title: Improved diagnostic sensitivity for tuberculous meningitis with Xpert(®) MTB/RIF of centrifuged CSF.
abstract: BACKGROUND
  TB meningitis (TBM) diagnosis is difficult and novel diagnostic methods are needed. The World Health Organization recommends Xpert(®) MTB/RIF as the initial TBM diagnostic test based on two studies reporting suboptimal sensitivity (~50-60%).
  
  
  OBJECTIVE
  To study the effect of cerebrospinal fluid (CSF) centrifugation on Xpert performance for TBM detection.
  
  
  METHODS
  A total of 107 predominantly human immunodeficiency virus (HIV) infected adults with presumed meningitis were screened prospectively in Kampala, Uganda. CSF was tested using 1) microscopy for acid-fast bacilli; 2) MGIT™ culture; 3) Xpert of 2 ml of unprocessed CSF; and 4) Xpert of centrifuged CSF. Diagnostic performance was measured against an a priori composite reference standard of any positive CSF tuberculosis test.
  
  
  RESULTS
  Of 107 participants, 18 (17%) had definite TBM. When CSF was centrifuged, Xpert had better sensitivity (13/18, 72%) than when using 2 ml of unprocessed CSF (5/18, 28%; P = 0.008). The median centrifuged CSF volume was 6 ml (IQR 4-10). Mycobacterial culture yielded 71% (12/17) sensitivity at a median delay of 27 days. Only 39% were positive by both culture and centrifuged Xpert, with additional cases detected by Xpert and culture.
  
  
  CONCLUSIONS
  CSF centrifugation optimizes the diagnostic performance of Xpert in the detection of TBM. A combination of culture and Xpert detected the largest number of cases.
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, USA; Center for Infectious Diseases & Microbiology Translational Research, University of Minnesota, Minneapolis, Minnesota, USA; Infectious Disease Institute, Makerere University, Kampala, Uganda.
authors.forename: N C
authors.initials: NC
authors.lastname: Bahr
authors.affiliation: Infectious Disease Institute, Makerere University, Kampala, Uganda.
authors.forename: L
authors.initials: L
authors.lastname: Tugume
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, USA.
authors.forename: R
authors.initials: R
authors.lastname: Rajasingham
authors.affiliation: Infectious Disease Institute, Makerere University, Kampala, Uganda.
authors.forename: R
authors.initials: R
authors.lastname: Kiggundu
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, USA; Infectious Disease Institute, Makerere University, Kampala, Uganda.
authors.forename: D A
authors.initials: DA
authors.lastname: Williams
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, USA; Center for Infectious Diseases & Microbiology Translational Research, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: B
authors.initials: B
authors.lastname: Morawski
authors.affiliation: Center for Infectious Disease, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA.
authors.forename: D
authors.initials: D
authors.lastname: Alland
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, USA; Infectious Disease Institute, Makerere University, Kampala, Uganda; School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: D B
authors.initials: DB
authors.lastname: Meya
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, USA; Center for Infectious Diseases & Microbiology Translational Research, University of Minnesota, Minneapolis, Minnesota, USA, Infectious Disease Institute, Makerere University, Kampala, Uganda.
authors.forename: J
authors.initials: J
authors.lastname: Rhein
authors.affiliation: Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, USA; Center for Infectious Diseases & Microbiology Translational Research, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Boulware
mesh_terms: D000328:Adult; D002498:Centrifugation / Q000379:methods; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008853:Microscopy / Q000379:methods; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D014390:Tuberculosis, Meningeal / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000382:microbiology; D014454:Uganda / Q000453:epidemiology