Comparison of the magnitude of TST and IGRA responses.

<p>A) PPD Diameter for 1^st and 2^nd TST in TST-negative (TST-), TST-converter (TSTc), and Prevalent TST positive (TST+) groups displayed by PPD testing visit and TST group*. B) IGRA results using Quantiferon Gold In-tube quantitative TB Ag – Nil by TST-, TSTc, and TST+ groups. 2^nd TST is only performed when PPD diameter in TST1 is <10 mm. Dashed line in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096564#pone-0096564-g002" target="_blank">Figure 2A</a> at 10 mm is the cutoff for a positive TST result. ∧ indicates values greater than 10 IU/ml (prior to December 2009 levels ≥10 IU/ml were reported as 10+). A dashed line in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096564#pone-0096564-g002" target="_blank">Figure 2B</a> is shown at 0.35 IU/ml, the cutoff for a positive IGRA test result.</p

Characteristics of Household Contacts.

<p>*Since those with PPD induration at entry of ≥10 mm did not have repeat testing, the induration for that group is from the entry TST but for those with entry TST<10 mm this variable uses the week 8–12 value.</p

Comparison of the magnitude of TST and IGRA responses.

<p>A) PPD Diameter for 1^st and 2^nd TST in TST-negative (TST-), TST-converter (TSTc), and Prevalent TST positive (TST+) groups displayed by PPD testing visit and TST group*. B) IGRA results using Quantiferon Gold In-tube quantitative TB Ag – Nil by TST-, TSTc, and TST+ groups. 2^nd TST is only performed when PPD diameter in TST1 is <10 mm. Dashed line in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096564#pone-0096564-g002" target="_blank">Figure 2A</a> at 10 mm is the cutoff for a positive TST result. ∧ indicates values greater than 10 IU/ml (prior to December 2009 levels ≥10 IU/ml were reported as 10+). A dashed line in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096564#pone-0096564-g002" target="_blank">Figure 2B</a> is shown at 0.35 IU/ml, the cutoff for a positive IGRA test result.</p

Sensitivity and specificity using alternate cutoff values.

<p>Identification of prevalent TST+, TST converters, and TST- using i) TB Ag − Nil cutoffs, ii) combinations of TB Ag-Nil and CXCL10 Stimulated levels or CXCL10 Stimulated/Unstimulated ratio and iii) Menzies definition (excludes those with difference in TST<6 mm), and TST- using TB Ag − Nil cutoff OF 0.25 IU/ml. Participants come from 74 (IGRA testing)/46 (IGRA and CXCL10 testing) households. Estimation uses a GEE approach with an independent working correlation matrix to adjust for clustering in households. Models based on the sample that included CXCL10 cutoffs were weighted to reflect the larger study cohort.</p><p>Pr(T+|Prevalent TST+) is the percentage test-positive among those who are were TST+ at week 1–2.</p><p>Pr(T+|TST Converter) is the percentage test-positive among those who are TST-converters (TST- at week 1–2 and TST+ at week 8–12).</p><p>Pr(T+|TST Menzies Converter) is the percentage test-positive among those who are TST-converters (TST- at week 1–2 and TST+ at week 8–12 and change of at least 6 mm).</p><p>Pr(T-| TST-) is the percentage test-negative among those who are TST-negative at weeks 1–2 and 8–12.</p

ROC curves for TBag − Nil.

<p>Statistics displayed on the curves are C = <i>X</i>: <i>Y</i>, <i>Z</i>, where <i>X</i> is the TB Ag − Nil (IU/ml) cutoff value for which IGRA would be declared positive. <i>Y</i> is Percentage of TST-negative (Specificity) that is below the cutoff and <i>Z</i> are the Percentage of TST-positive or TST converters at or above the cutoff (Sensitivity).</p

Additional file 1: Table S1. of Incident Mycobacterium tuberculosis infection in household contacts of infectious tuberculosis patients in Brazil

Additional characteristics of household contacts, index tuberculosis cases and study dwellings according to the tuberculin skin test (TST) outcome in contacts at study completion. (DOCX 20 kb

Additional file 2: Table S2. of Incident Mycobacterium tuberculosis infection in household contacts of infectious tuberculosis patients in Brazil

Qualitative and quantitative analysis of tuberculin skin test (TST) and interferon gamma release assay (IGRA) results in household contacts with TST conversion according to contact age and additional TST conversion criteria. (DOCX 17 kb

Importance of Cough and <i>M. tuberculosis</i> Strain Type as Risks for Increased Transmission within Households

<div><p>Rationale</p><p>The degree to which tuberculosis (TB) is transmitted between persons is variable. Identifying the factors that contribute to transmission could provide new opportunities for TB control. Transmission is influenced by host, bacterial and environmental factors. However, distinguishing their individual effects is problematic because measures of disease severity are tightly correlated, and assessing the virulence of <i>Mycobacterium tuberculosis</i> isolates is complicated by epidemiological and clinical confounders.</p><p>Objectives</p><p>To overcome these problems, we investigated factors potentially associated with TB transmission within households.</p><p>Methods</p><p>We evaluated patients with smear-positive (≥2+), pulmonary TB and classified <i>M. tuberculosis</i> strains into single nucleotide polymorphism genetic cluster groups (SCG). We recorded index case, household contact, and environmental characteristics and tested contacts with tuberculin skin test (TST) and interferon-gamma release assay. Households were classified as high (≥70% of contacts with TST≥10 mm) and low (≤40%) transmission. We used logistic regression to determine independent predictors.</p><p>Result</p><p>From March 2008 to June 2012, we screened 293 TB patients to enroll 124 index cases and their 731 contacts. There were 23 low and 73 high transmission households. Index case factors associated with high transmission were severity of cough as measured by a visual analog cough scale (VACS) and the Leicester Cough Questionnaire (LCQ), and cavitation on chest radiograph. SCG 3b strains tended to be more prevalent in low (27.3%) than in high (12.5%) transmission households (p = 0.11). In adjusted models, only VACS (p<0.001) remained significant. SCG was associated with bilateral disease on chest radiograph (p = 0.002) and marginally associated with LCQ sores (p = 0.058), with group 3b patients having weaker cough.</p><p>Conclusions</p><p>We found differential transmission among otherwise clinically similar patients with advanced TB disease. We propose that distinct strains may cause differing patterns of cough strength and cavitation in the host leading to diverging infectiousness. Larger studies are needed to verify this hypothesis.</p></div

Distribution of households according to study <i>M. tuberculosis</i> transmission categories by study time point.

<p>NA = Not applicable.</p

Household contacts with tuberculin skin test (TST) conversion from entry to week 8–12 by initial household transmission category and age of contact.

<p>n/N are number of converters divided by the number at risk as defined by the various criteria below.</p>1<p>TST conversion <u>Criterion 1 (Brazilian guidelines)</u>: 1^st TST<10 mm; 2^nd TST≥10 mm; difference ≥10 mm. Does not include contacts with 1^st TST≥10 mm (407, 56%), and those with missing 1^st (21, 3%) or 2^nd TST (31, 4%) because they are not considered “at risk” by this criterion.</p>2<p>TST conversion <u>Criterion 2</u>: 1^st TST<5 mm; 2^nd TST≥10 mm; difference ≥6 mm. Does not include contacts with 1^st TST≥5 mm (458, 65%), and those with missing 1^st TST (21, 3%) or 2^nd TST (31, 4%) because they are not considered “at risk” by this criterion.</p><p>*Score test from generalized estimating equation (GEE) estimation approach to logistic regression.</p><p>Only contacts “at risk” of TST conversion are included for each criterion.</p