Transmission of rabies virus from an organ donor to four transplant recipients

Arjun Srinivasan, Elizabeth C. Burton, Matthew J. Kuehnert, Charles Rupprecht, William L. Sutker, Thomas Ksiazek, Christopher D. Paddock, Jeannette Guarner, Wun Ju Shieh, Cynthia Goldsmith, Cathleen A. Hanlon, James Zoretic, Bernard Fischbach, Michael Niezgoda, Waleed H. El-Feky, Lillian Orciari, Edmund Q. Sanchez, Anna Likos, Goran B. Klintmalm, Denise Cardo & 4 others James LeDuc, Mary E. Chamberland, Daniel B. Jernigan, Sherif R. Zaki

Research output: Contribution to journalArticle

326 Citations (Scopus)

Abstract

BACKGROUND: In 2004, four recipients of kidneys, a liver, and an arterial segment from a common organ donor died of encephalitis of an unknown cause. METHODS: We reviewed the medical records of the organ donor and the recipients. Blood, cerebrospinal fluid, and tissues from the recipients were tested with a variety of assays and pathological stains for numerous causes of encephalitis. Samples from the recipients were also inoculated into mice. RESULTS: The organ donor had been healthy before having a subarachnoid hemorrhage that led to his death. Encephalitis developed in all four recipients within 30 days after transplantation and was accompanied by rapid neurologic deterioration characterized by agitated delirium, seizures, respiratory failure, and coma. They died an average of 13 days after the onset of neurologic symptoms. Mice inoculated with samples from the affected patients became ill seven to eight days later, and electron microscopy of central nervous system (CNS) tissue demonstrated rhabdovirus particles. Rabies-specific immunohistochemical and direct fluorescence antibody staining demonstrated rabies virus in multiple tissues from all recipients. Cytoplasmic inclusions consistent with Negri bodies were seen in CNS tissue from all recipients. Antibodies against rabies virus were present in three of the four recipients and the donor. The donor had told others of being bitten by a bat. CONCLUSIONS: This report documenting the transmission of rabies virus from an organ donor to multiple recipients underscores the challenges of preventing and detecting transmission of unusual pathogens through transplantation.

Original languageEnglish (US)
Pages (from-to)1103-1111
Number of pages9
JournalNew England Journal of Medicine
Volume352
Issue number11
DOIs
StatePublished - Mar 17 2005
Externally publishedYes

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Rabies virus
Tissue Donors
Encephalitis
Nerve Tissue
Viral Inclusion Bodies
Central Nervous System
Transplantation
Rhabdoviridae
Infectious Disease Transmission
Rabies
Delirium
Antibodies
Inclusion Bodies
Subarachnoid Hemorrhage
Coma
Neurologic Manifestations
Respiratory Insufficiency
Nervous System
Medical Records
Cerebrospinal Fluid

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Srinivasan, A., Burton, E. C., Kuehnert, M. J., Rupprecht, C., Sutker, W. L., Ksiazek, T., ... Zaki, S. R. (2005). Transmission of rabies virus from an organ donor to four transplant recipients. New England Journal of Medicine, 352(11), 1103-1111. https://doi.org/10.1056/NEJMoa043018

Transmission of rabies virus from an organ donor to four transplant recipients. / Srinivasan, Arjun; Burton, Elizabeth C.; Kuehnert, Matthew J.; Rupprecht, Charles; Sutker, William L.; Ksiazek, Thomas; Paddock, Christopher D.; Guarner, Jeannette; Shieh, Wun Ju; Goldsmith, Cynthia; Hanlon, Cathleen A.; Zoretic, James; Fischbach, Bernard; Niezgoda, Michael; El-Feky, Waleed H.; Orciari, Lillian; Sanchez, Edmund Q.; Likos, Anna; Klintmalm, Goran B.; Cardo, Denise; LeDuc, James; Chamberland, Mary E.; Jernigan, Daniel B.; Zaki, Sherif R.

In: New England Journal of Medicine, Vol. 352, No. 11, 17.03.2005, p. 1103-1111.

Research output: Contribution to journalArticle

Srinivasan, A, Burton, EC, Kuehnert, MJ, Rupprecht, C, Sutker, WL, Ksiazek, T, Paddock, CD, Guarner, J, Shieh, WJ, Goldsmith, C, Hanlon, CA, Zoretic, J, Fischbach, B, Niezgoda, M, El-Feky, WH, Orciari, L, Sanchez, EQ, Likos, A, Klintmalm, GB, Cardo, D, LeDuc, J, Chamberland, ME, Jernigan, DB & Zaki, SR 2005, 'Transmission of rabies virus from an organ donor to four transplant recipients', New England Journal of Medicine, vol. 352, no. 11, pp. 1103-1111. https://doi.org/10.1056/NEJMoa043018
Srinivasan, Arjun ; Burton, Elizabeth C. ; Kuehnert, Matthew J. ; Rupprecht, Charles ; Sutker, William L. ; Ksiazek, Thomas ; Paddock, Christopher D. ; Guarner, Jeannette ; Shieh, Wun Ju ; Goldsmith, Cynthia ; Hanlon, Cathleen A. ; Zoretic, James ; Fischbach, Bernard ; Niezgoda, Michael ; El-Feky, Waleed H. ; Orciari, Lillian ; Sanchez, Edmund Q. ; Likos, Anna ; Klintmalm, Goran B. ; Cardo, Denise ; LeDuc, James ; Chamberland, Mary E. ; Jernigan, Daniel B. ; Zaki, Sherif R. / Transmission of rabies virus from an organ donor to four transplant recipients. In: New England Journal of Medicine. 2005 ; Vol. 352, No. 11. pp. 1103-1111.
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abstract = "BACKGROUND: In 2004, four recipients of kidneys, a liver, and an arterial segment from a common organ donor died of encephalitis of an unknown cause. METHODS: We reviewed the medical records of the organ donor and the recipients. Blood, cerebrospinal fluid, and tissues from the recipients were tested with a variety of assays and pathological stains for numerous causes of encephalitis. Samples from the recipients were also inoculated into mice. RESULTS: The organ donor had been healthy before having a subarachnoid hemorrhage that led to his death. Encephalitis developed in all four recipients within 30 days after transplantation and was accompanied by rapid neurologic deterioration characterized by agitated delirium, seizures, respiratory failure, and coma. They died an average of 13 days after the onset of neurologic symptoms. Mice inoculated with samples from the affected patients became ill seven to eight days later, and electron microscopy of central nervous system (CNS) tissue demonstrated rhabdovirus particles. Rabies-specific immunohistochemical and direct fluorescence antibody staining demonstrated rabies virus in multiple tissues from all recipients. Cytoplasmic inclusions consistent with Negri bodies were seen in CNS tissue from all recipients. Antibodies against rabies virus were present in three of the four recipients and the donor. The donor had told others of being bitten by a bat. CONCLUSIONS: This report documenting the transmission of rabies virus from an organ donor to multiple recipients underscores the challenges of preventing and detecting transmission of unusual pathogens through transplantation.",
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T1 - Transmission of rabies virus from an organ donor to four transplant recipients

AU - Srinivasan, Arjun

AU - Burton, Elizabeth C.

AU - Kuehnert, Matthew J.

AU - Rupprecht, Charles

AU - Sutker, William L.

AU - Ksiazek, Thomas

AU - Paddock, Christopher D.

AU - Guarner, Jeannette

AU - Shieh, Wun Ju

AU - Goldsmith, Cynthia

AU - Hanlon, Cathleen A.

AU - Zoretic, James

AU - Fischbach, Bernard

AU - Niezgoda, Michael

AU - El-Feky, Waleed H.

AU - Orciari, Lillian

AU - Sanchez, Edmund Q.

AU - Likos, Anna

AU - Klintmalm, Goran B.

AU - Cardo, Denise

AU - LeDuc, James

AU - Chamberland, Mary E.

AU - Jernigan, Daniel B.

AU - Zaki, Sherif R.

PY - 2005/3/17

Y1 - 2005/3/17

N2 - BACKGROUND: In 2004, four recipients of kidneys, a liver, and an arterial segment from a common organ donor died of encephalitis of an unknown cause. METHODS: We reviewed the medical records of the organ donor and the recipients. Blood, cerebrospinal fluid, and tissues from the recipients were tested with a variety of assays and pathological stains for numerous causes of encephalitis. Samples from the recipients were also inoculated into mice. RESULTS: The organ donor had been healthy before having a subarachnoid hemorrhage that led to his death. Encephalitis developed in all four recipients within 30 days after transplantation and was accompanied by rapid neurologic deterioration characterized by agitated delirium, seizures, respiratory failure, and coma. They died an average of 13 days after the onset of neurologic symptoms. Mice inoculated with samples from the affected patients became ill seven to eight days later, and electron microscopy of central nervous system (CNS) tissue demonstrated rhabdovirus particles. Rabies-specific immunohistochemical and direct fluorescence antibody staining demonstrated rabies virus in multiple tissues from all recipients. Cytoplasmic inclusions consistent with Negri bodies were seen in CNS tissue from all recipients. Antibodies against rabies virus were present in three of the four recipients and the donor. The donor had told others of being bitten by a bat. CONCLUSIONS: This report documenting the transmission of rabies virus from an organ donor to multiple recipients underscores the challenges of preventing and detecting transmission of unusual pathogens through transplantation.

AB - BACKGROUND: In 2004, four recipients of kidneys, a liver, and an arterial segment from a common organ donor died of encephalitis of an unknown cause. METHODS: We reviewed the medical records of the organ donor and the recipients. Blood, cerebrospinal fluid, and tissues from the recipients were tested with a variety of assays and pathological stains for numerous causes of encephalitis. Samples from the recipients were also inoculated into mice. RESULTS: The organ donor had been healthy before having a subarachnoid hemorrhage that led to his death. Encephalitis developed in all four recipients within 30 days after transplantation and was accompanied by rapid neurologic deterioration characterized by agitated delirium, seizures, respiratory failure, and coma. They died an average of 13 days after the onset of neurologic symptoms. Mice inoculated with samples from the affected patients became ill seven to eight days later, and electron microscopy of central nervous system (CNS) tissue demonstrated rhabdovirus particles. Rabies-specific immunohistochemical and direct fluorescence antibody staining demonstrated rabies virus in multiple tissues from all recipients. Cytoplasmic inclusions consistent with Negri bodies were seen in CNS tissue from all recipients. Antibodies against rabies virus were present in three of the four recipients and the donor. The donor had told others of being bitten by a bat. CONCLUSIONS: This report documenting the transmission of rabies virus from an organ donor to multiple recipients underscores the challenges of preventing and detecting transmission of unusual pathogens through transplantation.

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