Heparin-binding-hemagglutinin-induced IFN-γ release as a diagnostic tool for latent tuberculosis

Abstract

Background. The detection of latent tuberculosis,infection (LTBI) is a major component of tubeculosis (TB) control strategies. In addition to the tuberculosis skin test (TST), novel blood tests, baged on in vitro release of IFN-γ in response to Mycobactedum tuberculosis-specific antigens ESAT-6 and CFP-10 (IGRAs), are used for TB diagnosis. However, neither IGRAs nor the TST can separate acute TB from LTBI, and there is concern that responses in IGRAs may decline with time after infection. We have therefore evaluated the potential of the novel antigen heparin-binding hemagglutinin (HBHA) for in vitro detection of LTBI. Methology and Principal Findings. HBHA was compared to purified protein derivative (PPD) and ESAT-6 in IGRAs on lymphocytes drawn from 20S individuals living in Belgium, a country with low TB prevalence, where BCG vaccination is not routinely used. Among these subjects, 89 had active TB, 65 had LTBI, based on well-4tandardized TST, reactions and 51 were negative controls. HBHA was significantly more sensitive than ESAT-6 and more specific than PPD for the detection of LTBI. PPD-based tests yielded 90.00% sensitivity and 70.00% specificity for the detection of LTBI, whereas the sensitivity and specificity for the ESAT-6-based tests were 40.74% and 90.91%, and those for the HBHA-based tests were 92.06% and 93.88%, respectively. The QuantiFERON-TB Gold In-Tube (QFT-IT) test applied on 20 LTBI subjects, yielded 50% sensitivity. The HBHA IGRA was not influenced by prior BCG vacanation, and, in contrast to the QFT-IT test, remote (>2 years) Infections were detected as well as recent (<2 years) infections by the HBHA-speciflc test. Conclusions. The use of ESAT-6-and CFP-10-based IGRAs may underestimate the incidence of LTBI, whereas the use of HBHA may combine the operational advantages of IGRAs with high sensitivity and specificity for latent infection. © 2007 Hougardy et al.