Molecular and microscopy results for the 11 isolates with MTBC and other organisms.

<p>Molecular and microscopy results for the 11 isolates with MTBC and other organisms.</p

BAL and blood IGRA results (N = 94).

<p><b><u>Abbreviations:</u></b> BAL (bronchoalveolar lavage), IGRA (interferon-gamma release assay).</p

Study flow.

<p>Of 110 smear-negative tuberculosis suspects referred for bronchoscopy, 104 (95%) underwent the procedure and 94 (85%) were included in the study. Bronchoalevolar lavage TSPOT and peripheral blood TSPOT provided interpretable results in 62 (66%) and 81 (86%) patients, respectively.</p

Evaluation of antibody responses to panels of <i>M</i>. <i>tuberculosis</i> antigens as a screening tool for active tuberculosis in Uganda

<div><p>Background</p><p>Improved systematic screening of high-risk groups is a key component of the tuberculosis (TB) elimination strategy endorsed by the World Health Organization (WHO). We used a multiplex microbead immunoassay to measure antibody responses to 28 <i>M</i>. <i>tuberculosis</i> (<i>M</i>.<i>tb</i>) antigens, and assessed whether combinations of antibody responses achieve accuracy thresholds required for a TB screening test.</p><p>Methods</p><p>A random selection of plasma samples obtained from consecutive HIV-negative adults who were admitted to Mulago Hospital in Kampala, Uganda with cough ≥2 weeks’ but <6 months’ duration were analyzed for serological response to 28 <i>M</i>.<i>tb</i> antigens using an in-house multiplex microbead immunoassay. We compared the median difference of the antibody response to each antigen between patients with and without culture-confirmed TB, ranked each antigen according to variable importance (VIM), and assessed the sensitivity and specificity of combinations of antibody responses using an advanced classification algorithm, SuperLearner.</p><p>Results</p><p>Among the 237 patients included in the analysis, 119 (50%) were female, median age was 32 years (IQR 25, 46), and 113 (48%) had TB. Median antibody levels to eight antigens were significantly different between patients with and without TB. A panel including eight of the top ranked antigens had a sensitivity of 90.6% (95% CI 89.4, 93.8) and a specificity of 88.6% (95% CI 78.2, 97.6) (Ag85B, Ag85A, Ag85C, Rv0934-P38, Rv3881, BfrB, Rv3873, and Rv2878c). With sensitivity constrained to be >90%, specificity remained close to 70% with as few as 3 antigens included in the panels.</p><p>Conclusions</p><p>Measuring antibody responses to combinations of antigens could facilitate TB screening and should be further evaluated in populations being targeted for systematic screening.</p></div

Flowchart of sample selection.

<p>Flowchart of sample selection.</p

Median serological response (MFI) to 28 recombinant <i>M</i>. <i>tuberculosis</i> antigens.

<p>Median serological response (MFI) to 28 recombinant <i>M</i>. <i>tuberculosis</i> antigens.</p

Specificity of panels consisting of top-ranked antigens in both full and excluded validation datasets.

<p>Specificity of panels consisting of top-ranked antigens in both full and excluded validation datasets.</p

Xpert proportion positive differences and unadjusted differences in sputum Xpert sensitivity and specificity, stratified by sputum quality*.

<p>Legend: * Mucoid sputum utilized as the reference group.</p

Ranking of 28 recombinant <i>M</i>. <i>tuberculosis</i> antigens based on variable importance (VIM).

<p>Ranking of 28 recombinant <i>M</i>. <i>tuberculosis</i> antigens based on variable importance (VIM).</p

Effect of chlorhexidine - nystatin oral rinse on culture contamination.

p<p>N = 177, Total HIV positive participants;</p>q<p>n = 92,</p>r<p>n = 85.</p>s<p>N = 43, Total HIV negative participants;</p>t<p>n = 18,</p>u<p>n = 25.</p