Transmission of Rabies Virus from an Organ Donor to Four Transplant Recipients

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Abstract

In 2004, four recipients of kidneys, a liver, and an arterial segment from a common organ donor died of encephalitis of an unknown cause. 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. 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. 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. Copyright 2005 Massachusetts Medical Society.

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Transmission of West Nile virus from an organ donor to four transplant recipients.

R Lanciotti, M. Pham, Andrea Winquist … (2003)

In August 2002, fever and mental-status changes developed in recipients of organs from a common donor. Transmission of West Nile virus through organ transplantation was suspected. We reviewed medical records, conducted interviews, and collected blood and tissue samples for testing with a variety of assays. Persons who donated blood to the organ donor and associated blood components were identified and tested for West Nile virus. We identified West Nile virus infection in the organ donor and in all four organ recipients. Encephalitis developed in three of the organ recipients, and febrile illness developed in one. Three recipients became seropositive for West Nile virus IgM antibody; the fourth recipient had brain tissue that was positive for West Nile virus by isolation and nucleic acid and antigen assays. Serum specimens obtained from the organ donor before and immediately after blood transfusions showed no evidence of West Nile virus; however, serum and plasma samples obtained at the time of organ recovery were positive on viral nucleic acid testing and viral culture. The organ donor had received blood transfusions from 63 donors. A review of blood donors and follow-up testing identified one donor who had viremia at the time of donation and who became seropositive for West Nile virus IgM antibodies during the next two months. Our investigation of this cluster documents the transmission of West Nile virus by organ transplantation. Organ recipients receiving immunosuppressive drugs may be at high risk for severe disease after West Nile virus infection. Blood transfusion was the probable source of the West Nile virus viremia in the organ donor. Copyright 2003 Massachusetts Medical Society

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Human-to-human transmission of rabies virus by corneal transplant.

Thomas Winkler, E Burton, T Henson … (1979)

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Epidemiology of human rabies in the United States, 1980 to 1996.

N D Noah, W. Krebs, M Fekadu … (1998)

To summarize the epidemiologic, diagnostic, and clinical features of the 32 laboratory-confirmed cases of human rabies diagnosed in the United States from 1980 to 1996. Data were obtained from case reports of human rabies submitted to the Centers for Disease Control and Prevention by state or local health authorities. All cases of human rabies reported in the United States from 1980 to 1996 in which infection with rabies virus was confirmed by laboratory studies. Patients were reviewed for demographic characteristics, exposure history, rabies prophylaxis, clinical presentation, treatment, clinical course, diagnostic laboratory tests, identification of rabies virus variants, and the number of medical personnel or family members who required postexposure prophylaxis after coming in contact with an exposed person. 32 cases of human rabies were reported from 20 states. Patients ranged in age from 4 to 82 years and were predominantly male (63%). Most patients (25 of 32) had no definite history of an animal bite or other event associated with rabies virus transmission. Of the 32 cases, 17 (53%) were associated with rabies virus variants found in insectivorous bats, 12 (38%) with variants found in domestic dogs outside the United States, 2 (6%) with variants found in indigenous domestic dogs, and 1 (3%) with a variant found in indigenous skunks. Among the 7 patients with a definite exposure history, 6 cases were attributable to dog bites received in foreign countries and 1 was attributable to a bat bite received in the United States. In 12 of the 32 patients (38%), rabies was not clinically suspected and was diagnosed after death. In the remaining 20 cases (63%), the diagnosis of rabies was considered before death and samples were obtained specifically for laboratory confirmation a median of 7 days (range, 3 to 17 days) after the onset of clinical signs. Of the clinical differences between patients in whom rabies was diagnosed before death and those in whom it was diagnosed after death, the presence of hydrophobia or aerophobia was significantly associated with antemortem diagnosis (odds ratio, 11.0 [95% CI, 1.05 to 273.34]). The median number of medical personnel or familial contacts of the patients who received postexposure prophylaxis was 54 per patient (range, 4 to 179). None of the 32 patients with rabies received postexposure prophylaxis before the onset of clinical disease. In the United States, human rabies is rare but probably underdiagnosed. Rabies should be included in the differential diagnosis of any case of acute, rapidly progressing encephalitis, even if the patient does not recall being bitten by an animal. In addition to situations involving an animal bite, a scratch from an animal, or contact of mucous membranes with infectious saliva, postexposure prophylaxis should be considered if the history indicates that a bat was physically present, even if the person is unable to reliably report contact that could have resulted in a bite. Such a situation may arise when a bat bite causes an insignificant wound or the circumstances do not allow recognition of contact, such as when a bat is found in the room of a sleeping person or near a previously unattended child.