Abstract
BackgroundThe detection of latent tuberculosis infection (LTBI) is a major component of tuberculosis (TB) control strategies. In addition to the tuberculosis skin test (TST), novel blood tests, based on in vitro release of IFN-γ in response to Mycobacterium 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.Methodology and Principal FindingsHBHA was compared to purified protein derivative (PPD) and ESAT-6 in IGRAs on lymphocytes drawn from 205 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-standardized 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 vaccination, and, in contrast to the QFT-IT test, remote (>2 years) infections were detected as well as recent (<2 years) infections by the HBHA-specific test.ConclusionsThe 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.
Highlights
Tuberculosis (TB) remains a major health problem even in the 21st century, with 1.6 million deaths globally recorded in 2005 by the World Health Organization, and more than 8.8 million new infections [1]
latent tuberculosis infection (LTBI) subjects were defined by documented TST conversion at the Occupational Medicine Department (n = 31) or by a diameter of induration of the TST$10 mm for household contacts of active TB case patients (n = 21) or by the clinical data and/or TST result at the time of employment as a health care worker, as assessed by the Occupational Medicine Department (n = 13)
Since the LTBI subjects were defined on the basis of a positive TST reaction, we first evaluated the in vitro purified protein derivative (PPD)-induced IFN-c secretion by PBMC from LTBI subjects and TB patients compared to that from CTRL
Summary
Tuberculosis (TB) remains a major health problem even in the 21st century, with 1.6 million deaths globally recorded in 2005 by the World Health Organization, and more than 8.8 million new infections [1]. HBHA was compared to purified protein derivative (PPD) and ESAT-6 in IGRAs on lymphocytes drawn from 205 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-standardized TST reactions and 51 were negative controls. The use of ESAT-6and 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
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