Publication date: Jan 02, 2025
Exposure to pulmonary tuberculosis (PTB) culminates in heterogeneous outcomes, including variation in Mtb antigen-specific interferon-gamma (IFN-γ) T-cell responses. IFN-γ-independent cytokines, including tumor necrosis factor (TNF) and interleukin (IL-2), offer potential diagnostic improvements and insights into pathogenesis. We hypothesized that ESAT6/CFP10 TNF and IL-2 responses improve Mtb infection detection among exposed household contacts (HHCs) and are associated with index case Mtb aerosolization (i. e., cough aerosol culture positive for Mtb growth, CAC+) and HIV co-infection. We enrolled individuals with PTB and their HHCs in a longitudinal study in Nairobi, Kenya. We measured TNF and IL-2 in HHCs from QuantiFERON-TB Plus TB1 tube supernatants. An additional 9. 2% (25) HHCs beyond the 58. 6% (129) with an IFN-γ response demonstrated an antigen-specific increase in IL-2 and TNF. HHCs of CAC + participants were more likely to have positive IL-2 (84. 6% vs. 53. 8%, p = 0. 02) and IFN-γ (88. 0% vs. 54. 9%, p = 0. 01), but not TNF responses, compared to CAC-negative individuals. While HIV co-infection in the index was negatively associated with IFN-γ responses in HHCs (35. 7% vs. 62. 3%, p = 0. 03), IL-2 and TNF responses did not differ. Antigen-specific ESAT6/CFP10 IL-2 and TNF may increase rates of Mtb infection detection and provide insights into Mtb transmission and pathogenesis.