Donor-Derived Infections With Central Nervous System Pathogens After Solid Organ Transplantation

Abstract

During the past decade, numerous instances have been reportedofdonor-derived infectionamongrecipientsof solidorgan transplants with pathogens associated with central nervous system (CNS) infections.1-7 Many cases have received significant attention both among the transplant community and the laymedia.Notablepathogenshave includedWestNile virus (WNV), Balamuthia mandrillaris, lymphocytic choriomeningitis virus, and rabies virus. In most cases, donorderived infection was suspected only after symptoms developed in recipients and further testing of archived specimens identified a donor source. In some cases, lack of recipient exposure to the pathogenprompted investigation for donor origin of the infection. Recipient outcomes were often poor; in part because even after identification of infection, effective treatment was not available. In this issueof JAMA, Vora andcolleagues8describe a case of donor-derived rabies in a recipient of a kidney transplant. The investigationwas prompted by the death from rabies of a recipient 18 months after transplant in the absence of exposures.Adetailed inquiry ledbyCenters forDiseaseControl and Prevention investigators confirmeddonor origin of the recipient’s infectionwith a raccoon rabies virus. The report contains a number of unexpected clinical features. Despite the immunosuppressed state of all 4 organ recipients, the affected patient remained asymptomatic for 18months after transplantation, and the 3 other patients did not develop rabies. The authors speculate that either a low dose of rabies virus or differential behavioral of the raccoon rabies variant explains these clinical features. Although the epidemiology and pathogenesis considerations are interesting, the most notable aspect of this report surrounds the implications for improving the safety of solid organ transplantation. Combined with previous cases,1-7 this report highlights a pattern of donor-derived infection caused by unidentified (at the time of procurement) donor infection with pathogens associated with CNS infection. Reducing the riskofdonor-derived infection requiresunderstanding thecurrent system of screening potential donors. Policy governing solid organ transplantation is established by the Organ Procurement and Transplantation Network (OPTN). Assessment of deceased donors for the risk of transmissible disease relies on amultipronged approach. The organ procurement organization (OPO)managing the process obtains amedical and social history from individuals familiar with the donor. Information that might reasonably be expected to affect potential recipients (eg, a history of recent intravenous drug usewould increase risk of acute viral hepatitis or human immunodeficiencyvirus [HIV] infection thatmightnotbedetectedon routine serologic donor screening tests) must be communicated to transplant programs.9 Limitations include the availability of friends and family and their familiaritywith thedonor’s exposures and behaviors. In addition, specific laboratory testingmust beperformedonall deceaseddonors. Required tests include serological testing forHIV, hepatitis C virus, hepatitis B virus, syphilis, cytomegalovirus, and Epstein-Barr virus as well as blood and urine cultures. At the time of a potential recipient being offered an organ for transplantation, the accepting transplant center must, in a time-pressured environment, integrate all this information, including the medical urgency of the potential recipient, andmake a decision regarding whether to accept the organs. Accepting centers necessarily rely on the clinical impression of treating physicians. For situations in which an increased riskof transmissible infection is present, specific informed consent must be obtained from the potential recipient.10 As an added safeguard, OPOs are required to report additional information that becomesavailable after transplant (eg, autopsy results) that might affect recipients. Furthermore, transplant centers must report any recipient events suggestive of donor-derived infection, thereby allowing notification of other centers that received organs from the same donor.For example, if a recipientwithnootherknownexposures is newly diagnosedwith hepatitis C after transplantation, the event should be reported to the OPTN. In the case described by Vora and colleagues,8 suspected donor-derived rabieswas reported to theOPTN, allowing rapidnotificationof the transplant centers caring for other recipients andadministrationof postexposure rabiesprophylaxis.AnOPTNcommittee, theDisease Transmission Advisory Committee (DTAC), reviews all such reports anddecideswhether theevent resulted indonorderived disease. Data are aggregated andused to guide policy development and educational efforts within the transplant community. Under the current system, episodes of unexpected donor-derived infection are rare. During 2008-2011, 113 622 patients received solid organ transplants from 57 488 donors.Donor-deriveddisease (infectionandmalignancy)developed in139 recipients (0.1%) resulting in29deaths (0.03%).11 A relevant comparison to make is that, during the same period, 26 852peoplediedwaiting for anorgan transplantation.12 Despite these safeguards, reports of CNS infection transmissionmandate consideration ofwhatmight be done to furRelated article page 398 Opinion