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Diagnosis of Tuberculosis in Dialysis Patients: Current Strategy
Liviu Segall and Adrian Covic
Nephrology Department, “Dr. C. I. Parhon” Hospital, University of Medicine and Pharmacy “Gr. T. Popa,” Iasi, ¸ Romania
Patients with ESRD undergoing chronic dialysis are much more prone to develop tuberculosis (TB) than the general population. In these patients, the diagnosis of TB disease is often difficult because of prevailing extrapulmonary involvement and nonspecific symptoms. The prevalence of latent TB infection (LTBI) in ESRD patients is elevated, and those who become infected are at high risk of developing active disease. Therefore, screening for LTBI in this population is recommended, aiming to prevent progression to active TB and secondary contamination of others. The tuberculin skin test (TST), the classic diagnostic tool for LTBI, has several major drawbacks, including poor sensitivity (because of a high prevalence of anergy in dialysis patients) and specificity [with false-positive tests in those vaccinated with bacille Calmette–Guerin (BCG)]. In the past ´ 10 years or so, new immunological tests using IFN- release assays (IGRAs) have become available and have shown superior sensitivity and specificity for the diagnosis of TB compared with the TST in several studies, some very recent ones including ESRD patients. Therefore, current strategy in dialysis patients should use these tests instead of TST for LTBI screening and as an aid for the diagnosis of active TB. Clin J Am Soc Nephrol 5: 1114 –1122, 2010. doi: 10.2215/CJN.09231209
atients with ESRD undergoing chronic dialysis are 6 to 25 times more likely to develop tuberculosis (TB) than the general population, mainly because of the impaired cellular immunity characteristic of this condition (1–3). Nosocomial transmission of TB has also been reported in hemodialysis (HD) centers (4). In a U.S. Renal Data System (USRDS) retrospective analysis, age, unemployment, Asian and Native American race, smoking, reduced body mass index, low serum albumin, ischemic heart disease, and anemia were all significant risk factors for HD patients to develop TB (5). The mortality rate of TB in dialysis patients is high, ranging from 17% to 75% (6). In the USRDS analysis mentioned above, TB was independently associated with a 42% increased mortality (5).
monly associated with fatigue, malnutrition, and other nonspecific complaints, possibly concealing the course of an underlying TB disease (7,11,12). This atypical presentation may often lead to a delay in accurate diagnosis and therapy, sometimes resulting in patients’ death. Therefore, nephrologists should always have a high degree of suspicion and consider the possibility of TB whenever confronted with an ESRD patient presenting with general symptoms such as fever, weight loss, and/or lymphadenopathy (10). The diagnosis would then require the isolation of acid-fast bacilli, the finding of typical caseating granuloma on biopsy, or the recovery of tubercle bacilli from the culture of the biopsy material (7).
Active TB in ESRD Patients: Atypical Clinical Presentation
In ESRD, the diagnosis of TB disease is often difficult because of prevailing extrapulmonary involvement and nonspecific symptoms. Extrapulmonary TB has been reported in as many as 60% to 80% of cases, either alone or associated with pulmonary TB. The most common forms of presentation are lymphadenitis, gastrointestinal, bone, genitourinary, peritonitis, pleural effusion, pericardial effusion, miliary TB, and pyrexia of unknown origin (7–10). On the other hand, uremia is com-
Difficulties in Diagnosing Latent TB Infection: The Limitations of the TST
According to several studies using different diagnostic approaches, the prevalence of latent TB infection (LTBI) in chronic dialysis patients is high, ranging between 20% and 70% (2,13,14), and those who become infected are at high risk of developing active disease (15,16). Therefore, screening for LTBI in this population is recommended, aiming to prevent progression to active TB and secondary contamination of other patients and healthcare workers (15). It has been shown that preventive treatment of latently infected people diminishes the risk of subsequent development of active TB by approximately 90% (17). In persons with LTBI, the very low bacterial burden makes it impossible to directly detect Mycobacterium tuberculosis: acidfast bacilli are rarely seen on sputum smear examination and tubercle bacilli are not found in cultures of respiratory speciISSN: 1555-9041/506 –1114
Published online ahead of print. Publication date available at www.cjasn.org. Correspondence: Dr. Liviu Segall, Clinica a IV-a Medicala—Nefrologie, Spitalul ˘ “Dr C. I. Parhon,” B-dul Carol I nr. 50, Iasi, Romania. Phone: 00-40-232-211834; ¸ Fax: 00-40-232-211752; E-mail: email@example.com Copyright © 2010 by the American Society of Nephrology
. On the other hand. a negative TST in these patients cannot be used to eliminate the possibility of latent or active TB (15). tuberculosis infection become sensitized to ESAT-6 or CFP-10 in vivo.27). tuberculosis proteins (18). avoiding the antigenic crossreactivity of PPD.. and the third and the fourth TST only resulted in an additional 4. measurement of PPD reactivity by in vitro quantitation of PPD-specific T cells was not affected by uremia-associated immunosuppression.” and recommend that both of them should be performed in every HD patient at the start of dialysis and repeated every year or whenever active TB disease is diagnosed in the unit. Also. the high-risk groups that are targeted for screening and preventive therapy are also those in which the TST most often fails to detect LTBI (15. Various strategies to improve the sensitivity of the TST in dialysis patients have been advocated. and there was no significant correlation between TST and chest radiograph results: patients with positive TST had negative chest x-rays and vice versa. positive TST results were only weakly correlated with previous TB disease. The prevalence of anergy to TST in the ESRD population is significantly higher than in the general population (44% versus 16%) (21).3% of 124 chronic HD patients showed a positive reaction with the first test. a T cell response to these antigens could serve as a specific marker of M. Therefore.2% and 4. tuberculosis (25). Carnegie. T cells from individuals with M. and they suggested that this assay might thus be a valuable alternative to TST. 2010 Diagnosis of Tuberculosis in Dialysis Patients 1115 mens. when the T cells re-encounter these antigens ex vivo in the overnight T-SPOT.18). meaning many individuals possibly exposed to unnecessary preventive treatment (18). The authors concluded that.TB test (Oxford Immunotec.g. the authors conclude that none of these methods can be used as the “gold standard. In one study in HD patients diagnosed with active TB. Serologic testing is unreliable and the chest radiograph is usually normal (15. The authors suggest that this lack of correlation could be due to the high anergy rate in HD patients. By the next morning. they release a cytokine. Lalvani and co-workers in the late 1990s (28). and some guidelines recommend ignoring the effect of BCG on TST (15.23). This same limitation of the skin test applies to its use as a diagnostic aid in the evaluation of patients with suspected active TB (when microbiological confirmation is awaited or not possible).Release Assays: Advantages over the TST These new tests use two proteins encoded by a unique genomic segment (stretch of DNA) termed “Region of Difference 1. anergy to TST was found in over 50% of patients (7). early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10). BCG. including two-step testing to induce a “booster phenomenon. Because they found no correlation between chest radiography and TST. The low sensitivity and specificity of the TST may explain the reported poor correlation of its results with the patients’ history and chest radiographs. which is based on the strong cell-mediated immune response induced by LTBI. in 127 HD patients and 218 controls (24): in vitro quantitation of PPD-specific T cells using a rapid 6-hour assay. repeated testing has operational limitations linked to the need of many return visits. However. unlike the skin test.1% more TST-positive patients.” which is absent from all strains of Mycobacterium bovis. the Centers for Disease Control and Prevention (CDC) recommended screening for LTBI with TST in persons with a medical condition that increases the risk of TB.. chest radiography could be false-negative in the presence of only small scars. Abingdon.1% more. In the aforementioned study of Wauters et al. IFN. which is the “footprint” of an individual M. tuberculosis-specific T cell (26).4% new positive patients. repeated testing most likely increases sensitivity at the expense of specificity.Clin J Am Soc Nephrol 5: 1114 –1122. but again it would do so at the cost of a larger number of false-positive TST reactions.” In a study by Dogan et al. tuberculosis infection. Whereas 85. Because PPD is a culture filtrate of tubercle bacilli containing many antigens shared with the bacille Calmette–Guerin (BCG) ´ vaccine and most nontuberculous mycobacteria (20). including those with ESRD. or false positive due to sequel lesions of previous pulmonary diseases other than TB. the respective percentage among HD patients was significantly lower—51. Wauters et al. a crude mixture of 200 M. respectively. causing a false-negative TST with a positive chest x-ray. A skin induration over 10 mm in diameter is considered positive (19). tuberculosis infection (26. Australia) is a wholeblood ELISA that measures the IFN. However. Specific T cells toward PPD were flow-cytometrically quantified from whole blood. each such T cell gives rise to a dark spot. However.concentration in the supernatant of a sample of diluted whole blood after 24 hours of incubation with ESAT-6 and CFP-10 (29). administered four consecutive TSTs (at 7-day intervals) to 224 HD patients (1): after the first test. The readout is thus the number of spots that are counted using a magnifying lens or automated reader. in the study of Wauters et al. and results were compared with skin testing. The TST measures the delayed-type hypersensitivity response to intradermal inoculation of tuberculin purified protein derivative (PPD). and most nontuberculous mycobacteria but is present in M. These proteins. United Kingdom) was developed by A. In 1995. The second major drawback of TST is its low specificity. are major targets of T-helper type 1 cells in patients with M. whereas the second test added 12. Multiple ( 2) testing does not seem to add significant benefit. the method did not receive further attention from researchers because other more specific blood assays for the diagnosis of LTBI have subsequently been developed and introduced in clinical practice. (1).4%.7% of the patients showed a positive reaction. 11. The QuantiFERON-TB Gold (QFT-G) test (Cellestis. Thus. (22). individuals vaccinated with BCG but not infected with M. An interesting new diagnostic approach was tried a few years ago by Sester et al. 14. However.20). 5-mm induration instead of 10) would also increase the sensitivity of the test.TB assay. a history of BCG vaccination did not correlate with positive TST. because of its poor sensitivity. The classic diagnostic tool for LTBI is the tuberculin skin test (TST). The IFN. Setting a lower TST threshold (e.7% of control patients with PPD reactivity in vitro were skin-test positive. Originally devel- . The T-SPOT. the main cause of poor specificity of the TST. the second test added 13. tuberculosis can test falsely positive using the TST.
TB has a higher sensitivity than the TST (27. establishing the diagnostic accuracy for LTBI of the IGRAs is a major challenge because a gold standard is lacking.TB PBMC Number of IFN. Reviews of several studies in various populations (18. much higher than for TST (35%) (29). Finally.TB has a specificity of 100% (26.TB. A summary of the characteristics of the IGRAs in comparison with the TST is presented in Table 1. Food and Drug Administration has approved it for in vitro diagnostics. in certain studies. Four case-control studies on 127 BCG-vaccinated low-risk individuals in aggregate showed that T-SPOT. 2010 oped in the 1980s for detecting TB in cattle.spot-forming cells T-SPOT. PBMC. The sensitivity of the IGRAs is at least equivalent to that of TST and. several studies in contacts have been undertaken with the aim of measuring the concordance between these biologic tests and the TST. a Mantoux test versus Heaf test. the so-called “InTube” test (QFT-GIT). which has notoriously low sensitivity in these settings (35). peripheral blood mononuclear cells. In HIV-seropositive persons. Studies in immunocompromised populations confirmed the superiority of IGRAs for the diagnosis of LTBI in comparison with TST.27. . the results with QFT-G seem to Table 1. it has been demonstrated that T-SPOT.TB QFT-G TST Antigens Positive internal control Uniformity of methods and reagents Potential for boosting effect in repeated tests Need for return visit Time required for results Setting of test Interpretation of test Readout units Technological platform Test’s substrate Outcome measure ESAT-6 and CFP-10 Yes Yes No ESAT-6 and CFP10 Yes Yes No PPD No Noa Yes No 16 to 20 hours In vitro Objective (instrumentbased) IFN. uses tubes prefilled with antigens. Characteristics of the TST and of the IGRAs (18) T-SPOT. whereas in another five studies on 330 cumulative patients the sensitivity of QFT-G ranged from 70% to 89%.TB seemed to be significantly higher compared with QFT-G (18). the sensitivity of T-SPOT.after it has diffused into the supernatant and become diluted in the total volume of the test sample (18). However.-release assays” (IGRAs). A newer version of the QuantiFERON-TB Gold assay. or automated counter No 16 to 24 hours In vitro Objective (instrumentbased) International units of IFNELISA Whole blood Serum concentration of IFN. In theory. The U.36 –39). The essential finding was a very good correlation between positivity of the blood tests and the degree of exposure of the contacts (31). When these results were pooled. the T-SPOT. On the other hand. making it more suitable for “on-field” usage in settings with limited resources (18).TB-based test should be more sensitive because it detects IFN. PPD-S versus PPD RT-23.in the immediate vicinity of the T cell from which it is released (where it is still at a locally high concentration).TB showed sensitivity ranging from 83% to 97% in five studies on 266 cumulative patients. whereas the ELISA detects IFN.producing T cells Enumeration of spots by naked eye.produced by T cells Measurement of optical density values using an automated reader Yes 48 to 72 hours In vivo Subjective (operator-based) Millimeters of induration NA NA NA Readout system Palpable induration NA. this simplifies the laboratory procedures. induration versus erythema. when testing patients with active TB.S. and a guideline from the CDC has been published (30). not applicable. particularly in subjects vaccinated by BCG.1116 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 5: 1114 –1122. However. The three of these assay platforms are sometimes collectively referred to as “T cell-based IFN. the assay was adapted for human use in the 1990s. magnifying lens. T-SPOT.31) suggested similar levels of specificity for the two IGRAs and these were statistically higher than those for TST. A case-control study on 216 Japanese BCG-vaccinated adults showed a 98% specificity of QFT-G. superior with T-SPOT.32– 34).
(56) Zoccali et al. Most of this cost is related to the laboratory. it is of paramount importance to also understand the limitations of the IGRAs: lower sensitivity in severe disease. Furthermore. In general. and $57 for T-SPOT. (57) Passalent et al. Most likely. Studies suggest that indeterminate results are relatively common with the ELISA. $25 for QFT-GIT.6 2. the experience with IGRAs in diagnosing LTBI is rather limited and is mainly drawn from small-scale cross-sectional studies (35). (14) Chung et al. higher sensitivity would identify more infected persons among those with a false-negative TST result. occurring in 0% to 5. although false-negative IGRA results may occur. (40) evaluated the QFT-G in a cross-sectional study of Zambian adults with smear-positive TB and found that the sensitivity of the QFT-G was significantly lower in HIV-positive than in HIV-negative individuals. no need for return visit. In contrast.0 4. the fact that most of the costs for TB control are incurred during diagnosis and treatment of patients with active TB suggests that higher diagnostic sensitivity and higher specificity could induce cost savings in the medium and long term by reducing the future burden of cases of active TB and decreasing the number of uninfected BCG-vaccinated people inappropriately treated for LTBI (18). the costs of IGRAs are likely to decline with increasing usage of these tests.7 62. occurring in 5% to 40% of patients with QFT-G but less frequently with the newer QFTGIT (46 – 48). The cost-effectiveness of this strategy is probably related to low prevalence of LTBI and high prevalence of BCG history in these countries.TB T-SPOT. a sample well stimulated with a potent nonspecific stimulator of IFNproduction by T cells). the diagnostic sensitivity of IGRAs is more robustly maintained than that of the TST (35). Subsequent studies have also confirmed that with decreasing CD4 count. fair (43– 45) and that.7 73..2 75.9 63. regions. indeterminate results are more rare with the T-SPOT.4 89. More truepositive results in infected people would increase the rate of diagnosis and treatment of LTBI before progression to active TB (18).6 22 46 65.TB. IGRA testing alone is only cost-effective at LTBI rates 40% (55). such as phlebotomy.7 NA 61. On the other hand. In patients with autoimmune diseases treated with immunosuppressive agents.8 12.7 64. Raby et al. the PPD used in the TST is only about $10. the single major disadvantage of IGRAs is their high cost.S. (3) Triverio et al. these studies have found that agreement between the TST and IGRAs is.42).0 8. thus avoiding unnecessary chemoprophylaxis.TB QFT-G T-SPOT.1 11.Clin J Am Soc Nephrol 5: 1114 –1122.41. A 2008 survey of the Infectious Disease Society of America’s Emerging Infections Network (IDSA EIN) showed that QFT-G was available for use in only 63% of U. the availability of these tests is even lower in low-income countries. Other important advantages of the IGRAs compared with the TST include lack of boosting effect in repeated tests.TB in the United States. and processing also count (51). specimen transport. Higher specificity will reduce false-positive test results. (59) 162 29 203 62 HD HD HD HD Diagnosis Diagnosis Diagnosis Diagnosis of of of of active TB active TB LTBI LTBI 167 HD 39 HD Diagnosis of LTBI Diagnosis of LTBI QFT-G T-SPOT. and objective (instrument-based) interpretation of the test (18). The introduction of blood tests in clinical practice is expected to initially increase the cost of TB control. Table 2.6 . which may affect the diagnostic utility of the QFT-G in this population (37. additional costs of the follow-up visit for reading the TST reaction must be considered (52).5 71. especially HIV infection (41). 2010 Diagnosis of Tuberculosis in Dialysis Patients 1117 be less convincing. negatively affecting T cell function in the in vitro stimulation (18). unknown predictive value for future development of active TB (because no studies have been performed on this subject). It is generally thought that the higher diagnostic accuracy together with the operational advantages of the IGRAs should improve the effectiveness of TB control programs.5 100 24. However. and lack of distinction between LTBI and active TB (31). Although a negative TST in immunosuppressed individuals can be a false negative. the failure of the positive control in the blood tests provides the important information that the test’s result cannot be reliably interpreted because it may reflect an underlying in vivo immunosuppression.5 41. false-negative and indeterminate results are seen more frequently.54). Studies in Switzerland and Germany have shown that the most cost-effective method for LTBI screening is the two-step strategy (TST followed by IGRA in TST-positive patients) (53.TB T-SPOT.TB QFT-G QFT-GIT 100 91. which is approximately $30 for QFT-G. For example. However. however. Nevertheless. Indeterminate QFT results seem to be associated with extremes of age ( 5 and 80 years) and immunosuppression. Limited availability of IGRAs (in contrast with the worldwide readily accessible TST) is another important issue.e.1 to 78. but other procedures. The IGRAs have an internal positive control (i. shorter time required for results (16 to 24 hours versus 48 to 72 hours). (58) Hoffmann et al. In comparison. at best.4% (49).1 NA 5. Summary of studies on the value of IGRAs for the diagnosis of TB in ESRD patients Study (Reference) n Objective IGRA Sensitivity (%) Specificity (%) Indeterminate Results (%) Inoue et al. with the lowest availability reported in the southern and eastern states (50).
IGRAs may be used as a supplementary test in individualized clinical assessment. for QFT-G (56) and 91.K. A summary of these studies is presented in Table 2. only a few studies have been published that tried to assess the value of the blood assays for the diagnosis of TB in HD patients.1118 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 5: 1114 –1122. the sensitivity and the specificity of the IGRAs were found to be 100% and 89. Netherlands (68) TST is the initial test. 2010 Table 3. sole test for LTBI when the TST may be falsely negative because of immunosuppression. an IGRA positive an IGRA should be should be carried out without a prior TST.7%. to be costeffective (especially in case of mass screening). performed. HPA. as the sole test for LTBI in individuals in whom the result of TST may be falsely negative because immunocompromised. the TST should be the initial test and children who are at relatively used to detect LTBI. Italy (67) TST should be carried out and when In immunosuppressed patients. United Kingdom – NICE (64) A two-step strategy is currently recommended: using a TST. immunocompetent adults child).TB (57). reliable” perform an IGRA without a prior TST. if available. – Australia (62) TST remains the preferred method of screening for LTBI. France (69) IGRAs should be used instead of TST. If TST is negative. U. HPA (65) TST should generally be used as the IGRA testing. For the diagnosis of active TB. and of progressing to active disease if infected. the value of the IGRAs for the diagnosis . if available. and if 5 mm or In subjects in whom the TST “may be less more followed by IGRA. if available. an low risk of being infected with TB IGRA test may be performed. On the other hand. Japan (63) QFT is preferred over TST in adults (18 In high-risk groups QFT is preferred and to 49 years old) can be used for deciding on LTBI treatment. National Institute for Clinical Excellence. can be considered first-line test for LTBI. Canada (61) IGRA may be performed in TSTIn an immunocompromised person (adult or positive. Switzerland (66) Confirm a positive TST with an IGRA. respectively. can be considered as the a TST. Even when QFT is preferred TST may be done first. respectively. and those with positive results (or in whom TST may be less reliable) should then be considered for IGRA testing.7%.7% and 64. Use only an IGRA in immunocompromised subjects. followed by QFT in TST-positive patients. – Ireland (70) IGRAs can be used in conjunction with IGRAs. QFT-G usually can be used in place of (and not in addition to) the TST. for T-SPOT. Health Protection Agency. NICE. The Value of IGRAs in ESRD Patients In recent years. National guidelines on detection of LTBI Country (Reference) Immunocompetent Individuals Immunocompromised Individuals United States-CDC (30) QFT-G can be used in all circumstances – in which the TST is used.
Triverio et al. Evenepoel P. if available. Any of the three types of assays may be used. or origin from a medium TB-prevalence region) as a proxy for LTBI. tuberculosis. almost all existing guidelines recommend using IGRAs. (13) performed TST. 2004 2. treatment of LTBI should be considered. Maes BD: The value of tuberculin skin testing in haemodialysis patients. LTBI was diagnosed by an expert panel of physicians on the basis of three elements: patient self-reported history of active TB.1% of patients. but QFTs are less expensive and probably more sensitive in these patients. (59) found that.TB (22%) and TST (25%). Peetermans WE. respectively. Winthrop et al.TB were not. or a history of TB infection.. Summarizing the findings in ESRD patients described above.Clin J Am Soc Nephrol 5: 1114 –1122.TB was positive in 78. References 1. Gardam M: Detecting latent tuberculosis infection in hemodialysis patients: A head-to-head comparison of the T-SPOT. and a TST of induration 10 mm. Indeterminate IGRA results cannot be interpreted. Lee et al. Transplant Proc 39: 883– 886.TB nor TST predicted the development of active TB in these patients. old TB lesions on chest x-rays.TB test. Eyuboglu FO: Value of the tuberculin skin test in screening for tuberculosis in dialysis patients. previous TB-disease. which may be severe and difficult to diagnose. Nephrol Dial Transplant 19: 433– 438. Vanrenterghem Y. they may entail repeated testing in patients with a high probability of having TB. which seems to be the most costeffective strategy. Vanwalleghem J. In immunocompetent persons.27 to 0. whereas the agreement between TST and IGRAs was only poor or fair ( 0. In the study of Chung et al.TB) (13. ranging from 71% (TST versus T-SPOT. (3).60). Stas K.TB) to 79% (TST versus QFT-G) to 87% (QFT-G versus T-SPOT. further evaluation (including chest radiographs and microbiologic or pathologic exams) is necessary. 2010 Diagnosis of Tuberculosis in Dialysis Patients 1119 of LTBI in dialysis patients. Defining “probable LTBI” as chest radiography suggestive of prior infection and/or established “at risk” contact with a patient with contagious TB. However. After TB has been excluded. Kuypers D. symptoms. we suggest that chronic dialysis patients should be screened for LTBI by using an IGRA test. Clin J Am Soc Nephrol 2: 68 –73.TB according to different studies (Table 2). A positive IGRA test requires excluding active disease before affirming LTBI. tuberculosis infection. In a study by Passalent et al.6%. and IGRAs may also be used in difficult situations as an aid for diagnosis. and sometimes examination of sputum or other clinical samples for the presence of M. and (5) the rate of indeterminate results of IGRA tests is rather low. (3) the IGRAs are more sensitive and specific than the TST for detecting LTBI. Van Den Brande P.2% of those with suggestive x-rays. (14) found a higher sensitivity (46%) for QFT-G than for T-SPOT. and 73. Khan K. Therefore. Torun D.4% of participants with positive history and in 18. On the other hand.58.TB results. the superiority of the new blood assays over the TST is indisputable and their introduction in clinical practice is certainly a major progress in the diagnosis of LTBI. On the other hand.27 for QFT-G and 0. Finally.16 to 0.. Keuleers H. including the place of IGRAs in this process (30. Similarly.TB (P 0. Habesoglu MA. and QFT-G in 32 ESRD patients that were subsequently followed up for 2 years. (4) the IGRAs also have operational advantages over the TST. On the other hand. They found that only QFT-G but neither T-SPOT. (58). Disclosures None. and.61–70) (Table 3). if available. the vast majority of these guidelines .02) and T-SPOT. The T-SPOT. a chest radiograph.58). in the study of Winthrop et al. radiographic findings consistent with previous TB infection. and this should include checking for specific symptoms and signs. in three of the previously mentioned studies in HD patients the agreement between the two tests has been found to be fair or moderate ( 0. De Moor B. they are very prone to develop active disease. Passalent L. (2) screening for LTBI is therefore recommended. Karatasli M. P 0. They showed that QFT was independently associated with the high-risk group (adjusted odds ratio 2. 2007 3. (58) defined patients as being at “high-risk for LTBI” if they had a history of close contact with TB patients. chest x-ray suggestive for LTBI. QFT-GIT was more closely related to “TB exposure” (i. Demiroglu YZ. T-SPOT. 72. Many countries (at least 17 so far) have developed new national guidelines for the detection of LTBI. (60) reported that patients in a dialysis center with TB case contact were likely to have a positive QFT-G (P 0. once infected.e. but not in those with a low probability (30).14. particularly in endemic areas. recommend a two-step approach (i. is difficult to estimate in the absence of a gold standard. but did not affect the QFT and T-SPOT. The high susceptibility to TB infection of dialysis patients must always be kept in mind.TB were used. In symptomatic patients. Wang J. the concordance between results was better. in immunocompromised individuals in whom the TST may be falsely negative. Furthermore.TB). Ozdemir N. a negative test cannot exclude TB when suggestive history. TST followed by IGRA to confirm TST-positive cases). The rate of indeterminate results in HD patients varies between 2% and 24% for QFT-G and 3% and 11% for T-SPOT. but the anergy rate to TST is high.e. When QFT-G and T-SPOT.7).32 for T-SPOT.04). Chung et al. Sen N. cost-effective studies are desirable to support the implementation of this strategy in dialysis units. Centers for Disease Control and Prevention: Tuberculosis Screening for LTBI in Dialysis Patients: Current Strategy With all of their limitations.7%. as the sole test for LTBI. Ermis H. but not a positive TST (P 0. we may point out that (1) these patients are at high risk for M. and an expert physician panel. whereas TST and T-SPOT. whereas TST was positive in only 21. Richardson R. instead of TST.036). 2007 4. Dedier H. (60). Hoffmann et al. in comparison with TST of induration 10 mm. or physical signs are present. Wauters A.TB. previous BCG vaccination significantly increased the rate of positive TST results. as well as in the general population.16 to 0.
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