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.
Highlights
Tuberculous meningitis (TBM) represents roughly 1% of all cases of tuberculosis (TB), but it is responsible for a disproportionate burden of TB-associated deaths and disability (Thwaites et al, 2013)
Using Xpert MTB/RIF® as the reference standard, modified Ziehl-Neelsen (MZN) had a sensitivity of 92.1% and specificity of 71.4%
Due to its enhanced sensitivity and ability to simultaneously detect rifampicin resistance, the World Health Organization (WHO) recommended that Xpert MTB/RIF R replace sputum smear microscopy for initial diagnosis of suspected human immunodeficiency virus (HIV)-associated TB (World Health Organization, 2010) WHO suggested that Xpert MTB/RIF R should be considered as the initial diagnostic test in cerebrospinal fluid (CSF) specimens from patients suspected of having TBM (World Health Organization, 2013), given its specificity and rapid turn-around time compared to Mycobacterium tuberculosis culture
Summary
Tuberculous meningitis (TBM) represents roughly 1% of all cases of tuberculosis (TB), but it is responsible for a disproportionate burden of TB-associated deaths and disability (Thwaites et al, 2013). Due to its enhanced sensitivity and ability to simultaneously detect rifampicin resistance, the World Health Organization (WHO) recommended that Xpert MTB/RIF R replace sputum smear microscopy for initial diagnosis of suspected human immunodeficiency virus (HIV)-associated TB (World Health Organization, 2010) WHO suggested that Xpert MTB/RIF R should be considered as the initial diagnostic test in CSF specimens from patients suspected of having TBM (World Health Organization, 2013), given its specificity and rapid turn-around time compared to Mycobacterium tuberculosis culture. WHO recommends CSF Xpert MTB/RIF R as an initial TBM diagnostic test (World Health Organization, 2013) based primarily on two studies that reported sensitivities of 50–60% compared to M. tuberculosis culture in patient cohorts with high rates of HIV coinfection (Patel et al, 2013; Nhu et al, 2014). We assessed the diagnostic performance of a modified Ziehl-Neelsen (MZN) staining method that showed promise in earlier studies
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