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Clinical Utility of the Interferon-γ Release Assay for Elderly Patients With Active Tuberculosis: A Word of Caution FREE TO VIEW

Jean-Paul Janssens, MD
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Geneva University Hospital, Geneva, Switzerland

Correspondence to: Jean-Paul Janssens, MD, Division of Pulmonary Diseases, Geneva University Hospital, 1211 Geneva 14, Switzerland; e-mail: Jean-Paul.Janssens@hcuge.ch



Chest. 2008;134(2):471-472. doi:10.1378/chest.08-0434
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To the Editor:

Kobashi et al1recently reported on the sensitivity of the QuantiFERON TB-2G (QFT-2G) [Cellestis Ltd; Carnegie, VIC, Australia] interferon-γ release assay (IGRA) in 30 subjects aged ≥80 years with active tuberculosis (TB) [77%], with similar results than a previous study by Mori et al2(n = 10; sensitivity, 80%), thus confirming the higher sensitivity of QFT-2G vs tuberculin skin testing (TST) in this population. We disagree, however, with the conclusion that the IGRA can be used as a diagnostic method for TB in elderly patients. The IGRA and TST are markers of infection by Mycobacterium tuberculosis complex, but are not reliable markers of activity of the disease. Although interferon-γ levels do reflect to some extent disease activity, IGRAs should not be used in a clinical setting to distinguish TB from latent tuberculosis infection (LTBI) and are not recommended in this indication.3 The infection rate by M tuberculosis in individuals aged ≥80 years (LTBI) in most developed countries is approximately 80%; thus, a positive test result only emphasizes the epidemiologic fact that most elderly patients were infected earlier in life.4 Conversely, a negative test result cannot rule out TB in elderly subjects.5Figure 1 shows the relationship between pretest and posttest probability of disease with a sensitivity of 77% and a specificity of 97% (ie, that of QFT-2G), according to the Bayes theorem.6 Because the IGRA yield positive results in TB and LTBI, pretest probability is based on estimated prevalence of LTBI in the population studied (ie, approximately 80%). As illustrated, with a negative QFT-2G result, the posttest probability of either LTBI or TB is still 50%. Assuming a hypothetical lower LTBI infection rate in Japan in the very old (40 to 60%), the posttest probability of disease is still 10 to 30% with a negative IGRA result. The IGRA should not be used in the very old as a diagnostic test for TB; the diagnosis must rely on clinical and radiologic evaluation and adequate bacteriologic sampling.

The author has no conflict of interest to disclose.

Figure Jump LinkFigure 1. Relationship between pretest and posttest probability of disease with a test having a sensitivity of 77% and a specificity of 97% (ie, that of QFT-2G [Bayes theorem]).6 The upper curve yields posttest probability if the test result is positive and the lower curve if the test result is negative. Pretest probability depends on estimated prevalence of disease in the population studied. Doted arrows show a pretest probability of 80% (estimated prevalence of LTBI in subjects aged >80 years), and a posttest probability of LTBI or TB of 50% if the QFT-2G result is negative.Grahic Jump Location
Kobashi, Y, Mouri, K, Yagi, S, et al (2008) Clinical utility of the QuantiFERON TB-2G test for elderly patients with active tuberculosis.Chest133,1196-1202. [PubMed] [CrossRef]
 
Mori, T, Sakatani, M, Yamagishi, F, et al Specific detection of tuberculosis infection: an interferon-γ–based assay using new antigens.Am J Respir Crit Care Med2004;170,59-64. [PubMed]
 
Janssens, JP, Roux-Lombard, P, Perneger, T, et al Quantitative scoring of an interferon-γ assay for differentiating active from latent tuberculosis.Eur Respir J2007;30,722-728. [PubMed]
 
Rieder, HL. Epidemiological basis of tuberculosis control. 1999; International Union Against Tuberculosis and Lung Disease. Paris, France:.
 
Mazurek, GH, Jereb, J, Lobue, P, et al Guidelines for using the QuantiFERON-TB Gold test for detectingMycobacterium tuberculosisinfection, United States.MMWR Recomm Rep2005;54(RR-15),49-55
 
Mayer, D Bayes’ theorem and predictive values.Essential evidence-based medicine.2004,222-236 Cambridge University Press. Cambridge, UK:
 

Figures

Figure Jump LinkFigure 1. Relationship between pretest and posttest probability of disease with a test having a sensitivity of 77% and a specificity of 97% (ie, that of QFT-2G [Bayes theorem]).6 The upper curve yields posttest probability if the test result is positive and the lower curve if the test result is negative. Pretest probability depends on estimated prevalence of disease in the population studied. Doted arrows show a pretest probability of 80% (estimated prevalence of LTBI in subjects aged >80 years), and a posttest probability of LTBI or TB of 50% if the QFT-2G result is negative.Grahic Jump Location

Tables

References

Kobashi, Y, Mouri, K, Yagi, S, et al (2008) Clinical utility of the QuantiFERON TB-2G test for elderly patients with active tuberculosis.Chest133,1196-1202. [PubMed] [CrossRef]
 
Mori, T, Sakatani, M, Yamagishi, F, et al Specific detection of tuberculosis infection: an interferon-γ–based assay using new antigens.Am J Respir Crit Care Med2004;170,59-64. [PubMed]
 
Janssens, JP, Roux-Lombard, P, Perneger, T, et al Quantitative scoring of an interferon-γ assay for differentiating active from latent tuberculosis.Eur Respir J2007;30,722-728. [PubMed]
 
Rieder, HL. Epidemiological basis of tuberculosis control. 1999; International Union Against Tuberculosis and Lung Disease. Paris, France:.
 
Mazurek, GH, Jereb, J, Lobue, P, et al Guidelines for using the QuantiFERON-TB Gold test for detectingMycobacterium tuberculosisinfection, United States.MMWR Recomm Rep2005;54(RR-15),49-55
 
Mayer, D Bayes’ theorem and predictive values.Essential evidence-based medicine.2004,222-236 Cambridge University Press. Cambridge, UK:
 
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