QuantiFERON®-TB gold in-tube performance for diagnosing active tuberculosis in children and adults in a high burden setting

Abstract

Aim: To determine whether QuantiFERON®-TB Gold In-Tube (QFT) can contribute to the diagnosis of active tuberculosis (TB) in children in a high-burden setting and to assess the performance of QFT and tuberculin skin test (TST) in a prospective cohort of TB suspect children compared to adults with confirmed TB in Tanzania.

Methods: Sensitivity and specificity of QFT and TST for diagnosing active TB as well as indeterminate QFT rates and IFN-γ levels were assessed in 211 TB suspect children in a Tanzanian district hospital and contrasted in 90 adults with confirmed pulmonary TB.

Results: Sensitivity of QFT and TST in children with confirmed TB was 19% (5/27) and 6% (2/31) respectively. In adults sensitivity of QFT and TST was 84% (73/87) and 85% (63/74). The QFT indeterminate rate in children and adults was 27% and 3%. Median levels of IFN-γ were lower in children than adults, particularly children <2 years and HIV infected. An indeterminate result was associated with age <2 years but not malnutrition or HIV status. Overall childhood mortality was 19% and associated with an indeterminate QFT result at baseline.

Conclusion: QFT and TST showed poor performance and a surprisingly low sensitivity in children. In contrast the performance in Tanzanian adults was good and comparable to performance in high-income countries. Indeterminate results in children were associated with young age and increased mortality. Neither test can be recommended for diagnosing active TB in children with immature or impaired immunity in a high-burden setting.

Figure 1. Summary of recruitment and diagnostic classification of children.

* Children without follow-up data were excluded since they could not be classified according to the TB classifications. However one child had culture confirmed TB and could therefore be classified without follow-up data. ** The first 61 QFT results were excluded, when the initial QFT analysis showed very poor response in all the QFT tubes, including the mitogen. This was attributed to incorrect storage in a room reaching temperatures above 30°C. Subsequent tubes were all stored at 5–10°C.

Figure 2. Childhood mortality according to Quantiferon TB Gold In-Tube result.

Childhood mortality recorded during admission and at 6 month follow-up, according to QFT results. Children who did not attend scheduled follow-up at 6 months were traced and follow-up visits were conducted in their homes within 7–12 months of inclusion. Both the mortality during admission and the overall mortality in children with an indeterminate QFT result was significantly higher than in children with a determinate QFT result, p<0.001. * One of 154 children with a determinate QFT result did not have follow-up data.