A new arenavirus in a cluster of fatal transplant-associated diseases
- PMID: 18256387
- DOI: 10.1056/NEJMoa073785
A new arenavirus in a cluster of fatal transplant-associated diseases
Erratum in
- N Engl J Med. 2008 Mar 13;358(11):1204
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Copyright 2008 Massachusetts Medical Society.
Comment in
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The new age of molecular diagnostics for microbial agents.N Engl J Med. 2008 Mar 6;358(10):988-9. doi: 10.1056/NEJMp0708085. Epub 2008 Feb 6. N Engl J Med. 2008. PMID: 18256386 No abstract available.
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A new arenavirus in transplantation.N Engl J Med. 2008 Jun 12;358(24):2638; author reply 2638-9. doi: 10.1056/NEJMc080743. N Engl J Med. 2008. PMID: 18550879 No abstract available.
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Metagenomics and the case of the deadly hamster.Hepatology. 2008 Aug;48(2):679-83. doi: 10.1002/hep.22452. Hepatology. 2008. PMID: 18666226 Free PMC article. No abstract available.
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