Evaluation of the GeneXpert MTB/RIF in patients with presumptive tuberculous meningitis

Tatiana Metcalf, Jaime Soria, Silvia M. Montano, Eduardo Ticona, Carlton A. Evans, Luz Huaroto, Matthew Kasper, Eric S. Ramos, Nicanor Mori, Podjanee Jittamala, Kesinee Chotivanich, Irwin F. Chavez, Pratap Singhasivanon, Sasithon Pukrittayakamee, Joseph R. Zunt

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Abstract

Background Meningitis caused by Mycobacterium tuberculosis is a major cause of morbidity and mortality worldwide. We evaluated the performance of cerebrospinal fluid (CSF) testing with the GeneXpert MTB/RIF assay versus traditional approaches for diagnosing tuberculosis meningitis (TBM). Methods Patients were adults (n = 37) presenting with suspected TBM to the Hospital Nacional Dos de Mayo, Lima, Peru, during 12 months until 1st January 2015. Each participant had a single CSF specimen that was divided into aliquots that were concurrently tested for M. tuberculosis using GeneXpert, Ziehl-Neelsen smear and culture on solid and liquid media. Drug susceptibility testing used Mycobacteria Growth Indicator Tube (MGIT 960) and the proportions method. Results 81% (30/37) of patients received a final clinical diagnosis of TBM, of whom 63% (19/30, 95% confidence intervals, CI: 44–80%) were HIV-positive. 22% (8/37, 95%CI: 9.8–38%), of patients had definite TBM. Because definite TBM was defined by positivity in any laboratory test, all laboratory tests had 100% specificity. Considering the 30 patients who had a clinical diagnosis of TBM: diagnostic sensitivity was 23% (7/30, 95%CI: 9.9–42%) for GeneXpert and was the same for all culture results combined; considerably greater than 7% (2/30, 95%CI: 0.82–22%) for microscopy; whereas all laboratory tests had poor negative predictive values (20–23%). Considering only the 8 patients with definite TBM: diagnostic sensitivity was 88% (7/8, 95%CI: 47–100%) for GeneXpert; 75% (6/8, 95%CI: 35–97%) for MGIT culture or LJ culture; 50% (4/8, 95%CI 16–84) for Ogawa culture and 25% (2/8, 95%CI: 3.2–65%) for microscopy. GeneXpert and microscopy provided same-day results, whereas culture took 20–56 days. GeneXpert provided same-day rifampicin-susceptibility results, whereas culture-based testing took 32–71 days. 38% (3/8, 95%CI: 8.5–76%) of patients with definite TBM with data had evidence of drug-resistant TB, but 73% (22/30) of all clinically diagnosed TBM (definite, probable, and possible TBM) had no drug-susceptibility results available. Conclusions Compared with traditional culture-based methods of CSF testing, GeneXpert had similar yield and faster results for both the detection of M. tuberculosis and drug-susceptibility testing. Including use of the GeneXpert has the capacity to improve the diagnosis of TBM cases.

Original languageEnglish
Article numbere0198695
JournalPLoS ONE
Volume13
Issue number6
DOIs
StatePublished - Jun 2018

Bibliographical note

Funding Information:
This project was supported by the National Institutes of Health Research Training Grant # D43 TW009345 funded by the Fogarty International Center, the National Institutes of Health Office of the Director Office of AIDS Research, the National Institutes of Health Office of the Director Office of Research on Women’s Health, the National Heart, Lung and Blood Institute, the National Institute of Mental Health and the National Institute of General Medical Sciences. ESM and CAE were funded by the Wellcome Trust (awards 057434/Z/99/Z, 070005/Z/02/Z, 078340/Z/ 05/Z, 105788/Z/14/Z and 201251/Z/16/Z); DFID-CSCF; the Joint Global Health Trials consortium (MRC, DFID, & Wellcome Trust award MR/ K007467/1); the STOP TB partnership’s TB REACH initiative funded by the Government of Canada and the Bill & Melinda Gates Foundation (awards W5_PER_CDT1_PRISMA and OPP1118545); and the charity IFHAD: Innovation For Health And Development. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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