Mycobacterium tuberculosis-specific cytokine biomarkers for the diagnosis of childhood TB in a TB-endemic setting. (August 2019)

• Record Type: Journal Article
• Authors: Sudbury, Eva L.; Otero, Larissa; Tebruegge, Marc; Messina, Nicole L.; Seas, Carlos; Montes, Martin; Rìos, Julia; Germano, Susie; Gardiner, Kaya; Clifford, Vanessa; Gotuzzo, Eduardo; Curtis, Nigel
• Is Part Of: Journal of clinical tuberculosis and other mycobacterial diseases. Volume 16(2019)
• Publication Date: 2019-08
• Subjects: Tuberculosis -- Cytokine biomarkers -- Interferon-gamma release assay -- Tuberculin skin test -- TB-endemic; Tuberculosis -- Periodicals; Mycobacterial diseases -- Periodicals; 616.995
• DOI: 10.1016/j.jctube.2019.100102
• Languages: English
• ISSNs: 2405-5794

Abstract

Abstract: The tuberculin skin test and interferon-gamma release assays have limitations in diagnosing tuberculosis (TB), particularly in children. This study investigated the performance of candidate M. tuberculosis -specific cytokine biomarkers for TB in children in a TB-endemic setting. A total of 237 children with a household contact with smear-positive pulmonary TB were recruited. Importantly, a group of children with illnesses other than TB (sick controls) was included to assess specificity. Median IFN-ɣ, IL-1ra, IL-2, IL-13, IP-10, MIP-1β and TNF-α responses were significantly higher in children with active TB and latent TB infection (LTBI) than in both healthy and sick control children. Three of these cytokines – IL-2, IL-13 and IP-10 – showed better performance characteristics than IFN-ɣ, with IL-2 achieving positive and negative predictive values of 97.7% and 90.7%, respectively. Furthermore, IL-1ra and TNF-α responses differed significantly between active TB and LTBI cases, suggesting that they may be stage-specific biomarkers. Our data indicate that incorporating these biomarkers into future blood-based TB assays could result in substantial performance gains.