TY - JOUR T1 - A new arenavirus in a cluster of fatal transplant-associated diseases. JF - N Engl J Med Y1 - 2008 A1 - Palacios,G. A1 - Druce,J. A1 - Du,L. A1 - Tran,T. A1 - Birch,C. A1 - Briese,T. A1 - Conlan,S. A1 - Quan,P. L. A1 - Hui,J. A1 - Marshall,J. A1 - Simons,J. F. A1 - Egholm,M. A1 - Paddock,C. D. A1 - Shieh,W. J. A1 - Goldsmith,C. S. A1 - Zaki,S. R. A1 - Catton,M. A1 - Lipkin,W. I. KW - Adult KW - Antibodies, Viral KW - Arenaviridae Infections KW - Arenavirus KW - Computational Biology KW - Disease Transmission, Infectious KW - Female KW - Humans KW - Immunohistochemistry KW - Kidney KW - Kidney Transplantation KW - Liver Transplantation KW - Middle Aged KW - Oligonucleotide Array Sequence Analysis KW - Polymerase Chain Reaction KW - RNA, Viral KW - Sequence Analysis, DNA AB -

Three patients who received visceral-organ transplants from a single donor on the same day died of a febrile illness 4 to 6 weeks after transplantation. Culture, polymerase-chain-reaction (PCR) and serologic assays, and oligonucleotide microarray analysis for a wide range of infectious agents were not informative.|We evaluated RNA obtained from the liver and kidney transplant recipients. Unbiased high-throughput sequencing was used to identify microbial sequences not found by means of other methods. The specificity of sequences for a new candidate pathogen was confirmed by means of culture and by means of PCR, immunohistochemical, and serologic analyses.|High-throughput sequencing yielded 103,632 sequences, of which 14 represented an Old World arenavirus. Additional sequence analysis showed that this new arenavirus was related to lymphocytic choriomeningitis viruses. Specific PCR assays based on a unique sequence confirmed the presence of the virus in the kidneys, liver, blood, and cerebrospinal fluid of the recipients. Immunohistochemical analysis revealed arenavirus antigen in the liver and kidney transplants in the recipients. IgM and IgG antiviral antibodies were detected in the serum of the donor. Seroconversion was evident in serum specimens obtained from one recipient at two time points.|Unbiased high-throughput sequencing is a powerful tool for the discovery of pathogens. The use of this method during an outbreak of disease facilitated the identification of a new arenavirus transmitted through solid-organ transplantation.

VL - 358 CP - 10 ID - 1119 ER -