{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:52:45Z","timestamp":1791942765206,"version":"4.3.4"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD064354"],"award-info":[{"award-number":["R01HD064354"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>For pregnant women living with human immunodeficiency virus (HIV), concurrent active tuberculosis (TB) disease increases the risk of maternal mortality and poor pregnancy outcomes. Plasma indoleamine 2,3-dioxygenase (IDO) activity measured by kynurenine-to-tryptophan (K\/T) ratio has been proposed as a blood-based TB biomarker. We investigated whether plasma K\/T ratio could be used to diagnose active TB among pregnant women with HIV.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Using an enzyme-linked immunosorbent assay (ELISA), we measured K\/T ratio in 72 pregnant women with and active TB and compared them to 117 pregnant women with HIB but without TB, matched by age and gestational age.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Plasma K\/T ratio was significantly elevated during pregnancy compared to sampling done after pregnancy (P\u2005&amp;lt;\u2005.0001). Pregnant women who had received isoniazid preventive therapy (IPT) before enrollment had decreased plasma K\/T ratio compared to those who had not received IPT (P\u2005=\u2005.0174). Plasma K\/T ratio was elevated in women with active TB at time of diagnosis compared to those without TB (P\u2005&amp;lt;\u2005.0001). Using a cutoff of 0.100, plasma K\/T ratio gave a diagnostic sensitivity of 94% (95% confidence interval [CI]: 82\u201395), specificity of 90% (95% CI: 80\u201391), positive predictive value (PPV) 85% and negative predictive value (NPV) 98%. A receiver operating characteristic curve (ROC) gave an area under the curve of 0.95 (95% CI: .92\u2013.97, P\u2005&amp;lt;\u2005.0001).<\/jats:p>\n                  <jats:p>In conclusion, plasma K\/T ratio is a sensitive blood-based diagnostic test for active TB disease in pregnant women living with HIV. Plasma K\/T ratio should be further evaluated as an initial TB diagnostic test to determine its impact on patient care.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciab232","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T20:10:53Z","timestamp":1615493453000},"page":"1027-1036","source":"Crossref","is-referenced-by-count":23,"title":["Plasma Kynurenine-to-Tryptophan Ratio, a Highly Sensitive Blood-Based Diagnostic Tool for Tuberculosis in Pregnant Women Living With Human Immunodeficiency Virus (HIV)"],"prefix":"10.1093","volume":"73","author":[{"given":"Clement","family":"Adu-Gyamfi","sequence":"first","affiliation":[{"name":"Center for Vaccines and Immunology, National Institute for Communicable Diseases, a division of the National Health Laboratory Service, Johannesburg, South Africa"},{"name":"Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences, University of The Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Savulescu","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunology, National Institute for Communicable Diseases, a division of the National Health Laboratory Service, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillian","family":"Mikhathani","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunology, National Institute for Communicable Diseases, a division of the National Health Laboratory Service, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kennedy","family":"Otwombe","sequence":"additional","affiliation":[{"name":"Perinatal Health Research Unit (PHRU), Soweto Matlosana Collaborating Centre for HIV\/AIDS and TB, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa"},{"name":"School of Public Health, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9875-9319","authenticated-orcid":false,"given":"Nicole","family":"Salazar-Austin","sequence":"additional","affiliation":[{"name":"Johns Hopkins University Centre for TB Research, Baltimore, MarylandUSA"},{"name":"Johns Hopkins School of Medicine, Baltimore, MarylandUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Chaisson","sequence":"additional","affiliation":[{"name":"Johns Hopkins University Centre for TB Research, Baltimore, MarylandUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Martinson","sequence":"additional","affiliation":[{"name":"Perinatal Health Research Unit (PHRU), Soweto Matlosana Collaborating Centre for HIV\/AIDS and TB, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa"},{"name":"Johns Hopkins University Centre for TB Research, Baltimore, MarylandUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaya","family":"George","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences, University of The Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Suchard","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunology, National Institute for Communicable Diseases, a division of the National Health Laboratory Service, Johannesburg, South Africa"},{"name":"Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences, University of The Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"2021091515513251800_CIT0001","first-page":"243","volume-title":"Global tuberculosis report 2019","author":"World Health Organization.","year":"2019"},{"key":"2021091515513251800_CIT0002","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S1473-3099(09)70043-X","article-title":"Approaches to tuberculosis screening and diagnosis in people with HIV in resource-limited settings","volume":"9","author":"Reid","year":"2009","journal-title":"Lancet Infect Dis"},{"key":"2021091515513251800_CIT0003","volume-title":"Partnership: the paradigm shift. 2016\u20132020. Global Plan to End TB","author":"Stop","year":"2015"},{"key":"2021091515513251800_CIT0004","volume-title":"High-priority target product profiles for new tuberculosis diagnostics. Report of a consensus meeting","author":"World Health Organization.","year":"2014"},{"key":"2021091515513251800_CIT0005","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ijid.2014.12.014","article-title":"Perspectives on tuberculosis in pregnancy","volume":"32","author":"Bates","year":"2015","journal-title":"Int J Infect Dis"},{"key":"2021091515513251800_CIT0006","doi-asserted-by":"crossref","first-page":"e62211","DOI":"10.1371\/journal.pone.0062211","article-title":"High prevalence of pulmonary tuberculosis but low sensitivity of symptom screening among HIV-infected pregnant women in South Africa","volume":"8","author":"Hoffmann","year":"2013","journal-title":"PLoS One"},{"key":"2021091515513251800_CIT0007","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1164\/rccm.201106-1083OC","article-title":"Risk of tuberculosis in pregnancy: a national, primary care-based cohort and self-controlled case series study","volume":"185","author":"Zenner","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2021091515513251800_CIT0008","first-page":"59","article-title":"Vertical transmission of Mycobacterium tuberculosis in KwaZulu Natal: impact of HIV-1 co-infection","volume":"8","author":"Pillay","year":"2004","journal-title":"Int J Tuberc and Lung Dis"},{"key":"2021091515513251800_CIT0009","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1097\/AOG.0b013e3181af33e6","article-title":"Effect of human immunodeficiency virus treatment on maternal mortality at a tertiary center in South Africa: a 5-year audit","volume":"114","author":"Black","year":"2009","journal-title":"Obstet Gynecol"},{"key":"2021091515513251800_CIT0010","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/j.1600-065X.2008.00610.x","article-title":"Indoleamine 2,3-dioxygenase in T-cell tolerance and tumoral immune escape","volume":"222","author":"Katz","year":"2008","journal-title":"Immunol Rev"},{"key":"2021091515513251800_CIT0011","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nrn2297","article-title":"From inflammation to sickness and depression: when the immune system subjugates the brain","volume":"9","author":"Dantzer","year":"2008","journal-title":"Nat Rev Neurosci"},{"key":"2021091515513251800_CIT0012","doi-asserted-by":"crossref","first-page":"521","DOI":"10.3389\/fimmu.2014.00521","article-title":"Immunological relevance of the coevolution of IDO1 and AHR","volume":"5","author":"Jaronen","year":"2014","journal-title":"Front Immunol"},{"key":"2021091515513251800_CIT0013","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.3389\/fimmu.2017.01360","article-title":"Indoleamine 2,3-dioxygenase and tolerance: where are we now?","volume":"8","author":"Mellor","year":"2017","journal-title":"Front Immunol"},{"key":"2021091515513251800_CIT0014","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.4049\/jimmunol.0903670","article-title":"An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells","volume":"185","author":"Mezrich","year":"2010","journal-title":"J Immunol"},{"key":"2021091515513251800_CIT0015","doi-asserted-by":"crossref","first-page":"19916","DOI":"10.1038\/srep19916","article-title":"Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration","volume":"6","author":"Zong","year":"2016","journal-title":"Sci Rep"},{"key":"2021091515513251800_CIT0016","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1042\/bj2300635","article-title":"Human indolylamine 2, 3-dioxygenase: its tissue distribution, and characterization of the placental enzyme","volume":"230","author":"Yamazaki","year":"1985","journal-title":"Biochem J"},{"key":"2021091515513251800_CIT0017","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1093\/cid\/cix550","article-title":"Plasma indoleamine 2, 3-dioxygenase, a biomarker for tuberculosis in human immunodeficiency virus-infected patients","volume":"65","author":"Adu-Gyamfi","year":"2017","journal-title":"Clin Infect Dis"},{"key":"2021091515513251800_CIT0018","doi-asserted-by":"crossref","first-page":"05402","DOI":"10.1128\/CVI.05402-11","article-title":"Serum indoleamine 2, 3-dioxygenase activity predicts prognosis of pulmonary tuberculosis","volume":"19","author":"Suzuki","year":"2012","journal-title":"Clin Vaccine Immunol"},{"key":"2021091515513251800_CIT0019","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1093\/cid\/ciz1024","article-title":"Isoniazid preventive therapy and pregnancy outcomes in HIV-infected women in the Tshepiso cohort","volume":"71","author":"Salazar-Austin","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2021091515513251800_CIT0020","volume-title":"Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings","author":"World Health Organization","year":"2011"},{"key":"2021091515513251800_CIT0021","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1093\/cid\/cix851","article-title":"Poor obstetric and infant outcomes in human immunodeficiency virus-infected pregnant women with tuberculosis in South Africa: the Tshepiso study","volume":"66","author":"Salazar-Austin","year":"2018","journal-title":"Clin Infect Dis"},{"key":"2021091515513251800_CIT0022","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1093\/cid\/cix550","article-title":"Plasma indoleamine 2, 3-dioxygenase, a biomarker for tuberculosis in human immunodeficiency virus-infected patients","volume":"65","author":"Adu-Gyamfi","year":"2017","journal-title":"Clin Infect Dis"},{"key":"2021091515513251800_CIT0023","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.2147\/IDR.S202369","article-title":"Plasma indoleamine 2,3-dioxygenase activity as a potential biomarker for early diagnosis of multidrug-resistant tuberculosis in tuberculosis patients","volume":"12","author":"Shi","year":"2019","journal-title":"Infect Drug Resist"},{"key":"2021091515513251800_CIT0024","doi-asserted-by":"crossref","first-page":"e12786","DOI":"10.1111\/aji.12786","article-title":"The role of indoleamine-2, 3-dioxygenase in normal and pathological pregnancies","volume":"79","author":"Chang","year":"2018","journal-title":"Am J Reproduct Immunol"},{"key":"2021091515513251800_CIT0025","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1126\/science.281.5380.1191","article-title":"Prevention of allogeneic fetal rejection by tryptophan catabolism","volume":"281","author":"Munn","year":"1998","journal-title":"Science"},{"key":"2021091515513251800_CIT0026","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0029-7844(96)00084-1","article-title":"Decreased plasma tryptophan in pregnancy","volume":"88","author":"Schr\u00f6cksnadel","year":"1996","journal-title":"Obstet Gynecol"},{"key":"2021091515513251800_CIT0027","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1067\/mob.2003.156","article-title":"Decreased tryptophan catabolism by placental indoleamine 2,3-dioxygenase in preeclampsia","volume":"188","author":"Kudo","year":"2003","journal-title":"Am J Obstet Gynecol"},{"key":"2021091515513251800_CIT0028","doi-asserted-by":"crossref","first-page":"718","DOI":"10.4049\/jimmunol.0801212","article-title":"Tuberculosis is associated with a down-modulatory lung immune response that impairs Th1-type immunity","volume":"183","author":"Almeida","year":"2009","journal-title":"J Immunol"},{"key":"2021091515513251800_CIT0029","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1086\/367544","article-title":"Nicotinamide: an oral antimicrobial agent with activity against both Mycobacterium tuberculosis and human immunodeficiency virus","volume":"36","author":"Murray","year":"2003","journal-title":"Clin Infect Dis"},{"key":"2021091515513251800_CIT0030","first-page":"bies201900220","article-title":"Indoleamine 2,3-dioxygenase and the tryptophan-kynurenine-nicotinamide pathway in tuberculosis: an evolutionary perspective","volume":"42","author":"Suchard","year":"2020","journal-title":"BioEssay"},{"key":"2021091515513251800_CIT0031","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1093\/cid\/ciy676","article-title":"Plasma indoleamine 2, 3-dioxygenase activity is associated with the size of the human immunodeficiency virus reservoir in patients receiving antiretroviral therapy","volume":"68","author":"Chen","year":"2018","journal-title":"Clin Infect Dis"},{"key":"2021091515513251800_CIT0032","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.ijid.2020.08.028","article-title":"Diagnostic accuracy of plasma kynurenine\/tryptophan ratio, measured by enzyme-linked immunosorbent assay, for pulmonary tuberculosis","volume":"99","author":"Adu-Gyamfi","year":"2020","journal-title":"Int J Infect Dis"},{"key":"2021091515513251800_CIT0033","doi-asserted-by":"crossref","first-page":"372","DOI":"10.3389\/fcimb.2019.00372","article-title":"Indoleamine 2, 3-dioxygenase-mediated tryptophan catabolism: a leading star or supporting act in the tuberculosis and HIV pas-de-deux?","volume":"9","author":"Adu-Gyamfi","year":"2019","journal-title":"Front Cell Infect Microbiol"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciab232\/39505112\/ciab232.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/73\/6\/1027\/40392303\/ciab232.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/73\/6\/1027\/40392303\/ciab232.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T15:53:48Z","timestamp":1631721228000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/73\/6\/1027\/6170938"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,15]]},"references-count":33,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3,15]]},"published-print":{"date-parts":[[2021,9,15]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciab232","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,9,15]]},"published":{"date-parts":[[2021,3,15]]}}}