Improving the microbiological diagnosis of tuberculous meningitis: a prospective, international, multicentre comparison of conventional and modified Ziehl-Neelsen stain, GeneXpert, and culture of cerebrospinal fluid
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Objectives
Tuberculous meningitis (TBM) is the severest form of tuberculosis, but current diagnostic tests are insensitive. Recent reports suggest simple modifications to conventional cerebrospinal fluid (CSF) Ziehl–Neelsen (ZN) staining may greatly improve sensitivity. We sought to define the performance of modified and conventional ZN stain for TBM diagnosis.
Methods
In hospitals in Vietnam, South Africa and Indonesia we conducted a prospective study of modified ZN with or without cytospin, conventional ZN smear, GeneXpert, and culture on CSF in adults with suspected TBM.
Results
A total of 618 individuals were enrolled across 3 sites. Compared with the TBM clinical diagnostic gold standard for research (definite probable or possible TBM), sensitivity of conventional ZN and modified ZN with cytospin were 33.9% and 34.5% respectively (p = 1.0 for the difference between tests), compared with culture 31.8% and Xpert 25.1%. Using culture as a reference, sensitivities of conventional ZN, modified ZN with cytospin, and Xpert were 66.4%, 67.5%, and 72.3%, respectively. Higher CSF volume and lactate, and lower CSF:blood glucose ratio were independently associated with microbiologically confirmed TBM.
Conclusions
Modified ZN stain does not improve diagnosis of TBM. Currently available tests are insensitive, but testing large CSF volumes improves performance. New diagnostic tests for TBM are urgently required.
Tuberculous meningitis (TBM) is the severest form of tuberculosis, but current diagnostic tests are insensitive. Recent reports suggest simple modifications to conventional cerebrospinal fluid (CSF) Ziehl–Neelsen (ZN) staining may greatly improve sensitivity. We sought to define the performance of modified and conventional ZN stain for TBM diagnosis.
Methods
In hospitals in Vietnam, South Africa and Indonesia we conducted a prospective study of modified ZN with or without cytospin, conventional ZN smear, GeneXpert, and culture on CSF in adults with suspected TBM.
Results
A total of 618 individuals were enrolled across 3 sites. Compared with the TBM clinical diagnostic gold standard for research (definite probable or possible TBM), sensitivity of conventional ZN and modified ZN with cytospin were 33.9% and 34.5% respectively (p = 1.0 for the difference between tests), compared with culture 31.8% and Xpert 25.1%. Using culture as a reference, sensitivities of conventional ZN, modified ZN with cytospin, and Xpert were 66.4%, 67.5%, and 72.3%, respectively. Higher CSF volume and lactate, and lower CSF:blood glucose ratio were independently associated with microbiologically confirmed TBM.
Conclusions
Modified ZN stain does not improve diagnosis of TBM. Currently available tests are insensitive, but testing large CSF volumes improves performance. New diagnostic tests for TBM are urgently required.
Date Issued
2018-12-01
Date Acceptance
2018-09-11
Citation
Journal of Infection, 2018, 77 (6), pp.509-515
ISSN
0163-4453
Publisher
Elsevier
Start Page
509
End Page
515
Journal / Book Title
Journal of Infection
Volume
77
Issue
6
Copyright Statement
© 2018 The Authors. Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY license. (http://creativecommons.org/licenses/by/4.0/)
Sponsor
Wellcome Trust
Grant Number
104803/Z/14/ZR
Subjects
Science & Technology
Life Sciences & Biomedicine
Infectious Diseases
Tuberculous meningitis
Diagnosis
Ziehl-Neelsen stain
Cytospin
Xpert MTB/RIF
INTRACELLULAR MYCOBACTERIUM-TUBERCULOSIS
ACCURACY
MTB/RIF
ADULTS
Ziehl–Neelsen stain
1103 Clinical Sciences
Microbiology
Publication Status
Published
Date Publish Online
2018-09-12