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  • 1.
    Aalto, Anne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Sjoewall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Davidsson, Leif
    Linköping University, Department of Medicine and Care, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Smedby, Örjan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis2007In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 48, no 7, p. 755-762Article in journal (Refereed)
    Abstract [en]

    Background: Borrelia infections, especially chronic neuroborreliosis ( NB), may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive. Purpose: To evaluate brain magnetic resonance imaging ( MRI) in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration. Material and Methods: Sixteen well- characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1- ( with and without gadolinium), T2-, and diffusion- weighted imaging plus fluid- attenuated inversion recovery ( FLAIR) imaging were used. Results: White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls ( no significant difference). Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients ( rho=0.83, P < 0.01) and in controls ( rho=0.61, P < 0.05), but not to the duration of disease. Most lesions were detected with FLAIR, but many also with T2- weighted imaging. Conclusion: A number of MRI findings were detected in patients with chronic NB, although the findings were unspecific when compared with matched controls and did not correlate with disease duration. However, subependymal lesions may constitute a potential finding in chronic NB.

  • 2.
    Appelgren, Daniel
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Enocsson, Helena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Skogman, Barbro H
    Center for Clinical Research Dalarna-Uppsala University, Region Dalarna and Faculty of Medicine and Health Sciences, Örebro University.
    Nordberg, Marika
    Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland.
    Perander, Linda
    Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland.
    Nyman, Dag
    Bimelix AB, AX-22 100 Mariehamn, Åland, Finland.
    Nyberg, Clara
    Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland.
    Knopf, Jasmin
    Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), DE-91 054 Erlangen, Germany.
    Muñoz, Luis E
    Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), DE-91 054 Erlangen, Germany.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections.2020In: Cells, E-ISSN 2073-4409, Vol. 9, no 1, article id E43Article in journal (Refereed)
    Abstract [en]

    Neutrophils operate as part of the innate defence in the skin and may eliminate the Borrelia spirochaete via phagocytosis, oxidative bursts, and hydrolytic enzymes. However, their importance in Lyme neuroborreliosis (LNB) is unclear. Neutrophil extracellular trap (NET) formation, which is associated with the production of reactive oxygen species, involves the extrusion of the neutrophil DNA to form traps that incapacitate bacteria and immobilise viruses. Meanwhile, NET formation has recently been studied in pneumococcal meningitis, the role of NETs in other central nervous system (CNS) infections has previously not been studied. Here, cerebrospinal fluid (CSF) samples from clinically well-characterised children (N = 111) and adults (N = 64) with LNB and other CNS infections were analysed for NETs (DNA/myeloperoxidase complexes) and elastase activity. NETs were detected more frequently in the children than the adults (p = 0.01). NET presence was associated with higher CSF levels of CXCL1 (p < 0.001), CXCL6 (p = 0.007), CXCL8 (p = 0.003), CXCL10 (p < 0.001), MMP-9 (p = 0.002), TNF (p = 0.02), IL-6 (p < 0.001), and IL-17A (p = 0.03). NETs were associated with fever (p = 0.002) and correlated with polynuclear pleocytosis (rs = 0.53, p < 0.0001). We show that neutrophil activation and active NET formation occur in the CSF samples of children and adults with CNS infections, mainly caused by Borrelia and neurotropic viruses. The role of NETs in the early phase of viral/bacterial CNS infections warrants further investigation.

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  • 3.
    Berglin, Ewa
    et al.
    Umea Univ, Sweden.
    Mohammad, Aladdin J.
    Lund Univ, Sweden; Univ Cambridge, England.
    Dahlqvist, Johanna
    Uppsala Univ, Sweden.
    Johansson, Linda
    Umea Univ, Sweden.
    Eriksson, Catharina
    Umea Univ, Sweden.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Rantapaa-Dahlqvist, Solbritt
    Umea Univ, Sweden.
    Anti-neutrophil cytoplasmic antibodies predate symptom onset of ANCA-associated vasculitis: A case-control study2021In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 117, article id 102579Article in journal (Refereed)
    Abstract [en]

    Objectives: Anti-neutrophil cytoplasmic autoantibodies [ANCA) are important for diagnosis of ANCA-associated vasculitides (AAV). The timing of antibody development is not well established. To investigate the development of proteinase 3 (PR3)and myeloperoxidase (MPO)-ANCA, blood samples collected before onset of symptoms of AAV were analysed. Methods: To identify AAV patients with blood samples predating symptoms, the National Patient Register and Cause of Death register were scrutinized for ICD codes for AAV and linked to the registers of five biobanks. Diagnoses of AAV and time point for symptom onset were confirmed by reviewing 504 case-record. Eighty-five AAV cases (34 males, 51 females) with samples 1 month &lt; 10 years from AAV symptom onset and two controls matched for sex, age, and sampling time for each case were included. Samples were screened using ELISAs for ANCA and further analysed for PR3-or MPO- specificities. Results: In ANCA-screen 35.7% of the pre-symptomatic cases and 3.5% of controls tested positive (p &lt; 0.01). 26.2% of the cases were PR3-ANCA+ and 10.7% MPO-ANCA+. Median (Q1-Q3) predating time for PR3-ANCA+ was 2.7 (0.3-7.7) years and MPO-ANCA+ 2.0 (0.9-3.5) years. PR3-ANCA was demonstrated in samples up to nine years before symptom onset. At symptom onset predating PR3-ANCA+ cases were younger than PR3-ANCA(P &lt; 0.01), and MPO-ANCA+ were older than MPO-ANCA(p &lt; 0.05). Predating MPO-ANCA+ cases vs. MPO ANCAand vs. PR3-ANCA+ cases had more often at symptoms onset manifestations from lungs, kidneys or peripheral nervous system (p &lt; 0.01 and p &lt; 0.05, respectively). Conclusion: The PR3-and MPO-ANCAs are present years before AAV symptom onset and represent distinct diseases.

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  • 4.
    Carlströmer Berthén, Nellie
    et al.
    Borrelia Research Group of the Aland Islands, The Aland Islands, Finland; Bimelix AB, The Aland Islands, Finland.
    Tompa, Eszter
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Olausson, Susanne
    Borrelia Research Group of the Aland Islands,The Aland Islands, Finland;Bimelix AB, The Aland Islands, Finland.
    Nyberg, Clara
    Borrelia Research Group of the Aland Islands, The Aland Islands, Finland.
    Nyman, Dag
    Borrelia Research Group of the Aland Islands, The Aland Islands, Finland;Bimelix AB, The Aland Islands, Finland.
    Ringbom, Malin
    Borrelia Research Group of the Aland Islands, The Aland Islands, Finland;The Aland Islands Healthcare Services, The Aland Islands, Finland.
    Perander, Linda
    Borrelia Research Group of the Aland Islands, The Aland Islands, Finland;The Aland Islands Healthcare Services, The Aland Islands, Finland.
    Svärd, Joel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Lindgren, Per-Eric
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Clinical Microbiology, Laboratory Medicine, County Hospital Ryhov, Sweden.
    Forsberg, Pia
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection.
    Wilhelmsson, Peter
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Clinical Microbiology, Laboratory Medicine, County Hospital Ryhov, 551 85 Jonkoping, Sweden.
    Sjöwall, Johanna
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Nordberg, Marika
    Borrelia Research Group of the Aland Island, The Aland Islands, Finland;The Aland Islands Healthcare Services, The Aland Islands, Finland.
    The AxBioTick Study: Borrelia Species and Tick-Borne Encephalitis Virus in Ticks, and Clinical Responses in Tick-Bitten Individuals on the Aland Islands, Finland2023In: Microorganisms, E-ISSN 2076-2607, Vol. 11, no 5, article id 1100Article in journal (Refereed)
    Abstract [en]

    The AxBioTick Study: Borrelia Species and Tick-Borne Encephalitis Virus in Ticks, and Clinical Responses in Tick-Bitten Individuals on the Aland Islands, Finlandby  Nellie Carlströmer Berthén 1,2,*,† , Eszter Tompa 3,† , Susanne Olausson 1,2, Clara Nyberg 1, Dag Nyman 1,2, Malin Ringbom 1,4, Linda Perander 1,4, Joel Svärd 3, Per-Eric Lindgren 3,5, Pia Forsberg 3, Peter Wilhelmsson 3,5,‡, Johanna Sjöwall 3,6,‡  and Marika Nordberg 1,4,‡  1Borrelia Research Group of the Aland Islands, 22100 Mariehamn, The Aland Islands, Finland2Bimelix AB, 22100 Mariehamn, The Aland Islands, Finland3Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linkoping University, 581 83 Linkoping, Sweden4The Aland Islands Healthcare Services, 22100 Mariehamn, The Aland Islands, Finland5Clinical Microbiology, Laboratory Medicine, County Hospital Ryhov, 551 85 Jonkoping, Sweden6Department of Infectious Diseases, Vrinnevi Hospital, 603 79 Norrkoping, Sweden*Author to whom correspondence should be addressed.†These authors contributed equally to the study.‡These authors contributed equally to the study.Microorganisms 2023, 11(5), 1100; https://doi.org/10.3390/microorganisms11051100Received: 30 March 2023 / Revised: 17 April 2023 / Accepted: 19 April 2023 / Published: 22 April 2023(This article belongs to the Special Issue Research on Ticks and Tick-Borne Pathogens)

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    AbstractThe AxBioTick study was initiated to investigate the prevalence of ticks and tick-borne pathogens and their impact on antibody and clinical responses in tick-bitten individuals on the Aland Islands. This geographical area is hyperendemic for both Lyme borreliosis (LB) and Tick-borne encephalitis (TBE). Blood samples and ticks were collected from 100 tick-bitten volunteers. A total of 425 ticks was collected, all determined to Ixodes ricinus using molecular tools. Of them 20% contained Borrelia species, of which B. garinii and B. afzelii were most common. None contained the TBE virus (TBEV). Blood samples were drawn in conjunction with the tick bite, and eight weeks later. Sera were analyzed for Borrelia- and TBEV-specific antibodies using an ELISA and a semiquantitative antibody assay. In total 14% seroconverted in Borrelia C6IgG1, 3% in TBEV IgG, and 2% in TBEV IgM. Five participants developed clinical manifestations of LB. The high seroprevalence of both Borrelia (57%) and TBEV (52%) antibodies are likely attributed to the endemic status of the corresponding infections as well as the TBE vaccination program. Despite the similar prevalence of Borrelia spp. detected in ticks in other parts of Europe, the infection rate in this population is high. The AxBioTick study is continuing to investigate more participants and ticks for co-infections, and to characterize the dermal immune response following a tick bite.

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  • 5.
    Eimer, Johannes
    et al.
    Visby County Hospital, Visby, Sweden.
    Fernström, Louise
    Linköping University. Kalmar County Hospital, Kalmar, Sweden.
    Rohlén, Louise
    Linköping University. Kalmar County Hospital, Kalmar, Sweden.
    Grankvist, Anna
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Loo, Kristoffer
    Kalmar County Hospital, Kalmar, Sweden.
    Nyman, Erik
    Visby County Hospital, Visby, Sweden.
    Henningsson, Anna J.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology. Jönköping County Hospital, Jönköping, Sweden.
    Haglund, Mats
    Kalmar County Hospital, Kalmar, Sweden .
    Hultqvist, Viktor
    Linköping University. Kalmar County Hospital, Kalmar, Sweden.
    Sjöwall, Johanna
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Wennerås, Christine
    Sahlgrenska University Hospital, Gothenburg, Sweden; University of Gothenburg.
    Schön, Thomas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases. Kalmar County Hospital, Kalmar, Sweden.
    Spiroplasma ixodetis Infections in Immunocompetent and Immunosuppressed Patients after Tick Exposure, Sweden2022In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 28, no 8, p. 1681-1685Article in journal (Refereed)
    Abstract [en]

    We report 2 cases of Spiroplasma ixodetis infection in an immunocompetent patient and an immunocompromised patient who had frequent tick exposure. Fever, thrombocytopenia, and increased liver aminotransferase levels raised the suspicion of anaplasmosis, but 16S rRNA PCR and Sanger sequencing yielded a diagnosis of spiroplasmosis. Both patients recovered after doxycycline treatment.

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  • 6.
    Enocsson, Helena
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Idoff, Cornelia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Annette
    Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Govender, Melissa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Hopkins, Francis
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Larsson, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Soluble Urokinase Plasminogen Activator Receptor (suPAR) Independently Predicts Severity and Length of Hospitalisation in Patients With COVID-192021In: Frontiers in Medicine, E-ISSN 2296-858X, Vol. 8, article id 791716Article in journal (Refereed)
    Abstract [en]

    Background: Efficient healthcare based on prognostic variables in hospitalised patients with COVID-19 could reduce the risk of complications and death. Recently, soluble urokinase Plasminogen Activator Receptor (suPAR) was shown to predict respiratory failure, kidney injury, and clinical outcome in patients with SARS-CoV-2 infection. The aim of this study was to investigate the value of suPAR as a prognostic tool, in comparison with other variables, regarding disease severity and length of hospital stay in patients with COVID-19.Patients and Methods: Individuals hospitalised with COVID-19 (40 males, 20 females; median age 57.5 years) with a median symptom duration of 10 days and matched, healthy controls (n = 30) were included. Admission levels of suPAR were measured in serum by enzyme-linked immunosorbent assay. Blood cell counts, C-reactive protein (CRP) levels, lactate dehydrogenase (LDH), plasma creatinine and estimated glomerular filtration rates were analysed and oxygen demand, level of care and length of hospitalisation recorded.Results: Patients had significantly higher suPAR levels compared to controls (P &lt; 0.001). Levels were higher in severely/critically (median 6.6 ng/mL) compared with moderately ill patients (median 5.0 ng/mL; P = 0.002). In addition, suPAR levels correlated with length of hospitalisation (rho = 0.35; P = 0.006). Besides suPAR, LDH, CRP, neutrophil count, neutrophil-to-monocyte and neutrophil-to-lymphocyte ratio, body mass index and chronic renal failure were discriminators of COVID-19 severity and/or predictors of length of hospitalisation.Conclusion: Admission levels of suPAR were higher in patients who developed severe/critical COVID-19 and associated with length of hospital stay. In addition, we showed that suPAR functioned as an independent predictor of COVID-19 disease severity.

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  • 7.
    Govender, Melissa
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Hopkins, Francis
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Göransson, Robin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Svanberg, Cecilia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Shankar, Esaki M.
    Cent Univ Tamil Nadu, India.
    Hjorth, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Nyström, Sofia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Larsson, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    T cell perturbations persist for at least 6 months following hospitalization for COVID-192022In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 13, article id 931039Article in journal (Refereed)
    Abstract [en]

    COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8(+) TEMRA and exhausted CD57(+) CD8(+) T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T cell activation were upregulated at inclusion, and in the case of CD69(+) CD4(+) T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.

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  • 8.
    Gyllemark, Paula
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Forsberg, Pia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Jonsson Henningsson, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology. Reg Jonkoping Cty, Sweden.
    Intrathecal Th17-driven inflammation is associated with prolonged post-treatment convalescence for patients with Lyme neuroborreliosis2023In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1Article in journal (Refereed)
    Abstract [en]

    Lyme neuroborreliosis (LNB) is associated with increased levels of pro-inflammatory cytokines and chemokines in the cerebrospinal fluid (CSF). Residual symptoms after antibiotic treatment can have deleterious effects on patients and knowledge regarding the pathogenesis linked to prolonged recovery is lacking. In this prospective follow-up study, we investigated the B cell-associated and T helper (Th) cell-associated immune responses in well-characterized patients with LNB and controls. The aims were to assess the kinetics of selected cytokines and chemokines involved in the inflammatory response and to identify potential prognostic markers. We investigated 13 patients with LNB according to a standardized clinical protocol before antibiotic treatment and after 1, 6 and 12 months of follow-up. CSF and blood samples were obtained at baseline and after 1 month. As controls, we used CSF samples from 37 patients who received spinal anesthesia during orthopedic surgery. The CSF samples were analyzed for CXCL10 (Th1-related), CCL22 (Th2-related) and IL-17A, CXCL1 and CCL20 (Th17-related), as well as for the B cell-related cytokines of a proliferation-inducing ligand (APRIL), B cell-activating factor (BAFF) and CXCL13. The CSF levels of all the cytokines and chemokines, with the exception of APRIL, were significantly higher at baseline in patients with LNB compared with controls. All the cytokines and chemokines, except for IL-17A were significantly reduced at 1-month follow-up. Patients with quick recovery (&lt; 1 month, n = 3) had significantly lower levels of CCL20 at baseline and lower levels of IL-17A at 1-month follow-up. Patients with time of recovery &gt; 6 months (n = 7) had significantly higher levels of IL-17A at the one-month follow-up. No other cytokines or chemokines were associated with prolonged recovery. Dominating residual symptoms were fatigue, myalgia, radiculitis and/or arthralgia. In this prospective follow-up study of patients with LNB, we found significantly lower levels of CCL20 in those who recovered rapidly, and increased levels of IL-17A in patients with delayed recovery post-treatment. Our findings indicate persistent Th17-driven inflammation in the CSF, possibly contributing to a longer convalescence, and suggest IL-17A and CCL20 as potential biomarker candidates for patients with LNB.

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  • 9.
    Gyllemark, Paula
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Dept Infect Dis, Sweden.
    Wilhelmsson, Peter
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Dept Clin Microbiol, Sweden.
    Elm, Camilla
    Dept Clin Microbiol, Sweden.
    Hoornstra, Dieuwertje
    Univ Med Ctr Locat AMC, Netherlands.
    Hovius, Joppe W.
    Univ Med Ctr Locat AMC, Netherlands; European Soc Clin Microbiol & Infect Dis, Switzerland.
    Johansson, Marcus
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Dept Clin Microbiol, Jönköping,Sweden.
    Tjernberg, Ivar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Dept Clin Chem & Transfus Med, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Dept Clin Microbiol, Sweden; European Soc Clin Microbiol & Infect Dis, Switzerland.
    Jonsson Henningsson, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology. Dept Clin Microbiol, Sweden; European Soc Clin Microbiol & Infect Dis, Switzerland.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Are other tick-borne infections overlooked in patients investigated for Lyme neuroborreliosis?: A large retrospective study from South-eastern Sweden2021In: Ticks and Tick-borne Diseases, ISSN 1877-959X, E-ISSN 1877-9603, Vol. 12, no 5, article id 101759Article in journal (Refereed)
    Abstract [en]

    In Europe, the hard tick Ixodes ricinus is considered the most important vector of human zoonotic diseases. Human pathogenic agents spread by I. ricinus in Sweden include Borrelia burgdorferi sensu lato (s.l.), Anaplasma phagocytophilum, Rickettsia helvetica, the recently described Neoehrlichia mikurensis, Borrelia miyamotoi, tick-borne encephalitis virus (TBEV), and Babesia spp. (Babesia microti, Babesia venatorum and Babesia divergens). Since these pathogens share the same vector, co-infections with more than one tick-borne pathogen may occur and thus complicate the diagnosis and clinical management of the patient due to possibly altered symptomatology. Borrelia burgdorferi s.l., TBEV and B. miyamotoi are well-known to cause infections of the central nervous system (CNS), whereas the abilities of other tick-borne pathogens to invade the CNS are largely unknown. The aim of this study was to investigate the presence and clinical impact of tick-borne pathogens other than B. burgdorferi s.l. in the cerebrospinal fluid (CSF) and serum samples of patients who were under investigation for Lyme neuroborreliosis (LNB) in a tick-endemic region of South-eastern Sweden. CSF and serum samples from 600 patients, recruited from the Regions of center dot Ostergo center dot tland County, Jo center dot nko center dot ping County and Kalmar County in South-eastern Sweden and investigated for LNB during the period of 2009-2013, were retrospectively collected for analysis. The samples were analysed by real-time PCR for the presence of nucleic acid from B. burgdorferi s.l., B. miyamotoi, A. phagocytophilum, Rickettsia spp., N. mikurensis, TBEV and Babesia spp. Serological analyses were conducted in CSF and serum samples for all patients regarding B. burgdorferi s.l., and for the patients with CSF mononuclear pleocytosis, analyses of antibodies to B. miyamotoi, A. phagocytophilum, spotted fever group (SFG) rickettsiae, TBEV and B. microti in serum were performed. The medical charts of all the patients with CSF mononuclear pleocytosis and patients with positive PCR findings were reviewed. Of the 600 patients, 55 (9%) presented with CSF mononuclear pleocytosis, 13 (2%) of whom had Borrelia-specific antibodies in the CSF. One patient was PCRpositive for N. mikurensis, and another one was PCR-positive for Borrelia spp. in serum. No pathogens were detected by PCR in the CSF samples. Four patients had serum antibodies to B. miyamotoi, four patients to A. phagocytophilum, five patients to SFG rickettsiae, and six patients to TBEV. One patient, with antibodies to SFG

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  • 10.
    Hagbom, Marie
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Carmona Vicente, Noelia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Sharma, Sumit
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Olsson, Henrik
    Noviral Sweden AB, Sweden.
    Jämtberg, Mikael
    Noviral Sweden AB, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Nordgren, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Evaluation of SARS-CoV-2 rapid antigen diagnostic tests for saliva samples2022In: Heliyon, E-ISSN 2405-8440, Vol. 8, no 2, article id e08998Article in journal (Refereed)
    Abstract [en]

    Using saliva samples would facilitate sample collection, diagnostic feasibility, and mass screening of SARS-CoV-2. We tested two rapid antigen (RAD) immunochromatographic tests designed for detection of SARS-CoV-2 in saliva: Rapid Response (TM) COVID-19 Antigen Rapid Test Cassette for oral fluids and DIAGNOS (TM) COVID-19 Antigen Saliva Test. Evaluation of detection limit was performed with purified SARS-CoV-2 nucleocapsid protein and live SARSCoV-2 virus. Sensitivity and specificity were further evaluated with reverse transcription quantitative PCR (RTqPCR) positive and negative saliva samples from hospitalized individuals with COVID-19 (n = 39) and healthcare workers (n = 20). DIAGNOS showed higher sensitivity than Rapid Response for both nucleocapsid protein and live virus. The limit of detection of the saliva test from DIAGNOS was further comparable with the Abbott Panbio (TM) COVID-19 Ag Rapid Test designed for nasopharyngeal samples. DIAGNOS and Rapid Response detected nine (50.0%) and seven (38.9%), respectively, of the 18 RT-qPCR positive saliva samples. All RT-qPCR negative saliva (n = 41) were negative with both tests. Only one of the RT-qPCR positive saliva samples contained infectious virus as determined by cell culture and was also positive using the saliva RADs. The results show that the DIAGNOS may be an important and easy-to-use saliva RAD complement to detect SARS-CoV-2 positive individuals, but validation with a larger sample set is warranted.

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  • 11.
    Hamid, Salik
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Gadré, Ashok
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping. Linköping University, Faculty of Medicine and Health Sciences.
    Fornander, Liselott
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Muhrbeck, Måns
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Clostridium septicum myonecrosis following gardening: A case report2023In: International Journal of Surgery Case Reports, E-ISSN 2210-2612, Vol. 105, article id 108000Article in journal (Refereed)
    Abstract [en]

    Introduction and importance

    Clostridial myonecrosis (CM), or gas gangrene, is a rare necrotizing muscle infection caused most often by Clostridium perfringens or C. septicum. Inoculation can occur either traumatically or spontaneously. CM has a high mortality rate if not treated promptly.

    Case presentation

    A 64-year-old male presented to the emergency department (ED) with sudden onset left flank pain and fever. Repeated CT scans demonstrated progressive edema around the left iliopsoas muscle with gas formation and bleeding. The patient received intravenous fluids, meropenem, and clindamycin. Emergency laparotomy was performed on suspicion of necrotizing fasciitis and revealed a necrotic left iliopsoas muscle which was partially excised. Blood cultures were positive at 12 h with growth of C. septicum. Prolonged stay in the intensive care unit, and six additional surgical interventions to the abdomen, left thigh, and flank were needed. The patient was discharged after four months to a nursing home.

    Clinical discussion

    C. septicum CM more often occurs spontaneously and is associated with colorectal malignancy. However, for our patient, CT colonography and proctoscopy did not reveal any pathology. Therefore, we believe the CM resulted from an injury the patient sustained while working in his backyard, either a cut from barbed wire on his arm or from soil contaminating his psoriatic lesions. Successful outcomes for patients with CM require a high index of suspicion, timely treatment with antibiotics, and repeated surgical debridements.

    Conclusion

    This case report describes the presentation and management of a presumably injury-related CM caused by C. septicum.

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  • 12.
    Hopkins, Francis
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Nordgren, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Fernandez-Botran, Rafael
    Univ Louisville, KY USA.
    Enocsson, Helena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Govender, Melissa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Svanberg, Cecilia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Svensson, Lennart
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Hagbom, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Nyström, Sofia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Larsson, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Pentameric C-reactive protein is a better prognostic biomarker and remains elevated for longer than monomeric CRP in hospitalized patients with COVID-192023In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 14, article id 1259005Article in journal (Refereed)
    Abstract [en]

    The differing roles of the pentameric (p) and monomeric (m) C-reactive protein (CRP) isoforms in viral diseases are not fully understood, which was apparent during the COVID-19 pandemic regarding the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Herein, we investigated the predictive value of the pCRP and mCRP isoforms for COVID-19 severity in hospitalized patients and evaluated how the levels of the protein isoforms changed over time during and after acute illness. This study utilized samples from a well-characterized cohort of Swedish patients with SARS-CoV-2 infection, the majority of whom had known risk factors for severe COVID-19 and required hospitalization. The levels of pCRP were significantly raised in patients with severe COVID-19 and in contrast to mCRP the levels were significantly associated with disease severity. Additionally, the pCRP levels remained elevated for at least six weeks post inclusion, which was longer compared to the two weeks for mCRP. Our data indicates a low level of inflammation lasting for at least six weeks following COVID-19, which might indicate that the disease has an adverse effect on the immune system even after the viral infection is resolved. It is also clear that the current standard method of testing pCRP levels upon hospitalization is a useful marker for predicting disease severity and mCRP testing would not add any clinical relevance for patients with COVID-19.

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  • 13.
    Hopkins, Francis R.
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Govender, Melissa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Svanberg, Cecilia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Nordgren, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Waller, Hjalmar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Region Östergötland, Medicine Center, Department of Infectious Diseases. Linköping University, Faculty of Medicine and Health Sciences.
    Henningsson, Anna J.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Division of Clinical Microbiology, Department of Laboratory Medicine in Jönköping, Ryhov County Hospital, Jönköping.
    Hagbom, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Region Östergötland, Medicine Center, Department of Infectious Diseases. Linköping University, Faculty of Medicine and Health Sciences.
    Nyström, Sofia N.
    Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Larsson, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-192023In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 13, article id 1082912Article in journal (Refereed)
    Abstract [en]

    Introduction: After more than two years the Coronavirus disease-19 (COVID-19) pandemic continues to burden healthcare systems and economies worldwide, and it is evident that the effects on the immune system can persist for months post-infection. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19.

    Methods: Here, we followed a cohort of COVID-19 patients hospitalized during the early waves of the pandemic for 6-7 months. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection.

    Results: We found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. Myeloid derived suppressor cells were also elevated over this period. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in program death ligand 1 (PD-L1) expression but increased CD86 expression across almost all cell types examined. Finally, C-reactive protein (CRP) correlated positively to the levels of intermediate monocytes and negatively to the recovery of DC subsets.

    Conclusion: By exploring the myeloid compartments, we show here that alterations in the immune landscape remain more than 6 months after severe COVID-19, which could be indicative of ongoing healing and/or persistence of viral antigens.

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  • 14.
    Jonsson Henningsson, Anna
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology. Lab Med, Sweden.
    Aase, Audun
    Norwegian Inst Publ Hlth, Norway.
    Bavelaar, Herjan
    Lab Med, Sweden.
    Flottorp, Signe
    Norwegian Inst Publ Hlth, Norway.
    Forsberg, Pia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Kirkehei, Ingvild
    Norwegian Coll Policing, Norway.
    Lövmar, Matilda
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Kenneth
    Uppsala Univ, Sweden.
    Nyman, Dag
    Aland Grp Borrelia Res, Finland.
    Ornstein, Katharina
    Skane Univ Hlth Care, Sweden.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Skogman, Barbro H.
    Dalarna Uppsala Univ, Sweden; Dalarna Uppsala Univ, Sweden; Orebro Univ, Sweden.
    Tjernberg, Ivar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Department of Clinical Chemistry and Transfusion Medicine, Region Kalmar County, Sweden.
    Aaberge, Ingeborg
    Norwegian Inst Publ Hlth, Norway.
    Laboratory Methods for Detection of Infectious Agents and Serological Response in Humans With Tick-Borne Infections: A Systematic Review of Evaluations Based on Clinical Patient Samples2021In: Frontiers In Public Health, ISSN 2296-2565, Vol. 9, article id 580102Article, review/survey (Refereed)
    Abstract [en]

    Background: For the most important and well-known infections spread by Ixodes ticks, Lyme borreliosis (LB) and tick-borne encephalitis (TBE), there are recommendations for diagnosis and management available from several health authorities and professional medical networks. However, other tick-borne microorganisms with potential to cause human disease are less known and clear recommendations on diagnosis and management are scarce. Therefore, we performed a systematic review of published studies and reviews focusing on evaluation of laboratory methods for clinical diagnosis of human tick-borne diseases (TBDs), other than acute LB and TBE. The specific aim was to evaluate the scientific support for laboratory diagnosis of human granulocytic anaplasmosis, rickettsiosis, neoehrlichiosis, babesiosis, hard tick relapsing fever, tularemia and bartonellosis, as well as tick-borne co-infections and persistent LB in spite of recommended standard antibiotic treatment. Methods: We performed a systematic literature search in 11 databases for research published from 2007 through 2017, and categorized potentially relevant references according to the predefined infections and study design. An expert group assessed the relevance and eligibility and reviewed the articles according to the QUADAS (diagnostic studies) or AMSTAR (systematic reviews) protocols, respectively. Clinical evaluations of one or several diagnostic tests and systematic reviews were included. Case reports, non-human studies and articles published in other languages than English were excluded. Results: A total of 48 studies fulfilled the inclusion criteria for evaluation. The majority of these studies were based on small sample sizes. There were no eligible studies for evaluation of tick-borne co-infections or for persistent LB after antibiotic treatment. Conclusions: Our findings highlight the need for larger evaluations of laboratory tests using clinical samples from well-defined cases taken at different time-points during the course of the diseases. Since the diseases occur at a relatively low frequency, single-center cross-sectional studies are practically not feasible, but multi-center case control studies could be a way forward.

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  • 15.
    Knopf, Jasmin
    et al.
    Friedrich Alexander Univ Erlangen Nurnberg FAU, Germany; Univ Klinikum Erlangen, Germany; Friedrich Alexander Univ Erlangen Nurnberg FAU, Germany.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Frodlund, Martina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Hinkula, Jorma
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Herrmann, Martin
    Friedrich Alexander Univ Erlangen Nurnberg FAU, Germany; Univ Klinikum Erlangen, Germany; Friedrich Alexander Univ Erlangen Nurnberg FAU, Germany.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    NET Formation in Systemic Lupus Erythematosus: Changes during the COVID-19 Pandemic2022In: Cells, E-ISSN 2073-4409, Vol. 11, no 17, article id 2619Article in journal (Refereed)
    Abstract [en]

    The severity of the coronavirus disease in 2019 (COVID-19) is strongly linked to a dysregulated immune response. This fuels the fear of severe disease in patients with autoimmune disorders continuously using immunosuppressive/immunomodulating medications. One complication of COVID-19 is thromboembolism caused by intravascular aggregates of neutrophil extracellular traps (NETs) occluding the affected vessels. Like COVID-19, systemic lupus erythematosus (SLE) is characterized by, amongst others, an increased risk of thromboembolism. An imbalance between NET formation and clearance is suggested to play a prominent role in exacerbating autoimmunity and disease severity. Serologic evidence of exposure to SARS-CoV-2 has a minor impact on the SLE course in a Swedish cohort reportedly. Herein, we assessed NET formation in patients from this cohort by neutrophil elastase (NE) activity and the presence of cell-free DNA, MPO-DNA, and NE-DNA complexes and correlated the findings to the clinical parameters. The presence of NE-DNA complexes and NE activity differed significantly in pre-pandemic versus pandemic serum samples. The latter correlated significantly with the hemoglobin concentration, blood cell counts, and complement protein 3 and 4 levels in the pre-pandemic but only with the leukocyte count and neutrophil levels in the pandemic serum samples. Taken together, our data suggest a change, especially in the NE activity independent of exposure to SARS-CoV-2.

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  • 16.
    Lindblom, Anders
    et al.
    Uppsala University, Sweden; Clin Research Centre, Sweden.
    Wallmenius, Katarina
    Uppsala University, Sweden.
    Sjöwall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Nilsson, Kenneth
    Uppsala University, Sweden; Clin Research Centre, Sweden.
    Prevalence of Rickettsia spp. in Ticks and Serological and Clinical Outcomes in Tick-Bitten Individuals in Sweden and on the Aland Island2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 11, article id e0166653Article in journal (Refereed)
    Abstract [en]

    Tick-transmitted diseases are an emerging health problem, and the hard tick Ixodes ricinus is the main vector for Borrelia spp., tick-borne encephalitis virus and most of the spotted fever Rickettsiae in Europe. The aim of the present study was to examine the incidence of rickettsial infection in the southernmost and south central parts of Sweden and the Aland Islands in Finland the risk of infection in humans and its correlation with a bite of a Rickettsia-infected tick, the self-reported symptoms of rickettsial disease, and the prevalence of co-infection between Rickettsia spp. and Borrelia spp. Persons with a recent tick bite were enrolled through public media and asked to answer a questionnaire, provide a blood sample and bring detached ticks at enlistment and at follow-up three months later. Blood samples were previously analysed for Borrelia spp. antibodies and, for this report, analysed for antibodies to Rickettsia spp. by immunofluorescence and in 16 cases also using Western Blot. Ninety-six (44.0%) of the 218 participants were seropositive for IgG antibodies to Rickettsia spp. Forty (18.3%) of the seropositive participants had increased titres at the follow-up, indicating recent/current infection, while four (1.8%) had titres indicating probable recent/current infection (amp;gt;= 1: 256). Of 472 ticks, 39 (8.3%) were Rickettsia sp. positive. Five (31.3%) of 16 participants bitten by a Rickettsia-infected tick seroconverted. Experience of the selfreported symptoms nausea (p = 0.006) and radiating pain (p = 0.041) was more common among those with recent, current or probable infection compared to those who did not seroconvert. Participants who showed seroreactivity or seroconversion to Rickettsia spp. had more symptoms than those who were seronegative. Seven (3.2%) participants showed seroconversion to Borrelia spp., and three (1.4%) of these showed seroconversion to both Rickettsia spp. and Borrelia spp., in accordance with previous studies in Sweden. Symptoms of rickettsial disease were in most of the cases vague and general that were difficult to differentiate from other tick-borne diseases.

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  • 17.
    Lindblom, Pontus
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Wilhelmsson, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Fryland, Linda
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Matussek, Andreas
    County Hospital Ryhov, Jönköping.
    Haglund, Mats
    Kalmar County hospital.
    Sjöwall, Johanna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Vene, Sirkka
    Swedish Institute for Communicable Disease Control, Stockholm.
    Nyman, Dag
    Åland Central Hospital, Åland, Finland.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Determining factors for successful vaccination against tick-borne encephalitis virus in older individuals2014Manuscript (preprint) (Other academic)
    Abstract [en]

    We performed a cross-sectional study including 533 persons (median age 61) from the highly TBE endemic Åland Islands in the archipelago between Sweden and Finland. Blood samples, questionnaires and vaccination records were obtained from all study participants. The aim was to investigate if there was any association between TBEV antibody titer and 14 healthrelated factors: [age, gender, number of vaccine doses (0-5), time since last vaccine dose, previous TBE disease, vaccination against other flaviviruses, ≥2 tick-bites during the previous 3 months, pet-ownership, asthma, smoking, allergy, diabetes, medication, and previous tumor]. Measurement of TBEV IgG antibodies was performed using two commercial ELISA assays (Enzygnost and Immunozym), and a third in-house rapid fluorescent focus inhibition test was used to measure TBEV neutralizing antibodies. The age of the person and the number of vaccine doses were the two most important factors determining successful vaccination. The response to each vaccine dose declined linearly with increased age. A 35 year age difference corresponds to a vaccine dose increment from 3 to 4 to achieve the same response. Participants receiving medication and participants previously vaccinated against other flaviviruses had lower TBEV antibody titers on average, while those with self-reported asthma had higher titers. By comparing the 3 serological assays we show that the Enzygnost and Immunozym assay differ due to choice of cutoffs, but not in overall accuracy.

  • 18.
    Lindblom, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Matussek, Andreas
    County Hospital Ryhov, Sweden .
    Haglund, Mats
    County Hospital Kalmar, Sweden .
    Sjöwall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Vene, Sirkka
    Public Health Agency Sweden, Stockholm.
    Nyman, Dag
    Aland Central Hospital, Finland .
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Factors Determining Immunological Response to Vaccination against Tick-Borne Encephalitis Virus in Older Individuals2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 6, p. e0100860-Article in journal (Refereed)
    Abstract [en]

    We performed a cross-sectional study including 533 individuals (median age 61) from the highly TBE endemic A land Islands in the archipelago between Sweden and Finland. Blood samples, questionnaires and vaccination records were obtained from all study participants. The aim was to investigate if there was any association between TBEV antibody titer and 12 health-related factors. Measurement of TBEV IgG antibodies was performed using two commercial ELISA assays (Enzygnost and Immunozym), and a third in-house rapid fluorescent focus inhibition test was used to measure TBEV neutralizing antibodies. The age of the individual and the number of vaccine doses were the two most important factors determining the immunological response to vaccination. The response to each vaccine dose declined linearly with increased age. A 35 year age difference corresponds to a vaccine dose increment from 3 to 4 to achieve the same immunological response. Participants previously vaccinated against other flaviviruses had lower odds of being seropositive for neutralizing TBEV antibodies on average, while participants with self-reported asthma had higher odds of being seropositive. By comparing the 3 serological assays we show that the Enzygnost and Immunozym assay differ due to choice of cutoffs, but not in overall accuracy.

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  • 19.
    Lindblom, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Sjowall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Haglund, Mats
    Kalmar County hospital.
    Matussek, Andreas
    County Hospital Ryhov, Jönköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vene, Sirkka
    Swedish Institute for Communicable Disease Control, Stockholm.
    Nyman, Dag
    Åland Central Hospital, Åland, Finland.
    Andreassen, Åshild
    Norwegian Institute of Public Health, Olso, Norway.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Tick-borne encephalitis virus in ticks detached from humans and follow-up of serological and clinical response.2014In: Ticks and Tick Borne Diseases, ISSN 1877-959X, Vol. 5, no 1, p. 21-28Article in journal (Refereed)
    Abstract [en]

    The risk of tick-borne encephalitis virus (TBEV) infection after a tick bite remains largely unknown. To address this, we investigated the presence of TBEV in ticks detached from humans in an attempt to relate viral copy number, TBEV subtype, and tick feeding time with the serological and clinical response of the tick-bitten participants. Ticks, blood samples, and questionnaires were collected from tick-bitten humans at 34 primary health care centers in Sweden and in the Aland Islands (Finland). A total of 2167 ticks was received from 1886 persons in 2008-2009. Using a multiplex quantitative real-time PCR, 5 TBEV-infected ticks were found (overall prevalence 0.23%, copy range <4 X 10(2)-7.7 X 10(6) per tick). One unvaccinated person bitten by a tick containing 7.7 x 10(6) TBEV copies experienced symptoms. Another unvaccinated person bitten by a tick containing 1.8 x 10(3) TBEV copies developed neither symptoms nor TBEV antibodies. The remaining 3 persons were protected by vaccination. In contrast, despite lack of TBEV in the detached ticks, 2 persons developed antibodies against TBEV, one of whom reported symptoms. Overall, a low risk of TBEV infection was observed, and too few persons got bitten by TBEV-infected ticks to draw certain conclusions regarding the clinical outcome in relation to the duration of the blood meal and virus copy number. However, this study indicates that an antibody response may develop without clinical symptoms, that a bite by an infected tick not always leads to an antibody response or clinical symptoms, and a possible correlation between virus load and tick feeding time. (C) 2013 Elsevier GmbH. All rights reserved.

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  • 20.
    Ocias, Lukas Frans
    et al.
    Statens Serum Inst, Denmark; Rigshosp, Denmark.
    Wilhelmsson, Peter
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, Sweden.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Henningsson, Anna J.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology. Division of Clinical Microbiology, Laboratory Medicine, Jönköping Region Jönköping County, Sweden.
    Nordberg, Marika
    Aland Cent Hosp, Finland.
    Jorgensen, Charlotte Svaerke
    Statens Serum Inst, Denmark.
    Krogfelt, Karen Angeliki
    Statens Serum Inst, Denmark; Roskilde Univ, Denmark.
    Forsberg, Pia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, Sweden.
    Emerging tick-borne pathogens in the Nordic countries: A clinical and laboratory follow-up study of high-risk tick-bitten individuals2020In: Ticks and Tick-borne Diseases, ISSN 1877-959X, E-ISSN 1877-9603, Vol. 11, no 1, article id UNSP 101303Article in journal (Refereed)
    Abstract [en]

    Despite the presence of several microorganisms, other than Borrelia burgdorferi sensu lato (Bbsl) and TBE virus, in Ixodes ricinus ticks from the Nordic countries, data is lacking on their pathogenic potential in humans. In this study, we wanted to investigate the aetiology and clinical manifestations of tick-transmitted infections in individuals seeking medical care following a tick-bite. The sampling frame was participants of a large-scale, prospective, multi-centre, follow-up study of tick-bitten volunteers recruited in Sweden, Finland and Norway in the years 2007-2015. Participants who sought medical care during the three-month follow-up period and from whom blood samples were collected during this healthcare visit (n=92) were tested, using PCR, for exposure to spotted fever group (SFG) Rickettsia spp., Anaplasma phagocytophilum and Babesia spp. Moreover, 86 of these individuals had two serum samples, collected three months apart, tested serologically for six tick-borne microorganisms. The selected organisms-Bbsl, SFG rickettsiae, Anaplasma phagocytophilum, TBE virus, Babesia microti and Bartonella henselae-have all been detected in field-collected ticks from the Nordic countries. Medical records were reviewed and questionnaires were completed to determine clinical manifestations. We found Lyme borreliosis to be the most common tick-transmitted infection as seen in 46 (54%) of the 86 participants with available medical records. Among the 86 participants with paired sera, serological or molecular evidence of recent exposure to other microorganisms than Bbsl could be demonstrated in eight (9%). Five participants (6%) exhibited serological evidence of recent concomitant exposure to more than one tick-borne microorganism. Clinical presentations were mild with one exception (TBE). In conclusion, our data suggest a low risk of infection with tick-borne microorganisms, other than Bbsl, in immunocompetent tick-bitten persons from the examined regions, a low occurrence of co-infection and mostly mild or no overt clinical signs of infection in immunocompetent persons exposed to the studied agents.

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  • 21.
    Ramezani, Amir
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Nägga, Katarina
    Department of Clinical Sciences Malmö, Lunds University, Malmö.
    Hansson, Oskar
    Department of Clinical Sciences Malmö, Lunds University, Malmö.
    Lönn, Johanna
    School of Health and Medical Sciences, Örebro University.
    Sjöwall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Katoozian, Fateme
    PEAS Institut, Linköping .
    Mansouri, Sepahdar
    PEAS Institut, Linköping .
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. PEAS Institut, Linköping .
    Hepatocyte growth factor in cerebrospinal fluid differentiates community-acquired or nosocomial septic meningitis from other causes of pleocytosis2015In: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 12, no 1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Due to anatomical restrictions, the inflammatory response to intracerebral bacterial infections exposes swollen brain tissues to pressure and ischemia, resulting in life-threatening damage. Rapid diagnosis and immediate empirical antibiotic therapy is highly important. However, diagnosing meningitis in patients after neurosurgery is complicated, due to brain tissue damage and changes in cerebrospinal fluid (CSF) caused by surgery. Hepatocyte growth factor (HGF) is a local, acute-phase protein with healing properties. Previous studies on community-acquired septic meningitis reported high levels of intrathecally produced HGF. The present study focused on nosocomial meningitis in assessing the levels of HGF in the CSF.

    METHODS: HGF concentrations (ELISA) and HGF binding to receptors; c-Met receptor and heparan sulfate proteoglycan were determined in CSF samples (surface plasmon resonance). CSF samples from patients with community-acquired or nosocomial meningitis (217 samples from 135 patients) were compared to those from controls without signs of cerebral nervous system involvement (N = 36) and patients with Alzheimer's disease (N = 20).

    RESULTS: Compared to samples from patients that had undergone neurosurgery and had other infectious diseases, CSF samples from patients with nosocomial meningitis had significantly higher HGF concentrations (p < 0.001) and binding affinity to c-Met (p < 0.001) and HSPG (p = 0.043) receptors. The sensitivity and specificity to identify nosocomial septic meningitis were 69.7 and 93.4 %, respectively. The HGF concentration and binding affinity to HGF receptors were significantly higher in CSF from patients with community-acquired septic meningitis compared to patients with aseptic (viral and subacute) meningitis as well as controls (p < 0.001). The sensitivity and specificity to identify community-acquired septic meningitis were 95.4 and 95.7 %, respectively.

    DISCUSSION: In febrile nosocomial infections that occurred post neurosurgery, HGF assessment could substantially improve the differentiation of meningitis from other infections and therefore might be a tool for rapid diagnosis, limiting injuries and guiding antibiotic therapy.

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  • 22. Order onlineBuy this publication >>
    Sjöwall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Clinical and Immunological Aspects of Lyme borreliosis2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Lyme borreliosis (LB) is a tick-borne infection caused by spirochetes of the Borrelia (B.) burgdorferi sensu lato complex. The infection is associated with several clinical features, of which erythema migrans (EM) and neuroborreliosis (NB) are the most common in Europe. The prognosis after antibiotic therapy is generally good. However, some patients may have residual symptoms post-treatment. The cause of the delayed convalescence is unclear. There are several factors that may affect the clinical outcome of LB, for example, the early interaction between the host’s immune response and B. burgdorferi, the spirochete genotype, antibiotic therapy, as well as the host’s vulnerability.

    This thesis aimed to explore the type of early immune response that is generated to B. burgdorferi and its importance for the clinical outcome of LB, and to study the condition of persistent symptoms post-NB from clinical, immunological and diagnostic perspectives. In total, 125 adult patients with different clinical features and outcomes of LB and 23 healthy controls were included.

    In a prospective follow-up study of EM, we confirmed that the prognosis of EM is good after antibiotic therapy, and that B. afzelii is the most common B. burgdorferi genotype associated with EM in the Nordic countries. Seven patients (8%) reported persistent symptoms more than six months post-treatment. These patients had also a decreased early expression of inflammatory, Th1-type cytokines in the EM lesions, suggesting an importance of early, local Th1-type immunity to B. burgdorferi for a successful clinical outcome of LB. No correlation between clinical characteristics, allergic predisposition, B. burgdorferi genotype or serology and the development of symptoms post-treatment was found.

    Asymptomatic B. burgdorferi-seropositive individuals are interesting from clinical and immunological points of view, since they apparently have encountered B. burgdorferi without developing symptoms of LB. In this thesis, asymptomatic individuals were shown to display an enhanced innate inflammatory immune response to live B. garinii spirochetes, induced by dendritic cells and whole blood cells, in comparison with patients with a history of subacute NB and healthy controls. Whether this is the optimal immune response to B. burgdorferi remains to be determined.

    A randomized, placebo-controlled cross-over study showed that three weeks of doxycycline therapy did not significantly improve objective neurological signs, subjective symptoms or quality of life in NB patients with persistent symptoms post-treatment. Nor could any doxycycline-mediated effects on systemic cytokine responses be demonstrated.

    Brain magnetic resonance imaging (MRI) findings in NB patients with persistent symptoms post-treatment were shown to be nonspecific and to correlate with age, but not with the duration of symptoms.

    In conclusion, this thesis shows that there is an association between the early immune response to B. burgdorferi sensu lato and the clinical outcome of LB. The cause of prolonged convalescence post-treatment remains unknown and needs further investigation. However, repeated treatment with doxycycline does not lead to improvement of the persistent symptoms; nor does brain MRI facilitate diagnosis of, or provide an explanation for the post-treatment symptoms.

    List of papers
    1. Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans
    Open this publication in new window or tab >>Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans
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    2011 (English)In: PLOS ONE, ISSN 1932-6203, Vol. 6, no 3, p. 0018220-Article in journal (Refereed) Published
    Abstract [en]

    Background: Despite the good prognosis of erythema migrans (EM), some patients have persisting symptoms of various character and duration post-treatment. Several factors may affect the clinical outcome of EM, e. g. the early interaction between Borrelia (B.) burgdorferi and the host immune response, the B. burgdorferi genotype, antibiotic treatment as well as other clinical circumstances. Our study was designed to determine whether early cytokine expression in the skin and in peripheral blood in patients with EM is associated with the clinical outcome. Methods: A prospective follow-up study of 109 patients with EM was conducted at the A land Islands, Finland. Symptoms were evaluated at 3, 6, 12 and 24 months post-treatment. Skin biopsies from the EM and healthy skin were immunohistochemically analysed for expression of interleukin (IL)-4, IL-10, IL-12p70 and interferon (IFN)-gamma, as well as for B. burgdorferi DNA. Blood samples were analysed for B. burgdorferi antibodies, allergic predisposition and levels of systemic cytokines. Findings: None of the patients developed late manifestations of Lyme borreliosis. However, at the 6-month follow-up, 7 of 88 patients reported persisting symptoms of diverse character. Compared to asymptomatic patients, these 7 patients showed decreased expression of the Th1-associated cytokine IFN-gamma in the EM biopsies (p = 0.003). B. afzelii DNA was found in 48%, B. garinii in 15% and B. burgdorferi sensu stricto in 1% of the EM biopsies, and species distribution was the same in patients with and without post-treatment symptoms. The two groups did not differ regarding baseline patient characteristics, B. burgdorferi antibodies, allergic predisposition or systemic cytokine levels. Conclusion: Patients with persisting symptoms following an EM show a decreased Th1-type inflammatory response in infected skin early during the infection, which might reflect a dysregulation of the early immune response. This finding supports the importance of an early, local Th1-type response for optimal resolution of LB.

    Place, publisher, year, edition, pages
    Public Library of Science (PLoS), 2011
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-67829 (URN)10.1371/journal.pone.0018220 (DOI)000289057200045 ()
    Note
    Original Publication: Johanna Sjöwall, Linda Fryland, Marika Nordberg, Florence Sjögren, Ulf Garpmo, Christian Jansson, Sten-Anders Carlsson, Sven Bergstrom, Jan Ernerudh, Dag Nyman, Pia Forsberg and Christina Ekerfelt, Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans, 2011, PLOS ONE, (6), 3, 0018220. http://dx.doi.org/10.1371/journal.pone.0018220 Copyright: Public Library of Science (PLoS) http://www.plos.org/Available from: 2011-04-29 Created: 2011-04-29 Last updated: 2021-12-29
    2. Innate immune responses in Lyme borreliosis: Enhanced tumour necrosis factor-a and interleukin-12 in asymptomatic individuals in response to live spirochetes
    Open this publication in new window or tab >>Innate immune responses in Lyme borreliosis: Enhanced tumour necrosis factor-a and interleukin-12 in asymptomatic individuals in response to live spirochetes
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    2005 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 141, no 1, p. 89-98Article in journal (Refereed) Published
    Abstract [en]

    Innate immunity is important for early defence against borrelia spirochetes and should play a role in the clinical outcome of the infection. In order to study early cytokine responses, in vitro differentiated dendritic cells (DCs) and whole blood cells from 21 patients with different clinical outcomes of Lyme neuroborreliosis were stimulated with live borrelia spirochetes. The borrelia-induced secretion of interleukin (IL)-4, IL-10, IL-12p70, Interferon (INF)-? and tumour necrosis factor (TNF)-a in DCs and IL-1ß, IL-6, IL-8, IL-10, IL-12p70, TNF-a, regulated upon activation normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1a, MIP-1ß and eotaxin in whole blood cells was measured by enzyme-linked immunospot (ELISPOT) and multiplex arrays, respectively. We found increased numbers of TNF-a-secreting DCs (P = 0.018) in asymptomatic seropositive individuals compared to patients with subacute neuroborreliosis and seronegative controls. Asymptomatic individuals were also found to have elevated levels of IL-12p70 (P = 0.031) in whole blood cell supernatants compared to seronegative controls. These results are in line with previous experiments using cells of the adaptive immune response, indicating that strong T helper type 1 (Th1) proinflammatory responses might be associated with a successful resolution of Lyme disease. © 2005 British Society for Immunology.

    Keywords
    Borrelia, Clinical outcome, Dendritic cell, IL-12p70, TNF-a
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-50469 (URN)10.1111/j.1365-2249.2005.02820.x (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2021-12-29
    3. Lack of doxycycline-mediated effects on systemic cytokine responses and persistent symptoms post-neuroborreliosis: A double-blind, randomized, cross-over study
    Open this publication in new window or tab >>Lack of doxycycline-mediated effects on systemic cytokine responses and persistent symptoms post-neuroborreliosis: A double-blind, randomized, cross-over study
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Persistent symptoms after treatment of neuroborreliosis (NB) are welldocumented, although the causative mechanisms are mainly unknown. The effect of repeated antibiotic treatment has not been studied in detail. The aim of this study was to determine whether: (1) persistent symptoms improve with doxycycline treatment; (2) doxycycline has an influence on systemic cytokine responses, and; (3) improvement of symptoms could be due to doxycycline-mediated immunomodulation.

    Methods: Fifteen NB patients with persistent symptoms ≥6 months post-treatment were double-blindly randomized to receive 200 mg of doxycycline or a placebo for three weeks. After a six-week wash-out period, a cross-over with a three-week course of a placebo or doxycycline was conducted. The primary outcome measures were improvement of persistent symptoms assessed by neurological examinations, a symptom severity score and estimation of the quality of life. The secondary outcome measure was change in systemic cytokine responses.

    Results: No serious adverse effects were registered. No doxycycline-mediated improvement of symptoms or quality of life was observed. Nor could any doxycycline-mediated changes in systemic cytokine responses be detected.

    Conclusions In this pilot study, no doxycycline-mediated improvement of persistent symptoms or quality of life was observed. Consequently, use of doxycycline for treatment of persistent symptoms post-NB cannot be recommended.

    Keywords
    Persistent symptoms, neuroborreliosis, doxycycline, immunomodulation, randomized, cross-over
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-68744 (URN)
    Available from: 2011-06-01 Created: 2011-06-01 Last updated: 2021-12-29Bibliographically approved
    4. Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis
    Open this publication in new window or tab >>Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis
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    2007 (English)In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 48, no 7, p. 755-762Article in journal (Refereed) Published
    Abstract [en]

    Background: Borrelia infections, especially chronic neuroborreliosis ( NB), may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive. Purpose: To evaluate brain magnetic resonance imaging ( MRI) in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration. Material and Methods: Sixteen well- characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1- ( with and without gadolinium), T2-, and diffusion- weighted imaging plus fluid- attenuated inversion recovery ( FLAIR) imaging were used. Results: White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls ( no significant difference). Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients ( rho=0.83, P < 0.01) and in controls ( rho=0.61, P < 0.05), but not to the duration of disease. Most lesions were detected with FLAIR, but many also with T2- weighted imaging. Conclusion: A number of MRI findings were detected in patients with chronic NB, although the findings were unspecific when compared with matched controls and did not correlate with disease duration. However, subependymal lesions may constitute a potential finding in chronic NB.

    Keywords
    adults, Borrelia, brain, brain stem, CNS, Lyme, meninges, MR imaging, neuroborreliosis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-45936 (URN)10.1080/02841850701367903 (DOI)000249137200010 ()
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2021-12-29
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    Clinical and Immunological Aspects of Lyme borreliosis
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  • 23.
    Sjöwall, Johanna
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Azharuddin, Mohammad
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Frodlund, Martina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Zhang, Yuming
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Sandner, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Dahle, Charlotte
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Hinkula, Jorma
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    SARS-CoV-2 Antibody Isotypes in Systemic Lupus Erythematosus Patients Prior to Vaccination: Associations With Disease Activity, Antinuclear Antibodies, and Immunomodulatory Drugs During the First Year of the Pandemic2021In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 12, article id 724047Article in journal (Refereed)
    Abstract [en]

    Objectives Impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on individuals with arthritis has been highlighted whereas data on other rheumatic diseases, e.g., systemic lupus erythematosus (SLE), are scarce. Similarly to SLE, severe SARS-CoV-2 infection includes risks for thromboembolism, an unbalanced type I interferon response, and complement activation. Herein, SARS-CoV-2 antibodies in longitudinal samples collected prior to vaccination were analyzed and compared with SLE progression and antinuclear antibody (ANA) levels. Methods One hundred patients (83 women) with established SLE and a regular visit to the rheumatologist (March 2020 to January 2021) were included. All subjects donated blood and had done likewise prior to the pandemic. SARS-CoV-2 antibody isotypes (IgG, IgA, IgM) to the cell receptor-binding S1-spike outer envelope protein were detected by ELISA, and their neutralizing capacity was investigated. IgG-ANA were measured by multiplex technology. Results During the pandemic, 4% had PCR-confirmed infection but 36% showed SARS-CoV-2 antibodies of &gt;= 1 isotype; IgA was the most common (30%), followed by IgM (9%) and IgG (8%). The antibodies had low neutralizing capacity and were detected also in prepandemic samples. Plasma albumin (p = 0.04) and anti-dsDNA (p = 0.003) levels were lower in patients with SARS-CoV-2 antibodies. Blood group, BMI, smoking habits, complement proteins, daily glucocorticoid dose, use of hydroxychloroquine, or self-reported coronavirus disease 2019 (COVID-19) symptoms (except fever, &gt;38.5 degrees C) did not associate with SARS-CoV-2 antibodies. Conclusion Our data from early 2021 indicate that a large proportion of Swedish SLE patients had serological signs of exposure to SARS-CoV-2 but apparently with a minor impact on the SLE course. Use of steroids and hydroxychloroquine showed no distinct effects, and self-reported COVID-19-related symptoms correlated poorly with all antibody isotypes.

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  • 24.
    Sjöwall, Johanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Carlsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery.
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics.
    Bergstrom, S.
    Bergström, S., Department of Microbiology, University of Umeå, Umeå, Sweden.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Innate immune responses in Lyme borreliosis: Enhanced tumour necrosis factor-a and interleukin-12 in asymptomatic individuals in response to live spirochetes2005In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 141, no 1, p. 89-98Article in journal (Refereed)
    Abstract [en]

    Innate immunity is important for early defence against borrelia spirochetes and should play a role in the clinical outcome of the infection. In order to study early cytokine responses, in vitro differentiated dendritic cells (DCs) and whole blood cells from 21 patients with different clinical outcomes of Lyme neuroborreliosis were stimulated with live borrelia spirochetes. The borrelia-induced secretion of interleukin (IL)-4, IL-10, IL-12p70, Interferon (INF)-? and tumour necrosis factor (TNF)-a in DCs and IL-1ß, IL-6, IL-8, IL-10, IL-12p70, TNF-a, regulated upon activation normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1a, MIP-1ß and eotaxin in whole blood cells was measured by enzyme-linked immunospot (ELISPOT) and multiplex arrays, respectively. We found increased numbers of TNF-a-secreting DCs (P = 0.018) in asymptomatic seropositive individuals compared to patients with subacute neuroborreliosis and seronegative controls. Asymptomatic individuals were also found to have elevated levels of IL-12p70 (P = 0.031) in whole blood cell supernatants compared to seronegative controls. These results are in line with previous experiments using cells of the adaptive immune response, indicating that strong T helper type 1 (Th1) proinflammatory responses might be associated with a successful resolution of Lyme disease. © 2005 British Society for Immunology.

  • 25.
    Sjöwall, Johanna
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases.
    Fryland, Linda
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology.
    Nordberg, Marika
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Sjögren, Florence
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Garpmo, Ulf
    Kalmar Hospital.
    Jansson, Christian
    Aland Borrelia Grp.
    Carlsson, Sten-Anders
    Aland Borrelia Grp.
    Bergstrom, Sven
    Umea University.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Nyman, Dag
    Aland Borrelia Grp.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology.
    Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans2011In: PLOS ONE, ISSN 1932-6203, Vol. 6, no 3, p. 0018220-Article in journal (Refereed)
    Abstract [en]

    Background: Despite the good prognosis of erythema migrans (EM), some patients have persisting symptoms of various character and duration post-treatment. Several factors may affect the clinical outcome of EM, e. g. the early interaction between Borrelia (B.) burgdorferi and the host immune response, the B. burgdorferi genotype, antibiotic treatment as well as other clinical circumstances. Our study was designed to determine whether early cytokine expression in the skin and in peripheral blood in patients with EM is associated with the clinical outcome. Methods: A prospective follow-up study of 109 patients with EM was conducted at the A land Islands, Finland. Symptoms were evaluated at 3, 6, 12 and 24 months post-treatment. Skin biopsies from the EM and healthy skin were immunohistochemically analysed for expression of interleukin (IL)-4, IL-10, IL-12p70 and interferon (IFN)-gamma, as well as for B. burgdorferi DNA. Blood samples were analysed for B. burgdorferi antibodies, allergic predisposition and levels of systemic cytokines. Findings: None of the patients developed late manifestations of Lyme borreliosis. However, at the 6-month follow-up, 7 of 88 patients reported persisting symptoms of diverse character. Compared to asymptomatic patients, these 7 patients showed decreased expression of the Th1-associated cytokine IFN-gamma in the EM biopsies (p = 0.003). B. afzelii DNA was found in 48%, B. garinii in 15% and B. burgdorferi sensu stricto in 1% of the EM biopsies, and species distribution was the same in patients with and without post-treatment symptoms. The two groups did not differ regarding baseline patient characteristics, B. burgdorferi antibodies, allergic predisposition or systemic cytokine levels. Conclusion: Patients with persisting symptoms following an EM show a decreased Th1-type inflammatory response in infected skin early during the infection, which might reflect a dysregulation of the early immune response. This finding supports the importance of an early, local Th1-type response for optimal resolution of LB.

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  • 26.
    Sjöwall, Johanna
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Hjorth, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Gustafsson, Annette
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Göransson, Robin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Larsson, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Waller, Hjalmar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Nordgren, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Nyström, Sofia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    SARS-CoV-2 Specific Antibody Response and T Cell-Immunity in Immunocompromised Patients up to Six Months Post COVID: A Pilot Study2022In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 11, no 12, article id 3535Article in journal (Refereed)
    Abstract [en]

    COVID-19 generates SARS-CoV-2-specific antibodies in immunocompetent individuals. However, in immunocompromised patients, the humoral immunity following infection may be impaired or absent. Recently, the assessment of cellular immunity to SARS-CoV-2, both following natural infection and vaccination, has contributed new knowledge regarding patients with low or no antibody responses. As part of a prospective cohort study which included hospitalized patients with COVID-19, we identified immunocompromised patients and compared them with age- and sex-matched immunocompetent patients regarding co-morbidities, biomarkers of COVID-19 and baseline viral load by real-time PCR in nasopharyngeal swabs. Spike and nucleocapsid antibody responses were analyzed at inclusion and after two weeks, six weeks and six months. Plasma immunoglobulin G (IgG) levels were quantified, lymphocyte phenotyping was performed, and SARS-CoV-2 specific CD4 and CD8 T cell responses after in vitro antigen stimulation were assessed at six months post infection. All patients showed IgG levels above or within reference limits. At six months, all patients had detectable SARS-CoV-2 anti-spike antibody levels. SARS-CoV-2 specific T cell responses were detected in 12 of 12 immunocompetent patients and in four of six immunocompromised patients. The magnitude of long-lived SARS-CoV-2 specific T cell responses were significantly correlated with the number of CD4 T cells and NK cells. Determining the durability of the humoral and cellular immune response against SARS-CoV-2 in immunocompromised individuals could be of importance by providing insights into the risk of re-infection and the need for vaccine boosters.

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  • 27.
    Sjöwall, Johanna
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Kling, Kristian
    Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Ochoa-Figueroa, Miguel
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Zachrisson, Helene
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Wennerås, Christine
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Neoehrlichia mikurensis Causing Thrombosis and Relapsing Fever in a Lymphoma Patient Receiving Rituximab2021In: Microorganisms, E-ISSN 2076-2607, Vol. 9, no 10, article id 2138Article in journal (Refereed)
    Abstract [en]

    Neoehrlichia (N.) mikurensis, an intracellular tick-borne bacterium not detected by routine blood culture, is prevalent in ticks in Scandinavia, Central Europe and Northern Asia, and may cause long-standing fever, nightly sweats, migrating pain, skin rashes and thromboembolism, especially in patients treated with rituximab. The multiple symptoms may raise suspicion of both infection, inflammation and malignancy, and lead in most cases to extensive medical investigations across many medical specialist areas and a delay of diagnosis. We describe a complex, albeit typical, case of neoehrlichiosis in a middle-aged splenectomised male patient with a malignant lymphoma, receiving treatment with rituximab. The multifaceted clinical picture associated with this tick-borne disease is addressed, and longitudinal clinical and laboratory data, as well as imaging, are provided. Longstanding relapsing fever in combination with thrombosis in superficial and deep veins in an immunocompromised patient living in a tick-endemic region should raise the suspicion of the emerging tick-borne disease neoehrlichiosis. Given the varied clinical presentation and the risk of delay in diagnosis and treatment, we believe it is important to raise clinicians awareness of this emerging infection, which is successfully treated with doxycycline.

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  • 28.
    Sjöwall, Johanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Ledel, Anna
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Doxycycline-mediated effects on persistent symptoms and systemic cytokine responses post-neuroborreliosis: a randomized, prospective, cross-over study2012In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 12, no 186, p. 1-12Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Persistent symptoms after treatment of neuroborreliosis (NB) are well-documented, although the causative mechanisms are mainly unknown. The effect of repeated antibiotic treatment has not been studied in detail. The aim of this study was to determine whether: (1) persistent symptoms improve with doxycycline treatment; (2) doxycycline has an influence on systemic cytokine responses, and; (3) improvement of symptoms could be due to doxycycline-mediated immunomodulation.

    METHODS/DESIGN:

    15 NB patients with persistent symptoms ≥6 months post-treatment were double-blindly randomized to receive 200 mg of doxycycline or a placebo for three weeks. After a six-week wash-out period, a cross-over with a three-week course of a placebo or doxycycline was conducted. The primary outcome measures were improvement of persistent symptoms assessed by neurological examinations, a symptom severity score and estimation of the quality of life. The secondary outcome measure was changes in systemic cytokine responses.

    RESULTS:

    All 15 patients finished the study. No doxycycline-mediated improvement of post-treatment symptoms or quality of life was observed. Nor could any doxycycline-mediated changes in systemic cytokine responses be detected. The study was completed without any serious adverse events.

    DISCUSSION:

    No doxycycline-mediated improvement of post-treatment symptoms or quality of life was observed. Nor could any doxycycline-mediated changes in systemic cytokine responses be detected. The study was completed without any serious adverse events. To conclude, in this pilot study, doxycycline-treatment did not lead to any improvement of either the persistent symptoms or quality of life in post-NB patients. Accordingly, doxycycline does not seem to be the optimal treatment of diverse persistent symptoms post-NB. However, the results need to be confirmed in larger studies.

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  • 29.
    Sjöwall, Johanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Ledel, Anna
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Lack of doxycycline-mediated effects on systemic cytokine responses and persistent symptoms post-neuroborreliosis: A double-blind, randomized, cross-over studyManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Persistent symptoms after treatment of neuroborreliosis (NB) are welldocumented, although the causative mechanisms are mainly unknown. The effect of repeated antibiotic treatment has not been studied in detail. The aim of this study was to determine whether: (1) persistent symptoms improve with doxycycline treatment; (2) doxycycline has an influence on systemic cytokine responses, and; (3) improvement of symptoms could be due to doxycycline-mediated immunomodulation.

    Methods: Fifteen NB patients with persistent symptoms ≥6 months post-treatment were double-blindly randomized to receive 200 mg of doxycycline or a placebo for three weeks. After a six-week wash-out period, a cross-over with a three-week course of a placebo or doxycycline was conducted. The primary outcome measures were improvement of persistent symptoms assessed by neurological examinations, a symptom severity score and estimation of the quality of life. The secondary outcome measure was change in systemic cytokine responses.

    Results: No serious adverse effects were registered. No doxycycline-mediated improvement of symptoms or quality of life was observed. Nor could any doxycycline-mediated changes in systemic cytokine responses be detected.

    Conclusions In this pilot study, no doxycycline-mediated improvement of persistent symptoms or quality of life was observed. Consequently, use of doxycycline for treatment of persistent symptoms post-NB cannot be recommended.

  • 30.
    Sjöwall, Johanna
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Xirotagaros, Georgios
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Dermatology and Venerology.
    Anderson, Chris
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Dermatology and Venerology.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Dahle, Charlotte
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Case Report: Borrelia-DNA Revealed the Cause of Arthritis and Dermatitis During Treatment With Rituximab2021In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 12, article id 645298Article in journal (Refereed)
    Abstract [en]

    Borrelia-specific antibodies in serum did not contribute to the diagnosis of Borrelia arthritis or Borrelia-associated dermatitis in a young woman with ongoing treatment with rituximab due to multiple sclerosis. The diagnosis was confirmed by the detection of Borrelia-DNA in a skin punch biopsy. The patient history did not reveal any tick exposure. She had suffered for several months from fluctuating pain and swelling of the right knee as well as skin involvement with redness and oedema around the ankle of the same leg. Monoarthritis was confirmed by a rheumatologist. Knee puncture was performed but the synovial fluid was only sufficient for microscopic examination of crystals. Neither monosodium urate crystals nor calcium pyrophosphate crystals were found. Borrelia serology in blood revealed borderline levels of immunoglobulin (Ig)M and IgG, respectively. Treatment with doxycycline resulted in resolution of the joint and skin manifestations within a month. This case highlights that Borrelia-specific antibody levels cannot be reliably interpreted in patients who have received B-cell depleting therapy. Under these circumstances, detection of the bacterial genome in different body fluids, such as in the skin, can be a useful complement to the diagnosis of Lyme disease. In this young female, the diagnosis would certainly have been further delayed without the detection of Borrelia-DNA in the skin.

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  • 31.
    Skogman, Barbro H.
    et al.
    Falun Gen Hospital, Sweden; Uppsala University, Sweden.
    Sjöwall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Faculty of Medicine and Health Sciences.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    The NeBoP score - a clinical prediction test for evaluation of children with Lyme Neuroborreliosis in Europe2015In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 15, no 214Article in journal (Refereed)
    Abstract [en]

    Background: The diagnosis of Lyme neuroborreliosis (LNB) in Europe is based on clinical symptoms and laboratory data, such as pleocytosis and anti-Borrelia antibodies in serum and CSF according to guidelines. However, the decision to start antibiotic treatment on admission cannot be based on Borrelia serology since results are not available at the time of lumbar puncture. Therefore, an early prediction test would be useful in clinical practice. The aim of the study was to develop and evaluate a clinical prediction test for children with LNB in a relevant European setting. Method: Clinical and laboratory data were collected retrospectively from a cohort of children being evaluated for LNB in Southeast Sweden. A clinical neuroborreliosis prediction test, the NeBoP score, was designed to differentiate between a high and a low risk of having LNB. The NeBoP score was then prospectively validated in a cohort of children being evaluated for LNB in Central and Southeast Sweden (n = 190) and controls with other specific diagnoses (n = 49). Results: The sensitivity of the NeBoP score was 90 % (CI 95 %; 82-99 %) and the specificity was 90 % (CI 95 %; 85-96 %). Thus, the diagnostic accuracy (i.e. how the test correctly discriminates patients from controls) was 90 % and the area under the curve in a ROC analysis was 0.95. The positive predictive value (PPV) was 0.83 (CI 95 %; 0.75-0.93) and the negative predictive value (NPV) was 0.95 (CI 95 %; 0.90-0.99). Conclusion: The overall diagnostic performance of the NeBoP score is high (90 %) and the test is suggested to be useful for decision-making about early antibiotic treatment in children being evaluated for LNB in European Lyme endemic areas.

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  • 32.
    Tjernberg, Ivar
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Reg Kalmar Cty, Sweden.
    Gyllemark, Paula
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Zetterberg, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; UCL Inst Neurol, England; UK Dementia Res Inst UCL, England; Hong Kong Ctr Neurodegenerat Dis, Peoples R China.
    Blennow, Kaj
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Forsberg, Pia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Jonsson Henningsson, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology. National Reference Laboratory for Borrelia and Other Tick-Borne Bacteria, Laboratory Medicine, Region Jönköping County, Jönköping, Sweden.
    Cerebrospinal fluid markers of inflammation and brain injury in Lyme neuroborreliosis - a prospective follow-up study2022In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 60, no 7, p. 1124-1132Article in journal (Refereed)
    Abstract [en]

    Objectives The purpose of this study was to evaluate levels and kinetics of cerebrospinal fluid (CSF) markers of inflammation and brain injury in patients with Lyme neuroborreliosis (LNB). Methods Adult patients with clinically suspected LNB were enrolled, in a prospective clinical study in the South East of Sweden. Patients were classified according to the European Federation of Neurological Societies guidelines. Definite cases of LNB were re-examined one month later including a repeat CSF investigation. Routine laboratory parameters were investigated along with CSF levels of neurodegenerative markers glial fibrillary acidic protein (GFAp), total tau (t-tau) and neurofilament light protein (NFL), as well as neuroinflammatory markers soluble triggering receptor expressed on myeloid cells 2 (sTREM2), YKL-40 and CXCL13. Non-LNB served as controls. An additional comparison group consisted of spinal anesthesia subjects (SAS) without known central nervous system conditions. Results CSF levels of sTREM2 and CXCL13 were elevated in definite LNB patients at diagnosis compared with non-LNB patients (p&lt;0.001) and SAS (p &lt;= 0.01). In addition, CSF levels of sTREM2, YKL-40 and CXCL13 rapidly declined in at follow-up after antibiotic treatment. In contrast, CSF levels of GFAp and t-tau did not differ across LNB groups, and did not change after treatment. Conclusions Although in a limited number of LNB patients, the results indicate a predominance of microglial and neuroinflammatory involvement rather than parenchymal CNS injury in CSF at diagnosis of LNB with a prompt decline after antibiotic treatment. The findings provide pathogenetic insights and may be of value in differential diagnosis of CSF findings.

  • 33.
    Waller, Hjalmar
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Carmona Vicente, Noelia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    James, Axel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Govender, Melissa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Hopkins, Francis
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Larsson, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Hagbom, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Svensson, Lennart
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Enocsson, Helena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Annette
    Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases. Vrinnevi Hosp, Sweden.
    Nordgren, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Viral load at hospitalization is an independent predictor of severe COVID-192023In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 53, no 1, article id e13882Article in journal (Refereed)
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  • 34.
    Wilhelmsson, Peter
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Lindblom, Pontus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Sjöwall, Johanna
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine.
    Ahlm, Clas
    Division of Infectious Diseases, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Berglund, Johan
    School of Health Science, Blekinge Institute of Technology, Karlskrona, Sweden.
    Haglund, Mats
    Department of Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden.
    Henningsson, Anna
    Department of Clinical Microbiology, Division of Medical Services, Ryhov County Hospital, Jönkoping, Sweden.
    Nolskog, Peter
    Department of Communicable Disease Control and Prevention, Region Västra Götaland, Skaraborg Hospital, Skövde, Sweden.
    Nordberg, Marika
    The Åland Group for Borrelia Research, Mariehamn, Åland, Finland.
    Nyberg, Clara
    The Åland Group for Borrelia Research, Mariehamn, Åland, Finland.
    Ornstein, Katharina
    Department of Internal Medicine, Hässleholm Hospital, Hässleholm, Sweden/Department of Clinical Sciences, Lund University, Lund, Sweden.
    Nyman, Dag
    The Åland Group for Borrelia Research, Mariehamn, Åland, Finland.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    A prospective study on the incidence of Borrelia infection after a tick bite in Sweden and on the Åland Islands, Finland (2008-2009)2016In: Ticks and Tick-borne Diseases, ISSN 1877-959X, E-ISSN 1877-9603, Vol. 7, no 1, p. 71-79Article in journal (Refereed)
    Abstract [en]

    Lyme borreliosis (LB) is a common and increasing tick-borne disease in Europe. The risk of acquiring a Borrelia infection after a tick bite is not fully known. Therefore, we investigated the incidence of Borrelia infection after a tick bite and if the Borrelia load and/or the duration of tick-feeding influenced the risk of infection. During 2008-2009, ticks and blood samples were collected from 1546 tick-bitten persons from Sweden and the Åland Islands, Finland. Follow-up blood samples were taken three months after the tick bite. The duration of tick feeding was microscopically estimated and Borrelia was detected and quantified in ticks by real-time PCR. Anti-Borrelia antibodies were detected in sera using ELISA assays and immunoblot.

    Even though 28 % of the participants were bitten by a Borrelia-positive tick, only 7.5% (32/428) of them developed a Borrelia infection, half of them LB. All who seroconverted removed “their” ticks significantly later than those who did not. The Borrelia load in the ticks did not explain the risk of seroconversion. Regional as well as gender differences in the Borrelia seroprevalence were found. The risk of developing a Borrelia infection after a bite by a Borrelia-infected tick is small but increases with the duration of tick feeding.

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