Correlation of mycobacterium tuberculosis specific and non-specific quantitative Th1 T-cell responses with bacillary load in a high burden setting.
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 non-specific 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 C(T) values, and are therefore poorly suited for monitoring treatment and prognostication.
Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Grant
G
Theron
Jonny
J
Peter
Laura
L
Lenders
Richard
R
van Zyl-Smit
Richard
R
Meldau
Ureshnie
U
Govender
Keertan
K
Dheda
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058491:Bacterial Load; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013183:Sputum / Q000382:microbiology; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology; D014376:Tuberculosis / Q000150:complications / Q000276:immunology* / Q000382:microbiology
D007371:Interferon-gamma