Utility of circulating cell-free Mycobacterium tuberculosis DNA for the improved diagnosis of abdominal tuberculosis
Abdominal tuberculosis (ATB) continues to pose a major diagnostic challenge for clinicians due to its nonspecific clinical presentation, variable anatomical location and lack of sensitive diagnostic tools. In spite of the development of several assays till date; no single test has proved to be adequ...
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| creator | Sharma, Pratibha Anthwal, Divya Kumari, Pooja Gupta, Rakesh Kumar Lavania, Surabhi Sharma, Neera Sharma, Lokesh Kumar Rath, Deepak Soraganvi, Pavan Kumar Sharma, Ashish Gadpayle, A.K Taneja, R.S Tyagi, Jaya Sivaswami Haldar, Sagarika |
| description | Abdominal tuberculosis (ATB) continues to pose a major diagnostic challenge for clinicians due to its nonspecific clinical presentation, variable anatomical location and lack of sensitive diagnostic tools. In spite of the development of several assays till date; no single test has proved to be adequate for ATB diagnosis. In this study, we for the first time report the detection of circulating cell-free Mycobacterium tuberculosis (M. tuberculosis) DNA (cfMTB-DNA) in ascitic fluid (AF) samples and its utility in ATB diagnosis. Sixty-five AF samples were included in the study and processed for liquid culture, cytological, biochemical and molecular assays. A composite reference standard (CRS) was formulated to categorize the patients into 'Definite ATB' (M. tuberculosis culture positive, n = 2), 'Probable ATB' (n = 16), 'Possible ATB' (n = 13) and 'Non-TB' category (n = 34). Two molecular assays were performed, namely, the novel cfMTB-DNA qPCR assay targeting M. tuberculosis devR gene and Xpert MTB/RIF assay (Xpert), and their diagnostic accuracy was assessed using CRS as reference standard. Clinical features such as fever, loss of weight, abdominal distension and positive Mantoux were found to be strongly associated with ATB disease (p |
| doi_str_mv | 10.1371/journal.pone.0238119 |
| format | Article |
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In spite of the development of several assays till date; no single test has proved to be adequate for ATB diagnosis. In this study, we for the first time report the detection of circulating cell-free Mycobacterium tuberculosis (M. tuberculosis) DNA (cfMTB-DNA) in ascitic fluid (AF) samples and its utility in ATB diagnosis. Sixty-five AF samples were included in the study and processed for liquid culture, cytological, biochemical and molecular assays. A composite reference standard (CRS) was formulated to categorize the patients into 'Definite ATB' (M. tuberculosis culture positive, n = 2), 'Probable ATB' (n = 16), 'Possible ATB' (n = 13) and 'Non-TB' category (n = 34). Two molecular assays were performed, namely, the novel cfMTB-DNA qPCR assay targeting M. tuberculosis devR gene and Xpert MTB/RIF assay (Xpert), and their diagnostic accuracy was assessed using CRS as reference standard. Clinical features such as fever, loss of weight, abdominal distension and positive Mantoux were found to be strongly associated with ATB disease (p<0.05). cfMTB-DNA qPCR had a sensitivity of 66.7% (95% CI:40.9,86.7) with 97.1% specificity (95% CI:84.7,99.9) in 'Definite ATB' and 'Probable ATB' group collectively. The sensitivity increased to 70.9% (95% CI:51.9,85.8) in the combined 'Definite', 'Probable' and 'Possible' ATB group with similar specificity. The cfMTB-DNA qPCR assay performed significantly better than the Xpert assay which demonstrated a poor sensitivity of [less than or equal to]16.7% with 100% (95% CI:89.7,100) specificity (p<0.001). We conclude that cfMTB-DNA qPCR assay is an accurate molecular test that can provide direct evidence of M. tuberculosis etiology and has promise to pave the way for improving ATB diagnosis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0238119</identifier><identifier>PMID: 32845896</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Apoptosis ; Ascites ; Ascitic fluid ; Assaying ; Biochemistry ; Biology and Life Sciences ; Biopsy ; Biotechnology ; Body fluids ; Cell culture ; Composition ; Deoxyribonucleic acid ; Diagnosis ; Diagnostic software ; Diagnostic systems ; Digestive system diseases ; Disease ; Distension ; DNA ; Ethics ; Etiology ; Fever ; Fluids ; Genetic aspects ; Hospitals ; Identification and classification ; Laboratories ; Laparoscopy ; Liquid culture ; Medical diagnosis ; Medical education ; Medicine ; Medicine and Health Sciences ; Mycobacterium tuberculosis ; Patients ; Research and Analysis Methods ; Sensitivity ; Supervision ; Tuberculosis</subject><ispartof>PloS one, 2020-08, Vol.15 (8), p.e0238119-e0238119</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Sharma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Sharma et al 2020 Sharma et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5849-145c317c48151aa416219923c5f94b37d2357f7ef9ded751ee42ddd2f13ffef03</citedby><cites>FETCH-LOGICAL-c5849-145c317c48151aa416219923c5f94b37d2357f7ef9ded751ee42ddd2f13ffef03</cites><orcidid>0000-0001-8787-7582 ; 0000-0001-8276-4458 ; 0000-0002-6052-1137</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449497/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449497/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids></links><search><creatorcontrib>Sharma, Pratibha</creatorcontrib><creatorcontrib>Anthwal, Divya</creatorcontrib><creatorcontrib>Kumari, Pooja</creatorcontrib><creatorcontrib>Gupta, Rakesh Kumar</creatorcontrib><creatorcontrib>Lavania, Surabhi</creatorcontrib><creatorcontrib>Sharma, Neera</creatorcontrib><creatorcontrib>Sharma, Lokesh Kumar</creatorcontrib><creatorcontrib>Rath, Deepak</creatorcontrib><creatorcontrib>Soraganvi, Pavan Kumar</creatorcontrib><creatorcontrib>Sharma, Ashish</creatorcontrib><creatorcontrib>Gadpayle, A.K</creatorcontrib><creatorcontrib>Taneja, R.S</creatorcontrib><creatorcontrib>Tyagi, Jaya Sivaswami</creatorcontrib><creatorcontrib>Haldar, Sagarika</creatorcontrib><title>Utility of circulating cell-free Mycobacterium tuberculosis DNA for the improved diagnosis of abdominal tuberculosis</title><title>PloS one</title><description>Abdominal tuberculosis (ATB) continues to pose a major diagnostic challenge for clinicians due to its nonspecific clinical presentation, variable anatomical location and lack of sensitive diagnostic tools. 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Clinical features such as fever, loss of weight, abdominal distension and positive Mantoux were found to be strongly associated with ATB disease (p<0.05). cfMTB-DNA qPCR had a sensitivity of 66.7% (95% CI:40.9,86.7) with 97.1% specificity (95% CI:84.7,99.9) in 'Definite ATB' and 'Probable ATB' group collectively. The sensitivity increased to 70.9% (95% CI:51.9,85.8) in the combined 'Definite', 'Probable' and 'Possible' ATB group with similar specificity. The cfMTB-DNA qPCR assay performed significantly better than the Xpert assay which demonstrated a poor sensitivity of [less than or equal to]16.7% with 100% (95% CI:89.7,100) specificity (p<0.001). We conclude that cfMTB-DNA qPCR assay is an accurate molecular test that can provide direct evidence of M. tuberculosis etiology and has promise to pave the way for improving ATB diagnosis.</description><subject>Apoptosis</subject><subject>Ascites</subject><subject>Ascitic fluid</subject><subject>Assaying</subject><subject>Biochemistry</subject><subject>Biology and Life Sciences</subject><subject>Biopsy</subject><subject>Biotechnology</subject><subject>Body fluids</subject><subject>Cell culture</subject><subject>Composition</subject><subject>Deoxyribonucleic acid</subject><subject>Diagnosis</subject><subject>Diagnostic software</subject><subject>Diagnostic systems</subject><subject>Digestive system diseases</subject><subject>Disease</subject><subject>Distension</subject><subject>DNA</subject><subject>Ethics</subject><subject>Etiology</subject><subject>Fever</subject><subject>Fluids</subject><subject>Genetic aspects</subject><subject>Hospitals</subject><subject>Identification and 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Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sharma, Pratibha</au><au>Anthwal, Divya</au><au>Kumari, Pooja</au><au>Gupta, Rakesh Kumar</au><au>Lavania, Surabhi</au><au>Sharma, Neera</au><au>Sharma, Lokesh Kumar</au><au>Rath, Deepak</au><au>Soraganvi, Pavan Kumar</au><au>Sharma, Ashish</au><au>Gadpayle, A.K</au><au>Taneja, R.S</au><au>Tyagi, Jaya Sivaswami</au><au>Haldar, Sagarika</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Utility of circulating cell-free Mycobacterium tuberculosis DNA for the improved diagnosis of abdominal tuberculosis</atitle><jtitle>PloS one</jtitle><date>2020-08-26</date><risdate>2020</risdate><volume>15</volume><issue>8</issue><spage>e0238119</spage><epage>e0238119</epage><pages>e0238119-e0238119</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Abdominal tuberculosis (ATB) continues to pose a major diagnostic challenge for clinicians due to its nonspecific clinical presentation, variable anatomical location and lack of sensitive diagnostic tools. In spite of the development of several assays till date; no single test has proved to be adequate for ATB diagnosis. In this study, we for the first time report the detection of circulating cell-free Mycobacterium tuberculosis (M. tuberculosis) DNA (cfMTB-DNA) in ascitic fluid (AF) samples and its utility in ATB diagnosis. Sixty-five AF samples were included in the study and processed for liquid culture, cytological, biochemical and molecular assays. A composite reference standard (CRS) was formulated to categorize the patients into 'Definite ATB' (M. tuberculosis culture positive, n = 2), 'Probable ATB' (n = 16), 'Possible ATB' (n = 13) and 'Non-TB' category (n = 34). Two molecular assays were performed, namely, the novel cfMTB-DNA qPCR assay targeting M. tuberculosis devR gene and Xpert MTB/RIF assay (Xpert), and their diagnostic accuracy was assessed using CRS as reference standard. Clinical features such as fever, loss of weight, abdominal distension and positive Mantoux were found to be strongly associated with ATB disease (p<0.05). cfMTB-DNA qPCR had a sensitivity of 66.7% (95% CI:40.9,86.7) with 97.1% specificity (95% CI:84.7,99.9) in 'Definite ATB' and 'Probable ATB' group collectively. The sensitivity increased to 70.9% (95% CI:51.9,85.8) in the combined 'Definite', 'Probable' and 'Possible' ATB group with similar specificity. The cfMTB-DNA qPCR assay performed significantly better than the Xpert assay which demonstrated a poor sensitivity of [less than or equal to]16.7% with 100% (95% CI:89.7,100) specificity (p<0.001). We conclude that cfMTB-DNA qPCR assay is an accurate molecular test that can provide direct evidence of M. tuberculosis etiology and has promise to pave the way for improving ATB diagnosis.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>32845896</pmid><doi>10.1371/journal.pone.0238119</doi><tpages>e0238119</tpages><orcidid>https://orcid.org/0000-0001-8787-7582</orcidid><orcidid>https://orcid.org/0000-0001-8276-4458</orcidid><orcidid>https://orcid.org/0000-0002-6052-1137</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2020-08, Vol.15 (8), p.e0238119-e0238119 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2437389420 |
| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Apoptosis Ascites Ascitic fluid Assaying Biochemistry Biology and Life Sciences Biopsy Biotechnology Body fluids Cell culture Composition Deoxyribonucleic acid Diagnosis Diagnostic software Diagnostic systems Digestive system diseases Disease Distension DNA Ethics Etiology Fever Fluids Genetic aspects Hospitals Identification and classification Laboratories Laparoscopy Liquid culture Medical diagnosis Medical education Medicine Medicine and Health Sciences Mycobacterium tuberculosis Patients Research and Analysis Methods Sensitivity Supervision Tuberculosis |
| title | Utility of circulating cell-free Mycobacterium tuberculosis DNA for the improved diagnosis of abdominal tuberculosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T04%3A46%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Utility%20of%20circulating%20cell-free%20Mycobacterium%20tuberculosis%20DNA%20for%20the%20improved%20diagnosis%20of%20abdominal%20tuberculosis&rft.jtitle=PloS%20one&rft.au=Sharma,%20Pratibha&rft.date=2020-08-26&rft.volume=15&rft.issue=8&rft.spage=e0238119&rft.epage=e0238119&rft.pages=e0238119-e0238119&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0238119&rft_dat=%3Cgale_plos_%3EA633597844%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2437389420&rft_id=info:pmid/32845896&rft_galeid=A633597844&rft_doaj_id=oai_doaj_org_article_3497948fa6c64cbabdd8c83857a76861&rfr_iscdi=true |