Is IP-10 a Better Biomarker? Figure 2. IFN-c and IP-10 levels (pg/ml) in Antigen stimulated samples of patients with active and latent TB and a control group. Horizontal lines indicate median values. Controls are represented by #, active TB by n, and LTBI by %. Open symbols represent IP-10, closed symbols represent IFNc samples. doi:10.1371/journal.pone.0003901.g002 range: 1–2131: median SI IP-10: 9.4, range: 1–125; p,0.0013) and latent TB groups (median SI IFNc: 271, range: 1.5–16331, median SI IP-10: 8.8, range: 0.32–68.7; p,0.0017). Discussion This is the first published study comparing the use of IP-10 as a biomarker for active and latent tuberculosis in children. Although we have demonstrated that IP-10 is a marker for tuberculosis – active and latent - in children, we did not find it to be discriminative between the two disease states. Chemokines are believed to play a role in the pathogenesis of tuberculosis, specifically in granuloma formation[18]. In particu- lar, raised levels of IP-10 are found in adult studies of patients with active TB[10]. Elevated levels have also been noted in household contacts of patients with active TB[15]. Many of these studies were measuring the unstimulated plasma level of IP-10 in confirmed cases of TB[19]. In our study we noted a high background level of IP-10, confirming this previously published work. It is noteworthy that the background level of IP-10 is significantly greater in LTBI than active TB, possibly due to a chronic state of inflammation as the immune system attempts to control TB infection. Alternatively, an immunosuppressive effect of active TB, modifying cytokine responses might also explain the differences seen. It is unclear at this stage whether the background levels of IP-10 could carry a prognostic value for the development of active TB from latent TB. We showed that IP-10 is produced in high levels following MTB antigen-specific stimulation of whole blood in both active TB and LTBI cases, demonstrating its potential as a biomarker for MTB in children. Ruhwald et al reported similar findings in adults with culture positive tuberculosis[10], and in children with presumed latent TB infection[17], but there are no published data for active TB in a paediatric population. The paediatric study by Ruhwald included 97 household contacts under 15 years of age (85%.5 yrs) and compared IP-10 levels in child contacts of smear positive adults with those in both smear negative contacts and a control group. A significant increase in IP-10 was found in the smear positive contact group. However, these children did not have active TB, as this study was essentially a household contact investigation. There was good correlation between the QFG-IT Figure 3. Stimulation index of IP-10 and IFN-c in active TB, LTBI and a control group. Horizontal lines indicate medians. Controls are represented by #, active TB by n, and LTBI by %. Open symbols represent IP-10, closed symbols represent IFNc samples. doi:10.1371/journal.pone.0003901.g003 PLoS ONE | www.plosone.org 4 December 2008 | Volume 3 | Issue 12 | e3901