Fatal hemorrhagic fever caused by West Nile virus in the United States.
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.
Paddock
Christopher D
CD
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
Nicholson
William L
WL
Bhatnagar
Julu
J
Goldsmith
Cynthia S
CS
Greer
Patricia W
PW
Hayes
Edward B
EB
Risko
Joseph A
JA
Henderson
Corey
C
Blackmore
Carina G
CG
Lanciotti
Robert S
RS
Campbell
Grant L
GL
Zaki
Sherif R
SR
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