Use of staged molecular analysis to determine causes of unexplained central nervous system infections

Emerg Infect Dis. 2013;19(9):1470-7. doi: 10.3201/eid1909.130474.

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.

Keywords: 16S rRNA PCR; CNS infections; MassTag PCR; bacteria; encephalitis; meningitis; microarray; pyrosequencing; viruses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Central Nervous System Infections / diagnosis*
  • Central Nervous System Infections / microbiology
  • Central Nervous System Infections / virology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Diagnostic Techniques* / methods
  • Workflow
  • Young Adult