{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:09:16Z","timestamp":1791216556007,"version":"4.1.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T00:00:00Z","timestamp":1572393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Intramural Research Program of the Funda\u00e7\u00e3o Oswaldo Cruz"},{"name":"Departamento de Ci\u00eancia e Tecnologia"},{"name":"Secretaria de Ci\u00eancia e Tecnologia"},{"DOI":"10.13039\/501100006506","name":"Minist\u00e9rio da Sa\u00fade","doi-asserted-by":"publisher","award":["25029.000507\/2013-07"],"award-info":[{"award-number":["25029.000507\/2013-07"]}],"id":[{"id":"10.13039\/501100006506","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006506","name":"Minist\u00e9rio da Sa\u00fade","doi-asserted-by":"publisher","award":["National Institutes of Allergy and Infectious Diseases"],"award-info":[{"award-number":["National Institutes of Allergy and Infectious Diseases"]}],"id":[{"id":"10.13039\/501100006506","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006506","name":"Minist\u00e9rio da Sa\u00fade","doi-asserted-by":"publisher","award":["U01-AI069923"],"award-info":[{"award-number":["U01-AI069923"]}],"id":[{"id":"10.13039\/501100006506","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006506","name":"Minist\u00e9rio da Sa\u00fade","doi-asserted-by":"publisher","award":["U01AI115940"],"award-info":[{"award-number":["U01AI115940"]}],"id":[{"id":"10.13039\/501100006506","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006506","name":"Minist\u00e9rio da Sa\u00fade","doi-asserted-by":"publisher","award":["U01AI069923"],"award-info":[{"award-number":["U01AI069923"]}],"id":[{"id":"10.13039\/501100006506","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007813","name":"Center for AIDS Research","doi-asserted-by":"publisher","award":["P30AI050409"],"award-info":[{"award-number":["P30AI050409"]}],"id":[{"id":"10.13039\/100007813","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007813","name":"Center for AIDS Research","doi-asserted-by":"publisher","award":["Emory University and the Yerkes National Primate Research Center"],"award-info":[{"award-number":["Emory University and the Yerkes National Primate Research Center"]}],"id":[{"id":"10.13039\/100007813","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Office of Research Infrastructure Programs","award":["OD P51OD11132"],"award-info":[{"award-number":["OD P51OD11132"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Diagnosis of active tuberculosis (ATB) currently relies on detection of Mycobacterium tuberculosis (Mtb). Identifying patients with extrapulmonary TB (EPTB) remains challenging because microbiological confirmation is often not possible. Highly accurate blood-based tests could improve diagnosis of both EPTB and pulmonary TB (PTB) and timely initiation of anti-TB therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A case-control study was performed using discriminant analyses to validate an approach using Mtb-specific CD4+T-cell activation markers in blood to discriminate PTB and EPTB from latent TB infection (LTBI) as well as EPTB from PTB in 270 Brazilian individuals. We further tested the effect of human immunodeficiency virus (HIV) coinfection on diagnostic performance. Frequencies of interferon-\u03b3\u200a+CD4+T cells expressing CD38, HLADR, and\/or Ki67 were assessed by flow cytometry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>EPTB and PTB were associated with higher frequencies of CD4+T cells expressing CD38, HLADR, or Ki67 compared with LTBI (all P values &amp;lt; .001). Moreover, frequencies of HLADR+ (P = .03) or Ki67+ (P &amp;lt; .001) cells accurately distinguished EPTB from PTB. HIV infection did not affect the capacity of these markers to distinguish ATB from LTBI or EPTB from PTB.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Cell activation markers in Mtb-specific CD4+T cells distinguished ATB from LTBI and EPTB from PTB, regardless of HIV infection status. These parameters provide an attractive approach for developing blood-based diagnostic tests for both active and latent TB.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciz1070","type":"journal-article","created":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T19:15:05Z","timestamp":1571944505000},"page":"1905-1911","source":"Crossref","is-referenced-by-count":48,"title":["Differential Expression of Activation Markers by <i>Mycobacterium tuberculosis<\/i>-specific CD4+ T Cell Distinguishes Extrapulmonary From Pulmonary Tuberculosis and Latent Infection"],"prefix":"10.1093","volume":"71","author":[{"given":"Paulo S","family":"Silveira-Mattos","sequence":"first","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz, Salvador, Bahia, Brazil"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Funda\u00e7\u00e3o Jos\u00e9 Silveira, Salvador, Bahia, Brazil"},{"name":"Curso de Medicina, Faculdade de Tecnologia e Ci\u00eancias, Salvador, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Barreto-Duarte","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz, Salvador, Bahia, Brazil"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Funda\u00e7\u00e3o Jos\u00e9 Silveira, Salvador, Bahia, Brazil"},{"name":"Universidade Salvador, Laureate Universities, Salvador, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz, Salvador, Bahia, Brazil"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Funda\u00e7\u00e3o Jos\u00e9 Silveira, Salvador, Bahia, Brazil"},{"name":"Escola Bahiana de Medicina e Sa\u00fade P\u00fablica, Salvador, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi F","family":"Fukutani","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz, Salvador, Bahia, Brazil"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Funda\u00e7\u00e3o Jos\u00e9 Silveira, Salvador, Bahia, Brazil"},{"name":"Curso de Medicina, Faculdade de Tecnologia e Ci\u00eancias, Salvador, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caian L","family":"Vinhaes","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz, Salvador, Bahia, Brazil"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Funda\u00e7\u00e3o Jos\u00e9 Silveira, Salvador, Bahia, Brazil"},{"name":"Curso de Medicina, Faculdade de Tecnologia e Ci\u00eancias, Salvador, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deivide","family":"Oliveira-De-Souza","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz, Salvador, Bahia, Brazil"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Funda\u00e7\u00e3o Jos\u00e9 Silveira, Salvador, Bahia, Brazil"},{"name":"Curso de Medicina, Faculdade de Tecnologia e Ci\u00eancias, Salvador, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris C","family":"Ibegbu","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA"},{"name":"Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina C","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R","family":"Sterling","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyothi","family":"Rengarajan","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA"},{"name":"Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6833-3811","authenticated-orcid":false,"given":"Bruno 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