Urine-based MTB/RIF-generated C_T values correlates with other markers of bacillary burden.

<p>In <i>m.tb</i> culture and urine MTB/RIF positive patients, MTB/RIF-generated C_T values were correlated with (A) urine LAM ELISA concentration, (B) urine LAM strip grading, (C) either sputum or non-sputum liquid culture time-to-positivity (TTP), (D) only sputum liquid culture time-to-positivity, and (E) smear-grade in smear positive patients.</p

Demographic, clinical and microbiological characteristics of <i>m.tb</i> culture positive and HIV-infected patients in the study population stratified by sputum smear microscopy and urine MTB/RIF results.

#<p>9 patients did not have data CD4 count data.</p>§<p>Includes the following <i>m.tb</i> culture positive samples: 7 blood cultures, 11 pleural fluid samples, 4 pericardial fluid samples, 3 ascitic fluid samples, 8 cerebrospinal fluid (CSF) samples, 1 hip biopsy, 2 Lymph node biopsies, 5 fine needle aspirate, 1 gastric washing, 1 faeces and 2 pus swabs.</p>†<p>P-values indicate significant differences between patient groups (marked with ^* to indicate comparison group) for demographic, clinical or microbiological characteristics.</p

Venn diagram showing the proportions of patients diagnosed by urine MTB/RIF and/or urine LAM ELISA in sputum scarce <i>m.tb</i> culture positive patients.

<p>6 patients were both urine MTB/RIF and LAM ELISA positive; 6 patients were urine LAM ELISA positive, but MTB/RIF negative, while 2 patients were urine MTB/RIF positive, LAM ELISA negative.</p

Diagnostic accuracy of sputum smear microscopy, urinary MTB/RIF, TB LAM ELISA, LAM strip test (grade 2 cut-point) and clinically relevant combinations thereof in any sputum/non-sputum <i>m.tb</i> culture positive patients overall, in sputum scarce patients only, and stratified by CD4 cell count^†.

#<p>Indicates p<0.05 for a comparison of the sensitivity between different tests (e.g. urine MTB/RIF vs. LAM strip test) or combinations thereof; specific p-value: ^#1p = 0.002; ^#2p = 0.003; ^#3p = 0.001; ^#4p = 0.01; ^#5p = 0.06; ^#6p = 0.02; ^#7p = 0.05; ^#8p = 0.02; ^#9p<0.001; ^#10p = 0.002; ^#11p = 0.03.</p>*<p>Indicates p<0.05 for a comparison of differences in sensitivity between CD4>200 and ≤200 groups for a specific test or combinations thereof; specific p-values: ^*1p = 0.04;^*2p<0.001; ^*3p = 0.009; ^*4p<0.001; ^*5p = 0.03; non-significant p-values not shown.</p>†<p>9 culture positive patients with no available CD4 cell count results.</p>§<p>Reference standard of culture was used which does not account for persons with culture-negative, clinical TB.</p

Associates of MTB/RIF positivity in HIV-infected <i>m.tb</i> culture positive patients stratified by smear status.

*<p>Glomerular filtration rate calculated using the modified Cochrane-Gault equation.</p

Patient flow diagram and diagnostic outcomes stratified by final diagnostic category.

<p>*128 patients had no chest X-ray data. ^†To be eligible for the study, patients needed to provide at least 2 sputum samples (spot or morning), both of which were used for concentrated fluorescent smear microscopy and liquid culture. When available, a paired second spot sputum sample was collected and archived. This was later used for Xpert MTB/RIF testing (n = 389). ^‡The TSOT.TB, QFT.GIT and the PPD ELISPOT tests were not all concurrently available throughout the duration of study and thus not all patients necessarily received a combination of all 3 IGRAs. The number of valid results for TSPOT.TB, QFT-GIT and PPD respectively were 457, 457, and 462, respectively. 9 TSPOT.TB indeterminate results and 52 indeterminate QFT-GIT results occurred and are excluded. Only patients with culture-confirmed TB were included in the main analysis for the comparison of IGRA-response with bacterial load.</p

Differences in IFN-γ responses between culture converters (positive-to-negative) and non-converters after 2 months of anti-TB treatment.

*<p>Per patient P-values are shown for each IGRA for comparisons between 0 and 2 months.</p

Demographic and clinical characteristics of patients stratified by culture status.

*<p>6 patients did not have a useable culture result (culture contaminated) and were excluded.</p>†<p>Performed if HIV-infected. Excludes 8 patients with no CD4 count data.</p

IFN-γ responses measured using the TSPOT.TB, QFT-GIT and PPD ELISPOT assays and correlated with liquid culture time-to-positivity, smear status and grade, and Xpert MTB/RIF-generated C_T values in individuals with culture-confirmed TB.

<p>Culture, smear-microscopy and the Xpert MTB/RIF assay were performed on a paired sputum sample collected at diagnosis. P-values and Spearman’s rank correlation coefficient (<i>r_S</i>) are shown where appropriate. Abbreviations: SFC, spot-forming colonies; IFN-γ, interferon–γ; QFT-GIT, QuantiFERON TB Gold-in-tube; ELISPOT, enzyme-linked immunosorbent spot; PBMCs, peripheral blood mononuclear cells; IU, international units; TTP, time-to-positivity; C_T, cycle threshold.</p

Longitudinal IFN-γ responses are shown for patients undergoing anti-TB treatment at 2 months (n = 35) and 6 months (n = 13).

<p>Capped horizontal bars represent the median IFN-γ response at each time-point.</p