Improved diagnostic sensitivity for tuberculous meningitis with Xpert® MTB/RIF of centrifuged CSF

Nathan C Bahr, L. Tugume, Radha Rajasingham, R. Kiggundu, D. A. Williams, B. Morawski, D. Alland, D. B. Meya, Joshua R Rhein, David R Boulware

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

BACKGROUND: TB meningitis (TBM) diagnosis is difficult and novel diagnostic methods are needed. The World Health Organization recommends Xpertw 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. DESIGN: 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 acidfast 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.

Original languageEnglish (US)
Pages (from-to)1209-1215
Number of pages7
JournalInternational Journal of Tuberculosis and Lung Disease
Volume19
Issue number10
DOIs
StatePublished - Oct 1 2015

Keywords

  • Extra-pulmonary tuberculosis
  • Human immunodeficiency virus
  • Laboratory diagnostics
  • Tuberculosis meningitis
  • Xpert

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