Reduction in ALS responses over time, based on drug resistance profile.

<p>Median ALS responses are displayed at two different time points by drug resistance profile. After four weeks of TB treatment, adults with drug-sensitive TB demonstrated a greater reduction in ALS responses, although this was not statistically significant (p = 0.057, Wilcoxon signed rank test).</p

Demographic and clinical characteristics.

<p>Demographic and clinical characteristics.</p

ALS response by disease status.

<p>Data are shows as median values and interquartile range within the boxplots, and range within the whiskers. Compared to controls, ALS responses were higher among both TB groups, p<0.001 by Kruskal-Wallis test.</p

Evaluation of the Antibody in Lymphocyte Supernatant Assay to Detect Active Tuberculosis

<div><p>Background</p><p>We aimed to evaluate the antibody in lymphocyte supernatant (ALS) assay as a biomarker to diagnose tuberculosis among adults from Tanzania with and without HIV.</p><p>Methods</p><p>Adults admitted with suspicion for tuberculosis had sputa obtained for GeneXpert MTB/RIF, acid-fast bacilli smear and mycobacterial culture; blood was obtained prior to treatment initiation and after 4 weeks. Adults hospitalized with non-infectious conditions served as controls. Peripheral blood mononuclear cells were cultured unstimulated for 72 hours. Anti-mycobacterial antibodies were measured from culture supernatants by ELISA, using BCG vaccine as the coating antigen. Median ALS responses were compared between cases and controls at baseline and between cases over time.</p><p>Results</p><p>Of 97 TB cases, 85 were microbiologically confirmed and 12 were clinically diagnosed. Median ALS responses from TB cases (0.366 OD from confirmed cases and 0.285 from clinical cases) were higher compared to controls (0.085, p<0.001). ALS responses did not differ based on HIV status, CD4 count or sputum smear status. Over time, the median ALS values declined significantly (0.357 at baseline; 0.198 after 4-weeks, p<0.001).</p><p>Conclusions</p><p>Robust ALS responses were mounted by patients with TB regardless of HIV status, CD4 count, or low sputum bacillary burden, potentially conferring a unique niche for this immunologic biomarker for TB.</p></div

Receiver operator characteristic curve.

<p>Receiver operator characteristic (ROC) curves were created using ALS responses from microbiologically-confirmed TB cases (n = 85) and non-TB controls (n = 28). The area under the curve is 0.970. The arrow indicates a proposed threshold for assay positivity which maximizes sensitivity (92%) and specificity (96%).</p

Sputum culture positive by week in MGIT system, N = 25.

<p>All patients (100%) culture positive from pretreatment sputum specimen.</p

Change in plasma drug activity measured at the time of estimated peak concentration (2hr) after 2 and 4 weeks of treatment.

<p>TDA = Tuberculosis drug activity, where values greater than 1.0 indicate <i>in vitro</i> killing of a patient’s plasma against their own <i>M</i>. <i>tuberculosis</i> isolate. p = 0.005 by paired sample t-test.</p

Clinical characteristics, patients treated for pulmonary multidrug-resistant tuberculosis (MDR-TB), N = 25.

<p>^aAt MDR-TB treatment initiation.</p><p>Clinical characteristics, patients treated for pulmonary multidrug-resistant tuberculosis (MDR-TB), N = 25.</p

Predictors of favorable interim treatment outcome using exact logistic regression.

<p>^aGreater change in time-to-positivity (TTP) reflects greater decrement in sputum bacterial burden.</p><p>Predictors of favorable interim treatment outcome using exact logistic regression.</p

Comparison of patients that completed intensive phase of MDR-TB therapy to those that died.

*<p>Excludes 3 patients that defaulted.</p>†<p>Excludes 8 patients for whom follow-up sputum culture results unavailable.</p><p>N/a =  not applicable.</p