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Saturday, 10/18/2014 7:06:54 AM

Saturday, October 18, 2014 7:06:54 AM

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Death, hemorrhage, and viremia were independently associated with elevated levels of several chemokines and cytokines.


Ebola Hemorrhagic Fever: Novel Biomarker Correlates of Clinical Outcome

Anita K. McElroy1,2,
Bobbie R. Erickson1,
Timothy D. Flietstra1,
Pierre E. Rollin1,
Stuart T. Nichol1,
Jonathan S. Towner1 and
Christina F. Spiropoulou1

+ Author Affiliations

1Viral Special Pathogens Branch, Centers for Disease Control and Prevention


2Division of Pediatric Infectious Disease, Emory University School of Medicine, Atlanta, Georgia

Correspondence: Christina Spiropoulou, PhD, 1600 Clifton Rd NE, MS G14, Atlanta, GA 30333


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.
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