Browsing by Author "Doherty, T. Mark"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Effect of non-tuberculous mycobacteria on host biomarkers potentially relevant for tuberculosis management
    (PLoS, 2014-10-16) Dhanasekaran, S.; Jenum, Synne; Stavrum, Ruth; Wiker, Harald G.; Kenneth, John; Vaz, Mario; Doherty, T. Mark; Grewal, Harleen M. S.; Hesseling, A. C.
    Background: Non-tuberculous mycobacteria (NTM) are different from Mycobacterium tuberculosis (MTB) both in their ubiquitous environmental distribution and in their reduced capacity to cause disease. While often neglected in favour of other infectious diseases, NTM may interfere with important aspects of TB control and management, namely the efficacy of new anti-tuberculosis (TB) vaccines; the immuno-diagnostic Tuberculin skin test (TST) and QuantiFERON TB Gold In Tube assay (QFTGIT); and immune biomarkers explored for their diagnostic and/or predictive potential. Our objective was therefore to explore host immune biomarkers in children who had NTM isolated from respiratory and/or gastric specimens. Methodology and Principle Findings: The present study was nested within a prospective cohort study of BCG-vaccinated neonates in Southern India. In this setting, immune biomarkers from peripheral blood were analyzed in 210 children aged , 3 years evaluated for TB using dual-colour-Reverse-Transcriptase-Multiple-Ligation-dependent-Probe-Amplification (dcRTMLPA) and Bio-Plex assays. The children were classified based on clinical examination, chest X-rays and mycobacterial culture reports as either: 1) TB disease, 2) NTM present and 3) controls. The study shows a down-regulation of RAB33A (p, 0.001) and up-regulation of TGFb1, IL-2 and IL-6 (all p,0.05) in children with TB disease, and that RAB33A, TGFBR2 and IL-10 (all p,0.05) were differentially expressed in children with NTM present when compared to children that were culture negative for MTB and NTM (controls). Conclusions and Significance: Carriage of NTM may reduce the specificity of future diagnostic and predictive immune biomarkers relevant to TB management.
  • Thumbnail Image
    Item
    Potential of novel Mycobacterium tuberculosis infection phase-dependent antigens in the diagnosis of TB disease in a high burden setting
    (BioMed Central, 2012-01) Chegou, Novel N.; Black, Gillian F.; Loxton, Andre G.; Stanley, Kim; Essone, Paulin N.; Klein, Michel R.; Parida, Shreemanta K.; Kaufmann, Stefan H. E.; Doherty, T. Mark; Friggen, Annemieke H.; Franken, Kees L.; Ottenhoff, Tom H.; Walzl, Gerhard
    Abstract Background Confirming tuberculosis (TB) disease in suspects in resource limited settings is challenging and calls for the development of more suitable diagnostic tools. Different Mycobacterium tuberculosis (M.tb) infection phase-dependent antigens may be differentially recognized in infected and diseased individuals and therefore useful as diagnostic tools for differentiating between M.tb infection states. In this study, we assessed the diagnostic potential of 118 different M.tb infection phase-dependent antigens in TB patients and household contacts (HHCs) in a high-burden setting. Methods Antigens were evaluated using the 7-day whole blood culture technique in 23 pulmonary TB patients and in 19 to 21 HHCs (total n = 101), who were recruited from a high-TB incidence community in Cape Town, South Africa. Interferon-gamma (IFN-γ) levels in culture supernatants were determined by ELISA. Results Eight classical TB vaccine candidate antigens, 51 DosR regulon encoded antigens, 23 TB reactivation antigens, 5 TB resuscitation promoting factors (rpfs), 6 starvation and 24 other stress response-associated TB antigens were evaluated in the study. The most promising antigens for ascertaining active TB were the rpfs (Rv0867c, Rv2389c, Rv2450c, Rv1009 and Rv1884c), with Areas under the receiver operating characteristics curves (AUCs) between 0.72 and 0.80. A combination of M.tb specific ESAT-6/CFP-10 fusion protein, Rv2624c and Rv0867c accurately predicted 73% of the TB patients and 80% of the non-TB cases after cross validation. Conclusions IFN-γ responses to TB rpfs show promise as TB diagnostic candidates and should be evaluated further for discrimination between M.tb infection states.