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. 2015 Oct;19(10):1209-15.
doi: 10.5588/ijtld.15.0253.

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

N C Bahr  1 , L Tugume  2 , R Rajasingham  3 , R Kiggundu  2 , D A Williams  4 , B Morawski  5 , D Alland  6 , D B Meya  7 , J Rhein  8 , D R Boulware  5
Affiliations

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

N C Bahr et al. Int J Tuberc Lung Dis. 2015 Oct.

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.

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 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.

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Conflict of interest statement

All authors contributed significantly to the work fulfilling the criteria for authorship and have no conflicts of interest.

Figures

Figure 1
Figure 1. Schematic of CSF processing after collection
The figure shows the process by which CSF was handled after collection in order to accomplish GeneXpert (Centrifuged/Un-centrifuged), microbiologic testing, and CSF culture (LJ and MGIT). Volumes are approximate.
Figure 2
Figure 2. Venn diagram of overlap in TB meningitis diagnostics
The Venn diagram displays 18 participants diagnosed by each diagnostic test and the overlap. One participant who was composite (Xpert on centrifuged CSF) positive had invalid culture results. Although the diagnostic sensitivity was similar between centrifuged CSF with Xpert and culture, only 39% (7/18) were positive by both culture and centrifuged Xpert.
Figure 3
Figure 3. Flow chart of methods by which each TBM case was detected microbiologically
18 subjects were microbiologically confirmed to have TBM. 13 cases were positive by Xpert of centrifuged CSF (right), among those cases the other methods by which M tuberculosis was detected are noted below. 5 cases were not detected by Xpert testing of centrifuged CSF (left) but were detected by culture.
See this image and copyright information in PMC

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