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Saudi Journal of Kidney Diseases and Transplantation
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BRIEF COMMUNICATION  
Year : 2014  |  Volume : 25  |  Issue : 6  |  Page : 1240-1243
Performance of QuantiFERON TB Gold test in detecting latent tuberculosis infection in brain-dead organ donors in Iran: A brief report


1 Clinical Tuberculosis and Epidemiology Research Center; Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Date of Web Publication10-Nov-2014
 

   Abstract 

With regard to the significant morbidity and mortality due to tuberculosis in lung transplant recipients, the identification of brain-dead organ donors with latent tuberculosis by use of the QuantiFERON TB Gold (QFT-G) test may be of help to reduce the risk of TB reactivation and mortality in lung recipients. This study was conducted in the National Research Institute of Tuber­culosis and Lung Diseases (NRITLD) in Iran, from January to March 2013. A total of 38 conse­cutive brain-dead donors, not currently infected with active tuberculosis, were recruited. The medi­cal records of all the study enrollees were reviewed. A whole-blood IFN- release assay (IGRA) in reaction to early secreted antigenic target 6 (ESAT-6), culture filtrate protein 10 (CFP-10), and TB7.7 antigens, was performed and the released Interferon- was measured via enzyme-linked immunosorbent assay (ELISA). The data was analyzed with QFT-G software which was provided by the company. The demographic, characteristics and other variables were entered into SPSS version 11.5. The QFT-G test results of three donors (7.9%) turned out to be positive, negative for 24 donors (63.1%), and indeterminate for 11 cases (28.9%). Our study revealed the potential advantages of QFT-G in lowering the incidence of donor-derived post-transplant tuberculosis among lung recipients. However, a high rate of indeterminate results restricted the performance of QFT-G in this study.

How to cite this article:
Tabarsi P, Yousefzadeh A, Najafizadeh K, Droudinia A, Bayati R, Marjani M, Shafaghi S, Farokhzad B, Javanmard P, Velayati AA. Performance of QuantiFERON TB Gold test in detecting latent tuberculosis infection in brain-dead organ donors in Iran: A brief report. Saudi J Kidney Dis Transpl 2014;25:1240-3

How to cite this URL:
Tabarsi P, Yousefzadeh A, Najafizadeh K, Droudinia A, Bayati R, Marjani M, Shafaghi S, Farokhzad B, Javanmard P, Velayati AA. Performance of QuantiFERON TB Gold test in detecting latent tuberculosis infection in brain-dead organ donors in Iran: A brief report. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2021 Jan 17];25:1240-3. Available from: https://www.sjkdt.org/text.asp?2014/25/6/1240/144258

   Introduction Top


The diagnosis and management of tuberculosis (TB) among transplant recipients is challenging due to a wide range of post-transplant condi­tions mimicking tuberculosis, the side effects of anti-TB medications, and metabolic interactions between the anti-TB and immunosuppressive drugs. [1],[2] With regard to the significant morbidity and mortality of post-transplant tubercu­losis, the identification of candidates with latent tuberculosis infection (LTBI) for preventive chemotherapy is an effective intervention to reduce the risk of TB reactivation and mortality in transplant recipients. [1] Although limited data is available regarding the appropriate manage­ment of living donors with LTBI, direct evi­dence to support the active screening of latent tuberculosis in brain-dead donors is lacking. The tuberculin skin test (TST test) has been the standard screening tool for identifying patients with latent tuberculosis. However, it is not feasible to perform the tuberculin skin test on deceased donors. [2],[3] Another recently developed screening tool for diagnosis of LTBI is the QuantiFERON-TB Gold (QFT-G) test, which is based on the quantification of Interferon-(IFN- ) released from sensitized lymphocytes, when incubated with PPD from Mycobacterium tuberculosis (MTB), and control antigen. IFN-release assays (IGRA) may be of help in the screening of brain-dead organ donors. Although the results would not necessarily be available early enough to change our decision to trans­plant, they could be a guide to provide an appropriate prophylaxis for the recipients. However, the performance of this test has not been studied yet in the screening of LTBI in brain-dead organ donors. [1],[2],[5],[6] In this study our main objective is to evaluate the potential advan­tages of screening for LTBI in brain-dead solid organ donors by use of QFT-G test, in Iran.


   Subjects and Methods Top


We enrolled 38 consecutive brain-dead solid organ donors referred to the Transplant Center of the National Research Institute of Tubercu­losis and Lung Diseases (NRITLD) in Iran, from January to March 2013. Questions regar­ding the details about age, past medical history, prior Bacillus Calmette-Guérin (BCG) vacci­nation, and prior TB exposure of all study enrollees were answered according to their medical records and information from their relatives. Subsequently, the chest radiographs of all the patients were reviewed. The donors with pulmonary infiltrates in their chest radio­graphy were tested for MTB with stain and cul­ture of the transtracheal aspirates. From all the patients, 3 mL of whole blood was taken. A whole-blood IFN- release assay (IGRA) in reaction to early secreted antigenic target 6 (ESAT-6), culture filtrate protein 10 (CFP-10), and TB7.7 antigens was performed, following which the released Interferon- was measured via the enzyme-linked immunosorbent assay (ELISA). Each patient's blood sample was poured into three separate tubes. After incuba­tion of the specimens in 37°C for 24 hours, the tubes were centrifuged at 2,000-3,000 rpm/ minute, for 15 minutes. The supernatant was frozen in -20°C. From the three tubes for each patient, the one containing only heparin served as the negative control. The second tube served as the positive control, with Phytohemagglutinin added as the mitogen. The third was the test tube containing ESAT-6, CFP-10, and TB7.7 antigens [6]. The IFN- released in each tube was measured via ELISA and the data was analyzed with the QFT-G software which was provided by the company. Positive control tubes with no reaction to mitogen were defined as indeterminate results. The obtained data were analyzed in the SPSS 11.5 software. This study was approved by the Research Ethical Committee of the National Research Institute of Tuberculosis and Lung Diseases (NRITLD).


   Results Top


The mean age of our cases was 37.7 years (range 19-59 years). Of the 38 brain-dead do­nors who entered the study, 24 (63%) were male and 14 (37%) were female. All cases had a positive history of inoculation of BCG vac­cine due to the national Extended Program for Immunization (EPI), in Iran. According to their medical history and chest radiography, no one had been diagnosed with active tuberculosis during their lifetime. In addition, no one had a known history of close contact with patients with active tuberculosis. Six of the 38 donors had pulmonary infiltrates in their chest radio­graphy. However, a stained smear and culture of their transtracheal aspirates for MTB were negative. The QFT-G test result of the three donors (7.9%) turned out to be positive. The results were negative for 24 donors (63. 1%) and indeterminate for 11 cases (28. 9%). Nine donors with indeterminate results (out of 11) showed inadequate reaction to the mitogen in the control tubes.


   Discussion Top


Active tuberculosis (TB) in solid organ trans­plant (SOT) recipients is 20-74 times more frequent than that in the general population and the mortality rate of infection among such pa­tients is estimated to be up to 31%. [3],[7] Further­more, allograft rejection ensues in up to 33% of the transplant recipients receiving anti-TB treatment. [8] Donor-derived TB is the least common source of active tuberculosis in transplant reci­pients. Approximately 5% of post-transplant tuberculosis in solid organ recipients is related to acquisition of MTB from the donated organ or tissue. However, this route of MTB infection has been reported more frequently in lung trans­plant recipients. [3],[7],[9] In regions with a high pre­valence of tuberculosis, preventive chemothe­rapy must be offered to all lung transplant reci­pients without screening for LTBI. Although in low-to-moderate risk areas such as Iran, [10] further investigations are needed to evaluate the performance of immunodiagnostic tests, inclu­ding the tuberculin skin test (TST) and IFN-γ release assays (IGRAs), as screening tools. [1] However, the performance of TST is limited to living organ donors. To the best of our know­ledge, the role of IGRAs in detecting LTBI in brain-dead donors has not been investigated yet. The QuantiFERON TB Gold test (QFT-G test) is a newly developed whole-blood IGRA, which is currently used in many countries. In this study, which was conducted in the Lung Trans­plant Center of Iran, we attempted to assess the function of QFT-G as a screening tool to iden­tify brain-dead donors with LTBI. As a result of the National Extended Program for Immuni­zation (EPI) in Iran, all cases in our study had a history of BCG vaccination in their childhood. IGRAs were able to distinguish responses due to previous BCG vaccination from true infec­tion with MTB. They also had other operational advantages compared to the conventional TST. IGRAs were able to differentiate anergy or overt immunosuppression from true negative responses, owing to their negative and positive controls. [11],[12] Unlike TST, IGRA tests could be used in brain-dead organ donors. According to the results of our study, 7.8% of the tested individuals were positive by QFT-G, which was nearly similar to the result of the study by Kariminia et al, in Iran, in which 7% (11 of 156) of low-risk Iranians, who had no known risk factors for MTB infection, tested positive by QFT-G. [13] On the other hand, a high rate of our QFT results (28.9%) turned out to be inde­terminate. A large proportion of our indeter­minate results (nine of eleven) showed inade­quate reaction to mitogen (23.7%). Although the indeterminate results are mostly caused by technical errors and are reported variably in different studies (from 1 up to 38.3%), [14] the high rate of indeterminate results in our study was probably related to the anergic status of our cases. Indeterminate results are reported more frequently in the following situations: lymphopenia, hypoalbuminemia, chronic lung disease, chronic renal disease, cardiovascular disease, and immunosuppressant drugs. [15],[16] Indeed, these situations are extremely common in brain-dead organ donors. Moreover, as the results of the QFT will not usually be available in a short time, repeat testing is not possible for brain-dead donors, to exclude technical errors leading to indeterminate results. In fact, this could be one of the performance limitations of IGRAs in detecting LTBI, in brain-dead organ donors.

The sample size in our study is quite small because of the limited number of brain-dead donors in our center. This prevents the interpre­tation of our results as a general conclusion. In addition, as the positive predictive value of QFT-G for the development of donor-derived tuberculosis in transplant recipients depends on the prevalence of TB infection, further investi­gations in both low- and high-prevalence coun­tries are needed, to compare the value of screening LTBI in the setting of transplantation.


   Conclusion Top


The performance of QFT-G in screening brain-dead donors for LTBI is a controversial issue that deserves further studies. Our study revealed the potential advantages of QFT-G in lowering the incidence of donor-derived post-transplant tuberculosis among the lung recipients. How­ever, a high rate of indeterminate results res­tricted the performance of QFT-G in this study. Larger studies with a longer follow-up may be of help in determining the prognosis of trans­plant recipients from brain-dead donors, with indeterminate QFT results.

Conflict of interest: None

 
   References Top

1.
Bumbacea D, Arend SM, Eyuboglu F, et al. The risk of tuberculosis in transplant candidates and recipients: A TBNET consensus statement. Eur Respir J 2012;40:990-1013.  Back to cited text no. 1
    
2.
Muñoz P, Rodríguez C, Bouza E. Mycobacterium tuberculosis infection in recipients of solid organ transplants. Clin Infect Dis 2005; 40:581-7.  Back to cited text no. 2
    
3.
Subramanian A, Dorman S; AST Infectious Di-seases Community of Practice. Mycobacterium tuberculosis in solid organ transplant recipients. Am J Transplant 2009;9 Suppl 4:S57-62.  Back to cited text no. 3
    
4.
Mazurek GH, LoBue PA, Daley CL, et al. Comparison of a whole-blood interferon g assay with tuberculin skin testing for detecting latent Mycobacterium tuberculosis infection. JAMA 2001;286:1740-7.  Back to cited text no. 4
    
5.
Kumar D, Humar A. Tuberculosis and trans-plantation: Battling the opportunist. Clin Infect Dis 2009;48:1666-8.  Back to cited text no. 5
    
6.
Mardani M, Tabarsi P, Mohammadtaheri Z, et al. Performance of Quanti FERON-TB Gold test compared to tuberculin skin test in detecting latent tuberculosis infection in HIV-positive individuals in Iran. Ann Thorac Med 2010;5:43-6.  Back to cited text no. 6
[PUBMED]  Medknow Journal  
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Singh N, Paterson DL. Mycobacterium tuberculosis infection in solid-organ transplant reci-pients: Impact and implications for manage-ment. Clin Infect Dis 1998;27:1266-77.  Back to cited text no. 7
    
8.
Aguado JM, Herrero JA, Gavaldá J, et al. Clinical presentation and outcome of tuber-culosis in kidney, liver, and heart transplant recipients in Spain. Transplantation 1997;63: 1278-86.  Back to cited text no. 8
    
9.
Peters TG, Reiter CG, Boswell RL. Transmission of tuberculosis by kidney transplantation. Transplantation 1984;38:514-6.  Back to cited text no. 9
    
10.
WHO TB burden estimates and ′Global tuber-culosis report 2012′. Available from: http://www.who.int/tb/publications/global_report. Last accessed on 9/5/2013].  Back to cited text no. 10
    
11.
Diel R, Goletti D, Ferrara G, et al. Interferon-γ release assays for the diagnosis of latent Mycobacterium tuberculosis infection: A systematic review and meta-analysis. EUR Respir J 2011; 37:88-99.  Back to cited text no. 11
    
12.
Diel R, Loddenkemper R, Niemann S, Meywald-Walter K, Nienhaus A. Negative and positive predictive value of a whole-blood interferon-c release assay for developing active tuberculosis: An update. Am J Respir Crit Care Med 2011; 183:88-95.  Back to cited text no. 12
    
13.
Kariminia A, Sharifnia Z, Aghakhani A, et al. Comparison of QuantiFERON TB-G-test to TST for detecting latent tuberculosis infection in a high-incidence area containing BCG-vaccinated population. J Eval Clin Pract 2009;15:148-51.  Back to cited text no. 13
    
14.
Ahmadinejad Z, Azmoudeh Ardalan F, Razzaqi M, Davoudi S, Jafarian A. Quanti FERON-TB Gold In-Tube test for diagnosis of latent tuberculosis (TB) infection in solid organ transplant candidates: A single-center study in an area endemic for TB. Transpl Infect Dis 2013; 15:90-5.  Back to cited text no. 14
    
15.
Jeong SJ, Han SH, Kim CO, et al. Predictive factors for indeterminate result on the QuantiFERON test in an intermediate tuber-culosis burden country. J Infect 2011;62:347-54.  Back to cited text no. 15
    
16.
Kobashi Y, Sugio T, Mouri K, Obase Y, Miyashita N, Oka N. Indeterminate results of QuantiFERON TB-2G test performed in routine clinical practice. Eur Respir J 2009;33:812-5.  Back to cited text no. 16
    

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Correspondence Address:
Dr. Amir Yousefzadeh
Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Disease, Shahid Beheshti University of Medical Sciences, Darabad, Niavaran, Tehran
Iran
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DOI: 10.4103/1319-2442.144258

PMID: 25394441

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    Abstract
   Introduction
   Subjects and Methods
   Results
   Discussion
   Conclusion
    References
 

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