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Roland Diel, MD, MPH; Robert Loddenkemper, MD, FCCP; Albert Nienhaus, MD, MPH
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From the Department of Pulmonary Medicine (Dr Diel), Medical School Hannover; German Central Committee Against Tuberculosis (Dr Loddenkemper), Lungenklinik Heckeshorn, HELIOS Klinikum Emil von Behring; and Institute for Health Service Research in Dermatology and Nursing (Dr Nienhaus), University Medical Center Hamburg-Eppendorf.

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


Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Diel has received travel reimbursement and/or fees for speaking at symposia sponsored by Cellestis, Oxford Immunotec, and Pharmore Ltd (exclusive supplier of Tuberculin RT23 for Germany). Drs Loddenkemper and Nienhaus have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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


Chest. 2012;142(3):811-812. doi:10.1378/chest.12-1449
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To the Editor:

We thank Drs Khurana and Khurana for their interest in our article in CHEST1 and their letter addressing the question of whether a follow-up of only 2 years for untreated people at risk for TB is appropriate, particularly in high-prevalence countries. The study by Lee et al2 performed in a high-prevalence Asian region and involving a very high number of untreated contacts demonstrates that the risk of progression is at its highest directly after Mycobacterium tuberculosis (MTB) infection and that more than one-half of those subjects who progressed to TB did so within the first 2 years. Thus, the statistical power of a progression study will be greatest when the period of high risk of progression is studied, that is, the first couple of years after exposure to infectious patients. Furthermore, the problem of participant dropout will be minimized if the focus is on the first few years following recent infection. From randomized studies on the preventive treatment of latent TB infection, such as the large-scale International Unit Against Tuberculosis Eastern European study published in 1982,3 we learned that following infection, there is a natural decline in the risk of developing TB over time.

Therefore, we agree with Drs Khurana and Khurana that a follow-up of people for 2 years at a given date makes little sense if infection with MTB occurred decades earlier (eg, in early childhood), unless there is impaired immunocompetence. Without any knowledge of the specific conditions of a previous MTB infection among the people tested, a positive result, irrespective of whether a tuberculin skin test (TST) or an interferon-γ release assay (IGRA) is used, cannot, per se, lead to the conclusion that there is a high risk of the person developing TB in the future. Thus, it follows that decisions on chemoprevention should not be based on IGRA or TST results alone. As neither the IGRA nor the TST distinguishes old from recent infection, the history of exposure needs to be analyzed to decide whether old or recent infection is likely.

This also pertains to the screening of health-care workers. The high prevalence of positive TST or IGRA results and the low rate of progression for health-care workers indicate that old infections with a low risk of progression prevail.4 Of particular note is the fact that in the small study (n =48) by Park et al,5 a considerable variation in IGRA results is observed, especially with concentrations around the cutoff. Again in agreement with Drs Khurana and Khurana, the meaning of these phenomena needs to be elucidated by generating data on risk of progression depending on IGRA variation.4

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 metaanalysis. Chest. 2012;142(1):63-75. [PubMed] [CrossRef]
 
Lee MSN, Leung CC, Kam KM, et al. Early and late tuberculosis risks among close contacts in Hong Kong. Int J Tuberc Lung Dis. 2008;12(3):281-287. [PubMed]
 
Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. International Union Against Tuberculosis Committee on Prophylaxis. Bull World Health Organ. 1982;60(4):555-564. [PubMed]
 
Loddenkemper R, Diel R, Nienhaus A. To repeat or not to repeat—that is the question! Serial testing of health-care workers for TB infection. Chest. 2012;142(1):10-11. [PubMed] [CrossRef]
 
Park JS, Lee JS, Kim MY, et al. Monthly follow-ups of interferon-γ release assays among healthcare workers in contact with TB patients [published online ahead of print May 3, 2012]. Chest. doi:10.1378/chest.11-3299.
 

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References

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 metaanalysis. Chest. 2012;142(1):63-75. [PubMed] [CrossRef]
 
Lee MSN, Leung CC, Kam KM, et al. Early and late tuberculosis risks among close contacts in Hong Kong. Int J Tuberc Lung Dis. 2008;12(3):281-287. [PubMed]
 
Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. International Union Against Tuberculosis Committee on Prophylaxis. Bull World Health Organ. 1982;60(4):555-564. [PubMed]
 
Loddenkemper R, Diel R, Nienhaus A. To repeat or not to repeat—that is the question! Serial testing of health-care workers for TB infection. Chest. 2012;142(1):10-11. [PubMed] [CrossRef]
 
Park JS, Lee JS, Kim MY, et al. Monthly follow-ups of interferon-γ release assays among healthcare workers in contact with TB patients [published online ahead of print May 3, 2012]. Chest. doi:10.1378/chest.11-3299.
 
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