial viability in water are largely unknown. We have studied water survival of seven C. jejuni and eight C. coli isolates originally isolated from Swedish waters, together with selected reference strains, over eight days at 4 °C in the dark in untreated water collected from a local lake and a private well. To study seasonality, lake water samples were collected during spring and autumn. Samples for culturable bacterial counts were taken on days 2, 4, 6, and 8 and compared to the start inoculum. For C. jejuni, a significantly better survival was observed in autumn than in spring lake water. Furthermore, C. jejuni had a significantly better survival than C. coli in autumn lake and well water samples; the rate of culturability loss was almost double for C. coli in autumn lake water. These findings contribute to a better understanding on the seasonality of waterborne Campylobacter infections and the general predominance of C. jejuni.

  • 23.
    Nilsson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Johansson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Skarp, Astrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Kaden, Rene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Engstrand, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Department of Microbiology, Tumor and Cell Biology, Karolinska Institute.
    Rautelin, Hilpi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Genomic and phenotypic characteristics of Swedish C. jejuni water isolates2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 12, article id e0189222Article in journal (Refereed)
    Abstract [en]

    Campylobacter jejuni is the most common cause of bacterial gastroenteritis. Major reservoirs are warm-blooded animals, poultry in particular, but Campylobacter can also be transmitted via water. In this paper, we have taken a closer look at the biology and potential virulence of C. jejuni water isolates. Seven C. jejuni isolates from incoming surface water at water plants in Sweden were characterized with whole genome sequencing and phenotypical testing. Multi locus sequence typing analysis revealed that these isolates belonged to groups known to include both common (ST48CC) and uncommon (ST1275CC, ST683, ST793 and ST8853) human pathogens. Further genomic characterization revealed that these isolates had potential for arsenic resistance (due to presence of arsB gene in all isolates), an anaerobic dimethyl sulfoxide oxidoreductase (in three isolates) and lacked the MarR-type transcriptional regulator gene rrpB (in all but one isolate) earlier shown to be involved in better survival under oxidative and aerobic stress. As putative virulence factors were concerned, there were differences between the water isolates in the presence of genes coding for cytolethal distending toxin (cdtABC), Type VI secretion system and sialylated LOS, as well as in biofilm formation. However, all isolates were motile and could adhere to and invade the human HT-29 colon cancer cell line in vitro and induce IL-8 secretion suggesting potential to infect humans. This is, to the best of our knowledge, the first study where C. jejuni water isolates have been characterized using whole genome sequencing and phenotypical assays. We found differences and shared traits among the isolates but also potential to infect humans.

  • 24.
    Nilsson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Skarp, Astrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Johansson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Kaden, Rene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institute; Sci Life Lab, Clin Genom, Stockholm, Sweden.
    Rautelin, Hilpi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Characterization of Swedish Campylobacter coli clade 2 and clade 3 water isolates2018In: MicrobiologyOpen, ISSN 2045-8827, E-ISSN 2045-8827, Vol. 7, no 4, article id e00583Article in journal (Refereed)
    Abstract [en]

    Campylobacter jejuni and Campylobacter coli are important bacterial enteropathogens. Poultry is the best-known reservoir for Campylobacter infection but natural bodies of water have also been shown to be important pathways for transmission. Campylobacter can survive in cold water but most of the studies have focused on C. jejuni only. In this paper, we take a closer look at the biology and water survival strategies of C. coil. Eight C. coil isolates cultivated from raw (incoming) surface water at water plants in Sweden were characterized using whole-genome sequencing and phenotypical assays. Phylogenetic analysis assigned the Swedish water isolates to clades 2 and 3, known to include C. coil of environmental origin. In addition, 53 earlier published sequences of C. coil clade 2 and 3 from environmental waters were included for in silico analyses. Generally, clade 2 isolates had larger genomes, which included a functional tricarballylate utilization locus, while clade 3 isolates contained different genes involved in oxidative stress as well as putative virulence factors. The Swedish water isolates of clade 2 formed large, blurry bacterial colonies on agar, whereas clade 3 colonies were smaller. All Swedish isolates were motile, but clade 3 isolates formed larger motility zones on soft agar, and none of these isolates produced biofilm. Although water survival varied between the analyzed isolates, there were hardly any clade-specific significant differences. Our results highlight the diversity of C. coil in general, and show differences in metabolic capabilities and ways to handle oxidative stress between clade 2 and 3 water isolates.

  • 25.
    Nilsson, Kenneth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Elfving, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Påhlson, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Rickettsia helvetica in patient with meningitis, Sweden, 20062010In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 16, no 3, p. 490-492Article in journal (Refereed)
    Abstract [en]

    Pathogenicity of Rickettsia helvetica is relatively unknown. We isolated a spotted fever group rickettsial organism from a patient with subacute meningitis. Nucleotide sequences of the 16S rRNA, ompB, and 17kDa genes identified the isolate as R. helvetica. This organism may be associated with serious infections such as central nervous system disorders.

  • 26.
    Nilsson, Kenneth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Wallménius, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Rundlöf-Nygren, Pernilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Strömdahl, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Påhlson, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    African tick bite fever in returning Swedish travellers: Report of two cases and aspects of diagnostics2017In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 7, no 1, article id 1343081Article in journal (Refereed)
    Abstract [en]

    Introduction: African tick-bite fever, caused by Rickettsia africae, is endemic in rural areas of sub-Saharan Africa and a possible cause of fever in returning Swedish travellers. Two patients are presented, and the advantages and disadvantages of different diagnostic methods are discussed.

    Patients and methods: Two middle-aged men fell ill with fever after returning home from South Africa. Both had single eschars and one also presented with a lymph node swelling. Samples were taken for serology, general bacterial culture from the wound (Patient 1) using a swab and additionally for Patient 2 PCR of a skin biopsy from the eschar.

    Results and discussion: Both patients seroconverted one month after onset. Real-time PCR of the biopsy was positive, where sequencing of the gltA gene was 99–100% consistent with R. africae. A drop of fluid from the biopsy contained a sufficient number of bacteria to also allow for isolation of rickettsiae in Vero cell culture. Direct molecular detection by PCR from a swab used for bacteria culture from the eschar from Patient 1 also yielded a positive result. In conclusion, the findings highlight the usefulness of swabs for early non-invasive diagnosis of African tick-bite fever in febrile travellers.

  • 27.
    Palanisamy, Navaneethan
    et al.
    Heidelberg Univ, BioQuant, Mol & Cellular Engn Grp, Heidelberg, Germany.;Heidelberg Univ, Hartmut Hoffmann Berling Int Grad Sch Mol & Cellu, Heidelberg, Germany..
    Akaberi, Dario
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Protein backbone flexibility pattern is evolutionarily conserved in the Flaviviridae family: A case of NS3 protease in Flavivirus and Hepacivirus2018In: Molecular Phylogenetics and Evolution, ISSN 1055-7903, E-ISSN 1095-9513, Vol. 118, p. 58-63Article in journal (Refereed)
    Abstract [en]

    Viruses belonging to the Flaviviridae family have been an important health concern for humans, animals and birds alike. No specific treatment is available yet for many of the viral infections caused by the members of this family. Lack of specific drugs against these viruses is mainly due to lack of protein structure information. It has been known that protein backbone fluctuation pattern is highly conserved in protein pairs with similar folds, in spite of the lack of sequence similarity. We hypothesized that this concept should also hold true for proteins (especially enzymes) of viruses included in different genera of the Flaviviridae family, as we know that the sequence similarity between them is low. Using available NS3 protease crystal structures of the Flaviviridae family, our preliminary results have shown that the C alpha (i.e. backbone) fluctuation patterns are highly similar between Flaviviruses and a Hepacivirus (i.e. hepatitis C virus, HCV). This has to be validated further experimentally.

  • 28.
    Palanisamy, Navaneethan
    et al.
    Univ Freiburg, Inst Biol 2, Mol & Cellular Engn Grp, Freiburg, Germany;Heidelberg Univ, Hartmut Hoffmann Berling Int Grad Sch Mol & Cellu, Heidelberg, Germany.
    Akaberi, Dario
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lundkvist, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Comparative genome analysis of Alkhumra hemorrhagic fever virus with Kyasanur forest disease and tick-borne encephalitis viruses by the in silico approach2018In: Pathogens and Global Health, ISSN 2047-7724, E-ISSN 2047-7732, Vol. 112, no 4, p. 210-226Article in journal (Refereed)
    Abstract [en]

    Alkhumra hemorrhagic fever virus (AHFV), a relatively new member of the Flaviviruses, was discovered in Saudi Arabia 23 years ago. AHFV is classified in the tick-borne encephalitis virus serocomplex, along with the Kyasanur forest disease virus (KFDV) and tick-borne encephalitis virus (TBEV). Currently, very little is known about the pathologies of AHFV. In this study, using the available genome information of AHFV, KFDV and TBEV, we have predicted and compared the following aspects of these viruses: evolution, nucleotide and protein compositions, recombination, codon frequency, substitution rate, N- and 0-glycosylation sites, signal peptide and cleavage site, transmembrane region, secondary structure of 5' and 3' UTRs and RNARNA interactions. Additionally, we have modeled the 3D protease and RNA-dependent RNA polymerase structures for AHFV, KFDV and TBEV. Recombination analysis showed no evidence of recombination in the AHFV genome with that of either KFDV or TBEV, although single break point analysis showed that nucleotide position 7399 (in the NS4B) is a breakpoint location. AHFV, KFDV and TBEV are very similar in terms of codon frequency, the number of transmembrane regions, properties of the polyprotein, RNA-RNA interaction sequences, NS3 protease and NS5 polymerase structures and 5' UTR structure. Using genome sequences, we showed the similarities between these closely- related viruses on several different areas.

  • 29.
    Palanisamy, Navaneethan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology. Heidelberg Univ, IPMB, Synthet Biol Grp, Neuenheimer Feld 267 BioQuant, D-69120 Heidelberg, Germany; Heidelberg Univ, Hartmut Hoffmann Berling Int Grad Sch Mol & Cellu, Heidelberg, Germany.
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Biophysical Studies on HCV 1a NS3/4A Protease and Its Catalytic Triad in Wild Type and Mutants by the In Silico Approach.2018In: Interdisciplinary sciences: computational life sciences, ISSN 1913-2751, Vol. 10, no 1, p. 143-156Article in journal (Refereed)
    Abstract [en]

    The hepatitis C virus (HCV), of the family flaviviridae, is one of the major causes of chronic liver diseases. Until the year 2012, HCV infections were treated using PEG-interferon and ribavirin combinations, which have a low cure rate and severe side effects. Currently, many direct-acting antivirals (DAAs) are available, e.g. protease inhibitors, NS5A and polymerase inhibitors. These drugs have proven to be efficient in interferon-free treatment combinations and capable of enhancing the cure rate to above 90 %. Unlike PEG-interferon and ribavirin combinations, DAAs select for resistance in HCV. The R155K mutation in the HCV was found to resist all the currently available protease inhibitors. Here, we studied biophysical parameters like pocket (cavity) geometries and stabilizing residues of HCV 1a NS3/4A protease in wild type and mutants. We also studied HCV 1a NS3/4A protease's catalytic residues: their accessibility, energy, flexibility and binding to Phase II oral protease inhibitor vedroprevir (GS-9451), and compared these parameters between wild type and mutant(s). All these studies were performed using various bioinformatics tools (e.g. Swiss-PdbViewer and Schrödinger's Maestro) and web servers (e.g. DoGSiteScorer, SRide, ASA-View, WHAT IF, elNémo, CABS-flex, PatchDock and PLIP). From our study, we found that introduction of R155K, A156T or D168A mutation to wild-type NS3/4A protease increases the pocket's volume, surface (in the R155K mutant, surface decreases), lipo surface and depth and decreases the number of stabilizing residues. Additionally, differences in catalytic residues' solvent accessibility, energy, root-mean-square deviation (RMSD) and flexibility between wild type and mutants might explain changes in the protease activity and the resistance to protease inhibitors.

  • 30.
    Pineiro, L.
    et al.
    Hosp Univ Donostia, Inst Invest Sanitaria Biodonostia, Microbiol Dept, San Sebastian, Spain.
    Isaksson, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Zapico, M.
    Hosp Univ Donostia, Inst Invest Sanitaria Biodonostia, Microbiol Dept, San Sebastian, Spain.
    Cilla, G.
    Hosp Univ Donostia, Inst Invest Sanitaria Biodonostia, Microbiol Dept, San Sebastian, Spain;Biomed Res Ctr Network Resp Dis CIBERES, San Sebastian, Spain.
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Chlamydia trachomatis genotypes A and B from urogenital specimens of patients in Spain: molecular characterization2018In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 24, no 8, p. 910.e5-910.e8Article in journal (Refereed)
    Abstract [en]

    Objectives: Chlamydia trachomatis ompA genotypes A and B, primarily associated with trachoma, were unexpectedly detected in urogenital samples of patients in Spain, a trachoma-free country. In this study, we aimed to explain this finding using analysis of organotropism-related genes and a multilocus sequence typing (MLST) technique.

    Methods: C trachomatis genotypes A or B were detected in 8/930 (0.9%) infection episodes between 2006 and 2012. In these strains, organotropism-related genes (polymorphic membrane protein gene H, tryptophan synthase gene A, CTA0934, and cytotoxin) were studied. Further, the strains were analysed by MLST, using a polymerase chain reaction that amplifies five highly variable genomic loci (hctB, CT058, CT144, CT172, and pbpB). Amplicons were sequenced and phylogenetic analysis was conducted.

    Results: Seven strains were detected in the eight infection episodes (in one patient, an identical strain being found in two episodes). Analysis of organotropism-related genes showed that these strains shared genetic features characteristic of genitotropic genotypes but not of trachoma strains. Three strains of genotype A showed a unique and new MLST-sequence type (ST551, allele profile 8-8-2-27-69). The four strains of genotype B belonged to ST138.

    Conclusions: C. trachomatis ompA genotypes A and B associated with trachoma, but detected sporadically in urogenital samples in trachoma-free countries, may be the result of recombination between strains adapted to trachoma and strains adapted to sexual transmission.

  • 31.
    Rivas, Lourdes
    et al.
    KTH Royal Inst Technol, Sci Life Lab, Div Prote & Nanobiotechnol, Stockholm, Sweden.
    Reuterswärd, Philippa
    KTH Royal Inst Technol, Sci Life Lab, Div Prote & Nanobiotechnol, Stockholm, Sweden.
    Rasti, Reza
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden;South Gen Hosp, Sachs Children & Youth Hosp, Stockholm, Sweden.
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Mårtensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH), International Child Health and Nutrition.
    Alfven, Tobias
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden;South Gen Hosp, Sachs Children & Youth Hosp, Stockholm, Sweden.
    Gantelius, Jesper
    KTH Royal Inst Technol, Sci Life Lab, Div Prote & Nanobiotechnol, Stockholm, Sweden;Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.
    Andersson-Svahn, Helene
    KTH Royal Inst Technol, Sci Life Lab, Div Prote & Nanobiotechnol, Stockholm, Sweden.
    A vertical flow paper-microarray assay with isothermal DNA amplification for detection of Neisseria meningitidis2018In: Talanta: The International Journal of Pure and Applied Analytical Chemistry, ISSN 0039-9140, E-ISSN 1873-3573, Vol. 183, p. 192-200Article in journal (Refereed)
    Abstract [en]

    Paper-based biosensors offer a promising technology to be used at the point of care, enabled by good performance, convenience and low-cost. In this article, we describe a colorimetric vertical-flow DNA microarray (DNAVFM) that takes advantage of the screening capability of DNA microarrays in a paper format together with isothermal amplification by means of Recombinase Polymerase Amplification (RPA). Different assay parameters such as hybridization buffer, flow rate, printing buffer and capture probe concentration were optimized. A limit of detection (LOD) of 4.4 nM was achieved as determined by tabletop scanning. The DNA-VFM was applied as a proof of concept for detection of Neisseria meningitidis, a primary cause of bacterial meningitis. The LOD was determined to be between 38 and 2.1 x 10(6) copies/VFMassay, depending on the choice of DNA capture probes. The presented approach provides multiplex capabilities of DNA microarrays in a paper-based format for future point-of-care applications.

  • 32.
    Rönnberg, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Gustafsson, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Univ Uppsala Hosp, Lab Clin Microbiol, Uppsala, Sweden..
    Vapalahti, Olli
    Univ Helsinki, Dept Vet Biosci & Virol, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland..
    Emmerich, Petra
    Bernhard Nocht Inst Trop Med, WHO Collaborating Ctr Arbovirus & Haemorrhag Feve, D-20359 Hamburg, Germany.;Univ Rostock, Dept Trop Med & Infect Dis, Ctr Internal Med 2, D-18057 Rostock, Germany..
    Lundkvist, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology. Univ Uppsala Hosp, Lab Clin Microbiol, Uppsala, Sweden..
    Schmidt-Chanasit, Jonas
    Bernhard Nocht Inst Trop Med, WHO Collaborating Ctr Arbovirus & Haemorrhag Feve, D-20359 Hamburg, Germany.;German Ctr Infect Res DZIF, Partner Site Hamburg Luebeck Borstel, Hamburg, Germany..
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Compensating for cross-reactions using avidity and computation in a suspension multiplex immunoassay for serotyping of Zika versus other flavivirus infections2017In: Medical Microbiology and Immmunology, ISSN 0300-8584, E-ISSN 1432-1831, Vol. 206, no 5, p. 383-401Article in journal (Refereed)
    Abstract [en]

    The recent spread of Zika virus (ZIKV) in the Americas and Asia necessitates an increased preparedness for improved maternal and perinatal health and blood safety. However, serological cross-reactions, especially to Dengue virus (DENV), complicate ZIKV antibody serodiagnosis. A novel "pan-Flavi" suspension multiplex immunoassay (PFSMIA) using 25 antigens, whole virus (WV), non-structural protein 1 (NS1), and envelope (E) proteins, from 7 zoonotic flaviviruses for specific detection of ZIKV and DENV IgM and IgG was developed. Patterns of antibody cross-reactivity, avidity, and kinetics were established in 104 sera from returning travelers with known ZIKV and DENV infections. PFSMIA gave IgM- and IgG-sensitivities for both viruses of 96-100%, compared to an immunofluorescence assay. Main IgM cross-reactions were to NS1, for IgG to the E and WV antigens. Infecting virus yielded reactivity to several antigens of the homologous virus, while cross-reactions tended to occur only to a single antigen from heterologous virus(es). A specificity-enhancing computer procedure took into account antibody isotype, number of antibody-reactive antigens per virus, avidity, average degree of cross-reactivity to heterologous flavivirus antigens, and reactivity changes in serial sera. It classified all 50 cases correctly. Applied to sera from 200 pregnant women and 173 blood donors from Sweden, one blood donor was found ZIKV NS1 IgM positive, and another as ZIKV NS1 IgG positive. These samples did not react with other ZIKV antigens and were thereby judged as false-positives. PFSMIA provided sensitive and specific ZIKV and DENV serology, warranting high-throughput serological surveillance and a minimized need for laborious and expensive virus neutralization assays.

  • 33.
    Wass, Linda
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Infect Dis, Gothenburg, Sweden.
    Grankvist, Anna
    Univ Gothenburg, Sahlgrenska Acad, Dept Infect Dis, Gothenburg, Sweden.
    Mattsson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Gustafsson, Helena
    Gavle Cent Hosp, Dept Hematol, Gavle, Sweden.
    Krogfelt, Karen
    Statens Serum Inst, Dept Bacteria Parasites & Fungi, Copenhagen, Denmark.
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Nilsson, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Mårtensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Quarsten, Hanne
    Sorlandet Hosp Hlth Enterprise, Dept Med Microbiol, Kristiansand, Norway.
    Henningsson, Anna J.
    Cty Hosp Ryhov, Dept Clin Microbiol, Jonkoping, Sweden.
    Wennerås, Christine
    Univ Gothenburg, Sahlgrenska Acad, Dept Infect Dis, Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Clin Microbiol, Guldhedsgatan 10, S-41346 Gothenburg, Sweden.
    Serological reactivity to Anaplasma phagocytophilum in neoehrlichiosis patients2018In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 37, no 9, p. 1673-1678Article in journal (Refereed)
    Abstract [en]

    The tick-borne bacterium Candidatus (Ca.) Neoehrlichia (N.) mikurensis is a cause of "fever of unknown origin" because this strict intracellular pathogen escapes detection by routine blood cultures. Case reports suggest that neoehrlichiosis patients may display serological reactivity to Anaplasma (A.) phagocytophilum. Since Anaplasma serology is part of the diagnostic work-up of undetermined fever in European tick-exposed patients, we wanted to investigate (1) the prevalence of A. phagocytophilum seropositivity among neoehrlichiosis patients, (2) the frequency of misdiagnosed neoehrlichiosis patients among A. phagocytophilum seropositive patients, and (3) the frequency of A. phagocytophilum and Ca. N. mikurensis co-infections. Neoehrlichiosis patients (n = 18) were analyzed for A. phagocytophilum IgM and IgG serum antibodies by indirect immunofluorescence assay. Serum samples from suspected anaplasmosis patients (n = 101) were analyzed for bacterial DNA contents by singleplex PCR specific for A. phagocytophilum and Ca. N. mikurensis, respectively. One fifth of the neoehrlichiosis patients (4/18) were seropositive for IgM and/or IgG to A. phagocytophilum at the time of diagnosis. Among the patients with suspected anaplasmosis, 2% (2/101) were positive for Ca. N. mikurensis by PCR whereas none (0/101) had detectable A. phagocytophilum DNA in the serum. To conclude, patients with suspected anaplasmosis may in fact have neoehrlichiosis. We found no evidence of A. phagocytophilum and Ca. N. mikurensis co-infections in humans with suspected anaplasmosis or confirmed neoehrlichiosis.

  • 34.
    Xia, Hongyan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine. Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, S-75007 Uppsala, Sweden..
    Gravelsina, Sabine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine. Riga Stradins Univ, August Kirchenstein Inst Microbiol & Virol, Riga, Latvia..
    Öhrmalm, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Ottoson, Jakob
    Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, S-75007 Uppsala, Sweden.;Natl Food Adm Toxicol Lab, Dept Risk & Benefit Assessment, Uppsala, Sweden..
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Development of single-tube nested real-time PCR assays with long internally quenched probes for detection of norovirus genogroup II2016In: BioTechniques, ISSN 0736-6205, E-ISSN 1940-9818, Vol. 60, no 1, p. 28-34Article in journal (Refereed)
    Abstract [en]

    The high sequence variation of RNA viruses necessitates use of degenerate primers and probes or multiple primers and probes in molecular diagnostic assays. We showed previously that PCR amplification in two rounds, first with long target-specific primers and then with short generic primers, followed by detection using long probes, can tolerate sequence variation. Here we demonstrate that long primers and probes of up to 56 nucleotides can also be applied in real-time PCR for the detection of norovirus genogroup II with improved sensitivity. Probe design (method of incorporating quenchers, use of Zen internal quencher or traditional quenchers) greatly affects the sensitivity of the real-time PCR assays.

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