Gamma interferon release assays for diagnosis of tuberculosis infection in immune-compromised children in a country in which the prevalence of tuberculosis is low.

摘要

Children have a higher risk than adults of developing severe active tuberculosis (TB), and this risk further increases in patients undergoing long-term immune-suppressive therapies, including treatment with tumor necrosis factor alpha (TNF-??) blockers (12). In this setting, detection of TB infection may be difficult due to high rates of falsely negative results of tuberculin skin testing (TST) (2). Blood tests detecting gamma interferon (IFN-??) release by effector memory T cells stimulated with Mycobacterium tuberculosis antigens are currently available (8, 13). They rely on the use of two region-of-difference (RD-1)-encoded genes, namely, ESAT-6 and CFP-10.A total of 80 consecutive Italian human immunodeficiency virus-negative immune-compromised children were enrolled. Demographics and clinical characteristics of the study population are reported in Table ???Table1.1. The diagnostic preliminaries included a physical examination, routine blood tests, a chest X-ray, TST, and IGRAs. A cutoff value of 5 mm was chosen to represent a positive TST result for all cases (1). Performance and data analysis of TS-TB and QFT-IT were realized according to the instructions of the manufacturers. Spot-forming cells were counted with an automated ELISPOT reader (AID Systems, Strassberg, Germany). IFN-?? concentrations (expressed in international units per milliliter) were measured with an automated ELISA reader. IGRAs were performed by highly specialized laboratory staff with more than 3 years of experience in the field. The local Ethics Committee approved the study, and the patients or their parents provided oral consent.TST and QFT-IT gave a positive result for one (1.2%) patient, while a significantly higher (9.4%) proportion of cases were positive by TS-TB (P = 0.02). Mean analytical TS-TB and QFT-IT results are shown in Table ???Table22 and Table ???Table3.3. The rate of TS-TB-positive results was higher for patients affected by rheumatic diseases compared with patients who had undergone a liver transplant (5/19 [26.3%] versus 2/54 [4%]; P = 0.01) and for patients treated with TNF-?? blockers compared with those receiving other medications (4/15 [26.6%] versus 3/59 [5.1%]; P = 0.026). TS-TB and QFT-IT yielded a high number of indeterminate results (13.5% and 20%, respectively; P = 0.3). IGRA result agreement was found in 62.1% of cases (?? = 0; P = 0.6). Excluding indeterminate results, IGRA agreement with TST was poor (?? = ???0.028 [P = 0.89] for TS-TB and ?? = ???0.016 [P = 0.89] for QFT-IT). IGRA performance was not associated with age, gender, blood leukocyte count, or treatment duration. No active TB cases were detected during the whole study period (median follow-up, 12 months).