title: Measurement of ESAT6-induced IFNγ responses adjunct with CXCL9 increases the rate of diagnosis of active tuberculosis in an endemic region.
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. tuberculosis early 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.
authors.affiliation: Aga Khan University, Karachi, Pakistan. Electronic address: zahra.hasan@aku.edu.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hasan
authors.affiliation: Ojha Institute of Chest Diseases, DUHS, Karachi, Pakistan.
authors.forename: Nisar
authors.initials: N
authors.lastname: Rao
authors.affiliation: Indus Hospital, Karachi, Pakistan.
authors.forename: Naseem
authors.initials: N
authors.lastname: Salahuddin
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Mussarat
authors.initials: M
authors.lastname: Ashraf
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Muniba
authors.initials: M
authors.lastname: Islam
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Bushra
authors.initials: B
authors.lastname: Jamil
keywords: CXCL9; Interferon-gamma; TB diagnosis