Screening for Latent Tuberculosis Infection in Solid Organ Transplant Recipients to Predict Active Disease: A Systematic Review and Meta-Analysis of Diagnostic Studies

Overview

Journal Open Forum Infect Dis

Specialty Infectious Diseases

Date 2023 Aug 10

PMID 37559757

Authors

Dafna Yahav

Melissa R Gitman

Ili Margalit

Tomer Avni

Mariska M G Leeflang

Shahid Husain

Affiliations

Soon will be listed here.

Abstract

Background: This is a systematic review and meta-analysis of diagnostic test accuracy studies to assess the predictive value of both tuberculin skin test (TST) and interferon-gamma release assays (IGRA) for active tuberculosis (TB) among solid organ transplantation (SOT) recipients.

Methods: Medline, Embase, and the CENTRAL databases were searched from 1946 until June 30, 2022. Two independent assessors extracted data from studies. Sensitivity analyses were performed to investigate the effect of studies with high or low risk of bias. Methodological quality of each publication was assessed using QUADAS-2.

Results: A total of 43 studies (36 403 patients) with patients who were screened for latent TB infection (LTBI) and who underwent SOT were included: 18 were comparative and 25 noncomparative (19 TST, 6 QuantiFERON-TB Gold In-Tube [QFT-GIT]). For IGRA tests taken together, positive predictive value (PPV) and negative predictive value (NPV) were 1.2% and 99.6%, respectively. For TST, PPV was 2.13% and NPV was 95.5%. Overall, PPV is higher when TB burden is higher, regardless of test type, although still low in absolute terms. Incidence of active TB was similar between studies using LTBI prophylaxis (mean incidence 1.22%; 95% confidence interval [CI], .2179-2.221) and those not using prophylaxis (mean incidence 1.045%; 95% CI, 0.2731-1.817; = .7717). Strengths of this study include the large number of studies available from multiple different countries; limitations include absence of gold standard for diagnosis of latent TB and low incidence of active TB.

Conclusions: We found both TST and IGRA had a low PPV and high NPV for the development of active TB posttransplant. Further studies are needed to better understand how to prevent active TB in the SOT population.

Citing Articles

Interferon-Gamma Release Assay Testing for Latent Tuberculosis Infection: A Health Technology Assessment.

Ont Health Technol Assess Ser. 2025; 24(11):1-183.

PMID: 39911267 PMC: 11792883.

The Cascade of Care in Management of Solid Organ Transplant Candidates With Latent Tuberculosis Infection.

Chiu C, Mahmood M, Brumble L, Vikram H, Theel E, Beam E Transplant Direct. 2024; 10(7):e1672.

PMID: 38911278 PMC: 11191954. DOI: 10.1097/TXD.0000000000001672.

References

Basiri A, Moghaddam S, Simforoosh N, Einollahi B, Hosseini M, Foirouzan A . Preliminary report of a nationwide case-control study for identifying risk factors of tuberculosis following renal transplantation. Transplant Proc. 2005; 37(7):3041-4. DOI: 10.1016/j.transproceed.2005.07.041. View

Shafeque A, Bigio J, Hogan C, Pai M, Banaei N . Fourth-Generation QuantiFERON-TB Gold Plus: What Is the Evidence?. J Clin Microbiol. 2020; 58(9). PMC: 7448650. DOI: 10.1128/JCM.01950-19. View

Whiting P, Rutjes A, Westwood M, Mallett S, Deeks J, Reitsma J . QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011; 155(8):529-36. DOI: 10.7326/0003-4819-155-8-201110180-00009. View

Torre-Cisneros J, Doblas A, Aguado J, San Juan R, Blanes M, Montejo M . Tuberculosis after solid-organ transplant: incidence, risk factors, and clinical characteristics in the RESITRA (Spanish Network of Infection in Transplantation) cohort. Clin Infect Dis. 2009; 48(12):1657-65. DOI: 10.1086/599035. View

Lauar I, Faria L, Romanelli R, Clemente W . Latent tuberculosis: Risk factors, screening and treatment in liver transplantation recipients from an endemic area. World J Transplant. 2022; 11(12):512-522. PMC: 8713304. DOI: 10.5500/wjt.v11.i12.512. View

Shankar M, Aravindan A, Sohal P, Kohli H, Sud K, Gupta K . The prevalence of tuberculin sensitivity and anergy in chronic renal failure in an endemic area: tuberculin test and the risk of post-transplant tuberculosis. Nephrol Dial Transplant. 2005; 20(12):2720-4. DOI: 10.1093/ndt/gfi141. View

Costa S, Sandes-Freitas T, Jacinto C, Martiniano L, Amaral Y, Paes F . Tuberculosis after kidney transplantation is associated with significantly impaired allograft function. Transpl Infect Dis. 2017; 19(5). DOI: 10.1111/tid.12750. View

Jafri S, Singal A, Kaul D, Fontana R . Detection and management of latent tuberculosis in liver transplant patients. Liver Transpl. 2011; 17(3):306-14. DOI: 10.1002/lt.22203. View

Jambaldorj E, Han M, Jeong J, Koo T, Min S, Song E . Poor predictability of QuantiFERON-TB assay in recipients and donors for tuberculosis development after kidney transplantation in an intermediate-TB-burden country. BMC Nephrol. 2017; 18(1):88. PMC: 5351170. DOI: 10.1186/s12882-017-0506-9. View

10.

Sherkat R, Yaran M, Shoaie P, Mortazavi M, Shahidi S, Hamidi H . Concordance of the tuberculin skin test and T-SPOT(®).TB test results in kidney transplant candidates. J Res Med Sci. 2014; 19(Suppl 1):S26-9. PMC: 4078377. View

11.

Ishikawa S, Igari H, Akutsu N, Tsuyuzaki M, Aoyama H, Hasegawa M . Comparison of interferon-γ release assays, QuantiFERON TB-GIT and T-Spot.TB, in renal transplantation. J Infect Chemother. 2017; 23(7):468-473. DOI: 10.1016/j.jiac.2017.04.002. View

12.

Munoz L, Gomila A, Casas S, Castellote J, Arnan M, Rafecas A . Immunodiagnostic Tests' Predictive Values for Progression to Tuberculosis in Transplant Recipients: A Prospective Cohort Study. Transplant Direct. 2016; 1(3):e12. PMC: 4946446. DOI: 10.1097/TXD.0000000000000520. View

13.

Alpaydin A, Ozbilgin M, Abdulleyeva M, Mersin S, Egeli T, Unek T . Determinants and characteristics of tuberculosis in liver transplant recipients. Turk J Med Sci. 2018; 48(6):1162-1166. DOI: 10.3906/sag-1803-144. View

14.

Agoglia L, Balbi E, Halpern M, Roma J, Carius L, Martinho J . Tuberculosis in liver transplant recipients: prophylaxis in an endemic area. Transplant Proc. 2011; 43(1):199-202. DOI: 10.1016/j.transproceed.2010.12.033. View

15.

Mojahedi M, Feizzadeh B, Aghdam B, Hekmat R . The prevalence of tuberculosis in recipients of renal transplantation. Saudi J Kidney Dis Transpl. 2011; 22(6):1266-8. View

16.

Apaydin S, Altiparmak M, Serdengecti K, Ataman R, Ozturk R, Erek E . Mycobacterium tuberculosis infections after renal transplantation. Scand J Infect Dis. 2000; 32(5):501-5. DOI: 10.1080/003655400458776. View

17.

Auguste P, Tsertsvadze A, Pink J, Court R, McCarthy N, Sutcliffe P . Comparing interferon-gamma release assays with tuberculin skin test for identifying latent tuberculosis infection that progresses to active tuberculosis: systematic review and meta-analysis. BMC Infect Dis. 2017; 17(1):200. PMC: 5343308. DOI: 10.1186/s12879-017-2301-4. View

18.

Ahmadinejad Z, Azmoudeh Ardalan F, Razzaqi M, Davoudi S, Jafarian A . QuantiFERON-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. 2012; 15(1):90-5. DOI: 10.1111/tid.12027. View

19.

Bravo C, Roldan J, Roman A, Degracia J, Majo J, Guerra J . Tuberculosis in lung transplant recipients. Transplantation. 2005; 79(1):59-64. DOI: 10.1097/01.tp.0000147784.53188.dc. View

20.

Moon H, Park S, Kim J, Park J, Kwon C, Peck K . Isoniazid Prophylaxis for Latent Tuberculosis Infections in Liver Transplant Recipients in a Tuberculosis-Endemic Area. Ann Transplant. 2017; 22:338-345. PMC: 6248040. DOI: 10.12659/AOT.902989. View