title: Ebola hemorrhagic Fever: novel biomarker correlates of clinical outcome.
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.
authors: Viral Special Pathogens Branch, Centers for Disease Control and Prevention Division of Pediatric Infectious Disease, Emory University School of Medicine, Atlanta, Georgia.
authors: Anita K
authors: AK
authors: McElroy
authors: Viral Special Pathogens Branch, Centers for Disease Control and Prevention.
authors: Bobbie R
authors: BR
authors: Erickson
authors: Viral Special Pathogens Branch, Centers for Disease Control and Prevention.
authors: Timothy D
authors: TD
authors: Flietstra
authors: Viral Special Pathogens Branch, Centers for Disease Control and Prevention.
authors: Pierre E
authors: PE
authors: Rollin
authors: Viral Special Pathogens Branch, Centers for Disease Control and Prevention.
authors: Stuart T
authors: ST
authors: Nichol
authors: Viral Special Pathogens Branch, Centers for Disease Control and Prevention.
authors: Jonathan S
authors: JS
authors: Towner
authors: Viral Special Pathogens Branch, Centers for Disease Control and Prevention.
authors: Christina F
authors: CF
authors: Spiropoulou
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D023201:CD40 Ligand / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D004196:Disease Outbreaks; D005260:Female; D005293:Ferritins / Q000097:blood; D006470:Hemorrhage / Q000097:blood / Q000473:pathology / Q000821:virology; D019142:Hemorrhagic Fever, Ebola / Q000097:blood* / Q000453:epidemiology / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D013397:Sudan / Q000453:epidemiology; D018180:Thrombomodulin / Q000097:blood; D014766:Viremia / Q000097:blood / Q000473:pathology / Q000821:virology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016207:Cytokines; D018180:Thrombomodulin; D023201:CD40 Ligand; D005293:Ferritins
keywords: Ebola virus; Gulu; biomarkers; hemorrhage; hemorrhagic fever virus