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Professional Med J 2017;24(5):656-664. www.theprofesional.com
TUBERCULOUS PERICARDITIS AND PLEURITIS
656
The Professional Medical Journal
www.theprofesional.com
TUBERCULOUS PERICARDITIS AND
PLEURITIS;
GENEXPERT ® TECHNOLOGY A BREAKTHROUGH FOR DIAGNOSIS IN LESS THAN
TWO HOURS
Prof. Dr. Hamid Mahmood1, Dr. Talmeez Zaib2, Dr. Zafar Hayat Maken3, Ammara Waqar4, Yasir Hassan5,
Dr. Hassan Mujtaba6, Dr. Faryal Murtaza7, Noor e Maham8
ORIGINAL PROF-3779
ABSTRACT… Background: Diagnosis of Tubercles Pericarditis and Pleuritis remains the
greatest challenge for clinicians. WHO has recommended GeneXpert MTB/RIF assay as a
screening test for substitution of conventional methods for the initial diagnosis and prognosis
of the extra pulmonary and pulmonary tuberculosis in developing countries. Objectives: To
nd out the diagnostic validity of GeneXpert assay for detection of Myco-bacterium tuberculosis
in the pericardial and pleural effusions samples, keeping MTB culture as “Gold Standard”.
Material and Methods: Total number of 286 samples of effusions (pericardial 128, pleural 158)
were received, and processed for Zn smear microscopy, LJ culture, GeneXpert MTB/RIF assay
according standard protocols. Efcacy for the detection of MTB was evaluated comparatively.
Results: Out of 286effusions samples AFB was detected by Zn smear in 11 (3.8%) samples while
GeneXpert detected MTB in 43 (15.0%) and LJ culture 51 (17.8%). Zn smear showed sensitivity
18.2%, specicity, 98.1%, Positive predictive value 81.8%, Negative predictive value 85.4 %, in
comparison GeneXpert showed high sensitivity 84.3%, specicity 100%, with Positive predictive
value 100%, and Negative predictive value 96.7%. Conclusion: GeneXpert assay is innovative
tool in resource limited settings for prompt detection of MTB along with drug résistance. It is
denitely an attractive point of care test, with High sensitivity and specicity along with turnout
time of two hours which facilitates timely diagnoses and appropriate management of tubercle
Pleuritis and Pericarditis.
Key words: GeneXpert MTB/RIF assay, Pleural effusions, pericardial effusion LJ culture.
1. Professor & HOD of Bio Chemistry,
CMH Institute of Medical Sciences,
(CIMS), Bahawalpur.
2. Assistant Professor,
Amna Inayat Medical College,
Sheikhupura.
3. Assistant Professor,
Federal Medical & Dental College,
Islamabad.
4. Department of Quality Assurance,
Amna Inayat Medical College,
Kishawar Fazal Teaching Hospital,
Shiekhupura.
5. University of Lahore, Lahore.
6. Allama Iqbal Medical College,
Lahore.
7. Allam Iqbal Medical College,
Lahore.
8. Amna Inayat medical College,
Shiekhupura.
Correspondence Address:
Dr. Hamid Mahmood
Professor of Bio Chemistry,
Amna Inayat Medical College,
Kishawar Fazal Teaching Hospital,
Sheikhupura.
drhamidmahmood373@gmail.com
Article received on:
14/12/2016
Accepted for publication:
16/03/2017
Received after proof reading:
06/05/2017
Article Citation: Mahmood H, Zaib T, Maken ZH, Waqar A, Hassan Y, Mujtaba H, Mutaza
F, Noor e Maham. Tuberculous pericarditis and pleuritis; genexpert ®
technology a breakthrough for diagnosis in less than two hours. Professional
Med J 2017;24(5):656-664. DOI: 10.17957/TPMJ/17.3779
INTRODUCTION
Despite molecular technological advances
in diagnostic methodologies reduction and
eradication of Tuberculosis (TB) still remains a
distant goal for clinicians. TB is known to be a
disease of mortality & morbidity worldwide. The
statics of World Health Organization (WHO) has
emphasized on the rapid diagnostic strategies
and effective treatment of TB has extremely
reduced mortality by 47% since 1990, yet TB
remains a major source of death, especially in
developing countries.1
TB caused by myco-bacterium tuberculosis
manifests itself in two forms, pulmonary tuberculosis
(PTB) or extra-pulmonary tuberculosis (EPTB).
Pulmonary TB is the commonly involving lungs
while extra pulmonary TB involves lymph nodes,
bone and joints, kidneys, intestine, abdominal
and serious membranes like plural, pericardial
and meninges.2
Globally, among 9.6 million reported TB patients
in 2012, estimated 15% were of EPTB while
European Center for Disease prevention and
Control euro surveillance report mentioned that
22% of notied TB patients in Europe were EPTB.3
Tubercles pleural effusion is well-known site of
EPTB.4 Tubercular Pericardial effusion is also one
of the common manifestation of EPTB occurring
in 1- 8% patients.5 Tuberculosis has been known
a cause of acute Pericarditis in 60-80% of the
patients in the developing world.5 pericardial
tuberculosis can be differentiated clinically from
other causes by using Tygerberg scoring system.
DOI: 10.17957/TPMJ/17.3779
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TUBERCULOUS PERICARDITIS AND PLEURITIS
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2
For the diagnosis of tubercular pleural and
pericardial effusion, Conventional methods
including ZN smear microscopy and LJ culture
are available in low to middle income countries.
Although ZN staining microscopy is rapid and
cheap, however it is less sensitive for diagnosis of
EPTB, because of pucibaciliary nature of samples
and non-uniform circulation of MTB. LJ Culture is
“Gold standard” methods, but its long turnaround
time of 2-6 weeks, as well as complexity of
procedure demand highly skilled staff along with
bio-safety level III lab, limits its applicability for its
routine use as diagnostic test.
For EPTB diagnosis, last few decades have
witnessed the advancement of molecular
techniques, with very good predictive value (PPV:
98–99%).7,8 Moreover eld of TB diagnosis is
revolutionized by targeting specic genes or gene
segments, and have shortened the turnaround
time of detection from weeks to days and days
to hours.8 Precise and accurate TB diagnosis
by new molecular tests necessitates specialized
infrastructure of laboratory with highly skilled and
efcient staff, demanding high cost, limits their
use in resource constrained settings.7
In 2010, WHO recommended the implementation
and the use of a new technology GeneXpert MTB/
RIF assay as a substitution over conventional
techniques.9 Later on In October 2013 again
WHO dispensed the importance of use of
this novel technique for the rapid detection of
tuberculosis infection among pediatric and extra-
pulmonary cases.10 Cepheid GeneXpert system
is innovative semi-automated real-time PCR
nucleic acid amplication technology, which can
simultaneously detect MTB and RIF’s resistance
in less than two hour. Molecular beacon
technology and ultrasensitive hemi nested PCR
are basis of GeneXpert system.11 As It is fully
closed system, hence there is minimal risk of any
type of contamination and biohazard. It also does
not require high expertise because of very simple
software based handling of the instrument.
A large body of literature is available regarding
the role of GeneXpert for the diagnosis of EPTB
including Pleuritis, but a paucity of evidence
exists concerning its use in Tubercular Pericarditis
for the detection of MTB. Thus Present study
was planned to highlight the role of GeneXpert
technology and to determine its validity for its
usage as future diagnostic tool for Tubercular
pericardial and pleural effusions.
METHODOLOGY
Ethical approval
Study protocols were approved from institutional
board of ethical certication Allama Iqbal medical
college & Jinnah hospital Lahore (AIMC&JHL).
Clinical specimens
A total of 286 specimens including 158 pleural
and 128 pericardial uids samples were received
from pulmonary and cardiology department of
tertiary care hospital Lahore Pakistan, during
January 2014 –august 2016.Samples were
selected on the basis of i) clinical presentation ,ii)
relative lab investigation, iii) echocardiography,
iv) radiological nding. Previously diagnosed TB
cases and patients on anti-tuberculosis therapy
(ATT) were excluded. All these samples were
processed at pathology department Myco-
bacteriology laboratory (AIMC&JHL), which is
among one of the largest referral center in Punjab
Pakistan.
Every specimen was processed for Ziehlneelson
(ZN) smears microscopy according to WHO12
GeneXpert MTB/RIF assay had been performed
directly in compliance with the manufacturer’s
SOP’s.13 LJ cultures were processed and reported
according to standard guidelines.14
QUALITY CONTROL & QUALITY ASSURANCE
ZN Smear
Positive and negative control slides were prepared
and stained with every batch. Every slide was
checked by two experienced Medical Laboratory
Technologist by using light microscope.
Random positive and negative, doubtful cases
were rechecked by highly experienced senior
microbiologists for quality assurance purposes.
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LJ Culture
culture media quality and mycobacterium growth
was conrmed by using American type culture
collection (ATCC) strains of H37rv. a bottle LJ
media was inoculated with sterile water as
negative control.15
GeneXpert Assay
Bacillus globigiispores has been used as an
internal sample processing and PCR control and
this assay is multiplexed with MTB assay 16
Data Presentation
SPSS 21.0 was used for determination of validity
of GeneXpert& Zn smear microscopy, in terms
of Sensitivity, specicity, positive predictive value
(PPV) negative predictive value (NPV) of ZN
Smear had been calculated as followed.
RESULTS
Out of total 286 specimens pericardial uids and
pleural uids were 44.7% (n=128), 55.3% (n=
158) respectively. Mean age was 44+10.2 years
while Males and female were 190 (66.4%) and
96(33.6%) respectively.
Figure-1 Shows Frequency distribution of
tuberculosis positive cases detected by different
techniques. LJ culture being “Gold standard” for
the diagnosis of pulmonary and extra pulmonary
tuberculosis, detected Maximum number of MTB
in total samples 51 (17.8%), 33 (20.8%) in pleural
and 18 (14.0%) in pericardial uids. It was followed
by GeneXpert MTB/Rif assay with detection of
MTB in 43 (15.0%) out of total samples, pleural
30 (18.9%) and pericardial 13 (10.1%). A low
numbers of positive cases were identied by
routinely used conventional technique Zn smear
microscopy. AFB was detected in 11 (3.8%),
pleural uid 8 (5.0%) and in pericardial uid
3(2.2%)
Table-I depicts the diagnostic validity of gene
expert assay for the purpose of detection of
MTB in the pericardial and pleural uid keeping
LJ culture as gold standard. It was seen that
the sensitivity of GeneXpert for pericardial uid
was 72.2%, specicity 100%, PPV 100% and
NPV 95.6% while for pleural uids the sensitivity,
specicity, PPV and NPV was 90%, 100%, 100%
and 97.6% was found respectively. Diagnostic
validity of GeneXpert for detection of MTB in
effusion overall was also determined in this study
and it was seen that it has a sensitivity of 84.3%,
specicity 100%, PPV 100% and NPV of 96.7%
respectively for total samples.
Figure-1. Frequency distribution of tuberculosis positive
cases detected by different techniques (n=286).
Samples type Technique LJ culture Total Sensitivity Specicity PPV NPV
+ve -ve
Pericardial uids Gene
Xpert
+ve 13 0 13
72.2% 100% 100% 95.6%-ve 5 110 115
Total 18 110 128
Pleural uids Gene
Xpert
+ve 30 0 30
90.0% 100% 100% 97.6%-ve 3 125 128
Total 33 125 158
Combine Gene
Xpert
+ve 43 0 43
84.3% 100% 100% 96.7%-ve 8 235 243
Total 51 235 286
Table-I. diagnostic validity of GeneXpert Assay
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The diagnostic validity of Zn smear microscopy
for the purpose of detection of AFB in pericardial
and pleural uid keeping LJ culture as gold
standard is shown in Table-II. It was seen that
the sensitivity of Zn smear for pericardial uid
was 11.7%, specicity 99.0%, PPV 66.6% and
NPV 88.0% while for pleural uids the sensitivity,
specicity, PPV and NPV was 21.8%, 99.2%,
87.5% and 83.3% respectively. Regarding,
Diagnostic validity of Gene Zn smear for detection
of AFB in effusions overall, it was seen that it has a
sensitivity of 18.3%, specicity 99.1%, PPV 81.8%
and NPV of 85.4% respectively for total samples.
Table-III. Presents the diagnostic validity of
GeneXpert in Zn smear negative pericardial
and pleural uid samples. It was seen that the
sensitivity of GeneXpert Smear negative for
pericardial uids was 68.7%, specicity 100%,
PPV 100% and NPV 95.6% while for pleural uids
the sensitivity, specicity, PPV and NPV was
88.4%, 100%, 100%, and 97.6%, respectively.
Diagnostic validity of Gene Zn smear for detection
of AFB overall was also determined in this study
and it was seen that it has a sensitivity of 80.9%,
specicity 100%, PPV 100%, and NPV 96.6%
respectively for total samples.
Figure-2 Showed sample-wise frequency
distribution of MDR cases detected by GeneXpert.
Among 13 MTB positive pericardial uids detected
by GeneXpert, 2 (15.3%) were drug resistance
and out of 30 MTB positive pleural uids 9(30%)
were drug resistant. Out of total 43 GeneXpert
positive samples 11(25.5%) were Multidrug
resistance tuberculosis (MDR).
DISCUSSION
Diagnosis of tuberculosis has always been a
challenge for health services and clinicians.
Despite the availability of anti-TB treatment
for more than 60 years, it is still a cause of an
unacceptably high mortality rate. EPTB is also
responsible for life threatening consequences
and to overcome this problem there is an urgent
Samples type Technique LJ culture Total Sensitivity Specicity PPV NPV
+ve -ve
Pericardial uids Zn
smear
+ve 2 1 3
11.75 99.0% 66.6% 88.0%-ve 15 110 125
Total 17 111 128
Pleural uids Zn
smear
+ve 7 1 8
21.8% 99.2% 87.5% 83.3%-ve 25 125 150
Total 32 126 158
Combine Zn
smear
+ve 92 11
18.3% 99.1% 81.8% 85.4%-ve 40 235 275
Total 49 237 286
Table-II. Statistics of Zn smear microscopy
Samples type Technique LJ culture Total Sensitivity Specicity PPV NPV
+ve -ve
Pericardial uids GeneXpert +ve 11 0 11
68.7% 100% 100% 95.6%-ve 4 110 114
Total 15 110 125
Pleural uids GeneXpert +ve 23 0 23
88.4% 100% 100% 97.6%-ve 2 125 127
Total 25 125 150
Combine GeneXpert +ve 32 0 32
80.9% 100% 100% 96.6%-ve 8 235 243
Total 40 235 275
Table-III. statistics of GeneXpert in Smear negative samples
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need for rapid diagnosis and proper treatment.
WHO endorsed GeneXpert has proven itself as
a breakthrough technique for the diagnosis of
EPTB, but limited literature is available about its
diagnostic validity in effusions. The present study
highlighted the role of Gene expert for rapid
diagnosis of tuberculosis Pericarditis and Pleuritis
in terms of sensitivity, specicity, PPV, NPV with LJ
culture being “Gold standard”. We also evaluated
sensitivity and specicity of Zn smear microscopy
in pleural and pericardial effusions for detecting
AFB.
Regarding ZN smear, Overall sensitivity of 18.3%
for both the sample with specicity of 99.1%,
was observed. While sensitivity and specicity
of 21.8% and 99.2% was seen for pleural uids
and 11.7% and 99.2% respectively for pericardial
uids was obtained. The results of our study are
signicantly higher as compared to those in study
from spain in which a sensitivity of 7.3% and
specicity of 100% was achieved by Zn smear
microscopy in tubercles pleural effusion. The
difference in the results might be attributed to the
difference in the endemicity of the disease in the
two regions with Pakistan being a high endemic
region as compared to Spain.18
Over all MTB positive rate was 17.8% detected by
LJ culture which is comparable with another study
conducted in similar province showing 18.1%
MTB positive rate among EPTB.19 This burden
is even greater in countries with high burden of
TB along with HIV shown by the results of study
conducted by Pandie et al. which reported a MTB
positive rate of about 49%.20
It was observed that GeneXpert has a high
sensitivity and specicity for detection of MTB
in effusions for diagnosis of tuberculouseffusion
i.e. 90% and 100% respectively. According to the
report published by WHO the pooled sensitivity of
GeneXpert in pleural uid is 43.7%, these results
are very lower then present study due to the use
of different gold standards in various studies
included in this meta- analysis.23
A recent meta-analysis reported the pooled
sensitivity and specicity of GeneXpert for pleural
uid as 46.4%and 99.1%, respectively, compared
with those of pleural uid mycobacterial culture24
Another meta-analysis conducted on 13 studies
reported pool sensitivity of GeneXpert as 37.0%
for pleural uids.25 Later on a systematic review
conducted on 24 studies reported pooled
sensitivity and specicity of GeneXpert as 51.4%
and 98.6%, respectively in pleural effusion.26
Results of these meta-analyses are different
due to difference in burden of disease, patients’
selection criteria and methodologies.
5
Figure-2. Sample-wise frequency distribution of MDR
cases detected by GeneXpert
Study Years TP FP FN TN Sensitivity Specicity REF
Friedrich et al 2011 5 0 4 16 56.0% 100% 27
Hanif et al 2011 3 0 0 8 100% 100% 28
Vadwai et al 2011 5 0 5 19 50% 100% 29
Al-Ateah et al 2012 3 0 0 10 100% 100% 30
Coleman et al 2014 90 4 37 69.0% 100% 31
Du et al 2015 25 0 7 94 78% 100% 32
Rufai et al 2015 23 0 19 120 55% 100% 33
Table-IV. previous studies reported Sensitivity and specicity of GeneXpert in tubercular pleural uids
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6
Another best diagnostic tool for pleural TB is
pleura biopsy which is an invasive procedure with
sensitivity ranging from 93 to 100%34,35 followed
by ADA level which has a variable sensitivity
ranging from 47-100%.36 This make GeneXpert a
favorable choice for the diagnosis of tubercular
pleuritis because of higher sensitivity, specicity,
rapidity and simplicity of the procedure
There is limited information on diagnostic utility of
this test in particular for pericardial uid which is
a highlight of this study. The results of this study
showed that GeneXpert exhibit a high diagnostic
validity for detection of MTB in pericardial uid
with a sensitivity 72.2% and specicity 100%.
Pandie et al.20 which showed a similar specicity
of 100% but a sensitivity of 63.8% which is less
as compared to our results because of inclusion
of a large proportion of immune-compromised
HIV patients in that study. Moreover, the strict
clinical diagnostic criteria for inclusion of patients
can also lead to the higher sensitivity reported
by current study. Cegielskiet al37 evaluated
diagnostic efcacy of PCR pericardial uid (n=13)
and pericardial tissue (n=15) from 20 patients,
and showed that accurate diagnosis of TB was
correctly made in 81% (n=13).
For the provisional diagnosis and initiation of
empirical therapy of tubercular pericarditis,
Tygerberg scoring system is usually applied
in clinical settings. However, due to increase
in multidrug resistance TB around the globe,
desirable treatment success rate is not achieved
with rst line drug making efcacy of therapy
questionable. The application of GeneXpert gives
additional information regarding drug resistance
thus optimizing and increasing the effectiveness
of therapy. The result of this study has pinpointed
25.5% MDR cases, 15.0% in pericardial and 30.0%
in pleural uids. All these drug resistance cases
can be timely managed according to the protocol
of drug resistance tuberculosis to achieve a
higher treatment success rate in minimum time.
Smear negative
Almost 3.553 GeneXpert instruments and 8.8
million cartridges were provided from WHO at
the end of 2014 among 110 high burden and
low-income countries.38 it is expected that there
will be scale up of this brilliant technology in future,
which will help in reducing not only the disease
burden, but also the cost of diagnosing and
managing the patients. WHO has recommended
in its revised guidelines that GeneXpert should
be used as an integral part for diagnosing
tuberculosis in high burden countries this assay,
as well as it will be a part of revised guidelines in
high burden countries.
In a study from South Africa in 2012, it is
documented that GeneXpert assay has replaced
the Zn smear microscopy for rapid detection
of mycobacterium tuberculosis, and has been
implemented on a very large scale among each
and every sector of the country.39
CONCLUSION
Considering the diagnostic validity of GeneXpert
along with detection of drug resistance in
2 hours turnout time, GeneXpert assay is a
boon for resource limited settings making it an
attractive tool for accurate diagnosis of tubercle
Pleuritis and Pericarditis with high sensitivity and
specicity point of care testing. This will facilitate
timely management and appropriate treatment of
patients to reduce the mortality and morbidity.
Limitations
One limitation in these study was that majority
of the respondents whom I approached were
not interested in participation. This did not
allow the research to be versatile in terms of
nding. The results may have diverse if there
were perceptions from a larger sample size.
Participants considered in this study do not
represent the general population of tuberculosis
patients and thus this study is limited to one city
or area of Pakistan. These ndings are principally
viewed through the laboratory lens. The number
of males in the research was greater with only
female participants.
Acknowledgments
The researchers are thankful for providing the free
kits. We are also grateful to the Jinnah Hospital
Professional Med J 2017;24(5):656-664. www.theprofesional.com
TUBERCULOUS PERICARDITIS AND PLEURITIS
662
staff, Allama Iqbal medical college, Ganga Ram
Hospital for providing assistance in this research.
Last but not least, we are grateful for all the
participants and the stake holders for their co-
operation.
Copyright© 16 Mar, 2017.
REFERENCES
1. Global Tuberculosis Report; 2015. Avail-
able from: http://www.apps.who.int/iris/bitstre
am/10665/191102/1/9789241565059_eng.pdf?ua=1.
[Last accessed on 2016 September 25].
2. Lee JY. Diagnosis and treatment of extrapulmonary
tuberculosis. TubercRespir Dis (Seoul) 2015; 78:47-55.
3. Global Tuberculosis Report; 2014. Available from:
http://www.who.int/tb/publications/global_report/
gtbr14_main_text.pdf. [2016 September 23].
4. Wares F, Balasubramanian R, Mohan A, Sharma SK.
2005. Extrapulmonary tuberculosis: management
and control. In AgarwalSP, ChauhanLS (ed), Tubercu-
losis control in India. Elsevier, New Delhi, India.
5. Value of Tygerberg Scoring for the Diagnosis and
Management of Tuberculous Pericarditis Achnes
Pangaribuan, 1 Kurniyanto, 2 Donnie Lumban Gaol,
2 Yunus Tanggo2 MajalahKedokteranFKUKI 2012 Vol
XXVIII No.4 Oktober-DesemberLaporanKasus.
6. Sharma SK, Mohan A. Extrapulmonary tuberculosis.
Indian J Med Res 2004; 120:316-53.
7. Purohit M, Mustafa T. Laboratory diagnosis of ex-
tra-pulmonary tuberculosis (EPTB) in resource-con-
strained setting: State of the art, challenges and the
need. J ClinDiagn Res 2015; 9:EE01-6.
8. Bisht D. Can newer diagnostic microbiological as-
says guide early tuberculosis management? Indian J
Tuberc 2011; 58:51-3.
9. Van Rie A, Page-Shipp L, Scott L, Sanne I, Stevens W.
Xpert(®) MTB/RIF for point-of-care diagnosis of TB
in high-HIV burden, resource-limited countries: Hype
or hope? Expert Rev MolDiagn 2010; 10:937-46.
10. Xpert MTB/RIF Assay for the Diagnosis of Pulmo-
nary and Extrapulmonary TB in Adults and Children,
Policy Update. Available from: http://www.apps.who.
int/iris/bitstream/10665/112472/1/9789241506335_eng.
pdf?ua=1. [Last accessed on 2015 Dec 4].
11. Alvarez-Uria G, AzconaJM, Midde M, NaikPK, Reddy
S, Reddy R. Rapid diagnosis of pulmonary and ex-
trapulmonary tuberculosis in HIV-infected patients.
Comparison of LED uorescent microscopy and the
GeneXpert MTB/RIF assay in a district hospital in India.
TubercResTreat 2012; 2012:932862.
12. WHO ZN staining manual.
13. World Health Organization. Xpert MTB/RIF imple-
mentation manual. WHO/HTM/TB/2014.1. Geneva,
Switzerland: WHO, 2014. http://apps.who.int/iris/bit-
stream/10665/112469/1/ 9789241506700_eng.pdf. Ac-
cessed November 2015.
14. Kudoh S, Kudoh T. A simple technique for culturing
tubercle bacilli. Bull World Health Organ 1974; 51: 71–
82.
15. Use of XpertW MTB/RIF assay in the rst national
antituberculosis drug resistance survey in Pakistan
S. Tahseen,* E. Qadeer, † F. M. Khanzada,* A. H. Riz-
vi,* A. Dean, ‡ A. Van Deun,§ M. Zignol‡ INT J TUBERC
LUNG DIS 20(4):448–455 Q 2016 The Union http://dx.
doi.org/10.5588/ijtld.15.0645 E-published ahead of print
1 February 2016.
16. Tyagi S, Kramer FR. Molecular beacons: Probes that
uoresce upon hybridization. Nat Biotechnol 1996;
14:303-8.
17. PorcelJM, Palma R, Valdes L,Bielsa S, San-Jose E,
Esquerda A. 2013. Xpert MTB/RIF in pleural uid for
the diagnosis of tuberculosis. Int J Tuberc Lung Dis
17:1217–1219. http://dx.doi.org/10.5588/ijtld.13.0178.
18. Du J, Huang Z, Luo Q, Xiong G, Xu X, Li W, Liu X, Li
J. 2015. Rapid diagnosis of pleural tuberculosis by
Xpert MTB/RIF assay using pleural biopsy and pleu-
ral uid specimens. J Res Med Sci20:26–31.
19. RAHMANI, MTH, et al. “Emergence of Tuberculo-
sis Infection: A Serious Threat to the Nation]’S
Health.” Biomedica 32.2 (2016): 93.
20. Pandie S, Peter JG, KerbelkerZS, Meldau R, Theron G,
Govender U, Ntsekhe M, Dheda K, Mayosi BM. Diag-
nostic accuracy of quantitative PCR (Xpert MTB/RIF)
for tuberculous pericarditis compared to adenosine
deaminase and unstimulated interferon-γ in a high
burden setting: a prospective study. BMC medicine.
2014 Jun 18; 12(1):1.
21. World Health Organization. The use of the Xpert MTB/
RIF® assay for the detection of pulmonary, extrapul-
monary tuberculosis and rifampicin resistance in
adults and children. Geneva. World health Organiza-
tion. 2013.
22. Albay A, Güney M, Tekin K, Kısa Ö, Sığ AK. Evaluation
of the geneXpert MTB/RIF assay for early diagnosis
of tuberculosis and detection of rifampicin resis-
tance in pulmonary and extrapulmonary specimens.
7
Professional Med J 2017;24(5):656-664. www.theprofesional.com
TUBERCULOUS PERICARDITIS AND PLEURITIS
663
Cukurova Medical Journal. 2016; 41(3):548-53.
23. World Health Organization. Policy update: automated
real time nucleic acid amplication technology for
rapid and simultaneous detection of tuberculosis
and rifampicin resistance: Xpert MTB/ RIF system for
the diagnosis of pulmonary and extra-pulmonary TB
in adults and children 2013; Availablehttp://apps.who.
int/iris/bitstream/10665/112472/1/9789241506335_eng.
pdf?ua=1. Accessed September August 2016.
24. Denkinger CM, Schumacher SG, Boehme CC, Denduku-
ri N, Pai M, Steingart KR. 2014. Xpert MTB/RIF assay for
the diagnosis of extrapulmonary tuberculosis: a sys-
tematic review and meta-analysis. EurRespir J 44:435–
446. http://dx.doi.org/10.1183/09031936.00007814.
25. Penz E, Boffa J, Roberts DJ, Fisher D, Cooper R, Ronks-
ley PE, James MT. Diagnostic accuracy of the Xpert®
MTB/RIF assay for extra-pulmonary tuberculosis: a
meta-analysis. The International Journal of Tuberculo-
sis and Lung Disease. 2015 Mar 1; 19(3):278-84.
26. Sehgal IS, Dhooria S, Aggarwal AN, Behera D, Agarwal
R. Diagnostic performance of Xpert MTB/RIF in tu-
berculous pleural effusion: systematic review and
meta-analysis. Journal of clinical microbiology. 2016
Apr 1; 54(4):1133-6.
27. Friedrich SO, von Groote-Bidlingmaier F, Diacon AH.
2011. Xpert MTB/RIF assay for diagnosis of pleural
tuberculosis. J ClinMicrobiol49:4341–4342. http://dx.
doi.org/10.1128/JCM.05454-11.
28. HanifSN, Eldeen HS, Ahmad S, Mokaddas E. 2011.
GeneXpert MTB/ RIF for rapid detection of Myco-
bacterium tuberculosis in pulmonary and extra-pul-
monary samples. Int J Tuberc Lung Dis 15:1274–1275.
http://dx.doi.org/10.5588/ijtld.11.0394.
29. Vadwai V, Boehme C, Nabeta P, Shetty A, Alland D, Ro-
drigues C. 2011. Xpert MTB/RIF: a new pillar in diag-
nosis of extrapulmonary tuberculosis? J ClinMicrobi-
ol49:2540–2545. http://dx.doi.org/10.1128/JCM.02319-
10.
30. Al-Ateah SM, Al-Dowaidi MM, El-Khizzi NA. 2012. Eval-
uation of direct detection of Mycobacterium tuber-
culosis complex in respiratory and nonrespiratory
clinical specimens using the Cepheid Gene Xpert
system. Saudi Med J 33:1100–1105.
31. Coleman M, Finney LJ, Komrower D, Chitani A, Bates
J, Chipungu GA, Corbett E, AllainTJ. 2015. Markers to
differentiate between Kaposi’s sarcoma and tuber-
culosis pleural effusions in HIV-positive patients. In-
ternational Journal of Tubercle Lung Diseases 19:144–
150. http://dx.doi.org/10.5588/ijtld.14.0289.
32. Du J, Huang Z, Luo Q, Xiong G, Xu X, Li W, Liu X, Li
J. 2015. Rapid diagnosis of pleural tuberculosis by
Xpert MTB/RIF assay using pleural biopsy and pleu-
ral uid specimens. J Res Med Sci20:26–31.
33. Rufai SB, Singh A, Kumar P, Singh J, Singh S. 2015. Per-
formance of Xpert MTB/RIF assay in the diagnosis
of pleural tuberculosis using pleural uid samples.
J ClinMicrobiol53:3636_3638. http://dx.doi.org/10.1128
/JCM.02182-15.
34. Rahman NM, Ali NJ, Brown G, Chapman SJ, Davies RJ,
Downer NJ, Gleeson FV, HowesTQ, Treasure T, Singh
S, Phillips GD. 2010. Local anaestheticthoracosco-
py: British Thoracic Society Pleural Disease Guide-
line 2010. Thorax 65(Suppl 2):ii54_ii60. http://dx.doi.
org/10.1136/thx.2010.137018.
35. Dhooria S, Singh N, Aggarwal AN, Gupta D, Agarwal
R. 2014. A randomized trial comparing the diagnos-
tic yield of rigid and semirigidthoracoscopy in undi-
agnosed pleural effusions. Respir Care 59:756–764.
http://dx.doi.org/10.4187/respcare.02738.
36. Liang QL, Shi HZ, Wang K, Qin SM, Qin XJ. 2008.
Diagnostic accuracy of adenosine deaminase
in tuberculous pleurisy: a meta-analysis. Re-
spirMed102:744–754. http://dx.doi.org/10.1016/j.
rmed.2007.12.007.
37. Cegielski JP, Devlin BH, Morris AJ, KitinyaJN, Pulipaka
UP, Lema LE, et al. Comparison of PCR, culture, and
histopathology for diagnosis of tuberculous pericar-
ditis. J ClinMicrobiol 1997; 35:3254-7.
38. World Health Organization. Stop TB Department. Road-
map for Rolling OutXpert MTB/RIF for Rapid Diagno-
sis of TB and MDR-TB; 2010. Available from: http://
www.who.int/tb/laboratory/roadmap_xpert_mtb-rif.pdf.
[Last accessed on 2015 Dec 25].
39. Meyer-Rath G, Schnippel K, Long L, MacLeod W, Sanne
I, Stevens W, et al. The impact and cost of scaling up
GeneXpert MTB/RIF in South Africa. PLoS One 2012;
7:e36966.
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Professional Med J 2017;24(5):656-664. www.theprofesional.com
TUBERCULOUS PERICARDITIS AND PLEURITIS
664
AUTHORSHIP AND CONTRIBUTION DECLARATION
Sr. # Author-s Full Name Contribution to the paper Author=s Signature
1
2
3
4
5
6
7
8
Prof. Dr. Hamid Mahmood
Dr. Talmeez Zaib
Dr. Zafar Hayat Maken
Ammara Waqar
Yasir Hassan
Dr. Hassan Mujtaba
Dr. Faryal Murtaza
Noor e Maham
Principal researcher
Co-researcher
Data collection
Data analysis
Data analysis
Proof reading
References
References
9
CORRECTION
The amendment of the Professional Vol: 24, No.02 (Prof-3711) page 335 titled: “Upper gastrointestinal bleeding;
Endoscopic ndings in patients” is as under;
INCORRECT
Dr. Mughees Ather1, Dr. Muhammad Sarfraz2, Dr. Muhammad Zikarya3
2. MBBS, FCPS (Med)
Assistant Professor of Medicine
Independent Medical College,
Independent University Hospital,
Faisalabad
3. MBBS, FCPS (Med)
Assistant Professor of Medicine
Independent Medical College,
Independent University Hospital,
Faisalabad
CORRECT
Dr. Mughees Ather1, Dr. Muhammad Sarfraz2, Dr. Muhammad Zakria3
2. MBBS, FCPS (Med)
Assistant Professor of Medicine
Independent Medical College,
Independent University Hospital,
Faisalabad
3. MBBS, FCPS (Med)
Associate Professor of Medicine
Independent Medical College,
Independent University Hospital,
Faisalabad
