Prevalence of TB among the study participants, July—September 2016, South Africa.

<p>Prevalence of TB among the study participants, July—September 2016, South Africa.</p

Preferred method of response to the survey among study participants, July—September 2016, South Africa (N = 459).

<p>Preferred method of response to the survey among study participants, July—September 2016, South Africa (N = 459).</p

Characteristics of the study participants, July—September 2016, South Africa.

<p>Characteristics of the study participants, July—September 2016, South Africa.</p

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

Comparative accuracy of the REBA MTB MDR and Hain MTBDR<i>plus</i> line probe assays for the detection of multidrug-resistant tuberculosis: A multicenter, non-inferiority study

<div><p>Introduction</p><p>Despite recent diagnostic advances, the majority of multidrug-resistant tuberculosis (MDR-TB) cases remain undiagnosed. Line probes assays (LiPAs) hold great promise to curb the spread of MDR-TB as they can rapidly detect MDR-TB even when laboratory infrastructure is limited, yet few of these assays are currently widely available or supported by World Health Organization (WHO) policy.</p><p>Methods</p><p>The aim of this prospective, blinded, non-inferiority study was to compare the performance of YD Diagnostics REBA MTB MDR LiPA (YD) to the WHO-endorsed Hain MTBDR<i>plus</i> V1 LiPA (Hain V1) for the detection of rifampicin and isoniazid resistance. In phase 1, YD and Hain V1 diagnostic performance was assessed with selected culture isolates and results were compared to phenotypic drug susceptibility testing (DST) results and targeted sequencing data. In phase 2, both assays were tested on processed sputum samples and results were compared to phenotypic DST results.</p><p>Results</p><p>In phase 1, YD did not achieve non-inferiority to Hain V1. For isoniazid resistance detection, Hain V1 had a sensitivity of 89% (95%CI 83.8–93%) and specificity of 99.4% (95%CI 96.9–100%). While YD had a similar sensitivity of 92% (95%CI 87.3–95.4%), the specificity was inferior at 92.6% (95%CI 87.6–96%). For rifampicin resistance detection, Hain V1 had a sensitivity of 90.2% (95%CI 84.8–94.2%) and specificity of 98.5% (95%CI 95.7–99.7%) while YD had an inferior sensitivity of 72.4% (95%CI 65.1–78.9%) and a comparable specificity of 98% (95%CI 95–99.5%). Similar results were observed in phase 2. For MDR-TB detection, the sensitivity and specificity of Hain V1 was 93.4% (95%CI 88.2–96.2%) and 96.2% (95%CI 88.2–96.8%), respectively, compared to 75.7% (95%CI 68–82.2%) and 92% (95%CI 88.2–94.9%) for YD.</p><p>Conclusions</p><p>YD did not achieve non-inferiority with Hain V1. Further improvements and repeat evaluation of YD is necessary prior to recommending its use for clinical settings.</p></div