title: Increased endothelial and macrophage markers are associated with disease severity and mortality in scrub typhus.
abstract: OBJECTIVE
  Scrub typhus is endemic in the Asia-Pacific region. Mortality is high even with treatment, and further knowledge of the immune response during this infection is needed. This study was aimed at comparing plasma levels of monocyte/macrophage and endothelial related inflammatory markers in patients and controls in South India and to explore a possible correlation to disease severity and clinical outcome.
  
  
  METHODS
  Plasma levels of ALCAM, VCAM-1, sCD163, sCD14, YKL-40 and MIF were measured in scrub typhus patients (n = 129), healthy controls (n = 31) and in infectious disease controls (n = 31), both in the acute phase and after recovery, by enzyme immunoassays.
  
  
  RESULTS
  Patients had markedly elevated levels of all mediators in the acute phase, differing from both healthy and infectious disease controls. During follow-up levels of ALCAM, VCAM-1, sCD14 and YKL-40 remained elevated compared to levels in healthy controls. High plasma ALCAM, VCAM-1, sCD163, sCD14, and MIF, and in particular YKL-40 were all associated with disease severity and ALCAM, sCD163, MIF and especially YKL-40, were associated with mortality.
  
  
  CONCLUSIONS
  Our findings show that scrub typhus is characterized by elevated levels of monocyte/macrophage and endothelial related markers. These inflammatory markers, and in particular YKL-40, may contribute to disease severity and clinical outcome.
authors.affiliation: Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway; Faculty of Medicine, University of Oslo, PO Box 1072 Blindern, 0316 Oslo, Norway. Electronic address: kari.otterdal@rr-research.no.
authors.forename: Kari
authors.initials: K
authors.lastname: Otterdal
authors.affiliation: Department of Medicine and Infectious Diseases, Christian Medical College, Vellore 632 004, Tamil Nadu, India.
authors.forename: Jeshina
authors.initials: J
authors.lastname: Janardhanan
authors.affiliation: Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway; Institute of Clinical Medicine, Akershus University Hospital, Sykehusveien 25, 1478 Lørenskog, Norway.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Astrup
authors.affiliation: Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway; Faculty of Medicine, University of Oslo, PO Box 1072 Blindern, 0316 Oslo, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.affiliation: Department of Microbiology, Christian Medical College, Vellore 632 004, Tamil Nadu, India.
authors.forename: John A J
authors.initials: JA
authors.lastname: Prakash
authors.affiliation: Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway; Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway; Faculty of Medicine, University of Oslo, PO Box 1072 Blindern, 0316 Oslo, Norway.
authors.forename: Tove
authors.initials: T
authors.lastname: Lekva
authors.affiliation: Department of Medicine and Infectious Diseases, Christian Medical College, Vellore 632 004, Tamil Nadu, India.
authors.forename: O C
authors.initials: OC
authors.lastname: Abraham
authors.affiliation: Department of Medicine, Christian Medical College, Vellore 632 004, Tamil Nadu, India.
authors.forename: Kurien
authors.initials: K
authors.lastname: Thomas
authors.affiliation: Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, St. Olavs Hospital, PO Box 3250 Sluppen, 7006 Trondheim, Norway; Norwegian University of Science and Technology, PO Box 8905, 7491 Trondheim, Norway.
authors.forename: Jan Kristian
authors.initials: JK
authors.lastname: Damås
authors.affiliation: Department of Medicine, Christian Medical College, Vellore 632 004, Tamil Nadu, India.
authors.forename: Prasad
authors.initials: P
authors.lastname: Mathews
authors.affiliation: Department of Medicine, Christian Medical College, Vellore 632 004, Tamil Nadu, India.
authors.forename: Dilip
authors.initials: D
authors.lastname: Mathai
authors.affiliation: Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway; Faculty of Medicine, University of Oslo, PO Box 1072 Blindern, 0316 Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Department of Medicine and Infectious Diseases, Christian Medical College, Vellore 632 004, Tamil Nadu, India.
authors.forename: George M
authors.initials: GM
authors.lastname: Varghese
mesh_terms: D054392:Adipokines / Q000097:blood; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015816:Cell Adhesion Molecules, Neuronal / Q000097:blood; D000071451:Chitinase-3-Like Protein 1; D042783:Endothelial Cells / Q000276:immunology*; D005260:Female; D005326:Fetal Proteins / Q000097:blood; D006801:Humans; D007194:India; D007249:Inflammation / Q000276:immunology; D019746:Intramolecular Oxidoreductases / Q000097:blood; D037102:Lectins / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008262:Macrophage Activation; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D011956:Receptors, Cell Surface / Q000097:blood; D012612:Scrub Typhus / Q000097:blood / Q000276:immunology* / Q000401:mortality; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D055815:Young Adult; D000098902:CD163 Antigen; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D054392:Adipokines; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D015816:Cell Adhesion Molecules, Neuronal; D000071451:Chitinase-3-Like Protein 1; D005326:Fetal Proteins; D019746:Intramolecular Oxidoreductases; D037102:Lectins; D018950:Lipopolysaccharide Receptors; D008263:Macrophage Migration-Inhibitory Factors; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1; D000098902:CD163 Antigen; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C084533:CHI3L1 protein, human; C515598:MIF protein, human
keywords: Adhesion molecules; Cytokines; Inflammation; Orientia tsutsugamushi; Scrub typhus