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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.
    Bartlett, Sofia R.
    et al.
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia.
    Grebely, Jason
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia.
    Eltahla, Auda A.
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia;Univ New South Wales, Fac Med, Sch Med Sci, Sydney, NSW, Australia.
    Reeves, Jacqueline D.
    Monogram Biosci, Lab Corp Amer Holdings, San Francisco, CA USA.
    Howe, Anita Y. M.
    St Pauls Hosp, British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
    Miller, Veronica
    Univ Calif Berkeley, Forum Collaborat HIV Res, Washington, DC USA.
    Ceccherini-Silberstein, Francesca
    Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy.
    Bull, Rowena A.
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia;Univ New South Wales, Fac Med, Sch Med Sci, Sydney, NSW, Australia.
    Douglas, Mark W.
    Univ Sydney, Westmead Inst Med Res, Storr Liver Ctr, Sydney, NSW, Australia.
    Dore, Gregory J.
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia.
    Harrington, Patrick
    US FDA, Ctr Drug Evaluat & Res, Div Antiviral Prod, Silver Spring, MD USA.
    Lloyd, Andrew R.
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia;Univ New South Wales, Fac Med, Sch Med Sci, Sydney, NSW, Australia.
    Jacka, Brendan
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia.
    Matthews, Gail V.
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia.
    Wang, Gary P.
    Univ Florida, Coll Med, Dept Med, Gainesville, FL USA.
    Pawlotsky, Jean-Michel
    Univ Paris Est, Hop Henri Mondor, Dept Virol, Natl Reference Ctr Viral Hepatitis B C & D, Creteil, France;Univ Paris Est, Hop Henri Mondor, INSERM, U955, Creteil, France.
    Feld, Jordan J.
    Univ Toronto, Univ Hlth Network, Toronto Western Hosp, Liver Ctr, Toronto, ON, Canada.
    Schinkel, Janke
    Acad Med Ctr, Dept Med Microbiol, Amsterdam, Netherlands.
    Garcia, Federico
    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, Tanya L.
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia.
    Sequencing of Hepatitis C Virus for Detection of Resistance to Direct-Acting Antiviral Therapy: A Systematic Review2017In: HEPATOLOGY COMMUNICATIONS, ISSN 2471-254X, Vol. 1, no 5, p. 379-390Article, review/survey (Refereed)
    Abstract [en]

    The significance of the clinical impact of direct-acting antiviral (DAA) resistance-associated substitutions (RASs) in hepatitis C virus (HCV) on treatment failure is unclear. No standardized methods or guidelines for detection of DAA RASs in HCV exist. To facilitate further evaluations of the impact of DAA RASs in HCV, we conducted a systematic review of RAS sequencing protocols, compiled a comprehensive public library of sequencing primers, and provided expert guidance on the most appropriate methods to screen and identify RASs. The development of standardized RAS sequencing protocols is complicated due to a high genetic variability and the need for genotype- and subtype-specific protocols for multiple regions. We have identified several limitations of the available methods and have highlighted areas requiring further research and development. The development, validation, and sharing of standardized methods for all genotypes and subtypes should be a priority.

  • 4.
    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.

  • 5.
    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)
  • 6.
    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.

  • 7.
    Blomberg, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Rizwan, Muhammad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Böhlin-Wiener, Agnes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Elfaitouri, Amal
    Benghazi Univ, Dept Infect Dis & Trop Med, Fac Publ Hlth, Benghazi, Libya.
    Julin, Per
    Stora Skondal, Neurol Rehabil Clin, Skondal, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Zachrisson, Olof
    Gottfries Clin AB, Molndal, Sweden.
    Rosen, Anders
    Linkoping Univ, Dept Clin & Expt Med, Div Cell Biol, Linkoping, Sweden.
    Gottfries, Carl-Gerhard
    Gottfries Clin AB, Molndal, Sweden.
    Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients2019In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 1946Article in journal (Refereed)
    Abstract [en]

    Myalgic encephalomyelitis, also referred to as chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by myalgia and a sometimes severe limitation of physical activity and cognition. It is exacerbated by physical and mental activity. Its cause is unknown, but frequently starts with an infection. The eliciting infection (commonly infectious mononucleosis or an upper respiratory infection) can be more or less well diagnosed. Among the human herpesviruses (HHV-1 -8), HHV-4 (Epstein-Barr virus; EBV), HHV-6 (including HHV-6A and HHV-6B), and HHV-7, have been implicated in the pathogenesis of ME/CFS. It was therefore logical to search for serological evidence of past herpesvirus infection/reactivation in several cohorts of ME/CFS patients (all diagnosed using the Canada criteria). Control samples were from Swedish blood donors. We used whole purified virus, recombinant proteins, and synthetic peptides as antigens in a suspension multiplex immunoassay (SMIA) for immunoglobulin G (IgG). The study on herpesviral peptides based on antigenicity with human sera yielded novel epitope information. Overall, IgG anti-herpes-viral reactivities of ME/CFS patients and controls did not show significant differences. However, the high precision and internally controlled format allowed us to observe minor relative differences between antibody reactivities of some herpesviral antigens in ME/CFS versus controls. ME/CFS samples reacted somewhat differently from controls with whole virus HHV-1 antigens and recombinant EBV EBNA6 and EA antigens. We conclude that ME/CFS samples had similar levels of IgG reactivity as blood donor samples with HHV-1-7 antigens. The subtle serological differences should not be over-interpreted, but they may indicate that the immune system of some ME/CFS patients interact with the ubiquitous herpesviruses in a way different from that of healthy controls.

  • 8.
    Chang, Ting-Chia
    et al.
    George Washington Univ, Med Ctr, Dept Biochem & Mol Med, Washington, DC 20037 USA.
    Goud, Santosh
    George Mason Univ, Sch Syst Biol, Manassas, VA USA.
    Torcivia-Rodriguez, John
    George Washington Univ, Med Ctr, Dept Biochem & Mol Med, Washington, DC 20037 USA.
    Hu, Yu
    George Washington Univ, Med Ctr, Dept Biochem & Mol Med, Washington, DC 20037 USA.
    Pan, Qing
    George Washington Univ, Dept Stat, Washington, DC 20052 USA.
    Kahsay, Robel
    George Washington Univ, Med Ctr, Dept Biochem & Mol Med, Washington, DC 20037 USA.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Mazumder, Raja
    George Washington Univ, Med Ctr, Dept Biochem & Mol Med, Washington, DC 20037 USA;George Washington Univ, McCormick Genom & Prote Ctr, Washington, DC 20037 USA.
    Investigation of somatic single nucleotide variations in human endogenous retrovirus elements and their potential association with cancer2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 4, article id e0213770Article in journal (Refereed)
    Abstract [en]

    Human endogenous retroviruses (HERVs) have been investigated for potential links with human cancer. However, the distribution of somatic nucleotide variations in HERV elements has not been explored in detail. This study aims to identify HERV elements with an over-representation of somatic mutations (hot spots) in cancer patients. Four HERV elements with mutation hotspots were identified that overlap with exons of four human protein coding genes. These hotspots were identified based on the significant over-representation (p<8.62e-4) of non-synonymous single-nucleotide variations (nsSNVs). These genes are TNN (HERV-9/LTR12), OR4K15 (HERV-IP10F/LTR10F), ZNF99 (HERV-W/HERV17/LTR17), and KIR2DL1 (MST/MaLR). In an effort to identify mutations that effect survival, all nsSNVs were further evaluated and it was found that kidney cancer patients with mutation C2270G in ZNF99 have a significantly lower survival rate (hazard ratio = 2.6) compared to those without it. Among HERV elements in the human non-protein coding regions, we found 788 HERVs with significantly elevated numbers of somatic single-nucleotide variations (SNVs) (p<1.60e-5). From this category the top three HERV elements with significantly over-represented SNVs are HERV-H/LTR7, HERV-9/LTR12 and HERV-L/MLT2. Majority of the SNVs in these 788 HERV elements are located in three DNA functional groups: long non-coding RNAs (lncRNAs) (60%), introns (22.2%) and transcriptional factor binding sites (TFBS) (14.8%). This study provides a list of mutational hotspots in HERVs, which could potentially be used as biomarkers and therapeutic targets.

  • 9.
    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.

  • 10.
    Feresiadou, Amalia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Nilsson, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Press, Rayomand
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden..
    Kmezic, Ivan
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden..
    Nygren, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Svenningsson, Anders
    Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden..
    Niemelä, Valter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Cunningham, Janet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Kultima, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Measurement of sCD27 in the cerebrospinal fluid identifies patients with neuroinflammatory disease2019In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 332, p. 31-36Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Laboratory tests to assist in the diagnosis and monitoring of neuroinflammatory diseases are scarce. The soluble form of the CD27 molecule (sCD27) is shed in high concentrations by activated T cells and can be detected in the cerebrospinal fluid. The aim of this study was to investigate whether CSF quantitation of sCD27 could discriminate between inflammatory and non-inflammatory neurological diseases.

    METHODS: The concentration of sCD27 was measured using a commercially available ELISA in 803 well-defined subjects from a study cohort comprised of 338 patients with neuroinflammatory disease, 338 with non-inflammatory neurological disease and 127 controls without neurological disease.

    RESULTS: The median value of cerebrospinal fluid sCD27 was 64 pg/mL (IQR 0-200) in controls, 58 pg/mL (IQR 0-130) in patients with non-inflammatory disease and 740 pg/mL (IQR 230-1800) in patients with inflammatory disease. The likelihood ratio of having an inflammatory disease was 10 (sensitivity 74% and specificity 93%) if the sCD27 concentration was >250 pg/mL. In patients with a known inflammatory condition, the likelihood ratio of having an infection was 10 (sensitivity 40% and specificity 96%) if the sCD27 concentration was >2500 pg/mL.

    CONCLUSIONS: The likelihood of having an inflammatory neurological condition is increased with elevated concentrations of sCD27 in cerebrospinal fluid. Rapid tests of sCD27 should be developed to assist clinicians in diagnosis of neuroinflammatory disease.

  • 11.
    Gideskog, Maria
    et al.
    Linkoping Univ Hosp, Dept Infect Control & Hyg, S-58185 Linkoping, Sweden.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology. Linkoping Univ Hosp, Dept Infect Control & Hyg, S-58185 Linkoping, Sweden.
    Outbreak of Methicillin-resistant Staphylococcus aureus in a Hospital Center for Children's and Women's Health in a Swedish County2019In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, no 4, p. 181-186Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to investigate a sudden increase in methicillin-resistant Staphylococcus aureus (MRSA) cases primarily in one maternity ward at the Center for Children's and Women's Health at Linkoping University Hospital, Sweden. Approximately 300 individuals including patients, their family members, and healthcare workers were screened for MRSA. The antibiotic susceptibility was tested and isolates polymerase chain reaction (PCR)-positive for the mecA gene were spa typed. Isolates with the same antibiogram and spa type were further whole genome sequenced. Compliance to current cleaning and hygiene routines was also controlled, and environmental samples collected. The results showed that a total of 13 individuals were involved in the outbreak. It was caused by a t386 MRSA strain (ST-1, NCBI-accession AB505628) with additional resistance to erythromycin and clindamycin. All cases were epidemiologically connected to the index patient, who had recently emigrated from a high-endemic area for MRSA. With improved cleaning and better compliance to basic hygiene routines, no further cases were reported. This study demonstrates how rapid an MRSA strain can disseminate in a ward with susceptible patients and insufficient cleaning and hygiene. For a better control of MRSA, clinical cultures and screening samples need to be obtained early and more extensively than according to the current recommendations.

  • 12.
    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.

  • 13.
    Goncalves, Odete Sofia Lopes
    et al.
    Aalborg Univ, Dept Hlth Sci & Technol, Fredrik Bajers Vej 7, DK-9220 Aalborg, Denmark.
    Christiansen, Gunna
    Loke Holdingselskab, Skaering Hedevej 185, DK-8250 Egaa, Denmark;Aarhus Univ, Dept Biomed, Bartholins Alle 6, DK-8000 Aarhus C, Denmark.
    Holm, Arne
    Aarhus Univ, Dept Biomed, Bartholins Alle 6, DK-8000 Aarhus C, Denmark.
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Klintstedt, Markus
    Q Linea AB, Dag Hammerskjolds Vag 54B, SE-75237 Uppsala, Sweden.
    Petersen, Steffen B.
    Aalborg Univ, Dept Hlth Sci & Technol, Fredrik Bajers Vej 7, DK-9220 Aalborg, Denmark.
    Birkelund, Svend
    Aalborg Univ, Dept Hlth Sci & Technol, Fredrik Bajers Vej 7, DK-9220 Aalborg, Denmark.
    The repeated 36 amino acid motif of Chlamydia trachomatis Hc2 protein binds to the major groove of DNA2019In: Research in Microbiology, ISSN 0923-2508, E-ISSN 1769-7123, Vol. 170, no 6-7, p. 256-262Article in journal (Refereed)
    Abstract [en]

    The gram-negative, obligate intracellular human pathogen, Chlamydia trachomatis has a bi-phasic developmental cycle. The histone H1-like C. trachomatis DNA binding protein, Hc2, is produced late during the developmental cycle when the dividing reticulate body transforms into the smaller, metabolically inactive elementary body. Together with Hc1, the two proteins compact the chlamydial chromosome and arrest replication and transcription. Hc2 is heterogeneous in length due to variation in the number of lysine rich pentamers. Six pentamers and one hexamer constitute a 36 amino acid long repetitive unit that, in spite of variations, is unique for Chlamydiaceae. Using synthetic peptides, the DNA-binding capacity of the 36 amino acid peptide and that of a randomized peptide was analyzed. Both peptides bound and compacted plasmid DNA, however, electron microscopy of peptide/DNA complexes showed major differences in the resulting aggregated structures. Fluorescence spectroscopy was used to analyze the binding. After complexing plasmid DNA with each of three different intercalating dyes, increasing amounts of peptides were added and fluorescence spectroscopy performed. The major groove binder, methyl green, was displaced by both peptides at low concentrations, while the minor groove binder, Hoechts, and the intercalating dye, Ethidium Bromide, were displaced only at high concentrations of peptides. (C) 2019 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  • 14.
    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.

  • 15.
    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.

  • 16.
    Gullsby, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Molecular detection and epidemiological studies of atypical bacteria causing respiratory tract infections2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Respiratory infections are common causes of morbidity and mortality. Chlamydia pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis cause respiratory infection, often with similar symptoms. Molecular diagnostic methods are preferred since these bacteria are difficult to culture. The aim of this thesis was to evaluate and improve the diagnostics and knowledge of the epidemiology of these bacteria.

    A real-time polymerase chain reaction (PCR) method targeting the IS481 element present in the genome of B. pertussis was compared to culture and serology results, and a duplex real-time PCR method was constructed for detecting C. pneumoniae and M. pneumoniae, which was compared to two endpoint PCR methods. Both real-time PCR methods showed high sensitivity and specificity.

    Typing of 624 M. pneumoniae samples, collected from 1996 to 2017 from four counties, was performed by P1 typing and multiple-locus variable number tandem repeat analysis (MLVA). A polyclonal distribution of strains was seen over all epidemic periods, but strains of P1 type 2/variant 2 and MLVA types 3-5-6-2 and 4-5-7-2 predominated in 2010−2013. A shift from type 2 strains to different variant 2 strains was seen and a new variant, 2e, was detected in 2016−2017. An A2063G mutation associated with macrolide resistance was detected by a fluorescence resonance energy transfer (FRET) PCR method in one (0.16%) of 608 M. pneumoniae strains.

    Molecular characterisation using whole-genome sequencing of 93 B. pertussis isolates, collected between 1986 and 2016 from three counties showed that there were polyclonal strains in the county of Dalarna, Gävleborg and Uppsala in the years 2014−2016. Changes in virulence-related genes were detected: a shift from isolates harbouring the ptxP3 allele in favour of ptxP1 was seen, and almost all isolates had a disrupted prn gene. No detection of macrolide resistance in B. pertussis was detected.

    In conclusion, the validated real-time PCR methods for detection of B. pertussis, C. pneumoniae and M. pneumoniae have led to improved diagnostic methods for use in clinical laboratories. The molecular characterisation of M. pneumoniae and B. pertussis strains has contributed to the wider understanding of the genetic changes that has occurred over the epidemic periods, but further studies is needed.

  • 17.
    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)
  • 18.
    Hanslin, Katja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Skorup, Paul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Wilske, Frida
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine. Perioperative Medicine and Intensive Care, Karolinska University Hospital and CLINTEC, Karolinska Institute, Stockholm, Sweden.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    The impact of the systemic inflammatory response on hepatic bacterial elimination in experimental abdominal sepsis2019In: Intensive Care Medicine Experimental, ISSN 2197-425X, Vol. 7, no 1, article id 52Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bacterial translocation from the gut has been suggested to induce a systemic inflammatory response syndrome (SIRS) and organ dysfunction. The liver has a pivotal role in eliminating circulating bacteria entering from the gut. We investigated whether pre-existing inflammation affects hepatic bacterial elimination.

    METHODS: Fifteen anaesthetised piglets were infused with E. coli in the portal vein for 3 h. The naive group (n = 6) received the bacterial infusion without endotoxin exposure. SIRS (SIRS group, n = 6) was induced by endotoxin infusion 24 h before the bacterial infusion. For effects of anaesthesia, controls (n = 3) received saline instead of endotoxin for 24 h. Bacterial counts and endotoxin levels in the portal and hepatic veins were analysed during bacterial infusion.

    RESULTS: The bacterial killing rate was higher in the naive group compared with the SIRS group (p = 0.001). The ratio of hepatic to portal venous bacterial counts, i.e. the median bacterial influx from the splanchnic circulation, was 0.06 (IQR 0.01-0.11) in the naive group and 0.71 (0.03-1.77) in the SIRS group at 3 h, and a magnitude lower in the naive group during bacteraemia (p = 0.03). Similar results were seen for hepatic endotoxin elimination. Peak log tumour necrosis factor alpha was higher in the naive 4.84 (4.77-4.89) vs. the SIRS group 3.27 (3.26-3.32) mg/L (p < 0.001).

    CONCLUSIONS: Our results suggest that hepatic bacterial and endotoxin elimination is impaired in pigs with pre-existing SIRS while the inflammatory response to bacterial infusion is diminished. If similar mechanisms operate in human critical illness, the hepatic elimination of bacteria from the gut could be impaired by SIRS.

  • 19.
    Harding-Esch, Emma M.
    et al.
    London Sch Hyg & Trop Med, Keppel St, London WC1E 7HT, England.
    Holland, Martin J.
    London Sch Hyg & Trop Med, Keppel St, London WC1E 7HT, England;MRC Labs, POB 273, Fajara, Banjul, Gambia.
    Schemann, Jean-Francois
    IRD, Dakar, Senegal.
    Sillah, Ansumana
    Minist Hlth & Social Welf, Natl Eye Hlth Programme, Kanifing, Gambia.
    Sarr, Boubacar
    Minist Sante, Programme Natl Lutte Cecite, BP 3817, Dakar, Senegal.
    Christerson, Linus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Pickering, Harry
    London Sch Hyg & Trop Med, Keppel St, London WC1E 7HT, England.
    Molina-Gonzalez, Sandra
    London Sch Hyg & Trop Med, Keppel St, London WC1E 7HT, England.
    Sarr, Isatou
    MRC Labs, POB 273, Fajara, Banjul, Gambia.
    Andreasen, Aura A.
    London Sch Hyg & Trop Med, Keppel St, London WC1E 7HT, England.
    Jeffries, David
    MRC Labs, POB 273, Fajara, Banjul, Gambia.
    Grundy, Chris
    London Sch Hyg & Trop Med, Keppel St, London WC1E 7HT, England.
    Mabey, David C. W.
    London Sch Hyg & Trop Med, Keppel St, London WC1E 7HT, England.
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Bailey, Robin L.
    London Sch Hyg & Trop Med, Keppel St, London WC1E 7HT, England.
    Impact of a single round of mass drug administration with azithromycin on active trachoma and ocular Chlamydia trachomatis prevalence and circulating strains in The Gambia and Senegal2019In: Parasites & Vectors, ISSN 1756-3305, E-ISSN 1756-3305, Vol. 12, article id 497Article in journal (Refereed)
    Abstract [en]

    Background: Mass drug administration (MDA) with azithromycin is a cornerstone of the trachoma elimination strategy. Although the global prevalence of active trachoma has declined considerably, prevalence persists or even increases in some communities and districts. To increase understanding of MDA impact, we investigated the prevalence of active trachoma and ocular C. trachomatis prevalence, organism load, and circulating strains at baseline and one-year post-MDA in The Gambia and Senegal.

    Methods: Pre- and one-year post-MDA, children aged 0-9 years were examined for clinical signs of trachoma in six Gambian and 12 Senegalese villages. Ocular swabs from each child's right conjunctiva were tested for evidence of ocular C. trachomatis infection and organism load (ompA copy number), and ompA and multi-locus sequence typing (MLST) was performed.

    Results: A total of 1171 children were examined at baseline and follow-up in The Gambia. Active trachoma prevalence decreased from 23.9% to 17.7%, whereas ocular C. trachomatis prevalence increased from 3.0% to 3.8%. In Senegal, 1613 and 1771 children were examined at baseline and follow-up, respectively. Active trachoma prevalence decreased from 14.9% to 8.0%, whereas ocular C. trachomatis prevalence increased from 1.8% to 3.6%. Higher organism load was associated with having active trachoma and severe inflammation. Sequence typing demonstrated that all Senegalese samples were genovar A, whereas Gambian samples were a mix of genovars A and B. MLST provided evidence of clustering at village and household levels and demonstrated differences of strain variant frequencies in Senegal, indicative of an "outbreak". MLST, including partial ompA typing, provided greater discriminatory power than complete ompA typing.

    Conclusions: We found that one round of MDA led to an overall decline in active trachoma prevalence but no impact on ocular C. trachomatis infection, with heterogeneity observed between villages studied. This could not be explained by MDA coverage or number of different circulating strains pre- and post-MDA. The poor correlation between active trachoma and infection prevalence supports the need for further work on alternative indicators to clinical signs for diagnosing ocular C. trachomatis infection. MLST typing has potential molecular epidemiology utility, including better understanding of transmission dynamics, although relationship to whole-genome sequence variability requires further exploration.

  • 20.
    Herrmann, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Isaksson, Jenny
    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, Åsa
    Karolinska Univ Hosp, Stockholm, Sweden.
    Strömdahl, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bratt, Göran
    South Gen Hosp, Stockholm, Sweden.
    LYMPHOGRANULOMA VENEREUM IN SWEDEN 2004-2016: INCREASED RATES AMONG HIV-NEGATIVE MEN WHO HAVE SEX WITH MEN AND CHANGED GENOTYPES2017In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 93, no Suppl. 2, p. A103-A103, article id P3.27Article in journal (Other academic)
  • 21.
    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)
  • 22.
    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.

  • 23.
    Ianevski, Aleksandr
    et al.
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Zusinaite, Eva
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Shtaida, Nastassia
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Kallio-Kokko, Hannimari
    Univ Helsinki, Dept Virol & Immunol, Helsinki, Finland.
    Valkonen, Miia
    HUS, Helsinki, Finland; Univ Helsinki, Helsinki, Finland.
    Kantele, Anu
    HUS, Helsinki, Finland; Univ Helsinki, Helsinki, Finland.
    Telling, Kaidi
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Lutsar, Irja
    Univ Tartu, Inst Med Microbiol, Tartu, Estonia.
    Letjuka, Pille
    Narva Haigla, Narva, Estonia.
    Metelitsa, Natalja
    Narva Haigla, Narva, Estonia.
    Oksenych, Valentyn
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Dumpis, Uga
    Latvian Biomed Res & Study Ctr, Riga, Latvia.
    Vitkauskiene, Astra
    Lithuanian Univ Hlth Sci, Dept Lab Med, Kaunas, Lithuania.
    Stasaitis, Kestutis
    Lithuanian Univ Hlth Sci, Dept Emergency Med, 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.
    Cox, Rebecca J.
    Univ Bergen, Dept Clin Sci, Influenza Ctr, Bergen, Norway.
    Tenson, Tanel
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Merits, Andres
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Kainov, Denis E.
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway; Univ Tartu, Inst Technol, Tartu, Estonia.
    Low Temperature and Low UV Indexes Correlated with Peaks of Influenza Virus Activity in Northern Europe during 2010-20182019In: Viruses, ISSN 1999-4915, E-ISSN 1999-4915, Vol. 11, no 3, article id 207Article in journal (Refereed)
    Abstract [en]

    With the increasing pace of global warming, it is important to understand the role of meteorological factors in influenza virus (IV) epidemics. In this study, we investigated the impact of temperature, UV index, humidity, wind speed, atmospheric pressure, and precipitation on IV activity in Norway, Sweden, Finland, Estonia, Latvia and Lithuania during 2010-2018. Both correlation and machine learning analyses revealed that low temperature and UV indexes were the most predictive meteorological factors for IV epidemics in Northern Europe. Our in vitro experiments confirmed that low temperature and UV radiation preserved IV infectivity. Associations between these meteorological factors and IV activity could improve surveillance and promote development of accurate predictive models for future influenza outbreaks in the region.

  • 24.
    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.

  • 25.
    Johansson, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Nilsson, Anna J. E.
    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.
    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 vitro2019In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 85, no 5, article id UNSP e02993-18Article in journal (Refereed)
    Abstract [en]

    Campylobacter are major human enteropathogens. C. coli show less genetic diversity than C. jejuni and cluster into three clades, of which clade 1 includes most human and farm animal isolates while environmental C. coli mainly belong to clades 2 and 3. Recently, we whole genome-sequenced eight C. coli clade 2 and 3 isolates cultivated from water, and here we studied their interaction with human HT-29 colon cancer cells compared to clinical clade 1 isolates. All C. coli clade 3 isolates caused cell necrosis already 1-2 hours after inoculation, whereas none of the clade 1 and 2 isolates analyzed induced cell death. Isolates from clades 2 and 3 adhered better than clade 1 isolates to epithelial cells but all isolates induced similar levels of IL-8. Alignment and phylogenetic analysis of translated putative virulence genes cadF, flpA, iamA, ciaB and ceuE revealed clade-specific protein sequence variations with clade 1 and 2 sequences more closely related and clade 3 sequences further apart in general.Moreover, when RNA levels were measured, clade 3 isolates showed a significantly lower expression of cadF, iamA and ceuE than clade 2 isolates, while flpA levels were higher in clade 3 isolates. The cytolethal distending toxin genes were also expressed in clades 2 and 3 although there was no difference between clades. Our findings demonstrate differences between effects of C. coli clade 1, 2 and 3 isolates on human cells and suggest that C. coli clade 3 might be more virulent than clade 2 due to the observed cytotoxicity.

    IMPORTANCECampylobacter coli is a common zoonotic cause of gastroenteritis in humans worldwide. The majority of infections are caused by C. coli clade 1 isolates, whereas infections due to clade 2 and 3 isolates are rare. Whether this depends on a low prevalence of clade 2 and 3 isolates in reservoirs important for human infections or their lower ability to cause human disease is unknown. Here, we studied the effects of C. coli clade 2 and 3 isolates on a human cell line. These isolates adhered to human cells to a higher degree than clinical clade 1 isolates. Furthermore, we could show that C. coli clade 3 isolates rapidly induced cell death suggesting differences in the virulence of C. coli The exact mechanism of cell death remains to be revealed but selected genes showed interesting clade-specific expression patterns.

  • 26.
    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. Swedish Univ Agr Sci, Dept Ecol, Uppsala, Sweden.
    Kaden, Rene
    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.
    Differences in virulence gene expression between human blood and stool Campylobacter coli clade 1 ST828CC isolates2019In: Gut Pathogens, ISSN 1757-4749, Vol. 11, no 1, article id 42Article in journal (Refereed)
    Abstract [en]

    Background: Campylobacter colonise the gastrointestinal tract of warm-blooded animals and are major enteropathogens in humans. C. coli is less common than C. jejuni and accounts for about 10% of the total number of Campylobacter infections although the two species seem to share many virulence determinants. Campylobacter bacteraemia is rare, estimated to occur in less than 1% of the infections, and the exact mechanisms regulating the progression of the infection from the gastrointestinal tract to the blood stream are unclear. Here, we looked at the contribution of C. coli to Campylobacter infections and further compared various virulence traits in C. coli clade 1 blood and stool isolates. Results: We assessed the numbers of C. jejuni and C. coli among typed isolates in the PubMLST database and found that C. coli accounted for 25.9% of blood isolates, but only 8.9% of the stool isolates. Phylogenetic analysis of 128 C. coli clade 1 whole genome sequences deposited to NCBI revealed no specific clustering of the human blood, stool or animal isolates. Of the six C. coli isolates chosen for phenotypic analyses, stool isolates adhered significantly better to human HT-29 colon cancer cells than the blood isolates, while there was no difference in induced IL-8 levels between the isolates. Furthermore, the stool isolates had two-to fourfold higher RNA expression levels of the flpA, ciaB, iamA and cdt virulence genes than the blood isolates. Finally, we looked at the gene structure of the cdtA, B and C toxin genes and found numerous nucleotide additions and deletions disrupting the open reading frames. In contrast to 58% isolates of animal origin, only 38% and 32% of human blood and stool isolates, respectively, had all three cdt genes intact, a prerequisite to produce functional toxins. Conclusions: This study reveals interesting differences between C. coli clade 1 isolates of human and animal origin on one hand, and also between human blood and stool isolates, on the other. The results suggest that C. coli might downregulate and/or inactivate various virulence determinants as the isolates pass from the animal host to the human gastrointestinal tract and enter the human blood stream.

  • 27.
    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)
  • 28.
    Johansson, Cecilia
    et al.
    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.
    Kaden, Rene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Staphylococcus argenteus and Staphylococcus schweitzeri are cytotoxic to human cells in vitro due to high expression of alpha-hemolysin Hla2019In: Virulence, ISSN 2150-5594, E-ISSN 2150-5608, Vol. 10, no 1, p. 502-510Article in journal (Refereed)
    Abstract [en]

    Staphylococcus argenteus and Staphylococcus schweitzeri are newly identified species of the S. aureus-related complex. S. argenteus, as occurring globally and showing significant prevalence and comparable infection and morbidity rates compared to S. aureus, is becoming clinically important. Whole genome sequencing has revealed the presence of several virulence genes but the molecular mechanisms of S. argenteus infection and virulence are largely unknown. Here, we studied the effect of a previously characterized clinical S. argenteus isolate on human cells in vitro. The clinical isolate, together with the S. argenteus type strain MSHR1132T and the S. schweitzeri type strain FSA084T, had a cytotoxic effect on the cells, which showed necrotic cell death after a few hours of treatment. The protein causing the cytotoxic effect was purified and identified by mass spectrometry as alpha-hemolysin, Hla, which is awell-known pore-forming toxin in S.aureus. The cytotoxic effect could be blocked with an antibody against Hla. S.argenteus showed 12-15 fold higher expression levels of hla at the RNA level and 4-6 fold higher expression levels at the protein level compared to S.aureus. The higher expression levels of hla were supported by higher RNA levels of the regulatory factors sarA and saeR. Also, the RNAIII component of the accessory gene regulator (agr) quorum sensing system was 8,000-10,000 fold higher in the S.argenteus isolates compared to S.aureus. This is the first study on the effect of S.argenteus on ahuman cell line and strengthens the idea of significant virulence of S.argenteus.

  • 29.
    Kaden, Rene
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Engstrand, Lars
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Solna, Sweden.
    Rautelin, Hilpi
    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.
    Which methods are appropriate for the detection of Staphylococcus argenteus and is it worthwhile to distinguish S. argenteus from S. aureus?2018In: Infection and Drug Resistance, ISSN 1178-6973, E-ISSN 1178-6973, Vol. 11, p. 2335-2344Article in journal (Refereed)
    Abstract [en]

    Purpose: To further analyze a clinical isolate originally identified as methicillin-resistant Staphylococcus aureus (MRSA) using whole-genome sequencing and comparative genomics.

    Materials and methods: Classical diagnostic methods such as cultivation, biochemical tests, and PCR were supplemented with whole-genome sequencing and comparative genomics, to identify the isolate.

    Results: The isolate was phenotypically similar to MRSA. However, the presence of the nuc gene could not be confirmed using PCR, while it was positive for the mecA gene. Whole-genome sequencing correctly identified the isolate as Staphylococcus argenteus. The isolate possessed several resistance genes, such as mecA, blaZ (beta-lactam antibiotics) and dfrG (trimethoprim). The me gene differed from that of MRSA. Six phylogenetic distinct clusters were identified by average nucleotide identity (ANI) analysis of all available S. argenteus whole-genome sequences. Our isolate, RK308, clustered with those isolated in Europe and Asia.

    Conclusion: Due to the invasive potential, the multi-drug resistance and the similarity to MRSA, S. argenteus should be included in the MRSA screening. Due to the divergent genome compared to MRSA, new PCR approaches have to be developed to avoid an unnoticed spreading of S. argenteus.

  • 30.
    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.

  • 31. Kileng, Hege
    et al.
    Kjellin, Midori
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Akaberi, Dario
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Bergfors, Assar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Duberg, Ann-Sofi
    Wesslén, Lars
    Danielsson, Astrid
    Gangsøy Kristiansen, Magnhild
    Gutteberg, Tore
    Goll, Rasmus
    Lannergård, Anders
    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, Infection medicine.
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Personalized treatment of hepatitis C genotype 1a in Norway and Sweden 2014-2016: a study of treatment outcome in patients with or without resistance-based DAA-therapy.2018In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 10-11, p. 1347-1353Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Resistance-associated substitutions (RASs) may impair treatment response to direct-acting antivirals (DAA) in hepatitis C virus (HCV) treatment. We investigated the effects of baseline NS3-RASs (Q80K and R155K) and clinically relevant NS5A-RASs in patients with HCV genotype (GT) 1a infection on treatment outcome, with or without resistance-based DAA-treatment. This multi-center study was carried out between 2014 and 2016.

    PATIENTS/METHODS: Treatment in the intervention group (n = 92) was tailored to baseline resistance. Detection of NS3-RAS led to an NS5A-inhibitor-based regimen and detection of NS5A-RAS to a protease-inhibitor regimen. Patients without baseline RAS in the intervention group and all patients in the control group (n = 101) received recommended standard DAA-treatment.

    RESULTS: The sustained virologic response rates (SVR) in the intervention and control groups were 97.8% (90/92) and 93.1% (94/101), respectively (p = .174). A trend toward higher SVR-rate in cirrhotic patients (p = .058) was noticed in the intervention group compared to the control group with SVR-rates 97.5% (39/40) and 83.3% (35/42), respectively. All patients with baseline NS3 (Q80K/R155K) or NS5A-RASs in the intervention group achieved SVR with personalized resistance-based treatment. In the control group, five patients with Q80K or R155K at baseline were treated with simeprevir + sofosbuvir and treatment failed in two of them. Furthermore, one of three patients who failed ledipasvir + sofosbuvir treatment had NS5A-RASs at baseline.

    CONCLUSIONS: In line with the findings of the OPTIMIST-2 trial for Q80K and the EASL-guidelines 2016 for NS5A-RASs, baseline RASs appeared to have an impact on treatment outcome albeit a statistical significance was not observed in this low-prevalence population.

  • 32.
    Kjellin, Midori
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Kileng, Hege
    UiT Arctic Univ Norway, Dept Clin Med, Gastroenterol & Nutr Res Grp, Tromso, Norway;Univ Hosp North Norway, Dept Med, Tromso, Norway.
    Akaberi, Dario
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Palanisamy, Navaneethan
    Heidelberg Univ, HBIGS, Heidelberg, Germany;Univ Freiburg, Inst Biol 2, Freiburg, Germany.
    Duberg, Ann-Sofi
    Orebro Univ, Fac Med & Hlth, Sch Med Sci, Dept Infect Dis, Orebro, Sweden.
    Danielsson, Astrid
    Falun Cent Hosp, Dept Infect Dis, Falun, Sweden.
    Kristiansen, Magnhild Gangsöy
    UiT Artic Univ Tromso, Dept Clin Med IKM, Nordlandssykehuset Bodo, Tromso, Norway.
    Nöjd, Johan
    UiT Artic Univ Tromso, Dept Clin Med IKM, Nordlandssykehuset Bodo, Tromso, Norway.
    Aleman, Soo
    Karolinska Univ Hosp, Karolinska Inst, Dept Infect Dis, Stockholm, Sweden.
    Gutteberg, Tore
    UiT Arctic Univ Norway, Dept Med Biol, Res Grp Host Microbe Interact, Tromso, Norway;Univ Hosp North Norway, Dept Microbiol & Infect Control, Tromso, Norway.
    Goll, Rasmus
    UiT Arctic Univ Norway, Dept Clin Med, Gastroenterol & Nutr Res Grp, Tromso, Norway;Univ Hosp North Norway, Dept Med, Tromso, Norway.
    Lannergård, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Effect of the baseline Y93H resistance-associated substitution in HCV genotype 3 for direct-acting antiviral treatment: real-life experience from a multicenter study in Sweden and Norway2019In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 8, p. 1042-1050Article in journal (Refereed)
    Abstract [en]

    Background: The NS5A resistance-associated substitution (RAS) Y93H is found quite frequently (5-10%) at baseline in direct-acting antiviral agents (DAA) treatment-naive genotype (GT) 3a patients when studied by the population-sequencing method (cut-off 20%). This RAS may impair HCV DAA treatment response, since it possesses a high fold in vitro resistance to daclatasvir (DCV) and velpatasvir (VEL) in GT 3. We investigated the effect of baseline Y93H in patients with GT 3a infection on treatment outcome, with or without resistance-based DAA-treatment during 2014-2017.

    Patients/Methods: Treatment in the intervention group (n = 130) was tailored to baseline resistance-findings by population-sequencing method. Detection of baseline Y93H above 20% prompted a prolonged treatment duration of NS5A-inhibitor and sofosbuvir (SOF) and/or addition of ribavirin (RBV). Patients without baseline Y93H in the intervention group and all patients in the control group (n = 78) received recommended standard DAA-treatment.

    Results: A higher sustained virologic response rate (SVR) in the intervention group was shown compared to the control group at 95.4% (124/130) and 88.5% (69/78), respectively (p = .06). All five patients with baseline Y93H in the intervention group achieved SVR with personalised treatment based on results from resistance testing; either with the addition of RBV or prolonged treatment duration (24w). In the control group, 2/4 patients with Y93H at baseline treated with ledipasvir/SOF/RBV or DCV/SOF without RBV, failed treatment.

    Conclusion: The results from this real-life study are in accordance with the findings of the randomised controlled trials in 2015 and the EASL-guidelines of 2016, thus, baseline Y93H impacts on DCV and VEL treatment outcome.

  • 33.
    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.

  • 34.
    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.

  • 35.
    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)
  • 36.
    Krupovic, Mart
    et al.
    Inst Pasteur, Dept Microbiol, Paris, France..
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Coffin, John M.
    Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA..
    Dasgupta, Indranil
    Univ Delhi, Dept Plant Mol Biol, New Delhi, India..
    Fan, Hung
    Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA..
    Geering, Andrew D.
    Univ Queensland, Queensland Alliance Agr & Food Innovat, Brisbane, Qld, Australia..
    Gifford, Robert
    Univ Glasgow, Ctr Virus Res, MRC, Glasgow, Lanark, Scotland..
    Harrach, Balazs
    Hungarian Acad Sci, Ctr Agr Res, Inst Vet Med Res, Budapest, Hungary..
    Hull, Roger
    Child Okeford, Blandford Forum, Dorset, England..
    Johnson, Welkin
    Boston Coll, Biol Dept, Chestnut Hill, MA 02167 USA..
    Kreuze, Jan F.
    Int Potato Ctr CIP, Crop & Syst Sci Div, Lima, Peru..
    Lindemann, Dirk
    Tech Univ Dresden, Inst Virol, Dresden, Germany..
    Llorens, Carlos
    Univ Valencia, Parc Cientif, Biotechvana, Valencia, Spain..
    Lockhart, Ben
    Univ Minnesota, Dept Plant Pathol, St Paul, MN USA..
    Mayer, Jens
    Univ Saarland, Inst Human Genet, Homburg, Germany..
    Muller, Emmanuelle
    CIRAD, UMR BGPI, Montpellier, France.;Univ Montpellier, CIRAD, INRA, BGPI,Montpellier SupAgro, Montpellier, France..
    Olszewski, Neil E.
    Univ Minnesota, Dept Microbial & Plant Biol, St Paul, MN 55108 USA..
    Pappu, Hanu R.
    Washington State Univ, Dept Plant Pathol, Pullman, WA 99164 USA..
    Pooggin, Mikhail M.
    INRA, UMR BGPI, Montpellier, France..
    Richert-Poeggeler, Katja R.
    Julius Kuhn Inst, Inst Epidemiol & Pathogen Diagnost, Braunschweig, Germany..
    Sabanadzovic, Sead
    Mississippi State Univ, Dept Biochem Mol Biol Entomol & & Plant Pathol, Mississippi State, MS 39762 USA..
    Sanfacon, Helene
    Agr & Agrifood Canada, Summerland Res & Dev Ctr, Summerland, BC, Canada..
    Schoelz, James E.
    Univ Missouri, Div Plant Sci, Columbia, MO USA..
    Seal, Susan
    Univ Greenwich, Nat Resources Inst, Chatham, Kent, England..
    Stavolone, Livia
    CNR, Ist Protez Sostenibile Piante, Bari, Italy.;Int Inst Trop Agr, Ibadan, Nigeria..
    Stoye, Jonathan P.
    Imperial Coll London, Fac Med, Francis Crick Inst, BB, London, England.;Imperial Coll London, Fac Med, Dept Med, BB, London, England..
    Teycheney, Pierre-Yves
    CIRAD, UMR AGAP, Capesterre Belle Eau, Guadeloupe, France.;Univ Montpellier, INRA, CIRAD, AGAP,Montpellier SupAgro, Montpellier, France..
    Tristem, Michael
    Imperial Coll London, Silwood Pk Campus, Ascot, Berks, England..
    Koonin, Eugene V.
    Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA..
    Kuhn, Jens H.
    NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD USA..
    Ortervirales: New Virus Order Unifying Five Families of Reverse-Transcribing Viruses2018In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 92, no 12, article id e00515-18Article in journal (Other academic)
  • 37.
    Lepuschitz, Sarah
    et al.
    Austrian Agcy Hlth & Food Safety, Vienna, Austria;Vienna Univ Technol, Vienna, Austria.
    Ruppitsch, Werner
    Austrian Agcy Hlth & Food Safety, Vienna, Austria.
    Pekard-Amenitsch, Shiva
    Austrian Agcy Hlth & Food Safety, Vienna, Austria.
    Forsythe, Stephen J.
    foodmicrobe.com, Keyworth, United Kingdom.
    Cormican, Martin
    Natl Univ Ireland, Galway, Ireland.
    Mach, Robert L.
    Vienna Univ Technol, Vienna, Austria.
    Pierard, Denis
    Univ Ziekenhuis Brussel, Brussels, Belgium.
    Allerberger, Franz
    Austrian Agcy Hlth & Food Safety, Vienna, Austria.
    Allerberger, F.
    Austrian Agcy Hlth & Food Safety, Vienna, Austria.
    Andrasevic, A. Tambic
    Univ Hosp Infect Dis, Zagreb, Croatia.
    Balode, A.
    Pauls Stradins Clin Univ Hosp, Riga, Latvia.
    Barbut, F.
    Hop St Antoine, Paris, France.
    Codita, Irina
    Carol Davila Univ Med & Pharm, Bucharest, Romania.
    Connican, M.
    Natl Univ Ireland Galway, Sch Med, Galway, Ireland.
    Ferguson, C.
    Victoria Hosp, Kirkcaldy, Scotland.
    Heczko, P.
    Jagiellonian Univ, Med Coll, Krakow, Poland.
    Holy, O.
    Palacky Univ, Dept Prevent Med, Olomouc, Czech Republic.
    Kantardjiev, T.
    Natl Ctr Infect & Parasit Dis, Sofia, Bulgaria.
    Kuijper, E. J.
    Leiden Univ, Med Ctr, Leiden, Netherlands.
    Leegaard, T. M.
    Akershus Univ Hosp, Lorenskog, Norway.
    Peixe, L. M. , V
    Pierard, D.
    Univ Ziekenhuis Brussel, Dept Lab Med, Brussels, Belgium.
    Rautelin, Hilpi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Rupnik, M.
    Nacl Lab Zdravje Okolje & Hrano, Maribor, Slovenia.
    Schonning, K.
    Hvidovre Univ Hosp, Hvidovre, Denmark.
    Stephan, R.
    Univ Zurich, Inst Food Safety & Hyg, Zurich, Switzerland.
    Toniolo, A.
    Univ Insubria, Varese, Italy.
    Tosic, T.
    Clin Ctr Serbia, Belgrade, Serbia.
    Valdezate, S.
    Inst Salud Carlos III, Madrid, Spain.
    von Mueller, L.
    Christophorus Kliniken GmbH, Coesfeld, Germany.
    Zerva, L.
    Attikon Hosp, Athens, Greece.
    Zinieri-Panayide, B.
    Gen Hosp, Paphos, Greece.
    Multicenter Study of Cronobacter sakazakii Infections in Humans, Europe, 20172019In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 25, no 3, p. 515-522Article in journal (Refereed)
    Abstract [en]

    Cronobacter sakazakii has been documented as a cause of life-threating infections, predominantly in neonates. We conducted a multicenter study to assess the occurrence of C. sakazakii across Europe and the extent of clonality for outbreak detection. National coordinators representing 24 countries in Europe were requested to submit all human C. sakazakii isolates collected during 2017 to a study center in Austria. Testing at the center included species identification by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, subtyping by whole-genome sequencing (WGS), and determination of antimicrobial resistance. Eleven countries sent 77 isolates, including 36 isolates from 2017 and 41 historical isolates. Fifty-nine isolates were confirmed as C. sakazakii by WGS, highlighting the challenge of correctly identifying Cronobacter spp. WGS-based typing revealed high strain diversity, indicating absence of multi-national outbreaks in 2017, but identified 4 previously unpublished historical outbreaks. WGS is the recommended method for accurate identification, typing, and detection of this pathogen.

  • 38.
    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.

  • 39.
    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.

  • 40.
    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.

  • 41.
    Nilsson, Anna J. E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Tervahartiala, Taina
    Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Stenbäckinkatu 9, PO Box 100, 00029 Helsinki, Finland.
    Lennebratt, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Lannergård, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Sorsa, Timo
    Department of Dental Medicine, Division of Periodontology, Karolinska Institute, SE-17177 Stockholm, Sweden.
    Rautelin, Hilpi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Enhanced Systemic Response of Matrix Metalloproteinases and Their Regulators in Campylobacter and Salmonella Patients2018In: Diagnostics (Basel), ISSN 2075-4418, Vol. 8, no 4, article id 82Article in journal (Refereed)
    Abstract [en]

    Campylobacters are major enteropathogens worldwide with a substantial financial burden. Matrix metalloproteinases (MMPs) are proteolytic metalloendopeptidases with ability to modify immune response and shown to be upregulated in patients with several tissue destructive diseases, including infections. We measured here serum concentrations of MMP-8 and MMP-9 together with their regulators myeloperoxidase (MPO), human neutrophil elastase (HNE), and tissue inhibitor of metalloproteinases (TIMP)-1 in 80 Campylobacter and 25 Salmonella patients as well as in 27 healthy controls. Paired serum samples were available for 73 and 23 patients, respectively. When the initial serum samples were compared to those from controls, both Campylobacter and Salmonella patients showed elevated concentrations of all biomarkers tested (p ≤ 0.037). In the follow-up samples, collected about 25 days afterwards, MMP-8 levels of Campylobacter patients had already turned to normal but all the other biomarkers still showed elevated, although from the initial levels significantly dropped, levels. For the follow-up samples of Salmonella patients, only MMP-9 and MPO levels were at a significantly higher level than in controls. It remains to be studied if the systematically enhanced neutrophil-derived proteolytic and oxidative stress, induced by Campylobacter infection as shown here and persisting for several weeks, is important for the development of late sequelae.

  • 42.
    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.

  • 43.
    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.

  • 44.
    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.

  • 45.
    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.

  • 46.
    Nilsson, Kenneth
    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 Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Friberg, M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Rollman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Impact of prolonged storage of clinical samples at 4 degrees C on the recovery of dermatophytes by culture or PCR analysis2019In: Journal de Mycologie Médicale, ISSN 1156-5233, E-ISSN 1773-0449, Vol. 29, no 1, p. 1-6Article in journal (Refereed)
    Abstract [en]

    Dermatophytes are common pathogens in superficial mycoses that are routinely identified by culture or PCR analysis of freshly collected skin, nail or hair specimens. Although clinical samples are normally processed without delay, practical or research issues may necessitate sample storage until later analysis. However, the influence of extended sample storage on the ability to recover fungi by culture vs. PCR analysis has not been specifically studied. Here, a total of 172 dermatological samples collected from 2013-2015 were examined before and after refrigerated storage at 4 degrees C for 10.2-32.3 (mean 25.6) months. By culture, 35% of the dermatophyte-containing fresh samples remained positive at reexamination. At species level, only 19% of initially Trichophyton rubrum-positive samples yielded a positive result after refrigeration, whereas few samples containing Trichophyton violaceum, Microsporum canis or Microsporum audouinii remained culture-positive. Using PCR, 76% of dermatophyte DNA-positive fresh samples were still positive at re-analysis. Notably, 92% of the samples targeted by the T. rubrum DNA primer remained positive after storage. Hence, PCR analysis is more favourable than cultivation with regard to the detectability of dermatophytes in long-term refrigerated clinical samples.

  • 47.
    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.

  • 48.
    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.

  • 49.
    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.

  • 50.
    Palanisamy, Navaneethan
    et al.
    Heidelberg Univ, HBIGS, Heidelberg, Germany;Heidelberg Univ, BioQuant, Mol & Cellular Engn Grp, Heidelberg, Germany.
    Kalaghatgi, Prabhav
    Max Planck Inst Informat, Computat Biol & Appl Algorithm, Saarbrucken, 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.
    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.
    Chen, Zhi-wei
    Chongqing Med Univ, Affiliated Hosp 2, Key Lab Mol Biol Infect Dis, Dept Infect Dis,Inst Viral Hepatitis,Chinese Mini, Chongqing, Peoples R China.
    Hu, Peng
    Chongqing Med Univ, Affiliated Hosp 2, Key Lab Mol Biol Infect Dis, Dept Infect Dis,Inst Viral Hepatitis,Chinese Mini, Chongqing, Peoples R China.
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Worldwide prevalence of baseline resistance-associated polymorphisms and resistance mutations in HCV against current direct-acting antivirals2018In: Antiviral Therapy, ISSN 1359-6535, E-ISSN 2040-2058, Vol. 23, no 6, p. 485-493Article in journal (Refereed)
    Abstract [en]

    Background: HCV infections can now be completely cured, thanks to the currently marketed direct-acting antivirals (DAAs). It is known that HCV patients carry viral populations with baseline polymorphisms and/or mutations that make them resistant against some of these DAAs, which can negatively impact the patient's treatment outcome. Using complete HCV coding sequences isolated from 1,306 treatment-naive patients of genotypes (GTs) 1, 2, 3, 4 and 6 from around the globe, we studied the prevalence of baseline resistance-associated polymorphisms (RAPs) and resistance mutations (RMs) against DAAs that are currently on the market or in clinical trials.

    Methods: The HCV genome sequences used in this study were retrieved from the NCBI database. RAPs and RMs, with reference to HCV GT1a, were identified using the HCV Geno2pheno web server.

    Results: Nearly 50% of the total amino acid positions (including NS3 protease, NS5A and NS5B) studied are baseline polymorphisms that differentiated one GT from the rest. A proportion of these baseline polymorphisms and baseline non-polymorphic RMs could confer a significant increase in resistance against DAAs.

    Conclusions: In this study, we show the presence and prevalence of RAPs and RMs in DAA treatment-naive patients against currently used DAAs or DAAs in clinical trials. Our study suggests that RAPs and RMs profiling of HCV patients should be performed before the start of the therapy. Our results should be relevant especially in low- and middle-income countries, where the patients have a large variation of GTs and subtypes, and where the generic HCV treatment is now increasingly available.

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