Added Value of Long-Term Cytokine Release Assays to Detect Mycobacterium tuberculosis Infection in HIV-Infected Subjects in Uganda.
To investigate whether mycobacterial antigen-induced cytokine secretions are helpful in detecting Mycobacterium tuberculosis (Mtb) infection in a cohort of HIV-infected patients living in a country with a high burden of Mtb and HIV infections, and to determine their predictive value for the development of tuberculosis (TB)-associated immune reconstitution inflammatory syndrome.



A total of 352 HIV-infected patients (186 with active TB) were prospectively enrolled when initiating antiretroviral therapy (ART). Sequential blood samples were collected during the first 6 months of ART. Eighty-three HIV-uninfected subjects (39 with active TB) were enrolled as controls.



The concentrations of 13 cytokines were measured in supernatants from blood mononuclear cells in vitro stimulated with purified protein derivative (PPD), heparin-binding hemagglutinin (HBHA) or early secreted antigen-6 (ESAT-6) and culture filtrate protein-10 (CFP-10), and results were compared with those of tuberculin skin tests (TST).



The best detection of Mtb infection was achieved by ESAT-6/CFP-10-induced interferon-γ concentrations, but results were often negative for patients with CD4 T-cell counts <50 per cubic millimeters. Patients with active TB were identified by high ESAT-6/CFP-10-induced interleukin-6. Conversions of interferon-γ-release assays (IGRA) and TST occurred under ART, and combined TB and antiretroviral treatments of coinfected patients resulted in a decrease of ESAT-6/CFP-10-induced and an increase of HBHA-induced interferon-γ responses. No Mtb antigen-induced cytokines allowed us to predict TB-immune reconstitution inflammatory syndrome or ART-associated TB.



In Uganda, ESAT-6/CFP-10-IGRA is better in detecting Mtb infection than TST and, when combined with an HBHA-IGRA, could help to evaluate anti-TB treatment success.
*Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (ULB), Brussels, Belgium; †Currently, CHU Pointe-à-Pitre, Pointe-à-Pitre, Guadeloupe; ‡Laboratory of Immunology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; §Currently, Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon; ‖Département de Bacterio-virologie, Université des Sciences de la Santé, Libreville, Gabon; ¶Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany; #Department of Medicine, Mulago Hospital, College of Health Sciences, Makarere University, Kampala, Uganda; **Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; ††Epidemiology and Social Medicine, University of Antwerp, Antwerp, Belgium; ‡‡Currently, International Health Unit, Faculty of Medicine and Health Sciences, Gouverneur Kinsbergen Centrum, University of Antwerp, Wilkrijk, Belgium; §§Lionex Diagnostics & Therapeutics, Braunschweig, Germany; ‖‖Inserm, U1019, Lille, France; ¶¶CNRS, UMR8204, Lille, France; ##University of Lille, U1019-UMR8204-CIIL-, Center for Infection and Immunity of Lille, Lille, France; ***Institut Pasteur de Lille, Lille, France; †††Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; and ‡‡‡Immunobiology Clinic, Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Violette
V
Dirix
Kinda
K
Schepers
Marguerite
M
Massinga-Loembe
William
W
Worodria
Robert
R
Colebunders
Mahavir
M
Singh
Camille
C
Locht
Luc
L
Kestens
Françoise
F
Mascart
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000032:analysis* / Q000378:metabolism*; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D006801:Humans; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000150:complications* / Q000175:diagnosis* / Q000276:immunology / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014454:Uganda
D016207:Cytokines