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the identification and management of individuals with LTBI&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">LTBI is diagnosed using immunological tests that detect an individual&#8217;s sensitization to antigens expressed by <span class="elsevierStyleItalic">Mycobacteria tuberculosis</span> in the absence of clinical and&#47;or radiological findings consistent with active tuberculous disease&#46; There is no gold standard for the diagnosis of LTBI&#44; so the tuberculin skin test &#40;TST&#41; and the interferon-gamma release assay &#40;IGRA&#41;&#44; alone or in combination&#44; are the techniques commonly used to indirectly diagnose this infection&#46; TST has some well-known limitations<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#44; including false negatives in immunocompromised patients and false positives in subjects vaccinated with BCG or sensitized to non-tuberculous mycobacteria&#46; IGRAs&#44; which measure the production of interferon gamma &#40;IFN-&#947;&#41; in response to specific antigens CFP-10 and ESAT-6 were introduced just over 10 years ago&#46; Two types of IGRA are available&#58; QuantiFERON&#8482; &#40;QTF&#41; &#40;Qiagen&#41; and T-SPOT&#46;TB&#8482; &#40;Oxford Immunotec&#41;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The interpretation of IGRA results is objective&#44; although sources of variability in these techniques can influence the results<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; In general&#44; the use of IGRAs is recommended in low-incidence countries due to their high specificity&#46; However&#44; neither IGRA nor TST differentiate between LTBI and active tuberculosis&#44; and their positive predictive value of disease progression is less than 5&#37;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#8211;6</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In Spain&#44; 2 consensus documents have been published that specifically address immunocompromised patients&#58; the guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology &#40;SEMMI&#41; and the Spanish Society of Pulmonology and Thoracic Surgery &#40;SEPAR&#41;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#59; and a multidisciplinary document on the prevention and treatment of tuberculosis in patients who are candidates for biological therapies<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46; Both recommend screening for LTBI with TST and IGRA&#46; Guidelines from the American Thoracic Society&#47;Infectious Diseases Society of America&#47;Centers for Disease Control and Prevention recommend dual testing &#40;TST&#8239;&#43;&#8239;IGRA&#41; in cases with a high probability of infection and&#47;or progression to disease<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; These recommendations are based on evidence accumulated using the QuantiFERON TB Gold-In-Tube&#8482; &#40;QTF-GIT&#41; version&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The new QuantiFERON TB Gold Plus &#40;QFT-Plus&#44; QuantiFERON fourth generation&#41; differs from QTF-GIT in that it incorporates a second tube containing modified antigens to stimulate the response of CD8&#43; T lymphocytes&#46; Previous studies have shown increased sensitivity in immunosuppressed patients<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> and in elderly patients<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46; It has been postulated that a greater release of IFN-&#947; in the TB2 tube compared to the TB1 tube could be due to recent infection&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">To date&#44; studies with QTF-Plus have been carried out mainly in patients with active tuberculosis<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12</span></a>&#44; in tuberculosis contact tracing<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#44; and in LTBI screening<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#8211;16</span></a>&#59; in these populations&#44; the yield of QTF-Plus was equivalent to that of QTF-GIT&#46; Less evidence has been published in immunocompromised patients<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The objectives of this study were to compare the results of QTF-GIT and QTF-Plus&#44; to compare these with T-SPOT&#46;TB results&#44; and to evaluate the benefit of an LTBI strategy that uses both IGRAs simultaneously in immunosuppressed patients and&#47;or candidates for biological therapies&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">This was a prospective study that included patients who were tested simultaneously with both IGRAs &#40;group 1&#58; T-SPOT&#46;TB and QTF-GIT from May 2015 to June 2016&#59; group 2&#58; T-SPOT&#46;TB and QTF-Plus from July 2016 to June 2017&#41; due to a immunosuppressive condition or a high individual risk of developing tuberculosis&#44; including immunosuppressed patients&#44; individuals with chronic immune-mediated inflammatory diseases who were candidates for biological therapies&#44; patients with hematological diseases or HIV-positive individuals&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">This observational study received a favorable opinion from the Research Ethics Committee of the Principality of Asturias&#44; and that ethics committee also approved the informed consent waiver&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In Asturias &#40;1 million inhabitants&#59; TB incidence rate of 10 cases&#47;100&#44;000 inhabitants&#41;&#44; the diagnosis of tuberculosis infection by IGRA is performed centrally in the Regional Mycobacteria Reference Unit of the Hospital Universitario Central de Asturias&#44; in coordination with the microbiology laboratories of the Health Service of the Principality of Asturias&#46; On May 21&#44; 2015&#44; the Directorate-General for Public Health &#40;Ministry of Health of the Principality of Asturias&#41; published Circular 04&#47;2015&#44; updating the procedures for the diagnosis of tuberculosis infection in Asturias<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#44; which recommends that two IGRA techniques be performed simultaneously &#40;QuantiFERON and T-SPOT&#46;TB&#41; in immunocompromised patients and&#47;or candidates for biological therapies&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">All patients included in our study were tested with two IGRAs&#58; <span class="elsevierStyleBold">ELISA</span> &#40;enzyme-linked immunosorbent assay&#41;-based QuantiFERON TB Gold&#44; which measures the amount of IFN-&#947; released into plasma after stimulation with specific antigens&#46; We used the version available in each of the analyzed periods&#58; &#40;1&#41; <span class="elsevierStyleItalic">from May 2015 to June 2016</span>&#58; QTF-GIT&#44; which consists of 3 tubes&#58; negative control &#40;nil&#41;&#44; positive control &#40;mitogen&#41; and ESAT-6&#44; CFP-10 and TB7&#46;7 antigen tube &#40;antigen&#41;&#59; and &#40;2&#41; <span class="elsevierStyleItalic">from July 2016 to June 2017</span>&#58; QFT-Plus&#44; which consists of 4 tubes&#58; nil&#44; mitogen&#44; TB1 tube &#40;contains ESAT-6 and CFP-10 peptides optimized to generate response from CD4&#43; helper T lymphocytes&#41; and TB2 tube &#40;same peptides optimized to induce responses of both CD4&#43; and CD8&#43; cytotoxic T lymphocytes&#41;&#59; and <span class="elsevierStyleBold">T-SPOT&#46;TB</span>&#44; based on an ELISPOT &#40;enzyme-linked immunospot assay&#41;&#44; which quantifies the number of effector T cells&#46; To this end&#44; mononuclear cells are extracted from peripheral blood and stimulated with the ESAT-6 and CFP-10 antigens individually in two separate wells &#40;2 wells are also required for positive and negative controls&#41;&#59; in the second period of the study&#44; cells that have released IFN-&#947;&#44; which will appear as spots at the bottom of the wells are quantified&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The recommendations of the manufacturers were followed when carrying out the IGRA tests&#46; QTF results were interpreted as&#58; positive&#44; when the antigen response &#40;antigen tube in QTF-GIT&#44; TB1 or TB2 in QTF-Plus&#41; minus the nil value was &#8805;0&#46;35&#8239;IU&#47;mL and &#8805;25&#37; of the nil value&#59; negative&#44; when the antigenic response minus the nil value was &#60;0&#46;35&#8239;IU&#47;mL or &#60;25&#37; of the nil value&#59; inconclusive&#44; when a&#41; the nil value was &#62;8&#8239;IU&#47;mL or b&#41; the antigenic response minus the nil value was &#60;0&#46;35&#8239;IU&#47;mL or &#60;25&#37; of the nil value and the mitogen value was &#60;0&#46;5&#8239;IU&#47;mL&#46; T-SPOT&#46;TB results were interpreted as&#58; positive when the difference in spots and the nil control in any of the antigen-containing wells &#91;ESAT-6 &#40;panel A&#41; or CFP-10 &#40;panel B&#41;&#93; was &#8805;8 spots&#59; negative when the difference was less than 8 spots&#59; inconclusive&#44; when &#40;a&#41; the nil control had &#62;10 spots or &#40;b&#41; the mitogen had &#60;20 spots&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Statistical analyses were performed using R Studio&#46; Cohen&#8217;s Kappa coefficient &#40;&#954;&#41; with 95&#37; confidence intervals &#40;CI&#41; was used to evaluate the agreement between the two versions of QTF and T-SPOT&#46;TB&#46; The &#954; were interpreted according to the classification of Landis and Koch&#58; 0&#46;01&#8211;0&#46;20 indicates poor agreement&#59; 0&#46;21&#8211;0&#46;40 fair&#59; 0&#46;41&#8211;0&#46;60 moderate&#59; 0&#46;61&#8211;0&#46;80 substantial&#59; 0&#46;80&#8211;1&#46;00 almost perfect&#46; The <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test was used to compare the demographic characteristics of the patients included in each study period&#46; Linear regression analysis was used to represent the amount of IFN-&#947; released in both QTF-Plus tubes TB1 and TB2&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">A total of 2999 patients were included&#44; 1535 during the first period and 1464 during the second period of the study&#46; The demographic characteristics of the subjects and the origin of the disease that caused the immunosuppression are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; No significant differences were found between the 2 groups of patients&#46; Overall&#44; patients with gastrointestinal &#40;44&#37;&#41; and hematological &#40;25&#8211;26&#37;&#41; diseases generated 70&#37; of the diagnostic demand for dual IGRA studies &#40;T-SPOT&#46;TB&#8239;&#43;&#8239;QTF-GIT or T-SPOT&#46;TB&#8239;&#43;&#8239;QTF-Plus&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">The percentage of patients with a positive IGRA result &#40;QTF and&#47;or T-SPOT&#46;TB&#41; during the first and second period was 20&#46;06&#37; &#40;308&#47;1535&#41; and 18&#46;71&#37; &#40;274&#47;1464&#41;&#44; respectively&#46; The overall results of the IGRAs for each period are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Overall agreement between QTF-Plus and T-SPOT&#46;TB was higher than between QTF-GIT and T-SPOT&#46;TB &#40;87&#46;57&#37; &#91;1282&#47;1464&#93;&#44; &#954;&#8239;&#61;&#8239;0&#46;609 &#91;95&#37; CI 0&#46;560&#8211;0&#46;657&#93; vs&#46; 83&#46;19&#37; &#91;1277&#47;1535&#93;&#44; &#954;&#8239;&#61;&#8239;0&#46;532 &#91;95&#37; CI 0&#46;486&#8211;0&#46;578&#93;&#41;&#44; and also in the positive results &#40;&#954;&#8239;&#61;&#8239;0&#46;727 &#91;95&#37; CI 0&#46;677&#8211;0&#46;777&#93; vs&#46; &#954;&#8239;&#61;&#8239;0&#46;671 &#91;95&#37; CI 0&#46;619&#8211;0&#46;722&#93;&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">With regard to QTF &#40;GIT or Plus&#41; and T-SPOT&#46;TB discrepancies&#44; the percentage of results between <span class="elsevierStyleItalic">QTF &#40;GIT or Plus&#41; positive&#47;T-SPOT&#46;TB negative or inconclusive</span>&#44; and <span class="elsevierStyleItalic">QTF &#40;GIT or Plus&#41; inconclusive&#47;T-SPOT&#46;TB negative</span>&#44; was practically identical in the first and second period &#40;3&#37; vs&#46; 3&#46;3&#37; and 1&#46;7&#37; vs&#46; 1&#46;4&#37;&#44; respectively&#41;&#44; whereas in the case of negative or inconclusive T-SPOT&#46;TB&#47;QTF &#40;GIT or Plus&#41; results&#44; the percentage fell from 5&#46;7&#37; &#40;QTF-GIT&#41; to 3&#46;6&#37; &#40;QTF-Plus&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">The individualized results of QTF-Plus tubes TB1 &#40;CD4&#43; stimulation&#41; and TB2 &#40;CD4&#43; and CD8&#43; stimulation&#41; showed an agreement of 98&#46;22&#37; &#40;1&#44;438&#47;1&#44;464&#44; &#954;&#8239;&#61;&#8239;0&#46;927 &#91;95&#37; CI 0&#46;899&#8211;0&#46;955&#93;&#41;&#46; The number of positive results was slightly higher in TB1 than in TB2 &#91;14&#46;41&#37; &#40;211&#47;1464&#41; vs&#46; 13&#46;87&#37; &#40;203&#47;1464&#41;&#41;&#46; The overall mismatch rate was 1&#46;77&#37; &#40;26&#47;1464&#41;&#44; with 17 cases being TB1 positive&#47;TB2 negative and being 9 TB1 negative&#47;TB2 positive&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Linear regression analysis of IFN-&#947; values recorded in tubes TB1 and TB2 showed a high correlation between tube readings &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The mean IFN-&#947; &#40;IU&#47;mL&#41; values recorded in samples with a positive result in at least one of the two tubes are presented individually in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46; In our series we found no case in which the differences between the readings of TB2 and TB1 were greater than 0&#46;6&#8239;IU&#47;mL &#40;limit set to establish significant differences and exclude intra-test variability<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0100" class="elsevierStylePara elsevierViewall">Our study was conducted in a region that uses a diagnostic strategy of 2 simultaneous IGRAs &#40;QTF&#8239;&#43;&#8239;T-SPOT&#46;TB&#41; in immunosuppressed patients and&#47;or candidates for biological therapies&#46; We compared the results of two different versions of QTF and then compared them to those of T-SPOT&#46;TB&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Overall&#44; we observed a greater overall agreement between QTF-Plus and T-SPOT&#46;TB&#44; with a reduction in the number of discordant negative or inconclusive QTF&#47;positive T-SPOT&#46;TB results&#46; In the specific case of positive IGRA results&#44; the degree of agreement between QTF-Plus and T-SPOT&#46;TB &#40;&#954;&#8239;&#61;&#8239;0&#46;727&#41; was higher than between QTF-GIT and T-SPOT&#46;TB during the first period &#40;&#954;&#8239;&#61;&#8239;0&#46;671&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In 2 recent studies comparing IGRA tests conducted in 154 patients with rheumatoid arthritis<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> and in 92 renal transplant patients<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#44; very similar degrees of agreement in positive IGRA results were found between QTF-Plus and T-SPOT&#46;TB &#40;&#954;&#8239;&#61;&#8239;0&#46;51&#41; and between QTF-GIT and T-SPOT&#46;TB &#40;&#954;&#8239;&#61;&#8239;0&#46;48&#41;&#44; although it should be noted that very few of the latter tests were performed&#44; probably because the series included very limited patient numbers&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Despite this&#44; we believe that our dual strategy of IGRA testing in immunocompromised patients is justified by the 12&#46;43&#37; mismatch rate between QTF-Plus and T-SPOT-TB&#44; which would mean that 103 patients would test positive if only one IGRA was used &#40;49 QTF-Plus&#59; 54 T-SPOT&#46;TB&#41;&#46; Furthermore&#44; another 79 patients had a negative result in one of the two IGRAs &#40;58 QTF-Plus&#59; 21 T-SPOT&#46;TB&#41;&#44; while the other test was inconclusive&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">A higher proportion of inconclusive IGRA results has been reported in immunocompromised populations<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a>&#46; Latorre et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> found that negative results were more frequent in patients with Crohn&#8217;s disease compared to patients with rheumatic diseases and psoriasis&#46; In our study&#44; fewer inconclusive results were obtained with QTF-Plus than with QTF-GIT&#44; an observation also reported in 2 other Japanese studies&#44; in which inconclusive results fell from 5&#46;2&#37; with QTF-GIT to 0&#46;7&#37; with QTF-Plus<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">For this reason&#44; we also believe that the simultaneous use of 2 IGRAs &#40;QTF and T-SPOT&#46;TB&#41; improves the efficiency of LTBI screening in at-risk patients&#44; as the inconclusive results of one IGRA largely correlated with a valid result in the other&#46; In fact&#44; inconclusive results were obtained simultaneously in both IGRAs in less than 1&#37; of patients &#40;14 patients in the first period and 4 in the second period&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Several authors have remarked on the high negative predictive value of IGRAs&#44; and with respect to the positive predictive value&#44; studies have found that T-SPOT&#46;TB is a better predictor of progression to tuberculosis than QTF-GIT and TST<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a>&#46; One of the limitations of our study is the absence of patient follow-up data&#44; so we cannot determine whether the lower number of mismatches between T-SPOT&#46;TB and QTF-Plus suggests that QTF-Plus offers better predictive values of disease progression than those reported in the QTF-GIT literature&#46; However&#44; it should be borne in mind that&#44; in the absence of a gold standard for tuberculosis infection&#44; the reliability of a diagnostic test cannot be precisely established&#46; In this regard&#44; we believe that our study shows that in a significant number of immunocompromised patients&#44; inconclusive &#40;positive&#47;negative&#41; results are obtained between simultaneous IGRA tests&#44; even in the absence of technical reasons &#40;it should be pointed out that these tests include negative and positive controls&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">As in other studies<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a>&#44; we found that the second TB2 tube in QTF-Plus also increased diagnostic yield&#46; Regarding the specific CD8&#43; response associated with active tuberculosis<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> and an increased exposure to <span class="elsevierStyleItalic">M&#46; tuberculosis</span> in contact tracing studies<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#44; a comparison of the mean IFN-&#947; values in our series showed that differences between TB2 and TB1 were never greater than 0&#46;6&#8239;IU&#47;mL &#40;not attributable to intra-test variability<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Similarly to other studies<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;20</span></a>&#44; the degree of agreement between TB1 and TB2 in our series was excellent &#40;&#954;&#8239;&#61;&#8239;0&#46;927&#41;&#46; Although&#44; overall&#44; we observed higher mean IFN-&#947; values in TB2&#44; the difference was not significant and was not associated with any specific population group&#46; In a recent study that included 317 immunocompromised patients<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#44; researchers found a high degree of agreement between TB1 and TB2&#44; but also observed a higher IFN-&#947; response in TB2&#44; particularly in solid organ transplant candidates&#46; This led them to conclude that QTF-Plus could improve the diagnosis of LTBI in these patients&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0145" class="elsevierStylePara elsevierViewall">In LTBI screening in an immunocompromised population&#44; QTF-Plus results showed greater agreement with T-SPOT&#46;TB compared to QTF-GIT&#46; Moreover&#44; there was a significant reduction in the rate of disagreement between QTF-Plus and T-SPOT&#46;TB&#44; and in inconclusive QTF results&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">As the reason for the discrepancies between the different LTBI screening tests has not yet been established&#44; our experience suggests that&#44; whenever feasible&#44; all available diagnostic tests should be performed in groups with a higher risk of disease&#44; such as immunocompromised patients and&#47;or candidates for biological therapies&#44; in whom any positive results should be considered evidence of LTBI&#46; Therefore&#44; we believe that the rate of mismatched positive results between T-SPOT&#46;TB and QTF-Plus&#44; although lower than those observed with QTF-GIT&#44; and the number of inconclusive results obtained with T-SPOT&#46;TB &#40;much higher than those obtained with QTF-Plus&#41; is sufficiently large in the diagnosis of LTBI to support the simultaneous use of QTF-Plus and T-SPOT&#46;TB in this specific group of patients&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interests</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors state that they have no conflict of interests&#46;</p></span></span>"
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          "identificador" => "xpalclavsec1594987"
          "palabras" => array:5 [
            0 => "Infecci&#243;n tuberculosa latente"
            1 => "IGRA"
            2 => "QuantiFERON"
            3 => "T-SPOT&#46;TB"
            4 => "Inmunomoduladores biol&#243;gicos"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">The diagnosis of latent tuberculous infection &#40;LTI&#41; by IGRA continues to generate debate&#46; Experience in the simultaneous use of 2 IGRA tests is scant&#46; The aim of this study was to compare the results of 2 versions of QuantiFERON-TB Gold &#40;In-Tube&#47;Plus&#41; with those of T-SPOT&#46;TB&#44; and to analyse the effectiveness of a dual strategy &#40;T-SPOT&#46;TB &#43; QTF&#41; for the diagnosis of LTI in an immunosuppressed population&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">We conducted a prospective study &#40;May 2015&#8211;June 2017&#41; that included 2999 immunosuppressed patients and&#47;or candidates for biologics&#44; in whom 2 simultaneous IGRA tests were performed&#58; Group 1 &#40;1535 patients&#41;&#58; T-SPOT&#46;TB&#8239;&#43;&#8239;QuantiFERON-TB Gold-In-Tube &#40;QTF-GIT&#41;&#59; Group 2 &#40;1464 patients&#41;&#58; T-SPOT&#46;TB&#8239;&#43;&#8239;QuantiFERON-TB Gold Plus &#40;QTF-Plus&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">The concordance between QTF-GIT and T-SPOT&#46;TB was 83&#46;19&#37; &#40;&#954;&#8239;&#61;&#8239;0&#46;532&#41;&#46; The percentage of positive&#44; negative&#44; and indeterminate results were&#44; respectively&#58; 14&#46;33&#37; vs&#46; 17&#46;06&#37;&#59; 82&#46;41&#37; vs&#46; 74&#46;46&#37;&#59; and 3&#46;25&#37; vs&#46; 8&#46;46&#37;&#46; The concordance between QTF-Plus and T-SPOT&#46;TB was 87&#46;56&#37; &#40;&#954;&#8239;&#61;&#8239;0&#46;609&#41;&#46; The percentage of positive&#44; negative&#44; and indeterminate results were&#44; respectively&#58; 15&#46;02&#37; vs&#46; 15&#46;36&#37;&#59; 82&#46;92&#37; vs&#46; 79&#46;37&#37;&#59; and 2&#46;04&#37; vs&#46; 5&#46;25&#37;&#46; Discrepancies between T-SPOT&#46;TB and QTF-Plus were 12&#46;43&#37;&#44; suggesting that 103 patients were positive and another 79 were negative due exclusively to 1 of the 2 IGRAs&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Greater concordance was found between QTF-Plus and T-SPOT&#46;TB than between QTF-GIT and T-SPOT&#46;TB&#46; However&#44; we believe that the proportion of discrepancies between T-SPOT&#46;TB and QTF-Plus is sufficiently important from a clinical point of view to justify the simultaneous use of 2 IGRA in this specific patient group&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">El diagn&#243;stico de la infecci&#243;n tuberculosa latente &#40;ITL&#41; mediante IGRA sigue generando debate&#46; La experiencia empleando dos pruebas IGRA de manera simult&#225;nea es escasa&#46; El objetivo de este estudio es comparar los resultados de dos versiones de QuantiFERON-TB Gold &#40;In-Tube&#47;Plus&#41; con los de T-SPOT&#46;TB y analizar la eficacia de esta estrategia dual &#40;T-SPOT&#46;TB&#8239;&#43;&#8239;QTF&#41; para el diagn&#243;stico de la ITL en poblaci&#243;n con alguna condici&#243;n inmunosupresora&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo &#40;mayo 2015&#8211;junio 2017&#41; que incluye 2&#46;999 pacientes inmunodeprimidos y&#47;o candidatos a terapias biol&#243;gicas&#44; a los que se les realiz&#243; de manera simult&#225;nea dos IGRA&#58; grupo-1 &#40;1&#46;535 pacientes&#41;&#58; T-SPOT&#46;TB&#8239;&#43;&#8239;QuantiFERON-TB Gold-In-Tube &#40;QTF-GIT&#41;&#59; grupo-2 &#40;1&#46;464 pacientes&#41;&#58; T-SPOT&#46;TB&#8239;&#43;&#8239;QuantiFERON-TB Gold Plus &#40;QTF-Plus&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">La concordancia entre QTF-GIT y T-SPOT&#46;TB fue del 83&#44;19&#37; &#40;&#954;&#8239;&#61;&#8239;0&#44;532&#41;&#46; Las proporciones de resultados positivos&#44; negativos e indeterminados fueron&#44; respectivamente&#58; 14&#44;33 vs&#46; 17&#44;06&#37;&#59; 82&#44;41 vs&#46; 74&#44;46&#37;&#59; y 3&#44;25 vs&#46; 8&#44;46&#37;&#46; La concordancia entre QTF-Plus y T-SPOT&#46;TB fue del 87&#44;56&#37; &#40;&#954;&#8239;&#61;&#8239;0&#44;609&#41;&#46; Las proporciones de resultados positivos&#44; negativos e indeterminados fueron&#44; respectivamente&#58; 15&#44;02 vs&#46; 15&#44;36&#37;&#59; 82&#44;92 vs&#46; 79&#44;37&#37;&#59; y 2&#44;04 vs&#46; 5&#44;25&#37;&#46; Las discordancias entre T-SPOT&#46;TB y QTF-Plus fueron del 12&#44;43&#37;&#44; que implicaban que hab&#237;a 103 pacientes positivos y otros 79 pacientes negativos a expensas exclusivamente de uno de los dos IGRA&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Se evidenci&#243; una mayor concordancia entre QTF-Plus y T-SPOT&#46;TB que entre QTF-GIT y T-SPOT&#46;TB&#46; Sin embargo&#44; creemos que la proporci&#243;n de resultados discordantes entre T-SPOT&#46;TB y QTF-Plus es lo suficientemente relevante cl&#237;nicamente como para justificar el empleo simult&#225;neo de dos IGRA en este grupo espec&#237;fico de pacientes&#46;</p></span>"
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            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">The SESPA Network of Microbiology Laboratories includes the Microbiology Services of&#58; Hospital de Jarrio&#44; Hospital Carmen y Severo Ochoa&#44; Hospital Universitario San Agust&#237;n&#44; Hospital Universitario de Cabue&#241;es&#44; Hospital de Jove&#44; Hospital Grande Covi&#225;n&#44; Hospital &#193;lvarez-Buylla&#44; Hospital Valle del Nal&#243;n and Central University Hospital of Asturias &#40;HUCA&#41;&#46;</p>"
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      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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          0 => array:4 [
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Linear regression analysis of IFN-&#947; values &#40;in IU&#47;mL&#41; recorded in QTF-Plus tubes TB1 and TB2&#46;</p>"
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                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">248 &#40;16&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">258 &#40;17&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">676 &#40;44&#46;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">653 &#40;44&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hematology&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">389 &#40;25&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">383 &#40;26&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rheumatology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">177 &#40;11&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">154 &#40;10&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dermatology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">98 &#40;6&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">87 &#40;5&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HIV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55 &#40;3&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61 &#40;4&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Others&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">140 &#40;9&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">126 &#40;8&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&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="spar0010" class="elsevierStyleSimplePara elsevierViewall">Demographic characteristics of patients and origin of immunosuppression and&#47;or indication of biological therapy&#46;</p>"
        ]
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      2 => array:8 [
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
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            "identificador" => "at0015"
            "detalle" => "Table "
            "rol" => "short"
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          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">QTF-GIT&#58; QuantiFERON TB Gold In-Tube&#59; QTF-Plus&#58; QuantiFERON TB Gold Plus&#46;</p>"
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            0 => array:1 [
              "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"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">First period</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">QTF-GIT</th><th class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Total T-SPOT&#46;TB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Negative&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Inconclusive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">T-SPOT&#46;TB</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">174&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">262 &#40;17&#46;06&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1089&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Inconclusive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">130 &#40;8&#46;46&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Total QTF-GIT</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">220 &#40;14&#46;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1265 &#40;82&#46;41&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;3&#46;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1535&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
            1 => array:1 [
              "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"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Second period</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">QTF-Plus</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Total T-SPOT&#46;TB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Inconclusive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">T-SPOT&#46;TB</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">171&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">225 &#40;15&#46;36&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1107&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1162 &#40;79&#46;37&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Inconclusive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77 &#40;5&#46;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Total QTF-Plus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">220 &#40;15&#46;02&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1214 &#40;82&#46;92&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;2&#46;04&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1464&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="spar0020" class="elsevierStyleSimplePara elsevierViewall">Overall IGRA results for each period &#40;QFT-GIT vs&#46; T-SPOT&#46;TB and QTF-Plus vs&#46; T-SPOT&#46;TB&#44; respectively&#41;&#46;</p>"
        ]
      ]
      3 => array:8 [
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        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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          0 => array:3 [
            "identificador" => "at0020"
            "detalle" => "Table "
            "rol" => "short"
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        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">QTF-GIT&#58; QuantiFERON TB Gold In-Tube&#59; QTF-Plus&#58; QuantiFERON TB Gold Plus&#59; QTF refers interchangeably to either of the two versions of QuantiFERON TB Gold &#40;GIT or Plus&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">QTF-GIT&#47;T-SPOT&#46;TB</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">QTF-Plus&#47;T-SPOT&#46;TB</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Overall agreement</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1277&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">83&#46;19</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1282&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">87&#46;57</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">QTF positive&#47;T-SPOT&#46;TB positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">174&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">171&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">QTF negative&#47;T-SPOT&#46;TB negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1089&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#46;94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1107&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&#46;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">QTF inconclusive &#47;T-SPOT&#46;TB inconclusive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Overall disagreement</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">258</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">16&#46;81</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">182</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">12&#46;43</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">QTF inconclusive &#47;T-SPOT&#46;TB negative or inconclusive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;35&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T-SPOT&#46;TB negative&#47;QTF inconclusive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">100</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">100</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">QTF-Plus positive&#47;T-SPOT&#46;TB negative or inconclusive</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;78 &#91;0&#46;00&#8722;10&#46;00&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1&#46;95 &#91;0&#46;25&#8722;10&#46;00&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TB1 positive&#47;TB2 positive&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;14 &#91;0&#46;35&#8722;10&#46;00&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;35 &#91;0&#46;35&#8722;10&#46;00&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TB1 positive&#47;TB2 negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;41 &#91;0&#46;35&#8722;0&#46;58&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;30 &#91;0&#46;25&#8722;0&#46;32&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">TB1 negative&#47;TB2 positive&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;54 &#91;0&#46;35&#8722;0&#46;75&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;29&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">TOTAL positive TB1 and TB2</span>&nbsp;\t\t\t\t\t\t\n
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Original Article
Diagnosis of tuberculous infection in immunosuppressed patients and/or candidates for biologics using a combination of 2 IGRA tests: T-SPOT.TB/QuantiFERON TB Gold In-Tube vs. T-SPOT.TB/QuantiFERON TB Gold Plus
Diagnóstico de la infección tuberculosa en pacientes inmunodeprimidos y/o candidatos a terapias biológicas mediante el uso combinado de dos pruebas IGRA: T-SPOT.TB/QuantiFERON TB Gold In-Tube vs. T-SPOT.TB/QuantiFERON TB Gold Plus
Ana Fernández-Blázqueza,b,
Corresponding author
anafdezblazquez@hotmail.com

Corresponding author.
, Pablo Argüelles Menéndeza, Christian Sabater-Cabreraa,b, José-María García-Garcíac, Víctor Asensi Álvarezd, Juan José Palacios Gutiérreza,b, on behalf of the Red de Laboratorios de Microbiología del SESPA 1
a Unidad de Referencia Regional de Micobacterias, Servicio de Microbiología, Hospital Universitario Central de Asturias, Spain
b Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Spain
c Servicio de Neumología, Hospital Universitario San Agustín, Asturias, Spain
d Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Universitario Central de Asturias, Facultad de Medicina, Universidad de Oviedo, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Despite effective treatment&#44; tuberculosis &#40;TB&#41; remains the leading cause of death from infection worldwide&#46; As the infected population &#40;one quarter of the world&#8217;s population&#41; constitutes the largest reservoir for developing active TB&#44; WHO recommends the use of latent TB infection &#40;LTBI&#41; screening within the framework of its &#8220;End-TB&#8221; strategy&#44; which sets targets of 95&#37; reduction in tuberculosis deaths and 90&#37; reduction in the global incidence in 2035 compared to the 2015 baseline<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; A raft of measures will be required to achieve these figures&#44; including&#44; importantly&#44; the identification and management of individuals with LTBI&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">LTBI is diagnosed using immunological tests that detect an individual&#8217;s sensitization to antigens expressed by <span class="elsevierStyleItalic">Mycobacteria tuberculosis</span> in the absence of clinical and&#47;or radiological findings consistent with active tuberculous disease&#46; There is no gold standard for the diagnosis of LTBI&#44; so the tuberculin skin test &#40;TST&#41; and the interferon-gamma release assay &#40;IGRA&#41;&#44; alone or in combination&#44; are the techniques commonly used to indirectly diagnose this infection&#46; TST has some well-known limitations<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#44; including false negatives in immunocompromised patients and false positives in subjects vaccinated with BCG or sensitized to non-tuberculous mycobacteria&#46; IGRAs&#44; which measure the production of interferon gamma &#40;IFN-&#947;&#41; in response to specific antigens CFP-10 and ESAT-6 were introduced just over 10 years ago&#46; Two types of IGRA are available&#58; QuantiFERON&#8482; &#40;QTF&#41; &#40;Qiagen&#41; and T-SPOT&#46;TB&#8482; &#40;Oxford Immunotec&#41;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The interpretation of IGRA results is objective&#44; although sources of variability in these techniques can influence the results<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; In general&#44; the use of IGRAs is recommended in low-incidence countries due to their high specificity&#46; However&#44; neither IGRA nor TST differentiate between LTBI and active tuberculosis&#44; and their positive predictive value of disease progression is less than 5&#37;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#8211;6</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In Spain&#44; 2 consensus documents have been published that specifically address immunocompromised patients&#58; the guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology &#40;SEMMI&#41; and the Spanish Society of Pulmonology and Thoracic Surgery &#40;SEPAR&#41;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#59; and a multidisciplinary document on the prevention and treatment of tuberculosis in patients who are candidates for biological therapies<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46; Both recommend screening for LTBI with TST and IGRA&#46; Guidelines from the American Thoracic Society&#47;Infectious Diseases Society of America&#47;Centers for Disease Control and Prevention recommend dual testing &#40;TST&#8239;&#43;&#8239;IGRA&#41; in cases with a high probability of infection and&#47;or progression to disease<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; These recommendations are based on evidence accumulated using the QuantiFERON TB Gold-In-Tube&#8482; &#40;QTF-GIT&#41; version&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The new QuantiFERON TB Gold Plus &#40;QFT-Plus&#44; QuantiFERON fourth generation&#41; differs from QTF-GIT in that it incorporates a second tube containing modified antigens to stimulate the response of CD8&#43; T lymphocytes&#46; Previous studies have shown increased sensitivity in immunosuppressed patients<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> and in elderly patients<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46; It has been postulated that a greater release of IFN-&#947; in the TB2 tube compared to the TB1 tube could be due to recent infection&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">To date&#44; studies with QTF-Plus have been carried out mainly in patients with active tuberculosis<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12</span></a>&#44; in tuberculosis contact tracing<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#44; and in LTBI screening<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#8211;16</span></a>&#59; in these populations&#44; the yield of QTF-Plus was equivalent to that of QTF-GIT&#46; Less evidence has been published in immunocompromised patients<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The objectives of this study were to compare the results of QTF-GIT and QTF-Plus&#44; to compare these with T-SPOT&#46;TB results&#44; and to evaluate the benefit of an LTBI strategy that uses both IGRAs simultaneously in immunosuppressed patients and&#47;or candidates for biological therapies&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">This was a prospective study that included patients who were tested simultaneously with both IGRAs &#40;group 1&#58; T-SPOT&#46;TB and QTF-GIT from May 2015 to June 2016&#59; group 2&#58; T-SPOT&#46;TB and QTF-Plus from July 2016 to June 2017&#41; due to a immunosuppressive condition or a high individual risk of developing tuberculosis&#44; including immunosuppressed patients&#44; individuals with chronic immune-mediated inflammatory diseases who were candidates for biological therapies&#44; patients with hematological diseases or HIV-positive individuals&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">This observational study received a favorable opinion from the Research Ethics Committee of the Principality of Asturias&#44; and that ethics committee also approved the informed consent waiver&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In Asturias &#40;1 million inhabitants&#59; TB incidence rate of 10 cases&#47;100&#44;000 inhabitants&#41;&#44; the diagnosis of tuberculosis infection by IGRA is performed centrally in the Regional Mycobacteria Reference Unit of the Hospital Universitario Central de Asturias&#44; in coordination with the microbiology laboratories of the Health Service of the Principality of Asturias&#46; On May 21&#44; 2015&#44; the Directorate-General for Public Health &#40;Ministry of Health of the Principality of Asturias&#41; published Circular 04&#47;2015&#44; updating the procedures for the diagnosis of tuberculosis infection in Asturias<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#44; which recommends that two IGRA techniques be performed simultaneously &#40;QuantiFERON and T-SPOT&#46;TB&#41; in immunocompromised patients and&#47;or candidates for biological therapies&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">All patients included in our study were tested with two IGRAs&#58; <span class="elsevierStyleBold">ELISA</span> &#40;enzyme-linked immunosorbent assay&#41;-based QuantiFERON TB Gold&#44; which measures the amount of IFN-&#947; released into plasma after stimulation with specific antigens&#46; We used the version available in each of the analyzed periods&#58; &#40;1&#41; <span class="elsevierStyleItalic">from May 2015 to June 2016</span>&#58; QTF-GIT&#44; which consists of 3 tubes&#58; negative control &#40;nil&#41;&#44; positive control &#40;mitogen&#41; and ESAT-6&#44; CFP-10 and TB7&#46;7 antigen tube &#40;antigen&#41;&#59; and &#40;2&#41; <span class="elsevierStyleItalic">from July 2016 to June 2017</span>&#58; QFT-Plus&#44; which consists of 4 tubes&#58; nil&#44; mitogen&#44; TB1 tube &#40;contains ESAT-6 and CFP-10 peptides optimized to generate response from CD4&#43; helper T lymphocytes&#41; and TB2 tube &#40;same peptides optimized to induce responses of both CD4&#43; and CD8&#43; cytotoxic T lymphocytes&#41;&#59; and <span class="elsevierStyleBold">T-SPOT&#46;TB</span>&#44; based on an ELISPOT &#40;enzyme-linked immunospot assay&#41;&#44; which quantifies the number of effector T cells&#46; To this end&#44; mononuclear cells are extracted from peripheral blood and stimulated with the ESAT-6 and CFP-10 antigens individually in two separate wells &#40;2 wells are also required for positive and negative controls&#41;&#59; in the second period of the study&#44; cells that have released IFN-&#947;&#44; which will appear as spots at the bottom of the wells are quantified&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The recommendations of the manufacturers were followed when carrying out the IGRA tests&#46; QTF results were interpreted as&#58; positive&#44; when the antigen response &#40;antigen tube in QTF-GIT&#44; TB1 or TB2 in QTF-Plus&#41; minus the nil value was &#8805;0&#46;35&#8239;IU&#47;mL and &#8805;25&#37; of the nil value&#59; negative&#44; when the antigenic response minus the nil value was &#60;0&#46;35&#8239;IU&#47;mL or &#60;25&#37; of the nil value&#59; inconclusive&#44; when a&#41; the nil value was &#62;8&#8239;IU&#47;mL or b&#41; the antigenic response minus the nil value was &#60;0&#46;35&#8239;IU&#47;mL or &#60;25&#37; of the nil value and the mitogen value was &#60;0&#46;5&#8239;IU&#47;mL&#46; T-SPOT&#46;TB results were interpreted as&#58; positive when the difference in spots and the nil control in any of the antigen-containing wells &#91;ESAT-6 &#40;panel A&#41; or CFP-10 &#40;panel B&#41;&#93; was &#8805;8 spots&#59; negative when the difference was less than 8 spots&#59; inconclusive&#44; when &#40;a&#41; the nil control had &#62;10 spots or &#40;b&#41; the mitogen had &#60;20 spots&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Statistical analyses were performed using R Studio&#46; Cohen&#8217;s Kappa coefficient &#40;&#954;&#41; with 95&#37; confidence intervals &#40;CI&#41; was used to evaluate the agreement between the two versions of QTF and T-SPOT&#46;TB&#46; The &#954; were interpreted according to the classification of Landis and Koch&#58; 0&#46;01&#8211;0&#46;20 indicates poor agreement&#59; 0&#46;21&#8211;0&#46;40 fair&#59; 0&#46;41&#8211;0&#46;60 moderate&#59; 0&#46;61&#8211;0&#46;80 substantial&#59; 0&#46;80&#8211;1&#46;00 almost perfect&#46; The <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test was used to compare the demographic characteristics of the patients included in each study period&#46; Linear regression analysis was used to represent the amount of IFN-&#947; released in both QTF-Plus tubes TB1 and TB2&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">A total of 2999 patients were included&#44; 1535 during the first period and 1464 during the second period of the study&#46; The demographic characteristics of the subjects and the origin of the disease that caused the immunosuppression are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; No significant differences were found between the 2 groups of patients&#46; Overall&#44; patients with gastrointestinal &#40;44&#37;&#41; and hematological &#40;25&#8211;26&#37;&#41; diseases generated 70&#37; of the diagnostic demand for dual IGRA studies &#40;T-SPOT&#46;TB&#8239;&#43;&#8239;QTF-GIT or T-SPOT&#46;TB&#8239;&#43;&#8239;QTF-Plus&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">The percentage of patients with a positive IGRA result &#40;QTF and&#47;or T-SPOT&#46;TB&#41; during the first and second period was 20&#46;06&#37; &#40;308&#47;1535&#41; and 18&#46;71&#37; &#40;274&#47;1464&#41;&#44; respectively&#46; The overall results of the IGRAs for each period are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Overall agreement between QTF-Plus and T-SPOT&#46;TB was higher than between QTF-GIT and T-SPOT&#46;TB &#40;87&#46;57&#37; &#91;1282&#47;1464&#93;&#44; &#954;&#8239;&#61;&#8239;0&#46;609 &#91;95&#37; CI 0&#46;560&#8211;0&#46;657&#93; vs&#46; 83&#46;19&#37; &#91;1277&#47;1535&#93;&#44; &#954;&#8239;&#61;&#8239;0&#46;532 &#91;95&#37; CI 0&#46;486&#8211;0&#46;578&#93;&#41;&#44; and also in the positive results &#40;&#954;&#8239;&#61;&#8239;0&#46;727 &#91;95&#37; CI 0&#46;677&#8211;0&#46;777&#93; vs&#46; &#954;&#8239;&#61;&#8239;0&#46;671 &#91;95&#37; CI 0&#46;619&#8211;0&#46;722&#93;&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">With regard to QTF &#40;GIT or Plus&#41; and T-SPOT&#46;TB discrepancies&#44; the percentage of results between <span class="elsevierStyleItalic">QTF &#40;GIT or Plus&#41; positive&#47;T-SPOT&#46;TB negative or inconclusive</span>&#44; and <span class="elsevierStyleItalic">QTF &#40;GIT or Plus&#41; inconclusive&#47;T-SPOT&#46;TB negative</span>&#44; was practically identical in the first and second period &#40;3&#37; vs&#46; 3&#46;3&#37; and 1&#46;7&#37; vs&#46; 1&#46;4&#37;&#44; respectively&#41;&#44; whereas in the case of negative or inconclusive T-SPOT&#46;TB&#47;QTF &#40;GIT or Plus&#41; results&#44; the percentage fell from 5&#46;7&#37; &#40;QTF-GIT&#41; to 3&#46;6&#37; &#40;QTF-Plus&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">The individualized results of QTF-Plus tubes TB1 &#40;CD4&#43; stimulation&#41; and TB2 &#40;CD4&#43; and CD8&#43; stimulation&#41; showed an agreement of 98&#46;22&#37; &#40;1&#44;438&#47;1&#44;464&#44; &#954;&#8239;&#61;&#8239;0&#46;927 &#91;95&#37; CI 0&#46;899&#8211;0&#46;955&#93;&#41;&#46; The number of positive results was slightly higher in TB1 than in TB2 &#91;14&#46;41&#37; &#40;211&#47;1464&#41; vs&#46; 13&#46;87&#37; &#40;203&#47;1464&#41;&#41;&#46; The overall mismatch rate was 1&#46;77&#37; &#40;26&#47;1464&#41;&#44; with 17 cases being TB1 positive&#47;TB2 negative and being 9 TB1 negative&#47;TB2 positive&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Linear regression analysis of IFN-&#947; values recorded in tubes TB1 and TB2 showed a high correlation between tube readings &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The mean IFN-&#947; &#40;IU&#47;mL&#41; values recorded in samples with a positive result in at least one of the two tubes are presented individually in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46; In our series we found no case in which the differences between the readings of TB2 and TB1 were greater than 0&#46;6&#8239;IU&#47;mL &#40;limit set to establish significant differences and exclude intra-test variability<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0100" class="elsevierStylePara elsevierViewall">Our study was conducted in a region that uses a diagnostic strategy of 2 simultaneous IGRAs &#40;QTF&#8239;&#43;&#8239;T-SPOT&#46;TB&#41; in immunosuppressed patients and&#47;or candidates for biological therapies&#46; We compared the results of two different versions of QTF and then compared them to those of T-SPOT&#46;TB&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Overall&#44; we observed a greater overall agreement between QTF-Plus and T-SPOT&#46;TB&#44; with a reduction in the number of discordant negative or inconclusive QTF&#47;positive T-SPOT&#46;TB results&#46; In the specific case of positive IGRA results&#44; the degree of agreement between QTF-Plus and T-SPOT&#46;TB &#40;&#954;&#8239;&#61;&#8239;0&#46;727&#41; was higher than between QTF-GIT and T-SPOT&#46;TB during the first period &#40;&#954;&#8239;&#61;&#8239;0&#46;671&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">In 2 recent studies comparing IGRA tests conducted in 154 patients with rheumatoid arthritis<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> and in 92 renal transplant patients<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#44; very similar degrees of agreement in positive IGRA results were found between QTF-Plus and T-SPOT&#46;TB &#40;&#954;&#8239;&#61;&#8239;0&#46;51&#41; and between QTF-GIT and T-SPOT&#46;TB &#40;&#954;&#8239;&#61;&#8239;0&#46;48&#41;&#44; although it should be noted that very few of the latter tests were performed&#44; probably because the series included very limited patient numbers&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Despite this&#44; we believe that our dual strategy of IGRA testing in immunocompromised patients is justified by the 12&#46;43&#37; mismatch rate between QTF-Plus and T-SPOT-TB&#44; which would mean that 103 patients would test positive if only one IGRA was used &#40;49 QTF-Plus&#59; 54 T-SPOT&#46;TB&#41;&#46; Furthermore&#44; another 79 patients had a negative result in one of the two IGRAs &#40;58 QTF-Plus&#59; 21 T-SPOT&#46;TB&#41;&#44; while the other test was inconclusive&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">A higher proportion of inconclusive IGRA results has been reported in immunocompromised populations<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a>&#46; Latorre et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> found that negative results were more frequent in patients with Crohn&#8217;s disease compared to patients with rheumatic diseases and psoriasis&#46; In our study&#44; fewer inconclusive results were obtained with QTF-Plus than with QTF-GIT&#44; an observation also reported in 2 other Japanese studies&#44; in which inconclusive results fell from 5&#46;2&#37; with QTF-GIT to 0&#46;7&#37; with QTF-Plus<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">For this reason&#44; we also believe that the simultaneous use of 2 IGRAs &#40;QTF and T-SPOT&#46;TB&#41; improves the efficiency of LTBI screening in at-risk patients&#44; as the inconclusive results of one IGRA largely correlated with a valid result in the other&#46; In fact&#44; inconclusive results were obtained simultaneously in both IGRAs in less than 1&#37; of patients &#40;14 patients in the first period and 4 in the second period&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Several authors have remarked on the high negative predictive value of IGRAs&#44; and with respect to the positive predictive value&#44; studies have found that T-SPOT&#46;TB is a better predictor of progression to tuberculosis than QTF-GIT and TST<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a>&#46; One of the limitations of our study is the absence of patient follow-up data&#44; so we cannot determine whether the lower number of mismatches between T-SPOT&#46;TB and QTF-Plus suggests that QTF-Plus offers better predictive values of disease progression than those reported in the QTF-GIT literature&#46; However&#44; it should be borne in mind that&#44; in the absence of a gold standard for tuberculosis infection&#44; the reliability of a diagnostic test cannot be precisely established&#46; In this regard&#44; we believe that our study shows that in a significant number of immunocompromised patients&#44; inconclusive &#40;positive&#47;negative&#41; results are obtained between simultaneous IGRA tests&#44; even in the absence of technical reasons &#40;it should be pointed out that these tests include negative and positive controls&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">As in other studies<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a>&#44; we found that the second TB2 tube in QTF-Plus also increased diagnostic yield&#46; Regarding the specific CD8&#43; response associated with active tuberculosis<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> and an increased exposure to <span class="elsevierStyleItalic">M&#46; tuberculosis</span> in contact tracing studies<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#44; a comparison of the mean IFN-&#947; values in our series showed that differences between TB2 and TB1 were never greater than 0&#46;6&#8239;IU&#47;mL &#40;not attributable to intra-test variability<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Similarly to other studies<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;20</span></a>&#44; the degree of agreement between TB1 and TB2 in our series was excellent &#40;&#954;&#8239;&#61;&#8239;0&#46;927&#41;&#46; Although&#44; overall&#44; we observed higher mean IFN-&#947; values in TB2&#44; the difference was not significant and was not associated with any specific population group&#46; In a recent study that included 317 immunocompromised patients<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#44; researchers found a high degree of agreement between TB1 and TB2&#44; but also observed a higher IFN-&#947; response in TB2&#44; particularly in solid organ transplant candidates&#46; This led them to conclude that QTF-Plus could improve the diagnosis of LTBI in these patients&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0145" class="elsevierStylePara elsevierViewall">In LTBI screening in an immunocompromised population&#44; QTF-Plus results showed greater agreement with T-SPOT&#46;TB compared to QTF-GIT&#46; Moreover&#44; there was a significant reduction in the rate of disagreement between QTF-Plus and T-SPOT&#46;TB&#44; and in inconclusive QTF results&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">As the reason for the discrepancies between the different LTBI screening tests has not yet been established&#44; our experience suggests that&#44; whenever feasible&#44; all available diagnostic tests should be performed in groups with a higher risk of disease&#44; such as immunocompromised patients and&#47;or candidates for biological therapies&#44; in whom any positive results should be considered evidence of LTBI&#46; Therefore&#44; we believe that the rate of mismatched positive results between T-SPOT&#46;TB and QTF-Plus&#44; although lower than those observed with QTF-GIT&#44; and the number of inconclusive results obtained with T-SPOT&#46;TB &#40;much higher than those obtained with QTF-Plus&#41; is sufficiently large in the diagnosis of LTBI to support the simultaneous use of QTF-Plus and T-SPOT&#46;TB in this specific group of patients&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interests</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors state that they have no conflict of interests&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">The diagnosis of latent tuberculous infection &#40;LTI&#41; by IGRA continues to generate debate&#46; Experience in the simultaneous use of 2 IGRA tests is scant&#46; The aim of this study was to compare the results of 2 versions of QuantiFERON-TB Gold &#40;In-Tube&#47;Plus&#41; with those of T-SPOT&#46;TB&#44; and to analyse the effectiveness of a dual strategy &#40;T-SPOT&#46;TB &#43; QTF&#41; for the diagnosis of LTI in an immunosuppressed population&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">We conducted a prospective study &#40;May 2015&#8211;June 2017&#41; that included 2999 immunosuppressed patients and&#47;or candidates for biologics&#44; in whom 2 simultaneous IGRA tests were performed&#58; Group 1 &#40;1535 patients&#41;&#58; T-SPOT&#46;TB&#8239;&#43;&#8239;QuantiFERON-TB Gold-In-Tube &#40;QTF-GIT&#41;&#59; Group 2 &#40;1464 patients&#41;&#58; T-SPOT&#46;TB&#8239;&#43;&#8239;QuantiFERON-TB Gold Plus &#40;QTF-Plus&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">The concordance between QTF-GIT and T-SPOT&#46;TB was 83&#46;19&#37; &#40;&#954;&#8239;&#61;&#8239;0&#46;532&#41;&#46; The percentage of positive&#44; negative&#44; and indeterminate results were&#44; respectively&#58; 14&#46;33&#37; vs&#46; 17&#46;06&#37;&#59; 82&#46;41&#37; vs&#46; 74&#46;46&#37;&#59; and 3&#46;25&#37; vs&#46; 8&#46;46&#37;&#46; The concordance between QTF-Plus and T-SPOT&#46;TB was 87&#46;56&#37; &#40;&#954;&#8239;&#61;&#8239;0&#46;609&#41;&#46; The percentage of positive&#44; negative&#44; and indeterminate results were&#44; respectively&#58; 15&#46;02&#37; vs&#46; 15&#46;36&#37;&#59; 82&#46;92&#37; vs&#46; 79&#46;37&#37;&#59; and 2&#46;04&#37; vs&#46; 5&#46;25&#37;&#46; Discrepancies between T-SPOT&#46;TB and QTF-Plus were 12&#46;43&#37;&#44; suggesting that 103 patients were positive and another 79 were negative due exclusively to 1 of the 2 IGRAs&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Greater concordance was found between QTF-Plus and T-SPOT&#46;TB than between QTF-GIT and T-SPOT&#46;TB&#46; However&#44; we believe that the proportion of discrepancies between T-SPOT&#46;TB and QTF-Plus is sufficiently important from a clinical point of view to justify the simultaneous use of 2 IGRA in this specific patient group&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">El diagn&#243;stico de la infecci&#243;n tuberculosa latente &#40;ITL&#41; mediante IGRA sigue generando debate&#46; La experiencia empleando dos pruebas IGRA de manera simult&#225;nea es escasa&#46; El objetivo de este estudio es comparar los resultados de dos versiones de QuantiFERON-TB Gold &#40;In-Tube&#47;Plus&#41; con los de T-SPOT&#46;TB y analizar la eficacia de esta estrategia dual &#40;T-SPOT&#46;TB&#8239;&#43;&#8239;QTF&#41; para el diagn&#243;stico de la ITL en poblaci&#243;n con alguna condici&#243;n inmunosupresora&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo &#40;mayo 2015&#8211;junio 2017&#41; que incluye 2&#46;999 pacientes inmunodeprimidos y&#47;o candidatos a terapias biol&#243;gicas&#44; a los que se les realiz&#243; de manera simult&#225;nea dos IGRA&#58; grupo-1 &#40;1&#46;535 pacientes&#41;&#58; T-SPOT&#46;TB&#8239;&#43;&#8239;QuantiFERON-TB Gold-In-Tube &#40;QTF-GIT&#41;&#59; grupo-2 &#40;1&#46;464 pacientes&#41;&#58; T-SPOT&#46;TB&#8239;&#43;&#8239;QuantiFERON-TB Gold Plus &#40;QTF-Plus&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">La concordancia entre QTF-GIT y T-SPOT&#46;TB fue del 83&#44;19&#37; &#40;&#954;&#8239;&#61;&#8239;0&#44;532&#41;&#46; Las proporciones de resultados positivos&#44; negativos e indeterminados fueron&#44; respectivamente&#58; 14&#44;33 vs&#46; 17&#44;06&#37;&#59; 82&#44;41 vs&#46; 74&#44;46&#37;&#59; y 3&#44;25 vs&#46; 8&#44;46&#37;&#46; La concordancia entre QTF-Plus y T-SPOT&#46;TB fue del 87&#44;56&#37; &#40;&#954;&#8239;&#61;&#8239;0&#44;609&#41;&#46; Las proporciones de resultados positivos&#44; negativos e indeterminados fueron&#44; respectivamente&#58; 15&#44;02 vs&#46; 15&#44;36&#37;&#59; 82&#44;92 vs&#46; 79&#44;37&#37;&#59; y 2&#44;04 vs&#46; 5&#44;25&#37;&#46; Las discordancias entre T-SPOT&#46;TB y QTF-Plus fueron del 12&#44;43&#37;&#44; que implicaban que hab&#237;a 103 pacientes positivos y otros 79 pacientes negativos a expensas exclusivamente de uno de los dos IGRA&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Se evidenci&#243; una mayor concordancia entre QTF-Plus y T-SPOT&#46;TB que entre QTF-GIT y T-SPOT&#46;TB&#46; Sin embargo&#44; creemos que la proporci&#243;n de resultados discordantes entre T-SPOT&#46;TB y QTF-Plus es lo suficientemente relevante cl&#237;nicamente como para justificar el empleo simult&#225;neo de dos IGRA en este grupo espec&#237;fico de pacientes&#46;</p></span>"
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hematology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">389 &#40;25&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">383 &#40;26&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rheumatology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">177 &#40;11&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">154 &#40;10&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dermatology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">98 &#40;6&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">87 &#40;5&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HIV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55 &#40;3&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61 &#40;4&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Others&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">140 &#40;9&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">126 &#40;8&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Demographic characteristics of patients and origin of immunosuppression and&#47;or indication of biological therapy&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">QTF-GIT&#58; QuantiFERON TB Gold In-Tube&#59; QTF-Plus&#58; QuantiFERON TB Gold Plus&#46;</p>"
          "tablatextoimagen" => array:2 [
            0 => array:1 [
              "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"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">First period</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">QTF-GIT</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Total T-SPOT&#46;TB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Inconclusive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">T-SPOT&#46;TB</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">174&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">262 &#40;17&#46;06&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1089&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1143 &#40;74&#46;46&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Inconclusive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">130 &#40;8&#46;46&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Total QTF-GIT</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">220 &#40;14&#46;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1265 &#40;82&#46;41&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;3&#46;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1535&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
            1 => array:1 [
              "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"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Second period</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">QTF-Plus</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Total T-SPOT&#46;TB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Inconclusive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">T-SPOT&#46;TB</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">171&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">225 &#40;15&#46;36&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  """
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Overall IGRA results for each period &#40;QFT-GIT vs&#46; T-SPOT&#46;TB and QTF-Plus vs&#46; T-SPOT&#46;TB&#44; respectively&#41;&#46;</p>"
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">QTF-GIT&#58; QuantiFERON TB Gold In-Tube&#59; QTF-Plus&#58; QuantiFERON TB Gold Plus&#59; QTF refers interchangeably to either of the two versions of QuantiFERON TB Gold &#40;GIT or Plus&#41;&#46;</p>"
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1282&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">87&#46;57</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">QTF positive&#47;T-SPOT&#46;TB positive&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">11&#46;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">171&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">11&#46;68&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1107&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">75&#46;61&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">182</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">12&#46;43</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">46&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T-SPOT&#46;TB positive&#47;QTF negative or inconclusive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">QTF negative&#47;T-SPOT&#46;TB inconclusive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T-SPOT&#46;TB negative&#47;QTF inconclusive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">TOTAL</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1535&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">100</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1464&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">100</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TB2 &#40;IU&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TB2-TB1<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">QTF-Plus positive&#47;T-SPOT&#46;TB positive</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">171&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;26 &#91;0&#46;19&#8722;10&#46;00&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;17 &#91;0&#46;03&#8722;10&#46;00&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TB1 positive&#47;TB2 positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">155&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;60 &#91;0&#46;37&#8722;10&#46;00&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;57 &#91;0&#46;36&#8722;10&#46;00&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TB1 positive&#47;TB2 negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;29 &#91;0&#46;35&#8722;10&#46;00&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;19 &#91;0&#46;03&#8722;0&#46;34&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TB1 negative&#47;TB2 positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;28 &#91;0&#46;19&#8722;0&#46;34&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;43 &#91;0&#46;35&#8722;0&#46;68&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">QTF-Plus positive&#47;T-SPOT&#46;TB negative or inconclusive</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;78 &#91;0&#46;00&#8722;10&#46;00&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;95 &#91;0&#46;25&#8722;10&#46;00&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TB1 positive&#47;TB2 positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;14 &#91;0&#46;35&#8722;10&#46;00&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;35 &#91;0&#46;35&#8722;10&#46;00&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TB1 positive&#47;TB2 negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;41 &#91;0&#46;35&#8722;0&#46;58&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;30 &#91;0&#46;25&#8722;0&#46;32&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TB1 negative&#47;TB2 positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;25 &#91;0&#46;00&#8722;0&#46;32&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;54 &#91;0&#46;35&#8722;0&#46;75&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">TOTAL positive TB1 and TB2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TB1&#58; 211&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;86 &#91;0&#46;35&#8722;10&#46;00&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;96 &#91;0&#46;35&#8722;10&#46;00&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TB2&#58; 203&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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Article information
ISSN: 03002896
Original language: English
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