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Original Research: RESPIRATORY INFECTIONS |

Performance of Tests for Latent Tuberculosis in Different Groups of Immunocompromised Patients FREE TO VIEW

Luca Richeldi, MD, PhD; Monica Losi, PhD; Roberto D'Amico, PhD; Mario Luppi, MD; Angela Ferrari, MD; Cristina Mussini, MD; Mauro Codeluppi, MD; Stefania Cocchi, MD; Francesca Prati, MD; Valentina Paci, MD; Marisa Meacci, BS; Barbara Meccugni, BS; Fabio Rumpianesi, MD; Pietro Roversi, MD; Stefania Cerri, MD; Fabrizio Luppi, MD; Giovanni Ferrara, MD; Irene Latorre, MSc; Giorgio E. Gerunda, MD; Giuseppe Torelli, MD; Roberto Esposito, MD; Leonardo M. Fabbri, MD, FCCP
Author and Funding Information

From University of Modena and Reggio Emilia (Drs. Richeldi, Losi, D'Amico, M. Luppi, Ferrari, Mussini, Codeluppi, Cocchi, Prati, Paci, Roversi, Cerri, F. Luppi, Ferrara, Gerunda, Torelli, Esposito, and Fabbri, and Ms. Latorre), Modena, Italy; and Policlinico Hospital (Dr. Rumpianesi, Ms. Meacci, and Ms. Meccugni), Modena, Italy.

Correspondence to: Luca Richeldi, MD, PhD, Section of Respiratory Diseases, Department of Oncology, Hematology and Respiratory Diseases, University of Modena and Reggio Emilia, Italy; e-mail: luca.richeldi@unimore.it

*Presently at the University of Perugia, Perugia, Italy.

†Presently at Servei de Microbiologia, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Respiratorias, Instituto de Salud Carlos III, Badalona, Spain.


This work was supported in part by the Azienda Ospedaliero-Universitaria Policlinico di Modena (Italy). Ms. Latorre is an Formación Profesorado Universitario (FPU) predoctoral student and the recipient of a grant from the Ministerio de Educación y Ciencia (Spain). T-SPOT.TB kits were kindly provided by Oxford Immunotec Ltd. and Nanogen Advanced Diagnostics Italy. Neither company had a role in the design or conduct of the study, collection, management, analysis, or interpretation of the data, preparation, review, or approval of this article.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;136(1):198-204. doi:10.1378/chest.08-2575
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Background:  Immunocompromised persons infected with Mycobacterium tuberculosis (MTB) have increased risk of tuberculosis (TB) reactivation, but their management is hampered by the occurrence of false-negative results of the tuberculin skin test (TST). The T-cell interferon (IFN)-γ release blood assays T-SPOT.TB (TS.TB) [Oxford Immunotec; Abingdon, UK] and QuantiFERON-TB Gold In-Tube (QFT-IT) [Cellestis Ltd; Carnegie, VIC, Australia] might improve diagnostic accuracy for latent TB infection (LTBI) in high-risk persons, although their performance in different groups of immunocompromised patients is largely unknown.

Methods and results:  Over a 1-year period, we prospectively enrolled patients in three different immunosuppressed groups, as follows: 120 liver transplantation candidates (LTCs); 116 chronically HIV-infected persons; and 95 patients with hematologic malignancies (HMs). TST, TS.TB, and QFT-IT were simultaneously performed, their results were compared, and intertest agreement was evaluated. Overall, TST provided fewer positive results (10.9%) than TS.TB (18.4%; p < 0.001) and QFT-IT (15.1%; p = 0.033). Significantly fewer HIV-infected individuals had at least one positive test (9.5%) compared with LTCs (35.8%; p < 0.001) and patients with HMs (29.5%; p < 0.001). Diagnostic agreement between tests was moderate (κ = 0.40 to 0.65) and decreased in the HIV-infected group when the results of the TS.TB were compared with either TST (κ = 0.16) or QFT-IT (κ = 0.19). Indeterminate blood test results due to low positive control values were significantly more frequent with QFT-IT (7.2%) than with TS.TB (0.6%; p < 0.001).

Conclusions:  Blood tests identified significantly more patients as being infected with MTB than TST, although diagnostic agreement varied across groups. Based on these results, we recommend tailoring application of the new blood IFN-γ assays for LTBI in different high-risk groups and advise caution in their current use in immunosuppressed patients.

Figures in this Article

Targeting persons at increased risk of disease reactivation once infected with Mycobacterium tuberculosis (MTB) is a key factor for an effective tuberculosis (TB) control strategy in low-prevalence countries.1,2 A weak component of this strategy is the less than ideal performance of the standard diagnostic tool for latent TB infection (LTBI), the century-old tuberculin skin test (TST).3 False-negative results, mainly due to immunosuppression, preclude the treatment of truly infected persons, and the treatment of individuals with false-positive results, often due to Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination, reduces the cost- effectiveness of preventive interventions. Because of their operational advantages and increased specificity, the interferon (IFN)-γ release assays (IGRAs) QuantiFERON-TB Gold In-Tube (QFT-IT) [Cellestis Ltd; Carnegie, VIC, Australia] and T-SPOT.TB (TS.TB) [Oxford Immunotec; Abingdon, UK] might improve the efficacy of interventions aimed at TB control.4 However, the performance of IGRA in various categories of high-risk patients is largely unknown and has been identified as a priority area for research.5

We performed a comparative study in three different groups of immunocompromised individuals, in whom the TST is the standard for the diagnosis of LTBI, despite its recognized lack of sensitivity, 3,6 as follows: liver transplantation candidates (LTCs) with end-stage disease7; HIV-infected individuals8; and patients with hematologic malignancies (HMs).9

Study participants were evaluated in three different wards of a single referral center (University Hospital of Modena, Italy) during a 12-month period (May 2006 to May 2007). Any consecutive patient with a clinical indication to be tested for LTBI who provided written informed consent was enrolled in the study. Patients with end-stage chronic liver disease in the liver transplantation candidacy period (the LTC group) were enrolled at the solid organ transplant clinic; individuals with chronic HIV infection (the HIV group) were enrolled at the infectious disease clinic; and patients with HMs (the HM group) were enrolled at the hematology clinic. To provide a real-life assessment of patients based on routine clinical practice, no other exclusion criteria were defined, and no patients refused to participate in the study. The research protocol was approved by the local ethics committee.

TST was performed using 5 international units of purified protein derivative (Biocine Test; Chiron; Siena, Italy) immediately after drawing blood samples for IGRA and was read 72 h later. A TST result was considered positive if the skin induration was ≥ 10 mm in patients in the LTC and HM groups, and ≥ 5 mm in the HIV group.2 Blood samples were processed according to the manufacturer's instructions within 4 h from blood drawing by trained technicians blinded to clinical and demographic identifiers.

Comparisons among tests within the same group were performed using the McNemar test, and comparisons across different groups were performed using the χ2 test. Bonferroni correction was used for multiple comparisons. Results were considered statistically significant when the p value was < 0.05. The κ statistic measure was used to assess agreement among different tests. This measure provides values from + 1 (perfect agreement) to 0 (no agreement above that expected by chance) to − 1 (complete disagreement). Analyses were performed using a statistical software package (Stata, version 10.0; Stata Corp; College Station, TX).

Three hundred sixty-nine participants were enrolled in the protocol. Fourteen patients (3.8%) were excluded from further analysis because IGRA results (TS.TB, 11 patients; QFT-IT, 3 patients) were deemed invalid due to high negative control values. For 24 patients (6.5%), TST results (LTC group, 6 patients; HM group, 1 patient; HIV group, 17 patients) were not read within the allotted time limit and were thus excluded, leaving 331 subjects for statistical analyses. The mean age was 51.4 years, most patients were white, and a few had been vaccinated with BCG (Table 1). Overall, 24 QFT-IT results (7.2%) and 2 TS.TB results (0.6%; p < 0.001) were indeterminate owing to low positive control values; 21 of the indeterminate QFT-IT results (87.5%) were negative using both TST and TS.TB. Compared with TS.TB, there were significantly more indeterminate QFT-IT results in both the LTC and HIV groups (p = 0.009 and p = 0.008, respectively), but not in the HM group (Table 2). Blood lymphocyte counts on the day of IGRA testing were available for 303 patients. Median lymphocyte counts were significantly lower in patients with indeterminate QFT-IT results (1,200 cells/mL vs 1,820 cells/mL in patients with determinate QFT-IT results; p = 0.001). In the LTC group, indeterminate QFT-IT results were significantly associated with a higher median model for end-stage liver disease score (21 vs 13, respectively; p = 0.002).

Table Graphic Jump Location
Table 1 Characteristics of the Study Population

Values are given as the mean (SD, range) or No. (%). Among HIV-infected individuals, 59.5% were receiving highly active antiretroviral treatment and had a mean CD4 count of 461.5/mm3. In the LTC group, 80% were affected by either alcoholic or hepatitis B or C virus-related cirrhosis, and the median model for end-stage liver disease score was 14. This score is based on objective laboratory variables and predicts the risk of mortality within 3 mo. In the HM group, 82.1% were affected by Hodgkin and non-Hodgkin lymphomas; none was receiving anticancer chemotherapy at the time of testing. Data on peripheral blood lymphocytes were available for 98 LTC, 112 HIV, and 93 HM patients.

*p < 0.001 vs LTC and HIV groups.

†p < 0.05 vs LTC and HIV groups.

‡p < 0.05 vs LTC and HM groups.

§p < 0.001 vs HIV and HM groups.

Table Graphic Jump Location
Table 2 Results of TST, TS.TB, and QFT-IT in the Different Groups of Immunocompromised Patients

Values are given as No. (%).

*p = 0.007 vs TS.TB positive and p = 0.02 vs QFT-IT positive in the LTC group.

†p < 0.001 vs TS.TB positive and p = 0.02 vs QFT-IT positive in the HM group.

‡p = 0.03 vs QFT-IT positive in the HM group.

Quantitative responses of IGRA, expressed as international units of IFN-γ or as spot-forming units (SFUs), showed good correlation with the size of the TST skin induration, expressed in millimeters (Fig 1). Overall, however, both TS.TB (18.4%) and QFT-IT (15.1%) identified more positive results than did TST (10.9%; p < 0.001 vs TS.TB; p = 0.033 vs QFT-IT). Significantly fewer persons were identified as latently infected by any test in the HIV group, compared with the LTC and HM groups (TST, p = 0.042; TS.TB, p < 0.001; QFT-IT, p < 0.001). Considering those patients with at least one positive test result to be infected, LTBI prevalence was significantly lower in the HIV group (9.5%) than in the LTC group (35.8%; p < 0.001) and HM group (29.5%; p < 0.001). Concordance among tests was substantial, ranging from 80.6% (TST vs TS.TB in LTC) to 95.4% (TST vs QFT-IT in HIV) [Table 3]. However, agreement between tests across different groups was moderate, with the κ statistic ranging from 0.40 to 0.65. In the HIV group, agreement between TS.TB and either TST (κ = 0.16) or QFT-IT (κ = 0.19) was slight (Table 3). In the 12 BCG-vaccinated individuals, agreement among all three tests was complete (κ = 1.00). “Highly discordant” results, that is, those clearly negative with one IGRA and clearly positive with another, were found in all groups and represented 12.1% of the whole population (Table 4). Patients with a positive TST and a negative IGRA (without a history of BCG vaccination) were also represented in all groups (LTC patients: TS.TB, 5 patients; QFT-IT, 4 patients; HIV patients: TS.TB, 5 patients; QFT-IT, 3 patients; HM: TS.TB, 1 patient; QFT-IT, 0 patients). Overall, the fraction of tests with borderline results (ie, close to the cutoff for a positive test result) was higher for TS.TB (18 tests with 4 to 5 SFUs) than for QFT-IT (8 tests with 0.20 to 0.34 international units of IFN-γ) [Table 4].

Figure Jump LinkFigure 1 Correlation between the IFN-γ response in QFT-IT (top) and TS.TB (bottom) and the size of the TST induration.Grahic Jump Location
Table Graphic Jump Location
Table 3 Diagnostic Agreement of TST, TS.TB, and QFT-IT in the Different Groups of Immunocompromised Patients

Indeterminate IGRA results were not included in the analyses.

Table Graphic Jump Location
Table 4 Distribution of TS.TB and QFT-IT Results by Quantitative Responses of the Assays

For TS.TB, the highest SFU value was considered for any of the two antigens (ESAT-6 and CFP10); for QFT-IT, the IU of IFN-γ in the antigens tube (ESAT-6, CFP10 and TB7.7) was considered. Negative control values were subtracted from antigen response before comparison. Indeterminate results were excluded from the analysis.

*Discordant results between IGRAs.

†Seven LTC patients, one HM patient, and four HIV patients.

‡Five LTC patients, six HM patients, and one HIV patient.

We report here the results of a comparative evaluation of all currently available diagnostic tests for LTBI in different categories of immunocompromised patients at increased risk of TB reactivation. We obtained at least three important results. First, TST detected fewer positive cases in some, but not all, high-risk groups. Therefore, a differential application of TST and IGRA among immunosuppressed patients might be beneficial. For example, in solid organ transplantation candidates, in whom the TST is still recommended as a standard of care,10 both TS.TB and QFT-IT could replace the TST. However, the lower rate of positive results with all three tests in HIV-infected individuals, which is well explained by the impaired IFN-γ-secreting capacity of MTB-specific CD4 T cells in HIV infection,11 coupled with the significant discordance among tests (previously reported in various populations of HIV-infected patients in low- and high-incidence settings),1214 would support an integrated diagnostic approach based on all three assays. However, in the particular group of HIV-infected persons included in our study, the lower rates of positive test results may simply reflect a higher degree of immunosuppression and therefore reduced reactivity to the assays.15

Our second important result is that the diagnostic agreement among different tests varied across groups of immunocompromised patients. Previous studies12,1621 have found that agreement of IGRA with the TST and agreement between QFT and TS.TB may vary from poor to substantial. In the present study, we showed that, among HIV-infected individuals, TS.TB detected a largely different fraction of persons infected by MTB, compared to TST and QFT-IT. Similar results were recently reported22 in a smaller sample of HIV-infected adults and children in an area in which the disease is endemic. Because identification and treatment of persons coinfected with MTB and HIV are a priority for TB control,23 these results could be clinically relevant.

To date, few studies are available on the value of IGRA in predicting the reactivation of TB in high-risk groups. Among adult24 and pediatric25 contacts of persons with active TB, the IGRA showed a better (or equivalent) positive predictive value than the TST for incident TB cases. However, a recent study from the Republic of The Gambia26 showed that only the combination of TST and IGRA (with infection defined as at least one positive result among the tests used) improved the detection of subjects at higher risk of progression to active disease. Unfortunately, only a small fraction of the subjects enrolled in the Gambian study were tested for HIV coinfection. Nevertheless, those results lend support to the concept that discordant results in specific risk groups are more likely due to the effects of different impairment of the immune response within the same risk groups on the sensitivity of the assays than to false-positive results due to the technical features of the assays. In addition, we have reported that about a third of discordant results were unlikely to be caused by inaccurate cutoff values, as suggested by others,21 because they were definitely positive with one assay and clearly negative with the other. These findings support the hypothesis that QFT-IT and TS.TB, based on some methodological differences,4 might measure slightly different immunologic phenomena. This conclusion is also supported by studies that have reported a different performance (and, most likely, different sensitivities) of the TST and IGRA in patients undergoing screening for LTBI and immunosuppressive treatments for cancer27 or in patients with autoimmune diseases before anti-tumor necrosis factor-α therapies.28 All these data suggest again that, in the absence of prospective studies, a combined approach aimed to maximize the efficacy of screening procedures might be preferable in severely immunocompromised patients who have an increased risk of reactivation and development of severe forms of TB.29

Finally, as reported for an earlier version of the same assay,16 indeterminate results of the QFT-IT are more affected by cellular immunosuppression than are those of TS.TB; interestingly, not all indeterminate QFT-IT results were negative with either TS.TB or TST, suggesting that individuals with an indeterminate QFT-IT result might still be infected. As previously reported for the gold version of the QFT,30 advanced liver disease is significantly associated also with indeterminate results of the QFT-IT. We have also reported here an association with lower peripheral blood lymphocyte counts. However, technical errors were more frequent with TS.TB than with QFT-IT, reflecting the higher complexity of the enzyme-linked immunospot assay compared with the enzyme-linked immunosorbent assay.

Both the QFT-IT and TS.TB have been recently approved for clinical use by the US Food and Drug Administration, and both tests have been included in guidelines published in several countries, including the United States, Canada, the United Kingdom, France, Italy, Germany, Switzerland, and Australia. These guidelines provide clinicians with various application strategies, although without strong evidence of their efficacy. However, in particular for TB, there is a need for in-field studies of the diagnostic accuracy of newer tools in high-risk populations.31 Our study shows for the first time that the performance of IGRA, both in terms of rates of positive results and in diagnostic agreement, varies greatly across different categories of patients who are at increased risk of TB reactivation. Because of the importance of targeting such high-risk groups for effective TB control, we advise caution when interpreting the results of IGRA among immunosuppressed patients.

BCG

bacillus Calmette-Gué rin

HM

hematologic malignancy

IFN

interferon

IGRA

interferon-γ release assay

LTBI

latent tuberculosis infection

LTC

liver transplantation candidate

MTB

Mycobacterium tuberculosis

QFT-IT

QuantiFERON-TB Gold In-Tube

SFU

spot-forming unit

TB

tuberculosis

TST

tuberculin skin test

TS.TB

T-SPOT.TB

We thank Robert J. Wilkinson (Imperial College, London, UK), Edward Nardell (Harvard Medical School, Boston), Jean-Pierre Zellweger (Lausanne University, Switzerland), and Andrea Cossarizza (University of Modena and Reggio Emilia, Italy) for their critical appraisal of the manuscript.

Jasmer RM, Nahid P, Hopewell PC. Clinical practice: latent tuberculosis infection. N Engl J Med. 2002;347:1860-1866. [PubMed] [CrossRef]
 
American Thoracic Society Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161suppl:S221-S247. [PubMed]
 
Huebner RE, Schein MF, Bass JB Jr. The tuberculin skin test. Clin Infect Dis. 1993;17:968-975. [PubMed]
 
Richeldi L. An update on the diagnosis of tuberculosis infection. Am J Respir Crit Care Med. 2006;174:736-742. [PubMed]
 
Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection; an update. Ann Intern Med. 2008;149:177-184. [PubMed]
 
Graham NM, Nelson KE, Solomon L, et al. Prevalence of tuberculin positivity and skin test anergy in HIV-1-seropositive and -seronegative intravenous drug users. JAMA. 1992;267:369-373. [PubMed]
 
Gomez F, Ruiz P, Schreiber AD. Impaired function of macrophage Fc gamma receptors and bacterial infection in alcoholic cirrhosis. N Engl J Med. 1994;331:1122-1128. [PubMed]
 
Selwyn PA, Hartel D, Lewis VA, et al. A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. N Engl J Med. 1989;320:545-550. [PubMed]
 
Silva FA, Matos JO, de Q Mello FC, et al. Risk factors for and attributable mortality from tuberculosis in patients with hematologic malignances. Haematologica. 2005;90:1110-1115. [PubMed]
 
Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med. 2007;357:2601-2614. [PubMed]
 
Sutherland R, Yang H, Scriba TJ, et al. Impaired IFN-γ-secreting capacity in mycobacterial antigen-specific CD4 T cells during chronic HIV-1 infection despite long-term HAART. AIDS. 2006;20:821-829. [PubMed]
 
Luetkemeyer AF, Charlebois ED, Flores LL, et al. Comparison of an interferon-γ release assay with tuberculin skin testing in HIV-infected individuals. Am J Respir Crit Care Med. 2007;175:737-742. [PubMed]
 
Stephan C, Wolf T, Goetsch U, et al. Comparing QuantiFERON-tuberculosis gold, T-SPOT tuberculosis and tuberculin skin test in HIV-infected individuals from a low prevalence tuberculosis country. AIDS. 2008;22:2471-2479. [PubMed]
 
Balcells ME, Perez CM, Chanqueo L, et al. A comparative study of two different methods for the detection of latent tuberculosis in HIV-positive individuals in Chile. Int J Infect Dis. 2008;12:645-652. [PubMed]
 
Dheda K, Lalvani A, Miller RF, et al. Performance of a T-cell-based diagnostic test for tuberculosis infection in HIV-infected individuals is independent of CD4 cell count. AIDS. 2005;19:2038-2041. [PubMed]
 
Ferrara G, Losi M, D'Amico R, et al. Use in routine clinical practice of two commercial blood tests for diagnosis of infection withMycobacterium tuberculosis: a prospective study. Lancet. 2006;367:1328-1334. [PubMed]
 
Lee JY, Choi HJ, Park IN, et al. Comparison of two commercial interferon-γ assays for diagnosingMycobacterium tuberculosisinfection. Eur Respir J. 2006;28:24-30. [PubMed]
 
Rangaka MX, Wilkinson KA, Seldon R, et al. Effect of HIV-1 infection on T-cell-based and skin test detection of tuberculosis infection. Am J Respir Crit Care Med. 2007;175:514-520. [PubMed]
 
Kang YA, Lee HW, Hwang SS, et al. Usefulness of whole-blood interferon-γ assay and interferon-γ enzyme-linked immunospot assay in the diagnosis of active pulmonary tuberculosis. Chest. 2007;132:959-965. [PubMed]
 
Detjen AK, Keil T, Roll S, et al. Interferon-γ release assays improve the diagnosis of tuberculosis and nontuberculous mycobacterial disease in children in a country with a low incidence of tuberculosis. Clin Infect Dis. 2007;45:322-328. [PubMed]
 
Arend SM, Thijsen SF, Leyten EM, et al. Comparison of two interferon-γ assays and tuberculin skin test for tracing tuberculosis contacts. Am J Respir Crit Care Med. 2007;175:618-627. [PubMed]
 
Mandalakas AM, Hesseling AC, Chegou NN, et al. High level of discordant IGRA results in HIV-infected adults and children. Int J Tuberc Lung Dis. 2008;12:417-423. [PubMed]
 
Churchyard GJ, Scano F, Grant AD, et al. Tuberculosis preventive therapy in the era of HIV infection: overview and research priorities. J Infect Dis. 2007;196suppl:S52-S62. [PubMed]
 
Diel R, Loddenkemper R, Meywald-Walter K, et al. Predictive value of a whole blood IFN-γ assay for the development of active tuberculosis disease after recent infection withMycobacterium tuberculosisAm J Respir Crit Care Med. 2008;177:1164-1170. [PubMed]
 
Bakir M, Millington KA, Soysal A, et al. Prognostic value of a T-cell-based, interferon-γ biomarker in children with tuberculosis contact. Ann Intern Med. 2008;149:777-787. [PubMed]
 
Hill PC, Jackson-Sillah DJ, Fox A, et al. Incidence of tuberculosis and the predictive value of ELISPOT and Mantoux tests in Gambian case contacts. PLoS ONE. 2008;3:e1379. [PubMed]
 
Piana F, Codecasa LR, Cavallerio P, et al. Use of a T-cell-based test for detection of tuberculosis infection among immunocompromised patients. Eur Respir J. 2006;28:31-34. [PubMed]
 
Bartalesi F, Vicidomini S, Goletti D, et al. QuantiFERON-TB Gold and TST are both useful for latent TB screening in autoimmune diseases. Eur Respir J. 2009;33:586-593. [PubMed]
 
Keane J, Bresnihan B. Tuberculosis reactivation during immunosuppressive therapy in rheumatic diseases: diagnostic and therapeutic strategies. Curr Opin Rheumatol. 2008;20:443-449. [PubMed]
 
Manuel O, Humar A, Preiksaitis J, et al. Comparison of quantiferon-TB gold with tuberculin skin test for detecting latent tuberculosis infection prior to liver transplantation. Am J Transplant. 2007;7:2797-2801. [PubMed]
 
Pai M, Ramsay A, O'Brien R. Evidence-based tuberculosis diagnosis. PLoS Med. 2008;5:e156. [PubMed]
 

Figures

Figure Jump LinkFigure 1 Correlation between the IFN-γ response in QFT-IT (top) and TS.TB (bottom) and the size of the TST induration.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 Characteristics of the Study Population

Values are given as the mean (SD, range) or No. (%). Among HIV-infected individuals, 59.5% were receiving highly active antiretroviral treatment and had a mean CD4 count of 461.5/mm3. In the LTC group, 80% were affected by either alcoholic or hepatitis B or C virus-related cirrhosis, and the median model for end-stage liver disease score was 14. This score is based on objective laboratory variables and predicts the risk of mortality within 3 mo. In the HM group, 82.1% were affected by Hodgkin and non-Hodgkin lymphomas; none was receiving anticancer chemotherapy at the time of testing. Data on peripheral blood lymphocytes were available for 98 LTC, 112 HIV, and 93 HM patients.

*p < 0.001 vs LTC and HIV groups.

†p < 0.05 vs LTC and HIV groups.

‡p < 0.05 vs LTC and HM groups.

§p < 0.001 vs HIV and HM groups.

Table Graphic Jump Location
Table 2 Results of TST, TS.TB, and QFT-IT in the Different Groups of Immunocompromised Patients

Values are given as No. (%).

*p = 0.007 vs TS.TB positive and p = 0.02 vs QFT-IT positive in the LTC group.

†p < 0.001 vs TS.TB positive and p = 0.02 vs QFT-IT positive in the HM group.

‡p = 0.03 vs QFT-IT positive in the HM group.

Table Graphic Jump Location
Table 3 Diagnostic Agreement of TST, TS.TB, and QFT-IT in the Different Groups of Immunocompromised Patients

Indeterminate IGRA results were not included in the analyses.

Table Graphic Jump Location
Table 4 Distribution of TS.TB and QFT-IT Results by Quantitative Responses of the Assays

For TS.TB, the highest SFU value was considered for any of the two antigens (ESAT-6 and CFP10); for QFT-IT, the IU of IFN-γ in the antigens tube (ESAT-6, CFP10 and TB7.7) was considered. Negative control values were subtracted from antigen response before comparison. Indeterminate results were excluded from the analysis.

*Discordant results between IGRAs.

†Seven LTC patients, one HM patient, and four HIV patients.

‡Five LTC patients, six HM patients, and one HIV patient.

References

Jasmer RM, Nahid P, Hopewell PC. Clinical practice: latent tuberculosis infection. N Engl J Med. 2002;347:1860-1866. [PubMed] [CrossRef]
 
American Thoracic Society Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161suppl:S221-S247. [PubMed]
 
Huebner RE, Schein MF, Bass JB Jr. The tuberculin skin test. Clin Infect Dis. 1993;17:968-975. [PubMed]
 
Richeldi L. An update on the diagnosis of tuberculosis infection. Am J Respir Crit Care Med. 2006;174:736-742. [PubMed]
 
Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection; an update. Ann Intern Med. 2008;149:177-184. [PubMed]
 
Graham NM, Nelson KE, Solomon L, et al. Prevalence of tuberculin positivity and skin test anergy in HIV-1-seropositive and -seronegative intravenous drug users. JAMA. 1992;267:369-373. [PubMed]
 
Gomez F, Ruiz P, Schreiber AD. Impaired function of macrophage Fc gamma receptors and bacterial infection in alcoholic cirrhosis. N Engl J Med. 1994;331:1122-1128. [PubMed]
 
Selwyn PA, Hartel D, Lewis VA, et al. A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. N Engl J Med. 1989;320:545-550. [PubMed]
 
Silva FA, Matos JO, de Q Mello FC, et al. Risk factors for and attributable mortality from tuberculosis in patients with hematologic malignances. Haematologica. 2005;90:1110-1115. [PubMed]
 
Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med. 2007;357:2601-2614. [PubMed]
 
Sutherland R, Yang H, Scriba TJ, et al. Impaired IFN-γ-secreting capacity in mycobacterial antigen-specific CD4 T cells during chronic HIV-1 infection despite long-term HAART. AIDS. 2006;20:821-829. [PubMed]
 
Luetkemeyer AF, Charlebois ED, Flores LL, et al. Comparison of an interferon-γ release assay with tuberculin skin testing in HIV-infected individuals. Am J Respir Crit Care Med. 2007;175:737-742. [PubMed]
 
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