Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2018 Jun 18;13(6):e0198695.
doi: 10.1371/journal.pone.0198695. eCollection 2018.

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

Tatiana Metcalf  1   2 , Jaime Soria  2   3 , Silvia M Montano  4 , Eduardo Ticona  3 , Carlton A Evans  5   6 , Luz Huaroto  3 , Matthew Kasper  4 , Eric S Ramos  6 , Nicanor Mori  2 , Podjanee Jittamala  1 , Kesinee Chotivanich  1 , Irwin F Chavez  7 , Pratap Singhasivanon  7 , Sasithon Pukrittayakamee  1 , Joseph R Zunt  8   9   10   11
Affiliations
Comparative Study

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

Tatiana Metcalf et al. PLoS One. .

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.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Study flowchart.
Fig 2
Fig 2. Performance of laboratory tests in definite, probable, and possible TBM diagnosis.
* Values in brackets are 95% confidence intervals.
Fig 3
Fig 3. Venn diagram showing positivity by GeneXpert, culture, and ZN smear microscopy using CSF samples in patients with definite TBM (n = 8).
Fig 4
Fig 4. Time to results for M.tuberculosis detection and drug sensitivity testing (DST).
See this image and copyright information in PMC

References

    1. WHO. The top 10 causes of death factsheet– 2017 Geneva: WHO, 2017.
    1. Berenguer J, Moreno S, Laguna F, Vicente T, Adrados M, Ortega A, et al. Tuberculous meningitis in patients infected with the human immunodeficiency virus. N Engl J Med.1992; 326(10):668–72. doi: 10.1056/NEJM199203053261004 - DOI - PubMed
    1. Kingkaew N, Sangtong B, Amnuaiphon W, Jongpaibulpatana J, Mankatittham W, Akksilp S, et al. HIV-associated extrapulmonary tuberculosis in Thailand: epidemiology and risk factors for death. Int J Infect Dis. 2009; 13(6):722–9. doi: 10.1016/j.ijid.2008.11.013 - DOI - PubMed
    1. Marais S, Thwaites G, Schoeman JF, Torok ME, Misra UK, Prasad K, et al. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis. 2010; 10(11):803–12. doi: 10.1016/S1473-3099(10)70138-9 - DOI - PubMed
    1. Thwaites GE, Duc Bang N, Huy Dung N, Thi Quy H, Thi Tuong Oanh D, Thi Cam Thoa N, et al. The influence of HIV infection on clinical presentation, response to treatment, and outcome in adults with Tuberculous meningitis. J Infect Dis. 2005; 192(12):2134–41. doi: 10.1086/498220 - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources