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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The prevalence of tuberculosis &#40;TB&#41; in Spain varies depending on the region&#46; The incidence of tuberculosis has dropped in Spain over the last decade&#59; however&#44; it is important to know that&#44; even in areas of low prevalence&#44; the occurrence of TB in immunocompromised patients is an important cause of morbidity and mortality&#46;<span class="elsevierStyleSup">1</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Uraemia is known to be associated with a large number of immune system disorders&#44; most of them linked to impaired cellular immunity&#46;<span class="elsevierStyleSup">2</span> Latent tuberculosis is characterised by a strong cellular immune response in the absence of detectable mycobacteria&#46; As this infection is controlled by the cellular immune response&#44; impairment in cellular immunity may lead to the reactivation of latent tuberculosis infection&#46;<span class="elsevierStyleSup">1</span> At present the skin sensitivity to the tuberculin is the method used to detect latent tuberculosis infection&#46; The response to this antigen depends on the infectious load and the condition of the individual&#8217;s cellular immunity&#46; It has low sensitivity and specificity&#46; Furthermore&#44; in uraemic patients the delayed immune response to skin tests<span class="elsevierStyleSup"> </span>is reduced<span class="elsevierStyleSup">3</span> as well as the macrophage function&#46;<span class="elsevierStyleSup">2</span> This may cause cutaneous anergy and alter the response to the tuberculin skin test &#40;TST&#41;&#46; For this reason&#44; TST is not routinely performed on dialysis patients&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Given the fact that there is no gold standard test to diagnose TB&#44; some groups have studied tests that use Interferon-Gamma Release Assays &#40;IGRA&#41;&#46; They have compared these with TST in order to determine their sensitivity and specificity in different subgroups of the population&#46;<span class="elsevierStyleSup">1&#44;4-6</span> The different regulations concerning the use of IGRA depend on each country&#46; For example&#44; the CDC &#40;Center for Disease Control&#41; in the USA recommends replacing TST with IGRA in all cases&#59; while in the United Kingdom&#44; the National Institute of Health and Clinical Excellence &#40;NICE&#41; recommends the use of IGRA in combination with TST only when the tuberculin skin test was positive&#46; Other countries such as France or Canada have adopted these recommendations&#46; However&#44; they are based on cost-effectiveness studies which compare TST with one of the IGRA &#40;QFT-GIT or T-SPOT&#46;TB&#41; available on the market&#46; In a recently published study&#44; Pooran et al<span class="elsevierStyleSup">7</span> compared the two types of IGRA&#46; They reached the conclusion that it was cheaper to use a regimen combining TST&#47;IGRA rather than using T-SPOT&#46;TB or QFT-GIT or TST on their own for contact tracing&#46; While T-SPOT&#46;TB and QFT-GIT on their own prevent more cases of active TB&#44; they do not better the lower cost of the combined use of TST&#47;IGRA&#46; However&#44; these conclusions depend largely on the population studied&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The aim of our study was to compare QFT-GIT with the TST as a screening method to detect latent tuberculosis in patients on peritoneal dialysis &#40;PD&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">PATIENTS AND METHODS</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Patients</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The study included patients with chronic renal failure &#40;CRF&#41; on PD from the Marqu&#233;s de Valdecilla Hospital in Santander and Asturias Central Hospital in Oviedo&#46; They had no signs or symptoms of active or extrapulmonary tuberculosis &#40;between December 2007 and July 2008&#41;&#46; They also had to accept to take part in the study&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The TST and the QFT-GIT were performed on all patients included in the study&#46; Patients with a high risk of latent tuberculosis were taken to be any patient living in a TB endemic area&#44; any patient that claimed to have been in contact with people infected with TB or any patient with previous history of TB and any patient who had a chest x-ray that was compatible with a previous TB infection&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Tuberculin skin test</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The TST was performed by TB specialist nurses&#46; All patients were administered 2 IU Rt-23 PPD on the inside of their forearm&#46; The results were assessed after 72 hours in accordance with the established regulations&#46; The test was considered positive with an induration of &#8805;5mm&#46; In patients that had been previously vaccinated with BCG&#44; the TST was considered to be positive with an induration of &#8805;10mm &#40;except in patients with previous contact with tuberculosis&#44; chest x-ray suggestive of TB&#44; infected by the human immunodeficiency virus &#91;HIV&#93; or diagnosed with silicosis&#41;&#46; The test was repeated 10 days later in patients that had no induration on the first test to rule out a possible booster effect&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Quantiferon<span class="elsevierStyleSup">&#174; </span>- TB Gold In Tube</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The QFT-GIT test &#40;Cellestis&#44; Carnegie&#44; Victoria&#44; Australia&#41; was performed according to the manufacturer&#8217;s instructions&#46; The blood samples were&#160; processed 6 to 8 hours after being extracted&#46; The blood was put into 3 different tubes&#58; one did not contain antigens &#40;control&#41;&#44; the second tube contained TB antigens and the third contained phytohaemagglutinin &#40;mitogen or positive control&#41;&#46; The incubation time was 18-24h at 37&#186;C&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The results were considered positive&#44; negative or inconclusive according to the criteria established in the manufacturer&#8217;s software&#46; TST and QFT-GIT were performed on the same day&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Pulmonologist&#8217;s assessment</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Two pulmonologists who are experts in TB &#40;one in each hospital&#41; assessed the risk factors for latent tuberculosis&#44; including medical history of active TB or contact with an active case&#44; vaccination&#44; or born in a TB endemic area&#46; The results of TST and chest x-ray were also assessed&#46; All the data was assessed to determine whether the patient had been previously infected with <span class="elsevierStyleItalic">M&#46; tuberculosis</span>&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Statistical analysis</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The data analysis was performed with the statistical software SPSS &#40;SPSS version 12&#46;0&#44; Chicago&#44; IL&#41; and <span class="elsevierStyleItalic">P </span>values less than 0&#46;05 were considered significant&#46; Cohen&#8217;s kappa coefficient was used to calculate the level of agreement between the two tests &#40;TST and QFT-GIT&#41;&#46; The following criteria were used to interpret the results &#40;according to Landis and Koch&#41;&#58; kappa below 0&#46;00 poor&#44; 0&#46;00-0&#46;20 slight&#44; 0&#46;21-0&#46;40 fair&#44; 0&#46;41-0&#46;60 moderate&#44; 0&#46;61-0&#46;80 substantial and 0&#46;81-1&#46;00 almost perfect&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Characteristics of the population studied </span>&#40;Table 1&#41;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">A total of 54 patients were included between December 2007 and July 2008&#46; All the patients were negative for HIV&#46; Eight had serum albumin levels below 3&#46;20mg&#47;dl&#46; The majority &#40;31&#59; 57&#46;4&#37;&#41; had not had the BCG vaccine&#46; Ten of the patients had a medical history of TB&#44; two of them had not been treated correctly and one suffered a relapse of tuberculosis&#46; No cases of primary infection or reactivation of tuberculosis were detected during the follow-up&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">TST&#44; QFT-GIT and pulmonologist&#8217;s assessment</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">TST had a 29&#46;6&#37; prevalence of positives &#40;16 patients&#41; for the first test and 31&#46;5&#37; &#40;17 patients&#41; for the second one&#46; TST had 5&#46;8&#37; of false positives and three false negatives &#40;8&#46;1&#37;&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">A positive chest x-ray detected 6 additional cases of latent TB &#40;42&#46;6&#37;&#41; and the pulmonologist&#8217;s assessment detected 7 additional cases &#40;44&#46;4&#37;&#41;&#46; The pulmonologist found evidence of previous tuberculosis infection in 14 cases &#40;26&#46;5&#37;&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">There were 10 positive cases &#40;18&#46;5&#37;&#41;&#44; 34 negative &#40;62&#46;96&#37;&#41; and 10 inconclusive results in the QFT-GIT&#46; Nine &#40;26&#37;&#41; of the negatives had a medical history of TB&#44; a chest x-ray or a positive pulmonologist&#8217;s assessment&#46; Five of the inconclusive cases were re-evaluated &#40;1 stayed negative and the other 4 inconclusive&#41;&#46; Of the 9 inconclusive results&#44; 1 patient had a positive TST and the others had an induration of 0mm&#46; Three of the patients had a low risk for TB and 6 had a high risk&#46; The factors associated with an inconclusive QFT-GIT are shown in Table 2&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">High-risk patients compared with low-risk patients</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">A total of 32 patients &#40;59&#37;&#41; were at high risk and the other 22 &#40;41&#37;&#41; were at low risk of latent tuberculosis&#46; Neither of the two tests &#40;TST&#47;QIT-GIT&#41; was able to distinguish between the high-risk and low-risk patients&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Agreement between the TST&#44; QFT-GIT and the </span><span class="elsevierStyleBold">pulmonologist&#8217;s assessment</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The agreement between the three diagnosis methods is shown in Table 3&#46; A posterior analysis between the conflicting tests showed that QFT-GIT was positive in 3 patients that were negative for tuberculin and was negative in 9 patients that were positive for tuberculin&#46; The TST was positive in 10 patients who were found to be positive by the pulmonologist and negative in 7 patients considered positive for TB by the pulmonologist&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">As there is no gold standard diagnosis technique for latent tuberculosis&#44; several authors have compared the use of IGRA with TST in different groups of patients &#40;general population&#44; children&#44; hospitalised patients at-risk and immunocompromised patients&#41;&#46;<span class="elsevierStyleSup">1&#44;4-5</span> TST has been used routinely despite its low specificity&#44; high number of false positives &#40;previous vaccination with BCG or infection by non-tuberculosis mycobacteria&#41;&#44; and low sensitivity &#40;high number of false negatives in immunocompromised patients and patients with cutaneous anergy&#41;&#46; Woeltje et al studied 307 patients on HD&#44; 32&#37; had cutaneous anergy to three different allergens and 9&#37; of the patients without anergy tested positive for TST&#46;<span class="elsevierStyleSup">8</span> In our study&#44; the positive response to TST was similar to that described for patients on HD&#46;<span class="elsevierStyleSup">2</span> The finding of 6 TST-negative patients with positive chest x-ray can be explained by the rate of cutaneous anergy described above in HD patients&#46; Immune system impairment has been described in uraemic patients leading to a high rate of infections and mortality&#46;<span class="elsevierStyleSup">9</span> This delayed immune response leads to interleukin-2 deficit&#44; B-cell lymphopenia&#44; increased cell apoptosis&#44; impaired T-lymphocyte activation and more antigen-presenting cells&#46;<span class="elsevierStyleSup">10-15</span> All these changes in the host&#8217;s responses may explain the negative results for TST&#44; regardless of whether they had cutaneous anergy or not&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The use of IGRA in HD patients has been researched with similar results to ours&#46; One of these studies was specifically designed to compare TST with QFT-GIT in 203 patients on HD and found a reasonable correlation between them&#46; Therefore&#44; TST for TB screening without a physician&#8217;s assessment was not recommended for this population&#44; but rather using a combination of IGRA with a physician&#8217;s assessment&#46;<span class="elsevierStyleSup">16</span> More recently&#44; Torres et al found a moderate level of agreement between both tests with a similar sample size to ours&#46; This study included hospitalised patients with a high risk of suffering from TB &#40;some on HD&#41;&#46; They recommended using QFT-GIT routinely in this type of patients&#44; at least in cases on HD&#44; to try and establish when to treat the tuberculosis&#46;<span class="elsevierStyleSup">4</span> These results in PD patients can be explained by cutaneous anergy as well as the low production of QFT-GIT and other cytokines&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">In this study&#44; 16&#37; of patients were inconclusive for QFT-GIT&#46; Our results coincide with those of Manuel et al&#44; although these authors studied a different group of immunocompromised patients &#40;with chronic liver disease&#41;&#46;<span class="elsevierStyleSup">5</span> By analysing all these data&#44; we could come to the conclusion that the inconclusive results are probably related to immunodeficiency&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">This study investigated for the first time the contribution of QFT-GIT to improving the diagnosis of tuberculosis in PD patients&#46; Its main weakness is the number of patients who had a positive skin test and&#47;or QTF-GIT&#46; Our results correlate well with the percentage of positive results found in the few publications there are&#44; and the number of patients studied is relatively high given the low incidence and prevalence of PD patients in Spain&#46;<span class="elsevierStyleSup">17</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">To conclude&#44; we believe that IGRA represent an important advance in the diagnosis of tuberculosis&#44; and at this moment they can complement the TST but not replace it&#46; The role of IGRA in the screening of at-risk people&#44; including PD patients diagnosed with CRF&#44; still has to be defined&#59; therefore&#44; longitudinal studies that provide solid evidence on their prognostic value in the long-term development of TB are needed&#46;</p><p class="elsevierStylePara"><a href="grande&#47;10765&#95;16025&#95;15371&#95;en&#95;pages&#95;from&#95;107651t1&#46;jpg" class="elsevierStyleCrossRefs"><img src="10765_16025_15371_en_pages_from_107651t1.jpg" alt="Patients&#191; characteristics"></img></a></p><p class="elsevierStylePara">Table 1&#46; Patients&#191; characteristics</p><p class="elsevierStylePara"><a href="grande&#47;10765&#95;16025&#95;15372&#95;en&#95;pages&#95;from&#95;107651t2r&#46;jpg" class="elsevierStyleCrossRefs"><img src="10765_16025_15372_en_pages_from_107651t2r.jpg" alt="Univariate analysis of the risk factors for inconclusive results of Quantiferon-TB gold &#40;QTF-G&#41;"></img></a></p><p class="elsevierStylePara">Table 2&#46; Univariate analysis of the risk factors for inconclusive results of Quantiferon-TB gold &#40;QTF-G&#41;</p><p class="elsevierStylePara"><a href="grande&#47;10765&#95;16025&#95;15373&#95;en&#95;pages&#95;from&#95;107651t3&#46;jpg" class="elsevierStyleCrossRefs"><img src="10765_16025_15373_en_pages_from_107651t3.jpg" alt="Agreement between the tuberculin skin test&#44; Quantiferon-TB Gold and assessment by a pulmonologist&#44; excluding patients with inconclusive results for QFT-GIT&#42;"></img></a></p><p class="elsevierStylePara">Table 3&#46; Agreement between the tuberculin skin test&#44; Quantiferon-TB Gold and assessment by a pulmonologist&#44; excluding patients with inconclusive results for QFT-GIT&#42;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Objective&#58;&#160;</span> The risk for tuberculosis &#40;TB&#41; is increased in patients with chronic renal failure and dialysis&#46; Tuberculin skin test &#40;TST&#41; is the classical diagnostic method for screening despite its low sensitivity&#46; New methods based on interferon-gamma have been developed&#46; The aim of this study was to evaluate if Quantiferon<span class="elsevierStyleSup">&#174;</span> TB-gold In Tube &#40;QFT-GIT&#41; could be useful in the diagnosis of TB infection in patients on peritoneal dialysis &#40;PD&#41;&#46; <span class="elsevierStyleBold">Patients and methods&#58;</span> Fifty-four patients on PD were included in the study&#46; They were evaluated for latent tuberculosis with QFT-GIT&#44; TST and an assessment by an expert pulmonologist using patient&#8217;s medical history and x-rays&#46; Agreement between test results was determined&#46; <span class="elsevierStyleBold">Results&#58;T</span>he prevalence of a positive TST was 29&#46;6&#37; for the first test and 31&#46;5&#37; for the second &#40;booster effect&#41;&#46; A positive chest x-ray increased the rate of detection of patients with latent TB infection up to 42&#46;6&#37; and the expert physician&#8217;s evaluation to 44&#46;4&#37;&#46; The correlation between QFT-GIT and TST was fair &#40;k&#61;0&#46;36&#59; P&#61;&#46;006&#41;&#44; as it was between TST and expert physician&#8217;s evaluation &#40;k&#61;0&#46;257&#59; P&#61;&#46;06&#41;&#46; <span class="elsevierStyleBold">Conclusions&#58;</span> According to our experience QFT-GIT represents an important advantage in the diagnosis of latent TB infection in chronic renal failure patients on PD&#46; It may complement but not replace TST&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleItalic">&#160;</span></p>"
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