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The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in Crimean-Congo hemorrhagic fever
Authors:Gurdal Yilmaz  Ahmet Mentese  Selcuk Kaya  Aysegul Uzun  S. Caner Karahan  Iftihar Koksal
Affiliation:1. Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Karadeniz Technical University, KTU Tip Fakültesi, Enfeksiyon Hastal?klar?, Trabzon, Turkey;2. Department of Biochemistry, Karadeniz Technical University, School of Medicine, Trabzon, Turkey;1. Arboviruses and Viral Haemorrhagic Fevers Laboratory (National Ref. Lab), Pasteur Institute of Iran, 60 Pasteur Ave., Tehran, Iran;2. Department of Disease, Medical University of Birjand, Khorasan-Jonobi, Iran;3. Department of Epidemiology, Pasteur Institute of Iran, Tehran, Iran;1. Microbial Containment Complex, National Institute of Virology, Sus Road, Pashan, Pune 410021, India;2. Bioinformatics Group, National Institute of Virology, 20-A Dr Ambedkar Road, Pune 411001, India;1. University of Veterinary and Animal Sciences, Lahore, Pakistan;2. Institute of Public Health, Lahore, Pakistan;3. Islamia University, Bahawalpur, Pakistan;4. Naval Medical Research Unit, Cairo, Egypt;1. Division of Infectious Diseases, Department of Internal Medicine, Patras University General Hospital, Patras, Greece;2. Department of Microbiology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, 54006, Greece;3. Laboratory of GeoInformatics, Department of Surveying Engineering, Technological Educational Institute of Athens, Athens, Greece
Abstract:BackgroundCrimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease caused by a tick-borne virus from the Bunyaviridae family. It has recently been reported that soluble urokinase-type plasminogen activator receptor (suPAR), secreted from endothelial cells and the mononuclear phagocyte system, one of the main targets of the CCHF virus, is a potential biomarker for several bacterial and viral infection diseases.ObjectivesThis study was intended to determine the diagnostic and prognostic significance of suPAR levels in CCHF.Study designThis retrospective study was conducted between June 2006 and August 2009 using plasma from patients monitored with a diagnosis of CCHF and from healthy blood donors. Levels of plasma suPAR were determined using an enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturer's instructions.ResultsOne hundred CCHF patients were enrolled in the study. The control group was made up of 53 healthy blood donors. suPAR values of 6.2 ± 4.2 were determined in the CCHF patients and of 2.3 ± 0.6 in the control group (p < 0.0001). A suPAR level optimum diagnostic cut-off point of 3.06 ng/mL was determined, with an area underneath the ROC (AUROC) curve of 0.94 (95% CI: 0.89–0.97), sensitivity of 87% (95% CI: 79–93%), specificity of 92% (95% CI: 82–98%), PPV of 95% and NPV of 79%. Five of the patients died. suPAR was 18.4 ± 9.1 in the patients that died and 5.6 ± 2.6 in the survivors (p = 0.034). In terms of mortality, suPAR level had an optimum diagnostic cut-off point of 10.6 ng/mL, AUROC of 0.97 (95% CI: 0.94–0.99), sensitivity of 100% (95% CI: 48–100%), specificity of 96% (95% CI: 90–99%), PPV of 50% and NPV of 100%.ConclusionsPlasma suPAR level, a new biomarker, is a test that can be used in the differential diagnosis and monitoring of CCHF in patients admitted to hospital with suspected infection. The test is at the same time important in being a possible predictor of mortality.
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