Hostname: page-component-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-11-25T00:33:42.805Z Has data issue: false hasContentIssue false

Discordant QuantiFERON-TB Gold Test Results Among US Healthcare Workers With Increased Risk of Latent Tuberculosis Infection: A Problem or Solution?

Published online by Cambridge University Press:  02 January 2015

Nira R. Pollock*
Affiliation:
Department of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts
Antonio Campos-Neto
Affiliation:
Department of Cytokine Biology, Forsyth Institute, Boston, Massachusetts
Suely Kashino
Affiliation:
Department of Cytokine Biology, Forsyth Institute, Boston, Massachusetts
Danielle Napolitano
Affiliation:
Department of Cytokine Biology, Forsyth Institute, Boston, Massachusetts
Samuel M. Behar
Affiliation:
Department of Rheumatology, Boston, Massachusetts
Daniel Shin
Affiliation:
Department of Rheumatology, Boston, Massachusetts
Alex Sloutsky
Affiliation:
Brigham and Women's Hospital, and , Massachusetts State Laboratory Institute, Boston, Massachusetts
Swati Joshi
Affiliation:
Brigham and Women's Hospital, and , Massachusetts State Laboratory Institute, Boston, Massachusetts
Jasmine Guillet
Affiliation:
Brigham and Women's Hospital, and , Massachusetts State Laboratory Institute, Boston, Massachusetts
Michael Wong
Affiliation:
Department of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts
Edward Nardell
Affiliation:
Division of Social Medicine and Health Inequalities, Boston, Massachusetts
*
Department of Infectious Diseases, Beth Israel Deaconess Medical Center, Lowry Medical Building, 110 Francis Street, Suite GB, Boston, MA 02215 ([email protected])

Abstract

Objective.

In late 2006, our hospital implemented use of the QuantiFERON-TB Gold (QFT-G) assay, a whole-blood interferon-γ release assay, for detection of tuberculosis infection. All newly hired healthcare workers (HCWs) with positive Mantoux tuberculin skin test (TST) results were routinely tested with the QFT-G assay, to take advantage of its higher specificity. We then undertook a quality assurance review to evaluate the QFT-G test results in HCWs with multiple risk factors for latent tuberculosis infection (LTBI).

Methods.

The clinical records for TST-positive HCWs tested with the QFT-G assay were reviewed. HCWs with 2 or more risk factors commonly associated with LTBI were classified as “increased risk” (IR). IR HCWs who had negative QFT-G test results underwent repeat QFT-G testing and were offered testing with a different interferon-γ release assay (T-SPOT.TB) and with extended T cell stimulation assays.

Results.

Ofl43 TST-positive HCWs tested with the QFT-G assay, 26 (18%) had positive results, 115 (81%) had negative results, and 2 (1 %) had indeterminate results. Of 82 IR HCWs, 23 (28%) had positive QFT-G test results, and 57 (70%) had negative results. Of the 57 IR HCWs with negative results, 43 underwent repeat QFT-G testing: 41 had negative results again, and 2 had positive results. These 43 HCWs were also offered additional testing with the T-SPOT.TB diagnostic, and 36 consented: 31/36 tested negative, and 5/36 tested positive. Extended assays using the antigens ESAT-6 and CFP-10 confirmed the positive results detected by the overnight assays and yielded positive results for an additional 7/36 (19%) of individuals; strikingly, all 36 HCWs had strongly positive test results with assays using purified protein derivative.

Conclusions.

The extreme discordance between the results of our clinical diagnostic algorithm and the results of QFT-G testing raises concern about the sensitivity of the QFT-G assay for detection of LTBI in our HCWs. Results of extended stimulation assays suggest that many of our IR HCWs have indeed been sensitized to Mycobacterium tuberculosis. It is possible that the QFT-G assay identifies those at higher reactivation risk rather than all previously infected, but, in the absence of long-term follow-up data, we should interpret negative QFT-G results with some caution.

Type
Original Article
Copyright
Copyright © The Society for Healthcare Epidemiology of America 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Mazurek, GH, Jereb, J, Lobue, P, Iademarco, MF, Metchock, B, Vernon, A. Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States [erratum appears in MMWR Morb Wkly Rep 2005;54:1288]. MMWR Recomm Rep 2005;54(RR-15):4955.Google ScholarPubMed
2.Farhat, M, Greenaway, C, Pai, M, Menzies, D. False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria? Int J Tuberc Lung Dis 2006;10:11921204.Google ScholarPubMed
3.National Collaborating Centre for Chronic Conditions. Tuberculosis: clinical diagnosis and management of tuberculosis, and measures for its prevention and control. London: Royal College of Physicians; 2006.Google Scholar
4.American Thoracic Society. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161(4 Pt 2):S221247.CrossRefGoogle Scholar
5.Jensen, PA, Lambert, LA, Iademarco, MF, Ridzon, R. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recomm Rep 2005;54:1141.Google ScholarPubMed
6.Public Health Agency of Canada. International Tuberculosis Incidence Rates. Available at: http://www.phac-aspc.gc.ca/tbpc-latb/itir-eng.php. Accessed December 12, 2007.Google Scholar
7.QuantiFERON-TB Gold assay notes [package insert]. Victoria, Australia: Victorian Infectious Diseases Reference Laboratory; 2006.Google Scholar
8.T-SPOT.TB [package insert]. Oxfordshire, UK: Oxford Immunotec; 2006.Google Scholar
9.T-SPOT.TB Visual Procedure Guide. Oxfordshire, UK: Oxford Immunotec; 2005.Google Scholar
10.QuantiFERON-TB Gold In Tube [package insert]. Victoria, Australia: Cellestis; 2006.Google Scholar
11.Mukherjee, S, Kashino, SS, Zhang, Y, et al.Cloning of the gene encoding a protective Mycobacterium tuberculosis secreted protein detected in vivo during the initial phases of the infectious process. J Immunol 2005;175:52985305.CrossRefGoogle ScholarPubMed
12.Seibert, FB, Glenn, J. Tuberculin purified protein derivative: preparation and analysis of a large quantity for standard. Am Rev Tuberc 1941;44:925.Google Scholar
13.Mazurek, GH, Zajdowicz, MJ, Hankinson, AL, 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;45:826836.CrossRefGoogle ScholarPubMed
14.Tuberculosis among foreign-born persons who had recently arrived in the United States-Hawaii, 1992–1993, and Los Angeles County. MMWR. 1993;44:703707.Google Scholar
15.Ferebee, SH. Controlled chemoprophylaxis trials in tuberculosis. A general review. Bibl tuberculosea 1970;26:28106.Google ScholarPubMed
16.Sutherland, I. The ten-year incidence of clinical tuberculosis following “conversion” in 2550 individuals aged 14 to 19 years. Tuberculosis Surveillance and Research Unit Progress Report. The Hague: Royal Netherlands Tuberculosis Association (KNCV); 1968.Google Scholar
17.Trends in tuberculosis—United States, 2005. MMWR Morb Mortal Wkly Rep 2006;55:305308.Google Scholar
18.Porsa, E, Cheng, L, Graviss, EA. Comparison of an ESAT-6/CFP-10 peptide-based enzyme-linked immunospot assay to a tuberculin skin test for screening of a population at moderate risk of contracting tuberculosis. Clin Vaccine Immunol 2007;14:714719.CrossRefGoogle ScholarPubMed
19.Arend, SM, Thijsen, SF, Leyten, EM, et al.Comparison of two interferon-gamma assays and tuberculin skin test for tracing tuberculosis contacts. Am J Respir Crit Care Med 2007;175:618627.CrossRefGoogle ScholarPubMed
20.Richeldi, L, Ewer, K, Losi, M, et al.T cell-based tracking of multidrug resistant tuberculosis infection after brief exposure. Am J Respir Crit Care Med 2004;170:288295.CrossRefGoogle ScholarPubMed
21.Brock, I, Weldingh, K, Lillebaek, T, Follmann, F, Andersen, P. Comparison of tuberculin skin test and new specific blood test in tuberculosis contacts. Am J Respir Crit Care Med 2004;170:6569.CrossRefGoogle ScholarPubMed
22.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;361:11681173.CrossRefGoogle Scholar
23.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;146:340354.CrossRefGoogle ScholarPubMed
24.Richeldi, L. An update on the diagnosis of tuberculosis infection. Am J Respir Crit Care Med 2006;174:736742.CrossRefGoogle ScholarPubMed
25.Cehovin, A, Cliff, JM, Hill, PC, Brookes, RH, Dockrell, HM. Extended culture enhances sensitivity of a gamma interferon assay for latent Mycobacterium tuberculosis infection. Clin Vaccine Immunol 2007;14:796798.CrossRefGoogle ScholarPubMed
26.Leyten, EM, Arend, SM, Prins, C, Cobelens, FG, Ottenhoff, TH, van Dissel, JT. Discrepancy between Mycobacterium tuberculosis-specific gamma interferon release assays using short and prolonged in vitro incubation. Clin Vaccine Immunol 2007;14:880885.CrossRefGoogle Scholar
27.Reece, ST, Stride, N, Ovendale, P, Reed, SG, Campos-Neto, A. Skin test performed with highly purified Mycobacterium tuberculosis recombinant protein triggers tuberculin shock in infected guinea pigs. Infect Immun 2005;73:33013306.CrossRefGoogle ScholarPubMed
28.Kamath, AB, Woodworth, J, Xiong, X, Taylor, C, Weng, Y, Behar, SM. Cytolytic CD8+ T cells recognizing CFP10 are recruited to the lung after Mycobacterium tuberculosis infection. J Exp Med 2004;200:14791489.CrossRefGoogle Scholar
29.Harada, N, Nakajima, Y, Higuchi, K, Sekiya, Y, Rothel, J, Mori, T. Screening for tuberculosis infection using whole-blood interferon-gamma and Mantoux testing among Japanese healthcare workers. Infect Control Hosp Epidemiol 2006;27:442448.CrossRefGoogle ScholarPubMed
30.Pai, M, Gokhale, K, Joshi, R, et al.Mycobacterium tuberculosis infection in health care workers in rural India: comparison of a whole-blood interferon gamma assay with tuberculin skin testing. JAMA 2005;293:27462755.CrossRefGoogle ScholarPubMed
31.Drobniewski, F, Balabanova, Y, Zakamova, E, Nikolayevskyy, V, Fedorin, I. Rates of latent tuberculosis in health care staff in Russia. PLoS Med 2007;4:e55.CrossRefGoogle ScholarPubMed
32.Horsburgh, CR Jr. Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med 2004;350:20602067.CrossRefGoogle ScholarPubMed
33.Comstock, GW, Livesay, VT, Woolpert, SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol 1974;99:131138.CrossRefGoogle ScholarPubMed
34.Jeyakumar, D. Tuberculin reactivity and subsequent development of tuberculosis in a cohort of student nurses. Med J Malaysia 1999;54:492495.Google Scholar
35.Leung, CC, Yew, WW, Chang, KC, et al.Risk of active tuberculosis among schoolchildren in Hong Kong. Arch Pediatr Adolesc Med 2006;160:247251.CrossRefGoogle ScholarPubMed
36.Comstock, GW, Baum, C, Snider, DE Jr. Isoniazid prophylaxis among Alaskan Eskimos: a final report of the bethel isoniazid studies. Am Rev Respir Dis 1979;119:827830.Google ScholarPubMed
37.Richeldi, L, Ewer, K, Losi, M, et al.T-cell-based diagnosis of neonatal multidrug-resistant latent tuberculosis infection. Pediatrics 2007;119:e15.CrossRefGoogle ScholarPubMed
38.Doherty, TM, Demissie, A, Olobo, J, et al.Immune responses to the Mycobacterium tuberculosis-specific antigen ESAT-6 signal subclinical infection among contacts of tuberculosis patients. J Clin Microbiol 2002;40:704706.CrossRefGoogle Scholar
39.Andersen, P, Doherty, TM, Pai, M, Weldingh, K. The prognosis of latent tuberculosis: can disease be predicted? Trends Mol Med 2007;13:175182.CrossRefGoogle ScholarPubMed