Highly Discordant T-Cell Responses In Individuals With Recent Household Tuberculosis Exposure

Anneke C Hesseling ^1*, Anna M Mandalakas ², Lester H Kirchner ³, Novel N Chegou ¹, Ben J Marais ¹, Xiaobei Zhu ², Gillian F Black ¹, Kim Stanley ¹, Nulda Beyers ¹ and Gerhard Walzl ¹

¹ Stellenbosch University, Tygerberg, South Africa
² School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States
³ Center for Health Research, Geisinger Health System, Danville, Pennsylvania, United States

^* To whom correspondence should be addressed. E-mail: annekeh{at}sun.ac.za.

Accepted 17 July 2008

Abstract

Introduction: There are limited data comparing Interferon-Gamma release assays (IGRAs) for the detection of Mycobacterium tuberculosis (M.tb) infection in highly endemic settings.

Methods: We conducted a cross-sectional household contact study to measure the agreement of two IGRAs in relation to the tuberculin skin test (TST) to detect M. tb infection and assess the influence of M. tb exposure and age.

Results: In 82 individuals in household contact, 93% of children and 42% of adults had a high M. tb contact score. The TST was positive in 78% adults vs. 54% children. The T SPOT.TB was positive in 89% children vs. 66% adults. QuantiFERON®TB Gold (QTF) was positive in a similar proportion of adults and children (38.1% vs.39.6%). In children there was poor agreement between the TST and T SPOT.TB (Kappa; k= -0.15), the T SPOT.TB and the QTF (K= -0.03), but good agreement between the TST and the QTF (k=0.78), using 10 mm cut-off. In adults there was fair to moderate agreement between the TST and T SPOT.TB (k=0.38), the TST and QTF (k=0.34) and T SPOT.TB and QTF (k= -0.50). High M.tb exposure was associated with at least a 7-fold odds of being T SPOT.TB positive (95% CI: 7.67-508.69) and 3-fold odds of being QTF positive (95% CI: 3.02-30.54). There was a significant difference in the magnitude of T SPOT.TB ESAT-6 and CFP-10 spot counts between adults and children.

Conclusions: The T SPOT.TB may be more sensitive than the TST or QTF to detect recent M. tb infection in children. Differences between assays and the predictive utility of these findings for subsequent disease development should be prospectively assessed.