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Roland Diel, MD, MPH
Author and Funding Information

From the Department of Pulmonary Medicine, Medical School Hannover (MHH).

Correspondence to: Roland Diel, MD, MPH, Medical School Hannover, Carl-Neuberg-Str 1, Hannover, Germany 30625; e-mail: Diel.Roland@mh-hannover.de


Financial/nonfinancial disclosures: The author has reported to CHEST the following conflicts of interest: Dr Diel has received travel reimbursement and/or fees for speaking at symposia sponsored by Cellestis Ltd, Oxford Immunotec Ltd, and Pharmore Ltd (exclusive supplier of Tuberculin RT23 for Germany).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;143(5):1515-1516. doi:10.1378/chest.13-0126
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To the Editor:

I thank Drs Hernández-Garduño and Huitrón Bravo for addressing some important aspects of testing close contacts of patients with TB for latent TB infection. The authors point out that in high-burden countries, where bacille Calmette-Guérin (BCG) vaccination is common,1 it is necessary to identify more vaccinated but truly infected individuals, and because of possibly false-positive cross-reactions this cannot be done effectively by testing with the tuberculin skin test (TST). Another important point not addressed by Drs Hernández-Garduño and Huitrón-Bravo is the advantage of interferon-γ release assays (IGRAs) over the TST in people with nontuberculous mycobacteria infections, which are distributed worldwide. The TST, but not IGRAs, cross-react against most nontuberculous mycobacteria, irrespective of any simultaneous coverage with BCG.2

I certainly agree with the authors that lowering IGRA costs would probably encourage the implementation of preventive therapy (PT). With respect to the cost-effectiveness of PT, it should be kept in mind that IGRAs may dramatically reduce the number of falsely positive contact people wrongly considered for PT, which may at least partially compensate higher IGRA costs.3

In previous letters4,5 in reference to our predictive value study in Germany,6 Dr Hernández-Garduño suggested that both tests, IGRAs and the TST, may predict TB disease in high-risk contacts similarly. However, in our reply at that time,5 we demonstrated that the lack of statistical significance for different QuantiFERON-TB Gold In Tube-Test (QFT-GIT) (Cellestis, a company of Qiagen GmBH) and TST progression rates in subjects not vaccinated with BCG in two-tailed testing (although there was a significantly higher progression rate in favor of the QFT-GIT in one-tailed testing) is most likely explained by the small sample size. Thus, it would be incorrect to conclude that TST predictive value is similar to QFT-GIT in the unvaccinated contacts.

In addition, although the IGRAs have a fixed cutoff for test positivity, TST cutoffs in BCG vaccines and subsequently the number of contacts with presumed latent TB infection who eventually progress to active TB depend on differing opinions of national committees on what constitutes test positivity in the TST; cutoffs vary between induration sizes of 5 and 15 mm. Therefore, as the authors of this letter stress, in the “real world” of high-burden settings, where most people can be expected to be BCG vaccinated, we do not see the need for any further research in BCG-unvaccinated close contacts of smear positive patients to clearly establish similarities or differences in the positive predictive value and negative predictive value between IGRAs and TST.

References

Zwerling A, Behr MA, Verma A, Brewer TF, Menzies D, Pai M. The BCG World Atlas: a database of global BCG vaccination policies and practices. PLoS Med. 2011;8(3):e1001012. [CrossRef] [PubMed]
 
Diel R, Loddenkemper R, Nienhaus A. Predictive value of interferon-γ release assays and tuberculin skin testing for progression from latent TB infection to disease state: a meta-analysis. Chest. 2012;142(1):63-75. [CrossRef] [PubMed]
 
Diel R, Wrighton-Smith P, Zellweger JP. Cost-effectiveness of interferon-gamma release assay testing for the treatment of latent tuberculosis. Eur Respir J. 2007;30(2):321-332. [CrossRef] [PubMed]
 
Hernández-Garduño E. Predictive value of the tuberculin skin test and the QuantiFERON-TB Gold In-Tube assay for the development of active tuberculosis disease. Am J Respir Crit Care Med. 2008;178(12):1282. [CrossRef]
 
Hernández-Garduño E. An update: the predictive value of QuantiFERON-TB-Gold In-Tube assay and the tuberculin skin test. Am J Respir Crit Care Med. 2011;183(3):414. [CrossRef] [PubMed]
 
Diel R, Loddenkemper R, Niemann S, Meywald-Walter K, Nienhaus A. Negative and positive predictive value of a whole-blood interferon-γ release assay for developing active tuberculosis: an update. Am J Respir Crit Care Med. 2011;183(1):88-95. [CrossRef] [PubMed]
 

Figures

Tables

References

Zwerling A, Behr MA, Verma A, Brewer TF, Menzies D, Pai M. The BCG World Atlas: a database of global BCG vaccination policies and practices. PLoS Med. 2011;8(3):e1001012. [CrossRef] [PubMed]
 
Diel R, Loddenkemper R, Nienhaus A. Predictive value of interferon-γ release assays and tuberculin skin testing for progression from latent TB infection to disease state: a meta-analysis. Chest. 2012;142(1):63-75. [CrossRef] [PubMed]
 
Diel R, Wrighton-Smith P, Zellweger JP. Cost-effectiveness of interferon-gamma release assay testing for the treatment of latent tuberculosis. Eur Respir J. 2007;30(2):321-332. [CrossRef] [PubMed]
 
Hernández-Garduño E. Predictive value of the tuberculin skin test and the QuantiFERON-TB Gold In-Tube assay for the development of active tuberculosis disease. Am J Respir Crit Care Med. 2008;178(12):1282. [CrossRef]
 
Hernández-Garduño E. An update: the predictive value of QuantiFERON-TB-Gold In-Tube assay and the tuberculin skin test. Am J Respir Crit Care Med. 2011;183(3):414. [CrossRef] [PubMed]
 
Diel R, Loddenkemper R, Niemann S, Meywald-Walter K, Nienhaus A. Negative and positive predictive value of a whole-blood interferon-γ release assay for developing active tuberculosis: an update. Am J Respir Crit Care Med. 2011;183(1):88-95. [CrossRef] [PubMed]
 
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