A new strategy for the diagnosis of tuberculosis based on secreted antigens: evaluation of the efficacy of alveolar lavage ESAT-6 and CFP-10 tests.

OBJECTIVES

To assess the diagnostic value of Mycobacterium tuberculosis (MTB)-specific secreted antigens ESAT-6 and CFP-10 in bronchoalveolar lavage fluid (BALF), and to explore novel adjunctive diagnostic strategies to enhance the diagnostic rate of pulmonary tuberculosis (PTB).

METHODS

104 patients with PTB (59 confirmed cases and 45 clinically diagnosed cases) and 72 patients with non-tuberculosis lung diseases (control group), hospitalized from May 2021 to July 2023, underwent bronchoscopy. The concentrations of ESAT-6 and CFP-10 antigens were detected by enzyme-linked immunosorbent assay (ELISA). Optimal cutoff values were determined by receiver operating characteristic (ROC) curves to evaluate antigen diagnostic capability for active PTB, compared with acid-fast bacilli (AFB) and Xpert MTB/RIF.

RESULTS

Antigen expression characteristics: Concentrations of ESAT-6 and CFP-10 were significantly higher in the PTB group compared to controls (both P < 0.001). ESAT-6 levels did not differ significantly between confirmed and clinically diagnosed cases (P > 0.05), whereas CFP-10 concentrations were significantly higher in confirmed cases (P = 0.045). Comparison of diagnostic efficacy: Sensitivities of AFB and Xpert MTB/RIF were 26.92% (95% CI 18.6-37.2%) and 56.73% (95% CI 46.1-66.8%). ESAT-6 and CFP-10 demonstrated significantly higher sensitivities (77.89%, 95% CI 68.5-85.1%; 67.31%, 95% CI 57.3-76.0%) compared to AFB (Δ = 50.97%, P < 0.001; Δ = 40.39%, P < 0.001) and Xpert MTB/RIF (Δ = 21.16%, P < 0.001; Δ = 10.58%, P = 0.021), but had lower specificity (P < 0.001). Combined testing strategy: Parallel testing (either antigen positive) yielded sensitivity of 94.23% (95% CI 87.4-97.6%) and negative predictive value of 99.2%, while tandem testing (both antigens positive) provided specificity of 95.83% (95% CI 88.1-98.6%). Subgroup analysis: No statistically significant difference was observed in antigen sensitivities between bacteriologically positive and negative PTB groups (P > 0.05).

CONCLUSIONS

(1) ESAT-6 and CFP-10 detection in BALF significantly improves PTB diagnostic sensitivity, unaffected by bacterial load, particularly benefiting the diagnosis of bacteriologically negative PTB. (2) Combined antigen testing strategies (parallel/tandem) optimally balance sensitivity and specificity, meeting clinical requirements for ruling out or confirming PTB diagnosis.