{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:46:37Z","timestamp":1791848797476,"version":"4.3.4"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>A pleural fluid adenosine deaminase (ADA) has been used globally to assist in the diagnosis of a tuberculous pleural effusion (TPE) with a notable negative predictive value.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>We report a case of a patient with a negative pleural fluid ADA who was found to have culture-positive and biopsy-proven <jats:italic>Mycobacterium tuberculosis.<\/jats:italic><\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This case shows the importance of pursuing gold standard diagnostic studies when clinical suspicion remains high despite negative preliminary testing. We further describe gaps in research to improve pleural fluid biomarkers for TPE.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12879-021-06276-4","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T08:03:02Z","timestamp":1623744182000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Adenosine deaminase negative pleural tuberculosis: a case report"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3551-3901","authenticated-orcid":false,"given":"Zachary H.","family":"Boggs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Heysell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Eby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Arnold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"issue":"4","key":"6276_CR1","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1378\/chest.99.4.883","volume":"99","author":"AF Seibert","year":"1991","unstructured":"Seibert AF, Haynes J, Middleton R, Bass JB. Tuberculous pleural effusion: twenty-year experience. Chest. 1991;99(4):883\u20136. https:\/\/doi.org\/10.1378\/chest.99.4.883.","journal-title":"Chest"},{"issue":"7","key":"6276_CR2","doi-asserted-by":"publisher","first-page":"E486","DOI":"10.21037\/jtd.2016.05.87","volume":"8","author":"K Zhai","year":"2016","unstructured":"Zhai K, Lu Y, Shi HZ. Tuberculous pleural effusion. J Thorac Dis. 2016;8(7):E486\u201394. https:\/\/doi.org\/10.21037\/jtd.2016.05.87.","journal-title":"J Thorac Dis"},{"issue":"6154","key":"6276_CR3","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1136\/bmj.2.6154.1751-a","volume":"2","author":"MA Piras","year":"1978","unstructured":"Piras MA, Gakis C, Budroni M, Andreoni G. Adenosine deaminase activity in pleural effusions: an aid to differential diagnosis. Br Med J. 1978;2(6154):1751\u20132. https:\/\/doi.org\/10.1136\/bmj.2.6154.1751-a PubMed PMID: 737480; PubMed Central PMCID: PMC1610017.","journal-title":"Br Med J"},{"issue":"5","key":"6276_CR4","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1016\/j.rmed.2007.12.007","volume":"102","author":"QL Liang","year":"2008","unstructured":"Liang QL, Shi HZ, Wang K, Qin SM, Qin XJ. Diagnostic accuracy of adenosine deaminase in tuberculous pleurisy: a meta-analysis. Respir Med. 2008;102(5):744\u201354. https:\/\/doi.org\/10.1016\/j.rmed.2007.12.007 Epub 2008 Jan 28. Review. PubMed PMID: 18222681.","journal-title":"Respir Med"},{"issue":"5","key":"6276_CR5","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.ejim.2010.03.011","volume":"21","author":"JM Porcel","year":"2010","unstructured":"Porcel JM, Esquerda A, Bielsa S. Diagnostic performance of adenosine deaminase activity in pleural fluid: a single-center experience with over 2100 consecutive patients. Eur J Intern Med. 2010;21(5):419\u201323. https:\/\/doi.org\/10.1016\/j.ejim.2010.03.011 Epub 2010 May 1. PubMed PMID: 20816597.","journal-title":"Eur J Intern Med"},{"issue":"3","key":"6276_CR6","doi-asserted-by":"publisher","first-page":"e0213728","DOI":"10.1371\/journal.pone.0213728","volume":"14","author":"AN Aggarwal","year":"2019","unstructured":"Aggarwal AN, Agarwal R, Sehgal IS, Dhooria S. Adenosine deaminase for diagnosis of tuberculous pleural effusion: a systematic review and meta-analysis. PLoS One. 2019;14(3):e0213728. Published 2019 Mar 26. https:\/\/doi.org\/10.1371\/journal.pone.0213728.","journal-title":"PLoS One"},{"issue":"4","key":"6276_CR7","doi-asserted-by":"publisher","first-page":"259","DOI":"10.18926\/AMO\/46851","volume":"65","author":"Y Ogata","year":"2011","unstructured":"Ogata Y, Aoe K, Hiraki A, Murakami K, Kishino D, Chikamori K, et al. Is adenosine deaminase in pleural fluid a useful marker for differentiating tuberculosis from lung cancer or mesothelioma in Japan, a country with intermediate incidence of tuberculosis? Acta Med Okayama. 2011;65(4):259\u201363. https:\/\/doi.org\/10.18926\/AMO\/46851 PubMed PMID: 21860532.","journal-title":"Acta Med Okayama"},{"issue":"3","key":"6276_CR8","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.diagmicrobio.2015.11.007","volume":"84","author":"JM Michot","year":"2016","unstructured":"Michot JM, Madec Y, Bulifon S, Thorette-Tcherniak C, Fortineau N, No\u00ebl N, et al. Adenosine deaminase is a useful biomarker to diagnose pleural tuberculosis in low to medium prevalence settings. Diagn Microbiol Infect Dis. 2016;84(3):215\u201320. https:\/\/doi.org\/10.1016\/j.diagmicrobio.2015.11.007 Epub 2015 Nov 10. PubMed PMID: 26707067.","journal-title":"Diagn Microbiol Infect Dis"},{"issue":"6","key":"6276_CR9","doi-asserted-by":"publisher","first-page":"697","DOI":"10.5588\/ijtld.16.0803","volume":"21","author":"P Sivakumar","year":"2017","unstructured":"Sivakumar P, Marples L, Breen R, Ahmed L. The diagnostic utility of pleural fluid adenosine deaminase for tuberculosis in a low prevalence area. Int J Tuberc Lung Dis. 2017;21(6):697\u2013701. https:\/\/doi.org\/10.5588\/ijtld.16.0803 PubMed PMID: 28482965.","journal-title":"Int J Tuberc Lung Dis"},{"issue":"2","key":"6276_CR10","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S0953-6205(03)00018-9","volume":"14","author":"L Vald\u00e9s","year":"2003","unstructured":"Vald\u00e9s L, Pose A, San Jos\u00e9 E, Mart\u00ednez V\u00e1zquez JM. Tuberculous pleural effusions. Eur J Intern Med. 2003;14(2):77\u201388. https:\/\/doi.org\/10.1016\/S0953-6205(03)00018-9 PubMed PMID: 12719023.","journal-title":"Eur J Intern Med"},{"key":"6276_CR11","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1186\/1471-2334-13-546","volume":"13","author":"TR Tay","year":"2013","unstructured":"Tay TR, Tee A. Factors affecting pleural fluid adenosine deaminase level and the implication on the diagnosis of tuberculous pleural effusion: a retrospective cohort study. BMC Infect Dis. 2013;13:546. Published 2013 Nov 16. https:\/\/doi.org\/10.1186\/1471-2334-13-546.","journal-title":"BMC Infect Dis"},{"issue":"5","key":"6276_CR12","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1097\/MAJ.0000000000000260","volume":"348","author":"SJ Lee","year":"2014","unstructured":"Lee SJ, Kim HS, Lee SH, Lee TW, Lee HR, Cho YJ, et al. Factors influencing pleural adenosine deaminase level in patients with tuberculous pleurisy. Am J Med Sci. 2014;348(5):362\u20135. https:\/\/doi.org\/10.1097\/MAJ.0000000000000260 PubMed PMID: 24762755.","journal-title":"Am J Med Sci"},{"issue":"10","key":"6276_CR13","first-page":"3126","volume":"7","author":"X Gui","year":"2014","unstructured":"Gui X, Xiao H. Diagnosis of tuberculosis pleurisy with adenosine deaminase (ADA): a systematic review and meta-analysis. Int J Clin Exp Med. 2014;7(10):3126\u201335 Published 2014 Oct 15.","journal-title":"Int J Clin Exp Med"},{"issue":"4","key":"6276_CR14","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1378\/chest.06-2273","volume":"131","author":"J Jiang","year":"2007","unstructured":"Jiang J, Shi HZ, Liang QL, Qin SM, Qin XJ. Diagnostic value of interferon-gamma in tuberculous pleurisy: a metaanalysis. Chest. 2007;131(4):1133\u201341. https:\/\/doi.org\/10.1378\/chest.06-2273.","journal-title":"Chest."},{"issue":"3","key":"6276_CR15","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1111\/j.1440-1843.2011.01941.x","volume":"16","author":"Q Zhou","year":"2011","unstructured":"Zhou Q, Chen YQ, Qin SM, Tao XN, Xin JB, Shi HZ. Diagnostic accuracy of T-cell interferon-\u03b3 release assays in tuberculous pleurisy: a meta-analysis. Respirology. 2011;16(3):473\u201380. https:\/\/doi.org\/10.1111\/j.1440-1843.2011.01941.x.","journal-title":"Respirology."},{"issue":"8","key":"6276_CR16","doi-asserted-by":"publisher","first-page":"2451","DOI":"10.1128\/JCM.00823-15","volume":"53","author":"AN Aggarwal","year":"2015","unstructured":"Aggarwal AN, Agarwal R, Gupta D, Dhooria S, Behera D. Interferon gamma release assays for diagnosis of pleural tuberculosis: a systematic review and meta-analysis. J Clin Microbiol. 2015;53(8):2451\u20139. https:\/\/doi.org\/10.1128\/JCM.00823-15 Epub 2015 May 20. Review. PubMed PMID: 25994163; PubMed Central PMCID: PMC4508404.","journal-title":"J Clin Microbiol"},{"issue":"1","key":"6276_CR17","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1471-2334-4-6","volume":"4","author":"M Pai","year":"2004","unstructured":"Pai M, Flores LL, Hubbard A, Riley LW, Colford JM Jr. Nucleic acid amplification tests in the diagnosis of tuberculous pleuritis: a systematic review and meta-analysis. BMC Infect Dis. 2004;4(1):6. https:\/\/doi.org\/10.1186\/1471-2334-4-6 Review. PubMed PMID: 15102325; PubMed Central PMCID: PMC387423.","journal-title":"BMC Infect Dis"},{"issue":"4","key":"6276_CR18","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1128\/JCM.03205-15","volume":"54","author":"IS Sehgal","year":"2016","unstructured":"Sehgal IS, Dhooria S, Aggarwal AN, Behera D, Agarwal R. Diagnostic performance of Xpert MTB\/RIF in Tuberculous pleural effusion: systematic review and meta-analysis. J Clin Microbiol. 2016;54(4):1133\u20136. https:\/\/doi.org\/10.1128\/JCM.03205-15 Epub 2016 Jan 27. PMID: 26818675; PMCID: PMC4809962.","journal-title":"J Clin Microbiol"},{"issue":"6","key":"6276_CR19","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1159\/000486963","volume":"95","author":"Q Liu","year":"2018","unstructured":"Liu Q, Yu YX, Wang XJ, Wang Z, Wang Z. Diagnostic accuracy of interleukin-27 between tuberculous pleural effusion and malignant pleural effusion: a meta-analysis. Respiration. 2018;95(6):469\u201377. https:\/\/doi.org\/10.1159\/000486963 Epub 2018 Mar 14. Review. PubMed PMID: 29539604.","journal-title":"Respiration."},{"issue":"1","key":"6276_CR20","doi-asserted-by":"publisher","first-page":"115306","DOI":"10.1016\/j.diagmicrobio.2020.115306","volume":"100","author":"M Huang","year":"2021","unstructured":"Huang M, Wang G, Sun Q, Jiang G, Li W, Ding Z, et al. Diagnostic accuracy of Xpert MTB\/RIF ultra for tuberculous meningitis in a clinical practice setting of China. Diagn Microbiol Infect Dis. 2021;100(1):115306. https:\/\/doi.org\/10.1016\/j.diagmicrobio.2020.115306 Epub ahead of print. PMID: 33516988.","journal-title":"Diagn Microbiol Infect Dis"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-021-06276-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12879-021-06276-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-021-06276-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T08:04:01Z","timestamp":1623744241000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-021-06276-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,15]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["6276"],"URL":"https:\/\/doi.org\/10.1186\/s12879-021-06276-4","relation":{},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,15]]},"assertion":[{"value":"19 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review on request.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"575"}}