title: Fatal hemorrhagic fever caused by West Nile virus in the United States.
abstract: BACKGROUND
  Most West Nile virus (WNV) infections in humans are asymptomatic; severe disease occurs in relatively few patients and typically manifests as encephalitis, meningitis, or acute flaccid paralysis. A few cases of life-threatening disease with diffuse hemorrhagic manifestations have been reported in Africa; however, this clinical presentation has not been documented for any of the >16,700 cases of WNV disease reported in the United States during 1999-2004. We describe a case of fulminant WNV infection in a 59-year-old Florida man who died following a brief illness that resembled hemorrhagic disease caused by Rickettsia reckettsii, dengue virus or yellow fever virus.
  
  
  METHODS
  Traditional and contemporary diagnostic assays, including culture isolation, electron microscopic examination, reverse-transcriptase polymerase chain reaction amplification, and immunohistochemical stains, were used to confirm systemic WNV infection in the patient.
  
  
  RESULTS
  WNV was isolated in a cell culture from a skin biopsy specimen obtained from the patient shortly prior to death. Electron microscopic examination identified the isolate as a flavivirus, and reverse-transcriptase polymerase chain reaction amplified specific WNV sequences from the isolate and patient tissue. Quantitative polymerase chain reaction identified approximately 1x10(7) viral copies/mL in the patient's serum. WNV antigens were detected by immunohistochemical stains in intravascular mononuclear cells and endothelium in skin, lung, liver, kidney, spleen, bone marrow, and central nervous system; no viral antigens were identified in neurons or glial cells of the central nervous system.
  
  
  CONCLUSIONS
  Although hemorrhagic disease is a rare manifestation of WNV infection, the findings provided by this report may offer new insights regarding the clinical spectrum and pathogenesis of WNV disease in humans.
authors.affiliation: Infectious Disease Pathology Activity, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. cpaddock@cdc.gov
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Paddock
authors.forename: William L
authors.initials: WL
authors.lastname: Nicholson
authors.forename: Julu
authors.initials: J
authors.lastname: Bhatnagar
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Goldsmith
authors.forename: Patricia W
authors.initials: PW
authors.lastname: Greer
authors.forename: Edward B
authors.initials: EB
authors.lastname: Hayes
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Risko
authors.forename: Corey
authors.initials: C
authors.lastname: Henderson
authors.forename: Carina G
authors.initials: CG
authors.lastname: Blackmore
authors.forename: Robert S
authors.initials: RS
authors.lastname: Lanciotti
authors.forename: Grant L
authors.initials: GL
authors.lastname: Campbell
authors.forename: Sherif R
authors.initials: SR
authors.lastname: Zaki
mesh_terms: D017809:Fatal Outcome; D006482:Hemorrhagic Fevers, Viral / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000473:pathology; D014481:United States / Q000453:epidemiology; D014901:West Nile Fever / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology