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

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

  • 2.
    Abednazari, Hossein
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Xu, Junyang
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Millinger, Eva
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Respiratory Medicine. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar, Sweden.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nayeri, Fariba
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Hepatocyte growth factor is a better indicator of therapeutic response than C-reactive protein within the first day of treatment in pneumonia2006In: Chemotherapy, ISSN 0009-3157, E-ISSN 1421-9794, Vol. 52, no 5, p. 260-263Article in journal (Refereed)
    Abstract [en]

    Acute bacterial infectious diseases are mostly treated empirically at admission before the culture results are available. According to the risk for serious complications in the case of therapeutic failure, it is important to evaluate the therapy results and change to a more appropriate antibiotic regime as soon as possible. In the present study, 40 patients with X-ray-verified community-acquired pneumonia were examined and blood specimens were collected before and within 24 h of treatment. Body temperature, C-reactive protein (CRP) and hepatocyte growth factor (HGF) were investigated. Thirty-two patients received an appropriate initial antibiotic therapy regarding clinical outcome, but in 8 patients the treatment was changed because of therapy failure. Changes of HGF levels after 18–24 h of treatment could predict the therapeutic results accurately in 38 of 40 cases (sensitivity 100%, specificity 94%, positive likelihood ratio 16.0). HGF was significantly better to predict therapy outcome than CRP (p < 0.0001).

  • 3.
    Antepohl, Wolfram
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Domeij, Erica
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    A follow-up of medical graduates of a problem-based learning curriculum2003In: Medical Education, ISSN 0308-0110, E-ISSN 1365-2923, Vol. 37, no 2, p. 155-162Article in journal (Refereed)
    Abstract [en]

    Introduction: There is little information available on the effects of problem-based undergraduate curricula on doctors and their performances after graduation. Therefore, we conducted a questionnaire study of all graduates of the new medical programme at the Faculty of Health Sciences, Link÷ping University. Methods: All 446 medical students who had graduated from the new programme were asked to fill in a questionnaire about selected activities during their studies and their careers after graduation. They were also asked to evaluate the quality of their undergraduate education retrospectively. Statistical analysis was performed using descriptive, multivariate and bivariate approaches. Results: A total of 77% of the graduates responded. They showed a high degree of overall contentment with their undergraduate education and felt well prepared for professional life during their preregistration period and specialist education (mean = 4.0 on a 6-point Likert scale ranging from 0 to 5). They felt especially well prepared in terms of skills for communication with patients, collaboration with other health professionals and development of critical thinking/scientific attitudes. The students' age at the beginning of their studies correlated positively with their contentment as graduates, especially in terms of preparation for patient communication and collaboration with other health professionals. No differences between students originally admitted via a local admission procedure and those admitted via a national procedure were detected concerning retrospective evaluation of undergraduate medical education. Conclusion: Graduates of the new curriculum showed a high degree of satisfaction with their undergraduate education and its preparation of them for medical practice. Specifically, they were very content with the particular emphases of the new curriculum.

  • 4.
    Asghar, Naveed
    et al.
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden.
    Lindblom, Pontus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Melik, Wessam
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden.
    Lindqvist, Richard
    Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Haglund, Mats
    Kalmar County hospital.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine.
    Överby, Anna K.
    Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Andreassen, Åshild
    Division of Infectious Disease Control, Department of Virology, Norwegian Institute of Public Health, Oslo, Norway.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Johansson, Magnus
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden / School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Tick-borne encephalitis virus sequenced directly from questing and blood-feeding ticks reveals quasispecies variance2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 7, p. e103264-Article in journal (Refereed)
    Abstract [en]

    The increased distribution of the tick-borne encephalitis virus (TBEV) in Scandinavia highlights the importance of characterizing novel sequences within the natural foci. In this study, two TBEV strains: the Norwegian Mandal 2009 (questing nymphs pool) and the Swedish Saringe 2009 (blood-fed nymph) were sequenced and phylogenetically characterized. Interestingly, the sequence of Mandal 2009 revealed the shorter form of the TBEV genome, similar to the highly virulent Hypr strain, within the 3´ non-coding region (3´NCR). A different genomic structure was found in the 3´NCR of Saringe 2009, as in-depth analysis demonstrated TBEV variants with different lengths within the poly(A) tract. This shows that TBEV quasispecies exists in nature and indicates a putative shift in the quasispecies pool when the virus switches between invertebrate and vertebrate environments. This prompted us to further sequence and analyze the 3´NCRs of additional Scandinavian TBEV strains and controls, Hypr and Neudoerfl. Toro 2003 and Habo 2011 contained mainly a short (A)3C(A)6 poly(A)  tract. A similar pattern was observed for the human TBEV isolates 1993/783 and 1991/4944; however, one clone of 1991/4944 contained an (A)3C(A)11 poly(A) sequence, demonstrating that quasispecies with longer poly(A) could be present in human isolates. Neudoerfl has previously been reported to contain a poly(A) region, but to our surprise the re-sequenced genome contained two major quasispecies variants, both lacking the poly(A) tract. We speculate that the observed differences are important factors for the understanding of virulence, spread, and control of the TBEV.

  • 5.
    Bjuremark, Anna
    et al.
    Linköping University, Department of Behavioural Sciences, Studies in Adult, Popular and Higher Education. Linköping University, Faculty of Arts and Sciences.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland. Linköping University, Faculty of Health Sciences.
    En orientering i det akademiska riket1998In: Läkare, doktor, kvinna / [ed] Elisabeth Hultcrantz, Lund: Studentlitteratur , 1998Chapter in book (Other (popular science, discussion, etc.))
  • 6.
    Brodszki, N B
    et al.
    Lund University Hospital.
    Matsols, H
    Falu Lasarett.
    Fasth, A
    Drottning Silvias Barnoch Ungdomssjukhus.
    Friman, V
    Sahlgrens University Hospital.
    Lofdahl, K
    Sahlgrens University Hospital.
    Oskarsdottir, S
    Drottning Silvias Barnoch Ungdomssjukhus.
    Marthinsen, L
    Lanssjukhuset, Halmstad.
    Olinder-Nielsen, A M
    Lanssjukhuset Ryhov.
    Wagstrom, P
    Lanssjukhuset Ryhov.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Jonsson, G
    Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Aurivillius, M
    University Sjukhuset, Malmö.
    Lanbeck, P
    University Sjukhuset, Malmö.
    Granert, C
    Karolinska University Sjukhuset.
    Gustafson, R
    Karolinska University Sjukhuset.
    Hammarstrom, L
    Karolinska University Sjukhuset.
    Ahlin, A
    Sachsska Barnsjukhuset.
    West, C
    Norrlands University Sjukhus.
    Gunther, G
    Uppsala University.
    Pauksen, K
    Uppsala University.
    Arneborn, P
    Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Björkqvist, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Bjorkander, J
    Lanssjukhuset Ryhov.
    Swedish guidelines for the assessment, diagnosis and management of 6 primary immunodeficiency states: CVID, IgG subclass deficiency, IgA deficiency, XLA, SCID and CGD2008In: CLINICAL AND EXPERIMENTAL IMMUNOLOGY,ISSN 0009-9104: Volume 154, 2008, Vol. 154, p. 140-141Conference paper (Refereed)
  • 7.
    Dahle, L. O.
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Hård af Segerstad, Helene
    Linköping University, Department of Behavioural Sciences, Studies in Adult, Popular and Higher Education. Linköping University, Faculty of Educational Sciences.
    Wyon, Yvonne
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Hammar, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Problem-based medical education: development of a theoretical foundation and a science-based professional attitude1997In: Medical Education, ISSN 0308-0110, E-ISSN 1365-2923, Vol. 31, no 6, p. 416-424Article in journal (Refereed)
    Abstract [en]

    Problem-based learning, combined with early patient contact, integration between different subject areas, elements of multiprofessional education, and special emphasis on the development of communications skills has become the basis for the medical curriculum at the Faculty of Health Sciences in Linköping. Critics have questioned the depth of the scientific and theoretical aspects of the curriculum. Through a series of specific measures in the organization of the curriculum and examinations, and due to the pedagogical principles involved per se, our claim is that students graduating at Linköping do possess the required theoretical knowledge and a scientific attitude to the practice of medicine, at least equivalent to that obtained in a more conventional medical curriculum. One such specific measure is that all students perform one field study and two scientific studies during the course of the curriculum. An investigation of student opinions regarding the value of performing scientific projects of their own have shown that these projects have had a positive impact on the students' general scientific attitude and their willingness to engage in future scientific work. The specific skills acquired, as confirmed by oral examinations, were largely determined by the scientific nature of the chosen field of study. Our graduates have not yet progressed far enough in their careers for comparisons to be made on the basis of the Swedish Licensing Board Internship Examinations, but continuing evaluations of students, graduates and licensed doctors emerging from the curriculum will provide future evi-dence as to whether our present evaluation is correct.

  • 8.
    Dessau, Ram B
    et al.
    Slagelse Hospital, Slagelse, Denmark.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Nyman, Dag
    Åland University, Mariehamn, Finlad.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and 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 Medicine and Health Sciences.
    Study of a Cohort of 1,886 Persons To Determine Changes in Antibody Reactivity to Borrelia burgdorferi 3 Months after a Tick Bite2015In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 22, no 7, p. 823-827Article in journal (Refereed)
    Abstract [en]

    Lyme borreliosis is a tick-borne disease caused by the bacterium Borrelia burgdorferi. The most frequent clinical manifestation is a rash called erythema migrans. Changes in antibody reactivity to B. burgdorferi 3 months after a tick bite are measured using enzyme-linked immunosorbent assays (ELISAs). One assay is based on native purified flagellum antigen (IgG), and the other assay is based on a recombinant antigen called C6 (IgG or IgM). Paired samples were taken at the time of a tick bite and 3 months later from 1,886 persons in Sweden and the Åland Islands, Finland. The seroconversion or relative change is defined by dividing the measurement units from the second sample by those from the first sample. The threshold for the minimum level of significant change was defined at the 2.5% level to represent the random error level. The thresholds were a 2.7-fold rise for the flagellar IgG assay and a 1.8-fold rise for the C6 assay. Of 1,886 persons, 102/101 (5.4%) had a significant rise in antibody reactivity in the flagellar assay or the C6 assay. Among 40 cases with a diagnosis of Lyme borreliosis, the sensitivities corresponding to a rise in antibodies were 33% and 50% for the flagellar antigen and the C6 antigen, respectively. Graphical methods to display the antibody response and to choose thresholds for a rise in relative antibody reactivity are shown and discussed. In conclusion, 5.4% of people with tick bites showed a rise in Borrelia-specific antibodies above the 2.5% threshold in either ELISA but only 40 (2.1%) developed clinical Lyme borreliosis.

  • 9.
    Ekerfelt, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical 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 Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Jönsson, Anna-Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Vrethem, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ärlehag, L
    Forsum, Urban
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Lyme borreliosis in Sweden - Diagnostic performance of five commercial Borrelia serology kits using sera from well-defined patient groups2004In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 112, no 1, p. 74-78Article in journal (Refereed)
    Abstract [en]

    Five commercial Borrelia serology kits available in Sweden were evaluated and compared for their diagnostic performance in sera from clinically well-characterized patient groups. With the clinically defined groups as the gold standard, i.e. without knowledge of antibody status in serum and cerebrospinal fluid, the diagnostic performance of the kits was compared and important differences in diagnostic usefulness were found. The kits from Abbot and DAKO, that often predict clinically relevant Borrelia infection and do not detect antibodies in sera from patients without strong suspicion of Borrelia infection, were considered the most useful in the population studied. This kind of validation study is an important part of good laboratory practice and should be performed by laboratories serving patient populations with varying endemicity of Borrelia.

  • 10.
    Ekerfelt, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Svenvik, Maria
    Roberg, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Bergström, S.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    A symptomatic Borrelia-seropositive individuals display the same incidence of Borrelia-specific interferon-gamma (IFN-gamma)-secreting cells in blood as patients with clinical Borrelia infection.1999In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 115, p. 498-502Article in journal (Refereed)
  • 11.
    Ekerfelt, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Jarefors, Sara
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Tynngard, N
    Hedlund, M
    Sander, B
    Bergström, S
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Phenotypes indicating cytolytic properties of Borrelia-specific interferon-? secreting cells in chronic Lyme neuroborreliosis2003In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 145, no 1-2, p. 115-126Article in journal (Refereed)
    Abstract [en]

    The immuno-pathogenetic mechanisms underlying chronic Lyme neuroborreliosis are mainly unknown. Human Borrelia burgdorferi (Bb) infection is associated with Bb-specific secretion of interferon-? (IFN-?), which may be important for the elimination of Bb, but this may also cause tissue injury. In order to increase the understanding of the pathogenic mechanisms in chronic neuroborreliosis, we investigated which cell types that secrete IFN-?. Blood mononuclear cells from 13 patients with neuroborreliosis and/or acrodermatitis chronicum atrophicans were stimulated with Bb antigen and the phenotypes of the induced IFN-?-secreting cells were analyzed with three different approaches. Cells expressing CD8 or TCR?d, which both have cytolytic properties, were the main phenotypes of IFN-?-secreting cells, indicating that tissue injury in chronic neuroborreliosis may be mediated by cytotoxic cells.

  • 12.
    Ekerfelt, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion.
    Masreliez, C
    Svenvik, M
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Roberg, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Antibodies and T-cell reactivity to Borrelia burgdorferi in an asymptomatic population: A study of healthy blood donors in an Inland town district in the South-East of Sweden2001In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 33, no 11, p. 806-808Article in journal (Refereed)
    Abstract [en]

    To address the issue of whether Borrelia infection can be asymptomatic, blood donors with no history of borreliosis (n = 408) were screened for antibodies against Borrelia burgdorferi. Seropositive individuals (n = 17) were further investigated with respect to Borrelia-specific T-cell reactivity, using an interferon-? ELISPOT assay. Anti-Borrelia antibodies as well as Borrelia-specific T-cell responses were evident in 9 asymptomatic donors, strongly supporting a current or previous asymptomatic Borrelia infection.

  • 13.
    Esamai, Fabian
    et al.
    Faculty of Health Sciences, Moi University, Eldoret, Kenya.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Janols, Helena
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Welin, Susanne
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Mining, Simeon
    Faculty of Health Sciences, Moi University, Eldoret, Kenya.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Cerebral malaria in children: Serum and cerebrospinal fluid TNF-α and TGF-ß levels and their relationship to clinical outcome2003In: Journal of Tropical Pediatrics, ISSN 0142-6338, E-ISSN 1465-3664, Vol. 49, no 4, p. 216-223Article in journal (Refereed)
    Abstract [en]

    This was a prospective study conducted at the Moi Teaching and Referral Hospital, Eldoret, Kenya. Twenty‐three children admitted to the hospital with cerebral (CM) and 10 children with noncerebral malaria (NCM) were studied. The aim of the study was to establish and compare levels of tumour necrosis factor (TNF‐α) and transforming growth factor (TGF‐β1) in these children. Serum and cerebrospinal fluid (CSF) cytokine levels were assayed using ELISA kits. In serum, TGF‐β1 and TNF‐α decreased over 5 days after admission to the hospital in both groups of patients with CM and NCM. In the CSF of cerebral cases the levels of TNF‐α and TGF‐β1 were low and inversely related. Children in deeper coma had lower levels in serum of TGF‐β and higher levels of TNF‐α than those in lighter levels of coma. The serum TNF‐α levels in CM children were the same irrespective of the duration of illness before admission, but children with NCM who had been sick for a shorter duration before admission tended to have higher serum levels of TNF‐α and higher levels of TGF‐β than those with a longer duration of illness before admission. In conclusion, this study shows that TNF‐α and TGF‐β1 may not be useful in predicting the outcome for CM. They may, however, be useful in detecting children at risk of developing deep coma. TNF‐α and TGF‐β levels were inversely related both in serum and CSF.

  • 14.
    Esamai, Fabian
    et al.
    Department of Child Health and Paediatrics, Faculty of Health Sciences, Moi University, Eldoret, Kenya.
    Jivaji, S.
    Department of Human Pathology, Faculty of Health Sciences, Moi University, Eldoret, Kenya.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Lewis, David H.
    Anabwani, G. M.
    Department of Child Health and Paediatrics, Faculty of Health Sciences, Moi University, Eldoret, Kenya.
    A comparison of core and skin temperature among normal and febrile children with cerebral malaria, uncomplicated malaria, and measles1995In: Pathophysiology, ISSN 0928-4680, Vol. 2, no 1, p. 55-59Article in journal (Refereed)
    Abstract [en]

    Forty-four children were studied to compare the pathogenesis of fever in cerebral malaria, uncomplicated malaria and measles at the Eldoret District Hospital (EDH). A control group of normal children was used. The three patient groups were studied for three consecutive days measuring skin and core temperature three-times a day using the Liquid Crystal Device (LCD) thermometer. A statistical analysis of the results within and between the groups was carried out for core and skin temperature over the study period. No statistical differences were found between the groups for either the skin or the core temperature, but a significant statistical difference was demonstrated between the core and the skin temperature for all of the groups for each of the three days. No statistical difference was found when the differences between the core and skin temperature were compared between cerebral malaria and uncomplicated malaria. The possible roles of fever in morbidity and mortality are discussed, with special reference to cerebral malaria.

  • 15.
    Esamai, Fabian
    et al.
    Department of Child Health and Paediatrics, Faculty of Health Sciences, Moi University, Eldoret, Kenya.
    Mining, Simeon
    Department of Child Health and Paediatrics, Faculty of Health Sciences, Moi University, Eldoret, Kenya.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Lewis, David H.
    A comparison of brain, core and skin temperature in children with complicated and uncomplicated malaria2001In: Journal of Tropical Pediatrics, ISSN 0142-6338, E-ISSN 1465-3664, Vol. 47, no 3, p. 170-175Article in journal (Refereed)
    Abstract [en]

    A prospective study was carried out in which brain, core and skin temperatures were studied in children with cerebral malaria (n = 23), uncomplicated malaria (n = 12) and normal children (n = 9) using the zero heat flow method. Patients with cerebral or uncomplicated malaria were admitted to the paediatric wards (mean age, 6 years 8 months ± 2 years 8 months). Normal children, children of the investigators, of the same age group, served as controls. Parasitaemia levels were similar in the cerebral and uncomplicated malaria cases. Higher brain than core temperatures would have been expected in cerebral malaria but not in uncomplicated malaria but this was not the case in this study. There was no statistical difference in brain, core and skin temperature between cerebral and uncomplicated malaria patients. However, there was a highly significant difference between normal children and cerebral and uncomplicated malaria patients. Brain temperature was 0.02–0.2°C below core temperature in all the groups with larger differences during the febrile period. Mean differences of brain minus core, brain minus skin and core minus skin between the two groups of patients were not statistically significant. There was no correlation between temperature and the level of coma or parasitaemia for cerebral and uncomplicated malaria patients. There was a positive correlation between brain and core temperature in both groups of patients during the febrile phase. Brain temperature remained lower than core temperature in cerebral and uncomplicated malaria as in normal children. Normal thermoregulation appears to be maintained in cerebral malaria.

  • 16.
    Esamai, Fabian
    et al.
    Department of Child Health and Paediatrics, Faculty of Health Sciences, Moi University, Eldoret, Kenya.
    Nabakwe, E.
    Department of Child Health and Paediatrics, Faculty of Health Sciences, Moi University, Eldoret, Kenya.
    Mining, S.
    Department of Immunology, Faculty of Health Sciences, Moi University, Eldoret, Kenya.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Lewis, David H.
    Clinical presentation and diagnosis of cerebral malaria in children in the highlands of western Kenya1999In: East African Medical Journal, ISSN 0012-835X, Vol. 76, no 2, p. 89-92Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The clinical presentation of cerebral malaria in children in the highlands has not been documented.

    OBJECTIVE:

    To describe the presentation of cerebral malaria in the age group one to twelve years.

    DESIGN:

    Prospective study conducted from May to September 1997, the rainy season during which malaria occurs in epidemics in the highlands of Kenya.

    SETTING:

    Paediatric wards of the Moi Teaching and Referral Hospital, Eldoret which is the Teaching Hospital for Moi University and the referral centre for surrounding districts of Western Kenya, with an altitude of over 2000 metres above sea level.

    PATIENTS:

    Twenty three consecutive children aged one to twelve years with cerebral malaria as defined by the WHO were studied. All children were treated with the standard quinine regimen for cerebral malaria.

    RESULTS:

    Majority of the children were six to ten years of age with 95.7% having a normal weight for age. 91.3%, 89.5% and 72.2% had fever, headache and convulsions respectively. 68.1% had a short duration of illness (less than three days) with only 9.5% presenting with hypoglycaemia. Severe anaemia was not observed but 72% had mild to moderate anaemia. Hyperparasitaemia (parasite counts greater than 100,000 per microlitre) was found in majority of the cases.

    CONCLUSION:

    Cerebral malaria presentation in the highlands is similar to that among non-immune populations and is an acute fulminant illness presenting with coma, hyperparasitaemia, fever and convulsions in children with normal nutritional status.

  • 17.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Fästingöverförda infektioner i Sverige2004In: Infektionsmedicin: epidemiologi, klinik, terapi / [ed] Iwarson-Norrby och Iwarson, Sten, Säve Förlag , 2004, p. 378-382Chapter in book (Other academic)
    Abstract [sv]

    Denna klassiska lärobok kom 2011 ut i sin 5:e, omarbetade upplaga. Boken innehåller 28 kapitel, vilka täcker hela infektionspanoramat, från influensa till AIDS. Samtliga författare är läkare och flertalet universitetslärare. Den innehåller även 16 sidor färgplanscher med fotoillustrationer av olika sjukdomar. Boken är avsedd att användas i undervisningen av blivande läkare och som uppslagsbok i sjukvården.

  • 18.
    Fryland, Linda
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology.
    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.
    Sandin, Linnea
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Lindblom, Pontus
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Nyman, Dag
    Aland Borrelia Grp.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. 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 Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology.
    Biomarkers in blood a few days after a bite by a Borrelia burgdorferi infected tick:: Asymptomatic Borrelia burgdorferi-infected subjects show higher Th1-associated response compared with subjects who later develop Lyme borreliosis2012Manuscript (preprint) (Other academic)
    Abstract [en]

    The clinical outcome following infection with Borrelia (B.) burgdorferi sensu lato (s.l.) differs between individuals, ranging from asymptomatic infection to Lyme borreliosis (LB) with persistent symptoms post-treatment. Previous studies in mice and humans have generated the hypothesis that a successful outcome of B. burgdorferi s.l. infection is associated with an early strong pro-inflammatory T helper (Th)1-like immune response. The aim of this study was to assess the early course of events in B. burgdorferi s.l.-associated inflammation by screening for possible early immune biomarkers in peripheral blood from newly tick-bitten persons. The study subjects bitten by B. burgdorferi s.l.-infected ticks were divided into (1) those later developing clinical LB, (2) those who developed anti-B. burgdorferi s.l. antibodies but not clinical LB, (3) those who neither developed antibodies nor clinical LB. A fourth group consisted of bitten study subjects without development of antibodies or clinical LB. Two sets of samples, both comprising all four groups, were collected in order to repeat the analyses and confirm the data. Sera or plasma collected a few days after the tick bite were analysed for 18 biomarkers (IL-1β, IL-6, CXCL8/IL-8, IL-12p70, IL-17A, IL-27, TNF, CCL18, CCL20, CCL22, CXCL1, CXCL9, CXCL10, CXCL11, calprotectin, MMP-3, MMP-8, MMP-9) by multiplex bead assay and ELISA. In the first set of samples, the neutrophil activation marker calprotectin was increased in subjects who developed clinical LB compared with subjects who developed antibodies against B. burgdorferi s.l. but did not develop LB. However, the finding could not be confirmed in the second set of samples, thus the study failed to identify an early prognostic marker for development of clinical LB. Interestingly, both sets of samples showed increases in two different Th1-associated markers, CXCL10 and IL-12p70, respectively, in subjects who following a bite by a B. burgdorferi s.l.-infected tick developed antibodies against B. burgdorferi s.l. but did not develop LB compared with subjects who developed clinical LB, thus supporting the hypothesis of an early strong Th1-response being important for optimal resolution of B. burgdorferi s.l. infection.

  • 19.
    Fryland, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Nyman, Dag
    Aland Borrelia Grp.
    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, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Low risk of developing Borrelia burgdorferi infection in the south-east of Sweden after being bitten by a Borrelia burgdorferi-infected tick2011In: INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, ISSN 1201-9712, Vol. 15, no 3, p. E174-E181Article in journal (Refereed)
    Abstract [en]

    Objectives: The risk of developing Lyme borreliosis (LB) from Borrelia burgdorferi sensu lato (Bb)-infected ticks in Sweden is largely unknown. In the current study, we investigated the prevalence of Bb in ticks that had bitten humans and the risk of developing LB from Bb-infected ticks. Methods: Health questionnaires, blood samples, and ticks were collected from 394 tick-bitten study subjects in the County of Ostergotland, Sweden, at the time of the tick bite. Questionnaires and blood samples were also collected 3 months later. Ticks were screened for Bb DNA with PCR, while sera were analyzed for antibodies against Bb using two ELISA assays. Seroconversion, i.e., an at least two-fold increase in anti-Bb antibodies after 3 months, was confirmed using a Strip-Immunoassay. Results: Seventy-five of 397 ticks collected from the study subjects were determined to be Bb-positive. Sixty-four of the tick-bitten subjects had been bitten by Bb-infected ticks. Four of them showed seroconversion and were therefore considered to have an active Bb infection. None of these four subjects had sought health care due to symptoms, but one reported symptoms. Conclusions: Our data suggest that the risk of developing LB after being bitten by a Bb-infected tick is low, and asymptomatic Bb infections appear to be more frequent than symptomatic infections.

  • 20.
    Grankvist, Anna
    et al.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Labbe Sandelin, Lisa
    Kalmar County Hospital, Sweden; Uppsala University, Sweden.
    Andersson, Jennie
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Wenneras, Christine
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Infections with Candidatus Neoehrlichia mikurensis and Cytokine Responses in 2 Persons Bitten by Ticks, Sweden2015In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 21, no 8, p. 1462-1465Article in journal (Refereed)
    Abstract [en]

    The prevalence of Candidatus Neoehrlichia mikurensis infection was determined in 102 persons bitten by ticks in Sweden. Two infected women had erythematous rashes; 1 was co-infected with a Borrelia sp., and the other showed seroconversion for Anaplasma phagocytophilum. Both patients had increased levels of Neoehrlichia DNA and serum cytokines for several months.

  • 21.
    Gyllemark, Paula
    et al.
    Department of Infectious Diseases, Region Jönköping County, Jönköping, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Henningsson, Anna J.
    Clinical Microbiology, Division of Medical Services, Jönköping, Region Jönköping County, Sweden.
    Intrathecal Th17- and B cell-associated cytokine and chemokine responses in relation to clinical outcome in Lyme neuroborreliosis: a large retrospective study.2017In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 14, no 1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: B cell immunity, including the chemokine CXCL13, has an established role in Lyme neuroborreliosis, and also, T helper (Th) 17 immunity, including IL-17A, has recently been implicated.

    METHODS: We analysed a set of cytokines and chemokines associated with B cell and Th17 immunity in cerebrospinal fluid and serum from clinically well-characterized patients with definite Lyme neuroborreliosis (group 1, n = 49), defined by both cerebrospinal fluid pleocytosis and Borrelia-specific antibodies in cerebrospinal fluid and from two groups with possible Lyme neuroborreliosis, showing either pleocytosis (group 2, n = 14) or Borrelia-specific antibodies in cerebrospinal fluid (group 3, n = 14). A non-Lyme neuroborreliosis reference group consisted of 88 patients lacking pleocytosis and Borrelia-specific antibodies in serum and cerebrospinal fluid.

    RESULTS: Cerebrospinal fluid levels of B cell-associated markers (CXCL13, APRIL and BAFF) were significantly elevated in groups 1, 2 and 3 compared with the reference group, except for BAFF, which was not elevated in group 3. Regarding Th17-associated markers (IL-17A, CXCL1 and CCL20), CCL20 in cerebrospinal fluid was significantly elevated in groups 1, 2 and 3 compared with the reference group, while IL-17A and CXCL1 were elevated in group 1. Patients with time of recovery <3 months had lower cerebrospinal fluid levels of IL-17A, APRIL and BAFF compared to patients with recovery >3 months.

    CONCLUSIONS: By using a set of markers in addition to CXCL13 and IL-17A, we confirm that B cell- and Th17-associated immune responses are involved in Lyme neuroborreliosis pathogenesis with different patterns in subgroups. Furthermore, IL-17A, APRIL and BAFF may be associated with time to recovery after treatment.

  • 22.
    Hedin Skogman, Barbro
    et al.
    Center for Clinical Research, Falun, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Vene, Sirkka
    Smittskyddsinstutet .
    Åkerlind, Britt
    Östergötlands Läns Landsting, Center for Health and Developmental Care, Department of Infection Control.
    Are There Undiagnosed TBE-, Herpes- or Enteroviral Infections among Children Being Evaluated for Lyme Neuroborreliosis?2014In: Open Journal of Clinical Diagnostics, ISSN 2162-5816, E-ISSN 2162-5824, Vol. 4, no 3, p. 123-129Article in journal (Refereed)
    Abstract [en]

    Lyme neuroborreliosis (LNB) in children is a challenging diagnosis based on clinical manifestations and laboratory findings. The aim of this study was to investigate whether herpes simplex virus (HSV) 1 or 2, varicella zoster virus (VZV), enterovirus or tick-borne encephalitis virus (TBEV) could be identified in cerebrospinal fluid (CSF) or serum from children being evaluated for LNB, in order to elucidate whether such infectious diseases may be missed by the clinician. Methods: Ninety-nine pediatric patients (n = 99) were retrospectively included from a previous study on LNB in southeast of Sweden. They had been diagnosed as “Possible LNB” or “Not determined” due to negative Borrelia antibody index in CSF. Routine polymerase chain reaction (PCR) methods were used for detection of herpes viral RNA or enteroviral DNA in CSF. An ELISA assay was used for detection of anti-TBEV antibodies (IgM and IgG) in serum. Results: One patient showed elevated anti-TBEV IgM and IgG antibodies in serum, indicating a current TBE infection. No positive PCR reactions for HSV 1 or 2, VZV or enterovirus were detected in CSF from any of the patients. In conclusion, our results suggest that undiagnosed herpes- or enteroviral infections are unlikely to explain CNS symptoms in children being evaluated for LNB, whereas missed TBE infections may occur. TBEV serology should be included when evaluating children for LNB in TBE endemic areas.

  • 23.
    Hedin-Skogman, Barbro
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Croner, Stefan
    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, 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.
    Lahdenne, Pekka
    Hospital for Children and Adolescents, Helsinki University Central Hospital.
    Sillanpää, Heidi
    Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki.
    Seppälä, Ilkka
    Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki.
    Improved Laboratory Diagnostics of Lyme Neuroborreliosis in Children2008In: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 27, no 7, p. 605-612Article in journal (Refereed)
    Abstract [en]

    Background: Laboratory diagnostics in Lyme neuroborreliosis need improvement. We hereby investigate 4 new recombinant or peptide Borrelia antigens in cerebrospinal fluid in children with neuroborreliosis to evaluate their performance as diagnostic antigens.

    Methods: An enzyme-linked immunosorbent assay was used to detect IgG antibodies to recombinant decorin binding protein A (DbpA), BBK32, outer surface protein C (OspC), and the invariable region 6 peptide (IR6). The recombinant antigens originated from 3 pathogenic subspecies; Borrelia afzelii, Borrelia garinii, and Borrelia burgdorferi sensu stricto. Cerebrospinal fluid and serum from children with clinical features indicative for neuroborreliosis (n = 57) were analyzed. Classification of patients was based on clinical symptoms and laboratory findings. Controls were children with other neurologic diseases (n = 20) and adult patients with no proven infection (n = 16).

    Results: Sensitivity for DbpA was 82%, for BBK32 70%, for OspC 58% and for IR6 70%. Specificities were 94%, 100%, 97%, and 97%, respectively. No single antigen was superior. When new antigens were combined in a panel, sensitivity was 80% and specificity 100%. The reference flagella antigen showed a sensitivity of 60% and a specificity of 100%. Over all, the B. garinii related antigens dominated.

    Conclusions: Recombinant DbpA and BBK32 as well as the peptide antigen IR6 perform well in laboratory diagnostics of neuroborreliosis in children. New antigens seem to improve diagnostic performance when compared with the routine flagella antigen. If different antigens are combined in a panel to cover the antigenic diversity, sensitivity improves further and a specificity of 100% can be achieve.

  • 24.
    Hedin-Skogman, Barbro
    et al.
    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.
    Croner, Stefan
    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.
    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.
    Eknefelt, Mattias
    Pediatric Clinic, Jönköping.
    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.
    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.
    Lyme Neuroborreliosis in Children - a Prospective Study of Clinical features, Prognosis, and Outcome2008In: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 27, no 12, p. 1089-1094Article in journal (Refereed)
    Abstract [en]

     

    Background: Evaluation of children with clinically suspected neuroborreliosis (NB) is difficult. With a prospective study design we wanted to characterize children with signs and symptoms indicative for NB, investigate clinical outcome and, if possible, identify factors of importance for recovery.

    Material/Methods: Children being evaluated for NB (n = 177) in Southeast Sweden were categorized into 3 groups: "confirmed neuroborreliosis" (41%) with Borrelia antibodies in the cerebrospinal fluid, "possible neuroborreliosis" (26%) with pleocytosis but 110 Borrelia antibodies in the cerebrospinal fluid, and "not determined" (33%) with no pleocytosis and no Borrelia antibodies in the cerebrospinal fluid, Antibiotic treatment was given to 69% of children. Patients were followed during 6 months and compared with a matched control group (n = 174).

    Results: Clinical recovery at the 6-month follow-up (n = 177) was generally good and no patient was found to have recurrent or progressive neurologic symptoms. However, persistent facial nerve palsy caused dysfunctional and cosmetic problems in 11% of patients. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls. Influence on daily life was reported to the same extent in patients and controls. Consequently, persistent headache and fatigue at follow-up should not be considered as attributable to NB. No prognostic factors could be identified.

    Conclusions: Clinical recovery was satisfactory in children being evaluated for NB although persistent symptoms from facial nerve palsy occurred. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls.

  • 25.
    Hedin-Skogman, Barbro
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Croner, Stefan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Kampanj för TBE vaccination av små barn oetisk och felaktig2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 37, p. 2832-2832Article in journal (Other academic)
  • 26.
    Hedin-Skogman, Barbro
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Croner, Stefan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    TBE-vaccinera barn över 7 år i endemiska områden, men låt de små barnen slippa.2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 43, p. 3367-3367Article in journal (Other (popular science, discussion, etc.))
  • 27.
    Henningsson, A J
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Malmvall, Bo-Eric
    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. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Matussek, Andreas
    Klinisk mikrobiologi, Länssjuhuset Ryhov, Jönköping.
    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.
    Neuroborreliosis-an epidemiological, clinical and healthcare cost study from an endemic area in the south-east of Sweden2010In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 16, no 8, p. 1245-1251Article in journal (Refereed)
    Abstract [en]

    We studied retrospectively the medical records of all patients (n = 150) diagnosed, by cerebrospinal fluid (CSF) analysis, with neuroborreliosis (NB) in Jonkoping County, Sweden during 2000-2005. The number of NB cases increased from 5/100 000 to 10/100 000 inhabitants/year. In 17% of the patients, anti-Borrelia antibodies were found in CSF but not in serum at the time of diagnosis. Facial palsy, headache and fever were frequent manifestations in children, whereas unspecific muscle and joint pain were the most commonly reported symptoms in older patients. Post-treatment symptoms persisting for more than 6 months occurred in 13%, and the patients concerned were significantly older, had longer-lasting symptoms prior to treatment, had higher levels of Borrelia-specific IgG in CSF, and more often had radiculitis. The total cost of NB-related healthcare was estimated to be euro500 000 for the entire study group (euro3300 per patient), and the cost of social benefits was estimated to be euro134 000 (euro2000 per patient). CSF analysis is necessary for the diagnosis of NB, because some patients develop antibodies in serum later than in CSF. Early diagnosis of borreliosis would result in reduced human suffering and in economic gain.

  • 28.
    Henningsson, Anna J.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Department of Infectious Diseases, Ryhov County Hospital, Jönköping.
    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.
    Sandholm, Kerstin
    Department of Chemistry and Biomedical Sciences, University of Kalmar, Kalmar.
    Carlsson, Sten-Anders
    Åland Borrelia Group, Åland Central Hospital, Finland.
    Granlund, Hans
    Åland Borrelia Group, Åland Central Hospital, Finland.
    Jansson, Christian
    Åland Borrelia Group, Åland Central Hospital, Finland.
    Nyman, Dag
    Åland Borrelia Group, Åland Central Hospital, Finland.
    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.
    Nilsson Ekdahl, Kristina
    Department of Chemistry and Biomedical Sciences, University of Kalmar, Kalmar.
    Complement activation in Lyme neuroborreliosis - Increased levels of C1q and C3a in cerebrospinal fluid indicate complement activation in the CNS2007In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 183, no 01-Feb, p. 200-207Article in journal (Refereed)
    Abstract [en]

    A strong initial inflammatory response is important in neuroborreliosis. Since complement is a main player in early inflammation, we monitored the concentration and activation of complement in plasma and cerebrospinal fluid from 298 patients, of whom 23 were diagnosed with neuroborreliosis. Using sandwich ELISAs, we found significantly elevated levels of C1q, C4, C3, and C3a in cerebrospinal fluid, but not in plasma, in patients with neuroborreliosis. This finding indicates that complement plays a role in the human immune response in neuroborreliosis, that the immunologic process is compartmentalized to the CNS, and that complement activation may occur via the classical pathway.

  • 29.
    Henningsson, Anna J.
    et al.
    Regional Jonköping County, Sweden.
    Lindqvist, Richard
    Umeå University, Sweden.
    Norberg, Peter
    University of Gothenburg, Sweden.
    Lindblom, Pontus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Roth, Anette
    University of Gothenburg, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Bergstrom, Tomas
    University of Gothenburg, Sweden.
    Overby, Anna K.
    Umeå University, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Regional Jonköping County, Sweden.
    Human Tick-Borne Encephalitis and Characterization of Virus from Biting Tick2016In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 22, no 8, p. 1485-1487Article in journal (Refereed)
    Abstract [en]

    We report a case of human tick-borne encephalitis (TBE) in which the TBE virus was isolated from the biting tick. Viral growth and sequence were characterized and compared with those of a reference strain. Virus isolation from ticks from patients with TBE may offer a new approach for studies of epidemiology and pathogenicity.

  • 30.
    Henningsson, Anna J
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Ryhov County Hospital, Jönköping.
    Tjernberg, Ivar
    Kalmar County Hospital, Kalmar.
    Malmvall, Bo-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. 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.
    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.
    Indications of Th1 and Th17 responses in cerebrospinal fluid from patients with Lyme neuroborreliosis: a large retrospective study2011In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 8, no 36Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies indicate that successful resolution of Lyme neuroborreliosis (NB) is associated with a strong T helper (Th) 1-type cytokine response in the cerebrospinal fluid (CSF) followed by a down-regulating Th2 response, whereas the role of the recently discovered Th17 cytokine response is unknown. Methods: To investigate the relative contribution of different Th associated cytokine/chemokine responses, we used a multiple bead array to measure the levels of CXCL10 (Th1 marker), CCL22 (Th2 marker), IL-17 (Th17 marker) and CXCL8 (general inflammation marker), in serum and in CSF from untreated patients with confirmed NB (n = 133), and non-NB patients (n = 96), and related the findings to clinical data. Samples from patients with possible early NB (n = 15) and possible late NB (n = 19) were also analysed, as well as samples from an additional control group with orthopaedic patients (n = 17), where CSF was obtained at spinal anaesthesia. Results: The most prominent differences across groups were found in the CSF. IL-17 was elevated in CSF in 49% of the patients with confirmed NB, but was not detectable in the other groups. Patients with confirmed NB and possible early NB had significantly higher CSF levels of CXCL10, CCL22 and CXCL8 compared to both the non-NB group and the control group (p andlt; 0.0001 for all comparisons). Patients in the early NB group, showing a short duration of symptoms, had lower CCL22 levels in CSF than did the confirmed NB group (p andlt; 0.0001). Furthermore, patients within the confirmed NB group showing a duration of symptoms andlt; 2 weeks, tended to have lower CCL22 levels in CSF than did those with longer symptom duration (p = 0.023). Cytokine/chemokine levels were not correlated with clinical parameters or to levels of anti-Borrelia-antibodies. Conclusion: Our results support the notion that early NB is dominated by a Th1-type response, eventually accompanied by a Th2 response. Interestingly, IL-17 was increased exclusively in CSF from patients with confirmed NB, suggesting a hitherto unknown role for Th17 in NB. However, for conclusive evidence, future prospective studies are needed.

  • 31.
    Henningsson, Anna J
    et al.
    Ryhov County Hospital, Jönköping.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Gyllemark, Paula
    Ryhov County Hospital, Jönköping.
    Kozak Ljunggren, Monika
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology.
    Matussek, Andreas
    Ryhov County Hospital, Jönköping.
    Nyman, Dag
    Ryhov County Hospital, Jönköping.
    Ekerfelt, Christina
    Bimelix Biomedical Laboratory, Mariehamn, Åland, Finland .
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Ryhov County Hospital, Jönköping.
    Forsberg, Pia
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine.
    Low risk of seroconversion or clinical disease in humans after a bite by an Anaplasma phagocytophilum-infected tick2015In: Ticks and Tick-borne Diseases, ISSN 1877-959X, E-ISSN 1877-9603, Vol. 6, no 6, p. 787-792Article in journal (Refereed)
    Abstract [en]

    The risk of contracting human granulocytic anaplasmosis (HGA) after a tick bite is mainly unknown. In this study we investigated the clinical and serological response in 30 humans bitten by ticks positive for Anaplasma phagocytophilum (Group A), 30 humans bitten by Borrelia burgdorferi sensu lato (s.l.)-positive ticks (Group B), and 30 humans bitten by ticks negative for both A. phagocytophilum and B. burgdorferi s.l. (Group C). Ticks, blood samples and questionnaires were collected from tick-bitten humans at 34 primary healthcare centres in Sweden and in the Åland Islands, Finland, at the time of the tick bite and after three months. A total of 2553 ticks detached from humans in 2007-2009 were analyzed by polymerase chain reaction, and 31 (1.2%) were positive for A. phagocytophilum, 556 (21.8%) were positive for B. burgdorferi s.l., and eight (0.3%) were co-infected by A. phagocytophilum and B. burgdorferi s.l. The overall prevalence of Anaplasma IgG antibodies in the included participants (n=90) was 17%, and there was no significant difference between the groups A-C. Only one of the participants (in Group C) showed a four-fold increase of IgG antibodies against A. phagocytophilum at the three-month follow-up, but reported no symptoms. The frequency of reported symptoms did not differ between groups A-C, and was unrelated to the findings of A. phagocytophilum and B. burgdorferi s.l. in the detached ticks. We conclude that the risk for HGA or asymptomatic seroconversion after a tick bite in Sweden or in the Åland Islands is low, even if the tick is infected by A. phagocytophilum.

  • 32.
    Jarefors, Sara
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Bennet, Louise
    Department of Clinical Sciences, University Hospital of Malmö, Lund University, Malmö .
    You, Elin
    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.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Berglund, Johan
    Department of Clinical Sciences, University Hospital of Malmö, Lund University, Malmö .
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Lyme borreliosis reinfection: might it be explained by gender difference in immune response?2006In: Immunology, ISSN 0019-2805, Vol. 118, no 2, p. 224-235Article in journal (Refereed)
    Abstract [en]

    Lyme borreliosis is a tick-borne disease often manifesting as a circular skin lesion. This cutaneous form of the disease is known as erythema migrans. In a 5-year follow-up study in southern Sweden, 31 of 708 individuals initially diagnosed with erythema migrans and treated with antibiotics were found to be reinfected with Borrelia burgdorferi. Although men and women were tick-bitten to the same extent, 27 of the 31 reinfected individuals were women, all of whom were over 44 years of age. The aim of this study was to determine whether this discrepancy in gender distribution could be a result of differences in immunological response. Twenty single-infected and 21 reinfected women and 18 single-infected and three reinfected men were included in the study. None of the participants showed any sign of an ongoing B. burgdorferi infection, and thus the habitual response was captured. Lymphocytes were separated from blood and stimulated with antigens. The secretion of interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-γ and tumour necrosis factor (TNF)-α was measured by enzyme-linked immunosorbent assay (ELISA), enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) or Immulite. No difference was detected in cytokine secretion between single-infected and reinfected individuals. We also compared the immunological response in men and women, regardless of the number of B. burgdorferi infections. Women displayed a significantly higher spontaneous secretion of all cytokines measured. The ratios of IL-4:IFN-γ and IL-10:TNF-α were significantly higher in women. Gender differences in immune reactivity might in part explain the higher incidence of reinfection in women. The higher IL-4:IFN-γ and IL-10:TNF-α ratios seen in women indicate that postmenopausal women have T helper type 2 (Th2)-directed reactivity with impaired inflammatory responses which might inhibit the elimination of spirochetes.

  • 33.
    Jarefors, Sara
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Janefjord, Camilla
    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, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Decreased up-regulation of the interleukin-12Rbeta2-chain and interferon-gamma secretion and increased number of forkhead box P3-expressing cells in patients with a history of chronic Lyme borreliosis compared with asymptomatic Borrelia-exposed individuals2007In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 147, no 1, p. 18-27Article in journal (Refereed)
    Abstract [en]

    Lyme borreliosis (LB) can, despite adequate antibiotic treatment, develop into a chronic condition with persisting symptoms such as musculoskeletal pain, subjective alteration of cognition and fatigue. The mechanism behind this is unclear, but it has been postulated that an aberrant immunological response might be the cause. In this study we investigated the expression of the T helper 1 (Th1) marker interleukin (IL)-12Rβ2, the marker for T regulatory cells, forkhead box P3 (FoxP3) and the cytokine profile in patients with a history of chronic LB, subacute LB, previously Borrelia-exposed asymptomatic individuals and healthy controls. Fifty-four individuals (12 chronic LB, 14 subacute LB, 14 asymptomatic individuals and 14 healthy controls) were included in the study and provided a blood sample. Mononuclear cells were separated from the blood and stimulated with antigens. The IL-12Rβ2 and FoxP3 mRNA expression was analysed with real-time reverse transcription–polymerase chain reaction (RT–PCR). The protein expression of IL-12Rβ2 on CD3+, CD4+, CD8+ and CD56+ cells was assessed by flow cytometry. Furthermore, the secretion of interferon (IFN)-γ, IL-4, IL-5, IL-10, IL-12p70 and IL-13 was analysed by enzyme-linked immunospot (ELISPOT) and/or enzyme-linked immunosorbent assay (ELISA). Chronic LB patients displayed a lower expression of Borrelia-specific IL-12Rβ2 on CD8+ cells and also a lower number of Borrelia-specific IFN-γ-secreting cells compared to asymptomatic individuals. Furthermore, chronic LB patients had higher amounts of Borrelia-specific FoxP3 mRNA than healthy controls. We speculate that this may indicate that a strong Th1 response is of importance for a positive outcome of a Borrelia infection. In addition, regulatory T cells might also play a role, by immunosuppression, in the development of chronic LB.

  • 34.
    Jarefors, Sara
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Karlsson, Marika
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Eliasson, I.
    Department of Clinical Microbiology, Kalmar County Hospital, 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.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Reduced number of interleukin-12 secreting cells in patients with Lyme borreliosis previously exposed to Anaplasma phagocytophilum2006In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 143, no 2, p. 322-328Article in journal (Refereed)
    Abstract [en]

    Lyme borreliosis and human granulocytic ehrlichiosis are tick-borne diseases caused by Borrelia burgdorferi and Anaplasma phagocytophilum, respectively. Infection with A. phagocytophilum has been observed to induce immunosuppression and animal studies suggest that the bacteria might also have prolonged inhibitory effects on immune cells. The aim of this study was to investigate the cytokine secretion in patients exposed previously to A. phagocytophilum and currently infected with B. burgdorferi compared with patients infected with B. burgdorferi and seronegative for A. phagocytophilum. Eight patients with erythema migrans and antibodies against A. phagocytophilum, 15 patients with erythema migrans and negative A. phagocytophilum serology and 15 non-exposed healthy individuals were included in the study. Blood mononuclear cells were stimulated with Borrelia-antigen and the number of cytokine [interleukin (IL)-4, IL-5, IL-12, IL-13 and interferon (IFN)-γ]-secreting cells was detected by enzyme-linked immunospot (ELISPOT). This study shows that patients with a previous exposure to A. phagocytophilum and a current infection with B. burgdorferi have a lower number of Borrelia-specific cells secreting IL-12 compared to Ap seronegative patients infected with B. burgdorferi (P < 0·001), indicating impairment in the ability to mount strong Th1-responses. We suggest that this mirrors a reduced Th1 response caused by A. phagocytophilum which could influence the outcome of the Borrelia infection and, speculatively, may also have implications in other conditions.

  • 35.
    Johansson, Joel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Sahin, Christofer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Pestoff, Rebecka
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Ignatova, Simone
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Edsjö, Anders
    Sahlgrenska University Hospital Göteborg .
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Stenmark Askmalm, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    A Novel SMAD4 Mutation Causing Severe Juvenile Polyposis Syndrome with Protein Losing Enteropathy, Immunodeficiency, and Hereditary Haemorrhagic Telangiectasia.2015In: Case Reports in Gastrointestinal Medicine, ISSN 2090-6528, E-ISSN 2090-6536, Vol. 2015, p. 1-5, article id 140616Article in journal (Refereed)
    Abstract [en]

    Juvenile polyposis syndrome (JPS) is a rare genetic disorder characterized by juvenile polyps of the gastrointestinal tract. We present a new pathogenic mutation of the SMAD4 gene and illustrate the need for a multidisciplinary health care approach to facilitate the correct diagnosis. The patient, a 47-year-old Caucasian woman, was diagnosed with anaemia at the age of 12. During the following 30 years, she developed numerous gastrointestinal polyps. The patient underwent several operations, and suffered chronic abdominal pain, malnutrition, and multiple infections. Screening of the SMAD4 gene revealed a novel, disease-causing mutation. In 2012, the patient suffered hypoalbuminemia and a large polyp in the small bowel was found. Gamma globulin was given but the patient responded with fever and influenza-like symptoms and refused more treatment. The patient underwent surgery in 2014 and made an uneventful recovery. At follow-up two months later albumin was 38 g/L and IgG was 6.9 g/L. Accurate diagnosis is essential for medical care. For patients with complex symptomatology, often with rare diseases, this is best provided by multidisciplinary teams including representatives from clinical genetics. Patients with a SMAD4 mutation should be followed up both for JPS and haemorrhagic hereditary telangiectasia and may develop protein loosing enteropathy and immunodeficiency.

  • 36.
    Lindblom, A.
    et al.
    Uppsala University, Sweden.
    Wallménius, K.
    Uppsala University, Sweden.
    Nordberg, M.
    Linköping University, Department of Clinical and Experimental Medicine. 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.
    Eliasson, I.
    Norra Älvsborg County Hospital (NÄL), Trollhättan, Sweden .
    Påhlson, C.
    Uppsala University, Sweden.
    Nilsson, K.
    Uppsala University, Sweden and Center of Clinical Research, Falun, Sweden.
    Seroreactivity for spotted fever rickettsiae and co-infections with other tick-borne agents amond habitants in central and southern Sweden2013In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 32, no 3, p. 317-323Article in journal (Refereed)
    Abstract [en]

    Patients seeking medical care with erythema migrans or flu-like symptoms after suspected or observed tick bite in the southeast of Sweden and previously investigated for Borrelia spp. and/or Anaplasma sp. were retrospectively examined for serological evidence of rickettsial infection (Study 1). Twenty of 206 patients had IgG and/or IgM antibodies to Rickettsia spp. equal to or higher than the cut-off titre of 1:64. Seven of these 20 patients showed seroconversion indicative of recent or current infection and 13 patients had titres compatible with past infection, of which five patients were judged as probable infection. Of 19 patients with medical records, 11 were positive for Borrelia spp. as well, and for Anaplasma sp., one was judged as positive. Five of the 19 patients had antibodies against all three pathogens. Erythema migrans or rash was observed at all combinations of seroreactivity, with symptoms including fever, muscle pain, headache and respiratory problems. The results were compared by screening an additional 159 patients (Study 2) primarily sampled for the analysis of Borrelia spp. or Mycoplasma pneumoniae. Sixteen of these patients were seroreactive for Rickettsia spp., of which five were judged as recent or current infection. Symptoms of arthritis, fever, cough and rash were predominant. In 80 blood donors without clinical symptoms, approximately 1 % were seroreactive for Rickettsia spp., interpreted as past infection. The study shows that both single and co-infections do occur, which illustrate the complexity in the clinical picture and a need for further studies to fully understand how these patients should best be treated.

  • 37.
    Lindblom, Anders
    et al.
    Uppsala University, Sweden; Clin Research Centre, Sweden.
    Wallmenius, Katarina
    Uppsala University, Sweden.
    Sjöwall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Nilsson, Kenneth
    Uppsala University, Sweden; Clin Research Centre, Sweden.
    Prevalence of Rickettsia spp. in Ticks and Serological and Clinical Outcomes in Tick-Bitten Individuals in Sweden and on the Aland Island2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11, article id e0166653Article in journal (Refereed)
    Abstract [en]

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

  • 38.
    Lindblom, Pontus
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Wilhelmsson, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Fryland, Linda
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Matussek, Andreas
    County Hospital Ryhov, Jönköping.
    Haglund, Mats
    Kalmar County hospital.
    Sjöwall, Johanna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Vene, Sirkka
    Swedish Institute for Communicable Disease Control, Stockholm.
    Nyman, Dag
    Åland Central Hospital, Åland, Finland.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Determining factors for successful vaccination against tick-borne encephalitis virus in older individuals2014Manuscript (preprint) (Other academic)
    Abstract [en]

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

  • 39.
    Lindblom, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Matussek, Andreas
    County Hospital Ryhov, Sweden .
    Haglund, Mats
    County Hospital Kalmar, Sweden .
    Sjöwall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Vene, Sirkka
    Public Health Agency Sweden, Stockholm.
    Nyman, Dag
    Aland Central Hospital, Finland .
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Factors Determining Immunological Response to Vaccination against Tick-Borne Encephalitis Virus in Older Individuals2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 6, p. e0100860-Article in journal (Refereed)
    Abstract [en]

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

  • 40.
    Lindblom, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Sjowall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Haglund, Mats
    Kalmar County hospital.
    Matussek, Andreas
    County Hospital Ryhov, Jönköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vene, Sirkka
    Swedish Institute for Communicable Disease Control, Stockholm.
    Nyman, Dag
    Åland Central Hospital, Åland, Finland.
    Andreassen, Åshild
    Norwegian Institute of Public Health, Olso, Norway.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Tick-borne encephalitis virus in ticks detached from humans and follow-up of serological and clinical response.2014In: Ticks and Tick Borne Diseases, ISSN 1877-959X, Vol. 5, no 1, p. 21-28Article in journal (Refereed)
    Abstract [en]

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

  • 41.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar.
    Nilsson, Ingela
    Department of Clinical Chemistry, County Hospital, Kalmar.
    Åkerlind, Britt
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    High hepatocyte growth factor levels in faeces during acute infectious gastroenteritis2003In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 35, no 11-12, p. 858-862Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor (HGF) is a potent mitogen of mature epithelial cells which is produced after organ injuries and acts as a trigger for regeneration in the impaired organ. The aim of the present study was to investigate local production of HGF during infectious gastroenteritis. We measured the concentration of HGF in serum and faeces in 49 patients with acute infectious gastroenteritis (bacterium=30, virus=10, amoebae=1, and probable infection=8) at the time of referral to hospital and at convalescence (n=31). The values were compared with normal healthy vaccination volunteers (n=11) as well as patients with acute non-infectious diarrhoea (n=10). The presence of HGF in faeces was confirmed by ELISA and Western immunoblot. HGF concentrations in faeces was significantly higher in the patients with infectious gastroenteritis compared to the control groups (p<0.0001). Using a cut-off concentration of 20 ng/g, the overall sensitivity of faeces HGF to distinguish infectious gastroenteritis (bacterial, viral, probable infection) was 98% with a specificity of 100%. At convalescence all patients had normal values. There was no significant correlation between HGF concentrations in faeces and serum. Determination of faeces HGF may identify cases of transmittable diarrhoea requiring isolation at an early stage.

  • 42.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar.
    Darelid, Johan
    Department of Infectious Diseases, County Hospital, Jönköping.
    Nilsson, Ingela
    Department of Clinical Chemistry, County Hospital, Kalmar, Sweden.
    Frydén, Aril
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Söderström, Claes
    Department of Infectious Diseases, County Hospital, Kalmar, Sweden.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Hepatocyte growth factor may act as an early therapeutic predictor in pneumonia2002In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 34, no 7, p. 500-504Article in journal (Refereed)
    Abstract [en]

    High serum levels of hepatocyte growth factor (HGF) may reflect the regenerative effect and enhanced local and systemic production of this cytokine after organ injuries. The possibility of using serial serum HGF values in order to predict the results of therapy for pneumonia was investigated in this study. In a prospective multicenter study we investigated the serum levels of HGF and CRP before and within 48 h after treatment in 70 patients with pneumonia. Serum levels of HGF before treatment were significantly higher than the HGF levels of a normal population (p < 0.0001). Within 48 h serum HGF levels had decreased significantly in those patients who ultimately responded to the initial antibiotic therapy (p < 0.0001). Serum HGF levels at 48 h were unchanged or increased in cases in whom the initial therapy was ineffective and had to be changed. CRP and HGF levels were significantly correlated. Using multivariate logistic regression analysis it was found that individual changes in acute serum HGF levels and serum HGF levels obtained within 48 h could predict the results of therapy at least as significantly (p < 0.003) as CRP (p = 0.05), although CRP levels were known and used by the physician to decide whether or not to change the initial therapy. We conclude that serial control of serum HGF levels can be used as an early indicator to predict the results of therapy during treatment of pneumonia.

  • 43.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar, Sweden.
    Nilsson, Ingela
    Department of Clinical Chemistry, County Hospital, Kalmar, Sweden.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Sample handling and stability of hepatocyte growth factor in blood samples2002In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 19, no 4, p. 201-205Article in journal (Refereed)
    Abstract [en]

    As regards clinical studies performed on hepatocyte growth factor (HGF) during recent years, we have aimed in the present study to investigate the eventual differences in sample handling of this cytokine that might influence the results of serum concentrations. Venous blood from patients with current infectious diseases and controls was used in different sub-studies. Compared with samples separated within one hour, no significant changes in serum HGF levels were observed when whole blood stayed 4, or 24 h at 6°C before or 6 h in room temperature after separation but HGF levels were significantly higher (P<0.01) when whole blood was kept at room temperature 4 and 24 h before separation. Serum HGF was stable up to 20 freeze-thaw cycles. The serum concentrations of HGF were significantly higher than levels in the plasma (19%; P<0.05). A significant increase in serum HGF levels (12%, P<0.05) was observed after shaking the whole blood sample to a visible haemolysis, although the HGF concentration in blood cells was around half of that in serum. HGF tolerated storage at −70°C for at least 4 months. We conclude that standardized methods in sample handling are important in the study of HGF concentrations in blood samples.

  • 44.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Holmgren Peterson, Kajsa
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Perskvist, Nasrin
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Peterson, Curt
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    An in vitro model for assessment of the biological activity of hepatocyte growth factor2007In: Growth Factors, ISSN 0897-7194, E-ISSN 1029-2292, Vol. 25, no 1, p. 33-40Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor (HGF) is a multifunctional growth factor with potent wound-healing properties that functions in the healing of chronic injuries. However, there may be a loss of HGF activity in certain chronic cases; this might be indicated by the presence of high amounts of HGF in body fluids and by the elevated expression of the HGF receptor in tissue biopsies. In such cases, a reliable means of assessing the activity of endogenous HGF would be valuable in allowing clinicians to decide if treatment with HGF would be useful. In this study, we developed an in vitro wound assay that used a mouse skin epithelial cell line to evaluate the biological activity of HGF. We showed that HGF accelerated the motility of the epithelial cells in a dose-dependent fashion with high sensitivity and specificity. This in vitro assay might be used to determine the activity of both endogenous and recombinant HGF.

  • 45.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Millinger, Eva
    Linköping University, Department of Medicine and Care, Pulmonary Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Ingela
    Departments of Clinical Chemistry, County Hospital, Kalmar, Sweden.
    Zetterström, Olle
    Linköping University, Department of Molecular and Clinical Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Departments of Clinical Physiology, County Hospital, Kalmar, Sweden.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Exhaled breath condensate and serum levels of hepatocyte growth factor in pneumonia2002In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 96, no 2, p. 115-119Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor (HGF) is a protein produced by mesenchymal cells in many organs, which can stimulate epithelial growth. An enhanced production and concentration of HGF is observed after injuries. The lung is one of the major sources of HGF. By cooling exhaled air, a condensate is formed containing molecules from bronchi and alveoli. In order to investigate HGF concentration and time course in pneumonia, paired serum and exhaled breath condensate was collected from 10 patients with pneumonia, 10 patients with non-respiratory infections and 11 healthy controls. The concentration of HGF was measured by an immunoassay kit. In the acute phase HGF-levels in breath condensate and serum were significantly higher in the patients with pneumonia compared to the control groups. Similar concentrations in breath condensate were seen in healthy controls and in patients with non-respiratory infections. In the patients with pneumonia a decrease in serum HGF was seen already after 4–7 days while HGF values in breath condensate remained elevated even after 4–6 weeks. These results might imply local production of HGF in the lungs and a long repair and healing process after pneumonia.

  • 46.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nilsson, Ingela
    Department of Clinical Chemistry, County Hospital, Kalmar.
    Hagberg, Lars
    Department of Infectious Diseases, Sahlgrenska Hospital, Göteborg.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar.
    Roberg, Magnus
    Department of Infectious Diseases, County Hospital, Norrköping, Sweden .
    Söderström, Claes
    Department of Infectious Diseases, County Hospital, Kalmar.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Hepatocyte Growth Factor Levels in Cerebrospinal Fluid: A Comparison between Acute Bacterial and Nonbacterial Meningitis2000In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 181, no 6, p. 2092-2094Article in journal (Refereed)
    Abstract [en]

    The organotrophic functions of the hepatocyte growth factor (HGF) have been the subject of several studies. In the more recent studies, this function has been reported in the brain. In the present study, we have measured the levels of HGF in cerebrospinal fluid (CSF) and sera from 78 patients divided into 6 different groups according to central nervous system (CNS) infection and control. Quantitative measurements of HGF in the CSF and serum were performed by an enzyme-linked immunosorbent assay. Elevated values of CSF HGF were found in the patients with acute bacterial/probable bacterial meningitis (P < .001), compared with nonbacterial CNS infections and facial palsy, as well as with a control group without signs of CNS involvement. The values of CSF HGF were not correlated to blood-brain-barrier disruption in the groups. These observations might indicate an intrathecal production of HGF in acute bacterial/probable bacterial meningitis.

  • 47.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Olsson, Hans
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Söderström, Claes
    Department of Infectious Diseases, County Hospital in Kalmar, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital in Kalmar, Sweden.
    Peterson, Curt
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Hepatocyte growth factor in chronic leg ulcers – no biological activity – no improvement2005In: Journal of dermatological science (Amsterdam), ISSN 0923-1811, E-ISSN 1873-569X, Vol. 39, no 1, p. 62-64p. 62-64Article in journal (Other academic)
    Abstract [en]

    No abstract available.

  • 48.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Perskvist, Nasrin
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Holmgren-Pettersson, Kajsa
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Hepatocyte growth factor accelerates restitution of damaged mouse melanocyte monolayer in vitroManuscript (preprint) (Other academic)
    Abstract [en]

    In a recent pilot study we observed enhanced wound repair properties in chronic leg ulcers after HGF administration. The aim of the present study was to assess the mechanism of HGF in the wound-healing process by an in vitro study of HGF on a transformed mouse skin epithelial cell line (CCL-53. 1) that expresses the HGF receptor, c-Met. HGF did not enhance cell proliferation, judged by [3H}thymidine incorporation. The restitution of injured epithelial cells was significantly increased by HGF. This effect was dose-dependant, beginning at low concentrations (1ng/ml) of HGF, and was inhibited by heparin. HGF enhanced migration of epithelial cells compared to untreated controls. The actin structure was changed by HGF, with less F-actin in the dense peripheral structures compared to untreated cells. Corresponding morphological changes in cells were found showing spread morphology with smaller intracellular spaces after HGF addition. We conclude that HGF may contribute to restitution of the damaged mouse epithelial cell monolayer by morphologic changes and enhanced motility of cells towards the injured area.

  • 49.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Health Sciences.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar, Sweden.
    Söderström, Charlotte
    Department of Infectious Diseases, County Hospital, Kalmar, Sweden.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Hepatocyte growth factor may accelerate healing in chronic leg ulcers: a pilot study2002In: Journal of dermatological treatment (Print), ISSN 0954-6634, E-ISSN 1471-1753, Vol. 13, no 2, p. 81-86Article in journal (Refereed)
    Abstract [en]

    BACKGROUND : Hepatocyte growth factor (HGF) is a heparin-binding protein with mitogenic, motogenic and morphogenic activities for various cell types. The regenerative properties of HGF have been the object of several animal and in vitro studies in recent years.

    OBJECTIVE : To investigate the physiological and therapeutic effects of HGF on chronic leg ulcers.

    METHODS : HGF in gel form was locally applied, once daily for 7 days, to 15 of 19 chronic leg ulcers in 11 elderly patients. All patients had previously been treated by conventional methods and their leg ulcers had been in stable conditions for between 1 and 14 years. Any signs of allergy, discomfort or pain were reported daily. Microcirculation perfusion in the ulcers, compared to the intact contiguous skin, was determined by laser Doppler at the beginning of the study, after 1 week and again after 3 months (in seven patients). Ulcer size and characteristics were also documented.

    RESULTS : It was observed that microcirculatory perfusion, which might reflect the angiogenic effect of HGF, was statistically significantly correlated ( r = 0.94, p < 0.002) to ulcer area reduction in the treated ulcers. Excellent (84-100% area reduction) or partial healing (58-59%) was seen in eight out of 11 patients. No control group was included in this pilot study, which must be completed by proper control studies.

    CONCLUSION : This study suggests that HGF may heal chronic leg ulcers, possibly by improving the microcirculation. Proper control studies need to be performed.

  • 50. Nilsson Ekdahl, Kristina
    et al.
    Henningsson, Anna J
    IKE Jönköping.
    Sandholm, Kerstin
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical 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 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.
    Ekerfelt, Christina
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Immunity in Borreliosis with special emphasis on the role of complement.2007In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 598, p. 198-213Article, review/survey (Refereed)
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