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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0007">Introduction</span><p id="para0005" class="elsevierStylePara elsevierViewall">Tuberculosis &#40;TB&#41;&#44; the world&#39;s leading cause of death due to a single infectious agent&#44; <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span>&#44; is one of the top-ten causes of preventable death globally&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> The World Health Organization &#40;WHO&#41; estimates that in 2019 alone&#44; around 10 million people suffered from TB and 1&#46;4 million people died from the disease&#44;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> with one-third of humans having <span class="elsevierStyleItalic">M&#46; tuberculosis</span> infection<span class="elsevierStyleItalic">&#46;</span><a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a></p><p id="para0006" class="elsevierStylePara elsevierViewall">Diagnosis and treatment of TB infection are core conceptual elements of the TB elimination strategy&#44;<a class="elsevierStyleCrossRefs" href="#bib0003"><span class="elsevierStyleSup">3-6</span></a> as reflected in WHO&#39;s emphasis on TB prevention in its End TB Strategy&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a></p><p id="para0007" class="elsevierStylePara elsevierViewall">Few tests are available to detect TB infection&#46; The century-old tuberculin skin test &#40;TST&#41; is based on delayed type hypersensitivity reaction in the skin upon intradermal injection of purified protein derivative &#40;PPD&#41; from mycobacterial culture&#46; Although TST is still widely utilized&#44; it has several limitations<a class="elsevierStyleCrossRefs" href="#bib0007"><span class="elsevierStyleSup">7-12</span></a> that interferon-&#947; &#40;IFN-&#947;&#41; release assays &#40;IGRAs&#41; have been developed to overcome&#46;<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> IGRAs are <span class="elsevierStyleItalic">in vitro</span> blood assays that measure the levels of IFN-&#947; released by T lymphocytes stimulated with antigenic peptides of <span class="elsevierStyleItalic">M&#46; tuberculosis&#46;</span><a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0012"><span class="elsevierStyleSup">12-17</span></a> Two WHO-endorsed IGRAs are commonly used to detect TB infection&#58; T-SPOT&#174;&#46;<span class="elsevierStyleItalic">TB</span> &#40;Oxford Immunotec&#44; Abingdon&#44; UK&#41; and QuantiFERON&#174;-TB Gold Plus &#40;QFT-Plus&#44; QIAGEN&#44; Hilden&#44; Germany&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0018"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> The QFT-Plus assay&#44; the fourth generation of QuantiFERON&#174;-TB&#44; is designed to measure IFN-&#947; released by both CD4 and CD8 T cells&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a> To date&#44; both WHO-endorsed IGRA tests need quality laboratory support&#44; potentially limiting their use in peripheral and&#47;or limited resource settings&#46;</p><p id="para0008" class="elsevierStylePara elsevierViewall">Lateral flow immunoassays &#40;LFAs&#41; are portable&#44; easy to use outside specialized laboratory environments&#44; and provide a quick readout&#44; making them ideal point-of-care &#40;POC&#41; tests&#46;<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a> QIAGEN has recently developed a new diagnostic test for TB infection&#44; the QIAreach<span class="elsevierStyleBold"><span class="elsevierStyleSup">TM</span></span> QuantiFERON-TB &#40;QIAreach QFT&#41; assay&#46; This novel digital fluorescence LFA uses nanoparticle technology to measure the levels of IFN-&#947; in plasma released from both CD4 and CD8 T cells&#44; thus eliminating the need for enzyme-linked immunosorbent assay &#40;ELISA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a> QIAreach QFT&#44; which uses the same test tube as the TB2 tube of QFT-Plus&#44; is an easy-to-use rapid test requiring less instrumentation and blood volume than QFT-Plus&#46; Key characteristics of the QIAreach QFT assay compared to QFT Plus are presented in <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia><p id="para0009" class="elsevierStylePara elsevierViewall">No previous study has compared the new QIAreach QFT test against the established &#40;FDA-approved and CE-marked&#41; QFT-Plus test in detecting TB infection&#46; Furthermore&#44; the potential role of QIAreach QFT as a diagnostic test for TB infection has never before been evaluated&#46;</p><p id="para0010" class="elsevierStylePara elsevierViewall">The aims of this study were to 1&#41; compare the QIAreach QFT and QFT-Plus tests to detect TB infection&#59; 2&#41; evaluate the clinical performance of QIAreach QFT for detection of TB infection by analyzing plasma samples from patients with active TB disease and healthy or low-TB-risk individuals in a clinical setting&#59; and 3&#41; conduct a preliminary evaluation of the QIAreach QFT test in immunocompromised individuals&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0008">Material and methods</span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">Study subjects</span><p id="para0011" class="elsevierStylePara elsevierViewall">This study was conducted at the Nagasaki Genbaku Isahaya Hospital&#44; a Nagasaki Prefecture-designated TB hospital in Japan&#46; Plasma samples were collected from consenting individuals with active TB &#40;September 2019-October 2020&#41; and from healthy low-TB-risk individuals &#40;August-October 2020&#41;&#46; The research protocols for this study were approved by the Institutional Review Board of the Nagasaki Genbaku Isahaya Hospital &#40;approval IRB no&#46;138&#41;&#46; Written informed consent was obtained from all recruited subjects&#46;</p><p id="para0012" class="elsevierStylePara elsevierViewall">Clinical and demographic data collected from patients included age&#44; gender as well as key white blood cell count parameters &#40;<a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a>&#41;&#46; Adult patients aged &#8805;20 years with active pulmonary TB were included in the study if they presented signs and symptoms compatible with TB&#44; imaging &#40;chest radiography and high-resolution computed tomography&#41; compatible with the disease&#44; and met one or both of the following criteria&#58; 1&#41; sputum-culture positive for <span class="elsevierStyleItalic">M&#46; tuberculosis</span> and&#47;or 2&#41; TB nucleic acid amplification test-positive specimens tested using polymerase chain reaction or loop-mediated isothermal amplification&#46; Study participants with active TB either had not been treated for TB or had received anti-TB drugs for a maximum 14 days&#46; Healthy low-TB-risk study participants were 1&#41; adults aged 20-65 years&#44; 2&#41; had never taken any anti-TB medication&#44; 3&#41; had no history of contact or exposure to TB&#44; 4&#41; had not lived or stayed in an area or country with a TB incidence rate of &#62;50&#47;100&#44;000 for &#62;1 month&#44; 5&#41; had no immunodeficiencies such as human immunodeficiency virus infection&#44; malignancy&#44; diabetes mellitus&#44; and treatment with steroids or immunosuppressant drugs&#46;</p><elsevierMultimedia ident="tbl0002"></elsevierMultimedia><p id="para0013" class="elsevierStylePara elsevierViewall">CD4 and CD8 T-cells in participants&#8217; peripheral blood were quantified using flow cytometry as a part of their routine diagnostic management&#46; Assays were performed on CELL-DYN Sapphire Hematology Analyzer &#40;Abbott Co&#46;&#44; USA&#41; using proprietary CD3&#47;4&#47;8 monoclonal antibody panels with automated gating&#46;</p></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">QFT-Plus assay</span><p id="para0014" class="elsevierStylePara elsevierViewall">For QFT-Plus test&#44; 4&#160;mL of whole blood was taken from all study participants directly into QFT-Plus blood collection tubes&#46; After centrifugation&#44; plasma specimens were harvested and stored at -30&#176;C for later analysis as per manufacturer&#39;s guidelines &#40;QIAGEN GmbH&#44; Hilden&#44; Germany&#41;&#46; The results of the QFT-Plus test&#44; given as a measurement of IFN-&#947;&#44; were expressed as IU&#47;mL&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011">QIAreach QFT assay</span><p id="para0015" class="elsevierStylePara elsevierViewall">One mL of whole blood was taken from all study participants directly into the QIAreach QFT blood collection tube &#40;equivalent to the TB2 tube of the QFT-Plus&#41;&#46; Upon centrifugation as per manufacturer&#39;s guidelines&#44; plasma was transferred to a microtiter tube and kept frozen at -30&#176;C until testing&#46; Upon thawing the specimens&#44; plasma specimens were centrifuged again at 3000&#160;&#215;&#160;<span class="elsevierStyleItalic">g</span> for 15&#160;min and tested according to the manufacturer&#39;s instructions&#46;</p><p id="para0016" class="elsevierStylePara elsevierViewall">Prior to starting the assay&#44; QIAreach-Software-x64-1&#46;1&#46;12&#46;0 was installed on a computer running the Microsoft Windows operating system&#46; A charged eHub&#44; connected to the computer via USB cable&#44; was powered on and the eStick was inserted into the eHub&#39;s port&#46; Once connected and turned on&#44; both the eHub and the computer software reported that the eHub was in ready mode&#46; A total of 150 &#181;L of diluent buffer was added to the processing tube&#46; Next&#44; 150 &#181;L of plasma specimen was transferred into the same processing tube&#46; The resulting solution was mixed by pipetting up and down at least four times&#46; A total of 150 &#181;L of this mixture was aliquoted from the processing tube into the sample port of the inserted eStick&#46; The assay began automatically&#44; with the status displayed on both the eHub and the computer upon sensing the mixture&#46; Upon assay completion&#44; the test result &#40;&#43; or -&#41; and time to result &#40;TTR&#41; were indicated on both the eHub and the software&#46;</p></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0012">Statistical analysis</span><p id="para0017" class="elsevierStylePara elsevierViewall">Data were statistically analyzed using the IBM&#174; SPSS&#174; Statistics V27 for Windows &#40;IBM Corp&#46;&#44; USA&#41; and presented as No &#40;&#37;&#41; or median &#40;interquartile range&#41; unless otherwise specified&#46; Sensitivity &#40;positive rate&#41;&#44; specificity &#40;negative rate&#41; and overall concordance &#40;proportion of true results overall&#41; of QIAreach QFT were calculated using QFT-Plus as a reference standard&#46; Culture-positive patients were considered the gold standard when evaluating the sensitivity of QIAreach as a tool for detecting TB infection&#46; A sub-analysis was also conducted on samples from immunocompromised patients &#40;CD4 cell counts &#60;200&#47;&#181;L&#41;&#46; A Mann-Whitney U test is performed for differences of CD4 or CD8 cell counts in the peripheral blood between active TB and healthy low-TB-risk individuals&#46; Linear regression analysis was performed to examine the relationship between the TTR &#40;second&#41; and the IFN-&#947; levels &#40;IU&#47;mL&#41;&#46; A p-value of less than 0&#46;05 was considered statistically significant&#46;</p></span></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0013">Results</span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0014">Characteristics of study participants</span><p id="para0018" class="elsevierStylePara elsevierViewall">Clinical information about the study subjects is shown in <a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a>&#46; The 41 study participants with active pulmonary TB were median aged 82 years &#40;interquartile range&#44; 76&#46;0-89&#46;0&#41; with median CD4 count&#58; 384 cells&#47;&#956;L &#40;interquartile range&#44; 256-529&#41; and median CD8 count&#58; 222 cells &#47;&#956;L &#40;interquartile range&#44; 148&#46;5-343&#46;5&#41;&#46; Both the CD4 and CD8 cell counts of active TB patients were significantly lower than those of the healthy individuals &#40;<span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001 for both comparisons&#41;&#46; Of the 41 patients recruited&#44; 7 were classified as immunocompromised&#59; differences in cell counts between active TB patients and controls maintained with removal of 7 immunocompromised patients&#46;</p></span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0015">Sensitivity&#44; specificity and concordance of QIAreach QFT TB compared with QFT-Plus</span><p id="para0019" class="elsevierStylePara elsevierViewall">Plasma samples from 41 active TB patients and 42 healthy or low-TB-risk individuals were tested&#46; The QIAreach QFT and QFT-Plus ELISA tests were simultaneously conducted on the same samples&#46; Test results are shown in <a class="elsevierStyleCrossRef" href="#tbl0003">Table 3</a>&#46;</p><elsevierMultimedia ident="tbl0003"></elsevierMultimedia><p id="para0020" class="elsevierStylePara elsevierViewall">Using the QIAreach QFT assay&#44; 100&#37; sensitivity and 97&#46;6&#37; specificity &#40;95&#37;CI&#58; 92-100&#37; and 88-99&#37;&#44; respectively&#41; were achieved&#44; with overall concordance of 98&#46;8&#37; &#40;95&#37;CI&#58; 94-100&#37; and kappa coefficient&#160;&#61;&#160;0&#46;976&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0003">Table 3</a>&#41;&#46; Six specimens had uncorrected TB2 tube values without Nil subtraction below 1 IU&#47;ml &#40;ranging from 0&#46;46 to 0&#46;77&#41; on QFT-Plus and all tested positive on QIAreach QFT &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;1</a> A&#41;&#46; All specimens tested negative on QIAreach had TB1-Nil and TB2-Nil values below 0&#46;2 on QFT-Plus&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0016">Evaluation of the sensitivity of the QIAreach QFT assay for active TB</span><p id="para0021" class="elsevierStylePara elsevierViewall">Sensitivity of QIAreach QFT for detection of active TB was also 100&#37;&#46; Our assessment of this cohort of plasma samples revealed a single false-positive result from a healthy individual&#46; This false-positive result case had normal CD4 and CD8 cell counts in blood&#59; CD4&#58; 1740&#47;&#956;L and CD8&#58; 711&#47;&#956;L&#46; TB1-Nil and TB2-Nil values measured by QFT-Plus were 0&#46;01 IU&#47;ml and 0&#46;00 IU&#47;ml&#44; respectively&#44; and TTR was 1200 s&#46; In the active TB group&#44; 7 participants aged 70-95 years &#40;median age&#58; 86 years&#41; were immunocompromised &#40;CD4 &#60;200&#47;&#956;L&#41; and tested positive by QIAreach QFT&#46;</p></span></span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0017">Relationship between IFN-&#947; level of positive sample and time to result</span><p id="para0022" class="elsevierStylePara elsevierViewall">The TTR was examined for all QIAreach QFT-positive results&#44; because TTR is related to the level of fluorescent signal generated in the test&#46; The TTR for QIAreach QFT- positive samples varied from 215-1200 seconds &#40;20&#160;min&#41;&#46;</p><p id="para0023" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;1</a> shows the distribution plot of plasma IFN-&#947; concentrations in IU&#47;ml &#40;presented as uncorrected TB2 values without Nil subtraction&#41; versus TTR for positive samples demonstrating negative correlation between TTR and IFN-&#947; in TB2 tube&#46; Data transformation of TTR and IFN-&#947; to a natural logarithmic scale showed high correlation &#40;<span class="elsevierStyleItalic">r</span>&#160;&#61;&#160;-0&#46;913&#44; <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#41; between IFN-&#947; levels and TTR when linear regression analysis was performed &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;3</a>&#41;&#46;</p><p id="para0024" class="elsevierStylePara elsevierViewall">Six samples testing positive on QFT-Plus had IFN-&#947; levels &#40;uncorrected and corrected TB2 values&#41; &#62;10 IU&#47;mL &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;1</a> B and <a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;2</a>&#46;B&#41;&#46; The TTR for these positive plasma samples&#44; taken from patients aged 71-95 years &#40;median age&#58; 82 years&#41;&#44; ranged from 215-305 seconds &#40;median&#58; 245 seconds&#41;&#46; The range of the CD4 cell counts for these samples was between 138 and 1270 cells&#47;&#181;L &#40;median&#58; 529 cells&#47;&#181;L&#41;&#44; and the CD8 cell counts ranged from 75-1230 cells&#47;&#181;L &#40;median&#58; 312 cells&#47;&#181;L&#41;&#46; In comparison&#44; six samples from patients aged 73-92 years &#40;median age&#58; 90 years&#41; that tested positive on QIAreach QFT&#44; with a TTR of 1200 seconds each&#44; had IFN-&#947; levels on QFT-Plus &#40;uncorrected TB2 values&#41; ranging between 0&#46;46 and 0&#46;77 IU&#47;mL &#40;median&#58; 0&#46;75 IU&#47;mL&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;1</a> A&#41;&#46; Also&#44; these 6 samples had IFN-&#947; levels on QFT-Plus &#40;corrected TB2 values&#41; ranging between 0&#46;36 and 0&#46;68 IU&#47;mL &#40;median&#58; 0&#46;555 IU&#47;mL&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;2</a> A&#41; showed positive results by QIAreach QFT&#46; The distribution plot and correlation analysis using plasma IFN-&#947; values &#40;corrected TB2 values&#41; versus TTR for positive samples showed similar results &#40;<span class="elsevierStyleItalic">r</span>&#160;&#61;&#160;-0&#46;918&#44; <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;2</a> and <a class="elsevierStyleCrossRef" href="#fig0001">1&#46;4</a>&#41;&#46;</p><p id="para0025" class="elsevierStylePara elsevierViewall">The ranges of their CD4 and CD8 cell counts in blood were between 101 and 284 cells&#47;&#181;L &#40;median&#58; 209 cells&#47;&#181;L&#41; and between 66 and 185 cells&#47;&#181;L &#40;median&#58; 115 cells&#47;&#181;L&#41;&#44; respectively&#46; Within this group of plasma samples&#44; three came from immunocompromised patients&#44; each with CD4 T-lymphocyte counts &#60;200 cells&#47;&#181;L&#46;</p></span></span><span id="sec0012" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0018">Discussion</span><p id="para0026" class="elsevierStylePara elsevierViewall">This is the first evaluation of a new diagnostic test&#44; QIAreach QFT&#44; in detecting TB infection compared with the QFT-Plus assay and as a screening tool for TB infection&#46;</p><p id="para0027" class="elsevierStylePara elsevierViewall">This new IGRA test is based on digital fluorescence LFA with nanoparticle technology&#46; Similar to the QFT-Plus assay&#44; it measures the levels of IFN-&#947; secreted from both CD4 and CD8 T lymphocytes in response to stimulation with <span class="elsevierStyleItalic">M&#46; tuberculosis</span>-specific antigens<span class="elsevierStyleItalic">&#44;</span> with advantages in use as point-of-care-test&#46;<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a></p><p id="para0028" class="elsevierStylePara elsevierViewall">The QIAreach QFT test exhibited high clinical performance&#58; 100&#37; sensitivity&#44; 97&#46;6&#37; specificity&#44; and 98&#46;8&#37; overall concordance using QFT-Plus as the reference standard&#46; Sensitivity for detection of active TB was also 100&#37;&#46; The specificity and sensitivity of the QIAreach QFT assay reported here are comparable to those previously reported for the QFT-Plus assay&#46; An assessment of the performance of the QFT-Plus assay among active TB patients and healthy individuals in Japan reported 96&#46;2&#37; sensitivity and 96&#46;7&#37; specificity&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a> According to a meta-analysis of 15 published reports&#44; the QFT-Plus assay had a pooled sensitivity of 94&#37; for active TB patients and a pooled specificity of 96&#37; for healthy individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0026"><span class="elsevierStyleSup">26</span></a> A multicenter investigation into the performance of QFT-Plus test at three U&#46;S&#46; sites and two Japanese sites found the test to have 93&#46;0&#37; sensitivity in adult TB patients&#46;<a class="elsevierStyleCrossRef" href="#bib0027"><span class="elsevierStyleSup">27</span></a></p><p id="para0029" class="elsevierStylePara elsevierViewall">Notably&#44; the values of the IFN-&#947; levels shown in <a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;1</a> and <a class="elsevierStyleCrossRef" href="#fig0001">1&#46;3</a> are the uncorrected and corrected values of TB2 tubes of the QFT-Plus assay for all the samples tested&#8212;i&#46;e&#46;&#44; the level of IFN-&#947; in each TB2 tube without and with subtracting the level of IFN-&#947; of the Nil tube &#40;background tube&#41;&#46; Our results demonstrated that the cut-off point of IFN-&#947; concentration for QIAreach QFT assay might be similar to that of the QFT-Plus assay &#40;0&#46;35 IU&#47;mL&#41;&#46; We did find a statistically significant relationship between levels of uncorrected and corrected IFN-&#947; in plasma of active TB patients and TTR &#40;natural logarithms conversion of each&#41; with a linear regression analysis &#40;<span class="elsevierStyleItalic">r</span>&#160;&#61;&#160;-0&#46;913&#44; <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001 and <span class="elsevierStyleItalic">r</span>&#160;&#61;&#160;-0&#46;918&#44; <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#44; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;3</a> and <a class="elsevierStyleCrossRef" href="#fig0001">1&#46;4</a>&#41;&#46; This study&#39;s results suggest that the higher the IFN-&#947; level of the sample&#44; the shorter the TTR&#44; which could be used as a surrogate marker of IFN-&#947; concentration in plasma when using QIAreach QFT assay&#46; Like QFT-Plus&#44; however&#44; QIAreach QFT may have variations in measured IFN-&#947; values near the cutoff &#40;i&#46;e&#46;&#44; 0&#46;2 - 0&#46;7 IU&#47;mL&#41;&#44; so there is a relatively high possibility of false negatives and&#47;or false positives for the QIAreach QFT results with a TTR close to 1200 seconds&#46;</p><p id="para0030" class="elsevierStylePara elsevierViewall">Seven cases in the active TB group who were immunocompromised &#40;CD4 &#60;200&#47;&#956;L&#41; returned positive results on QIAreach QFT&#44; suggesting this assay could be considered a promising digital fluorescence LFA for detecting TB infection among immunocompromised patients&#46; Larger studies on representative cohorts are needed to confirm its performance in those immunocompromised&#46;</p><p id="para0031" class="elsevierStylePara elsevierViewall">Our assessment of this cohort of plasma samples revealed a single false positive from a healthy individual&#46; This was a sole sample with a high triglyceride level &#40;1588 mg&#47;dL&#41; and was turbid following the freeze and thaw processes&#46; Testing on this individual was repeated by obtaining a new sample exhibiting a high triglyceride level &#40;1288 mg&#47;dL&#41; that was not subjected to freeze and thaw processes&#46; A negative result was obtained&#46; Various factors&#44; such as sample viscosity&#44; may have affected the development speed of the sample solution on the nitrocellulose membrane of the LFA system&#46; Of note&#44; the false-positive results of QIAreach QFT assay could be caused by milky plasma as well as autoimmune disease&#46;<a class="elsevierStyleCrossRef" href="#bib0028"><span class="elsevierStyleSup">28</span></a></p><p id="para0032" class="elsevierStylePara elsevierViewall">The QIAreach QFT assay offers a number of workflow advantages over more complex laboratory-based assays&#44; such as QFT-Plus &#40;<a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#41;&#46; The QIAreach QFT assay is objective&#8212;reporting test results as either positive or negative&#8212;and it requires only 1&#160;mL of blood from each patient&#44; compared with 4&#160;mL of blood required for the QFT-Plus assay&#46; In addition&#44; the QIAreach QFT test results can be obtained within a relatively short time of up to approximately 20&#160;min for each specimen analyzed&#46; In contrast&#44; the QFT-Plus test based on ELISA requires at least 150&#160;min to obtain a readout&#46; Moreover&#44; the QIAreach system can be used for a single test or up to eight tests at a time for each eHub being used&#46; The QIAreach QFT testing system and hardware can be used anywhere&#44; like the QIAreach anti-SARS-CoV-2 total test&#46;<a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a> Implementing the QIAreach QFT testing system does not require any specialized instruments &#40;e&#46;g&#46;&#44; an automated ELISA workstation&#41;&#44; trained laboratory officers to perform ELISA or a dedicated laboratory space&#59; importantly eHub is battery operated allowing its use in remote areas with limited electricity supply&#46; These features make the QIAreach QFT a suitable and highly attractive test to detect TB infection in decentralized settings&#46;</p><p id="para0033" class="elsevierStylePara elsevierViewall">A TB diagnostic test with these characteristics is of particular value for screening efforts in countries with high TB prevalence&#46;<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a> In 2019&#44; TB cases in countries in Southeast Asia and Africa accounted for 69&#37; of the total TB cases worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> However&#44; these settings often lack the resources for maintenance and calibration&#44; the infrastructure for complex instrumentation&#44; and the specialized laboratory staff needed for older laboratory-based assays&#46; Many of these low-resource settings that need TB infection screening are outside of major urban centers&#46; The QIAreach QFT test will also be useful for TB infection screening among special groups&#44; including&#8212;among others&#8212;immigrants&#44;<a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> inmates&#44;<a class="elsevierStyleCrossRef" href="#bib0029"><span class="elsevierStyleSup">29</span></a> and children&#46;</p><p id="para0034" class="elsevierStylePara elsevierViewall">The study has clear limitations&#44; including the fact it was conducted in a single center and on a convenience sample &#40;i&#46;e&#46;&#44; being a preliminary study&#44; no sample size calculation was performed&#41;&#44; thus requiring larger studies to confirm the findings&#46;</p></span><span id="sec0013" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0019">Conclusions</span><p id="para0035" class="elsevierStylePara elsevierViewall">In terms of clinical performance&#44; the QIAreach QFT assay displayed 100&#37; sensitivity&#44; 97&#46;6&#37; specificity&#44; and 98&#46;8&#37; overall concordance compared with the QFT-Plus test&#46; This assay is objective&#44; quicker to perform than QFT-Plus&#44; and requires only a small amount of blood &#40;1&#160;mL&#41; per test&#46; The test offers flexibility in that it can be easily performed anywhere and is not restricted to a laboratory environment&#46; This novel assay can be useful in screening for TB infection in high-TB-burden&#44; low-resource countries and&#44; also&#44; for screening of immunocompromised patients&#46; Larger studies are necessary to confirm these preliminary findings&#46;</p></span><span id="sec0014" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0020">Authors&#8217; contributions</span><p id="para0036" class="elsevierStylePara elsevierViewall">Authors&#8217; contributions were as follows&#58; study conception and design &#40;FK&#44; KT&#41;&#44; acquisition of data &#40;FK&#44; AK&#44; KA&#44; KT&#41;&#44; and analysis and interpretation of data &#40;FK&#44; KT&#44; SN&#44; MH&#41;&#46; All authors have contributed substantially to drafting and revising the article critically for important intellectual content&#46; All authors approved the submitted version of the article&#46; K&#46; Fukushima&#58; Conceptualization&#44; Data curation&#44; Formal analysis&#44; Investigation&#44; Methodology&#44; Validation&#44; Visualization&#44; Writing - original draft&#44; Writing - review &#38; editing&#46; K&#46; Akagi&#58; Data curation&#44; Writing - original draft&#44; Writing - review &#38; editing&#46; A&#46; Kondo&#58; Data curation&#44; Writing - original draft&#44; Writing - review &#38; editing&#46; T&#46; Kubo&#58; Data curation&#44; Formal analysis&#44; Investigation&#44; Methodology&#44; Writing - original draft&#44; Writing - review &#38; editing&#46; N&#46; Sakamoto&#58; Formal analysis&#44; Investigation&#44; Writing - original draft&#44; Writing - review &#38; editing&#46; H&#46; Mukae&#58; Formal analysis&#44; Investigation&#44; Supervision&#44; Validation&#44; Visualization&#44; Writing - original draft&#44; Writing - review &#38; editing&#46; All authors approved the submitted version of the article&#46;</p></span></span>"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Objective</span><p id="spara014" class="elsevierStyleSimplePara elsevierViewall">1&#41; to compare the QIAreach<span class="elsevierStyleBold"><span class="elsevierStyleSup">TM</span></span> QuantiFERON-TB &#40;QIAreach QFT&#41; vs&#46; QuantiFERON&#174;-TB Gold Plus assay &#40;QFT-Plus&#41; to detect tuberculosis &#40;TB&#41; infection&#59; 2&#41; to evaluate diagnostic sensitivity of QIAreach QFT using active TB as surrogate for TB infection&#59; 3&#41; to preliminarily evaluate QIAreach QFT in immunocompromised individuals&#46;</p></span> <span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Methods</span><p id="spara015" class="elsevierStyleSimplePara elsevierViewall">QIAreach QFT measures the level of interferon-&#947; &#40;IFN-&#947;&#41; in plasma specimens from blood stimulated by ESAT-6 and CFP-10 peptides in one blood collection tube &#40;equivalent to the TB2 tube of the QFT-Plus&#41;&#46; QIAreach QFT was applied to plasma samples from 41 patients with pulmonary TB and from 42 healthy or low-TB-risk individuals&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Results</span><p id="spara016" class="elsevierStyleSimplePara elsevierViewall">Sensitivity and specificity of QIAreach QFT vs&#46; QFT-Plus were 100&#37; &#40;41&#47;41&#41; and 97&#46;6&#37; &#40;41&#47;42&#41;&#44; respectively&#59; overall concordance was 98&#46;8&#37; &#40;82&#47;83&#41;&#46; All samples were measured within 20&#160;min&#46; The time to result of each sample was significantly correlated with IFN-&#947; level with a natural logarithmic scale &#40;<span class="elsevierStyleItalic">r</span>&#160;&#61;&#160;-0&#46;913&#44; <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#41;&#46; Seven cases in the active TB group were immunocompromised &#40;CD4 &#60;200&#47;&#956;L&#41; and tested positive by QIAreach QFT&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Conclusions</span><p id="spara017" class="elsevierStyleSimplePara elsevierViewall">QIAreach QFT provides an objective readout with a minimum blood sample volume &#40;1&#160;mL&#47;subject&#41;&#44; potentially being a useful point-of-care screening test for TB infection in high-TB-burden&#44; low-resource countries and for immunocompromised patients&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abss0001"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abss0002"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abss0003"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abss0004"
            "titulo" => "Conclusions"
          ]
        ]
      ]
    ]
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      0 => array:8 [
        "identificador" => "fig0001"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0004"
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        "descripcion" => array:1 [
          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Distribution plot and correlation analysis using plasma IFN-&#947; values &#40;uncorrected and corrected TB2 values&#41; versus TTR for positive samples &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;41 active TB patients&#41;</p> <p id="spara002" class="elsevierStyleSimplePara elsevierViewall">1 &#8211; uncorrected values&#59; 2&#8211; corrected IFN-&#947; values&#59; 3&#8211; natural logarithm converted uncorrected values&#59; 4&#8211; natural logarithm converted corrected IFN-&#947; values</p> <p id="spara003" class="elsevierStyleSimplePara elsevierViewall">Fig&#46; 1&#46;1A&#58; Six samples with IFN-&#947; levels &#40;uncorrected TB2 values&#41; between 0&#46;46-0&#46;77 IU&#47;mL &#40;median&#58; 0&#46;75 IU&#47;mL&#41; and time to result of 1200 s&#46;</p> <p id="spara004" class="elsevierStyleSimplePara elsevierViewall">Fig&#46; 1&#46;2A Corrected TB2 values ranging between 0&#46;36 and 0&#46;68 IU&#47;mL &#40;median&#58; 0&#46;555 IU&#47;mL&#41;</p> <p id="spara005" class="elsevierStyleSimplePara elsevierViewall">Fig&#46; 1&#46;1B and 1&#46;2B&#58; Six samples with IFN-&#947; levels &#62;10 IU&#47;mL &#40;uncorrected and correctedTB2 values&#41; and time to result between 215-305 s &#40;median&#58; 245 s&#41;&#46; Data transformation of TTR and IFN-&#947; of uncorrected and corrected TB2 values to a natural logarithmic scale showed a significantly high correlation &#40;<span class="elsevierStyleItalic">r</span>&#160;&#61;&#160;-0&#46;913&#44; <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001 and <span class="elsevierStyleItalic">r</span>&#160;&#61;&#160;-0&#46;918&#44; <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#44; respectively&#41; between IFN-&#947; levels and TTR by linear regression analysis &#40;Fig&#46; 1&#46;3 and 1&#46;4&#41;&#46; Corrected IFN-&#947; &#40;Fig&#46; 1&#46;2&#41; means IFN-&#947; levels with Nil subtraction&#46; IFN-&#947;&#58; interferon-&#947;&#59; TB&#58; tuberculosis&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0001"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
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          "leyenda" => "<p id="spara007" class="elsevierStyleSimplePara elsevierViewall">ELISA&#58; enzyme-linked immunosorbent assay&#59; ESAT-6&#58; early secretory antigenic 6 kDa&#59; CFP-10&#58; culture filtrate protein 10&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">QIAreach QFT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0003"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">QFT-Plus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0004"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Volume of blood sample and tubes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0005"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#160;mL&#44; one tube&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0006"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">total 4&#160;mL&#44; four tubes &#40;Nil&#44; TB1&#44; TB2&#44; Mitogen&#44;1mL each&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0007"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Stimulation antigens&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0008"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ESAT-6&#160;&#43;&#160;CFP-10&#43; short peptide CFP-10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0009"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">TB1&#58; ESAT-6&#160;&#43;&#160;CPF-10TB2&#58; ESAT-6&#160;&#43;&#160;CPF10&#43;short peptide CFP-10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0010"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Incubation time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0011"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16-24 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16-24 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0013"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Principle of IFN-&#947; detection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Digital fluorescence lateral flow nanoparticle technology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Enzyme-linked immunoassay&#59; ELISA &#40;colorimetric&#41; system&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0016"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">IFN-&#947; measurement time and number of samples&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0017"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Max 20&#160;min&#47;test&#44; 8 tests&#47;eHub&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">At least 150&#160;min&#47;test44 samples&#47;kit&#44; 22 samples&#47;plate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0019"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Data management&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Laptop PC&#47;QIAreach software&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0021"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ELISA workstation&#47;QFT-Plus software&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0022"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Instruments for assay&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Incubator&#47;centrifuge &#40;not always necessary&#41;&#44; eHub&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Workstation &#40;plate washer&#47;plate reader&#41;&#47;incubator&#47;centrifuge&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0025"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Power supply&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">USB or 100 &#8764;240 volt&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">100 &#8764;240 volt&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0028"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Assay handling&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0029"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Easy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0031"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Cut-off value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">TB2 &#40;or TB1&#41;-Nil 0&#46;35IU&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara006" class="elsevierStyleSimplePara elsevierViewall">Comparison of QIAreach QFT and QFT-Plus&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0002"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0002"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spara010" class="elsevierStyleSimplePara elsevierViewall">Data are presented as No&#46; &#40;&#37;&#41;&#44; or median &#40;IQR&#41;&#46;</p><p id="spara011" class="elsevierStyleSimplePara elsevierViewall">TB&#58; tuberculosis&#59; IQR&#58; interquartile range&#59; CD4&#58; CD4&#43; T lymphocyte in blood&#59; CD8&#58; CD8&#43; T lymphocyte in blood&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0034"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0035"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Patients with active TB &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;41&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0036"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Healthy &#47; low-TB-risk individuals &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0037"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">p value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Age&#44; years&#59; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">82&#46;0 &#40;76&#46;0-89&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">39&#46;5 &#40;30&#46;75-47&#46;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0041"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0042"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Sex&#44; male&#59; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">27 &#40;65&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10 &#40;23&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0045"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0046"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Pulmonary TB&#59; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">41 &#40;100&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0050"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">White blood cell count&#47;&#956;L&#59; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4930 &#40;4395-6965&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5655 &#40;5340-7232&#46;5&#41;<a class="elsevierStyleCrossRef" href="#tb2fn1"><span class="elsevierStyleSup">&#8270;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">p&#61;0&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0054"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Lymphocyte count&#47;&#956;L&#59; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1170 &#40;930-1610&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">2105 &#40;1662&#46;5-2412&#46;5&#41;<a class="elsevierStyleCrossRef" href="#tb2fn1"><span class="elsevierStyleSup">&#8270;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">384 &#40;256-529&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">CD8 cell count&#47;&#956;L&#59; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">222 &#40;148&#46;5-343&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">0&nbsp;\t\t\t\t\t\t\n
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                          "etal" => false
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                            0 => "J&#46;T&#46; Denholm"
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                            3 => "E&#46; Tabernero-Huguet"
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                            0 => "A&#46; Matteelli"
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                      "titulo" => "Interferon-gamma release assays"
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Original article
First clinical evaluation of the QIAreachTM QuantiFERON-TB for tuberculosis infection and active pulmonary disease
K. Fukushimaa,
Corresponding author
kiyofuku@isahaya.jrc.or.jp

Corresponding author at: Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, 986-2 Keya Tarami-cho Isahaya City, Nagasaki 859-0497, Japan.
, K. Akagia, A. Kondoa, T. Kubob, N. Sakamotoc, H. Mukaec
a Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, Nagasaki, Japan
b Department of Laboratory Medicine, Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, Nagasaki, Japan
c Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0007">Introduction</span><p id="para0005" class="elsevierStylePara elsevierViewall">Tuberculosis &#40;TB&#41;&#44; the world&#39;s leading cause of death due to a single infectious agent&#44; <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span>&#44; is one of the top-ten causes of preventable death globally&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> The World Health Organization &#40;WHO&#41; estimates that in 2019 alone&#44; around 10 million people suffered from TB and 1&#46;4 million people died from the disease&#44;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> with one-third of humans having <span class="elsevierStyleItalic">M&#46; tuberculosis</span> infection<span class="elsevierStyleItalic">&#46;</span><a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a></p><p id="para0006" class="elsevierStylePara elsevierViewall">Diagnosis and treatment of TB infection are core conceptual elements of the TB elimination strategy&#44;<a class="elsevierStyleCrossRefs" href="#bib0003"><span class="elsevierStyleSup">3-6</span></a> as reflected in WHO&#39;s emphasis on TB prevention in its End TB Strategy&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a></p><p id="para0007" class="elsevierStylePara elsevierViewall">Few tests are available to detect TB infection&#46; The century-old tuberculin skin test &#40;TST&#41; is based on delayed type hypersensitivity reaction in the skin upon intradermal injection of purified protein derivative &#40;PPD&#41; from mycobacterial culture&#46; Although TST is still widely utilized&#44; it has several limitations<a class="elsevierStyleCrossRefs" href="#bib0007"><span class="elsevierStyleSup">7-12</span></a> that interferon-&#947; &#40;IFN-&#947;&#41; release assays &#40;IGRAs&#41; have been developed to overcome&#46;<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> IGRAs are <span class="elsevierStyleItalic">in vitro</span> blood assays that measure the levels of IFN-&#947; released by T lymphocytes stimulated with antigenic peptides of <span class="elsevierStyleItalic">M&#46; tuberculosis&#46;</span><a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0012"><span class="elsevierStyleSup">12-17</span></a> Two WHO-endorsed IGRAs are commonly used to detect TB infection&#58; T-SPOT&#174;&#46;<span class="elsevierStyleItalic">TB</span> &#40;Oxford Immunotec&#44; Abingdon&#44; UK&#41; and QuantiFERON&#174;-TB Gold Plus &#40;QFT-Plus&#44; QIAGEN&#44; Hilden&#44; Germany&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0018"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> The QFT-Plus assay&#44; the fourth generation of QuantiFERON&#174;-TB&#44; is designed to measure IFN-&#947; released by both CD4 and CD8 T cells&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a> To date&#44; both WHO-endorsed IGRA tests need quality laboratory support&#44; potentially limiting their use in peripheral and&#47;or limited resource settings&#46;</p><p id="para0008" class="elsevierStylePara elsevierViewall">Lateral flow immunoassays &#40;LFAs&#41; are portable&#44; easy to use outside specialized laboratory environments&#44; and provide a quick readout&#44; making them ideal point-of-care &#40;POC&#41; tests&#46;<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a> QIAGEN has recently developed a new diagnostic test for TB infection&#44; the QIAreach<span class="elsevierStyleBold"><span class="elsevierStyleSup">TM</span></span> QuantiFERON-TB &#40;QIAreach QFT&#41; assay&#46; This novel digital fluorescence LFA uses nanoparticle technology to measure the levels of IFN-&#947; in plasma released from both CD4 and CD8 T cells&#44; thus eliminating the need for enzyme-linked immunosorbent assay &#40;ELISA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a> QIAreach QFT&#44; which uses the same test tube as the TB2 tube of QFT-Plus&#44; is an easy-to-use rapid test requiring less instrumentation and blood volume than QFT-Plus&#46; Key characteristics of the QIAreach QFT assay compared to QFT Plus are presented in <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia><p id="para0009" class="elsevierStylePara elsevierViewall">No previous study has compared the new QIAreach QFT test against the established &#40;FDA-approved and CE-marked&#41; QFT-Plus test in detecting TB infection&#46; Furthermore&#44; the potential role of QIAreach QFT as a diagnostic test for TB infection has never before been evaluated&#46;</p><p id="para0010" class="elsevierStylePara elsevierViewall">The aims of this study were to 1&#41; compare the QIAreach QFT and QFT-Plus tests to detect TB infection&#59; 2&#41; evaluate the clinical performance of QIAreach QFT for detection of TB infection by analyzing plasma samples from patients with active TB disease and healthy or low-TB-risk individuals in a clinical setting&#59; and 3&#41; conduct a preliminary evaluation of the QIAreach QFT test in immunocompromised individuals&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0008">Material and methods</span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">Study subjects</span><p id="para0011" class="elsevierStylePara elsevierViewall">This study was conducted at the Nagasaki Genbaku Isahaya Hospital&#44; a Nagasaki Prefecture-designated TB hospital in Japan&#46; Plasma samples were collected from consenting individuals with active TB &#40;September 2019-October 2020&#41; and from healthy low-TB-risk individuals &#40;August-October 2020&#41;&#46; The research protocols for this study were approved by the Institutional Review Board of the Nagasaki Genbaku Isahaya Hospital &#40;approval IRB no&#46;138&#41;&#46; Written informed consent was obtained from all recruited subjects&#46;</p><p id="para0012" class="elsevierStylePara elsevierViewall">Clinical and demographic data collected from patients included age&#44; gender as well as key white blood cell count parameters &#40;<a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a>&#41;&#46; Adult patients aged &#8805;20 years with active pulmonary TB were included in the study if they presented signs and symptoms compatible with TB&#44; imaging &#40;chest radiography and high-resolution computed tomography&#41; compatible with the disease&#44; and met one or both of the following criteria&#58; 1&#41; sputum-culture positive for <span class="elsevierStyleItalic">M&#46; tuberculosis</span> and&#47;or 2&#41; TB nucleic acid amplification test-positive specimens tested using polymerase chain reaction or loop-mediated isothermal amplification&#46; Study participants with active TB either had not been treated for TB or had received anti-TB drugs for a maximum 14 days&#46; Healthy low-TB-risk study participants were 1&#41; adults aged 20-65 years&#44; 2&#41; had never taken any anti-TB medication&#44; 3&#41; had no history of contact or exposure to TB&#44; 4&#41; had not lived or stayed in an area or country with a TB incidence rate of &#62;50&#47;100&#44;000 for &#62;1 month&#44; 5&#41; had no immunodeficiencies such as human immunodeficiency virus infection&#44; malignancy&#44; diabetes mellitus&#44; and treatment with steroids or immunosuppressant drugs&#46;</p><elsevierMultimedia ident="tbl0002"></elsevierMultimedia><p id="para0013" class="elsevierStylePara elsevierViewall">CD4 and CD8 T-cells in participants&#8217; peripheral blood were quantified using flow cytometry as a part of their routine diagnostic management&#46; Assays were performed on CELL-DYN Sapphire Hematology Analyzer &#40;Abbott Co&#46;&#44; USA&#41; using proprietary CD3&#47;4&#47;8 monoclonal antibody panels with automated gating&#46;</p></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">QFT-Plus assay</span><p id="para0014" class="elsevierStylePara elsevierViewall">For QFT-Plus test&#44; 4&#160;mL of whole blood was taken from all study participants directly into QFT-Plus blood collection tubes&#46; After centrifugation&#44; plasma specimens were harvested and stored at -30&#176;C for later analysis as per manufacturer&#39;s guidelines &#40;QIAGEN GmbH&#44; Hilden&#44; Germany&#41;&#46; The results of the QFT-Plus test&#44; given as a measurement of IFN-&#947;&#44; were expressed as IU&#47;mL&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011">QIAreach QFT assay</span><p id="para0015" class="elsevierStylePara elsevierViewall">One mL of whole blood was taken from all study participants directly into the QIAreach QFT blood collection tube &#40;equivalent to the TB2 tube of the QFT-Plus&#41;&#46; Upon centrifugation as per manufacturer&#39;s guidelines&#44; plasma was transferred to a microtiter tube and kept frozen at -30&#176;C until testing&#46; Upon thawing the specimens&#44; plasma specimens were centrifuged again at 3000&#160;&#215;&#160;<span class="elsevierStyleItalic">g</span> for 15&#160;min and tested according to the manufacturer&#39;s instructions&#46;</p><p id="para0016" class="elsevierStylePara elsevierViewall">Prior to starting the assay&#44; QIAreach-Software-x64-1&#46;1&#46;12&#46;0 was installed on a computer running the Microsoft Windows operating system&#46; A charged eHub&#44; connected to the computer via USB cable&#44; was powered on and the eStick was inserted into the eHub&#39;s port&#46; Once connected and turned on&#44; both the eHub and the computer software reported that the eHub was in ready mode&#46; A total of 150 &#181;L of diluent buffer was added to the processing tube&#46; Next&#44; 150 &#181;L of plasma specimen was transferred into the same processing tube&#46; The resulting solution was mixed by pipetting up and down at least four times&#46; A total of 150 &#181;L of this mixture was aliquoted from the processing tube into the sample port of the inserted eStick&#46; The assay began automatically&#44; with the status displayed on both the eHub and the computer upon sensing the mixture&#46; Upon assay completion&#44; the test result &#40;&#43; or -&#41; and time to result &#40;TTR&#41; were indicated on both the eHub and the software&#46;</p></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0012">Statistical analysis</span><p id="para0017" class="elsevierStylePara elsevierViewall">Data were statistically analyzed using the IBM&#174; SPSS&#174; Statistics V27 for Windows &#40;IBM Corp&#46;&#44; USA&#41; and presented as No &#40;&#37;&#41; or median &#40;interquartile range&#41; unless otherwise specified&#46; Sensitivity &#40;positive rate&#41;&#44; specificity &#40;negative rate&#41; and overall concordance &#40;proportion of true results overall&#41; of QIAreach QFT were calculated using QFT-Plus as a reference standard&#46; Culture-positive patients were considered the gold standard when evaluating the sensitivity of QIAreach as a tool for detecting TB infection&#46; A sub-analysis was also conducted on samples from immunocompromised patients &#40;CD4 cell counts &#60;200&#47;&#181;L&#41;&#46; A Mann-Whitney U test is performed for differences of CD4 or CD8 cell counts in the peripheral blood between active TB and healthy low-TB-risk individuals&#46; Linear regression analysis was performed to examine the relationship between the TTR &#40;second&#41; and the IFN-&#947; levels &#40;IU&#47;mL&#41;&#46; A p-value of less than 0&#46;05 was considered statistically significant&#46;</p></span></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0013">Results</span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0014">Characteristics of study participants</span><p id="para0018" class="elsevierStylePara elsevierViewall">Clinical information about the study subjects is shown in <a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a>&#46; The 41 study participants with active pulmonary TB were median aged 82 years &#40;interquartile range&#44; 76&#46;0-89&#46;0&#41; with median CD4 count&#58; 384 cells&#47;&#956;L &#40;interquartile range&#44; 256-529&#41; and median CD8 count&#58; 222 cells &#47;&#956;L &#40;interquartile range&#44; 148&#46;5-343&#46;5&#41;&#46; Both the CD4 and CD8 cell counts of active TB patients were significantly lower than those of the healthy individuals &#40;<span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001 for both comparisons&#41;&#46; Of the 41 patients recruited&#44; 7 were classified as immunocompromised&#59; differences in cell counts between active TB patients and controls maintained with removal of 7 immunocompromised patients&#46;</p></span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0015">Sensitivity&#44; specificity and concordance of QIAreach QFT TB compared with QFT-Plus</span><p id="para0019" class="elsevierStylePara elsevierViewall">Plasma samples from 41 active TB patients and 42 healthy or low-TB-risk individuals were tested&#46; The QIAreach QFT and QFT-Plus ELISA tests were simultaneously conducted on the same samples&#46; Test results are shown in <a class="elsevierStyleCrossRef" href="#tbl0003">Table 3</a>&#46;</p><elsevierMultimedia ident="tbl0003"></elsevierMultimedia><p id="para0020" class="elsevierStylePara elsevierViewall">Using the QIAreach QFT assay&#44; 100&#37; sensitivity and 97&#46;6&#37; specificity &#40;95&#37;CI&#58; 92-100&#37; and 88-99&#37;&#44; respectively&#41; were achieved&#44; with overall concordance of 98&#46;8&#37; &#40;95&#37;CI&#58; 94-100&#37; and kappa coefficient&#160;&#61;&#160;0&#46;976&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0003">Table 3</a>&#41;&#46; Six specimens had uncorrected TB2 tube values without Nil subtraction below 1 IU&#47;ml &#40;ranging from 0&#46;46 to 0&#46;77&#41; on QFT-Plus and all tested positive on QIAreach QFT &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;1</a> A&#41;&#46; All specimens tested negative on QIAreach had TB1-Nil and TB2-Nil values below 0&#46;2 on QFT-Plus&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0016">Evaluation of the sensitivity of the QIAreach QFT assay for active TB</span><p id="para0021" class="elsevierStylePara elsevierViewall">Sensitivity of QIAreach QFT for detection of active TB was also 100&#37;&#46; Our assessment of this cohort of plasma samples revealed a single false-positive result from a healthy individual&#46; This false-positive result case had normal CD4 and CD8 cell counts in blood&#59; CD4&#58; 1740&#47;&#956;L and CD8&#58; 711&#47;&#956;L&#46; TB1-Nil and TB2-Nil values measured by QFT-Plus were 0&#46;01 IU&#47;ml and 0&#46;00 IU&#47;ml&#44; respectively&#44; and TTR was 1200 s&#46; In the active TB group&#44; 7 participants aged 70-95 years &#40;median age&#58; 86 years&#41; were immunocompromised &#40;CD4 &#60;200&#47;&#956;L&#41; and tested positive by QIAreach QFT&#46;</p></span></span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0017">Relationship between IFN-&#947; level of positive sample and time to result</span><p id="para0022" class="elsevierStylePara elsevierViewall">The TTR was examined for all QIAreach QFT-positive results&#44; because TTR is related to the level of fluorescent signal generated in the test&#46; The TTR for QIAreach QFT- positive samples varied from 215-1200 seconds &#40;20&#160;min&#41;&#46;</p><p id="para0023" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;1</a> shows the distribution plot of plasma IFN-&#947; concentrations in IU&#47;ml &#40;presented as uncorrected TB2 values without Nil subtraction&#41; versus TTR for positive samples demonstrating negative correlation between TTR and IFN-&#947; in TB2 tube&#46; Data transformation of TTR and IFN-&#947; to a natural logarithmic scale showed high correlation &#40;<span class="elsevierStyleItalic">r</span>&#160;&#61;&#160;-0&#46;913&#44; <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#41; between IFN-&#947; levels and TTR when linear regression analysis was performed &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;3</a>&#41;&#46;</p><p id="para0024" class="elsevierStylePara elsevierViewall">Six samples testing positive on QFT-Plus had IFN-&#947; levels &#40;uncorrected and corrected TB2 values&#41; &#62;10 IU&#47;mL &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;1</a> B and <a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;2</a>&#46;B&#41;&#46; The TTR for these positive plasma samples&#44; taken from patients aged 71-95 years &#40;median age&#58; 82 years&#41;&#44; ranged from 215-305 seconds &#40;median&#58; 245 seconds&#41;&#46; The range of the CD4 cell counts for these samples was between 138 and 1270 cells&#47;&#181;L &#40;median&#58; 529 cells&#47;&#181;L&#41;&#44; and the CD8 cell counts ranged from 75-1230 cells&#47;&#181;L &#40;median&#58; 312 cells&#47;&#181;L&#41;&#46; In comparison&#44; six samples from patients aged 73-92 years &#40;median age&#58; 90 years&#41; that tested positive on QIAreach QFT&#44; with a TTR of 1200 seconds each&#44; had IFN-&#947; levels on QFT-Plus &#40;uncorrected TB2 values&#41; ranging between 0&#46;46 and 0&#46;77 IU&#47;mL &#40;median&#58; 0&#46;75 IU&#47;mL&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;1</a> A&#41;&#46; Also&#44; these 6 samples had IFN-&#947; levels on QFT-Plus &#40;corrected TB2 values&#41; ranging between 0&#46;36 and 0&#46;68 IU&#47;mL &#40;median&#58; 0&#46;555 IU&#47;mL&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;2</a> A&#41; showed positive results by QIAreach QFT&#46; The distribution plot and correlation analysis using plasma IFN-&#947; values &#40;corrected TB2 values&#41; versus TTR for positive samples showed similar results &#40;<span class="elsevierStyleItalic">r</span>&#160;&#61;&#160;-0&#46;918&#44; <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;2</a> and <a class="elsevierStyleCrossRef" href="#fig0001">1&#46;4</a>&#41;&#46;</p><p id="para0025" class="elsevierStylePara elsevierViewall">The ranges of their CD4 and CD8 cell counts in blood were between 101 and 284 cells&#47;&#181;L &#40;median&#58; 209 cells&#47;&#181;L&#41; and between 66 and 185 cells&#47;&#181;L &#40;median&#58; 115 cells&#47;&#181;L&#41;&#44; respectively&#46; Within this group of plasma samples&#44; three came from immunocompromised patients&#44; each with CD4 T-lymphocyte counts &#60;200 cells&#47;&#181;L&#46;</p></span></span><span id="sec0012" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0018">Discussion</span><p id="para0026" class="elsevierStylePara elsevierViewall">This is the first evaluation of a new diagnostic test&#44; QIAreach QFT&#44; in detecting TB infection compared with the QFT-Plus assay and as a screening tool for TB infection&#46;</p><p id="para0027" class="elsevierStylePara elsevierViewall">This new IGRA test is based on digital fluorescence LFA with nanoparticle technology&#46; Similar to the QFT-Plus assay&#44; it measures the levels of IFN-&#947; secreted from both CD4 and CD8 T lymphocytes in response to stimulation with <span class="elsevierStyleItalic">M&#46; tuberculosis</span>-specific antigens<span class="elsevierStyleItalic">&#44;</span> with advantages in use as point-of-care-test&#46;<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a></p><p id="para0028" class="elsevierStylePara elsevierViewall">The QIAreach QFT test exhibited high clinical performance&#58; 100&#37; sensitivity&#44; 97&#46;6&#37; specificity&#44; and 98&#46;8&#37; overall concordance using QFT-Plus as the reference standard&#46; Sensitivity for detection of active TB was also 100&#37;&#46; The specificity and sensitivity of the QIAreach QFT assay reported here are comparable to those previously reported for the QFT-Plus assay&#46; An assessment of the performance of the QFT-Plus assay among active TB patients and healthy individuals in Japan reported 96&#46;2&#37; sensitivity and 96&#46;7&#37; specificity&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a> According to a meta-analysis of 15 published reports&#44; the QFT-Plus assay had a pooled sensitivity of 94&#37; for active TB patients and a pooled specificity of 96&#37; for healthy individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0026"><span class="elsevierStyleSup">26</span></a> A multicenter investigation into the performance of QFT-Plus test at three U&#46;S&#46; sites and two Japanese sites found the test to have 93&#46;0&#37; sensitivity in adult TB patients&#46;<a class="elsevierStyleCrossRef" href="#bib0027"><span class="elsevierStyleSup">27</span></a></p><p id="para0029" class="elsevierStylePara elsevierViewall">Notably&#44; the values of the IFN-&#947; levels shown in <a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;1</a> and <a class="elsevierStyleCrossRef" href="#fig0001">1&#46;3</a> are the uncorrected and corrected values of TB2 tubes of the QFT-Plus assay for all the samples tested&#8212;i&#46;e&#46;&#44; the level of IFN-&#947; in each TB2 tube without and with subtracting the level of IFN-&#947; of the Nil tube &#40;background tube&#41;&#46; Our results demonstrated that the cut-off point of IFN-&#947; concentration for QIAreach QFT assay might be similar to that of the QFT-Plus assay &#40;0&#46;35 IU&#47;mL&#41;&#46; We did find a statistically significant relationship between levels of uncorrected and corrected IFN-&#947; in plasma of active TB patients and TTR &#40;natural logarithms conversion of each&#41; with a linear regression analysis &#40;<span class="elsevierStyleItalic">r</span>&#160;&#61;&#160;-0&#46;913&#44; <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001 and <span class="elsevierStyleItalic">r</span>&#160;&#61;&#160;-0&#46;918&#44; <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#44; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1&#46;3</a> and <a class="elsevierStyleCrossRef" href="#fig0001">1&#46;4</a>&#41;&#46; This study&#39;s results suggest that the higher the IFN-&#947; level of the sample&#44; the shorter the TTR&#44; which could be used as a surrogate marker of IFN-&#947; concentration in plasma when using QIAreach QFT assay&#46; Like QFT-Plus&#44; however&#44; QIAreach QFT may have variations in measured IFN-&#947; values near the cutoff &#40;i&#46;e&#46;&#44; 0&#46;2 - 0&#46;7 IU&#47;mL&#41;&#44; so there is a relatively high possibility of false negatives and&#47;or false positives for the QIAreach QFT results with a TTR close to 1200 seconds&#46;</p><p id="para0030" class="elsevierStylePara elsevierViewall">Seven cases in the active TB group who were immunocompromised &#40;CD4 &#60;200&#47;&#956;L&#41; returned positive results on QIAreach QFT&#44; suggesting this assay could be considered a promising digital fluorescence LFA for detecting TB infection among immunocompromised patients&#46; Larger studies on representative cohorts are needed to confirm its performance in those immunocompromised&#46;</p><p id="para0031" class="elsevierStylePara elsevierViewall">Our assessment of this cohort of plasma samples revealed a single false positive from a healthy individual&#46; This was a sole sample with a high triglyceride level &#40;1588 mg&#47;dL&#41; and was turbid following the freeze and thaw processes&#46; Testing on this individual was repeated by obtaining a new sample exhibiting a high triglyceride level &#40;1288 mg&#47;dL&#41; that was not subjected to freeze and thaw processes&#46; A negative result was obtained&#46; Various factors&#44; such as sample viscosity&#44; may have affected the development speed of the sample solution on the nitrocellulose membrane of the LFA system&#46; Of note&#44; the false-positive results of QIAreach QFT assay could be caused by milky plasma as well as autoimmune disease&#46;<a class="elsevierStyleCrossRef" href="#bib0028"><span class="elsevierStyleSup">28</span></a></p><p id="para0032" class="elsevierStylePara elsevierViewall">The QIAreach QFT assay offers a number of workflow advantages over more complex laboratory-based assays&#44; such as QFT-Plus &#40;<a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#41;&#46; The QIAreach QFT assay is objective&#8212;reporting test results as either positive or negative&#8212;and it requires only 1&#160;mL of blood from each patient&#44; compared with 4&#160;mL of blood required for the QFT-Plus assay&#46; In addition&#44; the QIAreach QFT test results can be obtained within a relatively short time of up to approximately 20&#160;min for each specimen analyzed&#46; In contrast&#44; the QFT-Plus test based on ELISA requires at least 150&#160;min to obtain a readout&#46; Moreover&#44; the QIAreach system can be used for a single test or up to eight tests at a time for each eHub being used&#46; The QIAreach QFT testing system and hardware can be used anywhere&#44; like the QIAreach anti-SARS-CoV-2 total test&#46;<a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a> Implementing the QIAreach QFT testing system does not require any specialized instruments &#40;e&#46;g&#46;&#44; an automated ELISA workstation&#41;&#44; trained laboratory officers to perform ELISA or a dedicated laboratory space&#59; importantly eHub is battery operated allowing its use in remote areas with limited electricity supply&#46; These features make the QIAreach QFT a suitable and highly attractive test to detect TB infection in decentralized settings&#46;</p><p id="para0033" class="elsevierStylePara elsevierViewall">A TB diagnostic test with these characteristics is of particular value for screening efforts in countries with high TB prevalence&#46;<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a> In 2019&#44; TB cases in countries in Southeast Asia and Africa accounted for 69&#37; of the total TB cases worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> However&#44; these settings often lack the resources for maintenance and calibration&#44; the infrastructure for complex instrumentation&#44; and the specialized laboratory staff needed for older laboratory-based assays&#46; Many of these low-resource settings that need TB infection screening are outside of major urban centers&#46; The QIAreach QFT test will also be useful for TB infection screening among special groups&#44; including&#8212;among others&#8212;immigrants&#44;<a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> inmates&#44;<a class="elsevierStyleCrossRef" href="#bib0029"><span class="elsevierStyleSup">29</span></a> and children&#46;</p><p id="para0034" class="elsevierStylePara elsevierViewall">The study has clear limitations&#44; including the fact it was conducted in a single center and on a convenience sample &#40;i&#46;e&#46;&#44; being a preliminary study&#44; no sample size calculation was performed&#41;&#44; thus requiring larger studies to confirm the findings&#46;</p></span><span id="sec0013" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0019">Conclusions</span><p id="para0035" class="elsevierStylePara elsevierViewall">In terms of clinical performance&#44; the QIAreach QFT assay displayed 100&#37; sensitivity&#44; 97&#46;6&#37; specificity&#44; and 98&#46;8&#37; overall concordance compared with the QFT-Plus test&#46; This assay is objective&#44; quicker to perform than QFT-Plus&#44; and requires only a small amount of blood &#40;1&#160;mL&#41; per test&#46; The test offers flexibility in that it can be easily performed anywhere and is not restricted to a laboratory environment&#46; This novel assay can be useful in screening for TB infection in high-TB-burden&#44; low-resource countries and&#44; also&#44; for screening of immunocompromised patients&#46; Larger studies are necessary to confirm these preliminary findings&#46;</p></span><span id="sec0014" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0020">Authors&#8217; contributions</span><p id="para0036" class="elsevierStylePara elsevierViewall">Authors&#8217; contributions were as follows&#58; study conception and design &#40;FK&#44; KT&#41;&#44; acquisition of data &#40;FK&#44; AK&#44; KA&#44; KT&#41;&#44; and analysis and interpretation of data &#40;FK&#44; KT&#44; SN&#44; MH&#41;&#46; All authors have contributed substantially to drafting and revising the article critically for important intellectual content&#46; All authors approved the submitted version of the article&#46; K&#46; Fukushima&#58; Conceptualization&#44; Data curation&#44; Formal analysis&#44; Investigation&#44; Methodology&#44; Validation&#44; Visualization&#44; Writing - original draft&#44; Writing - review &#38; editing&#46; K&#46; Akagi&#58; Data curation&#44; Writing - original draft&#44; Writing - review &#38; editing&#46; A&#46; Kondo&#58; Data curation&#44; Writing - original draft&#44; Writing - review &#38; editing&#46; T&#46; Kubo&#58; Data curation&#44; Formal analysis&#44; Investigation&#44; Methodology&#44; Writing - original draft&#44; Writing - review &#38; editing&#46; N&#46; Sakamoto&#58; Formal analysis&#44; Investigation&#44; Writing - original draft&#44; Writing - review &#38; editing&#46; H&#46; Mukae&#58; Formal analysis&#44; Investigation&#44; Supervision&#44; Validation&#44; Visualization&#44; Writing - original draft&#44; Writing - review &#38; editing&#46; All authors approved the submitted version of the article&#46;</p></span></span>"
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          "titulo" => "Introduction"
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          "titulo" => "Material and methods"
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          "identificador" => "sec0007"
          "titulo" => "Results"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0008"
              "titulo" => "Characteristics of study participants"
            ]
            1 => array:3 [
              "identificador" => "sec0009"
              "titulo" => "Sensitivity&#44; specificity and concordance of QIAreach QFT TB compared with QFT-Plus"
              "secciones" => array:1 [
                0 => array:2 [
                  "identificador" => "sec0010"
                  "titulo" => "Evaluation of the sensitivity of the QIAreach QFT assay for active TB"
                ]
              ]
            ]
            2 => array:2 [
              "identificador" => "sec0011"
              "titulo" => "Relationship between IFN-&#947; level of positive sample and time to result"
            ]
          ]
        ]
        5 => array:2 [
          "identificador" => "sec0012"
          "titulo" => "Discussion"
        ]
        6 => array:2 [
          "identificador" => "sec0013"
          "titulo" => "Conclusions"
        ]
        7 => array:2 [
          "identificador" => "sec0014"
          "titulo" => "Authors&#8217; contributions"
        ]
        8 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2021-05-09"
    "fechaAceptado" => "2021-07-09"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1463684"
          "palabras" => array:5 [
            0 => "QIAreach<span class="elsevierStyleSup">TM</span> QuantiFERON-TB"
            1 => "QuantiFERON&#174;-TB Gold Plus"
            2 => "Active tuberculosis"
            3 => "CD4 T-lymphocyte"
            4 => "CD8 T-lymphocyte"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Objective</span><p id="spara014" class="elsevierStyleSimplePara elsevierViewall">1&#41; to compare the QIAreach<span class="elsevierStyleBold"><span class="elsevierStyleSup">TM</span></span> QuantiFERON-TB &#40;QIAreach QFT&#41; vs&#46; QuantiFERON&#174;-TB Gold Plus assay &#40;QFT-Plus&#41; to detect tuberculosis &#40;TB&#41; infection&#59; 2&#41; to evaluate diagnostic sensitivity of QIAreach QFT using active TB as surrogate for TB infection&#59; 3&#41; to preliminarily evaluate QIAreach QFT in immunocompromised individuals&#46;</p></span> <span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Methods</span><p id="spara015" class="elsevierStyleSimplePara elsevierViewall">QIAreach QFT measures the level of interferon-&#947; &#40;IFN-&#947;&#41; in plasma specimens from blood stimulated by ESAT-6 and CFP-10 peptides in one blood collection tube &#40;equivalent to the TB2 tube of the QFT-Plus&#41;&#46; QIAreach QFT was applied to plasma samples from 41 patients with pulmonary TB and from 42 healthy or low-TB-risk individuals&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Results</span><p id="spara016" class="elsevierStyleSimplePara elsevierViewall">Sensitivity and specificity of QIAreach QFT vs&#46; QFT-Plus were 100&#37; &#40;41&#47;41&#41; and 97&#46;6&#37; &#40;41&#47;42&#41;&#44; respectively&#59; overall concordance was 98&#46;8&#37; &#40;82&#47;83&#41;&#46; All samples were measured within 20&#160;min&#46; The time to result of each sample was significantly correlated with IFN-&#947; level with a natural logarithmic scale &#40;<span class="elsevierStyleItalic">r</span>&#160;&#61;&#160;-0&#46;913&#44; <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#41;&#46; Seven cases in the active TB group were immunocompromised &#40;CD4 &#60;200&#47;&#956;L&#41; and tested positive by QIAreach QFT&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Conclusions</span><p id="spara017" class="elsevierStyleSimplePara elsevierViewall">QIAreach QFT provides an objective readout with a minimum blood sample volume &#40;1&#160;mL&#47;subject&#41;&#44; potentially being a useful point-of-care screening test for TB infection in high-TB-burden&#44; low-resource countries and for immunocompromised patients&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abss0001"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abss0002"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abss0003"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abss0004"
            "titulo" => "Conclusions"
          ]
        ]
      ]
    ]
    "multimedia" => array:4 [
      0 => array:8 [
        "identificador" => "fig0001"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2497
            "Ancho" => 3333
            "Tamanyo" => 239638
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        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0004"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Distribution plot and correlation analysis using plasma IFN-&#947; values &#40;uncorrected and corrected TB2 values&#41; versus TTR for positive samples &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;41 active TB patients&#41;</p> <p id="spara002" class="elsevierStyleSimplePara elsevierViewall">1 &#8211; uncorrected values&#59; 2&#8211; corrected IFN-&#947; values&#59; 3&#8211; natural logarithm converted uncorrected values&#59; 4&#8211; natural logarithm converted corrected IFN-&#947; values</p> <p id="spara003" class="elsevierStyleSimplePara elsevierViewall">Fig&#46; 1&#46;1A&#58; Six samples with IFN-&#947; levels &#40;uncorrected TB2 values&#41; between 0&#46;46-0&#46;77 IU&#47;mL &#40;median&#58; 0&#46;75 IU&#47;mL&#41; and time to result of 1200 s&#46;</p> <p id="spara004" class="elsevierStyleSimplePara elsevierViewall">Fig&#46; 1&#46;2A Corrected TB2 values ranging between 0&#46;36 and 0&#46;68 IU&#47;mL &#40;median&#58; 0&#46;555 IU&#47;mL&#41;</p> <p id="spara005" class="elsevierStyleSimplePara elsevierViewall">Fig&#46; 1&#46;1B and 1&#46;2B&#58; Six samples with IFN-&#947; levels &#62;10 IU&#47;mL &#40;uncorrected and correctedTB2 values&#41; and time to result between 215-305 s &#40;median&#58; 245 s&#41;&#46; Data transformation of TTR and IFN-&#947; of uncorrected and corrected TB2 values to a natural logarithmic scale showed a significantly high correlation &#40;<span class="elsevierStyleItalic">r</span>&#160;&#61;&#160;-0&#46;913&#44; <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001 and <span class="elsevierStyleItalic">r</span>&#160;&#61;&#160;-0&#46;918&#44; <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#44; respectively&#41; between IFN-&#947; levels and TTR by linear regression analysis &#40;Fig&#46; 1&#46;3 and 1&#46;4&#41;&#46; Corrected IFN-&#947; &#40;Fig&#46; 1&#46;2&#41; means IFN-&#947; levels with Nil subtraction&#46; IFN-&#947;&#58; interferon-&#947;&#59; TB&#58; tuberculosis&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0001"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0001"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spara007" class="elsevierStyleSimplePara elsevierViewall">ELISA&#58; enzyme-linked immunosorbent assay&#59; ESAT-6&#58; early secretory antigenic 6 kDa&#59; CFP-10&#58; culture filtrate protein 10&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">QIAreach QFT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0003"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">QFT-Plus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0004"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Volume of blood sample and tubes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0005"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#160;mL&#44; one tube&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0006"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">total 4&#160;mL&#44; four tubes &#40;Nil&#44; TB1&#44; TB2&#44; Mitogen&#44;1mL each&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0007"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Stimulation antigens&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0008"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ESAT-6&#160;&#43;&#160;CFP-10&#43; short peptide CFP-10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0009"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">TB1&#58; ESAT-6&#160;&#43;&#160;CPF-10TB2&#58; ESAT-6&#160;&#43;&#160;CPF10&#43;short peptide CFP-10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0010"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Incubation time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0011"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16-24 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16-24 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0013"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Principle of IFN-&#947; detection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Digital fluorescence lateral flow nanoparticle technology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Enzyme-linked immunoassay&#59; ELISA &#40;colorimetric&#41; system&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0016"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">IFN-&#947; measurement time and number of samples&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0017"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Max 20&#160;min&#47;test&#44; 8 tests&#47;eHub&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">At least 150&#160;min&#47;test44 samples&#47;kit&#44; 22 samples&#47;plate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0019"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Data management&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Laptop PC&#47;QIAreach software&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0021"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ELISA workstation&#47;QFT-Plus software&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0022"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Instruments for assay&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Incubator&#47;centrifuge &#40;not always necessary&#41;&#44; eHub&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Workstation &#40;plate washer&#47;plate reader&#41;&#47;incubator&#47;centrifuge&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0025"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Power supply&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">USB or 100 &#8764;240 volt&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">100 &#8764;240 volt&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0028"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Assay handling&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0029"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Easy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0031"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Cut-off value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">TB2 &#40;or TB1&#41;-Nil 0&#46;35IU&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2796875.png"
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            ]
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara006" class="elsevierStyleSimplePara elsevierViewall">Comparison of QIAreach QFT and QFT-Plus&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0002"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0002"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spara010" class="elsevierStyleSimplePara elsevierViewall">Data are presented as No&#46; &#40;&#37;&#41;&#44; or median &#40;IQR&#41;&#46;</p><p id="spara011" class="elsevierStyleSimplePara elsevierViewall">TB&#58; tuberculosis&#59; IQR&#58; interquartile range&#59; CD4&#58; CD4&#43; T lymphocyte in blood&#59; CD8&#58; CD8&#43; T lymphocyte in blood&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0034"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0035"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Patients with active TB &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;41&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0036"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Healthy &#47; low-TB-risk individuals &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0037"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">p value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Age&#44; years&#59; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">82&#46;0 &#40;76&#46;0-89&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">39&#46;5 &#40;30&#46;75-47&#46;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0041"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0042"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Sex&#44; male&#59; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">27 &#40;65&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10 &#40;23&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0045"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0046"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Pulmonary TB&#59; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">41 &#40;100&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0050"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">White blood cell count&#47;&#956;L&#59; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4930 &#40;4395-6965&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5655 &#40;5340-7232&#46;5&#41;<a class="elsevierStyleCrossRef" href="#tb2fn1"><span class="elsevierStyleSup">&#8270;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">p&#61;0&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0054"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Lymphocyte count&#47;&#956;L&#59; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1170 &#40;930-1610&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2105 &#40;1662&#46;5-2412&#46;5&#41;<a class="elsevierStyleCrossRef" href="#tb2fn1"><span class="elsevierStyleSup">&#8270;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0058"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">CD4 cell count&#47;&#956;L&#59; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">384 &#40;256-529&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">741 &#40;639&#46;5-950&#41;<a class="elsevierStyleCrossRef" href="#tb2fn1"><span class="elsevierStyleSup">&#8270;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0061"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0062"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">CD8 cell count&#47;&#956;L&#59; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">222 &#40;148&#46;5-343&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">516 &#40;358&#46;5-678&#41;<a class="elsevierStyleCrossRef" href="#tb2fn1"><span class="elsevierStyleSup">&#8270;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                0 => "xTab2796874.png"
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          "en" => "<p id="spara008" class="elsevierStyleSimplePara elsevierViewall">Characteristics of study participants with active pulmonary TB and healthy low-TB-risk individuals&#46;</p>"
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          "leyenda" => "<p id="spara013" class="elsevierStyleSimplePara elsevierViewall">Sensitivity&#58; 100&#46;0&#37; &#40;41&#47;41&#41;&#59; specificity&#58; 97&#46;6&#37; &#40;41&#47;42&#41;&#59; overall concordance&#58; 98&#46;8&#37; &#40;82&#47;83&#41;&#46;</p>"
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              "identificador" => "bib0001"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Global Tuberculosis Report 2020"
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                          "colaboracion" => "World Health Organization"
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              "identificador" => "bib0002"
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                      "titulo" => "The global prevalence of latent tuberculosis&#58; a systematic review and meta-analysis"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Cohen"
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                        ]
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                    0 => array:2 [
                      "doi" => "10.1183/13993003.00655-2019"
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                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2019"
                        "volumen" => "54"
                        "numero" => "3"
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                    ]
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                    0 => array:2 [
                      "titulo" => "Latent tuberculosis infection and the EndTB strategy&#58; ethical tensions and imperatives"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46;T&#46; Denholm"
                            1 => "J&#46;C&#46; Millan-Marcelo"
                            2 => "K&#46; Fiekert"
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                        ]
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                    0 => array:2 [
                      "doi" => "10.5588/ijtld.17.0756"
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                        "tituloSerie" => "Int J Tuberc Lung Dis"
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                        "volumen" => "24"
                        "numero" => "5"
                        "paginaInicial" => "21"
                        "paginaFinal" => "26"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32553039"
                            "web" => "Medline"
                          ]
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                    ]
                  ]
                ]
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                    0 => array:2 [
                      "titulo" => "Completion of treatment for latent TB infection in a low prevalence setting"
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                          "autores" => array:6 [
                            0 => "J&#46;A&#46; Gullon-Blanco"
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                            2 => "F&#46; Alvarez-Navascues"
                            3 => "E&#46; Tabernero-Huguet"
                            4 => "J&#46; Sabria-Mestres"
                            5 => "J&#46;M&#46; Garcia-Garcia"
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                    0 => array:2 [
                      "titulo" => "Towards tuberculosis elimination&#58; an action framework for low-incidence countries"
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                          "etal" => true
                          "autores" => array:3 [
                            0 => "K&#46; Lonnroth"
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                            2 => "I&#46; Abubakar"
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                      ]
                    ]
                  ]
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                      "doi" => "10.1183/09031936.00214014"
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                        "tituloSerie" => "Eur Respir J"
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                        "volumen" => "45"
                        "numero" => "4"
                        "paginaInicial" => "928"
                        "paginaFinal" => "952"
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                            "web" => "Medline"
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            5 => array:3 [
              "identificador" => "bib0006"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tuberculosis elimination&#58; where are we now&#63;"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46; Matteelli"
                            1 => "A&#46; Rendon"
                            2 => "S&#46; Tiberi"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Eur Respir Rev"
                        "fecha" => "2018"
                        "volumen" => "27"
                        "numero" => "148"
                      ]
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                ]
              ]
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            6 => array:3 [
              "identificador" => "bib0007"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interferon-gamma release assays"
                      "autores" => array:1 [
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                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46; Belknap"
                            1 => "C&#46;L&#46; Daley"
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cll.2014.02.007"
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                        "tituloSerie" => "Clin Lab Med"
                        "fecha" => "2014"
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Article information
ISSN: 25310437
Original language: English
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