Utility of host markers detected in Quantiferon supernatants for the diagnosis of tuberculosis in children in a high-burden setting

• Published in: PloS one 2013-05, Vol.8 (5), p.e64226-e64226
• Main Authors: Chegou, Novel N, Detjen, Anne K, Thiart, Lani, Walters, Elisabetta, Mandalakas, Anna M, Hesseling, Anneke C, Walzl, Gerhard
• Format: Article
• Language: English
• Subjects: Biomarkers - metabolism; Cellular biology; Child, Preschool; Children; Children & youth; Childrens health; Cytokines; Diagnosis; Diagnostic systems; Female; Health aspects; Health sciences; HIV; Human immunodeficiency virus; Humans; Hypothesis testing; Immunology; Infant; Infections; Interferon; Interleukin 1 receptor antagonist; Interleukin 1 receptors; IP-10 protein; Latent infection; Lung diseases; Male; Markers; Medical diagnosis; Medical research; Medicine; Molecular biology; Mycobacterium tuberculosis; Proteins; South Africa - epidemiology; Studies; Tuberculosis; Tuberculosis - diagnosis; Tuberculosis - epidemiology; Tubes; Tumor necrosis factor-TNF; Tutu, Desmond; Vascular endothelial growth factor
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0064226

The diagnosis of childhood tuberculosis (TB) disease remains a challenge especially in young and HIV-infected children. Recent studies have identified potential host markers which, when measured in Quantiferon (QFT-IT) supernatants, show promise in discriminating between Mycobacterium tuberculosis (M.tb) infection states. In this study, the utility of such markers was investigated in children screened for TB in a setting with high TB incidence. 76 children (29% HIV-infected) with or without active TB provided blood specimens collected directly into QFT-IT tubes. After overnight incubation, culture supernatants were harvested, aliquoted and frozen for future immunological research purposes. Subsequently, the levels of 12 host markers previously identified as potential TB diagnostic markers were evaluated in these supernatants for their ability to discriminate between M.tb infection and disease states using the Luminex platform. Of the 76 children included, 19 (25%) had culture confirmed TB disease; 26 (46%) of the 57 without TB had positive markers of M.tb infection defined by a positive QFT-IT test. The potentially most useful analytes for diagnosing TB disease included IFN-α2, IL-1Ra, sCD40L and VEGF and the most useful markers for discriminating between QFT-IT positive children as TB or latent infection included IL-1Ra, IP-10 and VEGF. When markers were used in combinations of four, 84% of all children were accurately classified into their respective groups (TB disease or no TB), after leave-one-out cross validation. Measurement of the levels of IFN-α2, IL-1Ra, sCD40L, IP-10 and VEGF in QFT-IT supernatants may be a useful method for diagnosing TB disease and differentiating between active TB disease and M.tb infection in children. Our observations warrant further investigation in larger well-characterized clinical cohorts.