Interferon-γ releasing assay versus tuberculin skin testing for latent tuberculosis infection in targeted screening programs for high risk immigrants
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Recent immigrants from developing countries (<2 years since immigration) are at very high risk of active TB disease due to reactivation of latent infections acquired in the country of origin. In industrialized low-incidence TB countries targeted testing programs for high risk groups could allow the detection of latently infected persons who would likely benefit from a course of preventive treatment. In this study we evaluated the tuberculin skin test (TST) and interferon-γ enzyme-linked immunosorbent assay (QuantiFERON TB-gold in tube, QFT-IT) strategies for TB infection screening programs in recent immigrants from highly endemic countries.
Patients and methods
This is a prospective cross-sectional study. Paired tests performed in 1,130 immigrants attending an outpatient ward, between 2005 and 2007 for any health problem were evaluated by intention-to-treat (ITT) and per-protocol (PP) analysis for efficiency and efficacy of screening program.
Positive TST and QFT-IT were observed in 36.04 versus 29.82% (ITT) and in 45.27 versus 30.22% (PP) respectively. A higher drop-out rate was observed for TST (20.35 vs. 1.33%) (p < 0.0001). Second level assessment was accepted by half of the TST positive patients. Overall agreement rate between 887 paired tests was fair (k = 0.38). Higher k values were observed for higher TB prevalence rate in the country of origin (k = 0.43), for TST induration diameters >20 mM (k = 0.47), in subjects aged 40–50 years (k = 0.41) and in unvaccinated persons (k = 0.40). In a multiple logistic regression model continent of origin, class of TB prevalence in the country of origin and contacts with TB patients were found to be significantly associated with the probability of TST and QFT-IT positive result. Low education levels were associated only to an increased risk of TST positive results.
The drawback of the TST screening strategy in recent immigrants from highly endemic countries is due to low sensitivity/specificity of the test and to high drop-out rate with an overall significant lowering in strategy efficacy/efficiency. The higher QFT-IT specificity prevents unnecessary overload of the health care system and, although more expensive, might represent a cost-effective alternative to TST in targeted screening programs directed to high risk populations.
KeywordsLatent TB infection Tuberculin skin test Interferon-γ releasing assay Immigrants TB screening
The authors acknowledge the Provincia di Milano, Assessorato alle Politiche Sociali for the financial support of the study.
Conflict of interest statement
- 2.American Thoracic Society, Centers for Disease Control and Prevention. Diagnostic standards and classification of tuberculosis in adults and children. Am J Respir Crit Care Med. 2000;161:1376–95.Google Scholar
- 3.Dick M, Madhukar P, George C. Meta-analysis: new tests for the diagnosis of latent tuberculosis infection—areas of uncertainty and recommendations for research. Ann Intern Med. 2007;146:340–354.Google Scholar
- 4.Royal College of Physicians. Tuberculosis: national clinical guidelines for diagnosis, management, prevention, and control. London: Royal College of Physicians; 2006. http://www.nice.org.uk.
- 6.CDC. Guide for primary health care providers: targeted tuberculin testing and treatment of latent tuberculosis infection. Department of Health and Human Services Centers for Disease Control and Prevention National Center for HIV, STD, and TB Prevention Division of Tuberculosis Elimination-Atlanta, Georgia 2005.Google Scholar
- 8.MMWR. Guidelines for using the QuantiFERON®-TB gold test for detecting mycobacterium tuberculosis infection, United States Recommendations and Reports December 16. 2005;54:49–55.Google Scholar
- 9.Arend SM, Engelhard AC, Groot G, De Boer K, Andersen P, Ottenhoff TH, et al. Tuberculin skin testing compared with T-cell responses to Mycobacterium tuberculosis-specific and nonspecific antigens for detection of latent infection in persons with recent tuberculosis contact. Clin Diagn Lab Immunol. 2001;8:1089–96.PubMedGoogle Scholar
- 15.CDC. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR 2000;49:1–54.Google Scholar
- 16.Tuuminen T, Sorva S, Liippo K, Vasankari T, Soini H, Eriksén-Neuman B, et al. Feasibility of commercial interferon-gamma-based methods for the diagnosis of latent Mycobacterium tuberculosis infection in Finland, a country of low incidence and high bacille Calmette-Guérin vaccination coverage. Clin Microbiol Infect. 2007;13:836–8.CrossRefPubMedGoogle Scholar
- 22.Mazurek GH, Zajdowicz MJ, Hankinson AL, Costigan DJ, Toney SR, Rothel JS, et al. Detection of Mycobacterium tuberculosis infection in United States Navy recruits using the tuberculin skin test or whole-blood interferon-gamma release assays. Clin Infect Dis. 2007;45:826–36.CrossRefPubMedGoogle Scholar
- 28.WHO: Addressing poverty in TB control options for national TB control programmes. who/htm/tb/2005.352.Google Scholar
- 29.Carvalho AC, Pezzoli MC, El-Hamad I, Arce P, Bigoni S, Scarcella C, Indelicato AM, Scolari C, Carosi G, Matteelli A. QuantiFERON-TB Gold test in the identification of latent tuberculosis infection in immigrants. J Infect. 2007;55:164–8Google Scholar
- 30.Broekmans JF, Migliori GB, Rieder HL, Lees J, Ruutu P, Loddenkemper R, et al. World Health Organization, International Union Against Tuberculosis and Lung Disease, and Royal Netherlands Tuberculosis Association Working Group. European framework for tuberculosis control and elimination in countries with a low incidence. Recommendations of the World Health Organization (WHO), International Union Against Tuberculosis and Lung Disease (IUATLD) and Royal Netherlands Tuberculosis Association (KNCV) Working Group. Eur Respir J. 2002;19:765–75.CrossRefPubMedGoogle Scholar
- 31.Ministero della Salute: Linee-guida per il controllo della malattia tubercolare, su proposta del Ministro della Sanità, ai sensi dell’art. 115, comma 1, lettera b), del decreto legislativo 31 marzo 1998, n. 112.Google Scholar
- 32.WHO: DOTS expansion plan to stop TB in the WHO European regions 2002–2006. ISBN 92 890 1367 2, World Health Organization 2002.Google Scholar
- 34.Diel R, Loddenkemper R, Meywald-Walter K, Niemann S, Nienhaus A. Predictive value of a whole blood IFN-gamma assay for the development of active tuberculosis disease after recent infection with Mycobacterium tuberculosis. Am J Respir Crit Care Med. 2008;177:1164–70Google Scholar
- 37.WHO: Selected vaccine introduction status into routine immunization. Selected vaccine introduction status into routine infant immunization worldwide, 2003. www.who.int/entity/immunization_monitoring/routine/schedule_analysis_2003.pdf.
- 38.Bocchino M, Matarese A, Bellofiore B, Giacomelli P, Santoro G, Balato N, Castiglione F, Scarpa R, Perna F, Signoriello G, Galati D, Ponticiello A, Sanduzzi A. Performance of two commercial blood IFN-gamma release assays for the detection of Mycobacterium tuberculosis infection in patient candidates for anti-TNF-alpha treatment. Eur J Clin Microbiol Infect Dis. 2008 May 10.Google Scholar
- 39.Ponce de Leon JD, Acevedo-Vasquez E, Alvizuri S, Gutierrez C, Cucho M, Alfaro J, Perich R, Sanchez-Torres A, Pastor C, Sanchez-Schwartz C, Medina M, Gamboa R, Ugarte M: Comparison of an interferon-gamma assay with tuberculin skin testing for detection of tuberculosis (TB) Infection in Patients with Rheumatoid Arthritis in a TB-Endemic Population. J Rheumatol. 2008 May;35:776–81.Google Scholar
- 40.Karam F, Mbow F, Fletcher H, Senghor CS, Coulibaly KD, LeFevre AM, Ngom Gueye NF, Dieye T, Sow PS, Mboup S, Lienhardt C. Sensitivity of IFN-gamma release assay to detect latent tuberculosis infection is retained in HIV-infected patients but dependent on HIV/AIDS progression. PLoS One. 2008;3:e1441.Google Scholar