The Effect of Previous Tuberculin Skin Test on the Follow-up Examination of Whole-Blood Interferon-γ Assay in the Screening for Latent Tuberculosis Infection

doi:10.1378/chest.07-2193

Chest

Volume 133, Issue 6, June 2008, Pages 1415-1420

https://doi.org/10.1378/chest.07-2193 Get rights and content

Background

A two-step procedure using a tuberculin skin test (TST) followed by an interferon (IFN)-γ assay in cases in which the TST result is positive has been advocated to screen for latent tuberculosis infection. However, TST could also boost the in vitro immune response. In this study, we evaluated the effect of TST on the results of the IFN-γ assay.

Methods

Our study included 84 health-care workers who had been working in the department of pulmonary medicine for >1 year. First, a whole-blood IFN-γ assay was performed, and then the TST was applied. Two to 4 weeks later, a follow-up IFN-γ assay was performed. A commercially available IFN-γ assay (QuantiFERON-TB GOLD; Cellestis Ltd; Carnegie, VIC, Australia) was used.

Results

Valid TST results were available in 82 individuals because 2 participants refused to undergo the TST after the IFN-γ assay. The TST result was positive in 36 of 82 participants (42.7%), and the IFN-γ assay was positive in 16 of 82 participants (19.5%). The overall agreement between the two tests was 67.5% (κ=0.31; 95% confidence interval, 0.22 to 0.40). The IFN-γ levels increased significantly from 0.05 to 0.19 (p=0.011), and 3 of 18 participants (16.7%) had conversion of their IFN-γ assay results in the TST-positive group. However, in the TST-negative group, the IFN-γ levels did not change after the TST.

Conclusion

The agreement between the results of the TST and the IFN-γ assay was low, and IFN-γ level could be influenced by the TST, in the TST-positive population, when a follow-up IFN-γ assay is performed 2 to 4 weeks later.

Section snippets

Study Design and Setting

A cross-sectional study was conducted from August 2006 until December 2006 at Chung-Ang University Hospital and Chung-Ang University Yong San Hospital in South Korea. The study protocol was approved by the Institutional Review Board at Yong San Hospital, Seoul, South Korea (No. 2006-012-07-1). At these hospitals, approximately 200 cases of smear-positive or culture-positive patients are treated for TB each year.

Participants

This study was designed to recruit HCWs who were directly involved in the clinical

Demographic Characteristics of HCWs

Eighty-four HCWs were included in this study. The median age of the HCWs was 28 years (age range, 23 to 45 years), and 75 HCWs (92%) were women. All participants had a history of BCG vaccination. The median working duration was 26 months (range, 12 to 240 months).

TST Results

Valid TST results were available in 82 individuals because two participants refused to take the TST after the IFN-γ assay. Ten individuals had undergone the TST 3 years before, but the remainder had no history of undergoing the TST

Discussion

The major findings of this study were as follows: (1) the IFN-γ level was increased significantly among TST-positive individuals when the IFN-γ assay was performed 2 to 4 weeks after the TST; (2) the IFN-γ level was not influenced by the TST among TST-negative individuals; (3) the percentage of concordant results between the TST and the IFN-γ assay was low (67.5%), with the κ coefficients indicative of poor agreement (0.31). Concordance between the results of the IFN-γ assay and the TST has

Acknowledgment

We thank the numerous individuals who volunteered to participate in this study. We also acknowledge the insightful contributions of Eun Ju Jun, MD, and Jae Woo Jung, MD.

References (29)

K Ewer 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)
D Bouros et al.
Palpation vs pen method for the measurement of skin tuberculin reaction (Mantoux test)
Chest
(1991)
JY Lee et al.
Comparison of two commercial interferon-gamma assays for diagnosing Mycobacterium tuberculosis infection
Eur Respir J
(2006)
GH Mazurek et al.
Comparison of a whole-blood interferon gamma assay with tuberculin skin testing for detecting latent Mycobacterium tuberculosis infection
JAMA
(2001)
RM Jasmer et al.
Clinical practice: latent tuberculosis infection
N Engl J Med
(2002)
E Panic
World Health Organization guidelines for prevention of tuberculosis in healthcare facilities in countries with limited resources (measures for prevention of tuberculosis)
Med Pregl
(2004)
JS Rothel et al.
A sandwich enzyme immunoassay for bovine interferon-gamma and its use for the detection of tuberculosis in cattle
Aust Vet J
(1990)
I Brock et al.
Comparison of tuberculin skin test and new specific blood test in tuberculosis contacts
Am J Respir Crit Care Med
(2004)
O John
Review: commercial interferon-gamma release assays have high specificity but suboptimal sensitivity for detecting latent TB
ACP J Club
(2007)
M Pai et al.
Serial testing of health care workers for tuberculosis using interferon-gamma assay
Am J Respir Crit Care Med
(2006)

National Institute for Health and Clinical Excellence

Tuberculosis: clinical diagnosis and management of tuberculosis, and measures for its prevention and control: clinical guideline 33

(2006)

L Richeldi et al.

Repeated tuberculin testing does not induce false positive ELISPOT results

Thorax

(2006)

M Pai 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)

AF Luetkemeyer et al.

Comparison of an interferon-gamma release assay with tuberculin skin testing in HIV-infected individuals

Am J Respir Crit Care Med

(2007)

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2015, Tuberculosis
Host- and pathogen-specific factors interplay with the environment in a complex fashion to determine the outcome of infection with Mycobacterium tuberculosis (Mtb), resulting in one of three possible outcomes: cure, latency or active disease. Although much remains unknown about its pathophysiology, latent tuberculosis infection (LTBI) defined by immunologic evidence of Mtb infection is a continuum between self-cure and asymptomatic, yet active tuberculosis (TB) disease. Strain virulence, intensity of exposure to the index case, size of the bacterial inoculum, and host factors such as age and co-morbidities, each contribute to where one settles on the continuum.
Currently, the diagnosis of LTBI is based on reactive tuberculin skin testing (TST) and/or a positive interferon-gamma release assay (IGRA). Neither diagnostic test reflects the activity of the infectious focus or the risk of progression to active TB. This is a critical shortcoming, as accurate and efficient detection of those with LTBI at higher risk of progression to TB disease would allow for provision of targeted preventive therapy to those most likely to benefit. Host biomarkers may prove of value in stratifying risk of development of TB. New guidelines are required for interpretation of discordance between TST and IGRA, which may be due in part to a lack of stability (that is reproducibility) of IGRA or TST results or to a delay in conversion of IGRA to positivity compared to TST.
In this review, the authors elaborate on the definition, diagnosis, pathophysiology and natural history of LTBI, as well as promising methods for better stratifying risk of progression to TB. The review is centered on the human host and the clinical and epidemiologic features of LTBI that are relevant to the development of new and improved diagnostic tools.
Incomplete restoration of Mycobacterium tuberculosis-specific-CD4 T cell responses despite antiretroviral therapy
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Citation Excerpt :
Mean PPD-Sp-CD4 T cells (as % of CD4 T cells) increased in patients not classified as TB-sensitised at baseline. There is evidence from the literature that boosting of IGRA responses 1–4 weeks after TST occurs in a small proportion of patients.38–41 The boosting effect from the TST administered at baseline may have accounted for some of the increase in the frequency of PPD-Sp-CD4 T cells.
Despite antiretroviral therapy (ART), HIV-infected persons have increased risk of active tuberculosis (TB). PPD and combined ESAT-6 and CFP-10-specific-CD4 (EC-Sp-CD4) responses were examined over 96 weeks.
HIV-infected, ART-naive Thai adults with CD4 T cell count ≤350 cells/μL starting ART were assessed at baseline, wk4, 8, 12, 24, 48 and 96. PPD and EC-Sp-CD4 T cells were detected by CD25/CD134 co-expression after stimulation with antigens.
Fifty subjects were enrolled, 39 were male, median age 32 yrs, median baseline CD4 T cell count 186 cells/μL and plasma HIV-viral-load 4.9log₁₀ copies/mL. Seventeen were TB-sensitised.
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At wk4, the number of subjects with positive PPD-Sp-CD4 response rose to 35 (P = 0.021). Mean PPD-Sp-CD4 T cells increased at wk4 (P = 0.017) in patients not classified as TB-sensitised.
The number of subjects with positive EC-Sp-CD4 response did not change significantly post ART. In TB-sensitised patients, mean EC-Sp-CD4 T cells declined to below baseline from wk12 (P = 0.010) onwards. EC-Sp-CD4 responses were undetectable in 3 out of 17 TB-sensitised patients.
Restoration of responses to TB-antigens was incomplete and inconsistent under the employed experimental conditions and may account for persistent increased risk of TB despite ART.
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A cross-sectional study on the prevalence of latent TB infection (LTBI) among HIV-negative men, using QuantiFERON-TB Gold In-tube (QFT-IT), was conducted at a prison in northern Taiwan with >3000 inmates. A QFT-IT ≥0.35 IU/ml was defined as LTBI. A QFT-IT ≥0.7 IU/ml was defined as recent LTBI. The association between the number of BCG scars and LTBI stratified by age was analysed. The study procedure was approved by the institutional review board, and all participants gave written informed consent before receiving screening tests.
Among the 2385 participants, 25% had a QFT-IT ≥0.35 IU/ml. Increasing LTBI (14%, 32% and 50%) was observed with increased age (18–34 years, 35–54 years and ≥55 years) (p<0.001 by the Cochran–Armitage Trend Test). The number of BCG scars were found to be inversely correlated with QFT-IT results for both LTBI and recent LTBI in all three age groups (p<0.001 by Cochran–Mantel–Haenszel statistics).
Our results suggest that BCG vaccine seems to have a protective effect in adults decades after vaccination according to the number of recent infections (QFT-IT ≥0.7 IU/ml). This finding has important implications for national policy of BCG vaccination. Further prospective cohort studies on the protective effect of BCG vaccination against TB infection in adults are warranted.
Low secondary attack rate after prolonged exposure to sputum smear positive miliary tuberculosis in a neonatal unit
2022, Antimicrobial Resistance and Infection Control
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Screening of healthcare workers for latent tuberculosis infection in the low tuberculosis burden country: QuantiFERON-TB gold in tube test or tuberculin skin test?
2019, Archives of Environmental and Occupational Health

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This Research was supported by the Chung-Ang University Research Grants in 2007.

The authors have reported to the ACCP that no significant 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 (www.chestjournal.org/misc/rerints.shtml).

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Chest

Original ResearchLatent TuberculosisThe Effect of Previous Tuberculin Skin Test on the Follow-up Examination of Whole-Blood Interferon-γ Assay in the Screening for Latent Tuberculosis Infection

Background

Methods

Results

Conclusion

Section snippets

Study Design and Setting

Participants

Demographic Characteristics of HCWs

TST Results

Discussion

Acknowledgment

Lancet

Chest

Eur Respir J

Comparison of a whole-blood interferon gamma assay with tuberculin skin testing for detecting latent Mycobacterium tuberculosis infection

JAMA

Clinical practice: latent tuberculosis infection

N Engl J Med

World Health Organization guidelines for prevention of tuberculosis in healthcare facilities in countries with limited resources (measures for prevention of tuberculosis)

Med Pregl

A sandwich enzyme immunoassay for bovine interferon-gamma and its use for the detection of tuberculosis in cattle

Aust Vet J

Comparison of tuberculin skin test and new specific blood test in tuberculosis contacts

Am J Respir Crit Care Med

Review: commercial interferon-gamma release assays have high specificity but suboptimal sensitivity for detecting latent TB

ACP J Club

Serial testing of health care workers for tuberculosis using interferon-gamma assay

Am J Respir Crit Care Med

Tuberculosis: clinical diagnosis and management of tuberculosis, and measures for its prevention and control: clinical guideline 33

Repeated tuberculin testing does not induce false positive ELISPOT results

Thorax

Mycobacterium tuberculosis infection in health care workers in rural India: comparison of a whole-blood interferon gamma assay with tuberculin skin testing

JAMA

Comparison of an interferon-gamma release assay with tuberculin skin testing in HIV-infected individuals

Am J Respir Crit Care Med

Original Research
Latent Tuberculosis
The Effect of Previous Tuberculin Skin Test on the Follow-up Examination of Whole-Blood Interferon-γ Assay in the Screening for Latent Tuberculosis Infection