Title

Measurement of ESAT6-induced IFNγ responses adjunct with CXCL9 increases the rate of diagnosis of active tuberculosis in an endemic region

Document Type

Article

Department

Pathology and Microbiology; Biological and Biomedical Sciences; Medicine

Abstract

Due to difficulties in direct diagnosis of Mycobacterium tuberculosis infection where site-specific specimens are not available, indirect methods of testing for infection are required. M. tuberculosisearly secreted antigen target-6 (ESAT6) induced IFN-γ responses are specific, but do not differentiate between latent and active TB. The use of adjunct biomarkers for TB diagnosis has been proposed, such as the chemokines: CXCL9, CXCL10 and CCL2.

ESAT6-induced IFN-γ CXCL9, CXCL10 and CCL2 was measured in whole blood cell supernatants of patients with pulmonary tuberculosis (PTB, n = 36) and extrapulmonary TB (ETB, n = 31) and compared with healthy endemic controls (EC, n = 33).

ESAT6-induced IFN-γ responses were positive in 32% of TB cases as compared with 15% of EC cases (p = 0.048). ESAT6-induced CXCL9 responses were positive in 42% of TB cases and 15% of EC cases (p = 0.006). ESAT6-induced-CXCL10 and -CCL2 responses did not discriminate between TB and EC groups. Measurement of IFN-γ or CXCL9 together diagnosed TB (53%) cases and was significant as compared with EC (p = 0.014) cases. IFN-γ and CXCL10 together did not increase the number of TB cases diagnosed.

Within TB groups, ESAT6-IFN-γ/CXCL9-based detection increased to 53% in PTB (p = 0.031) and 54% in ETB (p = 0.021), with comparable diagnosis in less severe extrapulmonary TB (L-ETB, 55%) and severe disseminated extrapulmonary TB (D-ETB, 50%). Given that 47% of TB cases remained undetected, this study shown that ESAT6-induced IFNγ and CXCL9 can support diagnosis, but must be supported by clinical correlation and other relevant investigations.

Publication

International Journal of Mycobacteriology