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  • 1.
    Albinsson, Bo
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Laboratory of Clinical Microbiology, Uppsala University Hospital, Uppsala.
    Vene, Sirkka
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. The Public Health Agency of Sweden, Solna.
    Rombo, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Department of Infectious diseases, Eskilstuna.
    Blomberg, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Lundkvist, Åke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Rönnberg, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Laboratory of Clinical Microbiology, Uppsala University Hospital .
    Distinction between serological responses following tick-borne encephalitis virus (TBEV) infection vs vaccination, Sweden 20172018Ingår i: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 23, nr 3, s. 2-7, artikel-id 17-00838Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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 resistance2017Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 66, nr 1, s. S323-S323Artikel i tidskrift (Övrigt vetenskapligt)
  • 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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 Review2017Ingår i: HEPATOLOGY COMMUNICATIONS, ISSN 2471-254X, Vol. 1, nr 5, s. 379-390Artikel, forskningsöversikt (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi. Department of Microbiology, Uppsala University Hospital, Uppsala, Sweden.
    Gustafsson, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnneurologi/Barnonkologi.
    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 Cystitis2017Ingår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, artikel-id 795Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Bondeson, Kåre
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Loss of DNA-binding and new transcriptional trans-activation function in polyomavirus large T-antigen with mutation of zinc finger motif.1990Ingår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962Artikel i tidskrift (Refereegranskat)
  • 6.
    Blomberg, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Rosén, Anders
    Linkoping Univ, Div Cell Biol, Dept Clin & Expt Med, Linkoping, Sweden..
    Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model2018Ingår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, artikel-id 229Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Rizwan, Muhammad
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Böhlin-Wiener, Agnes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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 Patients2019Ingår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, artikel-id 1946Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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 cancer2019Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 4, artikel-id e0213770Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Hadad, Ronza
    Elfving, Karin
    Larsson, Inger
    Isaksson, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Magnuson, Anders
    Fredlund, Hans
    Unemo, Magnus
    Herrmann, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Ten years transmission of the new variant of Chlamydia trachomatis in Sweden: prevalence of infections and associated complications.2018Ingår i: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 94, nr 2, s. 100-104Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Landtblom: Neurologi.
    Nilsson, Kenneth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Press, Rayomand
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden..
    Kmezic, Ivan
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden..
    Nygren, Ingela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Svenningsson, Anders
    Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden..
    Niemelä, Valter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Cunningham, Janet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Measurement of sCD27 in the cerebrospinal fluid identifies patients with neuroinflammatory disease2019Ingår i: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 332, s. 31-36Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi. 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 County2019Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, nr 4, s. 181-186Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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) loci2018Ingår i: Retrovirology, ISSN 1742-4690, E-ISSN 1742-4690, Vol. 15, artikel-id 59Artikel, forskningsöversikt (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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 DNA2019Ingår i: Research in Microbiology, ISSN 0923-2508, E-ISSN 1769-7123, Vol. 170, nr 6-7, s. 256-262Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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 Platyrrhini2018Ingår i: BMC Evolutionary Biology, ISSN 1471-2148, E-ISSN 1471-2148, Vol. 18, artikel-id 6Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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 diffusion2017Ingår i: Mobile DNA, ISSN 1759-8753, E-ISSN 1759-8753, Vol. 8, artikel-id 15Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Molecular detection and epidemiological studies of atypical bacteria causing respiratory tract infections2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    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.

    Delarbeten
    1. Performance of Bordetella pertussis IS481 real-time PCR in a vaccine trial setting
    Öppna denna publikation i ny flik eller fönster >>Performance of Bordetella pertussis IS481 real-time PCR in a vaccine trial setting
    2007 (Engelska)Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 115, nr 12, s. 1370-1375Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    A real-time PCR method targeting the Bordetella pertussis IS481 gene fragment was evaluated in a vaccine trial setting in which real-time PCR results could be validated against culture and serology results. Two commonly used DNA extraction methods, Amplicor((R)) Respiratory Preparation kit and the QIAamp((R)) DNA Mini Kit, were compared. An approximately 50-fold higher sensitivity was achieved using the Amplicor kit. 89 of 276 aspirates analysed with the IS481 real-time PCR were positive. Interestingly, six of these were culture negative and came from serology-negative patients. Defining true positive cases either as culture-positive or as PCR-positive cases that had been confirmed with a serology-positive result or verified with a newly constructed recA PCR, the sensitivity and specificity of the IS481 real-time PCR were 89% and 98%, respectively. This study confirms the specificity and high diagnostic sensitivity of IS481-based PCR methods for diagnosis of B. pertussis.

    Nyckelord
    Bordetella pertussis, IS481, real-time PCR
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-113051 (URN)10.1111/j.1600-0463.2007.00774.x (DOI)000251859600007 ()18184407 (PubMedID)
    Tillgänglig från: 2010-01-25 Skapad: 2010-01-25 Senast uppdaterad: 2019-04-06Bibliografiskt granskad
    2. Simultaneous detection of Chlamydophila pneumoniae and Mycoplasma pneumoniae by use of molecular beacons in a duplex real-time PCR
    Öppna denna publikation i ny flik eller fönster >>Simultaneous detection of Chlamydophila pneumoniae and Mycoplasma pneumoniae by use of molecular beacons in a duplex real-time PCR
    2008 (Engelska)Ingår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 46, nr 2, s. 727-31Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    A real-time PCR was designed for detection of Chlamydophila pneumoniae and Mycoplasma pneumoniae such that each pathogen could be detected in a single tube and differentiated using molecular beacons marked with different fluorochromes. This duplex PCR, targeting the P1 adhesion gene for M. pneumoniae and the ompA gene for C. pneumoniae, was compared with two conventional PCR assays targeting the 16S rRNA gene and the ompA gene. A total of 120 clinical throat and nasopharyngeal swab samples were tested. DNA extraction was performed using an alkali denaturation/neutralization method, and real-time amplification, detection, and data analysis were performed using a Rotor-Gene 2000 real-time rotary analyzer (Corbett Life Science, Sydney, Australia). Using conventional PCR as a reference in an analysis of 120 samples, 13 of 14 samples positive for C. pneumoniae were detected by the novel real-time PCR. In an analysis of M. pneumoniae, 22 samples were positive in the conventional PCR and the novel assay detected 24 positive samples. When using the conventional PCR as a reference, sensitivity and specificity were 93% and 100%, respectively, for C. pneumoniae and 100% and 98%, respectively, for M. pneumoniae. With an overall agreement of 98.8%, this suggests that performance of the new duplex real-time PCR is comparable to that of conventional PCR.

    Nyckelord
    Chlamydophila pneumoniae
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-103950 (URN)10.1128/JCM.01540-07 (DOI)000253100300047 ()18094125 (PubMedID)
    Tillgänglig från: 2009-05-26 Skapad: 2009-05-26 Senast uppdaterad: 2019-04-06
    3. No detection of macrolide-resistant Mycoplasma pneumoniae from Swedish patients, 1996-2013.
    Öppna denna publikation i ny flik eller fönster >>No detection of macrolide-resistant Mycoplasma pneumoniae from Swedish patients, 1996-2013.
    2016 (Engelska)Ingår i: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Infection ecology & epidemiology, Vol. 6, nr 1, artikel-id 31374Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: Mycoplasma pneumoniae is a common cause of respiratory infections which can cause life-threatening pneumonia and serious extrapulmonary manifestations. Since the year 2000, the emergence of macrolide-resistant M. pneumoniae strains has increased with varying incidences across countries. In China more than 90% of the strains are resistant. M. pneumoniae diagnostics is mostly done with molecular methods, and in Sweden antibiotic resistance surveillance is not routinely performed. The prevalence of macrolide-resistant M. pneumoniae has not previously been studied in Sweden.

    MATERIAL AND METHODS: A total of 563 M. pneumoniae-positive respiratory samples, collected from four counties in Sweden between 1996 and 2013, were screened for mutations associated with macrolide resistance using a duplex FRET real-time PCR method. The real-time PCR targets the 23S rRNA gene, and differentiation between wild-type and resistant strains was achieved with a melting curve analysis.

    RESULTS: Of the 563 samples included, 548 were analyzed for mutations associated with macrolide resistance. No mutations were found. The detection rate of macrolide-resistant M. pneumoniae in this study was 0% [0.00-0.84%].

    CONCLUSION: No macrolide-resistant M. pneumoniae has been detected in Sweden. However, the emergence and spread of macrolide-resistant M. pneumoniae strains in many countries commands continuous epidemiological surveillance.

    Nyckelord
    Mycoplasma pneumoniae, antibiotic resistance, diagnostics, macrolide, treatment
    Nationell ämneskategori
    Infektionsmedicin
    Identifikatorer
    urn:nbn:se:uu:diva-319205 (URN)10.3402/iee.v6.31374 (DOI)27258207 (PubMedID)
    Tillgänglig från: 2017-03-31 Skapad: 2017-03-31 Senast uppdaterad: 2019-04-06Bibliografiskt granskad
    4. Molecular typing of Mycoplasma pneumoniae strains in Sweden, 1996–2017, and the emergence of a new P1 cytadhesin gene, Variant 2e
    Öppna denna publikation i ny flik eller fönster >>Molecular typing of Mycoplasma pneumoniae strains in Sweden, 1996–2017, and the emergence of a new P1 cytadhesin gene, Variant 2e
    2019 (Engelska)Ingår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 57, nr 6, artikel-id e00049-19Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Mycoplasma pneumoniae causes respiratory infections, such as community-acquired pneumonia (CAP), with epidemics recurring every 3 to 7 years. In 2010 and 2011, many countries experienced an extraordinary epidemic peak. The cause of these recurring epidemics is not understood, but decreasing herd immunity and shifts in the strains' antigenic properties have been suggested as contributing factors. M. pneumoniae PCR-positive samples were collected between 1996 and 2017 from four neighboring counties inhabited by 12% of Sweden's population. A total of 578 isolates were characterized directly from 624 clinical samples using P1 typing by sequencing and multilocus variable number tandem repeat analysis (MLVA). A fluorescence resonance energy transfer (FRET)-PCR approach was also used to detect mutations associated with macrolide resistance in the 23S rRNA gene. Through P1 typing, the strains were classified into type 1 and type 2, as well as variants 2a, 2b, 2c, and a new variant found in nine of the strains, denoted variant 2e. Twelve MLVA types were distinguished, and 3-5-6-2 (42.4%), 4-5-7-2 (37.4%), and 3-6-6-2 (14.9%) predominated. Several P1 and MLVA types cocirculated each year, but type 2/variant 2 strains and MLVA types 3-5-6-2 and 4-5-7-2 predominated during the epidemic period comprising the peak of 2010 and 2011. In 2016 and 2017, type 1 became more common, and MLVA type 4-5-7-2 predominated. We also found that 0.2% (1/578) of the strains carried a macrolide resistance-associated mutation, indicating a very low prevalence of macrolide resistance in this region of Sweden.

    Ort, förlag, år, upplaga, sidor
    American Society for Microbiology, 2019
    Nyckelord
    MLVA, Mycoplasma pneumoniae, P1 typing, molecular typing
    Nationell ämneskategori
    Infektionsmedicin
    Identifikatorer
    urn:nbn:se:uu:diva-381150 (URN)10.1128/JCM.00049-19 (DOI)000469251500002 ()30918047 (PubMedID)
    Tillgänglig från: 2019-04-04 Skapad: 2019-04-04 Senast uppdaterad: 2019-06-24Bibliografiskt granskad
    5. Epidemiologic characterisation with whole-genome sequencing of Bordetella pertussis isolates during an endemic in three counties in Sweden, 2014-2016
    Öppna denna publikation i ny flik eller fönster >>Epidemiologic characterisation with whole-genome sequencing of Bordetella pertussis isolates during an endemic in three counties in Sweden, 2014-2016
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Infektionsmedicin
    Identifikatorer
    urn:nbn:se:uu:diva-381151 (URN)
    Tillgänglig från: 2019-04-04 Skapad: 2019-04-04 Senast uppdaterad: 2019-04-15
  • 17.
    Hambraeus, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Lytsy, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Infection Control and What to Wear in the Operating Room2018Ingår i: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 67, nr 1, s. 159-159Artikel i tidskrift (Övrigt vetenskapligt)
  • 18.
    Hanslin, Katja
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Skorup, Paul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Wilske, Frida
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin. Perioperative Medicine and Intensive Care, Karolinska University Hospital and CLINTEC, Karolinska Institute, Stockholm, Sweden.
    Tano, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    The impact of the systemic inflammatory response on hepatic bacterial elimination in experimental abdominal sepsis2019Ingår i: Intensive Care Medicine Experimental, ISSN 2197-425X, Vol. 7, nr 1, artikel-id 52Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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 Senegal2019Ingår i: Parasites & Vectors, ISSN 1756-3305, E-ISSN 1756-3305, Vol. 12, artikel-id 497Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Isaksson, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Carlsson, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Airell, Åsa
    Karolinska Univ Hosp, Stockholm, Sweden.
    Strömdahl, Susanne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    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 GENOTYPES2017Ingår i: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 93, nr Suppl. 2, s. A103-A103, artikel-id P3.27Artikel i tidskrift (Övrigt vetenskapligt)
  • 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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)2018Ingår i: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 68, s. 128A-128AArtikel i tidskrift (Övrigt vetenskapligt)
  • 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Bondeson, Kåre
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Bergqvist, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    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 agents2018Ingår i: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, Vol. 154, s. 174-182Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Bondeson, Kåre
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Bergqvist, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    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 2010-20182019Ingår i: Viruses, ISSN 1999-4915, E-ISSN 1999-4915, Vol. 11, nr 3, artikel-id 207Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Carlsson, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Airell, Asa
    Karolinska Univ Hosp Huddinge, Dept Clin Bacteriol, Stockholm, Sweden..
    Strömdahl, Susanne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Bratt, Goran
    South Gen Hosp, Dept Infect Dis, Venhalsan, Stockholm, Sweden..
    Herrmann, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Lymphogranuloma venereum rates increased and Chlamydia trachomatis genotypes changed among men who have sex with men in Sweden 2004-20162017Ingår i: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 66, nr 11, s. 1684-1687Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Nilsson, Anna J. E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Kaden, Rene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Rautelin, Hilpi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Campylobacter coli clade 3 isolates induce rapid cell death in vitro2019Ingår i: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 85, nr 5, artikel-id UNSP e02993-18Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Nilsson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi. Swedish Univ Agr Sci, Dept Ecol, Uppsala, Sweden.
    Kaden, Rene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Rautelin, Hilpi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Differences in virulence gene expression between human blood and stool Campylobacter coli clade 1 ST828CC isolates2019Ingår i: Gut Pathogens, ISSN 1757-4749, Vol. 11, nr 1, artikel-id 42Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Nilsson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Rautelin, Hilpi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Campylobacter coli clade 3 isolates induce rapid cell death in vitroIngår i: Artikel i tidskrift (Övrigt vetenskapligt)
  • 28.
    Johansson, Cecilia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Rautelin, Hilpi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Kaden, Rene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Staphylococcus argenteus and Staphylococcus schweitzeri are cytotoxic to human cells in vitro due to high expression of alpha-hemolysin Hla2019Ingår i: Virulence, ISSN 2150-5594, E-ISSN 2150-5608, Vol. 10, nr 1, s. 502-510Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Engstrand, Lars
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Solna, Sweden.
    Rautelin, Hilpi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Johansson, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Which methods are appropriate for the detection of Staphylococcus argenteus and is it worthwhile to distinguish S. argenteus from S. aureus?2018Ingår i: Infection and Drug Resistance, ISSN 1178-6973, E-ISSN 1178-6973, Vol. 11, s. 2335-2344Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi. 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 matrices2018Ingår i: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 18, artikel-id 259Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Akaberi, Dario
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Bergfors, Assar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Duberg, Ann-Sofi
    Wesslén, Lars
    Danielsson, Astrid
    Gangsøy Kristiansen, Magnhild
    Gutteberg, Tore
    Goll, Rasmus
    Lannergård, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Lennerstrand, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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.2018Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, nr 10-11, s. 1347-1353Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Lennerstrand, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    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 Norway2019Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, nr 8, s. 1042-1050Artikel i tidskrift (Refereegranskat)
    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 trea