Indian J Pediatr (November 2016) 83(11):1353–1355
DOI 10.1007/s12098-016-2096-0
CLINICAL BRIEF
GeneXpert for Diagnosis of Tubercular Meningitis
Rakesh Bhatia 1 & Rajeshwar Dayal 1 & Shishir Jindal 1 & Dipti Agarwal 1,3 & Ankur Goyal 2
Received: 20 August 2015 / Accepted: 16 March 2016 / Published online: 7 April 2016
# Dr. K C Chaudhuri Foundation 2016
Abstract Diagnosis of tubercular meningitis (TBM) is diffi-
cult in children. The GeneXpert MTB/RIF assay has been
recommended by WHO in 2013 to be used in children and
in extra pulmonary clinical specimens. The present study was
designed to assess the diagnostic utility of GeneXpert in de-
tecting Mycobacterium tuberculosis in cerebrospinal fluid
(CSF) in TBM cases and to compare the results with liquid
culture BACTEC 460. Thirty four subjects <15 y were diag-
nosed as TBM based on clinical, CSF and imaging details.
Sensitivity of GeneXpert in CSF was 38.24 % as compared to
Bactec culture which was only 14.71 % (p 0.0279). To con-
clude, GeneXpert MTB/RIF test is able to rapidly confirm
diagnosis of TBM with higher sensitivity as compared to con-
ventional methods and liquid culture.
Keywords Tubercular meningitis . GeneXpert . BACTEC .
Cerebrospinal fluid . Diagnosis
Introduction
Tubercular meningitis (TBM) is the most fatal form of infection
with Mycobacterium tuberculosis. In 2013, an estimated 9
* Dipti Agarwal
drdiptiagarwal@yahoo.co.in
1
Department of Pediatrics, S. N. Medical College, Agra, Uttar
Pradesh, India
2
Department of Microbiology, S. N. Medical College, Agra, Uttar
Pradesh, India
3
Flat no.310, Shivam Elegant Appt., Sikandra Bodla Rd.,
Agra 282007, Uttar Pradesh, India
million people developed TB globally with India accounting
for 24 % of the cases. There was an estimated 5,50,000 cases
and 80,000 deaths among children less than 15 y of age world-
wide [1]. Early diagnosis of TBM in children is difficult due to
vague clinical manifestations and paucibacillary nature. Various
laboratory tests such as microscopy and culture of CSF have
poor yield [2]. In 2013, WHO has recommended use of
GeneXpert MTB/RIF for diagnosis of TB in children and in
extrapulmonary forms [1]. Few studies have reported successful
use of the test in extrapulmonary samples with sensitivities rang-
ing from 29 to 100 % [3–5]. However the number of CSF sam-
ples tested in children in these studies are very few. Hence, this
study was conducted to assess the diagnostic utility of
GeneXpert test in detecting Mycobacterium tuberculosis in
TBM in children and to compare with BACTEC 460 TB culture.
Material and Methods
This cross sectional study was conducted in the Department of
Pediatrics, S.N. Medical College, Agra from March 2014
through February 2015. Subjects <15 y with clinically
suspected TBM (having fever >1 wk, headache, vomiting,
neck stiffness, convulsions, focal neurological deficits, altered
consciousness, history of tubercular contact) [6] were subject-
ed to CSF examination and imaging. Five ml of cerebrospinal
fluid was drawn; 2 ml of sample was sent for cytological/
biochemical estimation along with microscopy (gram
staining/Ziehl Neelson staining). One ml CSF was used for
Bactec culture 460 and 2 ml was used for Cepheid GeneXpert
MTB/RIF assay. GeneXpert used ultrasensitive hemi-nested
PCR and molecular beacons technology [1]. Cases with prior
anti-tubercular treatment were not included in the study.
Patients with CSF findings (cytology having <500 cells/
mm3 with lymphocytosis and biochemistry showing increased
1354 Indian J Pediatr (November 2016) 83(11):1353–1355

proteins [6] with or without imaging findings (hydrocephalus
or basal meningeal enhancement or infarcts) were included in
the suspected TBM group; alternative diagnosis was made in
patients not meeting the above CSF and imaging findings;
were subjected to repeat CSF examination where partially
treated septic meningitis was suspected and viral antibody
assays done where needed. These patients served as controls.
HIV screening test was done in all the TBM suspected cases.
A written informed consent was taken from guardians of the
subjects included in the study. The study was approved by the
ethical committee of the institute.
Sensitivity and specificity of the tests (GeneXpertMTB/RIF,
Bactec460) were calculated in the suspected TBM cases and the
tests were compared using chi-square test (software SPSS17).
Results
Fifty five patients were enrolled as clinically suspected TBM
cases, of which 34 patients were taken in the suspected TBM
group and in remaining 21 patients alternative diagnosis was
made; 13 were partially treated septic meningitis, 8 were viral
meningitis. Clinico demographic details of the suspected TBM
group is given in Table 1. GeneXpert was positive in 13/34 cases
while Bactec 460 culture detected mycobacteria in 5/34 cases
only. Sensitivity of GeneXpert was 38.24 % as compared to
Bactec culture showing a sensitivity of 14.71 %. which was
significantly higher (X2 = 4.8356, df = 1, p value =0.0279).
GeneXpert could detect additional 8 (23.5 %) cases over
Bactec culture. Rifampicin resistance was not detected in any
of the cases of TBM using GeneXpert. Microscopy using Zeihl
Neelson stain did not reveal any acid fast bacilli. CT scan showed
hydrocephalus in 30/34 (88.24 %) patients. Presence of basal
exudate and/or infarcts was seen in 19(55.89 %) patients. None
of the study subjects were positive for HIV infection.
Discussion
In this study diagnostic utility of GeneXpert was evaluated in
TBM cases in children. GeneXpert has been endorsed by WHO
in 2010 to be used in pulmonary specimens and also expanded
its use for extrapulmonary specimens in TB in 2013.
Sensitivity of GeneXpert in the index study in CSF is com-
parable to other Indian studies who have also shown lower
sensitivities in CSF (29 % and 24.6 %) respectively [3, 5].
Another study conducted by Nhu et al. has shown better
(59.3 %) sensitivity in CSF [4]. Paucibacillary nature of TBM
and small sample size may be the probable reason for low
positivity of GeneXpert in CSF. Sensitivity of BACTEC culture
in the index study was found to be lower than an another study
which reported it as 34.10 % in TBM cases [7]. However, there
was a significant improvement of GeneXpert over BACTEC in
diagnosis of TBM, as also shown in another study [3].
Rifampicin resistance was not demonstrated in the index study
in contrast to 3.7 % resistance reported in an another study [4].
This may be due to inclusion of new cases in the index study.
Neuroimaging served as an important non-invasive tool to
support the diagnosis of TBM. On CT scan of brain, hydro-
cephalus was the main finding in the index study as also noted
in other studies showing associated hydrocephalus in 94 %
and 80.3 % of TBM patients respectively [8, 9].

Table 1 Clinical profile of TBM cases in children (n = 34)

Conclusions
Characteristics N Percentage
GeneXpert has higher sensitivity compared to other diagnostic
Age (y), Mean 4.97 ± 2.82 modalities currently available including liquid culture. It is a
Males 20 58.82 promising diagnostic tool for early diagnosis of tubercular
H/o Contact meningitis. However in view of small sample size, further
Present 18 52.94 studies are required before any firm conclusion can be drawn.
Absent 16 47.06
Tuberculin test Acknowledgments The authors thank Dr. Shamrendra Narayan,
Positive 6 17.65 Assistant Professor, Department of Radiodiagnosis, S. N. Medical
Negative 28 82.35 College, Agra who helped in the reporting of the radiological investiga-
tions done for the study subjects.
Clinical Features
Seizures 32 94.12 Contributions RB, RD planned the study. SJ collected and analysed
Fever 29 85.29 the data. DA and AG contributed to draft of the manuscript. RB will act as
Altered sensorium 21 61.76 guarantor for the paper.
Vomiting 16 47.06
Compliance with Ethical Standards
Headache 5 14.70
Cranial nerve involvement 5 14.70 Conflict of Interest None.
Motor deficit 3 8.82
Source of Funding None.
Indian J Pediatr (November 2016) 83(11):1353–1355
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