Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
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I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : March | Volume : 16 | Issue : 3 | Page : OC25 - OC28 Full Version

Efficacy of CBNAAT versus Adenosine Deaminase in Fluids in Extrapulmonary Tuberculosis


Published: March 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/53715.16164
Abhinay Krishna Soni, Prashant Puraskar, Akash Shrikhande, Shweta Soni

1. Junior Resident, Department of Internal Medicine, People's College of Medical Sciences and Research Centre, Bhopal, Madhya Pradesh, India. 2. Professor, Department of Internal Medicine, People's College of Medical Sciences and Research Centre, Bhopal, Madhya Pradesh, India. 3. Associate Professor, Department of Pulmonary Medicine, People's College of Medical Sciences and Research Centre, Bhopal, Madhya Pradesh, India. 4. Junior Resident, Department of Internal Medicine, People's College of Medical Sciences and Research Centre, Bhopal, Madhya Pradesh, India.

Correspondence Address :
Dr. Akash Shrikhande,
HIG-C12, People’s College of Medical Sciences Campus, Bhanpur Road,
Bhopal, Madhya Pradesh, India.
E-mail: akashnshrikhande@gmail.com

Abstract

Introduction: Tuberculosis though primarily, is a pulmonary disease, it may manifest as Extrapulmonary Tuberculosis (EPTB). The gold standard method for the diagnosis of extrapulmonary tuberculosis is blood culture. Increased activity of Adenosine Deaminase (ADA) is observed in tuberculosis. Cartridge-based Nucleic Acid Amplification Test (CBNAAT) or Gene Xpert Mycobacterium tuberculosis/Rifampicin (MTB/RIF) is based on Real Time-Polymerase Chain Reaction (RT-PCR). Extrapulmonary tuberculosis may present with varied features, may mimic malignancy, and pose a diagnostic challenge.

Aim: To assess and compare the efficacy of Cartridge-based Nucleic Acid Amplification Test (CBNAAT) and Adenosine Deaminase (ADA) in cases with extrapulmonary tuberculosis.

Materials and Methods: This cross-sectional study was conducted on presumptive cases of extrapulmonary tuberculosis presenting in Department of Medicine at People’s College of Medical Sciences and Research Centre, Bhopal, Madhya Pradesh, India, from November 2019 to August 2021. All the patients were subjected to detailed history and clinical examination including series of blood and radiological investigations. Apart from this, ADA analysis and CBNAAT was done in all the cases and were treated accordingly. The two tests were compared using Chi-square test. The p-value <0.05 were considered statistically significant.

Results: Male predominance was observed and with no statistical difference in age (p-value=0.09) and gender (p-value=0.21). Out of 19 cases of Tubercular Meningitis (TBM) from total 125, ADA was raised in 10 (52.6%) cases, whereas out of 42 Tubercular Pleural Effusion (TBPE) and 24 Tubercular Peritonitis (TBP) cases, ADA was raised in 26 (61.9%) and 4 (16.7%) cases, respectively. Out of 19 cases of TBM, CBNAAT was positive in 4 (21.1%) cases, whereas out of 42 TBPE and 24 TBP cases, CBNAAT positivity was documented in 8 (19%) and 2 (8.3%) cases, respectively. Overall, the sensitivity of ADA was higher for detection of TBM and TBPE as compared to CBNAAT but the specificity of CBNAAT was higher for all the extrapulmonary tuberculosis. Overall diagnostic accuracy of ADA was higher (61.6%) as compared to CBNAAT (43.2%) for detection of extrapulmonary tuberculosis.

Conclusion: Extrapulmonary tuberculosis poses diagnostic challenge and thus for diagnosis, evaluation of each component i.e., history, physical examination, blood investigations, fluid analysis, ADA estimation, and CBNAAT is important. Relying solely on single diagnostic modality may be associated with low diagnostic yield, and thus each step of patient assessment must be given equal preference so as to improve the diagnostic yield.

Keywords

Cartridge-based nucleic acid amplification test, Tubercular meningitis, Tubercular peritoneal effusion, Tubercular pleural effusion

Tuberculosis (TB) is one of the oldest known infectious diseases which is still the single leading cause of mortality all over the globe (1). Though primarily, it is a pulmonary disease, the disease may manifest as Extrapulmonary Tuberculosis (EPTB) (2). World Health Organisation (WHO) (2020) estimates approximately, 10 million cases of tuberculosis worldwide. Of them, 1/4th of the cases are reported from India accounting for approximately 2.6 million cases. The burden of EPTB may range from 15-20% (3),(4). The most common sites affected in extrapulmonary tuberculosis include lymph nodes, bone, and joints, pleura, urogenital tract, and meninges (5). WHO recommends that EPTB must be suspected based upon relevant clinical manifestation, culture, histological features of the granulomatous lesion (6),(7). The gold standard method for the diagnosis of EPTB is blood culture. But it has been associated with certain disadvantages which include its high cost, non availability in resource-poor settings, and delay in getting the results i.e., 4 to 8 weeks (2).

Body fluids such as pleural, pericardial, and peritoneal fluids can be accessed easily and may be an important diagnostic clue for extrapulmonary tuberculosis. Increased activity of Adenosine Deaminase (ADA), an enzyme involved in purine metabolism, predominantly found in lymphocytes is observed in tuberculosis. ADA measurements in pleural, pericardial, and peritoneal fluids are widely used as a surrogate marker of EPTB (8),(9),(10). Different cut-off values have been proposed for ADA activity in various fluids. In pleural fluid, the cut-off value is suggested as 40 IU/L with a sensitivity of 92% and specificity of 89% (9). For Cerebrospinal Fluid (CSF) in meningitis, sensitivity and specificity of 59% and 96%, respectively have been documented at ADA cut-off of 8 IU/L (10). For peritoneal fluid, ADA estimation at 36 to 40 IU/L is 100% sensitive and 97% specific (11). However, for TB pericarditis, at a cut of 40 IU/L, EPTB can be diagnosed with 88% sensitivity and 83% specificity (12). The National Tuberculosis Elimination Program has promoted public-private partnerships and has certified private sector and Non Governmental Organisation (NGO) laboratories to provide quality assured services to all patients (13). For promoting the early diagnosis of EPTB, Cartridge-based Nucleic Acid Amplification Test (CBNAAT) or Gene Xpert Mycobacterium tuberculosis/Rifampicin (MTB/RIF) was introduced as a new technique by WHO in 2010 and Revised National TB Control Programme (RNTCP) in 2012 in central tuberculosis laboratories (14).

CBNAAT is based on Real Time-Polymerase Chain Reaction (RT-PCR). Its introduction was considered as a boon for the diagnosis of tuberculosis in developing countries like India, due to its high diagnostic yield and rapidity of results (within 2 hours). Also, it is helpful in detecting rifampicin resistance with minimum expertise (15). Extrapulmonary tuberculosis may present with varied features, may mimic malignancy, and pose a diagnostic challenge. The present study was therefore conducted to determine CBNAAT assay and ADA levels in pleural fluid, ascitic fluid and CSF in presumptive cases of extrapulmonary tuberculosis.

Material and Methods

This cross-sectional study was conducted on presumptive cases of extrapulmonary tuberculosis {Tubercular Meningitis (TBM), Tubercular Pleural Effusion (TBPE) and Tubercular Peritonitis (TBPE)} reported in Department of Medicine at People’s College of Medical Sciences and Research Centre, Bhopal, Madhya Pradesh, India, from November 2019 to August 2021. Ethical clearance from Institutional Ethical Committee (IEC No.-PCMS/OD/2019/1439/23) was obtained.

Inclusion and Exclusion criteria: All presumptive cases of extrapulmonary TB (pleural, peritoneal and meningeal) admitted in Department of Medicine and Pulmonary Ward and patient with informed consent were included in study. Patients <18 years of age and already receiving antitubercular medication were excluded from the study.

Procedure

Detailed data pertaining to socio-demographic variables and clinical history was obtained from all the study participants. Further, all the participants were subjected to detailed general, local and systemic examination and data was documented. Patients were subjected to a series of blood and radiological investigations. Further, ADA analysis and CBNAAT was done and patients were treated accordingly.

Adenosine deaminase analysis: ADA is an enzyme involved in purine metabolism that is found in many tissues, particularly in T-lymphocytes from the lymphoid tissue (7). A 20 mL each pleural fluid, ascitic fluid and 1mL CSF sample were taken and collected in a sterile vessel and ADA levels were estimated in cases of presumptive extrapulmonary tuberculosis. The cut-off limit of ADA levels for TBM was more than 10 IU/L, whereas that for TBPE and TBP was above 40 IU/L and 40 IU/ML, respectively. Technique used was Diazyme autoanalyser method (16).

Cartridge-based nucleic acid amplification test: CBNAAT is based upon the principle of Polymerase Chain Reaction (PCR) which helps in rapid detection of Mycobacterium tuberculosis. For CBNAAT, 1mL sputum sample was taken from the patients. It targets rpoB gene and helps in identification of rifampicin resistance as well. This method is highly specific as this method uses 3 primers and 5 molecular probes which specifically target rpoB gene of Mycobacterium tuberculosis (17).

As patients with suspected tuberculosis were enrolled, all the patients underwent complete diagnostic workup and were categorised into 4 groups:

• Extrapulmonary tuberculosis patients
- Tuberculous Pleural Effusion (TBPE)
- Tubercular Meningitis (TBM)
- Tubercular Peritonitis (TBP)
• Patients without tuberculosis

Statistical Analysis

The data was compiled using Microsoft Excel and analysed using IBM Statistical Package for the Social Sciences (SPSS) software version 20.0. Categorical variables were expressed as frequency and percentage whereas continuous variables were expressed as mean±Standard Deviation. The two tests were compared using Chi-square test. The p-value <0.05 was considered statistically significant. Sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of ADA and CBNAAT was calculated for diagnosis of EPTB and expressed as percentage.

Results

A total sample size of 125 was taken with presumptive diagnosis of TBP (n=60), TBPE (n=45) and TBM (n=20). These suspected cases were further categorised based upon final diagnosis as no tuberculosis (n=40), TBM (n=19), TBPE (n=42) and TBP (n=24). Mean age of the patients with TBM, TBPE and TBP was 38.26±17.94, 41.24±20.33 and 46±14.62 years, respectively. Male predominance was observed and with no statistical difference in age (p-value=0.09) and gender (p-value=0.21) (Table/Fig 1).

Out of 45 suspected TBPE cases, 93.3% (42) cases actually had TBPE, whereas out of 20 TBM and 60 TBP cases, 95% (19) and 40% (24) cases had respective tuberculosis. Majority of suspected TBP cases had no tuberculosis (Table/Fig 2).

Out of 19 cases of TBM, ADA was raised in 52.6% cases, whereas out of 42 TBPE and 24 TBP cases, ADA was raised in 61.9% and 16.7% cases, respectively (Table/Fig 3).

Out of 19 cases of TBM, CBNAAT was positive in 21.1% cases, whereas out of 42 TBPE and 24 TBP cases, CBNAAT positivity was documented in 19% and 8.3% cases, respectively (Table/Fig 4).

Overall, the sensitivity of ADA was higher for detection of TBM and TBPE as compared to CBNAAT but the specificity of CBNAAT was higher for all the extrapulmonary tuberculosis. Overall diagnostic accuracy of ADA was higher (61.6%) as compared to CBNAAT (43.2%) for detection of extrapulmonary tuberculosis (Table/Fig 5).

Discussion

For improving the diagnosis of EPTB, various methods have been suggested, depending upon the site of tuberculosis; e.g., for peritoneal tuberculosis, laparoscopic guided peritoneal biopsy is the investigation of choice. To increase the diagnostic yield, PCR assays have been suggested along with biopsy and culture. Assessment of various body fluids, depending upon the site of EPTB was identified as an important tool for predicting EPTB. The body fluid may show atypical features but the absence of these features does not rule out extrapulmonary tuberculosis (15). The role of ADA (an enzyme involved in purine metabolism) was suggested in the body fluids for detection of EPTB (15). Apart from ADA, the estimation of Interferon-gamma (IFN-γ) in pleural or pericardial fluid has been suggested as an important tool for early detection of EPTB cases. The introduction of CBNAAT was considered as a boon due to its high diagnostic value in pulmonary as well as extrapulmonary tuberculosis. Apart from this, availability of immediate results i.e., within 2 hours and simultaneous assessment of rifampicin resistance is the two major advantages of CBNAAT. Its introduction revolutionised the field of infectious disease (15).

The present study was conducted on a total of 125 suspected cases of extrapulmonary tuberculosis with the aim to find out utility of CBNAAT and ADA as laboratory tests for diagnosis of presumptive extrapulmonary tuberculosis cases of pleural effusion, meningitis and peritonitis. Out of 125 cases of suspected extrapulmonary tuberculosis, 60, 45 and 20 cases were suspected TBP, TBPE and TBM cases, respectively. Out of them, 40 cases were non tubercular cases which were wrongly suspected as TBPE (n=3), TBM (n=1) and TBP (n=36). The final diagnosis was established based upon clinical examination, fluid analysis and ADA and CBNAAT levels.

ADA levels and CBNAAT are two modern diagnostic tests which are valuable tool for diagnosis of tuberculosis. Though exact physiological role of ADA is not known, ADA activity in extrapulmonary tuberculosis is sensitive and specific method for diagnosis of EPTB (10),(11),(12). Different cut-off values have been proposed for ADA activity in various fluids. In our study, ADA cut-off of 10, 40 and 40 IU/L was considered for CSF, pleural and peritoneal fluid respectively. CBNAAT has no such cut-off values; it can give results either as positive or negative. Its introduction was considered as a boon and this method is based on RT-PCR. It has high diagnostic yield, give results rapidly (within 2 hours) and helps in detecting the rifampicin resistance (18).

For diagnosis of TBM, at the cut-off of 10 IU/L, the specificity and PPV of ADA was 100%, which is similar to CBNAAT, but sensitivity of ADA for diagnosis of TBM was much higher (52.6%) than CBNAAT (21.1%). Overall diagnostic accuracy of ADA was 55% whereas that of CBNAAT was 25% for diagnosis of TBM. Chotmongkol V et al., using the ROC curve identified the cut-off of 15.5 U/l for CSF ADA with a sensitivity of 75%, specificity of 93% (19). Barua R and Hossain MA at a cut-off point of 8.5 IU/l of ADA documented the sensitivity and specificity of 57% and 87%, respectively. They observed decline in sensitivity when the cut-off of ADA was raised to 10 IU/l (specificity-90%, sensitivity-36%) (20). Kohli M et al., however reported much higher sensitivity of CBNAAT for estimation of TBM i.e., 89% (21).

For diagnosis of TBPE, the cut-off level of ADA was 40 IU/L At this cut-off, the sensitivity of ADA was 61.9% whereas that of CBNAAT was 19.1%. However, PPV and specificity of CBNAAT was 100% i.e., much higher as compared to ADA. Overall, the diagnostic accuracy of ADA was better (60%) for diagnosis of TBPE as compared to CBNAAT (24.4%). Our study findings were concordant with the findings of Naik M et al., in which, ADA >40 units/liter was observed in 72% cases and the sensitivity, specificity, PPV and NPV of CBNAAT was 95.24%, 36.70%, 28.57%, and 96.67%, respectively (22). Modi SD et al documented the sensitivity of ADA for diagnosis of TBPE as 89.47%, whereas specificity was 48.28%, PPV was 81.9% and NPV was 63.65% (23). Similar to our study, Jain J et al., reported much lower sensitivity (16.7%) but 100% specificity with diagnostic accuracy of 52.5% of CBNAAT for diagnosis of TBPE (24). However, Phuljhele S et al., documented the sensitivity and specificity of CBNAAT for diagnosis of TBPE and TBM as 100% (25).

In present study, the cut-off of ADA for detection of TBP was 40 IU/L. At this cut-off value, the specificity and PPV of ADA was 97.2% and 80%, respectively but sensitivity and NPV was low. Similarly, the specificity and PPV of CBNAAT for TBP was 100% whereas sensitivity was much lower. Enas H et al., documented the sensitivity and specificity of 10% and 92.6% for ADA at the cut-off level of 35 IU/L (26). Lawn SD and Zumla AI observed the sensitivity of CBNAAT for estimation of TBP as 78.7% (27). However, Kohli M et al., documented the specificity of more than 98% for peritoneal fluid assessment in PTB (20). In third world countries, where newer and fancy investigations are not available, comparison between conventional and new investigations help us in determining EPTB.

Limitation(s)

Current study had certain limitations, firstly, the sample size was small and secondly, as sensitivity obtained for ADA was found to be low. A gold standard method like Acid-Fast Stain in pleural tissue or a growth of MTB on culture medium should have been employed in the study. The findings could not be generalised as it was a cross-sectional single centre based study.

Conclusion

Extrapulmonary tuberculosis cases pose diagnostic challenge and its diagnosis cannot be relied on single test. Each component i.e., history, physical examination, blood investigations, fluid analysis, ADA estimation, and CBNAAT are important in evaluation of such cases and provide some diagnostic clues. Relying solely on single diagnostic modality may be associated with low diagnostic yield, and thus each step of patient assessment must be given equal preference so as to improve the diagnostic yield. However, our study documented ADA as better tool as compared to CBNAAT for diagnosis of extrapulmonary tuberculosis.

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DOI and Others

DOI: 10.7860/JCDR/2022/53715.16164

Date of Submission: Jan 04, 2022
Date of Peer Review: Jan 28, 2022
Date of Acceptance: Feb 19, 2022
Date of Publishing: Mar 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Jan 05, 2022
• Manual Googling: Jan 25, 2022
• iThenticate Software: Feb 14, 2022 (8%)

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