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High Rate of Negative Results of Tuberculin and QuantiFERON Tests Among Individuals With a History of Positive Skin Test Results

Published online by Cambridge University Press:  21 June 2016

Lloyd N. Friedman*
Affiliation:
Yale University School of Medicine, New Haven, Milford Hospital, Milford, Connecticut Yale–New Haven Hospital, New Haven, Milford Hospital, Milford, Connecticut
Esther R. Nash
Affiliation:
Yale University School of Medicine, New Haven, Milford Hospital, Milford, Connecticut VA Connecticut Healthcare System, West Haven, Connecticut
June Bryant
Affiliation:
Yale University School of Medicine, New Haven, Milford Hospital, Milford, Connecticut VA Connecticut Healthcare System, West Haven, Connecticut
Susan Henry
Affiliation:
Central Medical Unit/APT Foundation, New Haven, Milford Hospital, Milford, Connecticut
Julia Shi
Affiliation:
Yale University School of Medicine, New Haven, Milford Hospital, Milford, Connecticut Central Medical Unit/APT Foundation, New Haven, Milford Hospital, Milford, Connecticut
Joyce D'Amato
Affiliation:
Yale–New Haven Hospital, New Haven, Milford Hospital, Milford, Connecticut
Ghada H. Khaled
Affiliation:
Yale University School of Medicine, New Haven, Milford Hospital, Milford, Connecticut Yale–New Haven Hospital, New Haven, Milford Hospital, Milford, Connecticut
Mark B. Russi
Affiliation:
Yale University School of Medicine, New Haven, Milford Hospital, Milford, Connecticut Yale–New Haven Hospital, New Haven, Milford Hospital, Milford, Connecticut
Patrick G. O'Connor
Affiliation:
Yale University School of Medicine, New Haven, Milford Hospital, Milford, Connecticut Yale–New Haven Hospital, New Haven, Milford Hospital, Milford, Connecticut
Stephen C. Edberg
Affiliation:
Yale University School of Medicine, New Haven, Milford Hospital, Milford, Connecticut Yale–New Haven Hospital, New Haven, Milford Hospital, Milford, Connecticut
Margaret A. Pisani
Affiliation:
Yale University School of Medicine, New Haven, Milford Hospital, Milford, Connecticut Yale–New Haven Hospital, New Haven, Milford Hospital, Milford, Connecticut
Hilary C. Cain
Affiliation:
Yale University School of Medicine, New Haven, Milford Hospital, Milford, Connecticut VA Connecticut Healthcare System, West Haven, Connecticut
Lynn Tanoue
Affiliation:
Yale University School of Medicine, New Haven, Milford Hospital, Milford, Connecticut Yale–New Haven Hospital, New Haven, Milford Hospital, Milford, Connecticut
David N. Weissman
Affiliation:
National Institute for Occupational Safety and Health-Health Effects Laboratory Division, Morgantown, West Virginia
*
Pulmonary and Critical Care Section, Department of Medicine, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208057, New Haven, CT 06520-8057 ([email protected])

Abstract

Objectives.

To evaluate individuals at high risk for tuberculosis exposure who had a history of a positive tuberculin skin test (TST) result in order to determine the prevalence of unsuspected negative TST results. To confirm these findings with the QuantiFERON-TB test (QFT), an in vitro whole-blood assay that measures tuberculin-induced secretion of interferon-γ.

Methods.

This survey was conducted from November 2001 through December 2003 at 3 sites where TST screening is regularly done. Detailed histories and reviews of medical records were performed. TSTs were placed and read by 2 experienced healthcare workers, and blood was drawn for QFT. Any subject with a negative result of an initial TST during the study (induration diameter, <10 mm) underwent a second TST and a second QFT. The TST-negative group comprised individuals for whom both TSTs had an induration diameter of <10 mm. The confirmed-negative group comprised individuals for whom both TSTs yielded no detectable induration and results of both QFTs were negative.

Results.

A total of 67 immunocompetent subjects with positive results of a previous TST were enrolled in the study. Of 56 subjects who completed the TST protocol, 25 (44.6%; 95% confidence interval [CI], 31.6%-57.6%) were TST negative (P<.001). Of 31 subjects who completed the TST protocol and the QFT protocol, 8 (25.8%; 95% CI, 10.4%-41.2%) were confirmed negative (P<.005).

Conclusions.

A significant proportion of subjects with positive results of a previous TST were TST negative in this study, and a subset of these were confirmed negative. These individuals' TST status may have reverted or may never have been positive. It will be important in future studies to determine whether such individuals lack immunity to tuberculosis and whether they should be considered for reentry into tuberculosis screening programs.

Type
Original Articles
Copyright
Copyright © The Society for Healthcare Epidemiology of America 2006

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References

1.Control of tuberculosis in the United States. American Thoracic Society. Am Rev Respir Dis 1992; 146:16231633.CrossRefGoogle Scholar
2.Bolyard, EA, Tablan, OC, Williams, WW, Pearson, ML, Shapiro, CN, Deitchmann, SD. Guideline for infection control in healthcare personnel, 1998. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol 1998; 19:407463.CrossRefGoogle ScholarPubMed
3.Houk, VN, Kent, DC, Sorensen, K, Baker, JH. The eradication of tuberculosis infection by isoniazid chemoprophylaxis. Arch Environ Health 1968; 16:4650.Google Scholar
4.Atuk, NO, Hunt, EH. Serial tuberculin testing and isoniazid therapy in general hospital employees. JAMA 1971; 218:17951798.CrossRefGoogle ScholarPubMed
5.Ferebee, SH. Controlled chemoprophylaxis trials in tuberculosis: a general review. Adv Tuberc Res 1970; 26:28106.Google ScholarPubMed
6.Daniel, TM, Bowerfind, ES. Reversion of recently acquired tuberculin reactivity during isoniazid prophylaxis. Am Rev Respir Dis 1967; 95:500502.Google ScholarPubMed
7.Dahlstrom, AW, Wilson, JL, Sedlacek, BB. The immediate effectiveness of isoniazid chemoprophylaxis as determined by the tuberculin test. Dis Chest 1960; 38:599603.Google Scholar
8.Perez-Stable, EJ, Flaherty, D, Schecter, G, Slutkin, G, Hopewell, PC. Conversion and reversion of tuberculin reactions in nursing home residents. Am Rev Respir Dis 1988; 137:801804.Google Scholar
9.Grzybowski, S, Allen, EA. The challenge of tuberculosis in decline: a study based on the epidemiology of tuberculosis in Ontario, Canada. Am Rev Respir Dis 1964; 90:707720.Google ScholarPubMed
10.Arneil, AS, McMichael, B. Effect of INH reversion rates of (very) recent converters. Can J Public Health 1974; 65:197.Google ScholarPubMed
11.Sepkowitz, KA. Tuberculin skin testing and the health care worker: lessons of the Prophit Survey. Tuber Lung Dis 1996; 77:8185.CrossRefGoogle ScholarPubMed
12.Wilson, LM. Reversal of the tuberculin reaction: its significance in case finding by survey skin testing. Am Rev Respir Dis 1970; 102:282284.Google Scholar
13.Adams, JM, Kalajan, VA, Mork, BO, Rosenblatt, M, Rothrock, WJ, O'Loughlin, BJ. Reversal of tuberculin reaction in early tuberculosis. Dis Chest 1959; 35:348356.Google Scholar
14.Robinson, A, Meyer, M, Middlebrook, G. Tuberculin hypersensitivity in tuberculous infants treated with isoniazid. N Engl J Med 1955; 252:983985.CrossRefGoogle ScholarPubMed
15.Mazurek, GH, Villarino, ME. Guidelines for using the QuantiFERON-TB test for diagnosing latent Mycobacterium tuberculosis infection. Centers for Disease Control and Prevention. MMWR Recomm Rep 2003; 52:1518.Google Scholar
16.Pottumarthy, S, Morris, AJ, Harrison, AC, Wells, VC. Evaluation of the tuberculin gamma interferon assay: potential to replace the Mantoux skin test. J Clin Microbiol 1999; 37:32293232.CrossRefGoogle ScholarPubMed
17.Streeton, JA, Desem, N, Jones, SL. Sensitivity and specificity of a gamma interferon blood test for tuberculosis infection. Int J Tuberc Lung Dis 1998; 2:443450.Google Scholar
18.Mazurek, GH, LoBue, PA, Daley, CL, et al. Comparison of a whole-blood interferon gamma assay with tuberculin skin testing for detecting latent Mycobacterium tuberculosis infection. JAMA 2001;286:17401747.Google Scholar
19.Bellete, B, Coberly, J, Barnes, GL, et al. Evaluation of a whole-blood interferon γ release assay for the detection of Mycobacterium tuberculosis infection in 2 study populations. Clin Infect Dis 2002; 34:14491456.Google Scholar
20.Comstock, GW, Bellete, B, Ko, C, Coberly, J, Chaisson, R, Bishai, WR. Whole-blood interferon-γ release assay versus the TST: newer not better. Clin Infect Dis 2003; 36:12071208.CrossRefGoogle Scholar
21.Nadal, D. Is the in vitro interferon-γ release assay an adequate replacement for the tuberculin skin test? Clin Infect Dis 2002; 34:14571459.CrossRefGoogle ScholarPubMed
22.Targeted tuberculin testing and treatment of latent tuberculosis infection. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. This is a Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). This statement was endorsed by the Council of the Infectious Diseases Society of America. (IDSA), September 1999. Am J Respir Crit Care Med 2000; 161:S221S247.CrossRefGoogle Scholar
23.Diagnostic Standards and Classification of Tuberculosis in Adults and Children. This official statement of the American Thoracic Society and the Centers for Disease Control and Prevention was adopted by the ATS Board of Directors, July 1999. This statement was endorsed by the Council of the Infectious Disease Society of America, September 1999. Am J Respir Crit Care Med 2000; 161:13761395.Google Scholar
24.Havlir, DV, Van Der Kuyp, F, Duffy, E, Marshall, R, Horn, D, Ellner, JJ. A 19-year follow-up of tuberculin reactors: assessment of skin test reactivity and in vitro lymphocyte responses. Chest 1991; 99:11721176.CrossRefGoogle ScholarPubMed
25.Bass, JB, Sanders, RV, Kirkpatrick, MB. Choosing an appropriate cutting point for conversion in annual tuberculin skin testing. Am Rev Respir Dis 1985; 132:379381.Google Scholar
26.Bass, JB Jr. How good is the tuberculin skin test? Infect Control Hosp Epidemiol 2003; 24:797798.CrossRefGoogle ScholarPubMed
27.Marsh, BJ, San Vicente, J, von Reyn, CF. Utility of dual skin tests to evaluate tuberculin skin test reactions of 10 to 14 mm in healthcare workers. Infect Control Hosp Epidemiol 2003; 24:821824.Google Scholar
28.Menzies, D. Interpretation of repeated tuberculin tests: boosting, conversion, and reversion. Am J Respir Crit Care Med 1999; 159:1521.CrossRefGoogle ScholarPubMed
29.Esser, MT, Marchese, RD, Kierstead, LS, et al. Memory T cells and vaccines. Vaccine 2003; 21:419430.Google Scholar
30.Ellner, JJ. Review: the immune response in human tuberculosis—implications for tuberculosis control. J Infect Dis 1997; 176:13511359.CrossRefGoogle ScholarPubMed
31.Smith, JA, Reichman, LB. Lymphocyte transformation: an aid in the diagnosis of tuberculosis in patients with nonreactive skin tests. Am Rev Respir Dis 1972; 106:194201.Google Scholar
32.Mori, T, Sakatani, M, Yamagishi, F, et al. Specific detection of tuberculosis infection: an interferon-gamma-based assay using new antigens. Am J Respir Crit Care Med 2004; 170:5964.CrossRefGoogle ScholarPubMed
33.Lalvani, A. Spotting latent infection: the path to better tuberculosis control. Thorax 2003; 58:916918.Google Scholar
34.Waxman, J, Lockshin, M. In vitro and in vivo cellular immunity in anergic miliary tuberculosis. Am Rev Respir Dis 1973; 107:661664.CrossRefGoogle ScholarPubMed
35.Miller, SD, Jones, HE. Correlation of lymphocyte transformation with tuberculin skin-test sensitivity. Am Rev Respir Dis 1973; 107:530538.Google Scholar
36.Cox, RA, Lundberg, DI, Arnold, DR. Lymphocyte transformation assays as a diagnostic tool in tuberculosis in children. Am Rev Respir Dis 1981; 123:627630.Google Scholar
37.Tager, IB, Kalaidjian, R, Baldini, L, Rocklin, RE. Variability in the intradermal and in vitro lymphocyte responses to PPD in patients receiving isoniazid chemoprophylaxis. Am Rev Respir Dis 1985; 131:214220.Google Scholar