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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Interferon γ responses to mycobacterial antigens protect against subsequent HIV-associated tuberculosis
Journal of Infectious Diseases, Volume 202, No. 8, Year 2010
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Description
Background. The cellular immune responses that protect against tuberculosis have not been identified. Methods. We assessed baseline interferon γ (IFN-γ) and lymphocyte proliferation assay (LPA) responses to antigen 85 (Ag85), early secretory antigenic target 6 (ESAT-6), and Mycobacterium tuberculosis whole cell lysate (WCL) in human immunodeficiency virus (HIV)-infected and bacille Calmette-Guérin (BCG)-immunized adults with CD4 cell counts of ≥200 cells/μL who received placebo in the DarDar tuberculosis vaccine trial in Tanzania. Subjects were followed prospectively to diagnose definite or probable tuberculosis. Results. Tuberculosis was diagnosed in 92 of 979 subjects during a mean follow-up of 3.2 years. The relative risk of tuberculosis among subjects with positive IFN-γ responses to Ag85 was 0.51 (95% confidence interval [CI], 0.26-0.99; P = .049), to ESAT-6 was 0.44 (95% CI, 0.23-0.85; P = .004), and to WCL was 0.67 (95% CI, 0.49-0.88; P = .002). The relative risk of tuberculosis was not significantly associated with baseline LPA responses. In a multivariate Cox regression model, subjects with IFN-γ responses to ESAT-6 and WCL had a lower hazard of developing tuberculosis, with a hazard ratio for ESAT-6 of 0.35 (95% CI, 0.16-0.77; P = .009) and a hazard ratio for WCL of 0.30 (95% CI, 0.16-0.56; P < .001). Conclusions. Baseline IFN-γ responses to ESAT-6 and WCL were associated with protection from subsequent tuberculosis among HIV-infected subjects with childhood BCG immunization in a region of high tuberculosis prevalence. Trial registration. ClinicalTrials.gov identifier: NCT00052195. © 2010 by the Infectious Diseases Society of America. All rights reserved.
Authors & Co-Authors
Lahey, Timothy P.
United States, Hanover
Geisel School of Medicine at Dartmouth
Sheth, Siddharth H.
United States, Hanover
Geisel School of Medicine at Dartmouth
Matee, Mecky Isaac N.
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Arbeit, Robert D.
United States, Boston
Tufts University School of Medicine
Horsburgh, Charles Robert
United States, Boston
Boston University
Mtei, Lillian N.
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
MacKenzie, Todd A.
United States, Hanover
Geisel School of Medicine at Dartmouth
Bakari, Muhammad
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Vuola, Jenni M.
Finland, Helsinki
Terveyden ja Hyvinvoinnin Laitos
Finland, Espoo
Glaxosmithkline oy
Pallangyo, Kisali J.
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
von Reyn, Charles Fordham
United States, Hanover
Geisel School of Medicine at Dartmouth
Statistics
Citations: 26
Authors: 11
Affiliations: 6
Identifiers
Doi:
10.1086/656332
ISSN:
00221899
Research Areas
Environmental
Infectious Diseases
Maternal And Child Health
Study Design
Cross Sectional Study
Cohort Study
Study Locations
Tanzania