Additional file 1: Figure S1. of Respiratory microbes present in the nasopharynx of children hospitalised with suspected pulmonary tuberculosis in Cape Town, South Africa

Seasonal distribution of viruses and bacteria. Figure S2. Canonical Variate Analysis (CVA) biplot depicting the spread of respiratory pathogens in the definite TB (red line) and not TB (blue line) groups only. Observations under each group are denoted by “+” signs and the median of each group by the red and blue ovals. Table S1. Target pathogens in the FTD respiratory pathogens 33 multiplex realtime PCR assay. Table S2. Summary of all paired pathogen co-occurrence counts *. Table S3. Risk factors associated with the occurrence of each microbes. (PDF 565 kb

A combination of baseline plasma immune markers can predict therapeutic response in multidrug resistant tuberculosis

<div><p>Objective</p><p>To identify plasma markers predictive of therapeutic response in patients with multidrug resistant tuberculosis (MDR-TB).</p><p>Methods</p><p>Fifty HIV-negative patients with active pulmonary MDR-TB were analysed for six soluble analytes in plasma at the time of initiating treatment (baseline) and over six months thereafter. Patients were identified as sputum culture positive or negative at baseline. Culture positive patients were further stratified by the median time to sputum culture conversion (SCC) as fast responders (< 76 days) or slow responders (≥ 76 days). Chest X-ray scores, body mass index, and sputum smear microscopy results were obtained at baseline.</p><p>Results</p><p>Unsupervised hierarchical clustering revealed that baseline plasma levels of IP-10/CXCL10, VEGF-A, SAA and CRP could distinguish sputum culture and cavitation status of patients. Among patients who were culture positive at baseline, there were significant positive correlations between plasma levels of CRP, SAA, VEGF-A, sIL-2Rα/CD40, and IP-10 and delayed SCC. Using linear discriminant analysis (LDA) and Receiver Operating Curves (ROC), we showed that a combination of MCP-1/CCL2, IP-10, sIL-2Rα, SAA, CRP and AFB smear could distinguish fast from slow responders and were predictive of delayed SCC with high sensitivity and specificity.</p><p>Conclusion</p><p>Plasma levels of specific chemokines and inflammatory markers measured before MDR-TB treatment are candidate predictive markers of delayed SCC. These findings require validation in a larger study.</p></div

Baseline plasma concentrations of analytes in slow and fast responders.

<p>Baseline plasma concentrations of analytes in slow and fast responders.</p

Baseline clinical and microbiological characteristics of MDR-TB patients.

<p>Baseline clinical and microbiological characteristics of MDR-TB patients.</p

Baseline levels of plasma markers.

<p>(A) Two-dimensional unsupervised hierarchical clustering of baseline analyte profiles in 50 patients, characterized by sputum smear (SS) and sputum culture (SC) status and cavitary vs non-cavitary disease. Normalized and log2 transformed values of analyte levels are indicated by the color scale, where yellow and blue represent expression levels above and below the median, respectively. Three-dimensional plots of principal component analysis (PCA) of (B) SS negative (orange) and SS positive (blue); (C) SC negative (yellow) and SC positive (blue); (D) cavitary (pink) and non-cavitary disease (green). Statistical comparisons using non-parametric Mann-Whitney U test were corrected for multiple comparisons through a false discovery rate (FDR) step down procedure (*: q<0.05, **: q<0.01, ***: q<0.001).</p

Plasma markers as predictors of fast vs slow response to treatment.

<p>Receiver Operating Characteristic (ROC) curve analysis and baseline LDA scores of (A and B) the optimal combination of plasma markers, and (C and D) the optimal combination of markers plus clinical data (sputum smear). Horizontal bars indicate median and interquartile range. Statistical analyses between unpaired groups were performed using non-parametric Wilcoxon paired tests. Differences between groups were assessed by Mann-Whitney U test. P<0.05 was considered significant.</p

Expression of plasma markers in fast and slow responders.

<p>(A) Distribution of time to culture conversion (TCC) in study cohort; (B–F) Correlation between baseline levels of individual plasma markers and TCC, shown as slow (red) or fast (black) responders. (G) Principal component analysis (PCA) plot of slow (red) and fast (black) responders, analyzed as above.</p