Correlation of Mycobacterium Tuberculosis Specific and Non-Specific Quantitative Th1 T-Cell Responses with Bacillary Load in a High Burden Setting

Theron, Grant; Peter, Jonny; Lenders, Laura; Zyl-Smit, Richard van; Meldau, Richard; Govender, Ureshnie; Dheda, Keertan
May 2012
PLoS ONE;May2012, Vol. 7 Issue 5, p1
Academic Journal
Background: Measures of bacillary load in patients with tuberculosis (TB) may be useful for predicting and monitoring response to treatment. The relationship between quantitative T-cell responses and mycobacterial load remains unclear. We hypothesised that, in a HIV-prevalent high burden setting, the magnitude of mycobacterial antigen-specific and nonspecific T-cell IFN-γ responses would correlate with (a) bacterial load and (b) culture conversion in patients undergoing treatment. Methods: We compared baseline (n = 147), 2 (n = 35) and 6 month (n = 13) purified-protein-derivative (PPD) and RD1-specific (TSPOT.TB and QFT-GIT) blood RD1-specific (TSPOT.TB; QFT-GIT) responses with associates of sputum bacillary load in patients with culture-confirmed TB in Cape Town, South Africa. Results: IFN-γ responses were not associated with liquid culture time-to-positivity, smear-grade, Xpert MTB/RIF-generated cycle threshold values or the presence of cavities on the chest radiograph in patients with culture-confirmed TB and irrespective of HIV-status. 2-month IGRA conversion rates (positive-to-negative) were negligible [<11% for TSPOT.TB (3/28) and QFT-GIT (1/29)] and lower compared to culture [60% (21/35); p<0.01]. Conclusions: In a high burden HIV-prevalent setting T-cell IFN-γ responses to M. tuberculosis-specific and non-specific antigens do not correlate with bacillary load, including Xpert MTB/RIF-generated CT values, and are therefore poorly suited for monitoring treatment and prognostication.


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