Abstract:
Background: Identifying novel TB diagnostics is a major public health priority. We explored the
diagnostic characteristics of antimycobacterial lymphocyte proliferation assays (LPA) in HIVinfected
subjects with latent or active TB.
Methods: HIV-infected subjects with bacille Calmette Guérin (BCG) scars and CD4 counts ≥ 200
cells/mm3 entering a TB booster vaccine trial in Tanzania had baseline in vivo and in vitro immune
tests performed: tuberculin skin tests (TST), LPA and five day assays of interferon gamma (IFN-γ)
release. Assay antigens were early secreted antigenic target 6 (ESAT-6), antigen 85 (Ag85), and
Mycobacterium tuberculosis whole cell lysate (WCL). Subjects were screened for active TB at
enrollment by history, exam, sputum smear and culture. We compared antimycobacterial immune
responses between subjects with and without latent or active TB at enrollment.
Results: Among 1885 subjects screened, 635 had latent TB and 13 had active TB. Subjects with
latent TB were more likely than subjects without TB to have LPA responses to ESAT-6 (13.2% vs.
5.5%, P < 0.0001), Ag85 (18.7% vs. 3.1%, P < 0.0001), and WCL (45.7% vs. 17.1%, P < 0.0001).
Subjects with active TB also were more likely than those without active TB to have detectable LPA
responses to ESAT-6 (38.5% vs. 8.1%, P = 0.0001), Ag85 (46.2% vs. 8.5%, P < 0.0001), and WCL
(61.5% vs. 27.0%, P = 0.0053). In subjects with a positive TST, LPA responses to ESAT-6, Ag85 and
WCL were more common during active TB (p < 0.0001 for all tests). In diagnosing active TB, in
vivo and in vitro tests of mycobacterial immune responses had sensitivity and specificity as follows:
TST 84.6% and 65.5%, ESAT-6 LPA 38.5% and 92.0%, Ag85 LPA 46.2% and 91.5%, and WCL LPA
61.5% and 73.0%. Detectable LPA responses were more common in patients with higher CD4
counts, and higher HIV viral loads.
Conclusion: Lymphoproliferative responses to mycobacteria are detectable during HIVassociated
active TB, and are less sensitive but more specific than TST.
