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    "textoCompleto" => "<p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">After many years without any new developments in this field&#44; new diagnostic tools have recently been incorporated in both the latent phase and in the active infection phase&#46; New methods were required in the study of the general population to improve the existing arsenal&#44; and in the case of the renal patient&#44; especially in advanced stages and in replacement therapy&#44; the need for improvement was evident&#46; As a result of the publication in this issue of the Journal on a study analysing the results of a comparison between the tuberculin skin test &#40;TST&#41; and new <span class="elsevierStyleItalic">in vitro </span>diagnostic methods for the detection of latent tuberculosis infection &#40;LTBI&#41;&#44; we will summarise the potential impact of these methods on the treatment of renal disease patients in these Editorial Comments&#46; </p><p class="elsevierStylePara"><br></br></p><p class="elsevierStylePara"><span class="elsevierStyleBold">TUBERCULOSIS DISEASE TODAY </span></p><p class="elsevierStylePara">According to data from the World Health Organization &#40;WHO&#41;&#44;1<span class="elsevierStyleSup"> </span>one third of the world population currently has LTBI&#46; In 2006&#44; there were more than 9200 000 new cases of tuberculosis &#40;TB&#41; worldwide&#44; with a prevalence of more than 14 million people and nearly 1&#46;7 million deaths&#44; which represents a mortality rate of 18&#37;&#46; The WHO believes that the global incidence rate reached its peak in 2002&#44; with variations related to population changes&#46; According to the latest data published by the <span class="elsevierStyleItalic">Red de Vigilancia Epidemiol&#243;gica de Espa&#241;a </span>&#40;Spanish epidemiological surveillance network&#41;&#44;2<span class="elsevierStyleSup"> </span>6070 cases of TB were recorded in 2009&#46; However&#44; these figures should be viewed with caution because even though TB is a notifiable disease&#44; it is estimated that at least one-third of the cases go unreported&#46; </p><p class="elsevierStylePara">According to the Registry of the Spanish Society of Nephrology &#40;S&#46;E&#46;N&#46;&#41;&#44; the incidence of patients receiving renal replacement therapy &#40;RRT&#41; in 2009 was 129 patients per million population &#40;pmp&#41;&#44; with the majority &#40;85&#37;&#41; in haemodialysis &#40;HD&#41;&#44; 12&#37; in peritoneal dialysis &#40;PD&#41; and 2&#46;8&#37; with pre-dialysis kidney transplant &#40;KT&#41;&#46; The prevalence was 1039&#46;4 patients pmp&#44; with 47&#46;67&#37; in HD&#44; 4&#46;8&#37; in PD and 47&#46;51&#37; with functioning grafts&#46; Although the incidence of patients receiving RRT has remained stable over the last ten years in Spain&#44; there are differences between the different regions of the country&#46; In Europe&#44; the incidence varies from 94&#46;6 to 263 patients pmp&#44; and the prevalence between 64&#46;9 and 1115&#46;1 patients pmp&#44; so we are in the average range compared to surrounding countries&#46;3<span class="elsevierStyleSup"> </span>It is clear that transplant patients&#44; who are immunocompromised&#44; as well as those undergoing dialysis&#44; which causes uraemia-related alterations in the immune system&#44; present a state of immunodeficiency that makes them more susceptible to infection&#46; These alterations primarily affect cellular immunity&#44;4<span class="elsevierStyleSup"> </span>including the decreased proliferative response of the lymphocytes&#44; Interleukin-2 deficit&#44; peripheral B-lymphocyte deficiency and the increase in cellular apoptosis&#46;5-7<span class="elsevierStyleSup"> </span>As LTBI is characterised by a significant cellular immune response &#40;in the absence of detectable mycobacteria&#41;&#44; the alteration of this response could lead to an increase in the reactivation of TB in uraemic patients and a hyporesponse in the tests based on delayed hypersensitivity&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DIAGNOSIS OF TUBERCULOSIS INFECTION </span></p><p class="elsevierStylePara">The usual method to diagnose tuberculosis infection is the TST&#44; which clearly shows&#44; after injecting a purified protein derivative &#40;PPD&#41;&#44; a state of prior hypersensitivity in the body when confronted with this substance&#46; The tuberculin used in Europe is the RT-23 PPD&#46; In recent years&#44; new diagnostic methods have been investigated and approved based on <span class="elsevierStyleItalic">in vitro </span>quantification of the cellular immune response&#46; These methods&#44; generically called by the acronym IGRA &#40;Interferon-Gamma-Release Assays&#41;&#44; detect the release of interferon gamma in response to specific TB antigens&#46;8<span class="elsevierStyleSup"> </span>Interferon-gamma is an indispensable molecule in the protective immune response against this microorganism&#46; This cytokine&#44; produced by CD4&#43; T lymphocytes&#44; CD8&#43; T lymphocytes and NK cells&#44; activates infected macrophages&#44; with the consequent release of IL-1 and TNF-alpha which limit the growth and multiplication of the mycobacteria&#46; Individuals with a deficit in the receptors or in genes that encode the synthesis of this molecule are likely to present mycobacterial infections more often and with greater severity&#46; The same can be said for patients undergoing immunosuppressive treatment which interferes with these signalling pathways of the immune response&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">IN VITRO </span></span><span class="elsevierStyleBold">TRIALS BASED ON INTERFERON PRODUCTION &#40;IGRA&#41; </span></p><p class="elsevierStylePara">There are two techniques on the market for <span class="elsevierStyleItalic">in vitro </span>diagnosis of TB infection&#58; QuantiFERON-TB-Gold In Tube &#40;Cellestis&#174;&#44; Victoria&#44; Australia&#41;9 and T-SPOT&#46;TB &#40;Oxford Immunotec&#174;&#44; Oxford&#44; United Kingdom&#41;10&#46; First generation QuantiFERON TB&#44; approved by the Food and Drug Administration &#40;FDA&#41; of the United States in 2001&#44; detected the release of interferon-gamma in response to the TST&#46; In 2004&#44; the FDA approved the second generation of this diagnostic test called QuantiFERON-TB Gold&#44; which unlike the first generation&#44; does not use the mycobacterial antigens of the TST&#44; but rather synthetic peptides which simulate more specific antigens such as the Early Secreted Antigenic Target-6 &#40;ESAT-6&#41; and the Culture Filtrate Protein-10 &#40;CFP-10&#41;&#46; These two molecules are encoded by the RD-1 region of the <span class="elsevierStyleItalic">Mycobacterium tuberculosis </span>genome and significantly increase the specificity compared to the TST&#46; These antigens are absent in <span class="elsevierStyleItalic">M&#46; bovis </span>and in the majority of non-tuberculous mycobacteria &#40;with the exception of <span class="elsevierStyleItalic">M&#46; kansasii</span>&#44; <span class="elsevierStyleItalic">M&#46; marinum </span>or <span class="elsevierStyleItalic">M&#46; szulgai</span>&#41;&#46; At present&#44; the third generation of this test&#44; called QuantiFERON-TB Gold In Tube &#40;QFT-GIT&#41;&#44; is already on the market and includes a third mycobacterial antigen&#58; the TB 7&#46;7 and tubes specifically designed to collect blood samples for this test&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">VALIDITY OF QTF-GIT AND T&#46;SPOT&#46;TB IN PREDICTING THE DEVELOPMENT OF TUBERCULOSIS DISEASE </span></p><p class="elsevierStylePara">The risk of developing active TB in a person with a positive TST is estimated at 5&#37;-10&#37;&#46;11&#44;12 However&#44; there are few longitudinal studies that allow us to conclude the ability of IGRA to predict the risk of developing active TB&#46; </p><p class="elsevierStylePara">A study was conducted in Germany on 601 close contacts of people who had an acid-fast bacilli smear and were culture-positive for <span class="elsevierStyleItalic">M&#46; tuberculosis</span>&#46; The QFT-GIT yielded better performance in predicting active TB13 than the TST&#44; using a cut-off point of 5mm&#46; Five &#40;2&#46;3&#37;&#41; out of the 219 close contacts with an induration of &#62;5mm developed TB&#44; whereas six &#40;14&#46;6&#37;&#41; of the 41 close contacts with positive results from the QFT-GIT developed the disease&#46; However&#44; 59&#37; of the close contacts had an induration &#40;TST&#41; of 5-9mm&#46; The percentage of those considered TST-positive with a cut-off point of 10mm and developed active TB &#40;5 out of 90 &#91;5&#46;6&#37;&#93;&#41; was similar to the percentage who were QFT-GIT-positive &#40;6 out of 41 &#91;14&#46;6&#37;&#93;&#41;&#46; Furthermore&#44; only 2 out of 6 close contacts that were QFT-GIT-positive and developed active TB were microbiologically confirmed&#46; In another study&#44; sensitivity to predict subsequent active TB did not show any difference between the two tests&#46;14 </p><p class="elsevierStylePara">The outcome of another study on 339 immigrants in the Netherlands demonstrated that the TST and the QFT-GIT had similar validity in predicting active TB&#46;<span class="elsevierStyleSup">15 </span>Follow-up was carried out for 2 years on those close contacts with a TST&#62;5 between 0 and 3 months after the diagnosis of the index patient&#46; Nine &#40;3&#46;1&#37;&#41; out of 288 close contacts with a TST&#62;10mm developed active TB&#44; and seven &#40;3&#46;8&#37;&#41; out of 184 with a TST&#62;15mm&#44; five &#40;2&#46;8&#37;&#41; out of 178 with a positive QFT-GIT&#44; and six &#40;3&#46;3&#37;&#41; out of 181 with a positive T-SPOT&#46;TB also developed the disease&#46; Sensitivity to detect the development of active TB in the follow-up period was 100&#37; for the TST with a cut-off point of 10mm&#44; 88&#37; for a TST with a cut-off of 15mm&#44; 63&#37; for the QFT-GIT and 75&#37; for the T-SPOT&#46;TB&#46; Although the TST with a cut-off point of 10mm detected the greatest number of close contacts who developed active TB &#40;100&#37;&#41; and the QFT-GIT identified the least number of close contacts who developed active TB &#40;5&#47;&#91;63&#37;&#93;&#41;&#44; the sensitivity of both tests were not any different&#46; In view of everything published&#44; IGRA do not seem to bring any added advantage in predicting the development of tuberculosis disease compared to the TST&#46; </p><p class="elsevierStylePara"><br></br></p><p class="elsevierStylePara"><span class="elsevierStyleBold">USE OF QTF-GIT AND T&#46;SPOT&#46;TB IN CONTACT TRACING </span></p><p class="elsevierStylePara">So far&#44; there have been numerous studies carried out based on TB contact tracing&#46; It was initially based on the TST&#44; but since the introduction of IGRA&#44; the latter have often been the subject of research in this group&#46;<span class="elsevierStyleSup">16&#44; 7 </span>In two papers&#44; it was observed that more recent exposure &#40;longer exposure or a greater number of alcohol-resistant bacilli in the sputum&#41; is associated with more positive IGRA than positive TST&#44; which suggests that IGRA could be more effective in the detection of recent infection&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">SENSITIVITY OF SCREENING TESTS </span></p><p class="elsevierStylePara">There are two meta-analyses<span class="elsevierStyleSup">18&#44; 9 </span>that summarise the results obtained so far on IGRA &#40;Table 1&#41;&#46; </p><p class="elsevierStylePara"><br></br></p><p class="elsevierStylePara"><span class="elsevierStyleBold">INVALID RESULTS FOR BOTH TESTS </span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Inconclusive results for QTF-GIT </span></p><p class="elsevierStylePara">Out of a total of 21 922 patients&#44; 469 &#40;2&#46;14&#37;&#41; presented inconclusive results &#40;CI 95&#37;&#44; 0&#46;02-0&#46;023&#41;&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Inconclusive results for T-SPOT&#46;TB </span></p><p class="elsevierStylePara">Out of a total of 12 165 patients&#44; 462 &#40;3&#46;80&#37;&#41; had inconclusive results &#40;CI 95&#37;&#44; 0&#46;035-0&#46;042&#41;&#46; If 80 cases were added in which there was not a sufficient number of cells available for testing&#44; the number of inconclusive results would rise to 4&#46;46 &#40;CI 95&#37;&#44; 0&#46;041-0&#46;048&#41;&#46; </p><p class="elsevierStylePara">The difference in the percentage of inconclusive results between the two IGRA is greater for the QTF-GIT&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Inconclusive results in immunocompromised patients </span></p><p class="elsevierStylePara">In cases where the QTF-GIT increases up to 4&#46;42&#37; and in cases where the T&#46;SPOT&#46;TB is up to 6&#46;12&#37;&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">ADVANTAGES OF TECHNIQUES FOR IGRA TESTING VERSUS TUBERCULIN SKIN TEST </span></p><p class="elsevierStylePara">IGRA techniques offer important advantages over the TST&#58; <span class="elsevierStyleItalic">1&#41; </span>They do not interfere with the BCG vaccine&#59; <span class="elsevierStyleItalic">2&#41; </span>They avoid subjectivity in interpreting and the reading visits&#44; and <span class="elsevierStyleItalic">3&#41; </span>They include a positive control that provides valuable information when interpreting a presumably false negative test as a true negative or inconclusive &#40;technical errors or immunosuppression&#41;&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Experience with dialysis patients </span></p><p class="elsevierStylePara">Due to the alterations in the immune system&#44; dialysis patients are particularly likely to develop active TB&#44; which could reach a TB incidence of up to eight times greater than in the general population&#46;<span class="elsevierStyleSup">20 </span>Moreover&#44; it is associated with a higher mortality&#44; which is why the detection of LTBI is an important issue in this population&#46; For decades&#44; the TST has yielded poor results in detecting latent tuberculosis in these patients and an anergy rate that could reach 44&#37;&#46;<span class="elsevierStyleSup">21-24 </span>Although they are beginning to publish studies on the validity of IGRA in the detection of LTBI&#44; comparing them occasionally with tuberculin&#44; we have little data on sensitivity and the rate of inconclusive results in patients with renal disease in general&#44; and specifically on treatment with replacement techniques&#46; </p><p class="elsevierStylePara">To date&#44; there are no similar studies available on the PD population&#46; In the study published in this issue&#44; the validity of IGRA versus TST was analysed for the detection of LTBI in 54 PD patients&#44; and it revealed promising results&#46; As in the study carried out on HD patients&#44; there is a substantial percentage of inconclusive results&#46; Therefore&#44; it is vital to accumulate new series to strengthen and clarify the results&#46; In that study&#44; an assessment by an expert pulmonologist is used as the <span class="elsevierStyleItalic">gold standard </span>to detect LTBI and the authors concluded that IGRA could complement the tuberculin skin test&#44; but there is still not sufficient evidence&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Kidney transplant patients </span></p><p class="elsevierStylePara">The prevalence of TB among kidney transplant recipients has been widely published&#46; The incidence of LTBI among these patients is estimated at 20-70 times higher than in the general population&#46;25 In these patients&#44; TB contributes to graft dysfunction through direct effects on the graft as well as drug interactions&#46; Furthermore&#44; it increases mortality&#46;26<span class="elsevierStyleSup"> </span>Reducing the risk of TB is an important priority in organ transplants&#44; especially in countries where the disease is endemic&#46; Anti-tuberculosis treatment is complicated&#44; particularly due to the anti-TB drugs that induce cytochrome P-450 &#40;rifampicin&#41;27 and liver dysfunction caused by Isoniazid&#46;28<span class="elsevierStyleSup"> </span>The results on IGRA in solid-organ transplant are controversial&#44; while in some studies the sensitivity is similar to the TST&#44; in others&#44; it is highe<span class="elsevierStyleSup">r&#46;</span><span class="elsevierStyleSup">25&#44;29</span><span class="elsevierStyleSup"> </span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Utility of IGRA in the future </span></p><p class="elsevierStylePara">With current knowledge&#44; the question is whether or not IGRA could replace TST to rule out tuberculosis infection in immunocompromised patients&#46; Pending further studies about this subject&#44; we can state that&#58; <span class="elsevierStyleItalic">1&#41; </span>Currently&#44; there is not enough data available on the long-term development of TB that enables us to make the decision whether or not to treat based solely on the results of IGRA in patients receiving RRT&#59; <span class="elsevierStyleItalic">2&#41; </span>The theoretical basis of IGRA indicates that these techniques measure a different type of immune response than that which occurs in the delayed hypersensitivity to the TST&#59; <span class="elsevierStyleItalic">3&#41; </span>Unlike what occurs in the contact tracing study&#44; in immunocompromised patients&#44; both recent and remote tuberculosis infections are just as important&#59; <span class="elsevierStyleItalic">4&#41; </span>There seems to be no sufficient evidence as of yet that shows that IGRA can replace the TST&#44; and <span class="elsevierStyleItalic">5&#41; </span>We can conclude that IGRA are supplemental assays to the TST as performing both tests simultaneously increases the likelihood of diagnosing TB&#46; In any event&#44; IGRA represent a significant advancement in the diagnosis of tuberculosis infection&#46; </p><p class="elsevierStylePara"><a href="grande&#47;10823&#95;16025&#95;15364&#95;en&#95;pages&#95;from&#95;10823t1&#46;jpg" class="elsevierStyleCrossRefs"><img src="10823_16025_15364_en_pages_from_10823t1.jpg" alt="Results of the study comparing different diagnostic methods for detecting confirmed tuberculosis"></img></a></p><p class="elsevierStylePara">Table 1&#46; Results of the study comparing different diagnostic methods for detecting confirmed tuberculosis</p>"
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Advances in the diagnosis of latent tuberculosis infection in patients receiving renal replacement therapy
Avances en el diagnóstico de la infección tuberculosa latente en pacientes en tratamiento renal sustitutivo
, M.. Arias Guillénb, R.. Palomarc, M.. Ariasc
b Servicio de Neumología, Hospital Universitario Central de Asturias-INS, Oviedo, Asturias,
c Servicio de Nefrología, Hospital Marqués de Valdecilla. Universidad de Cantabria. ISCIII (REDINREN 06/16). Fundación Marqués de Valdecilla-IFIMAV, Santander, Cantabria,
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    "textoCompleto" => "<p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">After many years without any new developments in this field&#44; new diagnostic tools have recently been incorporated in both the latent phase and in the active infection phase&#46; New methods were required in the study of the general population to improve the existing arsenal&#44; and in the case of the renal patient&#44; especially in advanced stages and in replacement therapy&#44; the need for improvement was evident&#46; As a result of the publication in this issue of the Journal on a study analysing the results of a comparison between the tuberculin skin test &#40;TST&#41; and new <span class="elsevierStyleItalic">in vitro </span>diagnostic methods for the detection of latent tuberculosis infection &#40;LTBI&#41;&#44; we will summarise the potential impact of these methods on the treatment of renal disease patients in these Editorial Comments&#46; </p><p class="elsevierStylePara"><br></br></p><p class="elsevierStylePara"><span class="elsevierStyleBold">TUBERCULOSIS DISEASE TODAY </span></p><p class="elsevierStylePara">According to data from the World Health Organization &#40;WHO&#41;&#44;1<span class="elsevierStyleSup"> </span>one third of the world population currently has LTBI&#46; In 2006&#44; there were more than 9200 000 new cases of tuberculosis &#40;TB&#41; worldwide&#44; with a prevalence of more than 14 million people and nearly 1&#46;7 million deaths&#44; which represents a mortality rate of 18&#37;&#46; The WHO believes that the global incidence rate reached its peak in 2002&#44; with variations related to population changes&#46; According to the latest data published by the <span class="elsevierStyleItalic">Red de Vigilancia Epidemiol&#243;gica de Espa&#241;a </span>&#40;Spanish epidemiological surveillance network&#41;&#44;2<span class="elsevierStyleSup"> </span>6070 cases of TB were recorded in 2009&#46; However&#44; these figures should be viewed with caution because even though TB is a notifiable disease&#44; it is estimated that at least one-third of the cases go unreported&#46; </p><p class="elsevierStylePara">According to the Registry of the Spanish Society of Nephrology &#40;S&#46;E&#46;N&#46;&#41;&#44; the incidence of patients receiving renal replacement therapy &#40;RRT&#41; in 2009 was 129 patients per million population &#40;pmp&#41;&#44; with the majority &#40;85&#37;&#41; in haemodialysis &#40;HD&#41;&#44; 12&#37; in peritoneal dialysis &#40;PD&#41; and 2&#46;8&#37; with pre-dialysis kidney transplant &#40;KT&#41;&#46; The prevalence was 1039&#46;4 patients pmp&#44; with 47&#46;67&#37; in HD&#44; 4&#46;8&#37; in PD and 47&#46;51&#37; with functioning grafts&#46; Although the incidence of patients receiving RRT has remained stable over the last ten years in Spain&#44; there are differences between the different regions of the country&#46; In Europe&#44; the incidence varies from 94&#46;6 to 263 patients pmp&#44; and the prevalence between 64&#46;9 and 1115&#46;1 patients pmp&#44; so we are in the average range compared to surrounding countries&#46;3<span class="elsevierStyleSup"> </span>It is clear that transplant patients&#44; who are immunocompromised&#44; as well as those undergoing dialysis&#44; which causes uraemia-related alterations in the immune system&#44; present a state of immunodeficiency that makes them more susceptible to infection&#46; These alterations primarily affect cellular immunity&#44;4<span class="elsevierStyleSup"> </span>including the decreased proliferative response of the lymphocytes&#44; Interleukin-2 deficit&#44; peripheral B-lymphocyte deficiency and the increase in cellular apoptosis&#46;5-7<span class="elsevierStyleSup"> </span>As LTBI is characterised by a significant cellular immune response &#40;in the absence of detectable mycobacteria&#41;&#44; the alteration of this response could lead to an increase in the reactivation of TB in uraemic patients and a hyporesponse in the tests based on delayed hypersensitivity&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DIAGNOSIS OF TUBERCULOSIS INFECTION </span></p><p class="elsevierStylePara">The usual method to diagnose tuberculosis infection is the TST&#44; which clearly shows&#44; after injecting a purified protein derivative &#40;PPD&#41;&#44; a state of prior hypersensitivity in the body when confronted with this substance&#46; The tuberculin used in Europe is the RT-23 PPD&#46; In recent years&#44; new diagnostic methods have been investigated and approved based on <span class="elsevierStyleItalic">in vitro </span>quantification of the cellular immune response&#46; These methods&#44; generically called by the acronym IGRA &#40;Interferon-Gamma-Release Assays&#41;&#44; detect the release of interferon gamma in response to specific TB antigens&#46;8<span class="elsevierStyleSup"> </span>Interferon-gamma is an indispensable molecule in the protective immune response against this microorganism&#46; This cytokine&#44; produced by CD4&#43; T lymphocytes&#44; CD8&#43; T lymphocytes and NK cells&#44; activates infected macrophages&#44; with the consequent release of IL-1 and TNF-alpha which limit the growth and multiplication of the mycobacteria&#46; Individuals with a deficit in the receptors or in genes that encode the synthesis of this molecule are likely to present mycobacterial infections more often and with greater severity&#46; The same can be said for patients undergoing immunosuppressive treatment which interferes with these signalling pathways of the immune response&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">IN VITRO </span></span><span class="elsevierStyleBold">TRIALS BASED ON INTERFERON PRODUCTION &#40;IGRA&#41; </span></p><p class="elsevierStylePara">There are two techniques on the market for <span class="elsevierStyleItalic">in vitro </span>diagnosis of TB infection&#58; QuantiFERON-TB-Gold In Tube &#40;Cellestis&#174;&#44; Victoria&#44; Australia&#41;9 and T-SPOT&#46;TB &#40;Oxford Immunotec&#174;&#44; Oxford&#44; United Kingdom&#41;10&#46; First generation QuantiFERON TB&#44; approved by the Food and Drug Administration &#40;FDA&#41; of the United States in 2001&#44; detected the release of interferon-gamma in response to the TST&#46; In 2004&#44; the FDA approved the second generation of this diagnostic test called QuantiFERON-TB Gold&#44; which unlike the first generation&#44; does not use the mycobacterial antigens of the TST&#44; but rather synthetic peptides which simulate more specific antigens such as the Early Secreted Antigenic Target-6 &#40;ESAT-6&#41; and the Culture Filtrate Protein-10 &#40;CFP-10&#41;&#46; These two molecules are encoded by the RD-1 region of the <span class="elsevierStyleItalic">Mycobacterium tuberculosis </span>genome and significantly increase the specificity compared to the TST&#46; These antigens are absent in <span class="elsevierStyleItalic">M&#46; bovis </span>and in the majority of non-tuberculous mycobacteria &#40;with the exception of <span class="elsevierStyleItalic">M&#46; kansasii</span>&#44; <span class="elsevierStyleItalic">M&#46; marinum </span>or <span class="elsevierStyleItalic">M&#46; szulgai</span>&#41;&#46; At present&#44; the third generation of this test&#44; called QuantiFERON-TB Gold In Tube &#40;QFT-GIT&#41;&#44; is already on the market and includes a third mycobacterial antigen&#58; the TB 7&#46;7 and tubes specifically designed to collect blood samples for this test&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">VALIDITY OF QTF-GIT AND T&#46;SPOT&#46;TB IN PREDICTING THE DEVELOPMENT OF TUBERCULOSIS DISEASE </span></p><p class="elsevierStylePara">The risk of developing active TB in a person with a positive TST is estimated at 5&#37;-10&#37;&#46;11&#44;12 However&#44; there are few longitudinal studies that allow us to conclude the ability of IGRA to predict the risk of developing active TB&#46; </p><p class="elsevierStylePara">A study was conducted in Germany on 601 close contacts of people who had an acid-fast bacilli smear and were culture-positive for <span class="elsevierStyleItalic">M&#46; tuberculosis</span>&#46; The QFT-GIT yielded better performance in predicting active TB13 than the TST&#44; using a cut-off point of 5mm&#46; Five &#40;2&#46;3&#37;&#41; out of the 219 close contacts with an induration of &#62;5mm developed TB&#44; whereas six &#40;14&#46;6&#37;&#41; of the 41 close contacts with positive results from the QFT-GIT developed the disease&#46; However&#44; 59&#37; of the close contacts had an induration &#40;TST&#41; of 5-9mm&#46; The percentage of those considered TST-positive with a cut-off point of 10mm and developed active TB &#40;5 out of 90 &#91;5&#46;6&#37;&#93;&#41; was similar to the percentage who were QFT-GIT-positive &#40;6 out of 41 &#91;14&#46;6&#37;&#93;&#41;&#46; Furthermore&#44; only 2 out of 6 close contacts that were QFT-GIT-positive and developed active TB were microbiologically confirmed&#46; In another study&#44; sensitivity to predict subsequent active TB did not show any difference between the two tests&#46;14 </p><p class="elsevierStylePara">The outcome of another study on 339 immigrants in the Netherlands demonstrated that the TST and the QFT-GIT had similar validity in predicting active TB&#46;<span class="elsevierStyleSup">15 </span>Follow-up was carried out for 2 years on those close contacts with a TST&#62;5 between 0 and 3 months after the diagnosis of the index patient&#46; Nine &#40;3&#46;1&#37;&#41; out of 288 close contacts with a TST&#62;10mm developed active TB&#44; and seven &#40;3&#46;8&#37;&#41; out of 184 with a TST&#62;15mm&#44; five &#40;2&#46;8&#37;&#41; out of 178 with a positive QFT-GIT&#44; and six &#40;3&#46;3&#37;&#41; out of 181 with a positive T-SPOT&#46;TB also developed the disease&#46; Sensitivity to detect the development of active TB in the follow-up period was 100&#37; for the TST with a cut-off point of 10mm&#44; 88&#37; for a TST with a cut-off of 15mm&#44; 63&#37; for the QFT-GIT and 75&#37; for the T-SPOT&#46;TB&#46; Although the TST with a cut-off point of 10mm detected the greatest number of close contacts who developed active TB &#40;100&#37;&#41; and the QFT-GIT identified the least number of close contacts who developed active TB &#40;5&#47;&#91;63&#37;&#93;&#41;&#44; the sensitivity of both tests were not any different&#46; In view of everything published&#44; IGRA do not seem to bring any added advantage in predicting the development of tuberculosis disease compared to the TST&#46; </p><p class="elsevierStylePara"><br></br></p><p class="elsevierStylePara"><span class="elsevierStyleBold">USE OF QTF-GIT AND T&#46;SPOT&#46;TB IN CONTACT TRACING </span></p><p class="elsevierStylePara">So far&#44; there have been numerous studies carried out based on TB contact tracing&#46; It was initially based on the TST&#44; but since the introduction of IGRA&#44; the latter have often been the subject of research in this group&#46;<span class="elsevierStyleSup">16&#44; 7 </span>In two papers&#44; it was observed that more recent exposure &#40;longer exposure or a greater number of alcohol-resistant bacilli in the sputum&#41; is associated with more positive IGRA than positive TST&#44; which suggests that IGRA could be more effective in the detection of recent infection&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">SENSITIVITY OF SCREENING TESTS </span></p><p class="elsevierStylePara">There are two meta-analyses<span class="elsevierStyleSup">18&#44; 9 </span>that summarise the results obtained so far on IGRA &#40;Table 1&#41;&#46; </p><p class="elsevierStylePara"><br></br></p><p class="elsevierStylePara"><span class="elsevierStyleBold">INVALID RESULTS FOR BOTH TESTS </span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Inconclusive results for QTF-GIT </span></p><p class="elsevierStylePara">Out of a total of 21 922 patients&#44; 469 &#40;2&#46;14&#37;&#41; presented inconclusive results &#40;CI 95&#37;&#44; 0&#46;02-0&#46;023&#41;&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Inconclusive results for T-SPOT&#46;TB </span></p><p class="elsevierStylePara">Out of a total of 12 165 patients&#44; 462 &#40;3&#46;80&#37;&#41; had inconclusive results &#40;CI 95&#37;&#44; 0&#46;035-0&#46;042&#41;&#46; If 80 cases were added in which there was not a sufficient number of cells available for testing&#44; the number of inconclusive results would rise to 4&#46;46 &#40;CI 95&#37;&#44; 0&#46;041-0&#46;048&#41;&#46; </p><p class="elsevierStylePara">The difference in the percentage of inconclusive results between the two IGRA is greater for the QTF-GIT&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Inconclusive results in immunocompromised patients </span></p><p class="elsevierStylePara">In cases where the QTF-GIT increases up to 4&#46;42&#37; and in cases where the T&#46;SPOT&#46;TB is up to 6&#46;12&#37;&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">ADVANTAGES OF TECHNIQUES FOR IGRA TESTING VERSUS TUBERCULIN SKIN TEST </span></p><p class="elsevierStylePara">IGRA techniques offer important advantages over the TST&#58; <span class="elsevierStyleItalic">1&#41; </span>They do not interfere with the BCG vaccine&#59; <span class="elsevierStyleItalic">2&#41; </span>They avoid subjectivity in interpreting and the reading visits&#44; and <span class="elsevierStyleItalic">3&#41; </span>They include a positive control that provides valuable information when interpreting a presumably false negative test as a true negative or inconclusive &#40;technical errors or immunosuppression&#41;&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Experience with dialysis patients </span></p><p class="elsevierStylePara">Due to the alterations in the immune system&#44; dialysis patients are particularly likely to develop active TB&#44; which could reach a TB incidence of up to eight times greater than in the general population&#46;<span class="elsevierStyleSup">20 </span>Moreover&#44; it is associated with a higher mortality&#44; which is why the detection of LTBI is an important issue in this population&#46; For decades&#44; the TST has yielded poor results in detecting latent tuberculosis in these patients and an anergy rate that could reach 44&#37;&#46;<span class="elsevierStyleSup">21-24 </span>Although they are beginning to publish studies on the validity of IGRA in the detection of LTBI&#44; comparing them occasionally with tuberculin&#44; we have little data on sensitivity and the rate of inconclusive results in patients with renal disease in general&#44; and specifically on treatment with replacement techniques&#46; </p><p class="elsevierStylePara">To date&#44; there are no similar studies available on the PD population&#46; In the study published in this issue&#44; the validity of IGRA versus TST was analysed for the detection of LTBI in 54 PD patients&#44; and it revealed promising results&#46; As in the study carried out on HD patients&#44; there is a substantial percentage of inconclusive results&#46; Therefore&#44; it is vital to accumulate new series to strengthen and clarify the results&#46; In that study&#44; an assessment by an expert pulmonologist is used as the <span class="elsevierStyleItalic">gold standard </span>to detect LTBI and the authors concluded that IGRA could complement the tuberculin skin test&#44; but there is still not sufficient evidence&#46; </p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Kidney transplant patients </span></p><p class="elsevierStylePara">The prevalence of TB among kidney transplant recipients has been widely published&#46; The incidence of LTBI among these patients is estimated at 20-70 times higher than in the general population&#46;25 In these patients&#44; TB contributes to graft dysfunction through direct effects on the graft as well as drug interactions&#46; Furthermore&#44; it increases mortality&#46;26<span class="elsevierStyleSup"> </span>Reducing the risk of TB is an important priority in organ transplants&#44; especially in countries where the disease is endemic&#46; Anti-tuberculosis treatment is complicated&#44; particularly due to the anti-TB drugs that induce cytochrome P-450 &#40;rifampicin&#41;27 and liver dysfunction caused by Isoniazid&#46;28<span class="elsevierStyleSup"> </span>The results on IGRA in solid-organ transplant are controversial&#44; while in some studies the sensitivity is similar to the TST&#44; in others&#44; it is highe<span class="elsevierStyleSup">r&#46;</span><span class="elsevierStyleSup">25&#44;29</span><span class="elsevierStyleSup"> </span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Utility of IGRA in the future </span></p><p class="elsevierStylePara">With current knowledge&#44; the question is whether or not IGRA could replace TST to rule out tuberculosis infection in immunocompromised patients&#46; Pending further studies about this subject&#44; we can state that&#58; <span class="elsevierStyleItalic">1&#41; </span>Currently&#44; there is not enough data available on the long-term development of TB that enables us to make the decision whether or not to treat based solely on the results of IGRA in patients receiving RRT&#59; <span class="elsevierStyleItalic">2&#41; </span>The theoretical basis of IGRA indicates that these techniques measure a different type of immune response than that which occurs in the delayed hypersensitivity to the TST&#59; <span class="elsevierStyleItalic">3&#41; </span>Unlike what occurs in the contact tracing study&#44; in immunocompromised patients&#44; both recent and remote tuberculosis infections are just as important&#59; <span class="elsevierStyleItalic">4&#41; </span>There seems to be no sufficient evidence as of yet that shows that IGRA can replace the TST&#44; and <span class="elsevierStyleItalic">5&#41; </span>We can conclude that IGRA are supplemental assays to the TST as performing both tests simultaneously increases the likelihood of diagnosing TB&#46; In any event&#44; IGRA represent a significant advancement in the diagnosis of tuberculosis infection&#46; </p><p class="elsevierStylePara"><a href="grande&#47;10823&#95;16025&#95;15364&#95;en&#95;pages&#95;from&#95;10823t1&#46;jpg" class="elsevierStyleCrossRefs"><img src="10823_16025_15364_en_pages_from_10823t1.jpg" alt="Results of the study comparing different diagnostic methods for detecting confirmed tuberculosis"></img></a></p><p class="elsevierStylePara">Table 1&#46; Results of the study comparing different diagnostic methods for detecting confirmed tuberculosis</p>"
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¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?