Univariate and multivariable analyses of factors associated with TST/IGRA discordance in household contacts.

<p>Values are mean [Standard deviation] or n (percent), unless otherwise specified.</p><p>P-values are calculated using a logistic regression model fit with generalized estimating equations (GEE) approach.</p><p>AFB = Acid fast-bacilli; CFU = Colony forming units of <i>M</i>. <i>tuberculosis</i> in aerosols.</p><p>Missing data: Index case HIV status (3), chest radiograph (22, 20 concordant and 2 discordant), contact HIV history (52), and meals shared with index case (1).</p><p>¹Univariate and multivariable model adjusted for correlation between contacts with the same index case using a GEE model. The final adjusted model only uses those that had p<0.2 in the univariate results + CASS and smear.</p><p>² Visual analog scale is per unit increase.</p><p>³ Cough peak flow is per 10 L/min increase.</p><p>Univariate and multivariable analyses of factors associated with TST/IGRA discordance in household contacts.</p

Distribution of tuberculin skin test (TST) and interferon gamma release assay (IGRA) results in household contacts at baseline and six weeks.

<p>Distribution of tuberculin skin test (TST) and interferon gamma release assay (IGRA) results in household contacts at baseline and six weeks.</p

Characteristics of index cases and household contacts and of tuberculin skin test (TST) and interferon gamma release assay (IGRA) results in contacts. Results are shown by sputum acid-fast bacilli (AFB) smear microscopy grade and colony forming units (CFU) of <i>M</i>. <i>tuberculosis</i> cultured in aerosols.

<p>Values are median [IQR] or n (%), unless otherwise specified.</p><p>^* Group includes one patient with smear = negative and one smear = scanty.</p><p>⁺P-values for index case factors obtained using Fisher exact test; ^P-values for contact factors obtained using GEE models.</p><p>AFB = Acid fast-bacilli; CFU = Colony forming units of <i>M</i>. <i>tuberculosis</i> in aerosols; VACS = Visual analog cough scale; CASS = Cough aerosol sampling system; and DTP = Days to positive.</p><p>¹ Visual analog cough scale is per unit increase.</p><p>² Cough peak flow is per 10 L/min increase.</p><p>Missing data for index TB cases: Week sick before enrollment (1), Extent of lung disease/cavitation (5).</p><p>Missing data for household contacts: Age (2).</p><p>³ Only includes contacts “at risk” of TST (<10mm at baseline) or IGRA (negative at baseline) conversion.</p><p>Characteristics of index cases and household contacts and of tuberculin skin test (TST) and interferon gamma release assay (IGRA) results in contacts. Results are shown by sputum acid-fast bacilli (AFB) smear microscopy grade and colony forming units (CFU) of <i>M</i>. <i>tuberculosis</i> cultured in aerosols.</p

Quantitative analysis of tuberculin skin test (TST) and interferon gamma release assay (IGRA) results among four groups of contacts exposed to a patient with pulmonary tuberculosis: 1) TST- = contacts who have TST<10mm at baseline and 6 weeks; 2) TSTc = contacts who undergo TST conversion at 6 weeks (see definition in <i>Methods</i>); 3) TST+/IGRA- = contacts with TST ≥10mm at baseline and IGRA-; and 4) TST+/IGRA+ = contacts with TST ≥10mm at baseline and IGRA+.

<p>Circles indicate baseline values and triangles indicate values at 6 weeks. The solid horizontal bars indicate the median value. The N for each group is the same for TST and IGRA results.</p

Analysis of tuberculin skin test (TST) and interferon gamma release assay (IGRA) readouts at six weeks among contacts TST and/or IGRA negative at baseline by exposure variables measured by AFB smear and CASS aerosol CFU.

<p>“c” = conversion (from negative to positive); “nc” = non-conversion</p

Cough Aerosol Cultures of <i>Mycobacterium tuberculosis</i>: Insights on TST / IGRA Discordance and Transmission Dynamics

<div><p>Rationale</p><p>The diagnosis of latent tuberculosis (TB) infection (LTBI) is complicated by the absence of a gold standard. Discordance between tuberculin skin tests (TST) and interferon gamma release assays (IGRA) occurs in 10–20% of individuals, but the underlying mechanisms are poorly understood.</p><p>Methods</p><p>We analyzed data from a prospective household contact study that included cough aerosol culture results from index cases, environmental and contact factors. We assessed contacts for LTBI using TST and IGRA at baseline and six weeks. We examined TST/IGRA discordance in qualitative and quantitative analyses, and used multivariable logistic regression analysis with generalized estimating equations to analyze predictors of discordance.</p><p>Measurements and Results</p><p>We included 96 TB patients and 384 contacts. Discordance decreased from 15% at baseline to 8% by six weeks. In adjusted analyses, discordance was related to less crowding (p = 0.004), non-cavitary disease (OR 1.41, 95% CI: 1.02–1.96; p = 0.03), and marginally with BCG vaccination in contacts (OR 1.40, 95% CI: 0.99–1.98, p = 0.06).</p><p>Conclusions</p><p>We observed significant individual variability and temporal dynamism in TST and IGRA results in household contacts of pulmonary TB cases. Discordance was associated with a less intense infectious exposure, and marginally associated with a BCG-mediated delay in IGRA conversion. Cough aerosols provide an additional dimension to the assessment of infectiousness and risk of infection in contacts.</p></div

Baseline tuberculin skin test (TST) and interferon gamma release assay (IGRA) results by BCG vaccination scar^* and contact age.

<p>* Five contacts had uncertain BCG scar results</p><p>Baseline tuberculin skin test (TST) and interferon gamma release assay (IGRA) results by BCG vaccination scar<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138358#t003fn001" target="_blank">^*</a> and contact age.</p