title: Sub-optimal Specificity of Modified Ziehl-Neelsen Staining for Quick Identification of Tuberculous Meningitis.
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 tuberculosisculture 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.
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical UniversityXi'an, China; Department of Neurology, Kunming Medical University affiliated Yan'an HospitalKunming, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical UniversityXi'an, China; Department of Neurology, Zhongshan Hospital, Fudan UniversityHaishang, China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Feng
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University Xi'an, China.
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Yang
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University Xi'an, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Dai
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University Xi'an, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University Xi'an, China.
authors.forename: Lin-Fu
authors.initials: LF
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical UniversityXi'an, China; Department of Neurology, The General Hospital of the People's Liberation Army Rocket ForceBeijing, China.
authors.forename: Jia-Lei
authors.initials: JL
authors.lastname: Yang
authors.affiliation: Department of Neurology, Kunming Medical University affiliated Yan'an Hospital Kunming, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Zhan
authors.affiliation: The Children's Hospital at Westmead and The Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney Sydney, NSW, Australia.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Marais
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention Beijing, China.
authors.forename: Yan-Lin
authors.initials: YL
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University Xi'an, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
keywords: TBM; Xpert MTB/RIF; Ziehl-Neelsen stain; specificity; tuberculosis meningitis