No added value of interferon-γ release to a prediction model for childhood tuberculosis.

The predictive value of a combination of clinical and radiological features with interferon-γ release assay (IGRA) for diagnosis of active tuberculosis (TB) disease among TB-exposed children is unknown.150 symptomatic HIV-negative children (aged 3 months to 14 years), prospectively recruited through active contact tracing, were included. Backward stepwise logistic regression and bootstrapping techniques were used for the development and internal validation of a clinical prediction model for active TB disease. Model discrimination and incremental value of a positive IGRA test were assessed by area under the receiver operating characteristic curve (AUC).35 (23%) children were diagnosed with active TB disease and started on treatment and 115 (77%) had other respiratory tract infections. A final parsimonious clinical model, comprising age <5 years (adjusted (a)OR 4.8, 95% CI 2.0-11.5) and lymphadenopathy on clinical examination (aOR 4.9, 95% CI 1.8-13.0) discriminated active TB disease from other disease with an AUC of 0.70 (95% CI 0.61-0.80). A positive IGRA result did not improve the discriminatory ability of the clinical model (c-statistic 0.72 versus 0.70; p=0.644).A clinical algorithm, including age <5 years and lymphadenopathy classified 70% of active TB disease among symptomatic TB-exposed children. IGRA does not add any discriminatory value to this prediction model.

Host Immune Responses Differ between M. africanum- and M. tuberculosis-Infected Patients following Standard Anti-tuberculosis Treatment.

Epidemiological differences exist between Mycobacterium africanum (Maf)- and Mycobacterium tuberculosis (Mtb)-infected patients, but to date, contributing host factors have not been characterised. We analysed clinical outcomes, as well as soluble markers and gene expression profiles in unstimulated, and ESAT6/CFP-10-, whole-Maf- and Mtb-stimulated blood samples of 26 Maf- and 49 Mtb-HIV-negative tuberculosis patients before, and after 2 and 6 months of anti-tuberculosis therapy. Before treatment, both groups had similar clinical parameters, but differed in few cytokines concentration and gene expression profiles. Following treatment the body mass index, skinfold thickness and chest X-ray scores showed greater improvement in the Mtb- compared to Maf-infected patients, after adjusting for age, sex and ethnicity (p = 0.02; 0.04 and 0.007, respectively). In addition, in unstimulated blood, IL-12p70, IL12A and TLR9 were significantly higher in Maf-infected patients, while IL-15, IL-8 and MIP-1α were higher in Mtb-infected patients. Overnight stimulation with ESAT-6/CFP-10 induced significantly higher levels of IFN-γ and TNF-α production, as well as gene expression of CCL4, IL1B and TLR4 in Mtb- compared to Maf-infected patients. Our study confirms differences in clinical features and immune genes expression and concentration of proteins associated with inflammatory processes between Mtb- and Maf-infected patients following anti-tuberculosis treatment These findings have public health implications for treatment regimens, and biomarkers for tuberculosis diagnosis and susceptibility.