Paulo S Silveira-Mattos1,2,3, Beatriz Barreto-Duarte1,2,4, Beatriz Vasconcelos1,2,5, Kiyoshi F Fukutani1,2,3, Caian L Vinhaes1,2,3, Deivide Oliveira-De-Souza1,2,3, Chris C Ibegbu6,7, Marina C Figueiredo8, Timothy R Sterling8, Jyothi Rengarajan6,7, Bruno B Andrade1,2,3,4,5,8,9. 1. Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil. 2. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Fundação José Silveira, Salvador, Bahia, Brazil. 3. Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Bahia, Brazil. 4. Universidade Salvador, Laureate Universities, Salvador, Bahia, Brazil. 5. Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil. 6. Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA. 7. Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. 8. Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. 9. Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Abstract
BACKGROUND: 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. METHODS: 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-γ +CD4+T cells expressing CD38, HLADR, and/or Ki67 were assessed by flow cytometry. RESULTS: EPTB and PTB were associated with higher frequencies of CD4+T cells expressing CD38, HLADR, or Ki67 compared with LTBI (all P values < .001). Moreover, frequencies of HLADR+ (P = .03) or Ki67+ (P < .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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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-γ +CD4+T cells expressing CD38, HLADR, and/or Ki67 were assessed by flow cytometry. RESULTS: EPTB and PTB were associated with higher frequencies of CD4+T cells expressing CD38, HLADR, or Ki67 compared with LTBI (all P values < .001). Moreover, frequencies of HLADR+ (P = .03) or Ki67+ (P < .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. CONCLUSIONS: 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.
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Authors: Caian L Vinhaes; Virginia Sheikh; Deivide Oliveira-de-Souza; Jing Wang; Adam Rupert; Gregg Roby; María B Arriaga; Kiyoshi F Fukutani; Fred Sawe; Doug Shaffer; Jintanat Ananworanich; Nittaya Phanuphak; Bruno B Andrade; Irini Sereti Journal: J Infect Dis Date: 2021-04-08 Impact factor: 5.226
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Authors: R Villar-Hernández; T Blauenfeldt; E García-García; B Muriel-Moreno; M L De Souza-Galvão; J P Millet; F Sabriá; A Sánchez-Montalvá; J Ruiz-Manzano; J Pilarte; M A Jiménez; C Centeno; C Martos; I Molina-Pinargote; Y D González-Díaz; J Santiago; A Cantos; I Casas; R M Guerola; C Prat; P Andersen; I Latorre; M Ruhwald; J Domínguez Journal: Sci Rep Date: 2020-08-06 Impact factor: 4.379