Increased endothelial and macrophage markers are associated with disease severity and mortality in scrub typhus

J Infect. 2014 Nov;69(5):462-9. doi: 10.1016/j.jinf.2014.06.018. Epub 2014 Jul 1.

Abstract

Objectives: 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.

Keywords: Adhesion molecules; Cytokines; Inflammation; Orientia tsutsugamushi; Scrub typhus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / blood
  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / blood
  • Antigens, Differentiation, Myelomonocytic / blood
  • Biomarkers / blood
  • Cell Adhesion Molecules, Neuronal / blood
  • Chitinase-3-Like Protein 1
  • Endothelial Cells / immunology*
  • Female
  • Fetal Proteins / blood
  • Humans
  • India
  • Inflammation / immunology
  • Intramolecular Oxidoreductases / blood
  • Lectins / blood
  • Lipopolysaccharide Receptors / blood
  • Macrophage Activation*
  • Macrophage Migration-Inhibitory Factors / blood
  • Macrophages / immunology*
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Receptors, Cell Surface / blood
  • Scrub Typhus / blood
  • Scrub Typhus / immunology*
  • Scrub Typhus / mortality
  • Vascular Cell Adhesion Molecule-1 / blood
  • Young Adult

Substances

  • ALCAM protein, human
  • Adipokines
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD163 antigen
  • CHI3L1 protein, human
  • Cell Adhesion Molecules, Neuronal
  • Chitinase-3-Like Protein 1
  • Fetal Proteins
  • Lectins
  • Lipopolysaccharide Receptors
  • Macrophage Migration-Inhibitory Factors
  • Receptors, Cell Surface
  • Vascular Cell Adhesion Molecule-1
  • Intramolecular Oxidoreductases
  • MIF protein, human