Advances in the Diagnosis of Latent Tuberculosis Infection

Abstract

Accurate diagnosis of tuberculosis (TB) infection is an important component of tuberculosis control programs in many countries. Identification of persons with asymptomatic, or latent, tuberculosis infection allows for treatment of individuals at high risk for progressing to active disease so that the overall burden of tuberculosis disease is diminished. In the United States, targeted testing and treatment of latent tuberculosis infection (LTI) are major components of the Centers for Disease Control and Prevention's efforts at TB elimination. This review focuses on the comparative utility of tuberculin skin testing and interferon-gamma release assays (IGRAs) to diagnose LTI. Commercially available IGRAs have superior sensitivity and specificity compared with conventional tuberculin skin testingin some settings (particularly bacille-Calmette Guérin–vaccinated individuals). Also discussed are the performance characteristics of these tests in specific populations, including foreign-born persons from high-prevalence countries, close contacts of actively infected patients, immunocompromised populations, and health care workers.

Keywords

tuberculosis - latent tuberculosis - tuberculin skin test - PPD - interferon gamma release assays - prophylaxis

• References

• 1 Mantoux C. Intradermo-reaction de la tuberculine. Comptes rendus de l'Academie des Sciences 1908; 147: 355-357
• 2 Rhoades ER, Bryant RE. The influence of local factors on the reaction to tuberculin, I: The effect of injection. Chest 1980; 77 (2) 190-193
• 3 Menzies D, Pai M, Comstock G. Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research. Ann Intern Med 2007; 146 (5) 340-354
• 4 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 (1) 88-99
• 5 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 (3) 177-184
• 6 Bergstedt W, Tingskov PN, Thierry-Carstensen B , et al. First-in-man open clinical trial of a combined rdESAT-6 and rCFP-10 tuberculosis specific skin test reagent. PLoS ONE 2010; 5 (6) e11277
• 7 American Thoracic Society. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR Recomm Rep 2000; 49: 1-51
• 8 Diel R, Loddenkemper R, Nienhaus A. Predictive value of interferon-gamma release assays and tuberculin skin testing for progression from latent TB infection to disease state: a meta-analysis. Chest 2012; 142 (1) 63-75
• 9 Geng E, Kreiswirth B, Driver C , et al. Changes in the transmission of tuberculosis in New York City from 1990 to 1999. N Engl J Med 2002; 346 (19) 1453-1458
• 10 Ewer K, Deeks J, Alvarez L , et al. Comparison of T-cell-based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak. Lancet 2003; 361 (9364) 1168-1173
• 11 Kang YA, Lee HW, Yoon HI , et al. Discrepancy between the tuberculin skin test and the whole-blood interferon gamma assay for the diagnosis of latent tuberculosis infection in an intermediate tuberculosis-burden country. JAMA 2005; 293 (22) 2756-2761
• 12 Brodie D, Lederer DJ, Gallardo JS, Trivedi SH, Burzynski JN, Schluger NW. Use of an interferon-gamma release assay to diagnose latent tuberculosis infection in foreign-born patients. Chest 2008; 133 (4) 869-874
• 13 Adetifa IM, Ota MO, Jeffries DJ , et al. Commercial interferon gamma release assays compared to the tuberculin skin test for diagnosis of latent Mycobacterium tuberculosis infection in childhood contacts in the Gambia. Pediatr Infect Dis J 2010; 29 (5) 439-443
• 14 Adetifa IM, Lugos MD, Hammond A , et al. Comparison of two interferon gamma release assays in the diagnosis of Mycobacterium tuberculosis infection and disease in The Gambia. BMC Infect Dis 2007; 7: 122
• 15 Bennett DE, Courval JM, Onorato I , et al. Prevalence of tuberculosis infection in the United States population: the national health and nutrition examination survey, 1999-2000. Am J Respir Crit Care Med 2008; 177 (3) 348-355
• 16 Mazurek GH, Jereb J, Vernon A, LoBue P, Goldberg S, Castro K. IGRA Expert Committee; Centers for Disease Control and Prevention (CDC). Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection—United States, 2010. MMWR Recomm Rep 2010; 59 (RR-5) 1-25
• 17 LoBue PA, Castro KG. Is it time to replace the tuberculin skin test with a blood test?. JAMA 2012; 308 (3) 241-242
• 18 Brassard P, Suissa S, Kezouh A, Ernst P. Inhaled corticosteroids and risk of tuberculosis in patients with respiratory diseases. Am J Respir Crit Care Med 2011; 183 (5) 675-678
• 19 Keane J, Gershon S, Wise RP , et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001; 345 (15) 1098-1104
• 20 Wallis RS. Biologics and infections: lessons from tumor necrosis factor blocking agents. Infect Dis Clin North Am 2011; 25 (4) 895-910
• 21 Wallis RS, Schluger NW. Pulmonary infectious complications of tumor necrosis factor blockade. Infect Dis Clin North Am 2010; 24 (3) 681-692
• 22 Aichelburg M, Rieger A, Breitenecker F , et al. Detection and prediction of active tuberculosis disease by a whole-blood interferon-gamma release assay in HIV-1-infected individuals. Clin Infect Dis 2009; 48: 954-962
• 23 Cattamanchi A, Smith R, Steingart KR , et al. Interferon-gamma release assays for the diagnosis of latent tuberculosis infection in HIV-infected individuals: a systematic review and meta-analysis. J Acquir Immune Defic Syndr 2011; 56 (3) 230-238
• 24 Hsia EC, Schluger N, Cush JJ , et al. Interferon-γ release assay versus tuberculin skin test prior to treatment with golimumab, a human anti-tumor necrosis factor antibody, in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis. Arthritis Rheum 2012; 64 (7) 2068-2077
• 25 Kleinert S, Tony HP, Krueger K , et al. Screening for latent tuberculosis infection: performance of tuberculin skin test and interferon-γ release assays under real-life conditions. Ann Rheum Dis 2012; 71 (11) 1791-1795
• 26 Menzies D, Fanning A, Yuan L, Fitzgerald M. Tuberculosis among health care workers. N Engl J Med 1995; 332 (2) 92-98
• 27 Fong KS, Tomford JW, Teixeira L , et al. Challenges of interferon-γ release assay conversions in serial testing of health-care workers in a TB control program. Chest 2012; 142 (1) 55-62
• 28 Park JS, Lee JS, Kim MY , et al. Monthly follow-ups of interferon-γ release assays among healthcare workers in contact with TB patients. Chest 2012; May 3. [Epub ahead of print]
• 29 Belknap R, Wall K, Teeter L , et al. Interferon-gamma release assays (IGRA) in serial testing for latent tuberculosis infection in U.S. health care workers [abstract]. Am J Respir Crit Care Med 2010; 181: A2263
• 30 Tuberculosis: Clinical Diagnosis and Management of Tuberculosis, and Measures for Its Prevention and Control. London: National Institute for Health and Clinical Excellence; 2011
• 31 Canadian Tuberculosis Committee. Recommendations on Interferon Gamma Release Assays for the Diagnosis of Latent Tuberculosis Infection—2010 Update. Ottawa, Ontario: Canadian Tuberculosis Committee; 2010
• 32 Dewan PK, Grinsdale J, Liska S, Wong E, Fallstad R, Kawamura LM. Feasibility, acceptability, and cost of tuberculosis testing by whole-blood interferon-gamma assay. BMC Infect Dis 2006; 6: 47
• 33 Mandalakas AM, Hesseling AC, Gie RP, Schaaf HS, Marais BJ, Sinanovic E. Modelling the cost-effectiveness of strategies to prevent tuberculosis in child contacts in a high-burden setting. Thorax 2012; Jun 20. [Epub ahead of print]
• 34 Pareek M, Bond M, Shorey J , et al. Community-based evaluation of immigrant tuberculosis screening using interferon γ release assays and tuberculin skin testing: observational study and economic analysis. Thorax 2012; Jun 12. [Epub ahead of print]
• 35 Eralp MN, Scholtes S, Martell G, Winter R, Exley AR. Screening of healthcare workers for tuberculosis: development and validation of a new health economic model to inform practice. BMJ Open 2012; 2 (2) e000630
• 36 Nienhaus A, Schablon A, Costa JT, Diel R. Systematic review of cost and cost-effectiveness of different TB-screening strategies. BMC Health Serv Res 2011; 11: 247
• 37 Linas BP, Wong AY, Freedberg KA, Horsburgh Jr CR. Priorities for screening and treatment of latent tuberculosis infection in the United States. Am J Respir Crit Care Med 2011; 184 (5) 590-601
• 38 Pareek M, Watson JP, Ormerod LP , et al. Screening of immigrants in the UK for imported latent tuberculosis: a multicentre cohort study and cost-effectiveness analysis. Lancet Infect Dis 2011; 11 (6) 435-444
• 39 Pooran A, Booth H, Miller RF , et al. Different screening strategies (single or dual) for the diagnosis of suspected latent tuberculosis: a cost effectiveness analysis. BMC Pulm Med 2010; 10: 7
• 40 Hardy AB, Varma R, Collyns T, Moffitt SJ, Mullarkey C, Watson JP. Cost-effectiveness of the NICE guidelines for screening for latent tuberculosis infection: the QuantiFERON-TB Gold IGRA alone is more cost-effective for immigrants from high burden countries. Thorax 2010; 65 (2) 178-180
• 41 Oxlade O, Schwartzman K, Menzies D. Interferon-gamma release assays and TB screening in high-income countries: a cost-effectiveness analysis. Int J Tuberc Lung Dis 2007; 11 (1) 16-26