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Abstract Objectives A novel 3-gene host transcriptional signature (GBP5, DUSP3 and KLF2) has been validated for tuberculosis (TB) treatment monitoring using laboratory-based RNA sequencing platforms. The signature was recently translated by Cepheid into a prototype cartridge-based test that can be run on the GeneXpert instrument. In this study, we prospectively evaluated the change in the expression of the cartridge-based 3-gene signature following treatment initiation among pulmonary TB patients who were microbiologically cured at the end of treatment. Results The 3-gene signature expression level (TB score) changed significantly over time with respect to baseline among 31 pulmonary TB patients. The greatest increase in TB score occurred within the first month of treatment (median fold-increase in TB score: 1.08 [IQR 0.54–1.52]) and plateaued after 4 months of treatment (median TB score: 1.97 [IQR: 1.03–2.33]). The rapid and substantial increase of the TB score in the first month of treatment holds promise for the early identification of patients that respond to TB treatment. The plateau in TB score at 4 months may indicate early clearance of disease and could direct treatment to be shortened. These hypotheses need to be further explored with larger prospective treatment monitoring studies.

Objectives: A novel 3-gene host transcriptional signature (GBP5, DUSP3 and KLF2) has been validated for tuberculosis (TB) treatment monitoring using laboratory-based RNA sequencing platforms. The signature was recently translated by Cepheid into a prototype cartridge-based test that can be run on the GeneXpert instrument. In this study, we prospectively evaluated the change in the expression of the cartridge-based 3-gene signature following treatment initiation among pulmonary TB patients who were microbiologically cured at the end of treatment. Results: The 3-gene signature expression level (TB score) changed significantly over time with respect to baseline among 31 pulmonary TB patients. The greatest increase in TB score occurred within the first month of treatment (median fold-increase in TB score: 1.08 [IQR 0.54–1.52]) and plateaued after 4 months of treatment (median TB score: 1.97 [IQR: 1.03–2.33]). The rapid and substantial increase of the TB score in the first month of treatment holds promise for the early identification of patients that respond to TB treatment. The plateau in TB score at 4 months may indicate early clearance of disease and could direct treatment to be shortened. These hypotheses need to be further explored with larger prospective treatment monitoring studies. [ABSTRACT FROM AUTHOR]

Children suffering from infectious diseases, both bacterial and viral, are often treated with empirical antibiotics. Keeping in mind both the menace of microorganisms and antibiotic toxicity, it is imperative to develop point-of-care testing (POCT) to discriminate bacterial from viral infections, and to define indications for antibiotic treatment. This article reviews potential protein biomarkers and host-derived gene expression signatures for differentiating between bacterial and viral infections in children, and focuses on emerging multiplex POCT devices for the simultaneous detection of sets of protein biomarkers or streamlined gene expression signatures that may provide rapid and cost-effective pathogen-discriminating tools. Bacteria and viruses activate or inhibit different signaling pathways in the cells they infect, and further give rise to different host transcriptional signatures as well as to unique protein biomarkers. Many of the newly evaluated protein biomarkers, especially in combination, have better discriminative value for distinguishing between bacterial and viral infections than the biomarkers that are currently used for examining infections in children. The transcriptomes of children undergo remarkable changes when they are infected by different types of bacteria and viruses. Approaches based on host-derived DNA/RNA signatures can accurately discriminate bacterial from viral infections. Emerging multiplex POCT techniques allow simultaneous testing of protein- or gene-based biomarkers in an outpatient setting. [ABSTRACT FROM AUTHOR]