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  • 101.
    Paues, Jakob
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Fatal progressive multifocal leukoencephalopathy in a patient with non-Hodgkin lymphoma treated with rituximab2010In: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 48, no 4, p. 291-293Article in journal (Refereed)
    Abstract [en]

    We report a case of progressive multifocal leukoencephalopathy (PML) in a woman with non-Hodgkin lymphoma treated with chemotherapy in combination with rituximab. She presented with rapid deterioration of vision and subsequently cognitive decline. Magnetic resonance imaging (MRI) of the brain raised the suspicion of PML. The first PCR analysis of the cerebrospinal fluid (CSF) was negative, but a second sample was positive for JC virus DNA. Anti-viral treatment was ineffective and the patient died 7 months after debut of symptoms. Our case emphasizes the importance of the awareness of PML in patients with progressive neurological symptoms treated with antilymphocytic drugs and that consecutive CSF analyses may be needed to detect the JC virus.

  • 102.
    Persson, Hans Lennart
    et al.
    Linköping University, Department of Medical and Health Sciences, Pulmonary Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Eklund, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Welin, Amanda
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Idh, Jonna
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Fransson, Sven-Göran
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Lerm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Alveolar macrophages from patients with tuberculosis exhibit reduced capacity of restricting growth of Mycobacterium tuberculosis: a pilot study of vitamin D stimulation in vitro2013In: HOAJ Biology, ISSN 2050-0874Article in journal (Refereed)
    Abstract [en]

    Background: The role of vitamin D supplementation as adjuvant treatment of tuberculosis (TB) has lately attracted increasing interest. Our aim was to investigate the capacity of alveolar macrophages (AMs) from patients with or without exposure to TB to control intracellular growth of virulent Mycobacterium tuberculosis (Mtb).

    Methods: AMs were freshly harvested from the bronchoalveolar lavage fluid of 7 patients with a history of TB (4 patients with previous TB and 3 patients with current TB) and 4 non-TB subjects. The H37Rv strain, genetically modified to express Vibrio harveyi luciferase, was used to determine the growth of Mtb by luminometry in the AMs from study subjects. Cytokine levels in culture supernatants were determined using a flow cytometry-based bead array technique.

    Results: AMs from patients with a TB history were less efficient in restricting Mtb growth. Stimulation with 100 nM1, 25-dihydroxyvitamin D (1,25D3) did not significantly influence the capacity of AMs from any study subjects to control the infection. Out of the cytokines evaluated (TNF-α, IL-1β, IL-10 and IL-12p40) only TNF-α demonstrated detectable levels in culture supernatants, but did not respond to stimulation with 1,25D3.

    Conclusions: We conclude that AMs of TB-patients show reduced ability to control mycobacterial growth in vitro, and, that AMs in this pilot study do no respond to 1, 25D3-stimulation. The former observation supports the concept that innate immunity is crucial for the control of TB infection.

  • 103.
    Samuelsson, Annika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology. Östergötlands Läns Landsting, Centre for Health and Developmental Care, Vårdhygien.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology. Östergötlands Läns Landsting, Centre for Health and Developmental Care, Vårdhygien.
    Chabok, Abbas
    Uppsala University, Sweden .
    Jonasson, Jon
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Eriksson, Olle
    Linköping University, Department of Computer and Information Science, Statistics. Linköping University, Faculty of Arts and Sciences.
    Hanberger, Håkan
    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.
    Changes in the aerobic faecal flora of patients treated with antibiotics for acute intra-abdominal infection2012In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 44, no 11, p. 820-827Article in journal (Refereed)
    Abstract [en]

    Background: An open observational study was performed to investigate changes in the rectal flora and antibiotic susceptibility among faecal bacteria in patients treated with antibiotics for acute intra-abdominal infection. Methods: One hundred and forty patients with acute intra-abdominal infection requiring antibiotic treatment and hospitalization were included. Eight surgical units from the southern part of Sweden participated, between January 2006 and November 2007. Antibiotic treatments were according to local guidelines. Rectal swabs were obtained on admission (sample 1) and 2-14 days after the end of antibiotic treatment (sample 2). Aerobic bacteria and yeasts were analysed. The material was divided into 2 groups: 1 group with Enterobacteriaceae and 1 group with non-fermentative Gram-negative bacteria. The susceptibility to antibiotics in each group was compared between samples 1 and 2. Results: The main finding of this study on patients with severe intra-abdominal infections was a shift in the aerobic faecal flora following antibiotic treatment, from Escherichia coli to other more resistant Enterobacteriaceae, Enterococcus faecium, and yeasts. The susceptibility to cephalosporins and piperacillin-tazobactam decreased in Enterobacteriaceae. Conclusions: Following antibiotic treatment, a shift in the aerobic rectal flora to species with intrinsic antibiotic resistance was observed. This indicates that the emergence of resistance is not due to new mutations, but rather to selection of more resistant species. This should be taken into account when designing treatments for secondary intra-abdominal infections.

  • 104.
    Samuelsson, Annika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Microbiology. Östergötlands Läns Landsting, Center for Health and Developmental Care, Department of Infection Control.
    Wefer, Hugo
    Department of Microbiology, Tumor and Cellbiology, Karolinska Institute, Solna, Sweden.
    Fahlén, Annika
    Department of Microbiology, Tumor and Cellbiology, Karolinska Institute, Solna, Sweden.
    Agréus, Lars
    Center for Family Medicine, Karolinska Institute, Huddinge, Sweden.
    Nixon Andreasson, Anna
    Center for Family Medicine, Karolinska Institute, Huddinge, Sweden.
    Chabok, Abbas
    Colorectal Unit, Department of Surgery and Center for Clinical Research, Uppsala University/Central Hospital, Västerås, Sweden.
    Lundin, Daniel
    Department of Microbiology, Tumor and Cellbiology, Karolinska Institute, Solna, Sweden.
    Hanberger, Håkan
    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.
    Engstrand, Lars
    Department of Microbiology, Tumor and Cellbiology, Karolinska Institute, Solna, Sweden.
    Disturbed intestinal microbiota (dysbiosis) and micro dynamics in patients treated for appendicitis and diverticulitisManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: The human gut microbiota is a large dynamic bacterial community, which is influenced by for instance antibiotic treatment and hospitalization. In patients with inflammatory bowel disease the diversity of gut microbiota is thought to be less diverse. The role of the gut microbiota in acute appendicitis and diverticulitis is still unclear. To investigate the microbial diversity in patients suffering from appendicitis or diverticulitis, and the microbiota dynamics after antibiotic therapy and hospitalization we performed an open observation study.

    Methods and population: We have performed 16S rRNA sequence analysis on 42 individuals diagnosed with appendicitis and 18 individuals with diverticulitis as well as 33 healthy controls. Cultivation of the aerobic bacterial flora was performed as a complement to sequence analysis.

    Results: In sequencing data at genus level, there are distinctive differences when comparing healthy controls to patients diagnosed with appendicitis. Healthy controls have a flora dominated by Bacteroides, and Faecalibacterium, Ruminococcus and Prevotella while appendicitis patients show an intestinal flora with a higher abundance of Escherichia/Shigella and unclassified Enterobacteriaceae. The same pattern, however not quite as distinct could be seen for the diverticulitis patients. The microbial diversity increases after treatment with antibiotics and hospitalization.

    In the cultivated aerobic flora there was a significant loss of Escherichia coli and a significant gain of Citrobacter species, in the appendicitis group. In the appendicitis group as well as in the diverticulitis group there was a significant gain of Enterococcus faecium and Yeasts.

    Conclusion: The main findings of this study are that patients arriving at the emergency department with acute appendicitis or diverticulitis have an already significant disturbed fecal microbiota previous to antibiotic treatment and hospitalization.

  • 105.
    Sandholm, Kerstin
    et al.
    School of Natural Sciences, Linneaus University, Kalmar.
    Henningsson, Anna J
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Säve, Susanne
    School of Natural Sciences, Linneaus University, Kalmar .
    Nordberg, Marika
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Garpmo, Ulf
    Department of Clinical Microbiology, Kalmar County Hospital, Sweden.
    Jansson, Christian
    The Åland Borrelia Group, the Åland Islands, Finland.
    Carlsson, Sten-Anders
    The Åland Borrelia Group, the Åland Islands, Finland.
    Nyman, Dag
    The Åland Borrelia Group, the Åland Islands, Finland.
    Bergström, Sven
    Department of Molecular Biology, Umeå University, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Nilsson Ekdahl, Kristina
    School of Natural Sciences, Linneaus University, Kalmar.
    Early Immune Responses to Borrelia garinii and Borrelia afzeliiin Lyme Borreliosis: Local Complement Activation in Erythema Migrans and in vitro Studies ofComplement Activation, Phagocytosis and Cytokine ProfileManuscript (preprint) (Other academic)
    Abstract [en]

    An optimal eradication of spirochetes in Lyme borreliosis depends on the early immune response, including the potent actions of the complement system. We here assessed possible differences between two Borrelia burgdorferi genospecies in their ability to activate complement, and the consequences of complement activation in terms of phagocytosis and induction of cytokines.

    Early local complement activation was assessed immunohistochemically in skin biopsies from patients with erythema migrans (EM) caused by B. afzelii or B. garinii. Complement activation, phagocytosis and early cytokine and chemokine release were studied in vitro by incubating clinical isolates of B. afzelii (K78 from a human skin biopsy) and B. garinii (LU59 from human cerebrospinal fluid) in human whole blood.

    B. afzelii and B. garinii were detected in skin biopsies from EM and deposition of C3-fragments and IgG was found adjacent to the spirochetes. In vitro, B. garinii LU59 induced higher complement activation (measured as the generation of C3a and C5b-9), while B. afzelii K78 recruited more factor H. Phagocytosis by granulocytes and monocytes was demonstrated to be largely dependent on complement activation since phagocytosis was substantially reduced by addition of the C3 inhibitor compstatin or a C5a receptor antagonist. The early cytokine and chemokine release in human blood in response to live spirochetes revealed a rapid and pronounced pro-inflammatory response, mainly associated with the Th1- and Th17-types.

    We conclude that complement is activated locally in the skin in EM, and that B. garinii LU59 activates complement more than B. afzelii K78. Complement activation is pivotal for efficient phagocytosis of Borrelia spirochetes, especially in early infection before specific antibodies are produced. Both B. garinii LU59 and B. afzelii K78 induce proinflammatory cytokines rapidly, but no clear differences were seen between the two genospecies in this respect.

  • 106.
    Schilling, S
    et al.
    University Hospital Frankfurt.
    Follin, Per
    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.
    Jarhall, Boo
    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.
    Tegnell, A
    Swedish National Board for Health & Welfare.
    Lastilla, M
    Italian AF.
    Bannister, B
    Royal Free Hospital.
    Maria Fusco, F
    National Institute for Infectious Disease L Spallanzani.
    Biselli, R
    Italian AF.
    Brodt, H-R
    University Hospital Frankfurt.
    Puro, V
    National Institute for Infectious Disease L Spallanzani.
    European concepts for the domestic transport of highly infectious patients2009In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 15, no 8, p. 727-733Article, review/survey (Refereed)
    Abstract [en]

    Highly infectious diseases involve clinical syndromes ranging from single to multiorgan infections and pose a constant threat to the public. In the absence of a definite treatment for most causative agents, patients benefit from maximum supportive care as clinical conditions may deteriorate in the short term. Hence, following initial case identification and isolation, rapid transportation to a specialized treatment unit must be considered in order to minimize the risk of secondary infections, but this is limited by available infrastructure, accessible care en route and the patients clinical condition. Despite the development of consensus curricula for the clinical management of highly infectious patients, medical transportation lacks a common European approach. This article describes, as examples, three current European concepts for the domestic relocation of highly infectious patients by ground vehicles and aircraft with respect to national legislation and geography.

  • 107.
    Sjöwall, Christoffer
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Cardell, Kristina
    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.
    Bokarewa, Maria I
    University of Gothenburg.
    Enocsson, Helena
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Lindvall, Liselott
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Frydén, Aril
    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.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation2012In: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, Vol. 73, no 4, p. 382-388Article in journal (Refereed)
    Abstract [en]

    The presence of autoantibodies against C-reactive protein (anti-CRP) has been reported in association with autoimmunity and histopathology in chronic hepatitis C virus (HCV) infection. Resistin could play a role in the pathogenesis of hepatitis, although results on HCV infection are ambiguous. Here we retrospectively analyzed anti-CRP and resistin levels in the sera of 38 untreated and well-characterized HCV patients at the time of their first liver biopsy. HCV activity and general health were assessed by a physician at least yearly until follow-up ended. Anti-CRP and resistin were also measured in patients with autoimmune hepatitis (AIH) and nonalcoholic fatty liver disease (NAFLD). Anti-CRP antibodies were registered in all HCV patients, whereas only a few AIH (11%) and NAFLD (12%) sera were positive. Anti-CRP levels were related to histopathological severity and were highest in patients with cirrhosis at baseline. Resistin levels were similar in HCV, AIH, and NAFLD patients, but high levels of resistin were associated with early mortality in HCV patients. Neither anti-CRP nor resistin predicted a response to interferon-based therapy or cirrhosis development or was associated with liver-related mortality. We conclude that anti-CRP antibodies are frequently observed in chronic HCV infection and could be a useful marker of advanced fibrosis and portal inflammation.

  • 108.
    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: 2013-08-29
    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: 2017-12-12
    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: 2013-08-29Bibliographically 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: 2017-12-13
  • 109.
    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.

  • 110.
    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.

  • 111.
    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, ISSN 1471-2334, 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.

  • 112.
    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.

  • 113.
    Skogman, Barbro H
    et al.
    Falun General Hospital.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    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.
    Seroprevalence of Borrelia IgG antibodies among young Swedish children in relation to reported tick bites, symptoms and previous treatment for Lyme borreliosis: a population-based survey2010In: ARCHIVES OF DISEASE IN CHILDHOOD, ISSN 0003-9888, Vol. 95, no 12, p. 1013-1016Article in journal (Refereed)
    Abstract [en]

    Background Lyme borreliosis (LB) is the most common tickborne infection in Sweden and the seroprevalence of Borrelia immunoglobulin G (IgG) antibodies varies between 2% and 26%. The seroprevalence in young Swedish children is unknown and the relation to clinical data has not been previously studied. Objective To determine the seroprevalence of Borrelia IgG antibodies in serum of young Swedish children and to relate it to gender, geographical location, reported tick bites, symptoms and previous treatment for LB. Methods 2000 healthy 5-year-old children (n=2000) were randomly selected from among participants of a larger prospective population-based study, the ABIS (All Babies in Southeast Sweden) study. Serum samples were collected and a Borrelia specific ELISA test (Dako) were performed for IgG antibody detection. Clinical data were collected from questionnaires completed by the parents. Results The seroprevalence of Borrelia IgG antibodies was 3.2% (64/2000). Previous tick bite had been noted in 66% of these seropositive children but the majority (94%) had not previously been treated for LB. In addition, another 55 children reported a history of LB but were negative to Borrelia IgG antibodies in serum. Many of these seronegative children had received treatment for erythema migrans (n=24), which is a clinical diagnosis. Whether children were correctly treated or overtreated for LB is however unknown. No differences in gender, geographical location or reported tick bites were found when comparing Borrelia-seropositive children (n=64) and seronegative children with previous LB (n=55). Conclusion This population-based study demonstrates a Borrelia IgG antibody seroprevalence of 3.2% in young Swedish children. Very few of these seropositive children report previous symptoms or treatment for LB. Thus the findings suggest that exposure to the Borrelia spirochaete (with subsequent antibody response in serum) does occur in young children, mostly without giving rise to clinical LB. Future studies on cell-mediated immune responses are needed to investigate explanatory immunological mechanisms.

  • 114.
    Skogman, Barbro H
    et al.
    Falun General Hospital, Sweden Centre Clin Research Dalarna, Sweden .
    Glimaker, Kajsa
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nordwall, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Norrköping.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ödkvist, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    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.
    Long-term Clinical Outcome After Lyme Neuroborreliosis in Childhood2012In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 130, no 2, p. 262-269Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To determine long-term clinical outcome in children with confirmed Lyme neuroborreliosis (LNB) and to evaluate persistent subjective symptoms compared with a control group. less thanbrgreater than less thanbrgreater thanMETHODS: After a median of 5 years, 84 children with confirmed LNB underwent a neurologic re-examination, including a questionnaire. Medical records were analyzed, and a control group (n = 84) was included. less thanbrgreater than less thanbrgreater thanRESULTS: The total recovery rate was 73% (n = 61). Objective neurologic findings, defined as "definite sequelae," were found in 16 patients (19%). The majority of these children had persistent facial nerve palsy (n = 11), but other motor or sensory deficits occurred (n = 5). Neurologic signs and/or symptoms defined as "possible sequelae" were found in another 7 patients (8%), mainly of sensory character. Nonspecific subjective symptoms were reported by 35 patients (42%) and 32 controls (38%) (nonsignificant). Affected daily activities or school performance were reported to the same extent in both groups (23% vs 20%, nonsignificant). less thanbrgreater than less thanbrgreater thanCONCLUSIONS: The long-term clinical recovery rate was 73% in children with confirmed LNB. Persistent facial nerve palsy occurred in 13%, whereas other motor or sensory deficits were found in another 14%. Neurologic deficits did not affect daily activities or school performance more often among patients than controls and should be considered as mild. Furthermore, nonspecific subjective symptoms such as headache, fatigue, or memory or concentration problems were reported as often among patients as controls and should not be considered as sequelae after LNB.

  • 115.
    Skogman, Barbro H
    et al.
    Falun General Hospital.
    Hellberg, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. 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.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Bergström, Sven
    Umeå University.
    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.
    Adaptive and Innate Immune Responsiveness to Borrelia burgdorferi sensu lato in Exposed Asymptomatic Children and Children with Previous Clinical Lyme Borreliosis2012In: Clinical & Developmental Immunology, ISSN 1740-2522, E-ISSN 1740-2530, Vol. 2012, no 294587Article in journal (Refereed)
    Abstract [en]

    Why some individuals develop clinical manifestations in Lyme borreliosis (LB) while others remain asymptomatic is largely unknown. Therefore, we wanted to investigate adaptive and innate immune responsiveness to Borrelia burgdorferi sensu lato in exposed Borrelia-antibody-positive asymptomatic children (n = 20), children with previous clinical LB (n = 24), and controls (n = 20). Blood samples were analyzed for Borrelia-specific interferon (IFN)-gamma, interleukin (IL)-4, and IL-17 secretion by ELISPOT and Borrelia-induced IL-1 beta, IL-6, IL-10, IL-12(p70), and tumor necrosis factor (TNF) secretion by Luminex. We found no significant differences in cytokine secretion between groups, but a tendency towards an increased spontaneous secretion of IL-6 was found among children with previous clinical LB. In conclusion, the adaptive or innate immune responsiveness to Borrelia burgdorferi sensu lato was similar in Borrelia-exposed asymptomatic children and children with previous clinical LB. Thus, the immunological mechanisms of importance for eradicating the spirochete effectively without developing clinical manifestations of LB remain unknown.

  • 116.
    Sorensen, O
    et al.
    Rigshosp, Dept Hematol, Granulocyte Res Lab, DK-2100 Copenhagen, Denmark Rigshosp, Dept Biochem, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Netherlands Canc Inst, Div Cell Biol, Amsterdam, Netherlands.
    Johnsen, AH
    Follin, Per
    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.
    Calafat, J
    Rigshosp, Dept Hematol, Granulocyte Res Lab, DK-2100 Copenhagen, Denmark Rigshosp, Dept Biochem, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Netherlands Canc Inst, Div Cell Biol, Amsterdam, Netherlands.
    Borregaard, N
    Rigshosp, Dept Hematol, Granulocyte Res Lab, DK-2100 Copenhagen, Denmark Rigshosp, Dept Biochem, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Netherlands Canc Inst, Div Cell Biol, Amsterdam, Netherlands.
    The human antibacterial cathelicidin, hCAP-18, is activated by extracellular cleavage by elastase.1999In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 94, no 10, p. 918-Conference paper (Other academic)
  • 117.
    Sorensen, OE
    et al.
    Rigshosp, Granulocyte Res Lab, Dept Hematol, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark Netherlands Canc Inst, Dept Cell Biol, Amsterdam, Netherlands Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands.
    Follin, Per
    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.
    Johnsen, AH
    Calafat, J
    Rigshosp, Granulocyte Res Lab, Dept Hematol, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark Netherlands Canc Inst, Dept Cell Biol, Amsterdam, Netherlands Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands.
    Tjabringa, GS
    Rigshosp, Granulocyte Res Lab, Dept Hematol, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark Netherlands Canc Inst, Dept Cell Biol, Amsterdam, Netherlands Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands.
    Hiemstra, PS
    Rigshosp, Granulocyte Res Lab, Dept Hematol, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark Netherlands Canc Inst, Dept Cell Biol, Amsterdam, Netherlands Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands.
    Borregaard, N
    Rigshosp, Granulocyte Res Lab, Dept Hematol, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark Netherlands Canc Inst, Dept Cell Biol, Amsterdam, Netherlands Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands.
    The human cathelicidin, hCAP-18, is processed extracellularly to the antimicrobial peptide LL-37 by proteinase 3.2000In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 96, no 11, p. 2608-Conference paper (Other academic)
  • 118.
    Sowdamini Nakka, Sravya
    et al.
    PEAS Institut, Linköping, Sweden.
    Johansson, Jessica
    Örebro University, Sweden.
    Shahzad, Fasial
    PEAS Institut, Linköping, Sweden.
    Hanning, Anders
    Episentec AB, Sollentuna, Sweden.
    Nayeri, Fariba
    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. PEAS Institut, Linköping.
    A methachromatic-based experimental model for identification of bowel as the focus of an acute inflammation2013In: Open Journal of Gastroenterology, ISSN 2163-9450, E-ISSN 2163-9469, Vol. 3, no 1, p. 42-48Article in journal (Refereed)
    Abstract [en]

    Diarrhea is the most common symptom of acute inflammation in gastrointestinal tract and the patients are isolated in order to inhibit transmission and to conduct investigations. Yet there is no standard test to distinguish gastrointestinal infection from more generalized diseases at admittance which might cause delay in therapy. Hepatocyte growth factor (HGF) is produced upon injury by mesenchymal cells. On the contrary to chronic inflammation, HGF produced in the course of acute inflammation is biologically active and shows binding affinity to heparan sulphate proteoglycan (HSPG) and dextran sulphate (DS). Based on this phenomenon, an agarose gel containing DS was prepared and immobilized on loops to investigate the feces samples for the presence or absence of growth factors such as HGF with affinity to DS. The study is conducted as a clinical evaluation of an experimental model to distinguish acute infectious gastroenteritis from other causes of diarrhea. 656 fecal samples gathered consequently from patients seeking for bowel disturbances and healthy were tested by the test and the medical reports were investigated. Upon interaction with DS, methylene blue changes color to pink. This phenomenon was inhibited by HGF and converted by addition of anti-HGF antibodies to the samples. The test distinguished acute infectious gastroenteritis with high sensitivity and specificity (96% and 92% respectively) from other causes of diarrhea. We introduce a metachromatic experimental model that might distinguish acute inflammation in alimentary tract from other causes of diarrhea. This model might be used in developing rapid diagnostic tests.

  • 119.
    Stjernman, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Grännö, Christer
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Bodemar, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Järnerot, Ggunnar
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Ockander, Leif
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Tysk, Curt
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Blomberg, Björn
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Evaluation of the Inflammatory Bowel Disease Questionnaire in Swedish patients with Crohn's disease2006In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 41, no 8, p. 934-943Article in journal (Refereed)
    Abstract [en]

    Objective. Health-related quality of life (HRQoL) is an important measure of inflammatory bowel disease (IBD) health outcome. The Inflammatory Bowel Disease Questionnaire (IBDQ) comprising 32 items grouped into four dimensions is a widely used IBD-specific HRQoL instrument. The purpose of this study was to evaluate the validity, reliability and responsiveness of the Swedish translation of the IBDQ in patients with Crohn's disease (CD). Material and methods. Four hundred and forty-eight patients with CD completed the IBDQ and three other HRQoL questionnaires (Rating Form of IBD Patient Concerns, Short Form-36, and the Psychological General Well-Being Index) in connection with their regular visit at the outpatient clinic. Disease activity was assessed by the physician on a 4-point Likert scale. Thirty-two patients who were stable in remission completed the questionnaires a second time, 4 weeks later. A total of 418 patients repeated all measurements after 6 months. Results. The dimensional scores were highly correlated with other measures of corresponding aspects of HRQoL and were significantly better in remission than in relapse. High test-retest correlations indicated good reliability. Responsiveness was confirmed in patients whose disease activity changed over time. However, high correlations between the dimensions, poor correlations between items within each dimension, and factor analysis all indicated that the original grouping of the items is not valid for Swedish CD patients. Conclusions. Although the Swedish IBDQ has good external validity, reliability and responsiveness for patients with CD, our results did not support the original grouping of the items. © 2006 Taylor & Francis.

  • 120.
    Stjernman, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Grännö, Christer
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Järnerot, Gunnar
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Ockander, Leif
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Tysk, Curt
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden, Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Blomberg, Björn
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Short health scale: A valid, reliable, and responsive instrument for subjective health assessment in Crohn's disease2008In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 14, no 1, p. 47-52Article in journal (Refereed)
    Abstract [en]

    Background: Health-related quality of life (HRQoL) is an essential part of inflammatory bowel disease (IBD) assessment. The Short Health Scale (SHS), an HRQoL questionnaire in which the patients rate the disease impact on 4 important aspects of subjective health (symptoms, function, worry, and general well-being) was demonstrated in a previous study to be valid, reliable, and responsive in patients with ulcerative colitis. The present study evaluates the SHS in patients with Crohn's disease (CD). Methods: In all, 367 CD patients completed the SHS and 4 other HRQoL questionnaires (IBDQ, SF-36, RFIPC, and PGWB) at their regular outpatient visits. Then 330 patients completed the questionnaires at a second visit 6 months later. In addition, reliability data were obtained from repeat measurements 4 weeks after the first visit in 40 patients stable in remission. Results: Patients in remission scored better on all 4 questions than those with active disease (P < 0.001). All 4 questions were strongly correlated with the corresponding dimensions of the other HRQoL questionnaires (rS = 0.74-0.83). Reliability was confirmed with strong test-retest correlations (rS = 0.69-0.82) and intraclass correlation coefficients (0.66-0.77). Patients who changed from remission to active disease or vice versa showed a significant change in all 4 SHS scores (P < 0.005). Conclusions: SHS is a valid, reliable and responsive HRQoL instrument also in patients with CD. It is easily completed by the patient and requires no further calculation by the investigator. SHS gives a comprehensive overview of the main aspects of the patient's subjective health perception and is a useful tool in both clinical practice and clinical studies. Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.

  • 121.
    Stjernman, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Svensson, Erland
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Structural Equation Modeling of the Relationship between Disease Activity and Health-related Quality of Life Variables in Crohn’s DiseaseManuscript (preprint) (Other academic)
    Abstract [en]

    Objective. Disease activity (DA) and health-related quality of life (HRQL) are two major endpoints in outcome assessment of Crohn’s disease (CD).  A health concept model of the relationship between DA and HRQL encompassing five dimensions (biological variables, symptoms, function, worries, and general well-being) in inflammatory bowel disease (IBD) has been postulated previously, forming the basis of the IBD HRQL instrument, the Short Health Scale (SHS). This study evaluates the model, using structural equation modeling technique (SEM) on DA and HRQL data from a cohort of CD patients.

    Methods. The relationships of the five dimensions represented by 14 health measures of 283 CD patients were analyzed by confirmatory factor analysis and SEM, using SPSS AMOS v18.0.

    Results. All parameter estimates proved significant, and the goodness-of-fit indices were good (χ2=104.2, df=69, p=0.004, CFI=0.986, RMSEA=0.043). A revision of the structural pathway, in which well-being precedes worries, was suggested from empirical data.

    Conclusion. The postulated health concept model proved to be a valid and plausible approximation of the relationship between disease activity and subjective health perception in CD. The results support the use of the SHS for subjective health assessment in CD.

  • 122.
    Stjernman, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Tysk, Curt
    Orebro Univ Hosp, Dept Med, Div Gastroenterol, Orebro, Sweden.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Factors Predicting the Outcome of Disease Activity Assessment in Crohns Disease2009In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 15, no 12, p. 1859-1866Article in journal (Refereed)
    Abstract [en]

    Background: The Crohns Disease Activity Index (CDAI) has become the gold standard for assessment of disease activity in CD. This study investigated the relationship between CDAI and the physicians global assessment of disease activity (PGA) and whether different demographic and disease-related factors predict the outcome. Methods: Multiple linear regression analysis was used to investigate the relationship between CDAI and PGA obtained from 405 CD patients. Predictors of the CDAI and the PGA outcome were identified. Results: The correlation between CDAI and PGA was moderate. In patients with CDAI greater than 150, 72% of the total score were derived froth the subjective variables. The regression coefficients were not significant for 3 of the CDAI variables. In regression analysis, C-reactive protein (CRP), stenosis, smoking, bowel resection, concomitant disease, and gender predicted the CDAI outcome. The PGA outcome was predicted only by CRP, stenosis, and fistula. Conclusions: The correlation between CDAI and PGA was moderate and the subjective variables had a high impact on CDAI. Factors with no obvious relation to inflammatory activity predicted the outcome of CDAI, but not PGA. In trials of CD therapies, separation of subjective (symptoms, well-being) from objective (endoscopy, inflammatory markers) variables should be considered in the assessment of disease activity.

  • 123.
    Stjernman, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Tysk, Curt
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, S-701 85 Örebro/School of Health and Medical Sciences, Örebro University, Örebro; Sweden.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Unfavourable outcome for women in a study of health-related quality of life, social factors, and work disability in Crohn’s disease2011In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 23, no 8, p. 671-679Article in journal (Refereed)
    Abstract [en]

    Objective. The aim was to describe health-related quality of life (HRQL) and social factors, sickness and disability variables in a large population-based cohort of patients with Crohn’s disease (CD).

    Methods. HRQL was measured with SF-36 in 497 adult CD patients at three outpatient clinics. Comparisons were made with age-gender-matched background population and with ulcerative colitis (UC). Social factors, employment, sickness compensation, and disability pension for CD, were compared with national population registers.

    Results. CD had a greater negative effect on HRQL than did UC. This difference was more pronounced for women. Compared with background population, CD patients had lower educational level, and had a two-fold rise in long-term sickness and disability pension rate. CD women had higher rates of sickness and disability than CD men and were more often living single, though procreation was not affected.

    Conclusion. This study characterized the burden of CD in a large population-based cohort. CD had higher impact on HRQL, compared with UC. CD women had worse outcome in subjective health status, but not in objective assessment of disease activity. Women also had higher rates of sickness, disability pension, and single living. The mechanism underlying the gender-related inequalities in outcome for CD warrants further elucidation.

  • 124.
    Sundén, Birgitta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Falkeborn, Tina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Forsum, Urban
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Lindh, Magnus
    University of Gothenburg.
    Ydrenius, Liselotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Åkerlind, Britt
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Real-time PCR detection of Human Herpesvirus 1-5 in patients lacking clinical signs of a viral CNS infection2011In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 11, no 220Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Infections of the central nervous system (CNS) with herpes- or enterovirus can be self-limiting and benign, but occasionally result in severe and fatal disease. The polymerase chain reaction (PCR) has revolutionized the diagnostics of viral pathogens, and by multiple displacement amplification (MDA) prior to real-time PCR the sensitivity might be further enhanced. The aim of this study was to investigate if herpes- or enterovirus can be detected in cerebrospinal fluid (CSF) from patients without symptoms.

    METHODS:

    Cerebrospinal fluid (CSF) samples from 373 patients lacking typical symptoms of viral CNS infection were analysed by real-time PCR targeting herpesviruses or enteroviruses with or without prior MDA.

    RESULTS:

    In total, virus was detected in 17 patients (4%). Epstein-Barr virus (EBV) was most commonly detected, in general from patients with other conditions (e.g. infections, cerebral hemorrhage). MDA satisfactorily amplified viral DNA in the absence of human nucleic acids, but showed poor amplification capacity for viral DNA in CSF samples, and did not increase the sensitivity for herpes virus-detection with our methodology.

    CONCLUSIONS:

    Viral pathogens are rarely detected in CSF from patients without signs of CNS infection, supporting the view that real-time PCR is a highly specific method to detect symptomatic CNS-infection caused by these viruses. However, EBV may be subclinically reactivated due to other pathological conditions in the CNS.

  • 125.
    Taxbro, Knut
    et al.
    Ryhov County Hospital, Sweden .
    Berg, Sören
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Hammarskjold, Fredrik
    Ryhov County Hospital, Sweden .
    Hanberger, Håkan
    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.
    Malmvall, Bo-Erik
    Jonköping County Council, Sweden .
    A prospective observational study on 249 subcutaneous central vein access ports in a Swedish county hospital2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 5, p. 893-901Article in journal (Refereed)
    Abstract [en]

    Background. Reliable central vein access is a fundamental issue in modern advanced oncological care. The aim of this study was to determine the incidence of complications and patient perception regarding central vein access ports. Methods. We prospectively studied 249 single lumen access ports implanted between 1 July 2008 and 15 March 2010 in a mixed patient population at a 500-bed secondary level hospital in Sweden. We determined the number of catheter days, infection rate and mechanical complications, as well as patient satisfaction regarding the access port, over a six-month follow-up period. Results. Two hundred and forty-four different patients received 249 ports yielding a total of 37 763 catheter days. Ultrasound and fluoroscopic guidance was used in 98% of procedures. Vein access was obtained percutanously by an anaesthesiologist in all cases. There was no case of pneumo- or haemothorax. The incidence of catheter-related bloodstream infection, was 0.05/1000 catheter days and the incidence of pocket/tunnel infection was 0.39/1000 catheter days. Clinically apparent deep vein thrombosis occurred in four patients (1.6%). Patient satisfaction was overall high. Conclusion. These results confirm that our team-based approach with written easily accessible evidence-based guidelines and a structured education programme leads to a very low complication rate and a high degree of patient satisfaction.

  • 126.
    Tegnell, Anders
    et al.
    The Swedish Institute of Infectious Disease Control, Solna, Sweden.
    Grabowska, Katarzyna
    The Swedish Institute of Infectious Disease Control, Solna, Sweden.
    Jacobsson, Anders
    Department of Mathematical Statistics, Stockholm University, Stockholm, Sweden.
    Andersson, Mikael
    Department of Mathematical Statistics, Stockholm University, Stockholm, Sweden.
    Giesecke, Johan
    The Swedish Institute of Infectious Disease Control, Solna, Sweden.
    Öhman, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Study of developed resistance due to antibiotic treatment of coagulase-negative staphylococci2003In: Microbial Drug Resistance, ISSN 1076-6294, E-ISSN 1931-8448, Vol. 9, no 1, p. 1-6Article in journal (Refereed)
    Abstract [en]

    Coagulase-negative Staphylococci (CoNS) are a major cause of postoperative infections. These infections are often associated with foreign material implants and/or a compromised immune system in the patient. Multiresistant strains are increasingly common in the hospital environment and there is concern that the infections will become difficult or impossible to treat. This report is based on a study of 75 patients, with postoperative infections caused by CoNS after thoracic surgery. All patients were treated with surgical revision and antibiotic therapy. One or more bacterial cultures were made in each case, and the resistance pattern of the CoNS found was determined. The goal of the study was to evaluate possible relationships between antibiotic therapy and the appearance of resistance to antibiotics in CoNS found. To describe this relationship, three models were constructed and analyzed by multiple logistic regression. The results indicate an increased resistance to β-lactam antibiotics and clindamycin after the use of cephalosporins. Also, the use of vancomycin or vancomycin combination with rifampicin or fusidic acid increases the risk for development of resistance to β-lactam antibiotics, ciprofloxacin, fusidic acid, clindamycin, netilmycin, and rifampicin. The hypothesis that a combination of antibiotics will curtail the development of resistance was not supported in this study.

  • 127.
    Tjernberg, Ivar
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Laboratory Diagnosis of Lyme Borreliosis: Anti-Borrelia Antibodies and the Chemokine CXCL132011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Lyme borreliosis (LB), the most common tick-borne disease in Europe and North America, is caused by spirochetes of the Borrelia burgdorferi sensu lato complex. The spirochetes can invade several different organs, thereby causing many different symptoms and signs. Diagnosis of LB relies on patient history, physical examination, and detection of anti-Borrelia antibodies. However, anti-Borrelia antibodies are not always detectable, and they commonly persist even after LB is successfully treated or spontaneously healed.

    The aim of my work was to study diagnostic aspects on clinical cases of LB and control subjects in an area endemic to LB, with a focus on newly developed anti-Borrelia antibody tests. A total of 617 patients with symptoms and/or signs consistent with LB, as well as 255 control subjects, were studied. The diagnostic panel included the following new LB tests: Immunetics Quick ELISA C6 Borrelia assay kit (C6), invariable region 6 peptide antibody assays (IR6), Liaison Borrelia CLIA (Li) and the chemokine CXCL13. Results were compared with the older Virotech Borrelia burgdorferi ELISA (VT) and with a Western blot method, the Virotech Borrelia Ecoline IgG/IgM Line Immunoblot (WB EL), when appropriate.

    In general, no significant differences were noted between the C6, VT and Li tests regarding serosensitivity in various LB manifestations. However, the seropositivity rate was lower for the C6 test compared with the VT and Li tests 2–3 and 6 months after diagnosis of erythema migrans (EM), indicating normalization of antibody levels. In addition, EM patients reporting a previous LB episode had a C6 seropositivity rate similar to that of patients without a previous LB episode, and seroprevalence in healthy blood donors was lower in the C6 test than the VT and Li tests. Taken together, these results support the recommendation of the serum C6 test as a Borrelia serological test due to its ability to reflect ongoing or recent infection.

    Although the majority of EM patients at presentation showed concordant serological responses to IR6 peptides representing the three main Borrelia species and the C6 peptide, there were also clinical EM cases that were C6-negative and could be detected mainly by a seroresponse to a B. burgdorferi sensu stricto-derived IR6 peptide. Thus, an antibody test combining antigens could be of value in the serodiagnosis of LB in Europe.

    The serosensitivity of the C6 test in cases of Lyme neuroborreliosis (LNB) was shown to be associated with symptom duration. A serosensitivity rate of 93% was found in LNB patients ³ 12 years of age with a symptom duration of more than 30 days. Therefore, a negative C6 test in serum in such a patient argues against an LNB diagnosis.

    The presence of chemokine CXCL13 in cerebrospinal fluid was confirmed to be a reliable marker of LNB. CXCL13 differentiated LNB from other conditions and also indicated a high probability of LNB in children with short symptom duration where anti-Borrelia antibodies were still lacking in the cerebrospinal fluid.

    A two-tiered approach (C6 test in combination with WB EL) showed no significant improvement in specificity over the C6 test alone. However, WB EL may be useful in diagnosing suspected cases of acrodermatitis chronicum atrophicans and Lyme arthritis, usually displaying multiple IgG bands.

    In conclusion, although the serodiagnosis of LB remains to be settled, this thesis provides some practical tools regarding the use and interpretation of Borrelia serology including proposed diagnostic routines.

    List of papers
    1. C6 peptide ELISA test in the serodiagnosis of Lyme borreliosis in Sweden.
    Open this publication in new window or tab >>C6 peptide ELISA test in the serodiagnosis of Lyme borreliosis in Sweden.
    2007 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 26, no 1, p. 37-42Article in journal (Refereed) Published
    Abstract [en]

    The aim of this study was to evaluate the synthetic C6 peptide test as a first-line test in a two-tiered scheme for Borrelia serology in a clinically well-characterized population of patients with Lyme borreliosis in Kalmar County, Sweden. The study population consisted of a prospective group (n = 200), a control group (n = 255), and a retrospective group (n = 29). The test panel consisted of the Immunetics Quick ELISA C6 Borrelia assay kit (Immunetics, Cambridge, MA, USA), the Virotech Borrelia burgdorferi ELISA (Genzyme Virotech, Rüsselsheim, Germany), and the Liaison Borrelia CLIA (DiaSorin, Saluggia, Vercelli, Italy). Seroprevalence among 200 healthy blood donors was significantly lower in the C6 test (8%) compared to the Virotech ELISA (14%) and the Liaison CLIA (12%). In convalescent sera (2-3 months and 6 months post infection) from 158 patients with erythema migrans, the seropositivity in the C6 test was also significantly lower compared to both the Virotech ELISA and the Liaison CLIA. Serosensitivity in the acute phase of erythema migrans and other clinical manifestations of borreliosis did not differ significantly between the C6 test and the Virotech ELISA or the Liaison CLIA. Overall, a positive C6 test seems to correlate well with acute borreliosis. Cross-reactivity was lower in the C6 test in sera positive for Epstein-Barr virus infection as compared to the Virotech ELISA. This study supports the use of the C6 test as a screening test for borreliosis, in endemic areas.

    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:liu:diva-64731 (URN)10.1007/s10096-006-0239-3 (DOI)17180348 (PubMedID)
    Available from: 2011-02-03 Created: 2011-02-03 Last updated: 2017-12-11
    2. C6-peptide serology as diagnostic tool in neuroborreliosis
    Open this publication in new window or tab >>C6-peptide serology as diagnostic tool in neuroborreliosis
    Show others...
    2008 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 5, p. 393-399Article in journal (Refereed) Published
    Abstract [en]

    The aim of this study was to evaluate the usefulness of borrelia serology (Quick ELISA C6 Borrelia assay kit) as a diagnostic tool in cases of suspected neuroborreliosis. A retrospective patient material consisting of 124 paired serum and cerebrospinal fluid samples with a positive anti-borrelia antibody index (AI) using the IDEIA Lyme Neuroborreliosis test was compared with 124 AI-negative matched control subjects. The patients were divided into four groups based on presence of pleocytosis and age above or below 12 years. The presence of positive C6 serology in AI-positive patients with pleocytosis was 89% (83/93), significantly different (p<0.01) from in patients without pleocytosis (58%, 18/31). In AI-positive patients aged ≥12 years with pleocytosis, 94% (51/54) had a positive C6 serology. Of AI-positive patients with a symptom duration of more than 30 days, 93% (27/29) were positive by the C6 test. We conclude that the C6 serum test, together with clinical evaluation, is a powerful diagnostic tool in adult (≥12 years) European patients with suspected neuroborreliosis with a symptom duration of more than 30 days. Patients with suspected neuroborreliosis and positive C6 results should be further investigated by lumbar puncture for definite diagnosis. © The Authors 2008.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-43521 (URN)10.1111/j.1600-0463.2008.00842.x (DOI)74047 (Local ID)74047 (Archive number)74047 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
    3. Antibody responses to borrelia IR6 peptide variants and the C6 peptide in Swedish patients with erythema migrans
    Open this publication in new window or tab >>Antibody responses to borrelia IR6 peptide variants and the C6 peptide in Swedish patients with erythema migrans
    Show others...
    2009 (English)In: International Journal of Medical Microbiology, ISSN 1438-4221, Vol. 299, no 6, p. 439-446Article in journal (Refereed) Published
    Abstract [en]

    The aim of this study was to evaluate the antibody responses to different VlsE protein IR6 peptide variants and the synthetic C6 peptide in acute and convalescent (2-3 and 6 months) serum samples from Swedish patients with clinical erythema migrans (EM). Serum samples were prospectively collected from 148 patients with EM and compared to serum samples obtained from 200 healthy blood donors. The IgG responses to 3 IR6 peptide variants originating from Borrelia burgdorferi (B. burgdorferi) sensu stricto, B. garinii, and B. afzelii were measured by enzyme-linked immunosorbent assays (ELISAs) and compared to a commercial C6 peptide ELISA. Seropositivity rate in the IR6 or C6 peptide ELISAs ranged from 32% to 58% at presentation, 30-52% after 2-3 months, and 20-36% after 6 months. At presentation, positive antibodies in any of the 4 ELISAs were found in 66%. In 7/52 (13%), C6-negative EM cases, serological reaction was found to the B. burgdorferi sensu stricto-derived IR6 peptide. In patients reporting previous LB compared to those without previous LB, significantly higher seropositivity rates were noted for all IR6 peptides, but not for the C6 peptide. In the serology of EM in Europe, C6 ELISA does not seem to cover all cases. An ELISA using a mixture of B. burgdorferi sensu stricto IR6 peptide and the C6 peptide could be of value in the serodiagnosis of LB in Europe. Further studies on combinations of variant IR6 peptides and the C6 peptide in other manifestations of LB are needed to address this issue.

    Keywords
    C6; ELISA; Erythema migrans; IR6 peptide; Lyme borreliosis; Serology
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-21262 (URN)10.1016/j.ijmm.2008.10.006 (DOI)
    Note
    Original Publication: Ivar Tjernberg, H. Sillanpaa, I. Seppala, I. Eliasson, Pia Forsberg and P. Lahdenne, Antibody responses to borrelia IR6 peptide variants and the C6 peptide in Swedish patients with erythema migrans, 2009, International Journal of Medical Microbiology, (299), 6, 439-446. http://dx.doi.org/10.1016/j.ijmm.2008.10.006 Copyright: Elsevier Science B. V. Amsterdam http://www.elsevier.com/ Available from: 2009-09-30 Created: 2009-09-30 Last updated: 2011-02-18
    4. Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to the C6-peptide in Lyme neuroborreliosis.
    Open this publication in new window or tab >>Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to the C6-peptide in Lyme neuroborreliosis.
    Show others...
    2011 (English)In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 62, no 2, p. 149-158Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: The aim of this study was to evaluate the chemokine CXCL13 and C6 antibodies separately and in combination in paired serum/cerebrospinal fluid (CSF) samples in the laboratory diagnosis of Lyme neuroborreliosis (LNB).

    METHODS: A large retrospective material with paired serum/CSF samples from 261 patients with clinically suspected LNB was investigated. Patients were divided into three main diagnostic groups based on original results of CSF pleocytosis and intrathecal anti-borrelia antibodies (purified flagellum). Levels of CXCL13, albumin, total IgM and IgG in paired samples and C6 antibodies in CSF were compared across diagnostic groups.

    RESULTS: A sensitivity of 99% and a specificity of 96% were achieved for CSF-Serum CXCL13 ratio. CSF-C6 antibodies performed with a sensitivity of 99% and a specificity of 88.0%. A combination of CSF-Serum CXCL13 ratio and CSF-C6 antibodies, evaluated in parallel, revealed a sensitivity of 99% and specificity of 98%.

    CONCLUSIONS: This study confirms CSF-CXCL13 as a reliable marker of LNB and suggests improved diagnostic performance especially in children with possible LNB.

    Place, publisher, year, edition, pages
    Elsevier, 2011
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-65725 (URN)10.1016/j.jinf.2010.11.005 (DOI)000286981200006 ()21087629 (PubMedID)
    Note
    Original Publication: Ivar Tjernberg, Anna J Henningsson, Ingvar Eliasson, Pia Forsberg and Jan Ernerudh, Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to the C6-peptide in Lyme neuroborreliosis., 2011, Journal of Infection, (62), 2, 149-158. http://dx.doi.org/10.1016/j.jinf.2010.11.005 Copyright: Elsevier Science B.V., Amsterdam http://www.elsevier.com/ Available from: 2011-02-18 Created: 2011-02-18 Last updated: 2017-12-11
  • 128.
    Tjernberg, Ivar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Carlsson, Martin
    Kalmar County Hospital.
    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.
    Eliasson, Ingvar
    NAL, Trollhattan, Sweden .
    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.
    Mapping of hormones and cortisol responses in patients after Lyme neuroborreliosis2010In: BMC INFECTIOUS DISEASES, ISSN 1471-2334, Vol. 10, no 20Article in journal (Refereed)
    Abstract [en]

    Background: Persistent symptoms after treatment for neuroborreliosis are common for reasons mainly unknown. These symptoms are often unspecific and could be caused by dysfunctions in endocrine systems, an issue that has not been previously addressed systematically. We therefore mapped hormone levels in patients with previous confirmed Lyme neuroborreliosis of different outcomes and compared them with a healthy control group. Methods: Twenty patients of a retrospective cohort of patients treated for definite Lyme neuroborreliosis were recruited 2.3 to 3.7 years (median 2.7) after diagnosis, together with 23 healthy controls. Lyme neuroborreliosis patients were stratified into two groups according to a symptom/sign score. All participants underwent anthropometric and physiological investigation as well as an extensive biochemical endocrine investigation including a short high-dose adrenocorticotropic hormone stimulation (Synacthen (R)) test. In addition to hormonal status, we also examined electrolytes, 25-hydroxy-vitamin D and interleukin-6. Results: Eight patients (40%) had pronounced symptoms 2-3 years after treatment. This group had a higher cortisol response to synacthen as compared with both controls and the Lyme neuroborreliosis patients without remaining symptoms (p andlt; 0.001 for both comparisons). No other significant differences in the various baseline biochemical parameters, anthropometric or physiological data could be detected across groups. Conclusions: Apart from a positive association between the occurrence of long-lasting complaints after Lyme neuroborreliosis and cortisol response to synacthen, no corticotropic insufficiency or other serious hormonal dysfunction was found to be associated with remaining symptoms after treatment for Lyme neuroborreliosis.

  • 129.
    Tjernberg, Ivar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Henningsson, Anna J
    Ryhov County Hospital.
    Eliasson, Ingvar
    Norra Älvsborgs Länssjukhus.
    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.
    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.
    Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to the C6-peptide in Lyme neuroborreliosis.2011In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 62, no 2, p. 149-158Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim of this study was to evaluate the chemokine CXCL13 and C6 antibodies separately and in combination in paired serum/cerebrospinal fluid (CSF) samples in the laboratory diagnosis of Lyme neuroborreliosis (LNB).

    METHODS: A large retrospective material with paired serum/CSF samples from 261 patients with clinically suspected LNB was investigated. Patients were divided into three main diagnostic groups based on original results of CSF pleocytosis and intrathecal anti-borrelia antibodies (purified flagellum). Levels of CXCL13, albumin, total IgM and IgG in paired samples and C6 antibodies in CSF were compared across diagnostic groups.

    RESULTS: A sensitivity of 99% and a specificity of 96% were achieved for CSF-Serum CXCL13 ratio. CSF-C6 antibodies performed with a sensitivity of 99% and a specificity of 88.0%. A combination of CSF-Serum CXCL13 ratio and CSF-C6 antibodies, evaluated in parallel, revealed a sensitivity of 99% and specificity of 98%.

    CONCLUSIONS: This study confirms CSF-CXCL13 as a reliable marker of LNB and suggests improved diagnostic performance especially in children with possible LNB.

  • 130.
    Tjernberg, Ivar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases .
    Schön, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology .
    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.
    Carlsson-Wistedt, Annika
    Clinical Microbiology Kalmar County Hospital, Kalmar.
    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.
    Eliasson, Ingvar
    Department of Clinical Microbiology and Immunology Lund University Hospital.
    C6-peptide serology as diagnostic tool in neuroborreliosis2008In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 5, p. 393-399Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate the usefulness of borrelia serology (Quick ELISA C6 Borrelia assay kit) as a diagnostic tool in cases of suspected neuroborreliosis. A retrospective patient material consisting of 124 paired serum and cerebrospinal fluid samples with a positive anti-borrelia antibody index (AI) using the IDEIA Lyme Neuroborreliosis test was compared with 124 AI-negative matched control subjects. The patients were divided into four groups based on presence of pleocytosis and age above or below 12 years. The presence of positive C6 serology in AI-positive patients with pleocytosis was 89% (83/93), significantly different (p<0.01) from in patients without pleocytosis (58%, 18/31). In AI-positive patients aged ≥12 years with pleocytosis, 94% (51/54) had a positive C6 serology. Of AI-positive patients with a symptom duration of more than 30 days, 93% (27/29) were positive by the C6 test. We conclude that the C6 serum test, together with clinical evaluation, is a powerful diagnostic tool in adult (≥12 years) European patients with suspected neuroborreliosis with a symptom duration of more than 30 days. Patients with suspected neuroborreliosis and positive C6 results should be further investigated by lumbar puncture for definite diagnosis. © The Authors 2008.

  • 131.
    Tjernberg, Ivar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Sillanpaa, H.
    Haartman Institute, Helsinki.
    Seppala, I.
    Haartman Institute, Helsinki.
    Eliasson, I.
    Lund University Hospital.
    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.
    Lahdenne, P.
    University of Helsinki, Helsinki.
    Antibody responses to borrelia IR6 peptide variants and the C6 peptide in Swedish patients with erythema migrans2009In: International Journal of Medical Microbiology, ISSN 1438-4221, Vol. 299, no 6, p. 439-446Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate the antibody responses to different VlsE protein IR6 peptide variants and the synthetic C6 peptide in acute and convalescent (2-3 and 6 months) serum samples from Swedish patients with clinical erythema migrans (EM). Serum samples were prospectively collected from 148 patients with EM and compared to serum samples obtained from 200 healthy blood donors. The IgG responses to 3 IR6 peptide variants originating from Borrelia burgdorferi (B. burgdorferi) sensu stricto, B. garinii, and B. afzelii were measured by enzyme-linked immunosorbent assays (ELISAs) and compared to a commercial C6 peptide ELISA. Seropositivity rate in the IR6 or C6 peptide ELISAs ranged from 32% to 58% at presentation, 30-52% after 2-3 months, and 20-36% after 6 months. At presentation, positive antibodies in any of the 4 ELISAs were found in 66%. In 7/52 (13%), C6-negative EM cases, serological reaction was found to the B. burgdorferi sensu stricto-derived IR6 peptide. In patients reporting previous LB compared to those without previous LB, significantly higher seropositivity rates were noted for all IR6 peptides, but not for the C6 peptide. In the serology of EM in Europe, C6 ELISA does not seem to cover all cases. An ELISA using a mixture of B. burgdorferi sensu stricto IR6 peptide and the C6 peptide could be of value in the serodiagnosis of LB in Europe. Further studies on combinations of variant IR6 peptides and the C6 peptide in other manifestations of LB are needed to address this issue.

  • 132.
    Tärnberg, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Östholm Balkhed, Åse
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Monstein, Hans-Jurg
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Hällgren, Anita
    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.
    Hanberger, Håkan
    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.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    In vitro activity of beta-lactam antibiotics against CTX-M-producing Escherichia coli2011In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 30, no 8, p. 981-987Article in journal (Refereed)
    Abstract [en]

    Beta-lactam antibiotics have been discussed as options for the treatment of infections caused by multiresistant extended-spectrum beta-lactamase (ESBL)-producing bacteria if the minimum inhibitory concentration (MIC) is low. The objective of this study was to investigate the in vitro activity of different beta-lactam antibiotics against CTX-M-producing Escherichia coli. A total of 198 isolates of E. coli with the ESBL phenotype were studied. Polymerase chain reaction (PCR) amplification of CTX-M genes and amplicon sequencing were performed. The MICs for amoxicillin-clavulanic acid, aztreonam, cefepime, cefotaxime, ceftazidime, ceftibuten, ertapenem, imipenem, mecillinam, meropenem, piperacillin-tazobactam, and temocillin were determined with the Etest. Susceptibility was defined according to the breakpoints of the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MIC(50) and MIC(90) values were calculated. Isolates from CTX-M group 9 showed higher susceptibility to the beta-lactam antibiotics tested than isolates belonging to CTX-M group 1. More than 90% of the isolates belonging to CTX-M group 9 were susceptible to amoxicillin-clavulanic acid, ceftazidime, ceftibuten, piperacillin-tazobactam, and temocillin. The susceptibility was high to mecillinam, being 91%, regardless of the CTX-M group. All isolates were susceptible to imipenem and meropenem, and 99% to ertapenem. This study shows significant differences in susceptibility to different beta-lactam antibiotics among the CTX-M-producing E. coli isolates and a significant difference for many antibiotics tested between the CTX-M-producing groups 1 and 9. The good in vitro activity of other beta-lactam antibiotics compared to carbapenems indicate that clinical studies are warranted in order to examine the potential role of these beta-lactam antibiotics in the treatment of infections caused by multiresistant ESBL-producing E. coli.

  • 133.
    Uhlin, Fredrik
    et al.
    Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL. Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Nayeri, Tayeb
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, Kalmar County Hospital.
    Nayeri, Fariba
    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.
    Almroth, Gabriel
    Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL. Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Decreased Biological Activity of Hepatocyte Growth Factor during Chronic Renal Failure2009In: J Am Soc Nephrol, 2009Conference paper (Refereed)
  • 134.
    Uhnoo, I.
    et al.
    Dept. of Preclin./Clin. Assessment, Medical Products Agency, PO Box 26, SE-75103 Uppsala, Sweden, Section of Infectious Diseases, Department of Medical Sciences, University Hospital, Uppsala, Sweden.
    Linde, A.
    Department of Virology, Swedish Inst. for Infect. Dis. Ctrl., Solna, Sweden.
    Pauksens, K.
    Section of Infectious Diseases, Department of Medical Sciences, University Hospital, Uppsala, Sweden.
    Lindberg, A.
    Smittskyddsenheten, Halland, Sweden.
    Eriksson, M.
    Department of Paediatrics, Karolinska Institute, Stockholm, Sweden.
    Norrby, R.
    Department of Virology, Swedish Inst. for Infect. Dis. Ctrl., Solna, Sweden.
    Beermann, B.
    Dept. of Preclin./Clin. Assessment, Medical Products Agency, PO Box 26, SE-75103 Uppsala, Sweden.
    Brandt, C.
    Dept. of Preclin./Clin. Assessment, Medical Products Agency, PO Box 26, SE-75103 Uppsala, Sweden.
    Frydén, Aril
    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.
    Gothefors, L.
    Department of Paediatrics, University Hospital, Umeå, Sweden.
    Hakansson, J.
    Håkansson, J., Krokom Health Center, Krokom, Sweden.
    Claesson, B.
    Department of Paediatrics, University Hospital, Gothenburg, Sweden.
    Nivenius, K.
    Department of Paediatrics, University Hospital, Lund, Sweden.
    Petersson, C.
    Health Center, Växjö, Sweden.
    Schwan, A.
    Läkemedelskommittén, Uppsala, Sweden.
    Stahle, L.
    Ståhle, L., Department of Clinical Pharmacology, Karolinska Institute, University Hospital, Huddinge, Sweden.
    Trolin, I.
    Dept. of Preclin./Clin. Assessment, Medical Products Agency, PO Box 26, SE-75103 Uppsala, Sweden.
    Zweygberg, Wirgart B.
    Zweygberg Wirgart, B., Department of Clinical Microbiology, Karolinska Institute, Stockholm, Sweden.
    Treatment and prevention of influenza: Swedish recommendations2003In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 35, no 1Article in journal (Refereed)
    Abstract [en]

    The introduction of the 2 neuraminidase inhibitors (NAIs) zanamivir and oseltamivir has offered new options for the prevention and treatment of influenza. This article summarizes a Swedish consensus guidance document on the rational use of antiviral drugs in the management of influenza virus infections. Vaccination remains the cornerstone for influenza prophylaxis. Target groups for the annual vaccination programme are the 'at-risk' individuals, i.e. elderly patients (= 65 y) and patients with chronic pulmonary disease or cardiovascular disease or other chronic diseases predisposing for a complicated course of influenza. Antiviral drugs are not a substitute for influenza vaccination, but could be used as adjuncts. Currently, 3 drugs have been approved for the treatment of influenza, including zanamivir and oseltamivir and the M2 inhibitor amantadin. Amantadin has come to very limited use, has recently been withdrawn from the Swedish market and is available only on a named patient basis. Compared with amantadin, the NAIs have clear advantages because of their broader anti-influenza activity against both type A and B, improved safety profiles and low potential for inducing drug resistance. The NAIs are therefore recommended as first options in the treatment of influenza. Oseltamivir can be taken orally, whereas zanamivir is for oral inhalation. Limited in vitro and in vivo data suggest that oseltamivir is less potent against influenza B, whereas zanamivir seems equally effective against influenza A and B. In influenza-positive healthy adults and children, treated within 48 h after symptom onset, the NAIs shorten the duration of illness by about 1 d. No significant effect on the duration of symptoms has been documented in treated at-risk patients with influenza. Owing to their limited therapeutic benefit, general use of the NAIs in the treatment of influenza is not recommended, but they can be advocated on an individualized basis for patients with severe influenza who can start therapy within 48 h of the onset of symptoms. Zanamivir is the preferred choice in a confirmed influenza B epidemic. For prevention of influenza, 2 drugs are approved, oseltamivir in adults above 12 y old and amantadin in people above 10 y old. The 70-90% protective efficacy of oseltamivir for household postexposure prophylaxis and for seasonal prophylaxis is comparable to that reported for amantadin. Oseltamivir is the preferred drug for prophylactic use. Chemoprophylaxis is targeted at high-risk groups and should be considered on a case-by-case basis depending on the circumstances and the population requiring protection. A broader preventive use of oseltamivir can be advocated in at-risk groups during seasons when there is a poor antigenic match between the epidemic strains and the vaccine strains. Oseltamivir prophylaxis is otherwise recommended for patients unable to be vaccinated and for families exposed to influenza which include a member of the at-risk groups. In high-risk hospital units and in institutions caring for the elderly, oseltamivir prophylaxis, in combination with vaccination, can be recommended as measures to control an influenza outbreak.

  • 135.
    Vrethem, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Widhe, Mona
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. 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.
    Garpmo, Ulf
    Kalmar Hospital.
    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.
    Clinical, diagnostic and immunological characteristics of patients with possible neuroborreliosis without intrathecal Ig-synthesis against Borrelia antigen in the cerebrospinal fluid2011In: Neurology International, ISSN 2035-8385, E-ISSN 2035-8377, Vol. 3, no 1, article id e2Article in journal (Refereed)
    Abstract [en]

    The diagnosis of neuroborreliosis is not always straightforward. Intrathecal immunoglobulin (Ig) synthesis against Borrelia antigen may not be detected, at least early in the disease course. Also other neurological and infectious diagnoses have to be considered. We have studied patients with clinical possible neuroborreliosis without intrathecal Ig synthesis against Borrelia antigen in the cerebrospinal fluid (CSF) (n=17). Diagnosis was based on typical clinical history and at least one of the following findings; mononuclear leucocytosis in the CSF (n=4); typical erythema migrans >5 cm in diameter in relation to debut of symptoms (n=8); prompt clinical response to antibiotic teratment (n=14). Also other possible diagnoses had to be excluded. Seventeen patients first investigated because of suspected neuroborreliosis but later confirmed with other diagnoses were used as controls. All patients had a lumbar puncture. Borrelia specific IFN-γ and IL-4 secretion was investigated in peripheral blood (PBL) and CSF with an ELISPOT assay. Polymerase chain reaction (PCR) was used to reveal any Borrelia antigen in the CSF. Six of 17 patients with possible neuroborreliosis showed high IFN-g secretion in peripheral blood, otherwise we found no statistically significant differences between the groups. PCR did not reveal any Borrelia antigen in CSF. The diagnosis and treatment of possible but not confirmed neuroborreliosis is a clinical challenge. The clinical response to treatment may be the best option in these cases.

  • 136.
    Walther, Sten
    et al.
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Erlandsson, M.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Olsson-Liljequist, B.
    Smittskyddsinstitutet, Solna, Sweden.
    Hanberger, Håkan
    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.
    The Icustrama Study Group (2002),
    Burman, L.G.
    Smittskyddsinstitutet, Solna, Sweden.
    Cars, O.
    Smittskyddsinstitutet, Solna, Sweden.
    Gill, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Hoffman, Mikael
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Kahlmeter, G.
    Department of Clinical Microbiology, Växjö lasarett.
    Lindgren, S.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Antibiotic prescription practices, consumption and bacterial resistance in a cross section of Swedish intensive care units2002In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, Vol. 46, no 9, p. 1075-1081Article in journal (Refereed)
    Abstract [en]

    Background: The purpose of this work was to study usage of antibiotics, its possible determinants, and patterns of bacterial resistance in Swedish intensive care units (ICUs).

    Methods: Prospectively collected data on species and antibiotic resistance of clinical isolates and antibiotic consumption specific to each ICU in 1999 were analyzed together with answers to a questionnaire. Antibiotic usage was measured as defined daily doses per 1000 occupied bed days (DDD1000).

    Results: Data were obtained for 38 ICUs providing services to a population of approximately 6 million. The median antibiotic consumption was 1257 DDD1000 (range 584–2415) and correlated with the length of stay but not with the illness severity score or the ICU category. Antibiotic consumption was higher in the ICUs lacking bedside devices for hand disinfection (2193 vs. 1214 DDD1000, p=0.05). In the ICUs with a specialist in infectious diseases responsible for antibiotic treatment the consumption pattern was different only for use of glycopeptides (58% lower usage than in other ICUs: 26 vs. 11 DDD1000,P=0.02). Only 21% of the ICUs had a written guideline on the use of antibiotics, 57% received information on antibiotic usage at least every 3 months and 22% received aggregated resistance data annually. Clinically significant antimicrobial resistance was found among Enterbacter spp. to cephalosporins and among Enterococcus spp. to ampicillin.

    Conclusions: Availability of hand disinfection equipment at each bed and a specialist in infectious diseases responsible for antibiotic treatment were factors that correlated with lower antibiotic consumption in Swedish ICUs, whereas patient-related factors were not associated with antibiotic usage.

  • 137.
    Widhe, Mona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Jarefors, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Hedin-Skogman, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Peterson, E. M.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Bergstrom, S.
    University of Umeå.
    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.
    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.
    T-Cell Epitope Mapping of the Borrelia garinii Outer Surface Protein A in Lyme Neuroborreliosis2009In: SCANDINAVIAN JOURNAL OF IMMUNOLOGY, ISSN 0300-9475, Vol. 70, no 2, p. 141-148Article in journal (Refereed)
    Abstract [en]

    We studied the T-cell reactivity to overlapping peptides of B. garinii OspA, in order to locate possible immunodominant T-cell epitopes in neuroborreliosis. Cells from cerebrospinal fluid (CSF) and blood from 39 patients with neuroborreliosis and 31 controls were stimulated with 31 overlapping peptides, and interferon-gamma secreting cells were detected by ELISPOT. The peptides OspA(17-36), OspA(49-68), OspA(105-124), OspA(137-156), OspA(193-212) and OspA(233-252) showed the highest frequency of positive responses, being positive in CSF from 38% to 50% of patients with neuroborreliosis. These peptides also elicited higher responses in CSF compared with controls (P = 0.004). CSF cells more often showed positive responses to these peptides than blood cells (P = 0.001), in line with a compartmentalization to the central nervous system. Thus, a set of potential T-cell epitopes were identified in CSF cells from patients with neuroborreliosis. Further studies may reveal whether these epitopes can be used diagnostically and studies involving HLA interactions may show their possible pathogenetic importance.

  • 138.
    Widhe, Mona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Grusell, Mattias
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Department of Neuroscience and Locomotion, Neurophysiology. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Cytokines in Lyme borreliosis: lack of early tumour necrosis factor-α and transforming growth factor-β1 responses are associated with chronic neuroborreliosis2002In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 107, no 1, p. 46-55Article in journal (Refereed)
    Abstract [en]

    The clinical outcome of the tick born infection Lyme borreliosis seems to be influenced by the type of immune response mounted during the disease, as suggested by various animal models. Here we report the serum and cerebrospinal fluid levels of tumour necrosis factor-α (TNF-α), transforming growth factor β1 (TGF-β1) and interleukin-6 (IL-6) in samples drawn at different disease intervals during the course of non-chronic neuroborreliosis (n=10), chronic neuroborreliosis (n=15), erythema migrans (n=8, serum only) and controls (n=7). When comparing early neuroborreliosis cerebrospinal fluid samples, significantly higher levels of TNF-α were found in non-chronic patients than in chronic patients (P<0·05). Moreover, TGF-β1 was increased in the early serum samples of non-chronic patients, as compared to chronic patients (P<0·01). Elevated serum levels of TGF-β1 were also found in erythema migrans as compared to neuroborreliosis and controls (P<0·05). The high TNF-α levels noted in early cerebrospinal fluid samples of non-chronic patients only, possibly reflects an ongoing pro-inflammatory immune response in the central nervous system, which could be beneficial in eliminating disease. High serum levels of TGF-β1 probably mirror an anti-inflammatory response, which might play a role in controlling the systemic immune response.

  • 139.
    Widhe, Mona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Hedin Skogman, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Bergström, Sven
    Department of Microbiology, University of Umeå, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Jarefors, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Eknefelt, Mattias
    Pediatric Clinic, Ryhov County Hospital, Jönköping, Sweden.
    Eneström, Gunilla
    Pediatric Clinic, Västervik Hospital, Västervik, Sweden.
    Nordwall, Maria
    Pediatric Clinic, Vrinnevi Hospital, Norrköping, Sweden.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Croner, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Up-regulation of Borrelia-specific IL-4 and IFN-gamma secreting cells in cerebrospinal fluid from children with Lyme neuroborreliosis2005In: International Immunology, ISSN 0953-8178, Vol. 17, no 10, p. 1283-1291Article in journal (Refereed)
    Abstract [en]

    The clinical course and outcome of several infectious diseases are dependent on the type of immune response elicited against the pathogen. In adults with neuroborreliosis (NB), a type 1 response with high production of Borrelia-specific IFN-, but no IL-4, has been reported. Since children have a more benign course of NB than adults, we wanted to investigate type 1 and type 2 responses in children with NB. Cerebrospinal fluid (CSF) and blood were collected from children during the acute stage of ‘confirmed NB’ (n = 34), ‘possible NB’ (n = 30) and ‘non-NB’ (n = 10). The number of Borrelia-specific IL-4- and IFN--secreting cells was measured by enzyme-linked immunospot assay. Borrelia-specific secretion of both IL-4 and IFN- was increased in CSF in confirmed (P < 0.05) and possible (P < 0.01) NB, when compared with non-NB controls. Furthermore, children with NB had significantly higher Borrelia-specific IL-4 secretion in CSF than an adult reference material with NB (P < 0.05). There were no differences in cytokine secretion in relation to onset or recovery of neurological symptoms. Since IL-4 is known to down-regulate the pro-inflammatory and possibly harmful effects of prolonged IFN- responses, the prominent IL-4 response observed in the central nervous system compartment might contribute to the more benign disease course seen in children with Lyme NB.

  • 140.
    Widhe, Mona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Jarefors, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Department of Neuroscience and Locomotion, Neurophysiology. Linköping University, Faculty of Health Sciences.
    Bergström, Sven
    Department of Molecular Biology, University of Umeå, Umeå, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences.
    Borrelia-specific interferon-γ and interleukin-4 secretion in cerebrospinal fluid and blood during Lyme borreliosis in humans: association with clinical outcome2004In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 189, no 10, p. 1881-1891Article in journal (Refereed)
    Abstract [en]

    The Borrelia-specific interferon (IFN)-γ and interleukin (IL)-4 responses of 113 patients and control subjects were analyzed using the sensitive enzyme-linked immunospot method. Cerebrospinal fluid (CSF) and blood samples were obtained, during the course of disease, from patients with chronic or nonchronic neuroborreliosis (NB) and from control subjects without NB. Blood samples were obtained from patients with Lyme skin manifestations and from healthy blood donors. Early increased secretion of Borrelia-specific IFN-γ (P < .05) and subsequent up-regulation of IL-4 ( P < .05) were detected in the CSF cells of patients with nonchronic NB. In contrast, persistent Borrelia-specific IFN-γ responses were observed in the CSF cells of patients with chronic NB ( P < .05). In patients with erythema migrans, increased IFN-γ (P < .001 ) was observed in blood samples obtained early during the course of disease, whereas increased IL-4 ( P < .05) was observed after clearance. On the contrary, patients with acrodermatitis chronica atrophicans had Borrelia-specific IFN-γ (P < .001 ), but not IL-4, detected in blood samples. The present data suggest that an initial IFN-γ response, followed by up-regulation of IL-4, is associated with nonchronic manifestations, whereas a persistent IFN-γ response may lead to chronic Lyme borreliosis.

  • 141.
    Wikby, Anders
    et al.
    Department of Natural Science and Biomedicine, School of Health Sciences, Jo¨nko¨ping University, Box 1026, 551 11 Jönköping, Sweden.
    Nilsson, Bengt-Olof
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Forsey, Rosalyn
    Unilever Corporate Research, Colworth House, Sharnbrook MK44 ILQ, UK.
    Thompson, Julie
    Unilever Corporate Research, Colworth House, Sharnbrook MK44 ILQ, UK.
    Strindhall, Jan
    Department of Natural Science and Biomedicine, School of Health Sciences, Jo¨nko¨ping University, Box 1026, 551 11 Jönköping, Sweden.
    Löfgren, Sture
    Department of Microbiology, Ryhov Hospital, 551 85 Jönköping, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Pawelec, Graham
    University of Tubingen Medical School, Center for Medical Research, ZMF, Waldho¨rnlestr. 22, D-72072 Tubingen, Germany.
    Ferguson, Frederick
    Department of Veterinary Science, College of Agricultural Sciences, The Pennsylvania State University, University Park, PA 16802-4803, USA.
    Johansson, Boo
    Institute of Gerontology, School of Health Sciences, Jo¨nko¨ping University, Box 1026, 551 11 Jönköping, Sweden.
    The immune risk phenotype is associated with IL-6 in the terminal decline stage: Findings from the Swedish NONA immune longitudinal study of very late life functioning2006In: Mechanisms of Ageing and Development, ISSN 0047-6374, E-ISSN 1872-6216, Vol. 127, no 8, p. 695-704Article in journal (Refereed)
    Abstract [en]

    In the present NONA immune longitudinal study, we further examine the previously identified T cell immune risk phenotype (IRP), relative inflammatory activity, morbidity and 2-year mortality in very old individuals >90 years. T-cell subsets as well as the inflammatory markers IL-6, IL-10, C-reactive protein, transthyretin and albumin were evaluated. IRP and low-grade inflammation predicted 57% of observed deaths and 97% of survival over 2 years, and was not significantly affected by individuals' health status, suggesting that the physiological ageing processes of T-cell immunosenescence and low-grade inflammation are of primary importance in late life survival. IRP non-survivors showed only a minor inflammatory activity at baseline, but had in contrast to survivors developed increased activity at follow-up. The results suggest a sequence of stages for IRP individuals that begin with acquisition of CMV infection in earlier life, followed by generation of CD8+CD28- cells to control persistent CMV infection and eventually the development of an IRP. Intriguingly, we also found that rare individuals moved out of the IRP category by a process of immune suppression, including increases in IL-6 and IL-10 and decreases in the number of CD3+CD8+CD28- cells. The further characterisation of these exceptional individuals may allow insight into remedial approaches for those who remain in the IRP category until death. © 2006 Elsevier Ireland Ltd. All rights reserved.

  • 142.
    Wilhelmsson, Peter
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Börjesson, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Bergström, Sven
    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.
    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.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Erratum: Prevalence and Diversity of Borrelia Species in Ticks That Have Bitten Humans in Sweden (vol 48, pg 4169, 2010)2011In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 49, no 1, p. 481-481Article in journal (Other academic)
    Abstract [en]

    n/a

  • 143.
    Wilhelmsson, Peter
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Börjesson, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Bergström, Sven
    Umeå University.
    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.
    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.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Prevalence and Diversity of Borrelia Species in Ticks That Have Bitten Humans in Sweden2010In: JOURNAL OF CLINICAL MICROBIOLOGY, ISSN 0095-1137, Vol. 48, no 11, p. 4169-4176Article in journal (Refereed)
    Abstract [en]

    Members of the genus Borrelia are among the most common infectious agents causing tick-borne disease in humans worldwide. Here, we developed a Light Upon eXtension (LUX) real-time PCR assay that can detect and quantify Borrelia species in ticks that have fed on humans, and we applied the assay to 399 such ticks. Borrelia PCR-positive ticks were identified to species level by sequencing the products of conventional PCR performed using Borrelia group-specific primers. There was a 19% prevalence of Borrelia spp. in the detached ticks, and the number of spirochetes per Borrelia PCR-positive tick ranged from 2.0 x 10(2) to 4.9 x 10(5), with a median of 7.8 x 10(3) spirochetes. Adult ticks had a significantly larger number of spirochetes, with a median of 8.4 x 10(4) compared to the median of nymphs of 4.4 x 10(4). Adult ticks also exhibited a higher prevalence of Borrelia (33%) than nymphs (14%). Among the identified species, Borrelia afzelii was found to predominate (61%) and was followed by B. garinii (23%), B. valaisiana (13%), B. burgdorferi sensu stricto (1%), B. lusitaniae (1%), and B. miyamotoi-like (1%). Also, 3% of the ticks were coinfected with multiple strains of B. afzelii. Notably, this is the first report of B. lusitaniae being detected in ticks in Sweden. Our LUX real-time PCR assay proved to be more sensitive than a corresponding TaqMan assay. In conclusion, the novel LUX real-time PCR method is a rapid and sensitive tool for detection and quantification of Borrelia spp. in ticks.

  • 144.
    Wilhelmsson, Peter
    et al.
    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.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nyman, Dag
    Jaenson, Thomas GT
    Uppsala University, Sweden .
    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.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Ryhov County Hospital, Jönköping, Sweden .
    Ixodes ricinus ticks removed from humans in Northern Europe: seasonal pattern of infestation, attachment sites and duration of feeding2013In: Parasites & Vectors, ISSN 1756-3305, E-ISSN 1756-3305, Vol. 6, no 362Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The common tick Ixodes ricinus is the main vector in Europe of the tick-borne encephalitis virus and of several species of the Borrelia burgdorferi sensu lato complex, which are the etiological agents of Lyme borreliosis. The risk to contract bites of I. ricinus is dependent on many factors including the behaviour of both ticks and people. The tick's site of attachment on the human body and the duration of tick attachment may be of clinical importance. Data on I. ricinus ticks, which were found attached to the skin of people, were analysed regarding potentially stage-specific differences in location of attachment sites, duration of tick attachment (= feeding duration), seasonal and geographical distribution of tick infestation in relation to age and gender of the tick-infested hosts.

    METHODS:

    During 2008-2009, 1770 tick-bitten persons from Sweden and the Åland Islands removed 2110 I. ricinus ticks. Participants provided information about the date of tick detection and location on their body of each attached tick. Ticks were identified to species and developmental stage. The feeding duration of each nymph and adult female tick was microscopically estimated based on the scutal and the coxal index.

    RESULTS:

    In 2008, participants were tick-bitten from mid-May to mid-October and in 2009 from early April to early November. The infestation pattern of the nymphs was bimodal whereas that of the adult female ticks was unimodal with a peak in late summer. Tick attachment site on the human body was associated with stage of the tick and gender of the human host. Site of attachment seemed to influence the duration of tick feeding. Overall, 63% of nymphs and adult female ticks were detected and removed more than 24 hours after attachment. Older persons, compared to younger ones, and men, compared to women, removed "their" ticks after a longer period of tick attachment.

    CONCLUSIONS:

    The infestation behaviour of the different tick stages concerning where on the host's body the ticks generally will attach and when such ticks generally will be detected and removed in relation to host age and gender, should be of value for the development of prophylactic methods against tick infestation and to provide relevant advice to people on how to avoid or reduce the risk of tick infestation.

  • 145.
    Wilsson, A.
    et al.
    Wilsson, Å., School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Lind, Susanne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Nursing Science.
    Öhman, Lena
    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.
    Nilsdotter-Augustinsson, Åsa
    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.
    Lundqvist-Setterud, H.
    Apoptotic neutrophils containing Staphylococcus epidermidis stimulate macrophages to release the proinflammatory cytokines tumor necrosis factor-a and interleukin-62008In: FEMS Immunology and Medical Microbiology, ISSN 0928-8244, E-ISSN 1574-695X, Vol. 53, no 1, p. 126-135Article in journal (Refereed)
    Abstract [en]

    Staphylococcus epidermidis infections are usually nosocomial and involve colonization of biomaterials. The immune defense system cannot efficiently control the bacteria during these infections, which often results in protracted chronic inflammation, in which a key event is disturbed removal of neutrophils by tissue macrophages. While ingesting uninfected apoptotic neutrophils, macrophages release anti-inflammatory cytokines that lead to resolution of inflammation. In clinical studies, we have previously found elevated levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-a) and interleukin-6 in synovial fluid from prostheses infected with coagulase negative staphylococci. We show that macrophages phagocytosing apoptotic neutrophils containing S. epidermidis released TNF-a and interleukin-6, whereas macrophages phagocytosing spontaneously apoptotic neutrophils did not. This difference was not due to dissimilar phagocytic capacities, because macrophages ingested both types of neutrophils to the same extent. The activation was induced mainly by the apoptotic neutrophils themselves, not by the few remaining extracellular bacteria. Macrophages were not activated by apoptotic neutrophils that contained paraformaldehyde-killed S. epidermidis. Proinflammatory reactions induced by clearance of apoptotic neutrophils containing S. epidermidis might represent an important mechanism to combat the infective agent. This activation of macrophages may contribute to the development of chronic inflammation instead of inflammation resolution. © 2008 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  • 146.
    Östholm Balkhed, Åse
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Monstein, Hans-Jurg
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Hällgren, Anita
    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.
    Hanberger, Håkan
    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.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    In vitro susceptibility of CTX-M-producing Escherichia coli to non-beta-lactam agentsManuscript (preprint) (Other academic)
    Abstract [en]

    Background: The objective of this study was to investigate the in vitro activity of different antibiotics against CTX-M-producing Escherichia coli, to determine the occurrence of multiresistance and plasmid mediated quinolone resistance among these isolates.

    Methods: A total of 198 isolates of E. coli with ESBL phenotype and mainly CTX-M genotype, were studied. The MICs for amikacin, chloramphenicol, ciprofloxacin, colistin, fosfomycin, gentamicin, nalidixic acid, nitrofurantoin, tigecycline, tobramycin, trimethoprim and trimethoprim-sulphamethoxazole were determined with the Etest. Susceptibility was defined according to the breakpoints of the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MIC(50) and MIC(90) values were calculated.

    Results: ≥95% of isolates were susceptible to amikacin, nitrofurantoin, colistin, tigecyclin, and fosfomycin. CTX-M group 9 was more susceptible than CTX-M group 1 to ciprofloxacin, gentamicin, and tobramycin. 68% of the isolates were multiresistant, and the most common multi-resistance pattern was ESBL-phenotype with decreased susceptibility to trimethoprim, trimethoprim-sulphamethoxazol, ciprofloxacin, gentamicin and  tobramycin. Only one isolate carried a qnrS1-gene, nine isolates carried aac(6’)-Ib-cr.

    Conclusions: The high frequency of multi-resistance found in this study is alarming and it is urgent to find strategies to limit the emergence and spread of these multi-resistant strains.

  • 147.
    Östholm Balkhed, Åse
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Monstein, Hans-Jürg
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Hällgren, Anita
    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.
    Hanberger, Håkan
    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.
    Nilsson, Lennart E.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    High frequency of co-resistance in CTX-M-producing Escherichia coli to non-beta-lactam antibiotics, with the exception of amikacin, nitrofurantoin, colistin, tigecycline, and fosfomycin, in a county of Sweden2013In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 45, no 4, p. 271-278Article in journal (Refereed)
    Abstract [en]

    Background: The objective of this study was to investigate the in vitro activity of different antibiotics against CTX-M-producing Escherichia coli in a county of Sweden, and to determine the occurrence of multi-resistance and plasmid- mediated quinolone resistance among these isolates. Methods: A total of 198 isolates of E. coli with extended-spectrum beta-lactamase (ESBL) phenotype and mainly CTX-M genotype were studied. The minimum inhibitory concentrations (MICs) for amikacin, chloramphenicol, ciprofloxacin, colistin, fosfomycin, gentamicin, nalidixic acid, nitrofurantoin, tigecycline, tobramycin, trimethoprim, and trimethoprim-sulfamethoxazole were determined with the Etest. Susceptibility was defined according to the breakpoints of the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MIC(50) and MIC(90) values were calculated. Results: Ninety-five percent or more of the isolates were susceptible to amikacin, nitrofurantoin, colistin, tigecycline, and fosfomycin. CTX-M group 9 was more susceptible than CTX-M group 1 to ciprofloxacin, gentamicin, and tobramycin. Sixty-eight percent of the isolates were multi-resistant, and the most common multi-resistance pattern was ESBL phenotype with decreased susceptibility to trimethoprim, trimethoprim-sulfamethoxazole, ciprofloxacin, gentamicin, and tobramycin. Only 1 isolate carried a qnrS1 gene, but 37% carried aac(6')-Ib-cr. Conclusions: A high frequency of co-resistance between ESBL-producing E. coli and non-beta-lactam antibiotics was seen. On the other hand, very high susceptibility was seen for amikacin, nitrofurantoin, colistin, tigecycline, and fosfomycin. These data support the replacement of gentamicin and tobramycin, normally used in Sweden, with amikacin, for severe infections.

  • 148.
    Östholm Balkhed, Åse
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Johansson, Anita
    Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Hanberger, Håkan
    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.
    Monstein, Hans-Jurg
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Molecular Biological Techniques.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae and trends in antibiotic consumption in a county of Sweden2010In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 42, no 11-12, p. 831-838Article in journal (Refereed)
    Abstract [en]

    In the last decade extended-spectrum beta-lactamase (ESBL)-producing bacteria have become an increasing problem. Our aims were to investigate the prevalence of ESBL-producing Enterobacteriaceae and trends in antibiotic use in the county of Ostergotland, Sweden. From 2002 through 2007 there were 224 ESBL-producing Escherichia coli and 23 Klebsiella pneumoniae isolates with an ESBL-phenotype identified among all Enterobacteriaceae isolated at the clinical laboratory. Trends in antibiotic consumption expressed as defined daily doses (DDD) per 1000 inhabitants and day (DID) were studied. The prevalence of ESBL-producing isolates among Enterobacteriaceae in our region is still low (andlt; 1%). Patients with ESBL-producing E. coli increased significantly (p andlt; 0.001) from 5 in y 2002 to 47 in y 2007. CTX-M group 1 was the dominant enzyme group in both E. coli and K. pneumoniae. Antibiotic susceptibility testing of ciprofloxacin, gentamicin and trimethoprim-sulfamethoxazole revealed that 58% of E. coli and 50% of K. pneumoniae isolates were multi-resistant. Antibiotic use remained unchanged from 2001 through 2009, but there was a trend towards increased use of drugs with low ESBL selection potential, which was probably due to the increased prevalence of ESBL producers.

  • 149.
    Östholm Balkhed, Åse
    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.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart E.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    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.
    Hällgren, Anita
    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.
    Travel-associated faecal colonization with ESBL-producing Enterobacteriaceae: incidence and risk factors2013In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 68, no 9, p. 2144-2153Article in journal (Refereed)
    Abstract [en]

    Objectives To study the acquisition of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) among the faecal flora during travel, with a focus on risk factors, antibiotic susceptibility and ESBL-encoding genes.

    Methods An observational prospective multicentre cohort study of individuals attending vaccination clinics in south-east Sweden was performed, in which the submission of faecal samples and questionnaires before and after travelling outside Scandinavia was requested. Faecal samples were screened for ESBL-PE by culturing on ChromID ESBL and an in-house method. ESBL-PE was confirmed by phenotypic and genotypic methods. Susceptibility testing was performed with the Etest. Individuals who acquired ESBL-PE during travel (travel-associated carriers) were compared with non-carriers regarding risk factors, and unadjusted and adjusted ORs after manual stepwise elimination were calculated using logistic regression.

    Results Of 262 enrolled individuals, 2.4% were colonized before travel. Among 226 evaluable participants, ESBL-PE was detected in the post-travel samples from 68 (30%) travellers. The most important risk factor in the final model was the geographic area visited: Indian subcontinent (OR 24.8, P < 0.001), Asia (OR 8.63, P < 0.001) and Africa north of the equator (OR 4.94, P  = 0.002). Age and gastrointestinal symptoms also affected the risk significantly. Multiresistance was seen in 77 (66%) of the ESBL-PE isolates, predominantly a combination of reduced susceptibility to third-generation cephalosporins, trimethoprim/sulfamethoxazole and aminoglycosides. The most common species and ESBL-encoding gene were Escherichia coli (90%) and CTX-M (73%), respectively.

    Conclusion Acquisition of multiresistant ESBL-PE among the faecal flora during international travel is common. The geographical area visited has the highest impact on ESBL-PE acquisition.

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