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. 2016 Dec 27:7:2096.
doi: 10.3389/fmicb.2016.02096. eCollection 2016.

Sub-optimal Specificity of Modified Ziehl-Neelsen Staining for Quick Identification of Tuberculous Meningitis

Ting Wang  1 , Guo-Dong Feng  2 , Yu Pang  3 , Yi-Ning Yang  4 , Wen Dai  4 , Lin Zhang  4 , Lin-Fu Zhou  4 , Jia-Lei Yang  5 , Li-Ping Zhan  6 , Ben J Marais  7 , Yan-Lin Zhao  3 , Gang Zhao  4
Affiliations

Sub-optimal Specificity of Modified Ziehl-Neelsen Staining for Quick Identification of Tuberculous Meningitis

Ting Wang et al. Front Microbiol. .

Abstract

Background: Microbiological confirmation of tuberculous meningitis (TBM) remains problematic. We assessed the diagnostic performance of a modified Ziehl-Neelsen (MZN) staining method that showed promise in earlier studies. Methods: Patients evaluated for TBM in Shaanxi province, China, were prospectively enrolled from May, 2011 to April, 2013. Cerebrospinal fluid (CSF) specimens were evaluated using the Xpert MTB/RIF® assay, MZN staining, and standard biochemical and microbiological tests, together with detailed clinical and radiological assessment. Results: Among 316 patients included in the study, 38 had definite TBM, 66 probable TBM, 163 possible TBM and 49 "no TBM," using consensus uniform research case definition criteria. Comparing "definite or probable TBM" to "no TBM" MZN staining had higher sensitivity than Xpert MTB/RIF® (88.5 vs. 36.5%), but greatly reduced specificity (71.4 vs. 100.0%); 14/49 (28.6%) cases with "no TBM" tested positive on MZN. Mycobacterium tuberculosis culture was performed in 104/179 (58.1%) of MZN positive samples; 12.5% (13/104) were positive. Using Xpert MTB/RIF® as the reference standard, MZN had a sensitivity of 92.1% (95% CI 79.2-97.3) and specificity of 71.4% (95% CI 57.6-82.2). Conclusion: Xpert MTB/RIF® offered a rapid and specific TBM diagnosis, but sensitivity was poor. MZN was mainly hampered by false positives. Strategies to enhance the sensitivity of Xpert MTB/RIF® or improve the diagnostic accuracy of MZN should be explored.

Keywords: TBM; Xpert MTB/RIF; Ziehl-Neelsen stain; specificity; tuberculosis meningitis.

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Figures

Figure 1
Figure 1
Flow diagram of patients evaluated for tuberculous meningitis. TBM, tuberculosis meningitis; MZN, modified Ziehl-Neelsen staining; IND, infectious neurological disorder other than tuberculosis; NIND, non-infectious neurological disorder. *Classification according to the consensus uniform research case definition criteria (Marais et al., 2010).
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