Highly discordant T cell responses in individuals with recent exposure to household tuberculosis.
BACKGROUND
There are limited data comparing interferon-gamma release assays (IGRAs) for the detection of Mycobacterium tuberculosis infection in highly endemic settings.


METHODS
A cross-sectional household contact study was conducted to measure the agreement of two IGRAs in relation to the tuberculin skin test (TST) to detect M tuberculosis infection and to assess the influence of M tuberculosis exposure and age.


RESULTS
In 82 individuals in household contact, 93% of children and 42% of adults had a high M tuberculosis contact score. The TST was positive in 78% of adults and 54% of children, the T-SPOT.TB was positive in 89% of children and 66% of adults and the QuantiFERON TB Gold (QTF) was positive in a similar proportion of adults and children (38.1% and 39.6%). In children there was poor agreement between the TST and T-SPOT.TB (kappa = -0.15) and the T-SPOT.TB and the QTF (kappa = -0.03), but good agreement between the TST and the QTF (kappa = 0.78) using 10 mm cut-off. In adults there was fair to moderate agreement between the TST and T-SPOT.TB (kappa = 0.38), the TST and QTF (kappa = 0.34) and T-SPOT.TB and QTF (kappa = -0.50). High levels of exposure to M tuberculosis were associated with at least a sevenfold odds of being T-SPOT.TB positive (95% CI 7.67 to 508.69) and a threefold odds of being QTF positive (95% CI 3.02 to 30.54). There was a significant difference in the magnitude of T-SPOT.TB early secretory antigenic target (ESAT)-6 and culture filtrate protein 10 kD (CFP-10) spot counts between adults and children.


CONCLUSIONS
The T-SPOT.TB may be more sensitive than the TST or QTF for detecting recent M tuberculosis infection in children. Differences between assays and the predictive utility of these findings for subsequent disease development should be prospectively assessed.
Hesseling
A C
AC
Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa. annekeh@sun.ac.za
Mandalakas
A M
AM
Kirchner
H L
HL
Chegou
N N
NN
Marais
B J
BJ
Stanley
K
K
Zhu
X
X
Black
G
G
Beyers
N
N
Walzl
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000378:metabolism; D001500:BCG Vaccine / Q000276:immunology; D001426:Bacterial Proteins / Q000378:metabolism; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D007371:Interferon-gamma / Q000378:metabolism*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014374:Tuberculin Test / Q000379:methods; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000276:immunology*; D055815:Young Adult
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007371:Interferon-gamma