Ebola Hemorrhagic Fever: Novel Biomarker Correlates of Clinical Outcome

• Type of Material: Article
• Authors: Anita Katherine McElroy, Emory University; Bobbie R. Erickson, Centers for Disease Control and Prevention; Timothy D. Flietstra, Centers for Disease Control and Prevention; Pierre E. Rollin, Centers for Disease Control and Prevention; Stuart T. Nichol, Emory University; Jonathan S. Towner, Centers for Disease Control and Prevention; Christina Spiropoulou, Emory University
• Language: English
• Date: 2014-08-15
• Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option C
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
• License: Creative Commons Universal : Public Domain Dedication
• Final Published Version (URL): http://dx.doi.org/10.1093/infdis/jiu088
• Title of Journal or Parent Work: Journal of Infectious Diseases
• ISSN: 0022-1899
• Volume: 210
• Issue: 4
• Start Page: 558
• End Page: 566
• Grant/Funding Information: This work was supported by the PIDS/St. Jude Fellowship (to A. K . M.); the National Institutes of Health Loan Repayment Award (to A. K. M.); and the Atlanta Pediatric Scholars Program is an NIH K12 (grant HD072245 to A. K. M.).
• Keywords: Ebola virus; TISSUE FACTOR; FERRITIN LEVELS; Immunology; Gulu; RESPONSES; UGANDA; Life Sciences & Biomedicine; OUTBREAK; PREVALENCE; FEATURES; hemorrhage; biomarkers; Science & Technology; VIRUS INFECTION; DC-SIGN; INVOLVEMENT; Infectious Diseases; hemorrhagic fever virus; Microbiology
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Virology

Abstract

Background. Ebola hemorrhagic fever (EHF) outbreaks occur sporadically in Africa and result in high rates of death. The 2000-2001 outbreak of Sudan virus-associated EHF in the Gulu district of Uganda led to 425 cases, of which 216 were laboratory confirmed, making it the largest EHF outbreak on record. Serum specimens from this outbreak had been preserved in liquid nitrogen from the time of collection and were available for analysis. Methods. Available samples were tested using a series of multiplex assays to measure the concentrations of 55 biomarkers. The data were analyzed to identify statistically significant associations between the tested biomarkers and hemorrhagic manifestations, viremia, and/or death. Results. Death, hemorrhage, and viremia were independently associated with elevated levels of several chemokines and cytokines. Death and hemorrhage were associated with elevated thrombomodulin and ferritin levels. Hemorrhage was also associated with elevated levels of soluble intracellular adhesion molecule. Viremia was independently associated with elevated levels of tissue factor and tissue plasminogen activator. Finally, samples from nonfatal cases had higher levels of sCD40L. Conclusions. These novel associations provide a better understanding of EHF pathophysiology and a starting point for researching new potential targets for therapeutic interventions.