Journal Article

Fatal Hemorrhagic Fever Caused by West Nile Virus in the United States

Christopher D. Paddock, William L. Nicholson, Julu Bhatnagar, Cynthia S. Goldsmith, Patricia W. Greer, Edward B. Hayes, Joseph A. Risko, Corey Henderson, Carina G. Blackmore, Robert S. Lanciotti, Grant L. Campbell and Sherif R. Zaki

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 42, issue 11, pages 1527-1535
Published in print June 2006 | ISSN: 1058-4838
Published online June 2006 | e-ISSN: 1537-6591 | DOI:
Fatal Hemorrhagic Fever Caused by West Nile Virus in the United States

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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 rickettsii, 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 1 × 107 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.

Journal Article.  5236 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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