title: Use of staged molecular analysis to determine causes of unexplained central nervous system infections.
abstract: No agent is implicated in most central nervous system (CNS) infections. To investigate cerebrospinal fluid samples from patients with CNS infections of unknown cause in 1 hospital in Taiwan, we used a staged molecular approach, incorporating techniques including multiplex MassTag PCR, 16S rRNA PCR, DNA microarray, and high-throughput pyrosequencing. We determined the infectious agent for 31 (24%) of 131 previously negative samples. Candidate pathogens were identified for 25 (27%) of 94 unexplained meningitis cases and 6 (16%) of 37 unexplained encephalitis cases. Epstein-Barr virus (18 infections) accounted for most of the identified agents in unexplained meningitis cases, followed by Escherichia coli (5), enterovirus (2), human herpesvirus 2 (1), and Mycobacterium tuberculosis. Herpesviruses were identified in samples from patients with unexplained encephalitis cases, including varicella-zoster virus (3 infections), human herpesvirus 1 (2), and cytomegalovirus (1). Our study confirms the power of multiplex MassTag PCR as a rapid diagnostic tool for identifying pathogens causing unexplained CNS infections.
authors: Chien-Chin
authors: CC
authors: Hsu
authors: Rafal
authors: R
authors: Tokarz
authors: Thomas
authors: T
authors: Briese
authors: Hung-Chin
authors: HC
authors: Tsai
authors: Phenix-Lan
authors: PL
authors: Quan
authors: W Ian
authors: WI
authors: Lipkin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002494:Central Nervous System Infections / Q000175:diagnosis* / Q000382:microbiology / Q000821:virology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D057188:Workflow; D055815:Young Adult
keywords: 16S rRNA PCR; CNS infections; MassTag PCR; bacteria; encephalitis; meningitis; microarray; pyrosequencing; viruses
references: Emerg Infect Dis. 2010 Jun;16(6):918-25
references: 20507741
references: J Clin Microbiol. 2007 Aug;45(8):2359-64
references: 17553978
references: Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15687-92
references: 12429852
references: Lancet. 1991 Oct 19;338(8773):969-73
references: 1681341
references: Jpn J Infect Dis. 2005 Jun;58(3):168-70
references: 15973009
references: N Engl J Med. 1993 Jan 7;328(1):21-8
references: 8416268
references: Vector Borne Zoonotic Dis. 2009 Apr;9(2):147-52
references: 18800864
references: J Med Virol. 1993 Aug;40(4):278-84
references: 8228918
references: J Clin Microbiol. 2003 Apr;41(4):1363-9
references: 12682115
references: Ann Neurol. 2007 Jan;61(1):25-36
references: 17262855
references: Emerg Infect Dis. 2005 Feb;11(2):310-3
references: 15752453
references: Clin Infect Dis. 2006 Dec 15;43(12):1578-9
references: 17109291
references: Clin Chem Lab Med. 2008;46(7):888-908
references: 18624614
references: Emerg Infect Dis. 2007 Jan;13(1):73-81
references: 17370518
references: Pediatrics. 2011 May;127(5):817-26
references: 21518717
references: J Med Virol. 2013 Mar;85(3):554-62
references: 23239485
references: Emerg Infect Dis. 2003 Feb;9(2):234-40
references: 12603996
references: N Engl J Med. 2008 Mar 6;358(10):991-8
references: 18256387
references: Pediatrics. 2001 Nov;108(5):1169-74
references: 11694698
references: Scand J Infect Dis. 2000;32(3):237-48
references: 10879592
references: Emerg Infect Dis. 2009 Sep;15(9):1359-65
references: 19788802
references: Clin Infect Dis. 2009 Dec 15;49(12):1838-47
references: 19929384
references: Lancet. 1993 Aug 14;342(8868):398-401
references: 8101902
references: N Engl J Med. 1970 Feb 12;282(7):361-5
references: 4312365
references: J Clin Microbiol. 2003 Apr;41(4):1763-5
references: 12682181
references: AIDS. 1996 Aug;10(9):951-8
references: 8853727
references: J Neurovirol. 2001 Oct;7(5):400-8
references: 11582512
references: J Clin Microbiol. 2004 Feb;42(2):734-40
references: 14766845
references: J Neurovirol. 2002 Oct;8(5):432-8
references: 12402169
references: J Clin Microbiol. 1997 Mar;35(3):691-6
references: 9041414
references: Clin Microbiol Rev. 2004 Oct;17(4):903-25, table of contents
references: 15489354
references: Clin Infect Dis. 2002 Jul 15;35(2):175-82
references: 12087524
references: Am J Pathol. 1991 Jan;138(1):149-63
references: 1846263
references: Emerg Infect Dis. 2006 Apr;12(4):692-5
references: 16704825
references: HIV Med. 2007 Jul;8(5):306-11
references: 17561877
references: J Mol Biol. 1990 Oct 5;215(3):403-10
references: 2231712
references: J Infect Dis. 2006 Nov 15;194(10):1398-402
references: 17054069
references: PLoS Pathog. 2008 Apr 25;4(4):e1000002
references: 18437241